PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 21058037-3 2011 As a result, CD117 has been identified as a target for therapy via the small molecule, tyrosine kinase inhibitor imatinib mesylate. Imatinib Mesylate 113-130 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 13-18 21785586-7 2011 Research into the effect of a c-kit receptor inhibitor, imatinib mesylate, on bladder function implies that KIT-positive ICCs may be therapeutic target cells to reduce bladder overactivity and that the blockage of c-kit receptor may offer a new therapeutic strategy for OAB treatment, although further study will be needed. Imatinib Mesylate 56-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 32-35 21785586-7 2011 Research into the effect of a c-kit receptor inhibitor, imatinib mesylate, on bladder function implies that KIT-positive ICCs may be therapeutic target cells to reduce bladder overactivity and that the blockage of c-kit receptor may offer a new therapeutic strategy for OAB treatment, although further study will be needed. Imatinib Mesylate 56-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 108-111 21785586-7 2011 Research into the effect of a c-kit receptor inhibitor, imatinib mesylate, on bladder function implies that KIT-positive ICCs may be therapeutic target cells to reduce bladder overactivity and that the blockage of c-kit receptor may offer a new therapeutic strategy for OAB treatment, although further study will be needed. Imatinib Mesylate 56-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 216-219 21140148-2 2011 Imatinib has exceptional activity in controlling gastrointestinal stromal tumor (GIST) due to inhibition of the constitutively active conformation of KIT and PDGFRA which is found in the majority of patients with GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 150-153 20978751-1 2011 Imatinib mesylate is a tyrosine kinase inhibitor used in the management of disorders in which activation of c-Abl, PDGFR, or c-Kit signaling plays a critical role. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 125-130 21181476-2 2011 Imatinib mesylate potently abrogates the effects of KIT signaling by directly binding into the ATP-binding pocket of the kinase. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 21181476-4 2011 Within KIT, patients whose tumor has an exon 9 mutation are treated by many clinicians with higher doses of imatinib than those patients with mutations within exon 11. Imatinib Mesylate 108-116 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 7-10 21181476-6 2011 Secondary KIT mutations generally occur at a codon where imatinib binds resulting in KIT reactivation and resistance. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-13 21181476-6 2011 Secondary KIT mutations generally occur at a codon where imatinib binds resulting in KIT reactivation and resistance. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-88 21181476-7 2011 Sunitinib malate, a second-generation KIT inhibitor is active in imatinib-resistant disease and is FDA-approved for use in this setting. Imatinib Mesylate 65-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 38-41 22606444-1 2011 Imatinib mesylate is a tyrosine kinase inhibitor of c-KIT and PDGFRA. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-57 22174597-5 2011 Imatinib is now also approved in adult patients following resection of KIT-positive GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-74 22262331-2 2011 The recognition that KIT mutations were present in the majority of patients with GIST led to clinical trials of imatinib in this disease. Imatinib Mesylate 112-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-24 22262331-3 2011 Indeed, imatinib inhibits KIT kinase activity and represents the best drug for the treatment of unresectable and advanced GIST, achieving a partial response or stable disease in 85-90% of patients with metastatic disease. Imatinib Mesylate 8-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 22262331-6 2011 The presence and the type of KIT or PDGFRA mutation status are predictive of response to imatinib therapy in patients with advanced or metastatic GIST, as well as prognostic for relapse-free survival (RFS) after surgical resection of primary GIST. Imatinib Mesylate 89-97 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-32 22262331-9 2011 Based on the results of ACOSOG Z9001 trial, in December 2008, the FDA approved imatinib for postoperative treatment of patients with resected KIT-positive GIST; optimum duration of adjuvant treatment was not stated. Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 142-145 20876428-0 2011 Good clinical response to imatinib mesylate in atypical thymic carcinoid With KIT overexpression. Imatinib Mesylate 26-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 78-81 22135725-9 2011 Imatinib mesylate decreased the rates of cell growth of osteosarcoma cells in low doses and invasion in high doses C-kit-positive tumors had worse response to chemotherapy and imatinib mesylate can play a role in blocking or decreasing the rate of growth of osteosarcoma cells, but not the invasive capacity of these neoplastic cells. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-120 22135725-9 2011 Imatinib mesylate decreased the rates of cell growth of osteosarcoma cells in low doses and invasion in high doses C-kit-positive tumors had worse response to chemotherapy and imatinib mesylate can play a role in blocking or decreasing the rate of growth of osteosarcoma cells, but not the invasive capacity of these neoplastic cells. Imatinib Mesylate 176-193 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-120 21125679-5 2011 Indeed, imatinib mesylate inhibits KIT kinase activity and represents the front-line drug for the treatment of unresectable and advanced GISTs, achieving a partial response or stable disease in about 80% of patients with metastatic GIST. Imatinib Mesylate 8-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 35-38 20427086-0 2010 A Phase 1 study of imatinib mesylate in combination with cytarabine and daunorubicin for c-kit positive relapsed acute myeloid leukemia. Imatinib Mesylate 19-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-94 21192792-3 2010 Imatinib and nilotinib directly inhibit the kinase activity of KIT, while RAD001 (everolimus) inhibits mTOR. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-66 20427086-2 2010 We conducted a Phase 1 study of the c-kit inhibitor, imatinib mesylate (IM), in combination with cytarabine and daunorubicin (7+3) in c-kit+ relapsed AML. Imatinib Mesylate 53-70 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 36-41 20427086-2 2010 We conducted a Phase 1 study of the c-kit inhibitor, imatinib mesylate (IM), in combination with cytarabine and daunorubicin (7+3) in c-kit+ relapsed AML. Imatinib Mesylate 53-70 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-139 21047493-0 2010 Imatinib as adjuvant treatment following resection of KIT-positive gastrointestinal stromal tumours. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 54-57 21037371-0 2010 Imatinib inhibits bone marrow-derived c-kit+ cell mobilisation in hypoxic pulmonary hypertension. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 38-43 20883053-1 2010 Imatinib is a protein-tyrosine kinase inhibitor with antitumour effects in patients with gastrointestinal stromal tumour (GIST) that is indicated for the treatment of unresectable and/or metastatic GIST and as adjuvant therapy in patients with KIT-positive GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 244-247 20883053-2 2010 Imatinib binds to and inhibits KIT and platelet-derived growth factor receptor (PDGFR)-alpha tyrosine kinases, interfering with their downstream tumourogenic processes. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 31-34 20883053-3 2010 Cell lines with KIT mutations that are common in patients with GIST were sensitive to imatinib at low in vitro concentrations. Imatinib Mesylate 86-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 16-19 20019577-1 2010 BACKGROUND: Imatinib mesylate (Gleevec) was evaluated as a treatment for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) based on the identification of strong c-KIT staining of these neoplasms. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 177-182 20019577-1 2010 BACKGROUND: Imatinib mesylate (Gleevec) was evaluated as a treatment for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) based on the identification of strong c-KIT staining of these neoplasms. Imatinib Mesylate 31-38 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 177-182 20943625-5 2010 Shortly after the detection of gain-of-function mutations in the type III receptor tyrosine kinases KIT and PDGFRalpha a targeted treatment with the tyrosine kinase inhibitor imatinib was introduced and became the gold standard in advanced GIST disease. Imatinib Mesylate 175-183 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-103 20690803-3 2010 Imatinib is more effective in patients with KIT exon 11 mutations compared with KIT exon 9 mutations and wild-type genotype, while sunitinib confers greater in vitro efficacy in patients with KIT exon 9 mutants and wild-type genotype than in KIT exon 11 mutants. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 20947481-4 2010 The introduction of the kinase inhibitor imatinib mesylate, and sunitinib in second line, against KIT and PDGFRA has provided the first evidence of directed therapy in GIST. Imatinib Mesylate 41-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-101 21047493-1 2010 This is a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of adjuvant imatinib post resection of KIT-positive gastrointestinal stromal tumours (GISTs) compared with resection only in patients at significant risk of relapse. Imatinib Mesylate 125-133 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 152-155 20425130-13 2010 The finding of a mutation in one of two acral melanomas suggests that KIT inhibitors, for example imatinib, which are already used in clinics for treatment of GIST, can also be used for melanoma. Imatinib Mesylate 98-106 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-73 20806443-9 2010 CONCLUSION: Most patients with different genotypes of GIST and KIT exon 11-mutant will benefit from the individualized treatment of imatinib. Imatinib Mesylate 132-140 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-66 20553795-0 2010 In vitro and in vivo growth-inhibitory effects of cladribine on neoplastic mast cells exhibiting the imatinib-resistant KIT mutation D816V. Imatinib Mesylate 101-109 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-123 20553795-1 2010 OBJECTIVE: In most patients with systemic mastocytosis (SM), including aggressive SM (ASM) and mast cell (MC) leukemia (MCL), neoplastic cells express the oncogenic KIT mutation D816V, which confers resistance to imatinib. Imatinib Mesylate 213-221 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 165-168 20691121-3 2010 Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-82 20658618-9 2010 Up-regulation of CD117 in NB cells correlated with increased sensitivity for the kinase inhibitor imatinib mesylate. Imatinib Mesylate 98-115 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-22 20726677-1 2010 BACKGROUND: Imatinib mesylate, an orally administered kinase inhibitor that targets the Kit (CD117) protein, currently has 10 approved indications including treatment of chronic myelogenous leukemia and metastatic gastrointestinal stromal tumors (GIST). Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-98 20953927-0 2010 Multicenter phase II trial assessing effectiveness of imatinib mesylate on relapsed or refractory KIT-positive or PDGFR-positive sarcoma. Imatinib Mesylate 54-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-101 20953927-3 2010 We conducted a multicenter Phase II trial of imatinib in patients with relapsed or refractory KIT-positive (excluding GISTs) or PDGFR-positive sarcomas. Imatinib Mesylate 45-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 94-97 20660757-1 2010 Although gastrointestinal stromal tumors (GISTs) harboring activating KIT or platelet-derived growth factor receptor A (PDGFRA) mutations respond to treatment with targeted KIT/PDGFRA inhibitors such as imatinib mesylate, these treatments are rarely curative. Imatinib Mesylate 203-220 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-73 20660757-1 2010 Although gastrointestinal stromal tumors (GISTs) harboring activating KIT or platelet-derived growth factor receptor A (PDGFRA) mutations respond to treatment with targeted KIT/PDGFRA inhibitors such as imatinib mesylate, these treatments are rarely curative. Imatinib Mesylate 203-220 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 173-176 20486169-1 2010 Imatinib is an inhibitor of the BCR-ABL fusion gene product that characterizes chronic myeloid leukemia (CML), and of the related tyrosine kinases c-KIT and platelet-derived growth factor (PDGF) receptor. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 147-152 20564079-1 2010 BACKGROUND: In KIT-expressing Ewing sarcoma cell lines, the addition of doxorubicin to imatinib increases apoptosis, compared with imatinib or doxorubicin alone. Imatinib Mesylate 87-95 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 15-18 19703239-1 2010 BACKGROUND: Imatinib mesylate (Gleevec) is a selective Bcr-Abl protein tyrosine-kinase inhibitor, and it also inhibits the receptor tyrosine kinases for stem cell factor (c-kit) and platelet-derived growth factor (PDGFR). Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 171-176 21086937-12 2010 Biological therapy with imatinib mesylate is recommended for patients with newly diagnosed, locally advanced, inoperable, or metastasizing gastrointestinal GISTs that express the c-KIT protein. Imatinib Mesylate 24-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 179-184 20598160-3 2010 Furthermore, in advanced GIST disease with proven KIT exon 9 mutation the doubled daily dose of 800 mg imatinib increases the progression free survival and is now recommended both in the European and the American Guidelines. Imatinib Mesylate 103-111 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-53 20551067-3 2010 In this study, we show that myeloid cells expressing activated c-KIT mutants that are imatinib sensitive (V560G) or imatinib resistant (D816V) can inhibit the tumor suppressor activity of protein phosphatase 2A (PP2A). Imatinib Mesylate 86-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-68 20551067-3 2010 In this study, we show that myeloid cells expressing activated c-KIT mutants that are imatinib sensitive (V560G) or imatinib resistant (D816V) can inhibit the tumor suppressor activity of protein phosphatase 2A (PP2A). Imatinib Mesylate 116-124 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-68 20630823-0 2010 Phase II trial of imatinib maintenance therapy after irinotecan and cisplatin in patients with c-Kit-positive, extensive-stage small-cell lung cancer. Imatinib Mesylate 18-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-100 20630823-2 2010 This trial was designed to evaluate irinotecan/cisplatin plus maintenance imatinib in patients with c-Kit-positive disease (the transmembrane receptor c-Kit is the product of the c-KIT protooncogene). Imatinib Mesylate 74-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-105 20489620-1 2010 PURPOSE OF REVIEW: Imatinib has exceptional activity in controlling gastrointestinal stromal tumor (GIST) due to inhibition of the constitutively active conformation of KIT and platelet-derived growth factor-alpha (PDGFRA), which is commonly seen in this tumor. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 169-172 20043176-1 2010 AIMS AND BACKGROUND: Most gastrointestinal stromal tumor (GIST) patients respond to KIT inhibition therapy of imatinib, but eventually become resistant with a median time to progression of 2 years. Imatinib Mesylate 110-118 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 20043176-8 2010 Secondary KIT mutations were identified in 11/14 (78.6%) imatinib-acquired-resistance patients, with nine patients in KIT gene exon17, and the other two in exon 13. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-13 20043176-8 2010 Secondary KIT mutations were identified in 11/14 (78.6%) imatinib-acquired-resistance patients, with nine patients in KIT gene exon17, and the other two in exon 13. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 118-121 20043176-9 2010 The expressions of p-KIT, p-AKT, PCNA and BCL-2 were higher in the samples of imatinib-resistant GISTs than those of imatinib-responsive ones. Imatinib Mesylate 78-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-24 20043176-10 2010 P-KIT, p-AKT expressions were higher in imatinib acquired-resistance GISTs with secondary KIT mutations than imatinib-responsive ones with primary mutation. Imatinib Mesylate 40-48 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 2-5 20043176-10 2010 P-KIT, p-AKT expressions were higher in imatinib acquired-resistance GISTs with secondary KIT mutations than imatinib-responsive ones with primary mutation. Imatinib Mesylate 40-48 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-93 20043176-12 2010 CONCLUSIONS: Novel additional mutations of KIT gene exon 13 or exon 17 indicate the likely mechanism of secondary resistance to imatinib. Imatinib Mesylate 128-136 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-46 20658364-0 2010 [Expression of MDR1 and KIT in imatinib-resistant gastrointestinal stromal tumor cells]. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 20658364-1 2010 OBJECTIVE: To explore the relationship between imatinib resistance and genes MDR1 and KIT in gastrointestinal stromal tumor (GIST) cells. Imatinib Mesylate 47-55 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 86-89 20533592-4 2010 Imatinib and sunitinib, both tyrosine kinase inhibitors directed to KIT, were approved for first- and second-line treatment of metastatic and unresectable GISTs. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-71 20500152-3 2010 Although previously refractory to any course of action but surgery, GIST heralded a triumph in targeted cancer therapy when administration of a specific first-generation tyrosine-kinase inhibitor Imatinib mesylate (STI571) was shown to inhibit c-Kit and demonstrated a significant increase in patient survival. Imatinib Mesylate 196-213 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 244-249 20525481-4 2010 By inhibiting KIT, imatinib has a cytostatic and cytotoxic effect on melanomas with KIT mutations, and probably has the same effect on another subgroup of melanomas with other as yet imperfectly understood KIT mutations. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 20525481-4 2010 By inhibiting KIT, imatinib has a cytostatic and cytotoxic effect on melanomas with KIT mutations, and probably has the same effect on another subgroup of melanomas with other as yet imperfectly understood KIT mutations. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 20525481-4 2010 By inhibiting KIT, imatinib has a cytostatic and cytotoxic effect on melanomas with KIT mutations, and probably has the same effect on another subgroup of melanomas with other as yet imperfectly understood KIT mutations. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 20407778-8 2010 In pediatric populations, GISTs of the small intestine were expected to show a better response to imatinib treatment than gastric GISTs because of the alterations in the c-kit gene. Imatinib Mesylate 98-106 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-175 20500152-7 2010 However, extensive research regarding both primary and secondary c-KIT mutations has illuminated the mechanisms of Imatinib resistance and has the potential to ameliorate this therapeutic setback. Imatinib Mesylate 115-123 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 65-70 20499309-4 2010 RESULTS: Three cases who showed response to imatinib carried primary mutations in KIT gene, with 2 cases possessing mutation in exon 11, 1 case in exon 13. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-85 20470368-7 2010 Secondary KIT mutations were additionally found in two of four samples obtained after imatinib treatment. Imatinib Mesylate 86-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-13 20180814-12 2010 A KIT-independent mechanism, such as activation of other RTKs, might participate in the proliferation of late-stage GISTs and might be a cause of secondary imatinib resistance. Imatinib Mesylate 156-164 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 2-5 20200154-13 2010 Additional calculations show that conformational selection also governs the relative binding of imatinib to the kinases c-Kit and Lck. Imatinib Mesylate 96-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-125 20231287-0 2010 Role for the proapoptotic factor BIM in mediating imatinib-induced apoptosis in a c-KIT-dependent gastrointestinal stromal tumor cell line. Imatinib Mesylate 50-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-87 20231287-2 2010 The identification of selective inhibitors of c-KIT, such as imatinib, has provided a novel therapeutic approach in the treatment of this chemotherapy refractory tumor. Imatinib Mesylate 61-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-51 20231287-4 2010 Here, we show that inhibition of c-KIT with imatinib in gastrointestinal stromal tumors (GISTs) triggered the up-regulation of the proapoptotic protein BIM via both transcriptional and post-translational mechanisms. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 33-38 20231287-5 2010 The inhibition of c-KIT by imatinib increased levels of the dephosphorylated and deubiquitinated form of BIM as well as triggered the accumulation of the transcription factor FOXO3a on the BIM promoter to activate transcription of BIM mRNA. Imatinib Mesylate 27-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-23 20499309-5 2010 One case with imatinib-resistance developed KIT secondary mutation, but all the cases had no PDGFRa mutation. Imatinib Mesylate 14-22 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 20499309-6 2010 p-KIT and p-AKT expressions were higher in the samples of imatinib-resistant GIST than those of imatinib-responsive GIST. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 2-5 20499309-10 2010 The KIT secondary mutation and PI3-K/AKT/MTOR pathway are particularly relevant for therapeutic targeting in imatinib-resistant GIST. Imatinib Mesylate 109-117 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-7 20372153-0 2010 Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT. Imatinib Mesylate 33-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-103 20146241-10 2010 On the other hand, the Abl/Kit inhibitor imatinib did not affect cell growth or apoptosis in the four types of spheroids. Imatinib Mesylate 41-49 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 27-30 20124512-7 2010 STI-571 (imatinib), a targeted therapy for BCR-ABL1(+) leukemias and inhibitor of c-Abl, platelet-derived growth factor receptor, and c-Kit, decreased endothelial apoptosis. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-139 20124512-7 2010 STI-571 (imatinib), a targeted therapy for BCR-ABL1(+) leukemias and inhibitor of c-Abl, platelet-derived growth factor receptor, and c-Kit, decreased endothelial apoptosis. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-139 19768386-1 2010 Imatinib, an orally administered tyrosine kinase inhibitor of PDGF receptor, c-abl and c-kit, is currently in clinical trials to assess its efficacy in malignant gliomas. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-92 20124181-10 2010 CONCLUSION: This analysis confirms a small PFS advantage of high-dose imatinib, essentially among patients with KIT exon 9 mutations, but no OS advantage. Imatinib Mesylate 70-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 112-115 20360932-6 2010 In keratinocyte-melanoma cocultures stained for the Ki67 proliferation marker, incubation with KGF induced enhanced growth not only of the keratinocytes but also of the melanoma cells, which could be blocked by the c-KIT inhibitor imatinib, demonstrating the establishment of a KGF-induced paracrine signaling network owing to the coexpression of biologically active SCF released from keratinocytes and functional c-KIT on melanoma cells. Imatinib Mesylate 231-239 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 215-220 20033343-0 2010 Emergence of imatinib resistance associated with downregulation of c-kit expression in recurrent gastrointestinal stromal tumor (GIST): optimal timing of resection. Imatinib Mesylate 13-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-72 20095048-2 2010 Biophysical, biochemical, and structural studies have provided insight into the molecular basis of resistance to the KIT inhibitors, imatinib and sunitinib. Imatinib Mesylate 133-141 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-120 20332468-0 2010 Phase II clinical trial of imatinib mesylate in therapy of KIT and/or PDGFRalpha-expressing Ewing sarcoma family of tumors and desmoplastic small round cell tumors. Imatinib Mesylate 27-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 59-62 19949796-1 2010 The discovery of activating oncogenic C-KIT and PDGFRA mutations in gastrointestinal stromal tumors (GIST) represented the key for the development of innovative targeted molecular therapy using the tyrosine kinase inhibitors (TKI) Imatinib (Glivec(R)), Sunitinib and other substances. Imatinib Mesylate 231-239 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 38-43 20332468-1 2010 BACKGROUND: We have previously shown that the receptor tyrosine kinases, KIT and PDGFRalpha, are expressed on ESFT cell lines, and that imatinib induces dose-dependent apoptosis (1). Imatinib Mesylate 136-144 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 20332468-2 2010 We conducted a Phase II trial to evaluate the effectiveness of imatinib for patients with recurrent ESFT or DSRCT expressing KIT and/or PDGFRalpha. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 125-128 20165865-6 2010 Although, KIT (CD117) immunohistochemistry is a reliable diagnostic tool in the diagnosis of GIST, KIT-negative GISTs, GISTs showing unusual morphology as well as GISTs which progress during or after treatment with imatinib/sunitinib can be a challenge for pathologists and clinicians. Imatinib Mesylate 215-223 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-13 20109338-7 2010 Pearson product moment correlation and t test were used to analyze the correlation betweeen C-KIT overexpression, C-KIT gene mutation, and the inhibitory effect of Imatinib. Imatinib Mesylate 164-172 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-97 20165865-6 2010 Although, KIT (CD117) immunohistochemistry is a reliable diagnostic tool in the diagnosis of GIST, KIT-negative GISTs, GISTs showing unusual morphology as well as GISTs which progress during or after treatment with imatinib/sunitinib can be a challenge for pathologists and clinicians. Imatinib Mesylate 215-223 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 15-20 19890095-6 2010 In particular, it examines recent studies suggesting that imatinib has direct effects on bone-resorbing osteoclasts and bone-forming osteoblasts through inhibition of c-fms, c-kit, carbonic anhydrase II, and the platelet-derived growth factor receptor. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 174-179 20137358-23 2010 Targeted therapy such as imatinib, a KIT tyrosine kinase inhibitor, may play an important role in the treatment of GIST. Imatinib Mesylate 25-33 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-40 20044640-1 2009 BACKGROUND: The tyrosine kinase inhibitors (TKI) sunitinib and imatinib were shown to induce macrocytosis in patients with renal cell cancer (RCC) and gastrointestinal stromal tumors (GIST), presumably through inhibition of the c-KIT dependent signaling pathway of erythroid progenitor cells of the bone marrow. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 228-233 20053766-2 2010 The various juxtamembrane type of KIT mutations, including V560G, are found in 60% to 70% of patients with gastrointestinal stromal tumors; loop mutant D816V, which exists in approximately 80% of SM patients, is completely resistant to imatinib. Imatinib Mesylate 236-244 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 20053766-4 2010 Imatinib-sensitive HMC-1.1 cells harboring the mutation V560G in the juxtamembrane domain of KIT, imatinib-resistant HMC-1.2 cells harboring both V560G and D816V mutations, and murine P815 cells were treated with HHT and analyzed in terms of growth, apoptosis, and signal transduction. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-96 20339585-0 2010 A V530I Mutation in c-KIT Exon 10 Is Associated to Imatinib Response in Extraabdominal Aggressive Fibromatosis. Imatinib Mesylate 51-59 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-25 20339585-5 2010 Here, we describe for the first time a V530I KIT exon 10 mutant that was associated to a dramatic imatinib response in an extraabdominal aggressive fibromatosis. Imatinib Mesylate 98-106 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-48 23960476-8 2010 CONCLUSIONS: These results suggested that c-kit could be used as a prognostic marker for ACC and specific c-kit tyrosine kinase inhibitors such as imatinib, might be used in future therapeutic approaches against subgroups of ACC. Imatinib Mesylate 147-155 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-111 20041122-0 2009 Steered molecular dynamics simulations reveal the likelier dissociation pathway of imatinib from its targeting kinases c-Kit and Abl. Imatinib Mesylate 83-91 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 119-124 20041122-4 2009 In this investigation, steered molecular dynamics simulations have been carried out to explore the possible dissociation pathways of typical type II inhibitor imatinib from its targeting protein kinases c-Kit and Abl. Imatinib Mesylate 159-167 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 203-208 20023271-1 2010 Mutational analysis of c-KIT or PDGFRA has become an important laboratory assay for patients with gastrointestinal stromal tumors (GISTs) because the results are useful in predicting the responsiveness to imatinib. Imatinib Mesylate 205-213 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-28 20146711-7 2010 Others have shown that dendritic cell treatment with inhibitors of c-kit activation, such as imatinib mesylate (Gleevec), favored breaking of T-cell tolerance, skewing of responses toward production of Th1 cytokines, and activation of natural killer cells. Imatinib Mesylate 93-110 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-72 20028869-7 2010 Proliferation of CSCs was inhibited by SCF-neutralizing antibodies or by imatinib (Gleevec), an inhibitor of c-kit. Imatinib Mesylate 73-81 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 109-114 20028869-7 2010 Proliferation of CSCs was inhibited by SCF-neutralizing antibodies or by imatinib (Gleevec), an inhibitor of c-kit. Imatinib Mesylate 83-90 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 109-114 19950162-0 2010 Novel imatinib derivatives with altered specificity between Bcr-Abl and FMS, KIT, and PDGF receptors. Imatinib Mesylate 6-14 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-80 19996579-2 2010 Imatinib has become the standard of care in other cancers with KIT mutations such as gastrointestinal stromal tumors. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-66 19996579-3 2010 Recently 12 cases of metastatic melanoma and KIT-activating mutations have been published to be successfully treated with c-KIT blockers such as imatinib, sunitinib, dasatinib or sorafenib. Imatinib Mesylate 145-153 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-48 19996579-3 2010 Recently 12 cases of metastatic melanoma and KIT-activating mutations have been published to be successfully treated with c-KIT blockers such as imatinib, sunitinib, dasatinib or sorafenib. Imatinib Mesylate 145-153 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 122-127 19996579-4 2010 We report here on one of our patients with KIT-activating mutation in metastatic anal mucosal melanoma, who showed a response to imatinib therapy and summarize the available literature regarding this new therapeutic option. Imatinib Mesylate 129-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-46 19968734-6 2010 The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. Imatinib Mesylate 206-214 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 126-129 19968734-9 2010 Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins. Imatinib Mesylate 89-97 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 137-140 20053766-4 2010 Imatinib-sensitive HMC-1.1 cells harboring the mutation V560G in the juxtamembrane domain of KIT, imatinib-resistant HMC-1.2 cells harboring both V560G and D816V mutations, and murine P815 cells were treated with HHT and analyzed in terms of growth, apoptosis, and signal transduction. Imatinib Mesylate 98-106 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-96 20053766-9 2010 Collectively, we show that HHT circumvents D816V KIT-elicited imatinib resistance. Imatinib Mesylate 62-70 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 19956885-3 2010 Imatinib mesylate (STI571) can inhibit c-kit tyrosine kinase activity, but clinical trials have resulted in failure. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 39-44 19956885-3 2010 Imatinib mesylate (STI571) can inhibit c-kit tyrosine kinase activity, but clinical trials have resulted in failure. Imatinib Mesylate 19-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 39-44 21344772-3 2010 Its employment in neuroblastoma treatment is potentially possible because of expression of c-kit and PDGFR, which are cellular targets of imatinib. Imatinib Mesylate 138-146 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 91-96 20072827-3 2010 Imatinib is a rationally designed oral signal transduction inhibitor that specifically targets several protein tyrosine kinases, Abl, Arg (Abl-related gene), the stem-cell factor receptor (c-KIT), platelet-derived growth factor receptor (PDGF-R), and their oncogenic forms, most notably Bcr-Abl. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 189-194 19861442-10 2009 In contrast, in vitro resistance to imatinib produces a broader spectrum of secondary mutations including mutations in both KIT kinase domains. Imatinib Mesylate 36-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-127 19917964-2 2009 Imatinib mesylate is an inhibitor of c-kit and is indicated in the treatment of chronic myeloid leukemia and GISTs. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-42 20032453-16 2009 Imatinib was effective against GIST that were positive for KIT protein, but future study is needed to clarify the risk factors for recurrence and indications for adjuvant therapy in cases of GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 59-62 19811659-8 2009 From all conventional RCC, CD 117 was detected (overexpression) in membrane of cells ChRCC.Overexpression of CD117 on cellular membranes of ChRCC could be a potential target for kinase inhibitors like: imatinib, dasatinib, nilotinib. Imatinib Mesylate 202-210 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 109-114 19652585-1 2009 KIT alterations have been identified in melanoma and treatment with imatinib has met with some success. Imatinib Mesylate 68-76 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 19732238-8 2009 However, both acute and prolonged inhibition of this receptor with the c-kit antagonist imatinib mesylate does not appear to affect the spontaneous contractility of myometrium. Imatinib Mesylate 88-105 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-76 19755855-5 2009 Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFRalpha/KIT small molecule inhibitors imatinib or sunitinib leads to cell growth inhibition. Imatinib Mesylate 110-118 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-83 19801102-4 2009 RESULTS: Dramatic phosphorylated (p)-c-Kit and p-PDGFRbeta attenuation, a modest dose- and time-dependent growth inhibition, and significant radiosensitization were observed after STI-571 treatment in view of apoptosis, although the levels of growth inhibition and increased radiosensitization were different according to cell lines. Imatinib Mesylate 180-187 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-42 19193436-2 2009 Twenty patients with SM were enrolled during 2003-2005 in phase II clinical trial with imatinib mesylate (400mg daily), a KIT inhibitor. Imatinib Mesylate 87-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 122-125 19446878-1 2009 Imatinib-induced macrocytic anemia was known to result from c-kit inhibition in chronic myeloid leukemia (CML). Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-65 19474800-4 2009 In addition to inhibiting the BCR-ABL kinase, imatinib and nilotinib target the same array of other tyrosine kinases, including c-KIT and platelet-derived growth factor receptor (PDGFR), albeit with differing potencies. Imatinib Mesylate 46-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 128-133 19617878-14 2009 Our study raises a prospect of correlation of c-kit mutation and a potential treatment of adenoid cystic carcinoma with tyrosine kinase inhibitor (imatinib). Imatinib Mesylate 147-155 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-51 19660459-3 2009 This work investigates the conformational changes that accompany the binding of Gleevec, or imatinib mesylate, to the tyrosine kinases c-Kit and c-Abl. Imatinib Mesylate 92-109 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 135-140 19737946-11 2009 CONCLUSION: Cellular and molecular analyses showed that sunitinib clinical activity is associated with inhibition of KIT in GIST following imatinib failure, illustrating the rational approach used to develop a therapy aimed at the underlying oncogenic signaling pathway aberrancy. Imatinib Mesylate 139-147 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-120 19737953-0 2009 Circulating levels of soluble KIT serve as a biomarker for clinical outcome in gastrointestinal stromal tumor patients receiving sunitinib following imatinib failure. Imatinib Mesylate 149-157 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-33 19737953-1 2009 PURPOSE: To evaluate changes in circulating levels of soluble KIT (sKIT) extracellular domain as a potential biomarker for clinical outcome in gastrointestinal stromal tumor patients treated with the multitargeted tyrosine kinase inhibitor sunitinib following imatinib failure in a previously reported phase III study. Imatinib Mesylate 260-268 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-65 19362466-2 2009 METHODS: Exploratory study on imatinib in tumours expressing, at least, one of the receptors KIT or platelet-derived growth factor receptor (PDGFR). Imatinib Mesylate 30-38 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-139 19722748-3 2009 c-KIT (CD117)-positive mast cells have been associated with chronic fibrosing diseases and may potentially be treated with imatinib (Gleevec), a c-KIT blocker. Imatinib Mesylate 123-131 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 19722748-3 2009 c-KIT (CD117)-positive mast cells have been associated with chronic fibrosing diseases and may potentially be treated with imatinib (Gleevec), a c-KIT blocker. Imatinib Mesylate 123-131 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 7-12 19722748-3 2009 c-KIT (CD117)-positive mast cells have been associated with chronic fibrosing diseases and may potentially be treated with imatinib (Gleevec), a c-KIT blocker. Imatinib Mesylate 123-131 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 145-150 19722748-14 2009 The possible role of c-KIT inhibitors such as imatinib (Gleevec) in the progression of fibrosis preceding the development of obliterative bronchiolitis is discussed. Imatinib Mesylate 46-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-26 19706776-1 2009 Gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT or platelet-derived growth factor receptor A (PDGFRA), and treatment with the tyrosine kinase inhibitor imatinib yields responses in the majority of patients. Imatinib Mesylate 192-200 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 19505817-1 2009 PURPOSE: To evaluate the safety, efficacy and pharmacokinetics of imatinib in children with recurrent or refractory central nervous system (CNS) tumours expressing KIT and/or PDGFRA. Imatinib Mesylate 66-74 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 164-167 19505817-9 2009 Our results suggest a possible relationship between KIT expression and maintenance of SD with imatinib treatment; KIT immunopositivity was seen in only 58% (11/19) of study participants overall, but in 100% of patients with SD at 38 weeks. Imatinib Mesylate 94-102 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 19505817-13 2009 Demonstration of SD in previously progressing patients (KIT-expressing) suggests cytostatic activity of imatinib. Imatinib Mesylate 104-112 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 56-59 20079191-12 2009 The responsiveness to imatinib mesylate therapy correlates with the mutation status of c-kit gene. Imatinib Mesylate 22-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-92 19723893-3 2009 In vitro findings point out that L576P/KIT is constitutively activated, and shows poor imatinib sensitivity. Imatinib Mesylate 87-95 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 39-42 19723893-5 2009 In parallel, the affinities of wild-type, L576P/KIT, and Delta559/KIT for imatinib were estimated by in silico studies. Imatinib Mesylate 74-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 66-69 19723893-8 2009 Computer modeling proved that L576P/KIT is two times less sensitive than the wild-type counterpart and considerably less affine to imatinib than the sensitive Delta559/KIT. Imatinib Mesylate 131-139 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 36-39 19620409-0 2009 Residual and recurrent gastrointestinal stromal tumors with KIT mutations: findings at first follow-up CT after imatinib treatment. Imatinib Mesylate 112-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 19620409-1 2009 OBJECTIVE: The purpose of this study was to correlate findings on the first follow-up CT after treatment with imatinib in patients with residual or recurrent gastrointestinal stromal tumors (GISTs) with the different types of KIT mutation present at initial resection. Imatinib Mesylate 110-118 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 226-229 19620409-2 2009 CONCLUSION: Residual and recurrent GISTs with KIT mutation of exon 11 deletion more frequently showed both tumor shrinkage and cystic change on 2-month follow-up CT images after the start of imatinib treatment than did other mutation types. Imatinib Mesylate 191-199 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-49 19617296-5 2009 Receptor tyrosine-kinase inhibitors (imatinib, dasatinib, sunitinib) may have a role in treatment of patients with melanoma harbouring c-Kit mutations. Imatinib Mesylate 37-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 135-140 19671763-5 2009 Molecular modeling studies found that the L576P mutation induces structural changes in KIT that reduce the affinity for imatinib (DeltaDeltaGbind = -2.52 kcal/mol) but not for dasatinib (DeltaDeltaGbind = +0.32 kcal/mol). Imatinib Mesylate 120-128 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-90 18990444-0 2009 A phase II trial of high-dose imatinib mesylate for relapsed or refractory c-kit positive and Bcr-Abl negative acute myeloid leukaemia: the AFR-15 trial. Imatinib Mesylate 30-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-80 20021947-6 2009 CONCLUSION: The mechanism of imatinib mesylate resistance after initial treatment with this agent in gastrointestinal stromal tumors is a novel mutation development in kinase domain of c-kit. Imatinib Mesylate 29-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 185-190 19276970-2 2009 High frequency of reported KIT reactivity by immunohistochemistry (IHC) in part prompted the initiation of a phase 2 clinical trial of imatinib mesylate (Gleevec, Novartis Pharmaceuticals, East Hanover, NJ) for the treatment of advanced MCC. Imatinib Mesylate 135-152 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 27-30 19620796-5 2009 The therapy of choice for resectable GIST is still surgery, but at present we can use imatinib, a selective tyrosine kinase inhibitor for KIT, PDGFRs and Bcr-Abl, for such advanced GIST patients. Imatinib Mesylate 86-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-141 19383029-2 2009 Most of the constitutively active KIT can be inhibited by imatinib; D816V KIT cannot. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 19383029-5 2009 Imatinib-sensitive HMC-1.1 cells harboring the mutation V560G in the juxtamembrane domain of KIT, imatinib-resistant HMC-1.2 cells harboring both V560G and D816V mutations, and murine P815 cells, were treated with triptolide, and analyzed in terms of growth, apoptosis, and signal transduction. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-96 19383029-5 2009 Imatinib-sensitive HMC-1.1 cells harboring the mutation V560G in the juxtamembrane domain of KIT, imatinib-resistant HMC-1.2 cells harboring both V560G and D816V mutations, and murine P815 cells, were treated with triptolide, and analyzed in terms of growth, apoptosis, and signal transduction. Imatinib Mesylate 98-106 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-96 19383029-11 2009 Our data demonstrate that triptolide inhibits imatinib-resistant mast cells harboring D816V KIT. Imatinib Mesylate 46-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-95 19620796-7 2009 Secondary mutations of the c-kit gene in addition to primary c-kit gene mutation are a major cause of secondary resistance to imatinib. Imatinib Mesylate 126-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 27-32 19620796-7 2009 Secondary mutations of the c-kit gene in addition to primary c-kit gene mutation are a major cause of secondary resistance to imatinib. Imatinib Mesylate 126-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-66 19469547-2 2009 Clinical treatment with imatinib targets the kinase domain of KIT, but tumor regrowth occurs as a result of the development of resistant mutations in the kinase active site. Imatinib Mesylate 24-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-65 19258052-6 2009 Imatinib mesylate is a specific inhibitor of three tyrosine kinase receptors, two of which, PDGF-R and c-Kit, are implicated in the pathogenesis of intimal hyperplasia. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-108 20641611-3 2004 In addition, imatinib has been shown to be an effective treatment against a variety of other conditions that are characterized by the expression of abl, c-kit, or PDGF TKs (3). Imatinib Mesylate 13-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 153-158 19509176-3 2009 EXPERIMENTAL DESIGN: We grafted the human GIST882 cell line with KIT exon 13 mutation and two biopsies from patients radiologically progressing under imatinib showing KIT exon11 and KIT exon9 mutations, respectively. Imatinib Mesylate 150-158 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 167-170 19509176-3 2009 EXPERIMENTAL DESIGN: We grafted the human GIST882 cell line with KIT exon 13 mutation and two biopsies from patients radiologically progressing under imatinib showing KIT exon11 and KIT exon9 mutations, respectively. Imatinib Mesylate 150-158 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 167-170 19509233-4 2009 Gleevec (STI571, imatinib mesylate), in addition to the bcr-abl oncogene in chronic myelogenous leukemia, inhibits c-kit and platelet-derived growth factor receptor (PDGFR) signaling, thereby expanding its use to several malignant and benign human diseases. Imatinib Mesylate 17-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-120 21475850-0 2009 Secondary resistance to imatinib in patients with gastrointestinal stromal tumors through an acquired KIT exon 17 mutation. Imatinib Mesylate 24-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-105 21475850-7 2009 In conclusion, the exon 17 missense mutation T2467G in the tyrosine kinase domain of the KIT gene is correlated with imatinib resistance. Imatinib Mesylate 117-125 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-92 19299048-6 2009 Inhibitors of KIT, a membrane receptor, are mainly represented by imatinib, an inhibitor of tyrosine kinase. Imatinib Mesylate 66-74 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 19417561-4 2009 In GIST-T1 IR cells, KIT and its downstream signaling molecules remained phosphorylated with the presence of 1 microM imatinib, and no new mutations were found in KIT, PDGFRA, PKCtheta and JAK2. Imatinib Mesylate 118-126 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-24 19417561-9 2009 We report for the first time that the mechanism of imatinib-resistant GISTs, at least in one cell line, involves KIT/Cas-L/SRC signaling. Imatinib Mesylate 51-59 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 113-116 19010635-1 2009 AIM: The use of a non-toxic tyrosine kinase receptor inhibitor, Imatinib Mesylate (IM), has become an ever-more common therapeutic alternative in some Kit (CD117) over-expressing neoplasms. Imatinib Mesylate 64-81 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 156-161 19580708-2 2009 INTRODUCTION: GISTs, a new nosological entity recently described, represent a peculiar model of solid tumor: the identification of the molecular mechanism responsible for the oncogenesis led to the development of a new drug (imatinib) active on the specific molecular target, represented by the product of the mutated proto-oncogene c-kit which is a tyrosine kinase receptor that becomes constitutively active by mutation. Imatinib Mesylate 225-233 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 318-338 19961019-8 2009 The mutations of c-kit influences the therapeutic effects of imatinib. Imatinib Mesylate 61-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-22 19411681-14 2009 Compared with previous studies in western populations, these results suggest that ethnic differences may influence the relationship between KIT genotype and clinical outcome to imatinib. Imatinib Mesylate 177-185 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 140-143 19335275-3 2009 With prolonged treatment imatinib resistance can develop, most likely due to secondary KIT mutations. Imatinib Mesylate 25-33 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-90 19390946-4 2009 RESULTS: All imatinib- as well as sunitinib-resistant lesions showed viable tumor cells strongly re-expressing the KIT protein. Imatinib Mesylate 13-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-118 19381023-6 2009 Inhibition of the KIT gene cis-mutations and antiangiogenesis activities may be essential for the strategy for Imatinib/Sunitinibresistant GIST. Imatinib Mesylate 111-119 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 19164557-0 2009 KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Imatinib Mesylate 64-72 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 19058199-1 2009 Imatinib is currently in early clinical trials as targeted therapy for relapsed neuroblastomas and other childhood solid tumors expressing platelet-derived growth factor receptors (PDGFR) or c-Kit. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 191-196 19236722-1 2009 BACKGROUND: Imatinib represents the first in a class of drugs targeted against chronic myelogenous leukemia to enter the clinic, showing excellent efficacy and specificity for Abl, Kit, and PDGFR kinases. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 181-184 19771231-5 2009 Thus RNAi targeted against Kit or its mutant form could be considered as a new antiproliferative agent against human mast leukemia cell lines, especially HMC1.2 cells which are resistant to the Kit tyrosine kinase inhibitor, imatinib mesylate. Imatinib Mesylate 225-242 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 27-30 19303137-2 2009 Imatinib mesylate is a small molecule that inhibits activation of the KIT and platelet-derived growth factor receptor alpha proteins, and is effective in first-line treatment of metastatic gastrointestinal stromal tumour. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-73 19035443-1 2009 Recent studies showed KIT gene aberrations in a substantial number of melanomas on acral skin and mucosa, suggesting the therapeutic benefit of tyrosine kinase inhibitors, such as imatinib. Imatinib Mesylate 180-188 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 19176456-2 2009 Patients who become resistant to imatinib treatment often develop secondary mutations, the most common of which results in a substitution of isoleucine for threonine at the same location in the ATP-binding domain in all three kinases (in KIT this occurs at amino acid 670). Imatinib Mesylate 33-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 238-241 19176456-5 2009 The resulting mutant KIT proteins were transiently expressed in COS1 African green monkey kidney cells grown with and without imatinib, and cell extracts were analyzed for KIT activation by immunoprecipitation and immunoblotting to determine autophosphorylation levels. Imatinib Mesylate 126-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-24 19176456-6 2009 We also performed molecular modeling to estimate the relative affinities of wild-type (Thr670) KIT and the KIT mutants for ATP and imatinib. Imatinib Mesylate 131-139 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-98 19176456-6 2009 We also performed molecular modeling to estimate the relative affinities of wild-type (Thr670) KIT and the KIT mutants for ATP and imatinib. Imatinib Mesylate 131-139 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 107-110 19176456-10 2009 CONCLUSIONS: This combination of in vitro and molecular modeling analyses shows why, among all possible amino acid substitutions at position 670 of KIT, only Ile is naturally selected as a resistance mutant in imatinib-treated GIST patients. Imatinib Mesylate 210-218 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 148-151 19164557-2 2009 The efficacy of the inhibitors imatinib mesylate and sunitinib malate in GIST patients has been linked to their inhibition of these mutant KIT proteins. Imatinib Mesylate 31-48 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 139-142 19164557-3 2009 However, patients on imatinib can acquire secondary KIT mutations that render the protein insensitive to the inhibitor. Imatinib Mesylate 21-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 19182535-1 2009 The tyrosine kinase (TK) inhibitor, imatinib, has revolutionized therapy of malignancies that are addicted to one of its target kinases, c-abl, c-kit and PDGF-R. Imatinib Mesylate 36-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 144-149 18607592-5 2009 There is an interest to use imatinib mesylate in the treatment of c-kit positive ESS. Imatinib Mesylate 28-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 66-71 19222892-2 2009 These tumors are characterized by somatic mutations of c-KIT (CD117), a proto-oncogene that encodes a receptor tyrosine kinase normally expressed in the interstitial cell of Cajal that control the GI smooth muscle peristalsis, and an exquisite sensitivity to the action of the tyrokinase inhibitor imatinib mesylate (STI571; Gleevec). Imatinib Mesylate 298-315 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 55-60 19222892-2 2009 These tumors are characterized by somatic mutations of c-KIT (CD117), a proto-oncogene that encodes a receptor tyrosine kinase normally expressed in the interstitial cell of Cajal that control the GI smooth muscle peristalsis, and an exquisite sensitivity to the action of the tyrokinase inhibitor imatinib mesylate (STI571; Gleevec). Imatinib Mesylate 298-315 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-67 19222892-2 2009 These tumors are characterized by somatic mutations of c-KIT (CD117), a proto-oncogene that encodes a receptor tyrosine kinase normally expressed in the interstitial cell of Cajal that control the GI smooth muscle peristalsis, and an exquisite sensitivity to the action of the tyrokinase inhibitor imatinib mesylate (STI571; Gleevec). Imatinib Mesylate 317-323 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 55-60 19222892-2 2009 These tumors are characterized by somatic mutations of c-KIT (CD117), a proto-oncogene that encodes a receptor tyrosine kinase normally expressed in the interstitial cell of Cajal that control the GI smooth muscle peristalsis, and an exquisite sensitivity to the action of the tyrokinase inhibitor imatinib mesylate (STI571; Gleevec). Imatinib Mesylate 317-323 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-67 19186237-2 2009 Although rare as a clinical entity, there is much interest in the pathology and treatment because the KIT protooncogene mutation common to most GISTs can be inhibited by imatinib mesylate. Imatinib Mesylate 170-187 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-105 19248972-2 2009 Although surgery remains the principle treatment of primary localized GIST, imatinib mesylate, a selective inhibitor of KIT protein, achieves dramatic responses in metastatic GIST. Imatinib Mesylate 76-93 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-123 19013895-2 2008 Indeed, imatinib mesylate inhibits KIT kinase activity and represents the front-line drug for the treatment of unresectable and metastatic GISTs. Imatinib Mesylate 8-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 35-38 20877672-18 2009 Imatinib inhibits PDGFR and c-kit. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-33 19118061-2 2009 These findings suggest KIT as a potential target for therapy with imatinib mesylate in these melanomas. Imatinib Mesylate 66-83 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-26 19118061-7 2009 This overexpression of both KIT and SCF suggests the clinical application of imatinib mesylate in metastatic UM. Imatinib Mesylate 77-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-31 18814279-1 2009 Imatinib mesylate (imatinib) is a potent and selective inhibitor of the tyrosine kinases, Bcr-Abl, c-Kit and platelet-derived growth factor receptors (PDGFRs). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-104 18814279-1 2009 Imatinib mesylate (imatinib) is a potent and selective inhibitor of the tyrosine kinases, Bcr-Abl, c-Kit and platelet-derived growth factor receptors (PDGFRs). Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-104 19915299-0 2009 Successful treatment of KIT D816V-positive, imatinib-resistant systemic mastocytosis with interferon-alpha. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 18973210-0 2009 Oncogenic and ligand-dependent activation of KIT/PDGFRA in surgical samples of imatinib-treated gastrointestinal stromal tumours (GISTs). Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-48 19073506-1 2008 BACKGROUND: Imatinib mesylate is a potent inhibitor of the Bcr-Abl, c-Kit, and platelet-derived growth factor receptor (PDGFR) tyrosine kinases. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-73 19047099-0 2008 Imatinib targeting of KIT-mutant oncoprotein in melanoma. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 19047099-3 2008 We recently reported a patient with metastatic mucosal melanoma harboring a known KIT mutation treated with imatinib mesylate who experienced a major response. Imatinib Mesylate 108-125 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-85 19047099-9 2008 RESULTS: Mucosal melanoma cells exhibited imatinib sensitivity correlating with KIT mutational status. Imatinib Mesylate 42-50 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-83 19047099-10 2008 Imatinib dramatically decreased proliferation and was cytotoxic to a KIT mutated and amplified cell culture. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-72 19047099-13 2008 In vitro analyses revealed major sensitivity to KIT kinase inhibition by imatinib, with potent induction of melanoma cell apoptosis. Imatinib Mesylate 73-81 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-51 19669326-1 2008 Imatinib (Gleevec, Novartis), an inhibitor of BCR-ABL, platelet-derived growth factor, and KIT receptor tyrosine kinases, is widely used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 91-94 19034614-10 2008 D816V c-kit mutation is frequent and associated with resistance against Imatinib. Imatinib Mesylate 72-80 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 6-11 18551246-2 2008 Numerous preclinical data (for example, 75% of MUM express c-kit) suggest that imatinib mesylate (IM) may be a potential treatment of UMM. Imatinib Mesylate 79-96 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 59-64 18465140-1 2008 PURPOSE: Imatinib is a small molecule inhibiting the tyrosine kinases bcr-abl, c-kit, PDGFR-alpha and PDGFR-beta. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 79-84 18486988-2 2008 In patients with GIST, overexpression of mutated KIT within the tumor is predictive of response to molecular targeted therapy using imatinib. Imatinib Mesylate 132-140 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 18955451-9 2008 CONCLUSION: We confirmed the favorable impact of KIT exon 11 genotype when compared with KIT exon 9 and wild-type genotype for patients with advanced GIST who are treated with imatinib. Imatinib Mesylate 176-184 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 18955451-9 2008 CONCLUSION: We confirmed the favorable impact of KIT exon 11 genotype when compared with KIT exon 9 and wild-type genotype for patients with advanced GIST who are treated with imatinib. Imatinib Mesylate 176-184 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-92 18955458-1 2008 PURPOSE: Most gastrointestinal stromal tumors (GISTs) harbor mutant KIT or platelet-derived growth factor receptor alpha (PDGFRA) kinases, which are imatinib targets. Imatinib Mesylate 149-157 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-71 18955458-5 2008 KIT/PDGFRA mutational status was determined for 78 patients by using tumor specimens obtained before and after prior imatinib therapy. Imatinib Mesylate 117-125 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 18795925-11 2008 Compared with cells expressing wild-type KIT at a similar level, M541L KIT-expressing cells displayed enhanced growth at low levels of SCF, and heightened sensitivity to the KIT inhibitor, imatinib mesylate. Imatinib Mesylate 189-206 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-74 18795925-11 2008 Compared with cells expressing wild-type KIT at a similar level, M541L KIT-expressing cells displayed enhanced growth at low levels of SCF, and heightened sensitivity to the KIT inhibitor, imatinib mesylate. Imatinib Mesylate 189-206 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-74 18980976-1 2008 PURPOSE: We recently identified a KIT exon 11 mutation in an anorectal melanoma of a patient who had an excellent response to treatment with imatinib. Imatinib Mesylate 141-149 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 18980976-8 2008 Almost all the KIT mutations were of the type predicted to be imatinib sensitive. Imatinib Mesylate 62-70 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 15-18 19119132-5 2008 Hypopigmentation induced by imatinib mesylate with possible molecular blockage to a melanin-dependent KIT signal has been well documented; however, our case with repigmentation suggested that KIT signal of melanin formation would be much more sophisticated than we have believed. Imatinib Mesylate 28-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-105 19119132-5 2008 Hypopigmentation induced by imatinib mesylate with possible molecular blockage to a melanin-dependent KIT signal has been well documented; however, our case with repigmentation suggested that KIT signal of melanin formation would be much more sophisticated than we have believed. Imatinib Mesylate 28-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 192-195 18809244-1 2009 INTRODUCTION: Imatinib mesylate is a tyrosine kinase receptor inhibitor targeted against PDGFR alpha and beta, c-kit and bcr-abl. Imatinib Mesylate 14-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 111-116 19810774-2 2009 The introduction of imatinib, a tyrosine kinase inhibitor mainly targeting BCR-ABL, c-KIT and PDGFR, has profoundly improved the prognosis of both entities, while being surprisingly well tolerated. Imatinib Mesylate 20-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-89 20047122-2 2009 Cure can be obtained only by complete surgical removal of the GIST; however, imatinib, an inhibitor of KIT and PDGFRA, is indicated for advanced, recurrent, and/or metastatic GISTs. Imatinib Mesylate 77-85 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-106 19690756-8 2009 The treatment of localized GISTs is surgical resection and that of advanced or unresecable GISTs is based on the use of targeted therapy, imatinib, which is a pharmacological antagonist of the c-kit protein. Imatinib Mesylate 138-146 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 193-198 19096980-0 2009 Secondary C-kit mutation is a cause of acquired resistance to imatinib in gastrointestinal stromal tumor. Imatinib Mesylate 62-70 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-15 19096980-2 2009 Imatinib is a selective tyrosine kinase inhibitor of KIT and achieves a partial response or stable disease in most patients with metastatic GIST, but there is increasing evidence of acquired resistance. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-56 19696984-4 2009 Based upon currently available data, the Austrian GIST-Panel recommends adjuvant treatment with 400 mg Imatinib/day for 1 year for KIT positive GIST patients with a high or moderate risk of relapse (according to Joensuu) [10] following complete resection of the primary tumor. Imatinib Mesylate 103-111 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 131-134 18932293-1 2008 The molecular targets of sunitinib are receptor tyrosine kinases (RTKs), and this drug has also been known to exert blocking effects on the activation of KIT, which is similar to the mechanism of action of imatinib. Imatinib Mesylate 206-214 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 154-157 20641266-3 2004 In addition, imatinib has been shown to be an effective treatment against a variety of other conditions that are characterized by the expression of Abl or c-Kit TKs (3). Imatinib Mesylate 13-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 155-160 20641266-5 2004 Dasatinib is a dual inhibitor of Src/Abl and c-Kit that was recently approved for treatment of imatinib-refractory CML and Ph+ acute lymphoblastic leukemia (ALL) (5, 6). Imatinib Mesylate 95-103 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-50 18515258-0 2008 Imatinib mesylate (Gleevec) in advanced breast cancer-expressing C-Kit or PDGFR-beta: clinical activity and biological correlations. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 65-70 18515258-0 2008 Imatinib mesylate (Gleevec) in advanced breast cancer-expressing C-Kit or PDGFR-beta: clinical activity and biological correlations. Imatinib Mesylate 19-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 65-70 18515258-2 2008 Imatinib mesylate (Gleevec) inhibits several protein tyrosine kinases, including platelet-derived growth factor receptor (PDGFR) and c-kit, which are preferentially expressed in tumor cells. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 133-138 18515258-2 2008 Imatinib mesylate (Gleevec) inhibits several protein tyrosine kinases, including platelet-derived growth factor receptor (PDGFR) and c-kit, which are preferentially expressed in tumor cells. Imatinib Mesylate 19-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 133-138 18515258-3 2008 We tested the activity of imatinib mesylate in MBC with overexpression of PDGFR or c-kit. Imatinib Mesylate 26-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 83-88 18671247-6 2008 Gene mutations of KIT or PDGFRA are critical in GISTs, because the aberrant versions not only are correlated with the specific cell morphology, histologic phenotype, metastasis, and prognosis, but also are the targets of therapy with imatinib and other agents. Imatinib Mesylate 234-242 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 18657349-3 2008 Inhibitors of heat shock protein 90 (HSP90), a chaperone for which Kit is a client protein, have demonstrated activity against human cancers and evidence suggests they downregulate several mutated and imatinib-resistant forms of Kit. Imatinib Mesylate 201-209 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-70 18657349-3 2008 Inhibitors of heat shock protein 90 (HSP90), a chaperone for which Kit is a client protein, have demonstrated activity against human cancers and evidence suggests they downregulate several mutated and imatinib-resistant forms of Kit. Imatinib Mesylate 201-209 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 229-232 18787413-6 2008 c-kit inhibition by imatinib mesylate (Gleevec) in DCs was previously shown to promote natural killer cell activation which may be due to dampening of IL-6 production by the DCs. Imatinib Mesylate 20-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 18622894-2 2008 Imatinib mesylate offers an effective therapeutic option in patients with various types of malignancies by inhibiting tyrosine kinases such as c-kit. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 143-148 18728664-9 2008 However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined. Imatinib Mesylate 98-106 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 160-165 18567837-0 2008 Successful treatment of progressive cutaneous mastocytosis with imatinib in a 2-year-old boy carrying a somatic KIT mutation. Imatinib Mesylate 64-72 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 112-115 18567837-3 2008 C-kit receptor mutations have been identified as causative for CM, some of which potentially respond to imatinib treatment as described for patients with systemic mastocytosis. Imatinib Mesylate 104-112 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 2-5 18567837-5 2008 KIT gene analysis revealed not only a somatic deletion of codon 419 in exon 8 (c.1255_1257delGAC) which responds to imatinib therapy, but also a novel germ line p. Ser840Asn substitution encoded by exon 18 in the c-kit kinase domain. Imatinib Mesylate 116-124 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 18514495-1 2008 AIMS: Imatinib mesylate, a selective tyrosine kinase receptor inhibitor of KIT and PDGFRalpha, is currently licensed for the treatment of unresectable or metastatic gastrointestinal stromal tumours (GISTs), which are KIT positive. Imatinib Mesylate 6-23 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-78 18514495-1 2008 AIMS: Imatinib mesylate, a selective tyrosine kinase receptor inhibitor of KIT and PDGFRalpha, is currently licensed for the treatment of unresectable or metastatic gastrointestinal stromal tumours (GISTs), which are KIT positive. Imatinib Mesylate 6-23 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 217-220 18808562-3 2008 Imatinib has been reported previously to be useful for treatment of hypereosinophilic syndrome and may work by selectively blocking protein-tyrosine kinases, such as platelet-derived growth factor receptor, and c-Kit. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 211-216 18618737-15 2008 CONCLUSIONS: The combination imatinib and docetaxel was tolerated in patients with heavily pretreated EOC that expressed c-kit or PDGFRalpha. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 121-126 18234489-5 2008 Certain specific mutations in an exon (such as in exon 9) of the KIT gene result in GISTs that are relatively unresponsive to the Imatinib treatment. Imatinib Mesylate 130-138 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 65-68 18312355-4 2008 There are primary KIT or PDGFRA mutations diagnosed before imatinib treatment, linked to GIST pathogenesis, and secondary mutations detected during treatment, causing drug resistance. Imatinib Mesylate 59-67 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 18312355-7 2008 KIT exon 11 mutants respond well to imatinib. Imatinib Mesylate 36-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 18670317-3 2008 Imatinib mesylate is a tyrosine kinase inhibitor targeting the platelet-derived growth factor (PDGFR-alpha and PDGFR-beta), the BCR-ABL, and c-KIT receptors. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 141-146 18510589-0 2008 Dose-dependent, complete response to imatinib of a metastatic mucosal melanoma with a K642E KIT mutation. Imatinib Mesylate 37-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-95 18632627-5 2008 Pharmacologic studies showed the KIT/CDK4-overexpressing subgroup to be resistant to BRAF inhibitors but sensitive to imatinib in both in vitro and in vivo melanoma models. Imatinib Mesylate 118-126 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 33-36 18718191-1 2008 Imatinib mesylate, a tyrosine kinase inhibitor targeting the Bcr-Abl protein, c-kit (KIT) and the platelet-derived growth factor receptors (PDGFR), is an important part of the therapeutic armamentarium used in chronic myelogenous leukemia and gastrointestinal stromal tumors. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 78-83 18718191-1 2008 Imatinib mesylate, a tyrosine kinase inhibitor targeting the Bcr-Abl protein, c-kit (KIT) and the platelet-derived growth factor receptors (PDGFR), is an important part of the therapeutic armamentarium used in chronic myelogenous leukemia and gastrointestinal stromal tumors. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-88 18612157-9 2008 At least one target of imatinib (KIT, PDGFR-alpha, or PDGFR-beta) was expressed in all tumors, and most tumors expressed all three receptors. Imatinib Mesylate 23-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 33-36 18525320-0 2008 Decrease of CD117 expression as possible prognostic marker for recurrence in the resected specimen after imatinib treatment in patients with initially unresectable gastrointestinal stromal tumors: a clinicopathological analysis. Imatinib Mesylate 105-113 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-17 18525320-16 2008 Loss or decrease of CD117 expression in the resected specimen after imatinib treatment may be associated with disease recurrence. Imatinib Mesylate 68-76 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-25 18751412-1 2008 The case of a young man with stage IV chemoresistant pure seminoma overexpressing KIT, who achieved complete remission (CR) after the administration of imatinib mesylate (400 mg once daily), along with a third-line chemotherapy regimen, consisting of paclitaxel (150 mg/m2), oxaliplatin (100 mg/m2) and gemcitabine (800 mg/m2) every 2 weeks with granulocyte colony-stimulating factor (G-CSF) support is reported. Imatinib Mesylate 152-169 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-85 18066563-8 2008 Correct diagnosis is essential for proper management since GISTs specifically respond to the c-kit selective tyrosine kinase inhibitor, Imatinib mesylate. Imatinib Mesylate 136-153 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-98 18548219-1 2008 Imatinib is a tyrosine kinase inhibitor directed against the KIT and the PDGF-alpha receptors. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-64 18778561-2 2008 Imatinib provides targeted therapy for GIST by inhibiting the KIT and PDGFR-alpha tyrosine kinases. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-65 18778561-4 2008 The mechanisms of acquired resistance to imatinib are heterogeneous, with most involving the emergence of secondary mutations in KIT exons 13, 14, or 17. Imatinib Mesylate 41-49 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 129-132 18525340-1 2008 PURPOSE OF REVIEW: Gastrointestinal stromal tumour patients with exon 9 KIT mutations have a worse outcome, but progression-free survival is improved by treatment with imatinib 800 mg daily. Imatinib Mesylate 168-176 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-75 18525340-8 2008 Patients with mutations in exon 9 of KIT should be considered for treatment with imatinib 800 mg daily, but current data do not indicate whether there is a survival advantage for immediate treatment at 800 mg. Imatinib Mesylate 81-89 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-40 18061664-1 2008 Imatinib mesylate is a selective inhibitor of the bcr/abl, c-kit and PDGF receptor tyrosine kinases. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 59-64 18515176-4 2008 Successful examples of personalizing molecularly targeted therapies based on biomarkers include the use of trastuzumab in HER-2 overexpressing breast cancer and imatinib in c-KIT expressing gastrointestinal stromal tumor. Imatinib Mesylate 161-169 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 173-178 18346844-1 2008 Imatinib mesylate (imatinib) inhibits the c-Kit-dependent tyrosine kinase activities and highly effective in the treatment of CML and GIST patients. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-47 18346844-1 2008 Imatinib mesylate (imatinib) inhibits the c-Kit-dependent tyrosine kinase activities and highly effective in the treatment of CML and GIST patients. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-47 18281615-13 2008 The combination of 17-DMAG with imatinib mesylate, the inhibitor of c-kit, had synergistic inhibitory effects on cell proliferation in WT B-Raf uveal melanoma cell lines. Imatinib Mesylate 32-49 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-73 18553235-1 2008 BACKGROUND: Imatinib mesylate, an inhibitor of KIT, ABL protein, and platelet-derived growth factor receptor alpha (PDGFRalpha) tyrosine kinase, has recently been found to have a dramatic antitumor effect on gastrointestinal stromal tumor (GIST). Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-50 18381383-7 2008 Negative KIT expression was an independent prognostic factor in multivariate Cox regression analysis when the risk of aggressive behaviour and the status of imatinib treatment were adopted as covariates. Imatinib Mesylate 157-165 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 9-12 18359865-1 2008 We determined the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of imatinib mesylate, an inhibitor of the receptor tyrosine kinases platelet-derived growth factor receptor (PDGFR), the proto-oncogene product c-kit, and the fusion protein Bcr-Abl, when administered for 8 days in combination with temozolomide (TMZ) to malignant glioma (MG) patients. Imatinib Mesylate 83-100 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 224-229 18537751-3 2008 The introduction of imatinib mesylate (inhibiting KIT/PDGFRA (platelet-derived growth factor receptor-alpha) and their downstream signaling cascade) has revolutionized the therapy of advanced (inoperable and/or metastatic) GISTs. Imatinib Mesylate 20-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-53 18820368-1 2008 BACKGROUND: Imatinib mesylate (Gleevec, Novartis, Basel, Switzerland) is a small-molecule tyrosine kinase inhibitor with activity against ABL, BCR-ABL, c-KIT, and PDGFR alpha. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 152-157 18483389-9 2008 In vitro studies showed that nilotinib, sunitinib, dasatinib, and sorafenib are more effective than imatinib against WT KIT. Imatinib Mesylate 100-108 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-123 18362061-3 2008 Since the tumor was weakly positive for c-kit, she was treated with imatinib mesylate for the recurrent liver tumors. Imatinib Mesylate 68-85 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 40-45 18451237-11 2008 One patient with systemic mastocytosis and a partial response to therapy had a novel imatinib-sensitive KIT mutation (D816T). Imatinib Mesylate 85-93 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 104-107 18843975-0 2008 [Imatinib induces c-kit positive myeloma cells apoptosis]. Imatinib Mesylate 1-9 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-23 18421059-0 2008 Major response to imatinib mesylate in KIT-mutated melanoma. Imatinib Mesylate 18-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 39-42 18413817-1 2008 PURPOSE: Gastrointestinal stromal tumors (GIST) are frequently associated with gain-of-function mutations of KIT, which can be inhibited by imatinib both in vitro and in vivo. Imatinib Mesylate 140-148 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 109-112 18413817-7 2008 Imatinib-induced inhibition of the phosphorylation of immature and mature mutant KIT proteins resulted in the restoration of KIT expression at the cell surface. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 18413817-7 2008 Imatinib-induced inhibition of the phosphorylation of immature and mature mutant KIT proteins resulted in the restoration of KIT expression at the cell surface. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 125-128 18294292-0 2008 Secondary mutations in the kinase domain of the KIT gene are predominant in imatinib-resistant gastrointestinal stromal tumor. Imatinib Mesylate 76-84 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-51 18294292-5 2008 All pre-imatinib samples have KIT mutations either in exon 9 (n = 3) or exon 11 (n = 22), identified in the KIT gene of corresponding resistant tumors. Imatinib Mesylate 8-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-33 18516991-7 2008 The patient was treated with imatinib, a KIT tyrosine kinase inhibitor; however, the tumors progressed. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 41-44 18487909-5 2008 Imatinib (gleevec) is an oral agent that selectively inhibits c-Kit, whose efficacy proves that a specific inhibitor can counteract the effects of a genetic defect responsible for cancer. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-67 18843975-1 2008 OBJECTIVE: To explore the influence of Imatinib on multiple myeloma cells expressing c-kit in vitro and its mechanism. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-90 18843975-6 2008 Imatinib inhibited expression of c-kit and provoked a decrease of IL-6 induced c-kit phosphorylation in vitro. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 33-38 18843975-6 2008 Imatinib inhibited expression of c-kit and provoked a decrease of IL-6 induced c-kit phosphorylation in vitro. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 79-84 18843975-7 2008 CONCLUSION: Imatinib inhibits KM3 cells proliferation and induces the cells apoptosis by inhibiting c-kit signalling transduction. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-105 19688062-4 2008 STI-571 may constitute a promising therapeutic agent against neuroblastoma, particularly in cases in which c-Kit is expressed preferentially in MYCN-amplified neuroblastoma. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 107-112 19254884-2 2008 The first oral inhibitor of Brc-Abl was imatinib, which also targets KIT and platelet-derived growth factor receptor kinase and has demonstrated improved outcomes when compared with interferon, the previous standard of care. Imatinib Mesylate 40-48 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-72 18234488-4 2008 However, two groups benefited from the treatment with 800 mg/d of imatinib: patients with disease progression on standard-dose therapy, and patients whose tumour harbours an exon 9 mutation in KIT. Imatinib Mesylate 66-74 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 193-196 18234488-5 2008 Initial treatment with 800 mg/d of imatinib (400mg BID) should be considered for patients with KIT exon 9-mutant GIST. Imatinib Mesylate 35-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-98 18376233-3 2008 Imatinib, a potent inhibitor of BCR-ABL and c-kit, also inhibits the platelet-derived growth factor receptor tyrosine kinase. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-49 17943734-13 2008 Germ-line deletion of KIT codon 579 in GIST is associated with clinical benefit from imatinib, limited utility of mitoses to predict malignant potential, and a novel homozygous deletion of this codon in one individual. Imatinib Mesylate 85-93 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 17591671-2 2007 With the development of the compound imatinib mesylate, which specifically inhibits tyrosine kinase receptors, C-kit has emerged as a potential therapeutic target. Imatinib Mesylate 37-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 111-116 17827398-10 2008 The great majority of mutations were located in KIT exon 11, statistically associated with worse prognosis and indicative of favourable response to imatinib-based therapy in this Portuguese series of GISTs. Imatinib Mesylate 148-156 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-51 18235121-0 2008 Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. Imatinib Mesylate 83-100 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 189-192 18223230-2 2008 Imatinib mesylate (STI571; Glivec) is a selective inhibitor of tyrosine kinases as bcr-abl, c-kit, c-fms, and PDGFRbeta and enhances tumor drug uptake by reducing the interstitial fluid pressure. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-97 18223230-2 2008 Imatinib mesylate (STI571; Glivec) is a selective inhibitor of tyrosine kinases as bcr-abl, c-kit, c-fms, and PDGFRbeta and enhances tumor drug uptake by reducing the interstitial fluid pressure. Imatinib Mesylate 19-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-97 18230576-3 2008 Several studies have shown that response to imatinib in GIST patients mainly depends on the mutational status of KIT or PDGFR alpha. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 113-116 18648736-10 2008 The interrelationship between the type of Kit gain-of-function mutation and the therapeutic effect of imatinib has been well characterized in GISTs. Imatinib Mesylate 102-110 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-45 18648736-12 2008 After long-term administration of imatinib, however, new imatinib-resistant clones develop a secondary mutation of the Kit or Pdgfr-alpha gene. Imatinib Mesylate 34-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 119-122 18648736-12 2008 After long-term administration of imatinib, however, new imatinib-resistant clones develop a secondary mutation of the Kit or Pdgfr-alpha gene. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 119-122 17976614-0 2007 Complete response after treatment with imatinib in pretreated disseminated testicular seminoma with overexpression of c-KIT. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 118-123 17196360-6 2007 However, their molecular genetics, i.e. the mutations of the genes coding for KIT or platelet-derived growth factor receptor alpha, two receptor tyrosine kinases, have been targeted for therapeutic intervention by imatinib mesylate -- a tyrosine kinase inhibitor. Imatinib Mesylate 214-231 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 78-81 17922620-3 2007 Recent elucidation of the mechanisms of resistance to imatinib, particularly the acquisition of secondary mutations of the KIT and PDGF receptors, has provided significant insight and potential for the development of novel therapies. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-126 17701051-13 2007 Secondary resistance to imatinib treatment is increasing, at least partly due to secondary mutations in the tyrosine kinase domain of the KIT receptor. Imatinib Mesylate 24-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-141 17452978-3 2007 Tyrosine-phosphorylated KIT oncoproteins interacted with PDGFRA, PDGFRB, phosphatidylinositol 3-kinase (PI3-K) and PKCtheta in GIST cells, and these interactions were abolished by KIT inhibition with imatinib or PKC412 or KIT RNAi. Imatinib Mesylate 200-208 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 17554062-5 2007 Cholesterol depletion by methyl-beta-cyclodextrin prevented Kit-mediated activation of the PI3-K downstream target Akt and inhibited cellular proliferation by KL-activated or oncogenic Kit, including mutants resistant to the Kit inhibitor imatinib-mesylate. Imatinib Mesylate 239-256 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 18230575-1 2008 Imatinib mesylate (Gleevec, Glivec, Novartis, Basel, Switzerland) is a small molecule inhibitor of the tyrosine kinase c-abl, c-kit and the platelet derived growth factor receptor (PDGFR). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 126-131 18230575-3 2008 Given its activity against both c-kit and PDGFR kinases and its remarkable safety profile, imatinib has been "tried" in several solid tumors; results however have often been deceiving. Imatinib Mesylate 91-99 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 32-37 18230576-1 2008 Approximately 90 % of gastrointestinal tumors (GISTs) harbor an activating mutation in KIT or PDGFR alpha oncogene known to confer imatinib sensitivity. Imatinib Mesylate 131-139 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-90 18230576-2 2008 Imatinib is a tyrosine kinase inhibitor of KIT and PDGFRs that yields a 6-months progression-free survival (PFS) rate of 80 % in patients with advanced GISTs. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-46 17667967-1 2008 Gastrointestinal stromal tumors (GISTs) may be caused by germline mutations of the KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes and treated by Imatinib mesylate (STI571) or other protein tyrosine kinase inhibitors. Imatinib Mesylate 167-175 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 83-86 18592792-3 2008 Imatinib mesylate acts against a tyrosine kinase encoded by the KIT gene in GISTs, and is more effective in tumors expressing this protein. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-67 18405654-3 2008 Due to their expression of c-kit protein, a positive diagnosis as well as a specific targeted treatment by molecular biology (imatinib) are available. Imatinib Mesylate 126-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 27-32 18028988-5 2008 METHODS: The expression of the imatinib-sensitive tyrosine kinases, c-kit, c-Abl, PDGFR-alpha and PDGFR-beta, was determined using RT-PCR in a panel of GCT. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-73 18648736-8 2008 When we reported gain-of-function mutations of the Kit gene in GISTs, the inhibitory effect of imatinib on KIT was already known. Imatinib Mesylate 95-103 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-54 18648736-8 2008 When we reported gain-of-function mutations of the Kit gene in GISTs, the inhibitory effect of imatinib on KIT was already known. Imatinib Mesylate 95-103 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 107-110 18792672-2 2008 The discovery of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of imatinib mesylate, a specific inhibitor of KIT tyrosine kinase function have revolutionized the treatment of GIST. Imatinib Mesylate 104-121 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 147-150 18085368-0 2008 Secondary c-kit mutation in a recurrent gastrointestinal stromal tumor under long-term treatment with imatinib mesylate: report of a case. Imatinib Mesylate 102-119 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-15 18085368-1 2008 Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the c-kit receptor gene, which are targets for imatinib mesylate. Imatinib Mesylate 126-143 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 83-88 18239881-9 2008 To preserve the anus, a rectal GIST expressing the c-kit gene is best treated with Imatinib as neoadjuvant therapy. Imatinib Mesylate 83-91 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-56 18061581-3 2007 In particular, imatinib inhibits Bcr-Abl kinase activity, c-kit and the phosphorylation of platelet-derived growth factor (PDGF) receptors. Imatinib Mesylate 15-23 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-63 18056005-0 2007 Imatinib mesylate in the treatment of newly diagnosed or refractory/resistant c-KIT positive acute myeloid leukemia. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 78-83 18265633-9 2007 In view of the result that c-kit protein expression was found in 8% of IDC of the pancreas, a clinical trial for STI-571 (Glivec) against pancreatic cancer may be warranted for selected pancreatic cancer patients with c-kit protein expression. Imatinib Mesylate 113-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 27-32 18265633-9 2007 In view of the result that c-kit protein expression was found in 8% of IDC of the pancreas, a clinical trial for STI-571 (Glivec) against pancreatic cancer may be warranted for selected pancreatic cancer patients with c-kit protein expression. Imatinib Mesylate 113-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 218-223 18060038-3 2007 The lack of specificity of the anticancer drug imatinib enables it to be used to treat chronic myeloid leukemia, where its target is the Bcr-Abl kinase, as well as a proportion of gastrointestinal stromal tumors (GISTs), where its target is the C-Kit kinase. Imatinib Mesylate 47-55 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 245-250 18060038-5 2007 Motivated by this finding, we made a modification to imatinib that hampers Bcr-Abl inhibition; refocuses the impact on the C-Kit kinase; and promotes inhibition of an additional target, JNK, a change that is required to reinforce prevention of cardiotoxicity. Imatinib Mesylate 53-61 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-128 17546049-0 2007 KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway. Imatinib Mesylate 38-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 17546049-1 2007 Most gastrointestinal stromal tumor (GIST) patients respond to KIT inhibition with imatinib, yet will eventually exhibit resistance. Imatinib Mesylate 83-91 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-66 17546049-2 2007 Imatinib-resistance mechanisms are heterogeneous, and little is known about KIT functional roles in imatinib-resistant GIST. Imatinib Mesylate 100-108 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 76-79 17546049-6 2007 After treatment with 1 muM imatinib, residual KIT activation was 6- and 2.8-fold higher in GIST430 and GIST48, respectively, compared to GIST882. Imatinib Mesylate 27-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-49 17546049-10 2007 We conclude that GIST secondary KIT mutations can be associated with KIT hyperactivation and imatinib resistance. Imatinib Mesylate 93-101 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 32-35 17990362-11 2007 Given the resistance of this tumor to conventional chemotherapy and radiation, the incidence of the c-kit alteration may represent a novel approach to a gene-directed treatment using a c-kit inhibitor (STI571) similar to that which has been proposed in GISTs. Imatinib Mesylate 202-208 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-105 17990362-11 2007 Given the resistance of this tumor to conventional chemotherapy and radiation, the incidence of the c-kit alteration may represent a novel approach to a gene-directed treatment using a c-kit inhibitor (STI571) similar to that which has been proposed in GISTs. Imatinib Mesylate 202-208 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 185-190 17824795-0 2007 Imatinib in the management of multiple gastrointestinal stromal tumors associated with a germline KIT K642E mutation. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-101 17687201-2 2007 Imatinib mesilate, which efficiently inhibits BCR-ABL,and KIT as well as platelet-derived growth factor receptor (PDGF-R) kinases, is highly effective for clinical treatment of CML, Ph+ALL, and advanced GIST with good tolerability, respectively. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-61 17458563-0 2007 Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-105 17458563-1 2007 THE PURPOSE: To analyze the outcomes of treatment and factors predicting effects of imatinib (IM) therapy in inoperable/metastatic gastrointestinal stromal tumors (GIST) CD117(+) patients. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-175 17923802-1 2007 Imatinib mesylate is a selective competitive inhibitor of the bcr-abl tyrosine kinase and c-KIT. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-95 17805064-2 2007 Imatinib targets KIT expression, providing rationale for studying its role in combination with chemotherapy in SCLC in a multicenter phase II trial. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-20 17699867-3 2007 EXPERIMENTAL DESIGN: In vitro drug screening of stable Ba/F3 KIT mutants recapitulating the genotype of imatinib-resistant patients harboring primary and secondary KIT mutations was investigated. Imatinib Mesylate 104-112 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-64 17661208-2 2007 Most GISTs have an activating mutation in KIT or PDGFR-alpha and respond to treatment with imatinib mesylate (Gleevec, Novartis), a small molecule tyrosine kinase inhibitor that blocks downstream signaling of the mutated kinase. Imatinib Mesylate 91-108 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-45 17705809-0 2007 Inhibition of tyrosine kinases PDGFR and C-Kit by imatinib mesylate interferes with postnatal testicular development in the rat. Imatinib Mesylate 50-67 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 41-46 17453242-15 2007 There have been established four kinases (p210(bcr/abl), c-kit, PDGFR-alfa, PDGFR-beta) suggested as the target for imatinib mesylate. Imatinib Mesylate 116-124 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-62 17921955-2 2007 Approximately 80% of c-Kit mutations occur in exon 11, being a response factor to imatinib (Gleevec) therapy. Imatinib Mesylate 82-90 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-26 17921955-2 2007 Approximately 80% of c-Kit mutations occur in exon 11, being a response factor to imatinib (Gleevec) therapy. Imatinib Mesylate 92-99 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-26 17559139-0 2007 A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a phase II clinical study with proteomic profiling. Imatinib Mesylate 26-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-48 17311837-2 2007 Imatinib mesylate is a selective inhibitor of tyrosine kinases such as bcr-abl, c-Kit, c-Fms and platelet derived growth factor receptor beta (PDGFRbeta). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-85 17581316-2 2007 NCI-H69 cells expressed one of the receptor tyrosine kinases, c-Kit, and STI571 inhibited the cell growth and stem cell factor-induced phosphorylation of c-Kit. Imatinib Mesylate 73-79 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 154-159 17547845-4 2007 In vitro experiments, however, showed that mast cells carrying the D816V c-kit mutation were resistant to the prototypical tyrosine kinase inhibitor imatinib. Imatinib Mesylate 149-157 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-78 17546507-0 2007 Effect of imatinib mesylate in a patient with a metastatic gastrointestinal stromal tumor with a c-kit mutation in exon 11. Imatinib Mesylate 10-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 97-102 17708241-0 2007 Lack of activity of imatinib in two cases of KIT+ retroperitoneal liposarcoma. Imatinib Mesylate 20-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-48 17533389-1 2007 Palliative imatinib treatment has dramatically improved survival in patients with malignant gastrointestinal stromal tumours, particularly in patients with tumours harbouring activating KIT mutations. Imatinib Mesylate 11-19 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 186-189 18542042-4 2007 Imatinib (STI571), used in the treatment of unresectable GIST, selectively inhibits the enzymatic activity of the tyrosine kinase c-KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 130-135 18542042-4 2007 Imatinib (STI571), used in the treatment of unresectable GIST, selectively inhibits the enzymatic activity of the tyrosine kinase c-KIT. Imatinib Mesylate 10-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 130-135 18542042-5 2007 However, it is known that some mutations in the c-kit gene lead to resistance to imatinib. Imatinib Mesylate 81-89 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-53 17591808-6 2007 Most GISTs express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. Imatinib Mesylate 175-183 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-66 17591830-6 2007 Recently, dasatinib emerged as a potent inhibitor of imatinib-resistant protein tyrosine kinase (KIT) activation loop mutants and it is able to induce apoptosis in mast cell and leukemic cell lines expressing these mutations. Imatinib Mesylate 53-61 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 97-100 17575668-16 2007 Imatinib (anti c-Kit) can now be offered to patients presenting with recurrent GIST, if further surgery is deemed inappropriate. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 15-20 17533047-6 2007 RESULTS: Imatinib showed a specific time- and dose-dependent growth inhibitory effect on FDCP cells expressing JAK2(V617F), wherein we observed imatinib"s inactivation of JAK2, STAT5 and cKIT proteins. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 187-191 17533047-6 2007 RESULTS: Imatinib showed a specific time- and dose-dependent growth inhibitory effect on FDCP cells expressing JAK2(V617F), wherein we observed imatinib"s inactivation of JAK2, STAT5 and cKIT proteins. Imatinib Mesylate 144-152 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 187-191 17498050-6 2007 Inhibition of the most important growth factor receptor of human MCs, c-Kit, by the selective tyrosine kinase inhibitor imatinib mesylate, induces apoptosis of synovial tissue MCs. Imatinib Mesylate 120-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-75 17289809-3 2007 Depletion of endogenous c-Kit or inhibition of c-Kit enzymatic activity by imatinib mesylate prevented adhesion of EPCs to activated ECs both in vitro and in vivo, indicating that a functional c-Kit on EPCs is essential. Imatinib Mesylate 75-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-52 17289809-3 2007 Depletion of endogenous c-Kit or inhibition of c-Kit enzymatic activity by imatinib mesylate prevented adhesion of EPCs to activated ECs both in vitro and in vivo, indicating that a functional c-Kit on EPCs is essential. Imatinib Mesylate 75-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-52 17268837-15 2007 C-kit positive tumors respond extremely well to chemotherapy with Imatinib (Glivec, Gleevec) [10-12]. Imatinib Mesylate 66-74 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 17437861-2 2007 Approximately 80% of patients with metastatic GIST show at least some clinical response to the targeted small molecule KIT inhibitor imatinib. Imatinib Mesylate 133-141 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 119-122 17437861-3 2007 The response to imatinib is closely correlated with the presence and type of KIT mutation. Imatinib Mesylate 16-24 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-80 17437861-4 2007 GISTs with the most common KIT exon 11 mutations have the highest response rate by far, whereas GISTs lacking mutations in KIT or the alternative receptor tyrosine kinase PDGFRA show much lower rates of response to imatinib. Imatinib Mesylate 215-223 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-126 17437861-6 2007 Most patients who initially respond to imatinib become resistant and eventually progress, which coincides with the selection of imatinib-resistant secondary KIT mutations in the kinase domain. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 157-160 17437861-6 2007 Most patients who initially respond to imatinib become resistant and eventually progress, which coincides with the selection of imatinib-resistant secondary KIT mutations in the kinase domain. Imatinib Mesylate 128-136 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 157-160 17396139-2 2007 A compelling example is the use of small molecule drugs, such as imatinib (Gleevec), which inhibit the KIT tyrosine kinase in gastrointestinal stromal tumors (GIST). Imatinib Mesylate 65-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-106 17396139-2 2007 A compelling example is the use of small molecule drugs, such as imatinib (Gleevec), which inhibit the KIT tyrosine kinase in gastrointestinal stromal tumors (GIST). Imatinib Mesylate 75-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-106 17396139-6 2007 KIT was inhibited with imatinib, and mTOR with RAD001. Imatinib Mesylate 23-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 17360660-1 2007 Gastrointestinal stromal tumor (GIST) has emerged as a clinically distinct type of sarcoma with frequent overexpression and mutation of the c-Kit oncogene and a favorable response to imatinib mesylate [also known as STI571 (Gleevec)] therapy. Imatinib Mesylate 183-200 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 140-145 17139461-0 2007 Surgical management after neoadjuvant imatinib therapy in gastrointestinal stromal tumours (GISTs) with respect to imatinib resistance caused by secondary KIT mutations. Imatinib Mesylate 115-123 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 155-158 17139461-1 2007 BACKGROUND: In metastasized GISTs, resistance to imatinib after initial tumour response has been associated with observation of secondary mutations in the activation loop of KIT. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 174-177 17139461-2 2007 The aim of the current study was to evaluate the tumour response and observance of secondary KIT mutations in a case of GIST undergoing neoadjuvant imatinib therapy. Imatinib Mesylate 148-156 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-96 17139461-10 2007 Since resistance relevant secondary mutations of the activation loop of KIT may be observed after neoadjuvant imatinib therapy, the time elapse with preoperative imatinib therapy should be chosen as short as curative tumour resection or function sparing surgery can be carried out. Imatinib Mesylate 110-118 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-75 17139461-10 2007 Since resistance relevant secondary mutations of the activation loop of KIT may be observed after neoadjuvant imatinib therapy, the time elapse with preoperative imatinib therapy should be chosen as short as curative tumour resection or function sparing surgery can be carried out. Imatinib Mesylate 162-170 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-75 17240308-0 2007 KIT-negative undifferentiated endometrial sarcoma with the amplified epidermal growth factor receptor gene showing a temporary response to imatinib mesylate. Imatinib Mesylate 139-156 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 17240308-5 2007 Multiple regional recurrences around the urinary bladder were noted after 5 months, and treatment with imatinib mesylate was started, based on the provisional interpretation of KIT immunoreactivity on a biopsy specimen of the recurrent tumor. Imatinib Mesylate 103-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 177-180 17218776-5 2007 Treatment with either PD16839, an EGFr antagonist, or imatinib mesylate (Gleevec), a PDGFr, c-kit and bcr/abl antagonist, enhanced the anti-proliferative effects of rapamycin. Imatinib Mesylate 54-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-97 17208434-2 2007 These rare neoplasms are remarkably sensitive to the KIT and PDGFRA kinase inhibitors imatinib (also known as Gleevec) and sunitinib (Sutent), which have recently been approved as the standard therapeutic courses for patients with inoperable GIST. Imatinib Mesylate 86-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-56 17208434-4 2007 Imatinib and sunitinib resistance generally result from secondary mutations in the KIT and/or PDGFRA kinase domains. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 83-86 17305499-6 2007 Imatinib induces high response rates in patients associated with constitutive activation of ABL, PDGFRalpha, PDGFRbeta and some KIT mutants. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 128-131 17305499-7 2007 Other inhibitors under development are promising candidates for effective treatment of patients with constitutive activation of JAK2, FGFR1 and imatinib-resistant KIT mutants. Imatinib Mesylate 144-152 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 163-166 17438095-0 2007 c-Kit/PDGFRA gene status alterations possibly related to primary imatinib resistance in gastrointestinal stromal tumors. Imatinib Mesylate 65-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 17169414-12 2007 CONCLUSIONS: This study demonstrates that KIT transduces anti-apoptotic signals and its inhibition with imatinib may represent a valuable therapeutic strategy for sensitizing chemoresistant ovarian cancer. Imatinib Mesylate 104-112 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-45 17883045-13 2007 CD117 positive cases are ideal candidates for treatment with molecularly targeted specific chemotherapeutic agents, e.g., imatinib as these tumours are non-responsive to conventional chemotherapy. Imatinib Mesylate 122-130 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 17381803-0 2007 Merkel cell carcinoma: evaluation of KIT (CD117) expression and failure to demonstrate activating mutations in the C-KIT proto-oncogene - implications for treatment with imatinib mesylate. Imatinib Mesylate 170-187 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-120 17381803-2 2007 However, it is not known if MCCs have activating mutations in KIT that would make them responsive to treatment with imatinib mesylate. Imatinib Mesylate 116-133 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-65 17381803-9 2007 Imatinib mesylate is unlikely to provide effective therapy in MCC unless activating mutations in other areas of KIT or activating mutations in other related genes can be detected. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 112-115 17384206-1 2007 Gastrointestinal stromal tumors (GISTs) frequently harbor mutations in the KIT and PDGFRA genes, the presence and type of which correlate with the response to the kinase inhibitor imatinib mesylate. Imatinib Mesylate 180-197 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-78 17259998-0 2007 Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation. Imatinib Mesylate 89-97 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 19-24 17259998-0 2007 Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation. Imatinib Mesylate 89-97 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 121-124 17259998-7 2007 Imatinib, at a concentration of 10 microM, inhibited autophosphorylation of the mutant KIT with Val559Asp, but not that with the Val559Ile. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-90 17259998-9 2007 These results suggest that different mutations, even at the same codon, in juxtamembrane domain of the c-kit gene show different inhibitory effects of imatinib, and that patients with GISTs or mast cell neoplasms possessing this Val559Ile mutation are resistant to imatinib therapy. Imatinib Mesylate 151-159 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-108 17259998-9 2007 These results suggest that different mutations, even at the same codon, in juxtamembrane domain of the c-kit gene show different inhibitory effects of imatinib, and that patients with GISTs or mast cell neoplasms possessing this Val559Ile mutation are resistant to imatinib therapy. Imatinib Mesylate 265-273 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-108 17486696-0 2007 Not all c-kit mutations can be corrected by imatinib. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 8-13 17454792-3 2007 This tyrosine kinase can be semi-selectively inhibited by signal transduction inhibitors such as imatinib mesylate (Glivec), which is a competitive inhibitor of c-kit, c-abl, platelet-derived growth factor receptor-alpha (PDGFR-alpha) and PDGFR-beta, and abl-related gene (arg). Imatinib Mesylate 97-114 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 161-166 17454792-3 2007 This tyrosine kinase can be semi-selectively inhibited by signal transduction inhibitors such as imatinib mesylate (Glivec), which is a competitive inhibitor of c-kit, c-abl, platelet-derived growth factor receptor-alpha (PDGFR-alpha) and PDGFR-beta, and abl-related gene (arg). Imatinib Mesylate 116-122 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 161-166 17363589-2 2007 GISTs can be successfully treated with imatinib mesylate, a selective small-molecule protein kinase inhibitor that was first clinically approved to target the oncogenic BCR-ABL fusion protein kinase in chronic myelogenous leukemia, but which also potently inhibits KIT and PDGFR family members. Imatinib Mesylate 39-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 265-268 17285599-1 2007 BACKGROUND: Imatinib (IM) is a potent tyrosine kinase inhibitor of c-Kit. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-72 17355219-3 2007 One of the most clear examples is the identification of KIT and platelet-derived growth factor receptor-alpha kinase mutations in gastrointestinal stromal tumours, a subset of sarcomas arising from precursors of the interstitial cells of Cajal in the digestive tract, which led to the development of imatinib, sunitinib and other tyrosine kinase inhibitors for the treatment of solid tumours. Imatinib Mesylate 300-308 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 56-59 17049587-3 2007 The primary target of imatinib is c-kit, but the drug also inhibits PDGFR-alpha and PDGFR-beta. Imatinib Mesylate 22-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-39 17327598-0 2007 Imatinib in melanoma: a selective treatment option based on KIT mutation status? Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 17309464-1 2007 BACKGROUND: Imatinib mesylate (IM), the first-line treatment of chronic myeloid leukaemia (CML), is a tyrosine kinase inhibitor that targets those proteins involved in BCR-ABL signal transduction in CML, c-kit (KIT) and platelet-derived growth-factor (PDGFR) receptor. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 204-209 17309464-1 2007 BACKGROUND: Imatinib mesylate (IM), the first-line treatment of chronic myeloid leukaemia (CML), is a tyrosine kinase inhibitor that targets those proteins involved in BCR-ABL signal transduction in CML, c-kit (KIT) and platelet-derived growth-factor (PDGFR) receptor. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 211-214 17294421-12 2007 Endothelial cell and tumour cell expression of activated KIT might explain in part the responsiveness of glioblastomas to the combination of imatinib (an inhibitor of KIT) and hydroxyurea. Imatinib Mesylate 141-149 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-60 17294421-12 2007 Endothelial cell and tumour cell expression of activated KIT might explain in part the responsiveness of glioblastomas to the combination of imatinib (an inhibitor of KIT) and hydroxyurea. Imatinib Mesylate 141-149 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 167-170 17363509-3 2007 The kinase inhibitor imatinib potently inhibits c-KIT and is approved for treatment of GIST. Imatinib Mesylate 21-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-53 17363509-12 2007 Analysis of the crystal structure of imatinib in complex with the kinase domain of c-KIT predicts that the V654A substitution directly affects the binding of imatinib to the receptor. Imatinib Mesylate 37-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 83-88 17363509-12 2007 Analysis of the crystal structure of imatinib in complex with the kinase domain of c-KIT predicts that the V654A substitution directly affects the binding of imatinib to the receptor. Imatinib Mesylate 158-166 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 83-88 17363509-13 2007 Alternative c-KIT inhibitors, nilotinib (AMN107) and PKC412, were also less active on V560G/V654A c-KIT than on the V560G single mutant; however, nilotinib, like imatinib, potently inhibited the V560G mutant. Imatinib Mesylate 162-170 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-17 17363509-14 2007 PKC412 strongly inhibited imatinib-resistant D816V c-KIT. Imatinib Mesylate 26-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-56 17355866-0 2007 c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-66 17355866-1 2007 The cancer drug imatinib inhibits the tyrosine kinases c-Abl, c-Kit, and the PDGF receptor. Imatinib Mesylate 16-24 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-67 17355866-2 2007 Imatinib is less effective against c-Src, which is difficult to understand because residues interacting with imatinib in crystal structures of Abl and c-Kit are conserved in c-Src. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 151-156 17355866-2 2007 Imatinib is less effective against c-Src, which is difficult to understand because residues interacting with imatinib in crystal structures of Abl and c-Kit are conserved in c-Src. Imatinib Mesylate 109-117 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 151-156 17355866-3 2007 The crystal structure of the c-Src kinase domain in complex with imatinib closely resembles that of Abl*imatinib and c-Kit*imatinib, and differs significantly from the inactive "Src/CDK" conformation of the Src family kinases. Imatinib Mesylate 65-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-122 17582306-1 2007 Imatinib (Glivec) is a specific inhibitor of tyrosine kinase receptor, in particular of the proto-oncogene c-kit. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-112 17582306-1 2007 Imatinib (Glivec) is a specific inhibitor of tyrosine kinase receptor, in particular of the proto-oncogene c-kit. Imatinib Mesylate 10-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-112 17279309-1 2007 Imatinib, a tyrosine kinase inhibitor directed against the enzymatic domain of KIT protein, was found to produce dramatic clinical responses in metastatic gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 79-82 17633880-3 2007 The developement of a tyrosine kinase inhibitor, STI571/imatinib mesylate/Gleevec, Glivec which inhibits the BCR-ABL, PDGF-R alpha, and C-Kit receptors, has changed the management of unresectable malignant GIST and has improved the survival of patients with metastaic disease. Imatinib Mesylate 49-55 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 136-141 17633880-3 2007 The developement of a tyrosine kinase inhibitor, STI571/imatinib mesylate/Gleevec, Glivec which inhibits the BCR-ABL, PDGF-R alpha, and C-Kit receptors, has changed the management of unresectable malignant GIST and has improved the survival of patients with metastaic disease. Imatinib Mesylate 56-64 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 136-141 17145623-2 2007 Approximately 80% of c-Kit mutations occur in exon 11, being a response factor to imatinib (Gleevec) therapy. Imatinib Mesylate 82-90 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-26 17145623-2 2007 Approximately 80% of c-Kit mutations occur in exon 11, being a response factor to imatinib (Gleevec) therapy. Imatinib Mesylate 92-99 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-26 16912224-2 2007 Whereas KIT juxtamembrane domain mutations seen in most patients with GIST are highly sensitive to imatinib, the kinase activation loop mutant D816V, frequently encountered in SM, hampers the binding ability of imatinib. Imatinib Mesylate 99-107 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 8-11 17352263-5 2007 Imatinib mesylate inhibited the proliferation of MFH cells that expressed PDGFRs and/or c-Kit. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 88-93 17352263-8 2007 Immunohistochemistry was used to analyze the inhibitory effect of imatinib mesylate on phosphorylation of PDGFRs and c-Kit in vivo. Imatinib Mesylate 66-74 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-122 17352263-11 2007 Imatinib mesylate inhibited PDGFRs and c-Kit phosphorylation in TNMY1 cells affecting the tumorigenicity, in the control group (139 mm3 SD +/- 1.03) and treatment group (126.2 mm3 SD +/- 1.63) but did not affect the tumorigenicity of Nara H cells. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 39-44 17352263-12 2007 CONCLUSION: Imatinib mesylate reduced in vivo tumor growth of MFH that express PDGFRs and c-Kit associated with phosphorylation suppression. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-95 17200352-13 2007 Second-site KIT mutations are rare in imatinib-responsive GISTs compared with imatinib-resistant tumors. Imatinib Mesylate 38-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-15 17607922-2 2007 Imatinib can block the activated receptor tyrosine kinase activity of c-kit. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-75 17346159-10 2007 Imatinib (STI571), which is a selective tyrosine kinase inhibitor and particularly of c-Kit and PDGF-R, exhibited encouraging results in respect to its inhibitory effect in cell growth and invasion potential in a panel of human breast cancer cell lines. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 86-91 17346159-10 2007 Imatinib (STI571), which is a selective tyrosine kinase inhibitor and particularly of c-Kit and PDGF-R, exhibited encouraging results in respect to its inhibitory effect in cell growth and invasion potential in a panel of human breast cancer cell lines. Imatinib Mesylate 10-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 86-91 17229632-8 2007 The imatinib-resistant KIT(D816V) mutant, associated with systemic mastocytosis, was found to be resistant to sorafenib. Imatinib Mesylate 4-12 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-28 16757202-3 2007 Imatinib mesylate (Gleevec) inhibits several protein-tyrosine kinases, including c-kit. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-86 16757202-3 2007 Imatinib mesylate (Gleevec) inhibits several protein-tyrosine kinases, including c-kit. Imatinib Mesylate 19-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-86 17298867-4 2007 Imatinib is a selective inhibitor of KIT, PDGFR, and ABL tyrosine kinase activity and exerts different anti-tumor effects according to the regions of mutations in c-kit and PDGFR genes. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-40 17298867-4 2007 Imatinib is a selective inhibitor of KIT, PDGFR, and ABL tyrosine kinase activity and exerts different anti-tumor effects according to the regions of mutations in c-kit and PDGFR genes. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 163-168 17607922-8 2007 Sunitinib, another tyrosine kinase inhibitor, seems to be useful especially in patients with exon 9 mutations of c-kit, who usually have a worse response to imatinib. Imatinib Mesylate 157-165 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 113-118 18314611-2 2007 One very effective tyrosine kinase inhibitor is imatinib mesylate inhibiting the KIT receptor tyrosine kinase in gastrointestinal stromal tumors (GISTs) which often carry activating mutations in the KIT gene. Imatinib Mesylate 48-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 18314612-9 2007 The expression of KIT in neoplastic MC has led to the development of targeted therapies using tyrosine kinase inhibitors (TKI) like STI571 (Imatinib, Gleevec). Imatinib Mesylate 140-148 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 18314611-2 2007 One very effective tyrosine kinase inhibitor is imatinib mesylate inhibiting the KIT receptor tyrosine kinase in gastrointestinal stromal tumors (GISTs) which often carry activating mutations in the KIT gene. Imatinib Mesylate 48-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 199-202 18314611-6 2007 RESULTS: The best response to treatment with imatinib is achieved in GISTs with an underlying KIT mutation in exon 11 encoding the juxtamembranous domain. Imatinib Mesylate 45-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 94-97 18314612-9 2007 The expression of KIT in neoplastic MC has led to the development of targeted therapies using tyrosine kinase inhibitors (TKI) like STI571 (Imatinib, Gleevec). Imatinib Mesylate 132-138 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 16983347-15 2006 Our data indicate that imatinib sensitizes T1 cells by directly downregulating c-FLIP(L), with the use of an alternative pathway for antitumor activity, because PDGFRalpha is not activated in T1 cells and these cells do not express c-kit, c-ABL or PDGFRbeta. Imatinib Mesylate 23-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 232-237 17217104-2 2006 The reason for this is explanation of the pathogenetic mechanism of tumor growth by activation of c-Kit protein, followed by a rationally designed suppressor, a drug named imatinib. Imatinib Mesylate 172-180 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-103 17044945-15 2006 CONCLUSION: Our results demonstrated that the SCF-KIT pathway enhanced the proliferation and invasiveness in KIT-positive pancreatic cancer cell lines and that the enhanced proliferation and invasion were inhibited by imatinib mesylate. Imatinib Mesylate 218-235 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-53 17040960-1 2006 BACKGROUND: The 2447 A > T pathogenic variation at codon 816 of exon 17 (D816V) in the KIT gene, occurring in systemic mastocytosis (SM), leads to constitutive activation of tyrosine kinase activity and confers resistance to the tyrosine kinase inhibitor imatinib mesylate. Imatinib Mesylate 258-275 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-93 17178293-3 2006 The dysregulated KIT protein is oncogenic and is an ideal target for imatinib, a KIT-selective inhibitor. Imatinib Mesylate 69-77 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-20 17178293-3 2006 The dysregulated KIT protein is oncogenic and is an ideal target for imatinib, a KIT-selective inhibitor. Imatinib Mesylate 69-77 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 17101065-2 2006 Imatinib, a specific inhibitor of the aberrant KIT protein, is an approved, well-tolerated oral drug for the management of metastatic or inoperable GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-50 17032555-7 2006 Imatinib, a potent inhibitor of KIT activity, is now standard front-line therapy for advanced GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 32-35 16942767-9 2006 In contrast, under defined conditions in organ cultures of metanephric kidneys, c-kit-positive cells, including the Flk-1-positive subset, undergo apoptosis after treatment with STI-571, an inhibitor of c-kit tyrosine phosphorylation. Imatinib Mesylate 178-185 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-85 16942767-9 2006 In contrast, under defined conditions in organ cultures of metanephric kidneys, c-kit-positive cells, including the Flk-1-positive subset, undergo apoptosis after treatment with STI-571, an inhibitor of c-kit tyrosine phosphorylation. Imatinib Mesylate 178-185 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 203-208 17001705-6 2006 As a very tangible example of how translational research has led to a marked improvement in patient outcome, the signal transduction inhibitor imatinib (a tyrosine kinase inhibitor of c-kit and PDGF) was administered to patients with KS whose tumors were serially biopsied. Imatinib Mesylate 143-151 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 184-189 16840725-0 2006 Newly identified c-KIT receptor tyrosine kinase ITD in childhood AML induces ligand-independent growth and is responsive to a synergistic effect of imatinib and rapamycin. Imatinib Mesylate 148-156 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-22 16908071-0 2006 Identification of a c-kit exon 8 internal tandem duplication in a feline mast cell tumor case and its favorable response to the tyrosine kinase inhibitor imatinib mesylate. Imatinib Mesylate 154-171 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-25 17085664-9 2006 The limited spectrum of TKI-resistant mutations in EGFR, which binds to erlotinib in the active conformation, contrasts with a wider range of second-site mutations seen with acquired resistance to imatinib, which binds to ABL and KIT, respectively, in closed conformations. Imatinib Mesylate 197-205 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 230-233 17419150-0 2006 Beyond imatinib: second generation c-KIT inhibitors for the management of gastrointestinal stromal tumors. Imatinib Mesylate 7-15 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 35-40 17419150-3 2006 Therapeutically, metastatic GISTs are effectively treated by imatinib, a tyrosine kinase inhibitor (TKI) with activity against KIT and platelet-derived growth factor receptor. Imatinib Mesylate 61-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 127-130 17065430-0 2006 Allele-specific polymerase chain reaction for the imatinib-resistant KIT D816V and D816F mutations in mastocytosis and acute myelogenous leukemia. Imatinib Mesylate 50-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-72 17065430-2 2006 The D816V substitution in the activation loop of KIT results in relative resistance to the kinase inhibitor imatinib (Gleevec). Imatinib Mesylate 108-116 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 17065430-2 2006 The D816V substitution in the activation loop of KIT results in relative resistance to the kinase inhibitor imatinib (Gleevec). Imatinib Mesylate 118-125 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 17077361-0 2006 Re: Response of a KIT-positive extra-abdominal fibromatosis to imatinib mesylate and KIT genetic analysis. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 16797704-5 2006 AMN107 was also as effective as imatinib in inhibiting phosphorylation of c-kit in HMC-1(560) cells. Imatinib Mesylate 32-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-79 16797704-7 2006 Based upon our results, AMN107 and imatinib are equipotent against mast cells with wild-type c-kit and those harboring the juxtamembrane D560G c-kit mutant but have no significant activity over the dose range tested against cells expressing the c-kit D816V mutant tyrosine kinase. Imatinib Mesylate 35-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-98 16954519-1 2006 PURPOSE: Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib. Imatinib Mesylate 176-184 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-95 16954519-6 2006 Secondary kinase mutations of KIT or PDGFRA that were identified in imatinib-resistant GISTs were biochemically profiled for imatinib sensitivity. Imatinib Mesylate 68-76 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-33 16954519-8 2006 Imatinib-resistant tumors had levels of activated KIT that were similar to or greater than those typically found in untreated GISTs. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-53 16954519-12 2006 Using RNAi technology, we demonstrated that imatinib-resistant GIST cells remain dependent on KIT kinase activity for activation of critical downstream signaling pathways. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 94-97 16751810-0 2006 Functional analyses and molecular modeling of two c-Kit mutations responsible for imatinib secondary resistance in GIST patients. Imatinib Mesylate 82-90 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-55 16964380-11 2006 Therefore, in the subset of CRC patients with concomitant KIT/SCF expression, the activity of Imatinib mesylate, a selective inhibitor of specific tyrosine kinases including KIT, may be exploited in combination with standard therapy. Imatinib Mesylate 94-111 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-61 16964380-11 2006 Therefore, in the subset of CRC patients with concomitant KIT/SCF expression, the activity of Imatinib mesylate, a selective inhibitor of specific tyrosine kinases including KIT, may be exploited in combination with standard therapy. Imatinib Mesylate 94-111 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 174-177 16924245-4 2006 More recently, imatinib has been used to inhibit KIT in gastrointestinal (GI) stromal tumor, a mesenchymal tumor that arises in the GI tract. Imatinib Mesylate 15-23 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 16981009-2 2006 Imatinib mesylate (imatinib) is a tyrosine kinase inhibitor developed to treat Bcr/Abl-expressing leukemias and subsequently found to treat c-Kit-expressing gastrointestinal stromal tumors. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 140-145 16981009-2 2006 Imatinib mesylate (imatinib) is a tyrosine kinase inhibitor developed to treat Bcr/Abl-expressing leukemias and subsequently found to treat c-Kit-expressing gastrointestinal stromal tumors. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 140-145 16981009-4 2006 We further show that micromolar concentrations of imatinib abrogate multiple signal transduction pathways implicated in RA pathogenesis, including mast cell c-Kit signaling and TNF-alpha release, macrophage c-Fms activation and cytokine production, and fibroblast PDGFR signaling and proliferation. Imatinib Mesylate 50-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 157-162 16460801-1 2006 Imatinib mesylate has recently been reported to have clinical activity in the treatment of polycythemia vera (PV), suggesting the involvement of one of the kinases targeted by this inhibitor, including c-Kit and PDGFR. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 202-207 17044945-15 2006 CONCLUSION: Our results demonstrated that the SCF-KIT pathway enhanced the proliferation and invasiveness in KIT-positive pancreatic cancer cell lines and that the enhanced proliferation and invasion were inhibited by imatinib mesylate. Imatinib Mesylate 218-235 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 109-112 16982758-8 2006 The dramatic inactivation of imatinib-resistant KIT oncoproteins suggests that HSP90 inhibition provides a therapeutic solution to the challenge of heterogeneous imatinib resistance mutations in GIST patients. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-51 16982758-1 2006 Inhibition of KIT oncoproteins by imatinib induces clinical responses in most gastrointestinal stromal tumor (GIST) patients. Imatinib Mesylate 34-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 16982758-2 2006 However, many patients develop imatinib resistance due to secondary KIT mutations. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-71 16919263-2 2006 We used imatinib mesylate (Glivec) to investigate whether c-kit activity of Cajal-like cells in human myometrium is involved in spontaneous rhythmic contractions of human uterine smooth muscle, taking intestinal smooth muscle as a reference tissue. Imatinib Mesylate 8-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-63 16982758-8 2006 The dramatic inactivation of imatinib-resistant KIT oncoproteins suggests that HSP90 inhibition provides a therapeutic solution to the challenge of heterogeneous imatinib resistance mutations in GIST patients. Imatinib Mesylate 162-170 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-51 17018739-4 2006 Most KIT mutations occur in untreated GISTs in the juxtamembrane exon 11 and only rarely in the kinase domain, whereas in imatinib-treated patients secondary mutations are frequent in exons encoding for the ATP/imatinib binding pocket or the kinase activation loop. Imatinib Mesylate 122-130 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 5-8 16908931-9 2006 Because the majority of the KIT mutations we found in melanoma also occur in imatinib-responsive cancers of other types, imatinib may offer an immediate therapeutic benefit for a significant proportion of the global melanoma burden. Imatinib Mesylate 77-85 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-31 16908931-9 2006 Because the majority of the KIT mutations we found in melanoma also occur in imatinib-responsive cancers of other types, imatinib may offer an immediate therapeutic benefit for a significant proportion of the global melanoma burden. Imatinib Mesylate 121-129 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-31 17018739-4 2006 Most KIT mutations occur in untreated GISTs in the juxtamembrane exon 11 and only rarely in the kinase domain, whereas in imatinib-treated patients secondary mutations are frequent in exons encoding for the ATP/imatinib binding pocket or the kinase activation loop. Imatinib Mesylate 211-219 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 5-8 16778826-5 2006 Successful treatment of metastatic and unresectable gastrointestinal stromal tumors with KIT kinase inhibitor, imatinib mesylate (Gleevec), makes it intriguing to look at the status of KIT in solid-pseudopapillary neoplasms of the pancreas. Imatinib Mesylate 111-128 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-92 16778826-13 2006 Experience in gastrointestinal stromal tumors and other tumors have shown that mutation-mediated activation of KIT or PDGFRA is a prerequisite for clinical response with imatinib mesylate. Imatinib Mesylate 170-187 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 111-114 16779792-3 2006 Imatinib mesylate is a potent inhibitor of c-kit receptor tyrosine kinase activity. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-48 16906325-1 2006 Imatinib (Gleevec/STI-571/CGP57148B, Novartis) is a small-molecule, tyrosine kinase inhibitor developed to target BCR-ABL, c-Kit, and PDGF-R. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-128 16858179-5 2006 The discovery of the centrality of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of imatinib mesylate, a specific inhibitor of KIT tyrosine kinase function have revolutionized the treatment of GIST. Imatinib Mesylate 122-139 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 165-168 16858179-11 2006 The benefit of adjuvant treatment with the KIT tyrosine kinase inhibitor imatinib is the subject of investigation. Imatinib Mesylate 73-81 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-46 16952848-5 2006 Imatinib mesilate is a drug that inhibits c-kit activity expressed by GIST and its activity in these tumours has been demonstrated. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-47 16434489-8 2006 Computer modeling suggests that the KITD816V mutation destabilizes the inactive conformation of the KIT activation loop to which imatinib binds, but it is not predicted to impair binding of KIT by dasatinib. Imatinib Mesylate 129-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 36-39 16434489-8 2006 Computer modeling suggests that the KITD816V mutation destabilizes the inactive conformation of the KIT activation loop to which imatinib binds, but it is not predicted to impair binding of KIT by dasatinib. Imatinib Mesylate 129-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-103 16721136-4 2006 The success of the Kit tyrosine kinase inhibitor, imatinib mesylate (Gleevec, formerly STI-571), has caught the attention of the medical community. Imatinib Mesylate 50-67 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 19-22 16721136-4 2006 The success of the Kit tyrosine kinase inhibitor, imatinib mesylate (Gleevec, formerly STI-571), has caught the attention of the medical community. Imatinib Mesylate 69-76 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 19-22 16721136-4 2006 The success of the Kit tyrosine kinase inhibitor, imatinib mesylate (Gleevec, formerly STI-571), has caught the attention of the medical community. Imatinib Mesylate 87-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 19-22 17022716-10 2006 CONCLUSIONS: In our experience, imatinib is an effective, well tolerated therapy for malignant [c-Kit (CD117)-positive], non-resectable and/or metastatic GIST. Imatinib Mesylate 32-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-101 17022716-10 2006 CONCLUSIONS: In our experience, imatinib is an effective, well tolerated therapy for malignant [c-Kit (CD117)-positive], non-resectable and/or metastatic GIST. Imatinib Mesylate 32-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-108 16842246-0 2006 KIT immunohistochemistry and mutation status in gastrointestinal stromal tumours (GISTs) evaluated for treatment with imatinib. Imatinib Mesylate 118-126 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 16842259-0 2006 Pathological response of gastrointestinal stromal tumour to imatinib treatment correlates with tumour KIT mutational status in individual tumour clones. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-105 16803953-7 2006 A normal genetically balanced genotype was shown by comparative genomic hybridisation, which, together with the expression of c-kit, a known therapeutic target for imatinib, may have prognostic and therapeutic implications. Imatinib Mesylate 164-172 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 126-131 16786129-3 2006 Imatinib is a selective tyrosine-kinase inhibitor of ABL, KIT and PDGFR, and provides a clinical benefit in about 85% of patients with advanced GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-61 16614006-2 2006 However, because imatinib inhibits c-kit, the stem cell factor receptor, it could interfere with bone marrow engraftment. Imatinib Mesylate 17-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 35-40 16784237-2 2006 c-kit activity is elevated in gastrointestinal stromal tumors (GISTs), and its therapeutic inhibition by small molecules such as imatinib is clinically validated. Imatinib Mesylate 129-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 16707477-2 2006 Imatinib mesylate, a small-molecule inhibitor against several receptor tyrosine kinases, including KIT, platelet-derived growth factor receptor-alpha, and BCR-ABL, has therapeutic benefit for GISTs both via KIT and via unknown mechanisms. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-102 16487996-0 2006 A case of c-kit positive high-grade stromal endometrial sarcoma responding to Imatinib Mesylate. Imatinib Mesylate 78-95 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-15 16487996-4 2006 CASE: A 41-year-old woman suffering HGES, with positive staining for CD117 (c-kit) and large abdominal and retroperitoneal mass progressing after chemotherapy, was treated with Imatinib Mesylate. Imatinib Mesylate 177-194 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-74 16487996-4 2006 CASE: A 41-year-old woman suffering HGES, with positive staining for CD117 (c-kit) and large abdominal and retroperitoneal mass progressing after chemotherapy, was treated with Imatinib Mesylate. Imatinib Mesylate 177-194 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 76-81 16818499-0 2006 Imatinib inhibits c-Kit-induced hypoxia-inducible factor-1alpha activity and vascular endothelial growth factor expression in small cell lung cancer cells. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-23 16818499-11 2006 These data indicate that activation of c-Kit by SCF leads to a predominantly HIF-1alpha-mediated enhancement of VEGF expression and that inhibition of c-Kit signaling with imatinib could result in inhibition of tumor angiogenesis. Imatinib Mesylate 172-180 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 151-156 16740027-2 2006 GISTs exhibit activating mutations in the c-kit proto-oncogene, which render them amenable to treatment with imatinib mesylate. Imatinib Mesylate 109-126 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-47 16740725-2 2006 Imatinib mesylate has been shown to effectively block constitutively active KIT and delay tumor growth. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 76-79 16740725-8 2006 In contrast, imatinib mesylate, which inhibits KIT kinase activity but does not suppress total KIT expression, fails to cause apoptosis. Imatinib Mesylate 13-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-50 16865565-0 2006 Response to imatinib in KIT- and PDGFRA-wild type gastrointestinal stromal associated with neurofibromatosis type 1. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 16728580-0 2006 The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-115 16728580-1 2006 Imatinib mesylate (IM), a small molecule that is a selective inhibitor of the ABL, platelet derived growth factor receptor (PDGFR-R) and stem cell ligand receptor (c-kit) tyrosine kinases (TK). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 164-169 16728580-1 2006 Imatinib mesylate (IM), a small molecule that is a selective inhibitor of the ABL, platelet derived growth factor receptor (PDGFR-R) and stem cell ligand receptor (c-kit) tyrosine kinases (TK). Imatinib Mesylate 19-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 164-169 16850123-4 2006 Imatinib mesylate is a selective tyrosine kinase inhibitor on ABL, c-Kit and PGDF-receptor, and functions through competitive inhibition at the ATP-binding site of the enzyme, which leads to growth arrest or apoptosis in cells that express BCR-ABL. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-72 16638875-10 2006 In agreement with these results, two of the three imatinib-resistant patients with the KIT-V654A mutation responded to SU11248 treatment. Imatinib Mesylate 50-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-90 16638875-11 2006 CONCLUSIONS: These studies suggest that SU11248 may be a useful therapeutic agent to treat gastrointestinal stromal tumors harboring the imatinib-resistant KIT-V654A or KIT-T670I mutations, but it has no effect on the activity of the PDGFRA-D842V mutant. Imatinib Mesylate 137-145 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 156-159 16539879-8 2006 Specific therapy targeting the KIT receptor with imatinib has resulted in improved outcomes for patients with unresectable, metastatic, and recurrent disease. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 31-34 16565971-2 2006 Imatinib mesylate is an oral tyrosine kinase inhibitor that targets bcr-Abl, c-kit, platelet-derived growth factor receptor (PDGFR)-alpha, and PDGFR-beta, leading to remarkable clinical responses in several cancers. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-82 16624552-5 2006 The presence of exon 9-activating mutations in KIT was the strongest adverse prognostic factor for response to imatinib, increasing the relative risk of progression by 171% (P<0.0001) and the relative risk of death by 190% (P<0.0001) when compared with KIT exon 11 mutants. Imatinib Mesylate 111-119 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-50 16624552-5 2006 The presence of exon 9-activating mutations in KIT was the strongest adverse prognostic factor for response to imatinib, increasing the relative risk of progression by 171% (P<0.0001) and the relative risk of death by 190% (P<0.0001) when compared with KIT exon 11 mutants. Imatinib Mesylate 111-119 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 259-262 16596277-1 2006 STI571 is a specific inhibitor of tyrosine kinases, such as BCR-ABL, platelet-derived growth factor receptor, and c-KIT, and has recently been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 114-119 16703880-13 2006 CONCLUSIONS: This represents the first report of c-KIT sequencing in desmoid-type fibromatoses and suggests a possible biological basis for continuing to explore the use of adjuvant imatinib mesylate therapy. Imatinib Mesylate 182-199 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-54 16910417-2 2006 Most GISTs respond to imatinib mesylate, which selectively inhibits both KIT and PDGFRalpha, and is now considered standard systemic therapy for advanced GIST. Imatinib Mesylate 22-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 17193822-1 2006 Mutually exclusive KIT and PDGFRA mutations are central events in GIST pathogenesis, and their understanding is becoming increasingly important, because specific treatment targeting oncogenic KIT and PDGFRA activation (especially imatinib mesylate) has become available. Imatinib Mesylate 230-238 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 19-22 17193822-15 2006 Secondary mutations usually occur in KIT kinase domains in patients after imatinib treatment resulting in resistance to this drug. Imatinib Mesylate 74-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-40 16622127-0 2006 Response of a KIT-positive extra-abdominal fibromatosis to imatinib mesylate and KIT genetic analysis. Imatinib Mesylate 59-67 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 16638875-1 2006 PURPOSE: The majority of gastrointestinal stromal tumors harbor mutations in the receptor tyrosine kinases KIT or platelet-derived growth factor receptor A (PDGFRA), and respond to treatment with the tyrosine kinase inhibitor imatinib. Imatinib Mesylate 226-234 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 107-110 16638875-3 2006 The most common mechanism of imatinib resistance involves specific mutations in the kinase domains of KIT or PDGFRA. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-105 16638875-4 2006 We tested the activity of SU11248, an orally active small-molecule tyrosine kinase inhibitor, to inhibit important imatinib-resistant KIT and PDGFRA mutants. Imatinib Mesylate 115-123 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-137 16638875-5 2006 EXPERIMENTAL DESIGN: Primary imatinib-resistant tumor cells and cell lines expressing clinically identified imatinib-resistant KIT-V654A, KIT-T670I, or PDGFRA-D842V mutant isoforms were evaluated for sensitivity to SU11248 by Western immunoblotting and proliferation assays. Imatinib Mesylate 108-116 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 127-130 16638875-5 2006 EXPERIMENTAL DESIGN: Primary imatinib-resistant tumor cells and cell lines expressing clinically identified imatinib-resistant KIT-V654A, KIT-T670I, or PDGFRA-D842V mutant isoforms were evaluated for sensitivity to SU11248 by Western immunoblotting and proliferation assays. Imatinib Mesylate 108-116 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-141 16689459-19 2006 Importantly, the lack of an activating mutation of KIT tyrosine kinase is good evidence that imatinib will not be effective. Imatinib Mesylate 93-101 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-54 16551858-0 2006 Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Imatinib Mesylate 113-130 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-46 16551858-3 2006 Both PDGFRalpha and KIT receptors are targets of the tyrosine kinase inhibitor imatinib (Glivec) which has improved the treatment of advanced GISTs significantly. Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-23 16551858-3 2006 Both PDGFRalpha and KIT receptors are targets of the tyrosine kinase inhibitor imatinib (Glivec) which has improved the treatment of advanced GISTs significantly. Imatinib Mesylate 89-95 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-23 16570351-0 2006 Expression of c-kit receptor in human cholangiocarcinoma and in vivo treatment with imatinib mesilate in chimeric mice. Imatinib Mesylate 84-101 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-19 16570351-1 2006 AIM: To investigate the c-kit expression in biliary tract cancer cell lines and histological sections from patients with extrahepatic cholangiocarcinoma (CC) and to evaluate the efficacy of in vitro and in vitro treatment with imatinib mesilate. Imatinib Mesylate 227-244 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-29 16570351-11 2006 Imatinib mesilate at a low concentration of 5 micromol/L caused a significant growth inhibition in the c-kit positive cell line Mz-ChA-2 (31%), but not in the c-kit negative cell line EGI-1 (0%) (P<0.05). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-108 16570351-11 2006 Imatinib mesilate at a low concentration of 5 micromol/L caused a significant growth inhibition in the c-kit positive cell line Mz-ChA-2 (31%), but not in the c-kit negative cell line EGI-1 (0%) (P<0.05). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 159-164 16183119-0 2006 A novel K509I mutation of KIT identified in familial mastocytosis-in vitro and in vivo responsiveness to imatinib therapy. Imatinib Mesylate 105-113 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 16183119-2 2006 For those malignancies associated with KIT mutation or over-expression, imatinib offers a specific therapeutic option, yet it has no effect on D816V mutation commonly seen in sporadic mastocytosis. Imatinib Mesylate 72-80 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 39-42 16567968-3 2006 STI571 is a new antineoplastic compound, which selectively inhibits the tyrosine kinase activity of ABL, c-Kit and platelet-derived growth factor receptor (PDGFR). Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 105-110 16570351-18 2006 Imatinib mesilate exerts marked effects on tumor growth in vitro and in vitro dependent on the level of c-kit expression. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 104-109 16707477-2 2006 Imatinib mesylate, a small-molecule inhibitor against several receptor tyrosine kinases, including KIT, platelet-derived growth factor receptor-alpha, and BCR-ABL, has therapeutic benefit for GISTs both via KIT and via unknown mechanisms. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 207-210 16707477-9 2006 Imatinib treatment markedly reduces glucose uptake via decreased levels of plasma membrane-bound Glut4 and induces apoptosis or growth arrest by inhibiting KIT activity. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 156-159 16629079-4 2006 The treatment options have evolved rapidly with the discovery of imatinib (Gleevec) that selectively inhibits KIT. Imatinib Mesylate 65-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 16254134-8 2006 The KIT-D816V receptor expressed in Ba/F3 cells was resistant to growth inhibition by the selective PTK inhibitors imatinib and SU5614 but fully sensitive to PKC412. Imatinib Mesylate 115-123 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-7 16469036-1 2006 OBJECTIVE: To describe the effect of a specific c-kit receptor inhibitor (imatinib mesylate) on human detrusor strips in vitro and guinea-pig cystometry in vivo, and to show histological data suggesting differences in the distribution of interstitial cells of Cajal (ICC)-like cells in "normal" and overactive human detrusor, as these cells have been identified as possible mediators of spontaneous activity and excitability in bladder smooth muscle. Imatinib Mesylate 74-91 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-53 16357008-14 2006 In summary, PDGFRA, PDGF and KIT dysregulation as well as growth inhibition of cell culture S462 by imatinib may suggest that MPNST patients benefit from treatment with imatinib. Imatinib Mesylate 169-177 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-32 16572634-2 2006 The authors investigated the mutation of c-kit and the expression of its product KIT in IGCTs to identify tumors susceptible to imatinib mesylate, a synthetic agent targeting KIT. Imatinib Mesylate 128-145 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 175-178 15893416-1 2006 Imatinib targets KIT and platelet-derived growth factor receptors (PDGFR) and is highly effective in the treatment of CML and GIST patients. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-20 17163160-8 2006 Activating mutations in two related receptor tyrosine kinases (RTKs), KIT, and platelet-derived growth factor receptor alpha (PDGFRA) is central to the pathogenesis of gastrointestinal stromal tumors (GISTs), and countering the mutational activation by specific tyrosine kinase inhibitors, such as Imatinib mesylate, is now standard treatment for metastatic GISTs. Imatinib Mesylate 298-315 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-73 16521182-8 2006 RESULTS: Activation of c-KIT was inhibited by STI571 treatment. Imatinib Mesylate 46-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-28 16441423-7 2006 Furthermore, in the case of neoadjuvant imatinib therapy, LOH of the c-kit gene was shown in the high cellularity area in the primary lesion and metastatic liver GIST. Imatinib Mesylate 40-48 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-74 16441423-8 2006 It is suggested that LOH of the c-kit gene is an important event that leads to imatinib resistance and metastatic progression of GIST. Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 32-37 16321856-1 2006 The present study evaluated the expression and mutations of c-kit in peripheral T-cell lymphomas (PTCLs), except for extra-nodal NK/T cell lymphomas, as a potential target for treatment with imatinib mesylate. Imatinib Mesylate 191-208 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-65 16342249-2 2006 Imatinib inhibits KIT kinase activity. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 16462496-0 2006 Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors expressing KIT. Imatinib Mesylate 18-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 91-94 16462496-1 2006 OBJECTIVE: This phase II study was conducted to determine the activity of imatinib (gleevec) in heavily pretreated patients with KIT-positive metastatic germ cell tumor. Imatinib Mesylate 74-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 129-132 16462496-1 2006 OBJECTIVE: This phase II study was conducted to determine the activity of imatinib (gleevec) in heavily pretreated patients with KIT-positive metastatic germ cell tumor. Imatinib Mesylate 84-91 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 129-132 16445822-4 2006 In 2004, imatinib therapy, a tyrosine kinase inhibitor known to be effective against gastrointestinal stromal tumors, was reported to be effective also in a case of KIT-positive FATWO. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 165-168 17016042-0 2006 Atypical chronic myeloid leukaemia with CD117-positive blast cells treated with imatinib: A report of two cases. Imatinib Mesylate 80-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 40-45 16397263-2 2006 The small-molecule tyrosine kinase inhibitor imatinib mesylate is a potent inhibitor of wild-type (WT) KIT and certain mutant KIT isoforms and has become the standard of care for treating patients with metastatic GIST. Imatinib Mesylate 45-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-106 16781490-8 2006 Imatinib mesylate therapy might result in complete remission of SM cases with wild-type KIT, certain KIT mutations, such as F522C, or the FIP1L1-PDGFRA fusion gene, but not of D816V-KIT-bearing SM. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 88-91 16781490-8 2006 Imatinib mesylate therapy might result in complete remission of SM cases with wild-type KIT, certain KIT mutations, such as F522C, or the FIP1L1-PDGFRA fusion gene, but not of D816V-KIT-bearing SM. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 101-104 16781490-8 2006 Imatinib mesylate therapy might result in complete remission of SM cases with wild-type KIT, certain KIT mutations, such as F522C, or the FIP1L1-PDGFRA fusion gene, but not of D816V-KIT-bearing SM. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 101-104 16397263-2 2006 The small-molecule tyrosine kinase inhibitor imatinib mesylate is a potent inhibitor of wild-type (WT) KIT and certain mutant KIT isoforms and has become the standard of care for treating patients with metastatic GIST. Imatinib Mesylate 45-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 126-129 16397263-3 2006 However, KIT activation loop mutations involving codon D816 that are typically found in AML, systemic mastocytosis, and seminoma are insensitive to imatinib mesylate (IC50 > 5-10 micromol/L), and acquired KIT activation loop mutations can be associated with imatinib mesylate resistance in GIST. Imatinib Mesylate 261-278 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 9-12 16397263-8 2006 Furthermore, dasatinib is a potent inhibitor of imatinib-resistant KIT activation loop mutants and induces apoptosis in mast cell and leukemic cell lines expressing these mutations (potency against KIT D816Y >> D816F > D816V). Imatinib Mesylate 48-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-70 16265655-9 2005 Use of imatinib to treat cancers without c-kit or PDGFR-alpha mutation should be approached with caution. Imatinib Mesylate 7-15 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 41-46 16506600-3 2006 The first case was classified as a indolent systemic mastocytosis without any proven genetic alteration, the second one met the criteria of aggressive systemic mastocytosis with eosinophilia, where the point mutation asp816val in c-kit gene was confirmed and the patient responded unexpectedly well to Gleevec. Imatinib Mesylate 302-309 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 230-235 18369405-6 2006 Imatinib which is known to inhibit constitutively activated BCR-ABL tyrosine kinase in chronic myelogenous leukemia also inhibits constitutive activation of mutated KIT and PDGFRA, and is now being used for metastatic or unresectable GISTs as a molecular target drug. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 165-168 18369405-7 2006 Mutational analyses of c-kit and PDGFRA genes are considered to be significant for prediction of effectiveness of imatinib and newly developed/developing other agents on GISTs. Imatinib Mesylate 114-122 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-28 16699280-5 2006 Imatinib mesylate (Glivec) is an orally administered competitive inhibitor of tyrosine kinases associated with the KIT, ABL protein, licensed for the treatment of metastatic GIST since 2002 in Germany. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-118 16699280-5 2006 Imatinib mesylate (Glivec) is an orally administered competitive inhibitor of tyrosine kinases associated with the KIT, ABL protein, licensed for the treatment of metastatic GIST since 2002 in Germany. Imatinib Mesylate 19-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-118 16952044-0 2006 Recurrent gastrointestinal stromal tumor (GIST) of the stomach associated with a novel c-kit mutation after imatinib treatment. Imatinib Mesylate 108-116 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-92 16306788-10 2006 Judicious decision is mandatory before applying Imatinib therapy to KIT-positive gynecologic tumors. Imatinib Mesylate 48-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-71 16205964-2 2006 The TK inhibitor imatinib mesylate selectively targets PDGFR-alpha, -beta, c-kit, c-abl and arg and has proven successful in the treatment of chronic myeloid leukaemia. Imatinib Mesylate 17-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-80 16406868-1 2006 PURPOSE: RCCs with sarcomatoid differentiation have been reported to frequently express KIT protein, suggesting that imatinib mesylate (STI-571 or Gleevectrade mark) may be effective treatment for these aggressive tumors. Imatinib Mesylate 117-125 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 88-91 16321825-1 2006 Although imatinib was designed to specifically inhibit the bcr-abl gene product, it inhibits other receptor tyrosine kinases including c-kit. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 135-140 16401709-1 2006 The introduction of imatinib, an orally administered inhibitor of the KIT receptor tyrosine kinase, is prompting revision of the management algorithms that have traditionally guided the treatment of gastrointestinal stromal tumor (GIST). Imatinib Mesylate 20-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-73 16398673-12 2006 The effect of imatinib mesylate is different in various types of c-kit and PDGFRA gene mutations, and the secondary resistance against imatinib mesylate is often acquired by the second mutation of the identical genes. Imatinib Mesylate 14-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 65-70 16860492-1 2006 The use of a relatively nontoxic tyrosine kinase receptor inhibitor, imatinib mesylate (IM) (STI-571), has increasingly become a valuable therapeutic alternative in some KIT (CD117)-overexpressing neoplasms potentially because of the presence of KIT-activating mutations. Imatinib Mesylate 69-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-173 16860492-1 2006 The use of a relatively nontoxic tyrosine kinase receptor inhibitor, imatinib mesylate (IM) (STI-571), has increasingly become a valuable therapeutic alternative in some KIT (CD117)-overexpressing neoplasms potentially because of the presence of KIT-activating mutations. Imatinib Mesylate 69-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 175-180 16860492-1 2006 The use of a relatively nontoxic tyrosine kinase receptor inhibitor, imatinib mesylate (IM) (STI-571), has increasingly become a valuable therapeutic alternative in some KIT (CD117)-overexpressing neoplasms potentially because of the presence of KIT-activating mutations. Imatinib Mesylate 69-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 246-249 16534250-1 2006 Imatinib and AMN107 are protein tyrosine kinase inhibitors which reduce KIT autophosphorylation with similar potency. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-75 18393778-2 2006 STI-571 (imatinib mesylate), a selective KIT tyrosine kinase inhibitor, has changed the natural history of this disease, since it has shown high effectiveness in metastatic GIST, and it is currently under investigation also in the adjuvant and neoadjuvant setting. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 41-44 18393778-2 2006 STI-571 (imatinib mesylate), a selective KIT tyrosine kinase inhibitor, has changed the natural history of this disease, since it has shown high effectiveness in metastatic GIST, and it is currently under investigation also in the adjuvant and neoadjuvant setting. Imatinib Mesylate 9-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 41-44 18393778-6 2006 In addition, other KIT tyrosine kinase inhibitors with anti-VEGF receptor inhibitory activity, such as SU11248, PTK787/ZK787 and AMG 706, are currently being explored as second line monotherapy for imatinib mesylate-resistant GIST. Imatinib Mesylate 198-215 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 19-22 17072721-0 2006 Predicting the antitumor effects of STI571 by analysis of c-kit gene mutations in gastrointestinal stromal tumors of the stomach: Report of a case. Imatinib Mesylate 36-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-63 17072721-5 2006 Patients with an exon 11 mutation of the c-kit gene are reported to have a high response to STI571 (imatinib mesylate, Glivec). Imatinib Mesylate 92-98 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 41-46 17072721-5 2006 Patients with an exon 11 mutation of the c-kit gene are reported to have a high response to STI571 (imatinib mesylate, Glivec). Imatinib Mesylate 100-117 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 41-46 17072721-7 2006 Thus, it may be important to analyze c-kit gene mutations in patients presenting with GISTs to predict the effectiveness of STI571 in suppressing GISTs, especially tumors thought to have malignant potential. Imatinib Mesylate 124-130 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-42 17867582-10 2006 Mutational subtype in KIT or PDGF receptor alpha not only influences the biological behavior of GISTs but also their response to treatment with imatinib, a tyrosine kinase inhibitor also inhibiting ARG, PDGF receptor beta and BCR-ABL. Imatinib Mesylate 144-152 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 17867582-12 2006 GISTs without detectable KIT mutation in these both exons often are resistant to imatinib. Imatinib Mesylate 81-89 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 25-28 17867582-13 2006 The development of secondary resistance to imatinib in GIST patients occurs in up to 40% of cases and is partly due to secondary KIT mutations occuring additionally to the primary mutation. Imatinib Mesylate 43-51 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 129-132 16226710-13 2005 STI-571, a clinically effective targeted protein-tyrosine kinase inhibitor, binds to an inactive conformation of Kit. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 113-116 16226710-15 2005 STI-571 binds to Kit and Bcr-Abl (the oncoprotein of chronic myelogenous leukemia) at their ATP-binding sites. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-20 16288076-6 2005 DISCUSSION: Imatinib mesylate is a protein tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the receptor tyrosine kinases for platelet-derived growth factor, and stem cell factor c-kit. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 199-204 16373716-0 2005 Imatinib binding and cKIT inhibition is abrogated by the cKIT kinase domain I missense mutation Val654Ala. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-61 16373716-4 2005 We sequenced cKIT exons from two patients with GIST after the development of imatinib resistance, revealing a point mutation in kinase domain I (exon 13), Val654Ala, which has been associated previously with relapse and resistance. Imatinib Mesylate 77-85 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 13-17 16373716-5 2005 Molecular modeling of cKIT-imatinib complexes shows that this residue is located in the drug-binding site and that the Val654Ala mutation disrupts drug binding by removing hydrophobic contacts with the central diaminophenyl ring of imatinib. Imatinib Mesylate 27-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-26 16373716-6 2005 Loss of these contacts results in a destabilizing effect on two key hydrogen bonds between imatinib and Asp310 and Thr670 of cKIT. Imatinib Mesylate 91-99 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 125-129 16373716-8 2005 When present on the same cKIT allele as an oncogenic mutation, the Val654Ala mutation abolishes imatinib-mediated inhibition of cKIT phosphoactivation in vitro. Imatinib Mesylate 96-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 25-29 16373716-8 2005 When present on the same cKIT allele as an oncogenic mutation, the Val654Ala mutation abolishes imatinib-mediated inhibition of cKIT phosphoactivation in vitro. Imatinib Mesylate 96-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 128-132 16161057-0 2005 Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a Phase II clinical trial. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-78 16087693-0 2005 A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: a CALGB and NCCTG study. Imatinib Mesylate 20-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 55-60 16087693-1 2005 BACKGROUND: The aim of the present study was to evaluate the clinical activity of imatinib mesylate in patients with recurrent and refractory c-kit-expressing small-cell lung cancer. Imatinib Mesylate 82-99 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 142-147 16294026-0 2005 Activating mutations in c-KIT and PDGFRalpha are exclusively found in gastrointestinal stromal tumors and not in other tumors overexpressing these imatinib mesylate target genes. Imatinib Mesylate 147-155 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-29 16294026-1 2005 Previous studies have shown that Imatinib mesylate (Gleevec), a selective tyrosine kinase inhibitor of c-KIT and platelet-derived growth factor receptors (PDGFR), is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumors (GIST), especially in those having activating mutations in c-kit exon 11. Imatinib Mesylate 33-50 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-108 16294026-1 2005 Previous studies have shown that Imatinib mesylate (Gleevec), a selective tyrosine kinase inhibitor of c-KIT and platelet-derived growth factor receptors (PDGFR), is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumors (GIST), especially in those having activating mutations in c-kit exon 11. Imatinib Mesylate 33-50 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 186-191 16294026-1 2005 Previous studies have shown that Imatinib mesylate (Gleevec), a selective tyrosine kinase inhibitor of c-KIT and platelet-derived growth factor receptors (PDGFR), is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumors (GIST), especially in those having activating mutations in c-kit exon 11. Imatinib Mesylate 33-50 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 298-303 16294026-3 2005 Importantly, the presence and type of these mutually exclusive c-KIT or PDGFRalpha mutations were found to be associated with the response to imatinib. Imatinib Mesylate 142-150 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-68 16242052-3 2005 Because imatinib could also inhibit the activity of KIT, a 145-kD transmembrane glycoprotein, and because gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, are characterized by expression of a gain-of-function mutation in KIT, imatinib was used in therapeutic trials of GISTs beginning in 1999. Imatinib Mesylate 8-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 16242052-3 2005 Because imatinib could also inhibit the activity of KIT, a 145-kD transmembrane glycoprotein, and because gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, are characterized by expression of a gain-of-function mutation in KIT, imatinib was used in therapeutic trials of GISTs beginning in 1999. Imatinib Mesylate 8-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 272-275 16242052-6 2005 Clinically, GIST patients with KIT exon 11 mutations (ie, the juxtamembrane region) are the most prevalent and sensitive to imatinib. Imatinib Mesylate 124-132 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 31-34 16242052-8 2005 What is becoming evident is that there are patients with GIST who lack mutations in KIT or PDGFRalpha, or possess "imatinib-resistant" mutations (such as exon 17 mutations in KIT and exon 18 mutations in PDGFRalpha). Imatinib Mesylate 115-123 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 175-178 16334774-4 2005 He was medicated with STI571, which works by blocking proliferation of malignant cells with expression of c-kit. Imatinib Mesylate 22-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-111 15887238-1 2005 Imatinib mesylate is a tyrosine kinase inhibitor of the ABL, platelet-derived growth factor receptor (PDGFR), and c-kit kinases. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 114-119 16357454-2 2005 Recently it has been demonstrated that a majority of GIST patients with c-kit mutations respond to therapy with imatinib, a c-kit tyrosine kinase inhibitor. Imatinib Mesylate 112-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-77 16357454-2 2005 Recently it has been demonstrated that a majority of GIST patients with c-kit mutations respond to therapy with imatinib, a c-kit tyrosine kinase inhibitor. Imatinib Mesylate 112-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-129 16082245-13 2005 KIT tyrosine kinase inhibitors such as imatinib mesylate are the generally accepted treatment of metastatic GISTs, and their availability has prompted an active search for other treatment targets among KIT-positive tumors such as myeloid leukemias and small cell carcinoma of the lung, with variable and often nonconvincing results. Imatinib Mesylate 39-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 16236162-3 2005 Imatinib mesylate is a FDA approved compound that inhibits tyrosine quinase receptors, as well as c-kit. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-103 15972446-1 2005 The majority of patients with systemic mast cell disease express the imatinib-resistant Asp816Val (D816V) mutation in the KIT receptor tyrosine kinase. Imatinib Mesylate 69-77 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 122-125 16203604-3 2005 Imatinib mesylate (IM) is one such therapy that also targets Abl, c-kit and PDGF-R tyrosine kinases. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 66-71 16210056-7 2005 SCF synergized with chemoattractants in causing basophil upregulation of the integrin CD11b, and this effect was inhibited by a c-kit antibody, the tyrosine kinase inhibitor imatinib mesylate (STI-571), and a phosphatidylinositol 3 kinase inhibitor but not by inhibitors of p38 mitogen-activated protein kinase or mitogen-activated protein kinase/extracellular signal-regulated kinase kinase. Imatinib Mesylate 193-200 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 128-133 16498290-12 2005 The treatment of localized GIST is surgical resection, which must be complete; that of advanced or unresectable GIST is based on the use of a targeted therapy, imatinib, which is a pharmacological antagonist of the KIT protein. Imatinib Mesylate 160-168 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 215-218 16101197-3 2005 A substantial fraction of the tumors expresses c-Kit or the platelet-derived growth factor receptor beta (PDGFRbeta), both targets for imatinib mesylate. Imatinib Mesylate 135-143 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-52 16049512-0 2005 Imatinib mesylate for refractory acute myeloblastic leukemia harboring inv(16) and a C-KIT exon 8 mutation. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-90 16077968-0 2005 Effects of imatinib vary with the types of KIT-mutation in gastrointestinal stromal tumor cell lines. Imatinib Mesylate 11-19 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-46 16077968-2 2005 Imatinib has therapeutic potential for GISTs because of its inhibitory effect on KIT kinase activity. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 16077968-8 2005 In two types of activating mutant KIT, imatinib could inhibit the constitutive activation of both types of KIT mutant, although the antiproliferative effect on GIST882 was weaker than on GIST-T1. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 16077968-8 2005 In two types of activating mutant KIT, imatinib could inhibit the constitutive activation of both types of KIT mutant, although the antiproliferative effect on GIST882 was weaker than on GIST-T1. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 107-110 16077968-10 2005 Our results suggest that the apoptotic signal trans-duction caused by imatinib in GISTs is susceptible to various types of KIT mutation. Imatinib Mesylate 70-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-126 16142999-5 2005 The administration of new chemotherapeutic agents, such as imatinib for gastrointestinal tumors (GIST), requires the study of genetic polymorphisms possibly affecting the integrity of the target (c-KIT), which may provide valid information regarding possible developments of therapy. Imatinib Mesylate 59-67 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 196-201 16046538-6 2005 The KIT/FLT3 inhibitor SU-11248 potently inhibits the imatinib-resistant KIT(V559D/T670I) kinase, consistent with the clinical efficacy of SU-11248 against imatinib-resistant gastrointestinal tumors, and the EGFR inhibitors EKB-569 and CI-1033, but not GW-572016 and ZD-6474, potently inhibit the gefitinib- and erlotinib-resistant EGFR(L858R/T790M) kinase. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-7 16046538-6 2005 The KIT/FLT3 inhibitor SU-11248 potently inhibits the imatinib-resistant KIT(V559D/T670I) kinase, consistent with the clinical efficacy of SU-11248 against imatinib-resistant gastrointestinal tumors, and the EGFR inhibitors EKB-569 and CI-1033, but not GW-572016 and ZD-6474, potently inhibit the gefitinib- and erlotinib-resistant EGFR(L858R/T790M) kinase. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 16046538-6 2005 The KIT/FLT3 inhibitor SU-11248 potently inhibits the imatinib-resistant KIT(V559D/T670I) kinase, consistent with the clinical efficacy of SU-11248 against imatinib-resistant gastrointestinal tumors, and the EGFR inhibitors EKB-569 and CI-1033, but not GW-572016 and ZD-6474, potently inhibit the gefitinib- and erlotinib-resistant EGFR(L858R/T790M) kinase. Imatinib Mesylate 156-164 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-7 16014680-0 2005 Inhibition of c-kit tyrosine kinase by imatinib mesylate induces apoptosis in mast cells in rheumatoid synovia: a potential approach to the treatment of arthritis. Imatinib Mesylate 39-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-19 16014680-5 2005 Inhibition of the c-kit tyrosine kinase with imatinib mesylate (1.0-10 micromol/l) induced profound apoptosis in cultured mast cells as judged by typical apoptotic morphology, increased number of apoptotic nucleosomes, and activation of caspases 8 and 9. Imatinib Mesylate 45-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-23 16167051-3 2005 The discovery that constitutive activation of the c-kit gene drives malignant behavior in GISTs exposed a weakness that was soon exploited through the application of the novel targeted therapy imatinib, a small-molecule tyrosine kinase inhibitor of Bcr-Abl, KIT, and the platelet-derived growth factor receptor-alpha and -beta. Imatinib Mesylate 193-201 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-55 16167051-3 2005 The discovery that constitutive activation of the c-kit gene drives malignant behavior in GISTs exposed a weakness that was soon exploited through the application of the novel targeted therapy imatinib, a small-molecule tyrosine kinase inhibitor of Bcr-Abl, KIT, and the platelet-derived growth factor receptor-alpha and -beta. Imatinib Mesylate 193-201 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 258-261 16143881-7 2005 Imatinib mesylate, a tyrosine kinase inhibitor known to inhibit the activities of BCR-ABL, KIT, and PDGFR, is currently being used for the treatment of both chronic myeloid leukemia and metastatic GIST. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 91-94 16143881-8 2005 The clinical response to imatinib therapy correlates with the types of mutations of KIT and PDGFRA, and the determination of KIT and PDGFRA mutations is useful for predicting the effect of imatinib. Imatinib Mesylate 25-33 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 16143881-8 2005 The clinical response to imatinib therapy correlates with the types of mutations of KIT and PDGFRA, and the determination of KIT and PDGFRA mutations is useful for predicting the effect of imatinib. Imatinib Mesylate 189-197 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 125-128 16143881-9 2005 Resistance to imatinib after an initial response has been reported; secondary point mutations in KIT or PDGFRA that confer imatinib resistance are the most common mechanisms responsible for acquired resistance to imatinib. Imatinib Mesylate 123-131 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 97-100 16143881-9 2005 Resistance to imatinib after an initial response has been reported; secondary point mutations in KIT or PDGFRA that confer imatinib resistance are the most common mechanisms responsible for acquired resistance to imatinib. Imatinib Mesylate 123-131 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 97-100 16034302-16 2005 Results of ongoing pilot phase II studies may validate the efficacy of imatinib mesylate in malignant melanoma expressing KIT. Imatinib Mesylate 71-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 122-125 16034306-1 2005 In order to determine whether imatinib mesylate (Gleevec), a tyrosine kinase inhibitor that binds the CD-117 (c-kit) receptor, may be of value in the treatment of malignant melanoma, an immunohistochemical analysis of 40 cases of primary and metastatic melanoma was undertaken. Imatinib Mesylate 30-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-108 16034306-1 2005 In order to determine whether imatinib mesylate (Gleevec), a tyrosine kinase inhibitor that binds the CD-117 (c-kit) receptor, may be of value in the treatment of malignant melanoma, an immunohistochemical analysis of 40 cases of primary and metastatic melanoma was undertaken. Imatinib Mesylate 30-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-115 16383232-1 2005 OBJECTIVE: To explore the effect of Imatinib mesylate on proliferation, differentiation and apoptosis of leukemic Kasumi-1 cells bearing c-kit mutation. Imatinib Mesylate 36-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 137-142 16383232-6 2005 Imatinib treatment induced a decrease in the mean fluorescence value of c-kit antigen, a progressive decline in S-phase cell fraction and an increase in G0/G1 cells. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-77 16383232-9 2005 Tyrosine phosphorylation level of c-kit protein was decreased by Imatinib treatment. Imatinib Mesylate 65-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-39 16383232-10 2005 CONCLUSION: Tyrosine kinase inhibitor Imatinib mesylate treatment could inhibit proliferation of Kasumi-1 cells which bear a c-kit mutation, induce differentiation, apoptosis and G0/G1 cells accumulation. Imatinib Mesylate 38-55 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 125-130 15790786-0 2005 Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412. Imatinib Mesylate 49-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-35 15790786-2 2005 Reports of the resistance of the kinase domain mutation D816V to the adenosine triphosphate (ATP)-competitive kinase inhibitor imatinib mesylate prompted us to characterize 14 c-KIT mutations reported in association with human hematologic malignancies for transforming activity in the murine hematopoietic cell line Ba/F3 and for sensitivity to the tyrosine kinase inhibitor PKC412. Imatinib Mesylate 127-144 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 176-181 15790786-4 2005 c-KIT D816Y and D816V transformed cells were sensitive to PKC412 despite resistance to imatinib mesylate. Imatinib Mesylate 87-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 15790786-7 2005 These findings suggest that PKC412 may be a useful therapeutic agent for c-KIT-positive malignancies harboring the imatinib mesylate-resistant D816V or D816Y activation mutations. Imatinib Mesylate 115-132 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-78 15933471-11 2005 Finally, gastrointestinal tumors harbor specific activating mutations in KIT or PDGFRA genes, which are responsive to imatinib. Imatinib Mesylate 118-126 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 15933471-12 2005 Specific mutations of the KIT and PDGFRA genes have now repeatedly been found correlated to response or resistance to imatinib. Imatinib Mesylate 118-126 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 15985189-1 2005 OBJECTIVES: To assess the clinical and cost-effectiveness of imatinib in the treatment of unresectable and/or metastatic, KIT-positive, gastrointestinal stromal tumours (GISTs), relative to current standard treatments. Imatinib Mesylate 61-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 122-125 15985189-20 2005 CONCLUSIONS: Evidence from uncontrolled studies indicates that the treatment with imatinib brings about clinically significant shrinkage of tumour mass in about half of patients with unresectable and/or metastatic, KIT-positive GIST. Imatinib Mesylate 82-90 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 215-218 15800027-9 2005 Selective inhibitor of ERK, PD098059, and c-kit inhibitors, STI571 and PP1, suppressed the combined SCF and TNF-alpha-induced ICAM-1 expression. Imatinib Mesylate 60-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-47 15911092-6 2005 RESULTS: The use of STI 571-mediated inhibition impaired the tyrosine phosphorylation of KIT(Asn822Lys) and its association with the p85 subunit of phosphatidylinositol 3"-kinase (p85PI3K). Imatinib Mesylate 20-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-92 15911092-8 2005 STI 571 inhibited the KIT-mediated proliferation of Kasumi-1 cells in a dose-dependent manner. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 15939196-2 2005 The management of GISTs has been altered significantly by the development of imatinib mesylate, a tyrosine kinase inhibitor with activity against KIT and platelet-derived growth factor receptors. Imatinib Mesylate 77-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 146-149 15953881-9 2005 The mechanism by which imatinib induces gynecomastia and hydrocele is thought to be associated with an inhibition of c-KIT and platelet-derive growth factor. Imatinib Mesylate 23-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-122 15895440-6 2005 Imatinib, an inhibitor of KIT kinase activity, is now the standard front-line therapy for patients with advanced GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 16143141-5 2005 This mutation activates KIT, and the mutant KIT is inhibited by the tyrosine kinase inhibitor imatinib mesylate. Imatinib Mesylate 94-111 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 16143141-5 2005 This mutation activates KIT, and the mutant KIT is inhibited by the tyrosine kinase inhibitor imatinib mesylate. Imatinib Mesylate 94-111 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 16135502-0 2005 Imatinib mesylate can induce objective response in progressing, highly expressing KIT adenoid cystic carcinoma of the salivary glands. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-85 16015387-8 2005 We demonstrate that KIT exon 8 mutations result in constitutive ligand-independent kinase activation that can be inhibited by clinically relevant concentrations of imatinib. Imatinib Mesylate 164-172 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-23 16046538-2 2005 Mutant forms of BCR-ABL, KIT, and the EGF receptor (EGFR) have been found that confer resistance to the drugs imatinib, gefitinib, and erlotinib. Imatinib Mesylate 110-118 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 25-28 15704192-5 2005 She was placed on a trial of imatinib mesylate based on tumor expression of c-KIT, a tyrosine kinase targeted by this drug. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 76-81 15917650-3 2005 Imatinib also inhibits the c-abl, platelet derived growth factor receptor (PDGFR), abl-related gene and stem cell factor receptor, c-kit, protein tyrosine kinases. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 131-136 15917650-4 2005 It is through inhibition of c-kit that imatinib is also used clinically in the treatment of gastrointestinal stromal tumours. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-33 15946589-2 2005 Imatinib (STI571, Gleevec, Glivec; Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL, BCR-ABL, PDGFRA, and PDGFRB, represents a new paradigm of targeted cancer therapy and has revolutionized the treatment of patients with chronic myelogenous leukemia and GISTs. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 105-108 15946589-4 2005 The reported mechanism of imatinib resistance in GISTs involves missense mutation in the kinase domain of KIT, including Thr670Ile, Tyr823Asp, and Val654Ala. Imatinib Mesylate 26-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-109 15976348-1 2005 AIMS: Neuroblastic tumours (NTs) have been shown to respond to imatinib treatment in vivo and in vitro, possibly via inactivating the c-kit receptor. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-139 15976348-2 2005 The purpose of this study was to identify gastrointestinal stromal tumour (GIST)-type c-kit gene associated mutations in exons 9, 11, 13, and 17 in NTs to recognise a subset of tumours that would probably respond to imatinib treatment. Imatinib Mesylate 216-224 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 86-91 15976348-7 2005 Oncogenic activation of c-kit in NTs presumably differs from that of GISTs, which may influence their responsiveness to imatinib treatment. Imatinib Mesylate 120-128 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-29 16018942-5 2005 Additional therapy with imatinib (Gleevec, Novartis Pharmaceuticals Corporation, East Hanover, NJ), an inhibitor of CD117 tyrosine kinase activity, treated recurrence in one patient and effected complete remission. Imatinib Mesylate 24-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 116-121 15822120-3 2005 Because many GISTs display a definitive response to the KIT inhibitor imatinib, accurate diagnosis of these neoplasms is of great clinical importance. Imatinib Mesylate 70-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 56-59 16052979-11 2005 The imatinib mesylate is a selective inhibitor of the KIT tyrosine kinase receptor and it also blocks the activity of the PDGFRA kinase. Imatinib Mesylate 4-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 54-57 15894928-5 2005 STI 571 (imatinib mesylate [Gleevec]) might be an effective therapy in this case, since Gleevec targets both PDGFRA and c-kit oncoproteins. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-125 15894928-5 2005 STI 571 (imatinib mesylate [Gleevec]) might be an effective therapy in this case, since Gleevec targets both PDGFRA and c-kit oncoproteins. Imatinib Mesylate 9-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-125 15930355-10 2005 That acquired resistance to imatinib in GIST commonly occurs via secondary gene mutation in the KIT kinase domain has implications for strategies to delay or prevent imatinib resistance and to employ newer targeted therapies. Imatinib Mesylate 28-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-99 15930355-10 2005 That acquired resistance to imatinib in GIST commonly occurs via secondary gene mutation in the KIT kinase domain has implications for strategies to delay or prevent imatinib resistance and to employ newer targeted therapies. Imatinib Mesylate 166-174 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-99 15812822-0 2005 Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a phase II clinical trial. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-78 15812822-1 2005 BACKGROUND: Imatinib inhibits the c-kit tyrosine kinase, which, accounts for its activity in gastrointestinal stromal tumors. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-39 15812822-3 2005 The authors conducted a Phase II single-institution study of imatinib in patients with recurrent SCLC whose tumor specimens expressed c-kit protein. Imatinib Mesylate 61-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-139 15897563-2 2005 Imatinib mesylate, a tyrosine kinase inhibitor, has activity against GISTs that contain oncogenic mutations of KIT. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 111-114 15897563-3 2005 In this study, KIT and PDGFRalpha mutation status was analyzed and protein modeling approaches were used to assess the potential effect of KIT mutations in response to imatinib therapy. Imatinib Mesylate 168-176 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 139-142 16158966-1 2005 BACKGROUND: c-kit expression by immunohistochemistry has been utilized to identify cancer patients who can be treated with imatinib-mesylate. Imatinib Mesylate 123-140 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-17 15815732-3 2005 Imatinib mesylate is a recently introduced KIT tyrosine kinase inhibitor with effect on metastatic GIST. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-46 15966213-1 2005 Imatinib, an inhibitor of the tyrosine kinase activity of c-kit, was used as an adjuvant chemotherapy in two patients who underwent curative surgery for recurrent gastrointestinal stromal tumors. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-63 15846297-1 2005 This two-centre phase-II trial aimed at investigating the efficacy of imatinib in metastasised melanoma patients in correlation to the tumour expression profile of the imatinib targets c-kit and platelet-derived growth factor receptor (PDGF-R). Imatinib Mesylate 168-176 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 185-190 15853160-7 2005 Imatinib mesylate is an oral drug designed to inhibit the kinase enzyme activity of KIT. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 15725473-0 2005 Imatinib mesylate in the treatment of Core Binding Factor leukemias with KIT mutations. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 15811621-0 2005 Acquired resistance to imatinib in gastrointestinal stromal tumours caused by multiple KIT mutations. Imatinib Mesylate 23-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-90 15725473-2 2005 Aim of this study is to investigate the capability of Imatinib to induce an anti-leukemic effect in Core Binding Factor (CBF)-leukemia patients presenting either with extracellular juxtamembrane or kinase KIT mutations. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 205-208 15725473-7 2005 Whether Imatinib, in combination with other agents, may play a role in the treatment of AML with more sensitive extracellular juxtamembrane KIT mutation remains to be determined. Imatinib Mesylate 8-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 140-143 15803362-1 2005 BACKGROUND: Imatinib mesylate is a potent inhibitor of Abl, KIT, and PDGFR tyrosine kinases. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 15756436-2 2005 Imatinib mesylate is a tyrosine kinase inhibitor initially developed against the bcr-abl fusion protein of CML, but also shows therapeutic inhibitory activity against c-Kit expressed in GISTs. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 167-172 15756436-4 2005 Our aim was to test NETs for c-Kit expression and hence identify patients for the consideration of therapy with imatinib mesylate. Imatinib Mesylate 112-129 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-34 15756436-9 2005 Studies need to be performed to determine if c-kit expression by NETs can be translated into therapeutic benefit by agents such as imatinib mesylate. Imatinib Mesylate 131-148 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-50 15727903-1 2005 Imatinib mesylate is a small molecule inhibitor of the c-Abl, platelet-derived growth factor (PDGF) receptor and c-Kit tyrosine kinases that is approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) and gastrointestinal stromal tumors. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 113-118 15794712-4 2005 Imatinib is a small-molecule tyrosine kinase inhibitor of the ABL fusion gene, platelet derived growth factor receptors (PDGFR) and KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 132-135 15756019-3 2005 Imatinib is a novel tyrosine kinase inhibitor effective against Abl kinases, c-Kit, and platelet-derived growth factor receptor. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-82 15717993-5 2005 Imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp., East Hanover, NJ) is a tyrosine kinase inhibitor with activity against abl, c-kit, and platelet derived growth factor receptor (PDGFR), and is approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumor. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 136-141 15717993-5 2005 Imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp., East Hanover, NJ) is a tyrosine kinase inhibitor with activity against abl, c-kit, and platelet derived growth factor receptor (PDGFR), and is approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumor. Imatinib Mesylate 19-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 136-141 15705916-0 2005 KIT/Val654 Ala receptor detected in one imatinib-resistant GIST patient. Imatinib Mesylate 40-48 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 15685537-15 2005 Our findings show the sensitivity of the imatinib-resistant KIT -T670I and KIT -V654A and of PDGFRA -D842V mutants to PKC412. Imatinib Mesylate 41-49 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 15685537-15 2005 Our findings show the sensitivity of the imatinib-resistant KIT -T670I and KIT -V654A and of PDGFRA -D842V mutants to PKC412. Imatinib Mesylate 41-49 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-78 15822404-4 2005 Inhibitors of KIT tyrosine kinase activity can have a therapeutic role, particularly in seminomas with a c-kit mutation sensitive to imatinib mesylate. Imatinib Mesylate 133-150 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 105-110 15659505-0 2005 Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: a Princess Margaret Hospital phase II consortium study. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-97 15659505-1 2005 PURPOSE: This study aimed to assess the antitumor activity of imatinib in adenoid cystic carcinoma (ACC) of the salivary gland expressing c-kit. Imatinib Mesylate 62-70 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-143 15659505-3 2005 Imatinib specifically inhibits autophosphorylation of the bcr-abl, platelet-derived growth factor receptor beta, and c-kit tyrosine kinases. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-122 15632213-0 2005 Imatinib mesylate in the treatment of c-kit-positive acute myeloid leukemia: is this the real target? Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 38-43 15945512-3 2005 Imatinib mesylate, a molecularly targeted agent that inhibits the KIT receptor tyrosine kinase, has now been demonstrated to be highly effective at inducing objective responses in GIST patients, and it improves overall survival. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 66-69 16373964-4 2005 In addition, signal transduction mediated by activating mutations of c-Kit and PDGFR can be effectively blocked by specific tyrosine kinase inhibitors, such as Imatinib mesylate. Imatinib Mesylate 160-177 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-74 15589595-4 2005 Clinical evidences showing the effect of a tyrosine kinase inhibitor, STI571, in c-KIT-positive gastrointestinal tumors, the role of COX-inhibitors chemotherapy-associated in colorectal cancer patients and the successful therapeutic possibility of anti-HER2 therapy in metastatic breast carcinoma, have encouraged us to study the expression of c-KIT, COX-2 and HER-2/neu in uterine carcinosarcomas. Imatinib Mesylate 70-76 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-86 17462285-4 2005 Targeted therapy (imatinib) can inhibit C-KIT and thereby aberrant tumoural proliferation. Imatinib Mesylate 18-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 40-45 17462285-15 2005 With the emergence of techniques enabling identification of the precise mutational status of the C-KIT oncogene, the imatinib/surgery sequence could be tailored to the type of C-KIT mutation. Imatinib Mesylate 117-125 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 97-102 17462285-15 2005 With the emergence of techniques enabling identification of the precise mutational status of the C-KIT oncogene, the imatinib/surgery sequence could be tailored to the type of C-KIT mutation. Imatinib Mesylate 117-125 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 176-181 15545668-1 2005 PURPOSE: Mutated KIT and platelet-derived growth factor receptor alpha (PDGFRalpha) tyrosine kinases are the principal targets for imatinib mesylate in the treatment of gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 131-148 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-20 16319507-3 2005 The aim of this trial was to evaluate imatinib, a tyrosine kinase inhibitor of PDGFR and c-kit, in patients with advanced HCC and impaired liver function. Imatinib Mesylate 38-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-94 16381169-4 2005 STI571, a small molecule inhibitor of the BCR/ABL, c-Kit and platelet derived growth factor receptor tyrosine kinase, produced pronounced clinical responses in patients with BCR/ABL positive chronic myeloid leukemia and c-Kit positive gastrointestial stromal tumors. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-56 16381169-4 2005 STI571, a small molecule inhibitor of the BCR/ABL, c-Kit and platelet derived growth factor receptor tyrosine kinase, produced pronounced clinical responses in patients with BCR/ABL positive chronic myeloid leukemia and c-Kit positive gastrointestial stromal tumors. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 220-225 15850018-0 2005 Lack of response to imatinib mesylate as second-line therapy in a patient with c-kit positive metastatic soft tissue leiomyosarcoma. Imatinib Mesylate 20-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 79-84 15583854-4 2004 The ICC tumors are called gastrointestinal stromal tumors (GISTs), and GISTs are a good target for the Kit inhibitor imatinib mesylate. Imatinib Mesylate 117-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-106 15583854-5 2004 The interrelationship between the type of Kit gain-of-function mutations and the therapeutic effect of imatinib mesylate has been well characterized in GISTs. Imatinib Mesylate 103-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-45 22900354-3 2004 The present review focuses mainly on the development of PTK inhibitors in clinical trials, with special emphasis on imatinib mesylate, a rationally designed, potent oral anticancer agent and selective inhibitor for Abl tyrosine kinase, including Bcr-Abl, C-kit and platelet-derived growth factor-receptor tyrosine kinases, which has been implicated in several malignancies, including chronic myeloid leukemia and gastrointestinal stromal tumour. Imatinib Mesylate 116-133 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 255-260 15547187-0 2004 Development of c-Kit-expressing small-cell lung cancer in a chronic myeloid leukemia patient during imatinib treatment. Imatinib Mesylate 100-108 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 15-20 15542802-1 2004 PURPOSE: KIT is a target for imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Imatinib Mesylate 29-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 9-12 15372471-2 2004 Imatinib mesylate is a tyrosine kinase inhibitor targeting platelet-derived growth factor receptor-beta (PDGFRB), BCR-ABL, and KIT. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 127-130 15618851-6 2004 Because of the tumour"s intense expression of CD117 (c-kit), the patient is now treated with the tyrosine kinase inhibitor imatinib (STI571). Imatinib Mesylate 123-131 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-51 15618851-6 2004 Because of the tumour"s intense expression of CD117 (c-kit), the patient is now treated with the tyrosine kinase inhibitor imatinib (STI571). Imatinib Mesylate 123-131 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-58 15777512-3 2004 Among them, CD117 was detected positive in 29 patients; 2 patients received imatinib mesylate before operation and 28 patients with unresectable and(or) metastatic GIST received oral imatinib mesylate daily at dose of 200-600 mg. Three patients were lost in follow-up and the objective effect was evaluated in 25 patients. Imatinib Mesylate 183-200 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-17 15326474-3 2004 For example, GISTs with KIT exon 11 mutations are typically gastric and have excellent imatinib response, whereas those with KIT exon 9 mutations generally arise in the small bowel and are less responsive to imatinib. Imatinib Mesylate 87-95 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 15330987-3 2004 As it is possible to inhibit C-KIT by innovative kinase inhibitors like STI571, it may be an attractive target for new therapeutical approaches. Imatinib Mesylate 72-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-34 15510603-2 2004 With the introduction of Imatinib, an oral drug able to inhibit the KIT receptor tyrosine kinase, new questions arise regarding our ability to monitor treatment response with conventional methods and optimally manage such patients on treatment with new agents. Imatinib Mesylate 25-33 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-71 15309514-0 2004 Imatinib mesylate acts in metastatic or unresectable gastrointestinal stromal tumor by targeting KIT receptors--a review. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 97-100 15309514-4 2004 Imatinib mesylate, a KIT tyrosine kinase inhibitor, is an oral agent that has been found to have a dramatic antitumor effect on metastatic GIST with either wild-type or mutant KIT. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-24 15309514-4 2004 Imatinib mesylate, a KIT tyrosine kinase inhibitor, is an oral agent that has been found to have a dramatic antitumor effect on metastatic GIST with either wild-type or mutant KIT. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 176-179 15355900-14 2004 One patient with gastrointestinal stromal tumor who had rapid progression during SU5416 treatment was subsequently treated with another KIT inhibitor, imatinib mesylate, and had a partial response lasting >36 months. Imatinib Mesylate 151-168 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 136-139 15289888-1 2004 A therapeutic role of STI571 (imatinib mesylate) has been anticipated in patients with c-Kit positive neuroectodermal tumors. Imatinib Mesylate 22-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-92 15289888-1 2004 A therapeutic role of STI571 (imatinib mesylate) has been anticipated in patients with c-Kit positive neuroectodermal tumors. Imatinib Mesylate 30-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-92 15627886-12 2004 The results of this study support clinical trials targeting the c-kit receptor with specific c-kit inhibitors (e.g. imatinib). Imatinib Mesylate 116-124 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-69 15627886-12 2004 The results of this study support clinical trials targeting the c-kit receptor with specific c-kit inhibitors (e.g. imatinib). Imatinib Mesylate 116-124 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-98 15499612-1 2005 STI571, or imatinib, selectively inhibits BCR/ABL, PDGFR and c-kit kinase activity. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-66 15499612-1 2005 STI571, or imatinib, selectively inhibits BCR/ABL, PDGFR and c-kit kinase activity. Imatinib Mesylate 11-19 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-66 15723656-0 2005 STI571 (Glivec) inhibits the interaction between c-KIT and heat shock protein 90 of the gastrointestinal stromal tumor cell line, GIST-T1. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-54 15723656-2 2005 We report that STI571 (Glivec; Novartis, Basel, Switzerland), a specific inhibitor of c-KIT, inhibits the clustering of c-KIT at the cell membrane of the GIST-T1 cells. Imatinib Mesylate 15-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 86-91 15723656-2 2005 We report that STI571 (Glivec; Novartis, Basel, Switzerland), a specific inhibitor of c-KIT, inhibits the clustering of c-KIT at the cell membrane of the GIST-T1 cells. Imatinib Mesylate 15-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-125 15723656-3 2005 Furthermore, STI571 prevents the interaction between c-KIT and the molecular chaperone, heat shock protein 90 (Hsp90). Imatinib Mesylate 13-19 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-58 16122278-1 2005 Imatinib is a potent and selective inhibitor of the protein tyrosine kinase Bcr-Abl, platelet-derived growth factor receptors (PDGFRalpha and PDGFRbeta) and KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 157-160 15785039-8 2005 Imatinib at concentrations >5 microM inhibited cell proliferation and induced apoptosis in both c-Kit-positive and c-Kit-negative cell lines. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-104 15785039-8 2005 Imatinib at concentrations >5 microM inhibited cell proliferation and induced apoptosis in both c-Kit-positive and c-Kit-negative cell lines. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 118-123 15586222-1 2005 Imatinib mesylate, an inhibitor of tyrosine kinases including BCR-ABL and KIT, inhibits the growth inhibition of small cell lung cancer (SCLC) cell lines in vitro. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-77 16015044-1 2005 OBJECTIVE: Overexpression of KIT (CD117), a tyrosine kinase receptor, has been reported in a variety of tumors, some of which are susceptible to therapy with imatinib mesylate. Imatinib Mesylate 158-175 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-32 16015044-1 2005 OBJECTIVE: Overexpression of KIT (CD117), a tyrosine kinase receptor, has been reported in a variety of tumors, some of which are susceptible to therapy with imatinib mesylate. Imatinib Mesylate 158-175 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-39 15505216-3 2004 Imatinib mesylate has also been shown to inhibit KIT, ARG, and platelet-derived growth factor receptors alpha and beta, and potentially other tyrosine kinases. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 15505216-5 2004 In contrast, imatinib mesylate effectively eliminated BCR-ABL(+) KIT(+)-expressing leukemic cells. Imatinib Mesylate 13-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 65-68 15583695-1 2004 KIT and PDGFRA are receptor tyrosine kinases that can be specifically inactivated by small-molecule tyrosine kinase inhibitors, notably imatinib mesylate. Imatinib Mesylate 136-144 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 15618926-3 2004 c-kit expression has been demonstrated previously in primary MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit expressing tumors. Imatinib Mesylate 117-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 15618926-3 2004 c-kit expression has been demonstrated previously in primary MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit expressing tumors. Imatinib Mesylate 117-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 210-215 15549490-2 2004 Imatinib offers the first effective treatment for patients with GISTs, but the therapeutic outcome strongly depends on the type of KIT mutation. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 131-134 15638956-2 2004 In addition to paralleling what is already known about c-kit mutations that drive the proliferation of gastrointestinal stromal tumors and their response to imatinib, and providing the possibility of prospectively selecting patients with NSCLC who have a high probability of responding to EGFR TK inhibitors, these reports will likely have much broader implications with regard to the optimal and most expeditious means to develop rationally designed, target-based therapeutic agents--first establishing proof of principle in patients whose malignancies are dependent or driven by aberrations of the therapeutic"s target. Imatinib Mesylate 157-165 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 55-60 15507676-2 2004 Screening GISTs for KIT gene mutations is important for translational research studies and for providing prognostic information on the likelihood of tumor response to treatment with the kinase inhibitor imatinib mesylate (Gleevec). Imatinib Mesylate 203-220 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-23 15553717-3 2004 The development of a tyrosine kinase inhibitor, STI571 (imatinib mesylate, Glivec, Gleevec), which inhibits the BCR-ABL, PDGF-R alpha and c-kit receptors, has changed the management of unresectable malignant GIST and has improved the survival of patients with metastatic disease. Imatinib Mesylate 48-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-143 15553717-3 2004 The development of a tyrosine kinase inhibitor, STI571 (imatinib mesylate, Glivec, Gleevec), which inhibits the BCR-ABL, PDGF-R alpha and c-kit receptors, has changed the management of unresectable malignant GIST and has improved the survival of patients with metastatic disease. Imatinib Mesylate 56-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-143 15385107-1 2004 PURPOSE: Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets c-Kit, Abl, and platelet-derived growth factor receptor (PDGFR). Imatinib Mesylate 9-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-89 15469479-1 2004 AIMS: Imatinib mesylate specifically inhibits KIT tyrosine kinase activity, and has been proven to be effective in the treatment of gastrointestinal stromal tumours. Imatinib Mesylate 6-14 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-49 15469479-2 2004 Because other KIT-expressing malignancies might benefit from Imatinib therapy, we evaluated the distribution and expression of KIT in 1166 cases of malignant lymphoma. Imatinib Mesylate 61-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 15365079-8 2004 In particular, the responsiveness of GISTs to treatment with the kinase inhibitor imatinib varies substantially depending on the exonic location of the KIT or PDGFRA mutation. Imatinib Mesylate 82-90 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 152-155 15517872-3 2004 STI571 also selectively inhibits platelet-derived growth factor receptors (PDGFRs) and c-kit. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-92 15342366-0 2004 A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Imatinib Mesylate 59-67 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-26 15342366-2 2004 Imatinib is a selective tyrosine kinase inhibitor of ABL, platelet-derived growth factor receptor (PDGFR), and KIT and represents a new paradigm of targeted therapy against GISTs. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 111-114 15342366-3 2004 Here we report for the first time that, after imatinib treatment, an additional specific and novel KIT mutation occurs in GISTs as they develop resistance to the drug. Imatinib Mesylate 46-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-102 15342366-8 2004 All six rapidly progressive imatinib-resistant implants from five patients show an identical novel KIT missense mutation, 1982T-->C, that resulted in Val654Ala in KIT tyrosine kinase domain 1. Imatinib Mesylate 28-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-102 15342366-8 2004 All six rapidly progressive imatinib-resistant implants from five patients show an identical novel KIT missense mutation, 1982T-->C, that resulted in Val654Ala in KIT tyrosine kinase domain 1. Imatinib Mesylate 28-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 166-169 15471556-7 2004 Moreover, molecular targeting drugs such as imatinib mesylate (STI571), which is a selective inhibitor of KIT, might be promising agents for the treatment of intracranial germinomas with c-kit gene mutations. Imatinib Mesylate 44-61 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-109 15471556-7 2004 Moreover, molecular targeting drugs such as imatinib mesylate (STI571), which is a selective inhibitor of KIT, might be promising agents for the treatment of intracranial germinomas with c-kit gene mutations. Imatinib Mesylate 44-61 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 187-192 15471556-7 2004 Moreover, molecular targeting drugs such as imatinib mesylate (STI571), which is a selective inhibitor of KIT, might be promising agents for the treatment of intracranial germinomas with c-kit gene mutations. Imatinib Mesylate 63-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-109 15471556-7 2004 Moreover, molecular targeting drugs such as imatinib mesylate (STI571), which is a selective inhibitor of KIT, might be promising agents for the treatment of intracranial germinomas with c-kit gene mutations. Imatinib Mesylate 63-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 187-192 15689683-8 2004 Moreover, a unique therapeutic agent, imatinib, has been devised that specifically targets the aberrant KIT receptor and has demonstrated dramatic therapeutic efficacy in this otherwise resistant malignancy. Imatinib Mesylate 38-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 104-107 15289315-1 2004 KIT expression is a key diagnostic feature of gastrointestinal stromal tumors (GISTs), and virtually all of the GISTs express oncogenic forms of the KIT or PDGFRA receptor tyrosine kinase proteins, which serve as therapeutic targets of imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). Imatinib Mesylate 236-253 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 15289315-1 2004 KIT expression is a key diagnostic feature of gastrointestinal stromal tumors (GISTs), and virtually all of the GISTs express oncogenic forms of the KIT or PDGFRA receptor tyrosine kinase proteins, which serve as therapeutic targets of imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). Imatinib Mesylate 236-253 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 149-152 15270663-3 2004 Imatinib (Gleevec, Novartis) is an orally administered competitive inhibitor of the tyrosine kinase domain of receptors such as KIT, ABL, and BCR-ABL fusion proteins, and the platelet-derived growth factor receptor. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 128-131 15332547-3 2004 Imatinib mesylate (IM), an agent for chronic myeloid leukemia, was reported to inhibit tyrosine kinase activity of KIT and to be highly effective for GIST. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-118 15332547-3 2004 Imatinib mesylate (IM), an agent for chronic myeloid leukemia, was reported to inhibit tyrosine kinase activity of KIT and to be highly effective for GIST. Imatinib Mesylate 19-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-118 15286804-1 2004 Mutant isoforms of the KIT or PDGF receptors expressed by gastrointestinal stromal tumors (GISTs) are considered the therapeutic targets for STI571 (imatinib mesylate; Gleevec), a specific inhibitor of these tyrosine kinase receptors. Imatinib Mesylate 141-147 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-26 15105813-2 2004 Imatinib mesylate, a well-established inhibitor of bcr-abl tyrosine kinase, and currently used for the treatment of patients with chronic myeloid leukemia, also inhibits c-kit receptor kinase activity. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-175 15286804-1 2004 Mutant isoforms of the KIT or PDGF receptors expressed by gastrointestinal stromal tumors (GISTs) are considered the therapeutic targets for STI571 (imatinib mesylate; Gleevec), a specific inhibitor of these tyrosine kinase receptors. Imatinib Mesylate 149-166 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-26 15123710-5 2004 A 1.6-A crystal structure of c-Kit in complex with STI-571 (Imatinib or Gleevec) demonstrates that inhibitor binding disrupts this natural mechanism for maintaining c-Kit in an autoinhibited state. Imatinib Mesylate 51-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-34 15123710-5 2004 A 1.6-A crystal structure of c-Kit in complex with STI-571 (Imatinib or Gleevec) demonstrates that inhibitor binding disrupts this natural mechanism for maintaining c-Kit in an autoinhibited state. Imatinib Mesylate 51-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 165-170 15123710-5 2004 A 1.6-A crystal structure of c-Kit in complex with STI-571 (Imatinib or Gleevec) demonstrates that inhibitor binding disrupts this natural mechanism for maintaining c-Kit in an autoinhibited state. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-34 15123710-5 2004 A 1.6-A crystal structure of c-Kit in complex with STI-571 (Imatinib or Gleevec) demonstrates that inhibitor binding disrupts this natural mechanism for maintaining c-Kit in an autoinhibited state. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 165-170 15215166-10 2004 Reactivity for DOG1 may aid in the diagnosis of GISTs, including PDGFRA mutants that fail to express KIT antigen, and lead to appropriate treatment with imatinib mesylate, an inhibitor of the KIT tyrosine kinase. Imatinib Mesylate 153-170 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 192-195 15150562-0 2004 Late resistance to imatinib therapy in a metastatic gastrointestinal stromal tumour is associated with a second KIT mutation. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 112-115 15239791-3 2004 c-kit is selectively and competitively bound by STI-571, a newly developed tyrosine kinase inhibitor. Imatinib Mesylate 48-55 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 15283152-2 2004 Recently treatment with imatinib mesylate, a molecular targeted agent that inhibits the KIT tyrosine kinase receptor showed 81.6% of outstanding clinical response (PR 53.7%, SD 27.9%). Imatinib Mesylate 24-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 88-91 15383930-3 2004 Blockade of c-kit by imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp, East Hanover, NJ) has been successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal tumors. Imatinib Mesylate 21-38 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-17 15223958-12 2004 Notably, some KIT-negative GISTs contain imatinib-sensitive KIT or PDGFRA mutations; therefore, patients with KIT-negative GISTs should not, a priori, be denied imatinib therapy. Imatinib Mesylate 41-49 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 15223958-12 2004 Notably, some KIT-negative GISTs contain imatinib-sensitive KIT or PDGFRA mutations; therefore, patients with KIT-negative GISTs should not, a priori, be denied imatinib therapy. Imatinib Mesylate 41-49 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 15223958-12 2004 Notably, some KIT-negative GISTs contain imatinib-sensitive KIT or PDGFRA mutations; therefore, patients with KIT-negative GISTs should not, a priori, be denied imatinib therapy. Imatinib Mesylate 41-49 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 15236194-0 2004 A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 15236194-1 2004 BACKGROUND & AIMS: Imatinib, a tyrosine kinase inhibitor of BCR-ABL, KIT, and platelet-derived growth factor receptor, is used in patients with chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST). Imatinib Mesylate 23-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 15236194-10 2004 CONCLUSIONS: This new mutation was confined to the progressing lesion; the resulting amino acidic substitution, T670I, affecting the ATP/imatinib pocket of KIT, makes it insensitive to the drug. Imatinib Mesylate 137-145 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 156-159 15150562-3 2004 Mutation analysis showed that the imatinib-resistant liver tumour contained two c-kit mutations. Imatinib Mesylate 34-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-85 15126780-0 2004 C-kit expression in sarcomatoid renal cell carcinoma: potential therapy with imatinib. Imatinib Mesylate 77-85 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 15126780-3 2004 A relatively nontoxic tyrosine kinase inhibitor, imatinib (STI-571) has been approved as a target therapy in neoplasms that express c-Kit. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 132-137 15126780-3 2004 A relatively nontoxic tyrosine kinase inhibitor, imatinib (STI-571) has been approved as a target therapy in neoplasms that express c-Kit. Imatinib Mesylate 59-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 132-137 15007386-2 2004 KIT oncoproteins are detected early in GIST tumorigenesis, and most GIST patients respond well to treatment with the KIT kinase inhibitor imatinib mesylate (STI571, Gleevec). Imatinib Mesylate 138-155 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 15044919-2 2004 The recent observations that c-kit proto-oncogene, a tyrosine kinase, is overexpressed in small cell lung cancers and that advanced c-kit-expressing gastrointestinal stromal tumors were successfully treated with a selective tyrosine kinase inhibitor STI-571 (Gleevec, imatinib mesylate) prompted us to investigate c-kit protein expression in cervical small cell carcinomas. Imatinib Mesylate 250-257 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-49 15044919-2 2004 The recent observations that c-kit proto-oncogene, a tyrosine kinase, is overexpressed in small cell lung cancers and that advanced c-kit-expressing gastrointestinal stromal tumors were successfully treated with a selective tyrosine kinase inhibitor STI-571 (Gleevec, imatinib mesylate) prompted us to investigate c-kit protein expression in cervical small cell carcinomas. Imatinib Mesylate 250-257 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-34 15044919-2 2004 The recent observations that c-kit proto-oncogene, a tyrosine kinase, is overexpressed in small cell lung cancers and that advanced c-kit-expressing gastrointestinal stromal tumors were successfully treated with a selective tyrosine kinase inhibitor STI-571 (Gleevec, imatinib mesylate) prompted us to investigate c-kit protein expression in cervical small cell carcinomas. Imatinib Mesylate 250-257 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 132-137 15044919-2 2004 The recent observations that c-kit proto-oncogene, a tyrosine kinase, is overexpressed in small cell lung cancers and that advanced c-kit-expressing gastrointestinal stromal tumors were successfully treated with a selective tyrosine kinase inhibitor STI-571 (Gleevec, imatinib mesylate) prompted us to investigate c-kit protein expression in cervical small cell carcinomas. Imatinib Mesylate 259-266 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-49 15044919-2 2004 The recent observations that c-kit proto-oncogene, a tyrosine kinase, is overexpressed in small cell lung cancers and that advanced c-kit-expressing gastrointestinal stromal tumors were successfully treated with a selective tyrosine kinase inhibitor STI-571 (Gleevec, imatinib mesylate) prompted us to investigate c-kit protein expression in cervical small cell carcinomas. Imatinib Mesylate 259-266 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-34 15044919-2 2004 The recent observations that c-kit proto-oncogene, a tyrosine kinase, is overexpressed in small cell lung cancers and that advanced c-kit-expressing gastrointestinal stromal tumors were successfully treated with a selective tyrosine kinase inhibitor STI-571 (Gleevec, imatinib mesylate) prompted us to investigate c-kit protein expression in cervical small cell carcinomas. Imatinib Mesylate 259-266 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 132-137 15044919-2 2004 The recent observations that c-kit proto-oncogene, a tyrosine kinase, is overexpressed in small cell lung cancers and that advanced c-kit-expressing gastrointestinal stromal tumors were successfully treated with a selective tyrosine kinase inhibitor STI-571 (Gleevec, imatinib mesylate) prompted us to investigate c-kit protein expression in cervical small cell carcinomas. Imatinib Mesylate 268-285 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-49 15044919-2 2004 The recent observations that c-kit proto-oncogene, a tyrosine kinase, is overexpressed in small cell lung cancers and that advanced c-kit-expressing gastrointestinal stromal tumors were successfully treated with a selective tyrosine kinase inhibitor STI-571 (Gleevec, imatinib mesylate) prompted us to investigate c-kit protein expression in cervical small cell carcinomas. Imatinib Mesylate 268-285 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-34 15044919-2 2004 The recent observations that c-kit proto-oncogene, a tyrosine kinase, is overexpressed in small cell lung cancers and that advanced c-kit-expressing gastrointestinal stromal tumors were successfully treated with a selective tyrosine kinase inhibitor STI-571 (Gleevec, imatinib mesylate) prompted us to investigate c-kit protein expression in cervical small cell carcinomas. Imatinib Mesylate 268-285 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 132-137 14726395-0 2004 Efficacy and safety of imatinib in adult patients with c-kit-positive acute myeloid leukemia. Imatinib Mesylate 23-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 55-60 14726395-1 2004 This phase 2 pilot study was conducted to determine the efficacy and safety of imatinib mesylate in patients with c-kit-positive acute myeloid leukemia (AML) refractory to or not eligible for chemotherapy. Imatinib Mesylate 79-96 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 114-119 14726395-6 2004 Further, imatinib treatment of primary AML cells inhibited c-Kit tyrosine-phosphorylation. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 59-64 14726395-8 2004 Although some of the responses derived from relatively small reductions in leukemic blasts and may be attributable, in part, to prior chemotherapy, these cases suggest that imatinib has interesting clinical activity in a subset of patients with c-kit-positive AML. Imatinib Mesylate 173-181 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 245-250 15105658-7 2004 Finally, it should be determined whether KIT plays a role in the tumorigenesis of ChRCC and oncocytoma and whether targeted therapy with STI-571, an inhibitor of KIT, could be effective in exceptional cases of ChRCC with metastatic extension or recurrence. Imatinib Mesylate 137-144 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 162-165 15123459-6 2004 Imatinib is a potent, specific inhibitor of KIT that has demonstrated significant activity and tolerability in the treatment of malignant unresectable or metastatic GIST, inducing tumor shrinkage of 50% or more or stabilizing disease in most patients. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 15139047-5 2004 Imatinib is a selective inhibitor of PDGFRs, c-Kit, Abl and Arg protein-tyrosine kinases, as well as Bcr-Abl, the oncogenic tyrosine kinase that causes chronic myeloid leukemia. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-50 15007386-2 2004 KIT oncoproteins are detected early in GIST tumorigenesis, and most GIST patients respond well to treatment with the KIT kinase inhibitor imatinib mesylate (STI571, Gleevec). Imatinib Mesylate 138-155 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-120 15007386-2 2004 KIT oncoproteins are detected early in GIST tumorigenesis, and most GIST patients respond well to treatment with the KIT kinase inhibitor imatinib mesylate (STI571, Gleevec). Imatinib Mesylate 157-163 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 15007386-2 2004 KIT oncoproteins are detected early in GIST tumorigenesis, and most GIST patients respond well to treatment with the KIT kinase inhibitor imatinib mesylate (STI571, Gleevec). Imatinib Mesylate 157-163 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-120 15126530-3 2004 In chronic myeloid leukemia and gastrointestinal stromal tumors, imatinib inhibits the constitutive tyrosine kinase activity of BCR-ABL and c-KIT, respectively. Imatinib Mesylate 65-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 140-145 15206509-3 2004 On the other hand, imatinib is also active against other tyrosine kinases, such as ABL, the stem cell factor receptor (c-kit) and the platelet-derived growth factor receptor, whose inhibition might have potential implications for the treatment of several malignancies. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 119-124 15036937-4 2004 Kit is a convenient target in Kit-induced tumors and inhibition of this receptor with the small molecule drug Gleevec (imatinib mesylate, STI571) in GIST has shown dramatic efficacy. Imatinib Mesylate 119-136 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 15036937-4 2004 Kit is a convenient target in Kit-induced tumors and inhibition of this receptor with the small molecule drug Gleevec (imatinib mesylate, STI571) in GIST has shown dramatic efficacy. Imatinib Mesylate 119-136 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-33 14985355-6 2004 STI-571, a c-kit inhibitor, dose-dependently attenuated these phosphorylations and inhibited stem cell factor-promoted survival and capillary tube formation over the same dose range. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 11-16 15141010-2 2004 Previous data suggested that IGF-I protects cells from apoptosis induced by STI571, an efficient inhibitor of Kit signal transduction, by activating the critical phosphatidylinositol 3-kinase-Akt pathway. Imatinib Mesylate 76-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 15100500-1 2004 BACKGROUND: The new anti-cancer drug imatinib mesylate inhibits the tyrosine kinase growth factor receptor, c-KIT, and has shown spectacular activity in patients with gastrointestinal stromal tumours (GISTs). Imatinib Mesylate 37-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 108-113 15070666-0 2004 Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib. Imatinib Mesylate 94-102 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 6-9 15070666-4 2004 After 1 and 6 months of imatinib treatment the average serum KIT levels decreased 31% and 52% from pretreatment levels, whereas SCF levels increased 11% and 33%, respectively. Imatinib Mesylate 24-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-64 15070666-7 2004 A high serum SCF/KIT ratio may increase SCF-induced cell signaling with prolonged imatinib treatment, at the time when imatinib treatment is withdrawn, and in patients whose GIST has wild-type receptors. Imatinib Mesylate 82-90 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-20 15070666-7 2004 A high serum SCF/KIT ratio may increase SCF-induced cell signaling with prolonged imatinib treatment, at the time when imatinib treatment is withdrawn, and in patients whose GIST has wild-type receptors. Imatinib Mesylate 119-127 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-20 15070706-0 2004 A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib. Imatinib Mesylate 92-100 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-66 15070706-2 2004 Transfection experiments revealed that the mutation caused ligand-independent autophosphorylation of Kit, which was inhibited by the tyrosine kinase inhibitor imatinib mesylate. Imatinib Mesylate 159-176 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 101-104 15070706-5 2004 These results highlight the significance of the transmembrane region of Kit in activation of the molecule and its importance in mast cell development and suggest a role for screening for transmembrane c-kit mutations in patients with mastocytosis in association with the decision to use imatinib mesylate. Imatinib Mesylate 287-295 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-75 15070666-1 2004 Imatinib mesylate is a selective inhibitor of a few tyrosine kinases including KIT, and it is the first effective treatment for gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 79-82 15188667-6 2004 Most GISTs respond to imatinib mesylate, which selectively inhibits both KIT and PDGFRA, and is now considered as the standard systemic therapy for advanced GIST. Imatinib Mesylate 22-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 15087667-12 2004 Furthermore, STI-571, targeting c-kit and PDGFR tyrosine kinase, seems to be a possible therapeutic strategy for EGISTs, especially advanced cases. Imatinib Mesylate 13-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 32-37 15033665-7 2004 This study suggests the necessity for clinical trials confirming the utility of the tyrosine kinase inhibitor, STI571, in ovarian advanced cancer patients with c-KIT overexpression when these patients have shown no clinical response to conventional chemotherapy. Imatinib Mesylate 111-117 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 160-165 15057146-5 2004 The prognosis of these diseases improved enormously since the drug imatinib, a tyrosine kinase inhibitor of c-kit and bcr-abl, was introduced. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 108-113 14726674-5 2004 Here we describe that blocking c-Kit with STI571 inhibits these malignant traits not only in DLD-1 cells but also in two early passage colorectal carcinoma cell strains. Imatinib Mesylate 42-48 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 31-36 14726674-3 2004 In addition to BCR/ABL, STI571 inhibits the tyrosine kinase moieties of several cell surface receptors including the platelet-derived growth factor (PDGF) receptors and c-Kit. Imatinib Mesylate 24-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 169-174 14718589-1 2004 The 2-phenylaminopyrimidine derivative imatinib-mesylate, a powerful protein tyrosine kinase (PTK) inhibitor that targets abl, c-kit, and the platelet-derived growth factor receptors, is rapidly gaining a relevant role in the treatment of several types of neoplasms. Imatinib Mesylate 39-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 127-132 15024716-13 2004 GISTs with very low levels of KIT expression may respond to imatinib mesylate therapy if the receptors are activated by specific mechanisms. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-33 15175998-3 2004 Tumors caused by chromosomal translocations that lead to overexpression of PDGFR ligand, resulting in continuous activation of wild-type PDGFRs, are likely to respond to imatinib, as are malignancies caused by gene amplification and overexpression of wild-type PDGFR or KIT receptors. Imatinib Mesylate 170-178 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 270-273 15175998-4 2004 Malignancies linked to chromosomal translocations that express PDGFR or KIT fusion protein-tyrosine kinases are also likely to respond to imatinib. Imatinib Mesylate 138-146 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-75 14726714-6 2004 The identification of a novel tumor-specific target in c-KIT resulted in the development of a tyrosine kinase-inhibitor (imatinib mesylate) that provides an encouraging option for treating GISTs. Imatinib Mesylate 121-138 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 55-60 15106018-11 2004 This new tyrosine kinase inhibitor, imatinib mesylate, which inhibits the c-kit receptor, has proved highly effective against GIST and has improved survival in metastatic GIST. Imatinib Mesylate 36-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 76-79 15703627-3 2004 The clinical application of imatinib mesylate, a selective inhibitor of the KIT kinase activity, has provided a novel molecularly targeted therapy for these tumors. Imatinib Mesylate 28-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 76-79 15010069-0 2004 Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Imatinib Mesylate 76-84 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 7-12 15010069-1 2004 Previous studies have shown that activating mutations of c-KIT/PDGFRA, potential therapeutic targets for imatinib mesylate, are implicated in the pathophysiology of gastrointestinal stromal tumours (GISTs). Imatinib Mesylate 105-113 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-62 15010069-11 2004 These findings indicate that the mutational status of the c-KIT/PDGFRA oncoproteins could be useful to predict the clinical response of patients imatinib therapy. Imatinib Mesylate 145-153 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-63 14677065-0 2004 Rare KIT (CD117) expression in multiple myeloma abrogates the usefulness of imatinib mesylate treatment. Imatinib Mesylate 76-93 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 5-8 14677065-0 2004 Rare KIT (CD117) expression in multiple myeloma abrogates the usefulness of imatinib mesylate treatment. Imatinib Mesylate 76-93 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-15 14677065-1 2004 BACKGROUND: Imatinib mesylate blocks the tyrosine kinase activity of KIT (CD117) and is an effective treatment for gastrointestinal stromal tumors. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-72 14677065-1 2004 BACKGROUND: Imatinib mesylate blocks the tyrosine kinase activity of KIT (CD117) and is an effective treatment for gastrointestinal stromal tumors. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-79 15022111-7 2004 The third case of a 40-year-old patient with a malignant GIST recurrence after surgery and exhibiting secondary resistance after one year of successful therapy with the receptor tyrosine kinase inhibitor imatinib (Gleevec), antagonizing pathogenetically relevant constitutive c-KIT activation, illustrates the potential and limitations of the only effective drug treatment for advanced GIST. Imatinib Mesylate 204-212 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 276-281 14760098-0 2004 Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 86-89 14760098-2 2004 We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines. Imatinib Mesylate 51-59 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 35-38 14760098-6 2004 Treatment with KIT tyrosine kinase inhibitor imatinib (0.5-20 micro M) induced down-regulation of KIT phosphorylation and dose response inhibition of cell proliferation (IC(50), 12-15 micro M). Imatinib Mesylate 45-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 15-18 14760098-6 2004 Treatment with KIT tyrosine kinase inhibitor imatinib (0.5-20 micro M) induced down-regulation of KIT phosphorylation and dose response inhibition of cell proliferation (IC(50), 12-15 micro M). Imatinib Mesylate 45-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-101 14760098-8 2004 We then analyzed if blockade of KIT loop through imatinib (10 micro M) was able to increase the antitumor in vitro effect of doxorubicin (DXR) and vincristine (VCR), drugs usually used in Ewing tumor treatment. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 32-35 14760098-10 2004 CONCLUSIONS: Inhibition of Ewing tumor cell proliferation by imatinib is mediated through blockade of KIT receptor signaling. Imatinib Mesylate 61-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-105 14710199-2 2004 The leading drug in this area is imatinib mesylate, which targets ABL, KIT and PDGFR. Imatinib Mesylate 33-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-74 15327887-4 2004 As imatinib also inhibits the tyrosine kinase activity of KIT and the platelet-derived growth factor receptors, the extension of imatinib to malignancies driven by these kinases will be described. Imatinib Mesylate 3-11 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-61 15327887-4 2004 As imatinib also inhibits the tyrosine kinase activity of KIT and the platelet-derived growth factor receptors, the extension of imatinib to malignancies driven by these kinases will be described. Imatinib Mesylate 129-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-61 14967957-0 2004 Metastatic gastrointestinal stromal tumor with an exon 11 c-kit mutation responding to the tyrosine kinase inhibitor imatinib. Imatinib Mesylate 117-125 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-63 14745431-0 2004 High incidence of BCR-ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib. Imatinib Mesylate 158-166 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-95 14745431-1 2004 Imatinib, a specific inhibitor of the Abl, Kit and platelet-derived growth factor receptor (PDGFR) tyrosine kinases, is effective in all phases of chronic myelogenous leukemia. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-46 15015226-2 2004 Imatinib potently inhibits several protein tyrosine kinases, including BCR-ABL, c-Kit, and PDGF receptor. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-85 14635203-1 2003 Imatinib mesylate targets the adenosine triphosphate (ATP)-binding sites of the protein tyrosine kinase domains associated with Bcr-abl, the platelet-derived growth factor (PDGF) and c-kit. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 183-188 14672776-1 2003 BACKGROUND: Imatinib mesylate (Gleevec) is being studied as adjuvant chemotherapy for the treatment of cKIT+ gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-107 15045935-3 2004 Although the first-line therapy of resectable GISTs is surgery, imatinib mesylate, a target-based molecule against KIT and PDGF-R alpha proteins, showed remarkable clinical effects and good tolerability for non-resectable GISTs. Imatinib Mesylate 64-72 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-118 15018431-12 2004 These results suggest that such drugs as imatinib mesylate, which inhibit the c-kit tyrosine kinase, should be investigated for these mesenchymal neoplasms. Imatinib Mesylate 41-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 78-83 15027317-1 2004 Imatinib mesylate is a new drug that can inhibit the tyrosine kinase activity of Bcr-Abl, the receptors for platelet-derived growth factor receptor(PDGF) and stem cell factor, or c-kit. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 179-184 14735360-5 2004 Imatinib is a small-molecule inhibitor that selectively blocks the activity of the PDGF-R, ABL and KIT receptor tyrosine kinases by competitive binding to the adenosine triphosphate binding site of their catalytic domains. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-102 15032571-4 2004 Imatinib mesylate (Gleevec, STI571, or CP57148B) is a direct inhibitor of ABL (ABL1), ARG (ABL2), KIT, and PDGFR tyrosine kinases. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-101 15032571-4 2004 Imatinib mesylate (Gleevec, STI571, or CP57148B) is a direct inhibitor of ABL (ABL1), ARG (ABL2), KIT, and PDGFR tyrosine kinases. Imatinib Mesylate 28-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-101 15250677-9 2004 Research studies have identified imatinib as a potential treatment option for a diverse range of malignancies associated with BCR-Abl, platelet-derived growth factor receptor (PDGFr) and c-Kit pathways. Imatinib Mesylate 33-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 187-192 15069768-7 2004 Recently, a small molecule tyrosine kinase inhibitor (STI571, imatinib mesylate, Gleevec) directed against the enzymatic (kinase) domain of the KIT protein was found to produce dramatic clinical responses as monotherapy for metastatic GISTs. Imatinib Mesylate 54-60 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 144-147 15069768-7 2004 Recently, a small molecule tyrosine kinase inhibitor (STI571, imatinib mesylate, Gleevec) directed against the enzymatic (kinase) domain of the KIT protein was found to produce dramatic clinical responses as monotherapy for metastatic GISTs. Imatinib Mesylate 62-79 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 144-147 15532894-2 2004 This review outlines present-day experiences with imatinib (Glivec), a potent inhibitor of the tyrosine kinases bcr-abl, c-kit and platelet-derived growth factor receptor kinase. Imatinib Mesylate 50-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 121-126 15532894-2 2004 This review outlines present-day experiences with imatinib (Glivec), a potent inhibitor of the tyrosine kinases bcr-abl, c-kit and platelet-derived growth factor receptor kinase. Imatinib Mesylate 60-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 121-126 14734467-2 2004 Some KIT-overexpressing solid tumors have responded favorably to STI571, potentially because of the presence of KIT-activating mutations. Imatinib Mesylate 65-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 5-8 14734467-2 2004 Some KIT-overexpressing solid tumors have responded favorably to STI571, potentially because of the presence of KIT-activating mutations. Imatinib Mesylate 65-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 112-115 15511212-9 2004 Using STI571 (5 microM, 16 hours) to inhibit the c-Kit pathway following stimulation with SCF (100 ng/mL), an upregulation of topo-I activity was observed in H526 cells but not in H82 cells. Imatinib Mesylate 6-12 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-54 14632777-2 2003 We have investigated the effect of imatinib mesylate (STI571), an inhibitor of c-Kit, on MM cells. Imatinib Mesylate 35-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 79-84 14632777-2 2003 We have investigated the effect of imatinib mesylate (STI571), an inhibitor of c-Kit, on MM cells. Imatinib Mesylate 54-60 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 79-84 14635084-1 2003 BACKGROUND: Imatinib mesylate is a tyrosine kinase inhibitor that targets the BCR-ABL protein in CML, c-kit (KIT) and platelet-derived growth factor receptors. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-107 14635084-1 2003 BACKGROUND: Imatinib mesylate is a tyrosine kinase inhibitor that targets the BCR-ABL protein in CML, c-kit (KIT) and platelet-derived growth factor receptors. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 109-112 14635084-9 2003 Several lines of evidence have previously reported that KIT and its ligand stem cell factor (SCF) have a regulatory role in melanocyte development and survival, suggesting a rational mechanism of action for imatinib mesylate in the pathogenesis of hypopigmentation. Imatinib Mesylate 207-224 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 56-59 14676110-14 2003 Further testing of imatinib in patients with SCLC will focus on demonstration of KIT expression in the setting of confirmed SCLC histology. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 14645423-1 2003 PURPOSE: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. Imatinib Mesylate 218-235 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-109 14645423-7 2003 All KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in vitro. Imatinib Mesylate 88-96 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-7 14645423-10 2003 CONCLUSION: Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib. Imatinib Mesylate 177-185 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 36-39 16767900-0 2003 Tyrosine kinase inhibitor imatinib mesylate as anticancer agent for advanced ocular melanoma expressing immunoistochemical C-KIT (CD 117): preliminary results of a compassionate use clinical trial. Imatinib Mesylate 26-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-128 16767900-0 2003 Tyrosine kinase inhibitor imatinib mesylate as anticancer agent for advanced ocular melanoma expressing immunoistochemical C-KIT (CD 117): preliminary results of a compassionate use clinical trial. Imatinib Mesylate 26-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 130-136 16767900-1 2003 Imatinib mesylate (IM), is a selective and competitive inhibitor of tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 16767900-1 2003 Imatinib mesylate (IM), is a selective and competitive inhibitor of tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). Imatinib Mesylate 19-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 14686698-4 2003 Imatinib is the first rationally designed selective inhibitor of specific protein tyrosine kinases, including KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 12960256-2 2003 We thus examined the effects of STI571, an inhibitor of the c-kit tyrosine kinase receptor, on the proliferation and function of human mast cells. Imatinib Mesylate 32-38 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-65 14639002-7 2003 STI571 is also a potent inhibitor of a receptor-type c-Kit tyrosine kinase. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-58 14986524-4 2003 The rewardable clinical response of tumors that express C-Kit to treatment with the tyrosine kinase inhibitor STI 571 is a triumph of molecular pharmacology. Imatinib Mesylate 110-117 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 56-61 14686005-3 2003 Imatinib (2-fenilaminopirimidine) is a selective inhibitor of the mutated C-KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-79 14682111-4 2003 Imatinib mesylate (Gleevec) is a specific inhibitor of KIT kinase activation, and in phase II clinical trials has proven to be remarkably efficacious in heavily pretreated GIST patients with advanced disease. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 55-58 14682111-4 2003 Imatinib mesylate (Gleevec) is a specific inhibitor of KIT kinase activation, and in phase II clinical trials has proven to be remarkably efficacious in heavily pretreated GIST patients with advanced disease. Imatinib Mesylate 19-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 55-58 14551510-8 2003 Imatinib (10 and 20 micromol/l) alone inhibited cell growth significantly higher in c-kit+ cell lines (p<0.02) and inhibition was independent of PDGFR status. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-89 14606348-1 2003 One of the undoubted major breakthroughs in the recent treatment of cancer is imatinib, a tyrosine-kinase inhibitor of the bcr-abl fusion protein, the stem-cell factor receptor c-kit (KIT) and the platelet-derived growth-factor receptor. Imatinib Mesylate 78-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 177-182 14606348-1 2003 One of the undoubted major breakthroughs in the recent treatment of cancer is imatinib, a tyrosine-kinase inhibitor of the bcr-abl fusion protein, the stem-cell factor receptor c-kit (KIT) and the platelet-derived growth-factor receptor. Imatinib Mesylate 78-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 184-187 14606348-3 2003 However, experience so far with imatinib in KIT-positive tumours indicates that imatinib seems only to be effective in those tumours with a gain-of-function mutation in c-kit. Imatinib Mesylate 32-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 14606348-3 2003 However, experience so far with imatinib in KIT-positive tumours indicates that imatinib seems only to be effective in those tumours with a gain-of-function mutation in c-kit. Imatinib Mesylate 80-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 14606348-3 2003 However, experience so far with imatinib in KIT-positive tumours indicates that imatinib seems only to be effective in those tumours with a gain-of-function mutation in c-kit. Imatinib Mesylate 80-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 169-174 14606351-4 2003 The correct diagnosis of GISTs is crucial for the new treatment option with imatinib, the tyrosine-kinase inhibitor specifically targeted against KIT. Imatinib Mesylate 76-84 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 146-149 14551510-11 2003 We conclude that imatinib alone exerts marked effects on c-kit+ biliary tract cancer cell lines only at intermediate and high concentrations, but there is a potential role of low-dose imatinib in combination with 5-FU for the treatment of biliary tract cancers. Imatinib Mesylate 17-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-62 12800187-10 2003 These data demonstrate that both c-Kit and SCF are preferentially expressed in vivo in the most aggressive neuroblastic tumors and that their signaling is active in promoting in vitro NB cell proliferation that can be selectively inhibited by treatment with STI-571. Imatinib Mesylate 258-265 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 33-38 14515284-4 2003 GISTs are notoriously unresponsive to chemotherapy and, until the recent introduction of the KIT inhibitor imatinib, there has been no effective therapy for advanced, metastatic disease. Imatinib Mesylate 107-115 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-96 14613030-2 2003 This quest has taken a major leap forward with the demonstration that STI-571 (imatinib mesylate) induces clinical and molecular remissions in the majority of patients with interferon-refractory chronic myelogenous leukemia and gastrointestinal stromal tumors through inhibition of the Bcr/Abl fusion protein required for the initiation and progression of chronic myelogenous leukemia and inhibition of a mutant, activated c-kit present in gastrointestinal stromal tumors. Imatinib Mesylate 70-77 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 423-428 14613030-2 2003 This quest has taken a major leap forward with the demonstration that STI-571 (imatinib mesylate) induces clinical and molecular remissions in the majority of patients with interferon-refractory chronic myelogenous leukemia and gastrointestinal stromal tumors through inhibition of the Bcr/Abl fusion protein required for the initiation and progression of chronic myelogenous leukemia and inhibition of a mutant, activated c-kit present in gastrointestinal stromal tumors. Imatinib Mesylate 79-96 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 423-428 14531349-2 2003 A new drug, Imatinib, is a potent inhibitor of a subgroup of the tyrosine kinase family comprising BCR-ABL, platelet-derived growth factor, and c-kit. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 144-149 12970769-2 2003 Inhibition of the c-abl, platelet-derived growth factor receptor and stem cell factor receptor (c-kit) tyrosine kinases by imatinib has also been reported. Imatinib Mesylate 123-131 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-101 12951180-6 2003 At least, tyrosine kinase inhibitors, a new family of molecules, are able of inhibiting some types of the mutated c-kit protein and one of them, imatinib mesylate, has shown a great efficacy in the treatment of gastro intestinal stromal tumors (GIST) which also involves the c-kit mutation. Imatinib Mesylate 145-153 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 114-119 12951180-6 2003 At least, tyrosine kinase inhibitors, a new family of molecules, are able of inhibiting some types of the mutated c-kit protein and one of them, imatinib mesylate, has shown a great efficacy in the treatment of gastro intestinal stromal tumors (GIST) which also involves the c-kit mutation. Imatinib Mesylate 145-153 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 275-280 12944919-4 2003 The involvement of PDGFRA led us to treat the patient with the small organic compound imatinib mesylate/STI571 (Glivec) that blocks the ATP binding site of tyrosine kinases such as Abelson, KIT and platelet-derived growth factor receptors. Imatinib Mesylate 86-103 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 190-193 12944919-4 2003 The involvement of PDGFRA led us to treat the patient with the small organic compound imatinib mesylate/STI571 (Glivec) that blocks the ATP binding site of tyrosine kinases such as Abelson, KIT and platelet-derived growth factor receptors. Imatinib Mesylate 104-110 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 190-193 12888812-4 2003 Imatinib, a KIT tyrosine kinase inhibitor, has recently been found to have a dramatic antitumour effect on GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-15 12938280-3 2003 Because imatinib also inhibits c-kit and platelet-derived growth-factor (PDGF) receptor, it may be efficacious against some tumors which possess c-kit or PDGF receptors. Imatinib Mesylate 8-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 31-36 12938280-3 2003 Because imatinib also inhibits c-kit and platelet-derived growth-factor (PDGF) receptor, it may be efficacious against some tumors which possess c-kit or PDGF receptors. Imatinib Mesylate 8-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 145-150 12939459-8 2003 On a functional level, we demonstrated that imatinib inhibited phosphorylation of KIT, AKT, and extracellular signal-regulated kinase 1/2 without affecting the total level of these proteins and that differential expression of these response genes involved activation of mitogen-activated protein kinase-dependent and -independent pathways. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-85 12798163-1 2003 Imatinib mesylate (Gleevec, Glivec, STI571) is a targeted, small molecule inhibitor of the oncogenes, BCR/ABL and c-KIT, and has striking antitumor activity in patients with chronic myelogenous leukemia or gastrointestinal stromal tumors. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 114-119 12798163-1 2003 Imatinib mesylate (Gleevec, Glivec, STI571) is a targeted, small molecule inhibitor of the oncogenes, BCR/ABL and c-KIT, and has striking antitumor activity in patients with chronic myelogenous leukemia or gastrointestinal stromal tumors. Imatinib Mesylate 36-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 114-119 12916883-2 2003 The decision to try Imatinib was guided by bright expression of c-kit on the patient"s blasts. Imatinib Mesylate 20-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-69 12916883-9 2003 This is the first report demonstrating that Imatinib can induce complete remission in relapsed c-kit positive AML in an elderly patient. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-100 12912938-5 2003 Success of inhibition of KIT in malignant gastrointestinal stromal tumors with imatinib mesylate seems mutation-dependent, with a favorable response in the presence of exon 11 mutations. Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 25-28 12912938-25 2003 Still, without the availability of effective therapies, treatment with the KIT inhibitor imatinib mesylate might be considered for patients with postradiation sarcomas. Imatinib Mesylate 89-106 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-78 12901973-4 2003 RESULTS: STI571 failed to inhibit the growth of HMC-1(560,816) cells bearing a codon 816 mutation but effectively suppressed the proliferation of HMC-1(560) carrying c-kit with the wild-type codon 816. Imatinib Mesylate 9-15 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 166-171 12767088-1 2003 BACKGROUND: Imatinib mesylate is a selective tyrosine kinase inhibitor of c-abl, bcr/abl, c-kit, and platelet-derived growth factor-receptor (PDGF-R). Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-95 12783584-4 2003 Imatinib mesylate (Gleevec), Glivec, Novartis) is a specific inhibitor of Kit kinase activation and in Phase II clinical trials, it has proven to be remarkably effective in heavily pre-treated patients with advanced GIST. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-77 12783584-4 2003 Imatinib mesylate (Gleevec), Glivec, Novartis) is a specific inhibitor of Kit kinase activation and in Phase II clinical trials, it has proven to be remarkably effective in heavily pre-treated patients with advanced GIST. Imatinib Mesylate 19-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-77 12743148-11 2003 Accordingly, the dose of STI-571 required to give a significant ES growth inhibition is much higher than for those tumors in which mutations of c-kit constitute a relevant pathogenetic event. Imatinib Mesylate 25-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 144-149 12844407-0 2003 [In vitro effect of STI571 on expression of c-kit in bone marrow cells from patients with acute non-lymphocytic leukemia]. Imatinib Mesylate 20-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-49 12844407-1 2003 This study was designed to explore the influence of STI571, a tyrosine kinase inhibitor, on the expression of c-kit in the bone marrow cells from patients with acute non-lymphocytic leukemia (ANLL). Imatinib Mesylate 52-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-115 12844407-3 2003 The results showed that STI571 treatment induced concentration-dependent decrease of c-kit and CD117 expression, which was significant lower than that in group before treatment and untreated control groups (P < 0.05) and 0.1 micro mol/L STI571 group was significantly higher than that in 10 micro mol/L group (P < 0.05). Imatinib Mesylate 24-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-90 12844407-3 2003 The results showed that STI571 treatment induced concentration-dependent decrease of c-kit and CD117 expression, which was significant lower than that in group before treatment and untreated control groups (P < 0.05) and 0.1 micro mol/L STI571 group was significantly higher than that in 10 micro mol/L group (P < 0.05). Imatinib Mesylate 24-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-100 12743148-7 2003 In vitro growth of ES cell lines showing high levels of c-kit demonstrated limited inhibition by exposure to STI-571 (10 micromol/L is required to obtain 40% to 50% of growth inhibition). Imatinib Mesylate 109-116 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 56-61 12702540-0 2003 Potential use of imatinib mesylate in ocular melanoma and liposarcoma expressing immunohistochemical c-KIT (CD117). Imatinib Mesylate 17-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 101-106 12702540-0 2003 Potential use of imatinib mesylate in ocular melanoma and liposarcoma expressing immunohistochemical c-KIT (CD117). Imatinib Mesylate 17-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 108-113 12759750-7 2003 STI-571 (imatinib mesylate) is a molecule that inhibits the function of various receptors with tyrosine kinase activity, such as abl, the bcr-abl chimeric product, platelet-derived growth factor receptor, and KIT. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 209-212 12781364-2 2003 Imatinib is a potent inhibitor of ABL, ARG, PDGFRalpha, PDGFRbeta, and KIT and induces durable hematologic responses in HES patients. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-74 12739051-8 2003 Imatinib (STI571/Glivec) is a selective inhibitor of BCR/ABL, PDGFR and KIT receptor-tyrosine kinases. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-75 12759750-7 2003 STI-571 (imatinib mesylate) is a molecule that inhibits the function of various receptors with tyrosine kinase activity, such as abl, the bcr-abl chimeric product, platelet-derived growth factor receptor, and KIT. Imatinib Mesylate 9-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 209-212 12679736-9 2003 As c-KIT was expressed in 78% of the pancreatic IDCs, it suggests that STI571 may be a beneficial agent for chemotherapy against human pancreatic IDCs. Imatinib Mesylate 71-77 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 5-8 12480706-1 2003 Imatinib mesylate, a tyrosine kinase inhibitor targeting bcr-abl, platelet-derived growth factor receptor (PDGF-R), and c-Kit, effectively induces hematologic and cytogenetic remissions in bcr-abl(+) chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) with only mild to moderate side effects. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-125 12824897-7 2003 Imatinib mesylate also inhibits the mutated KIT observed in most GISTs, and this explains the effectiveness of Imatinib mesylate on GISTs. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 12824897-7 2003 Imatinib mesylate also inhibits the mutated KIT observed in most GISTs, and this explains the effectiveness of Imatinib mesylate on GISTs. Imatinib Mesylate 111-128 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 12651205-1 2003 Previous studies have shown that STI571, a selective tyrosine kinase inhibitor of c-KIT, is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumours (GIST), especially those that have activating mutations in the c-kit exon 11 that encodes the juxtamembrane (JM) domain of the c-KIT oncoprotein. Imatinib Mesylate 33-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-87 12651205-1 2003 Previous studies have shown that STI571, a selective tyrosine kinase inhibitor of c-KIT, is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumours (GIST), especially those that have activating mutations in the c-kit exon 11 that encodes the juxtamembrane (JM) domain of the c-KIT oncoprotein. Imatinib Mesylate 33-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 112-117 12651205-1 2003 Previous studies have shown that STI571, a selective tyrosine kinase inhibitor of c-KIT, is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumours (GIST), especially those that have activating mutations in the c-kit exon 11 that encodes the juxtamembrane (JM) domain of the c-KIT oncoprotein. Imatinib Mesylate 33-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 118-123 12651205-1 2003 Previous studies have shown that STI571, a selective tyrosine kinase inhibitor of c-KIT, is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumours (GIST), especially those that have activating mutations in the c-kit exon 11 that encodes the juxtamembrane (JM) domain of the c-KIT oncoprotein. Imatinib Mesylate 33-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 229-234 12651205-1 2003 Previous studies have shown that STI571, a selective tyrosine kinase inhibitor of c-KIT, is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumours (GIST), especially those that have activating mutations in the c-kit exon 11 that encodes the juxtamembrane (JM) domain of the c-KIT oncoprotein. Imatinib Mesylate 33-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 112-117 12660384-3 2003 Recent reports of responses to imatinib in patients with the syndrome suggested that an activated kinase such as ABL, platelet-derived growth factor receptor (PDGFR), or KIT, all of which are inhibited by imatinib, might be the cause. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-173 12660384-3 2003 Recent reports of responses to imatinib in patients with the syndrome suggested that an activated kinase such as ABL, platelet-derived growth factor receptor (PDGFR), or KIT, all of which are inhibited by imatinib, might be the cause. Imatinib Mesylate 205-213 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-173 12435730-1 2003 The tyrosine kinase inhibitor STI-571 potently blocks BCR-Abl, platelet-derived growth factor (PDGF) alpha- and beta-receptors, and c-Kit kinase activity. Imatinib Mesylate 30-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 101-137 12640290-2 2003 This effect is consistent with the inhibitory effect of imatinib mesylate on c-kit"s tyrosine kinase activity as demonstrated by its effectiveness in patients with gastrointestinal stromal tumors. Imatinib Mesylate 56-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-82 12610357-1 2003 The presence of c-Kit immunoreactivity in gastrointestinal stromal tumor (GIST), currently guides treatment with the selective c-Kit inhibitor STI571 (or Gleevec) in clinical trials and establishes a precedent of immunohistochemistry-guided treatment decisions. Imatinib Mesylate 143-149 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 16-21 12610357-1 2003 The presence of c-Kit immunoreactivity in gastrointestinal stromal tumor (GIST), currently guides treatment with the selective c-Kit inhibitor STI571 (or Gleevec) in clinical trials and establishes a precedent of immunohistochemistry-guided treatment decisions. Imatinib Mesylate 143-149 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 127-132 12655446-0 2003 Response to imatinib mesylate of a gastrointestinal stromal tumor with very low expression of KIT. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 94-97 12655446-2 2003 Imatinib mesylate (formerly STI571) is a potent inhibitor of KIT kinase activity and has been proven to be highly active in patients with unresectable or metastatic GIST expressing immunohistochemically detectable KIT protein. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-64 12655446-2 2003 Imatinib mesylate (formerly STI571) is a potent inhibitor of KIT kinase activity and has been proven to be highly active in patients with unresectable or metastatic GIST expressing immunohistochemically detectable KIT protein. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 214-217 12655446-2 2003 Imatinib mesylate (formerly STI571) is a potent inhibitor of KIT kinase activity and has been proven to be highly active in patients with unresectable or metastatic GIST expressing immunohistochemically detectable KIT protein. Imatinib Mesylate 28-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-64 12655446-2 2003 Imatinib mesylate (formerly STI571) is a potent inhibitor of KIT kinase activity and has been proven to be highly active in patients with unresectable or metastatic GIST expressing immunohistochemically detectable KIT protein. Imatinib Mesylate 28-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 214-217 12655446-5 2003 Our experience with this patient suggests that even GISTs with very low levels of KIT expression may respond to imatinib mesylate therapy. Imatinib Mesylate 112-129 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-85 12475982-5 2003 SCF-induced c-Kit phosphorylation was also inhibited by the related inhibitor 4-amino-5- (4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP2) and by STI571 but not by the Src inhibitor SU6656. Imatinib Mesylate 157-163 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-17 12569358-0 2003 Effect of tyrosine kinase inhibitor STI571 on the kinase activity of wild-type and various mutated c-kit receptors found in mast cell neoplasms. Imatinib Mesylate 36-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-104 12569358-5 2003 Here, we show that STI571 inhibits both wild-type and juxtamembrane mutant c-kit kinase activity, but has no effect on the activity of the D816 V mutant. Imatinib Mesylate 19-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-80 12569358-6 2003 Accordingly, STI571 selectively decreases the survival of normal mast cell and of mast cell lines either with juxtamembrane c-kit mutations, but not that of tumoral mast cell from patient with SM or of mast cell lines with the D816 V mutation. Imatinib Mesylate 13-19 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-129 12528772-2 2002 The specific identification of GIST has become increasingly important because a Kit-selective tyrosine kinase inhibitor, imatinib (Glivec, formerly known as STI571, Novartis Pharma AG, Basel, Switzerland), has shown promise as an effective adjuvant therapy treatment. Imatinib Mesylate 131-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-83 12573349-1 2003 Imatinib (STI571 or CGP57148B) is an innovative treatment for tumours with a constitutively activated form of c-ABL, c-KIT, or PDGFR. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-122 12522257-1 2003 Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Imatinib Mesylate 153-160 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 78-81 12522257-1 2003 Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Imatinib Mesylate 153-160 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 177-180 12600228-1 2003 Imatinib mesylate (imatinib) is an orally administered competitive inhibitor of the tyrosine kinases associated with the KIT protein (stem cell factor receptor), ABL protein and platelet-derived growth factor receptors. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 121-124 12600228-1 2003 Imatinib mesylate (imatinib) is an orally administered competitive inhibitor of the tyrosine kinases associated with the KIT protein (stem cell factor receptor), ABL protein and platelet-derived growth factor receptors. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 121-124 12600228-11 2003 One such drug is imatinib mesylate (imatinib, Glivic/Gleevec), an orally administered 2-phenylaminopyrimidine derivative that is a competitive inhibitor of the tyrosine kinases associated with platelet-derived growth factor (PDGF) receptors, the Abelson (ABL) protein and the KIT protein (also known as stem cell factor [SCF] receptor). Imatinib Mesylate 17-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 276-279 12600228-11 2003 One such drug is imatinib mesylate (imatinib, Glivic/Gleevec), an orally administered 2-phenylaminopyrimidine derivative that is a competitive inhibitor of the tyrosine kinases associated with platelet-derived growth factor (PDGF) receptors, the Abelson (ABL) protein and the KIT protein (also known as stem cell factor [SCF] receptor). Imatinib Mesylate 17-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 276-279 12600228-13 2003 More recently, imatinib has been approved for the treatment of patients with advanced gastrointestinal stromal tumour (GIST), in which KIT, a tyrosine kinase receptor, is abnormally expressed. Imatinib Mesylate 15-23 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 135-138 12600228-24 2003 Imatinib selectively inhibits the tyrosine kinase activity associated with KIT, which forms the rationale for evaluating its effects in GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-78 12600228-25 2003 Subsequent to initial evidence of the clinical efficacy of imatinib in a single patient with progressive, metastatic, CD117-positive GIST, formal studies of imatinib in this new indication were initiated. Imatinib Mesylate 59-67 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 118-123 12898363-4 2003 STI571 selectively inhibits c-Kit, BCR-ABL, and PDGFR tyrosine kinases. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-33 12898363-5 2003 Based on this potential to inhibit critical c-Kit function in GISTs, case studies have reported effective outcomes following treatment with STI571. Imatinib Mesylate 140-146 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-49 14689066-0 2003 The clinical characteristics and the role of surgery and imatinib treatment in patients with liver metastases from c-Kit positive gastrointestinal stromal tumors (GIST). Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-120 12817876-2 2003 The specific identification of GIST has become more important after the availability of KIT-selective tyrosine kinase inhibitor Imatinib mesylate, STI571, commercially known as Gleevec/Glivec (Novartis Pharma, Basel, Switzerland) in the treatment of unresectable and metastatic tumors. Imatinib Mesylate 128-145 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 88-91 12817876-2 2003 The specific identification of GIST has become more important after the availability of KIT-selective tyrosine kinase inhibitor Imatinib mesylate, STI571, commercially known as Gleevec/Glivec (Novartis Pharma, Basel, Switzerland) in the treatment of unresectable and metastatic tumors. Imatinib Mesylate 147-153 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 88-91 12354363-4 2002 Promising preclinical results have provided the driving force for the rapid clinical development of imatinib mesylate, a selective tyrosine kinase inhibitor of c-Kit. Imatinib Mesylate 100-117 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 160-165 12678420-5 2003 Lately reports of efficacy of a specific anticancer drug with imatinib (ST1571) based on specific molecular abnormalities of proto-oncogene c-kit present in gastrointestinal stromal tumors induced us to identify the c-kit phenotype also in uterine leiomyosarcomas. Imatinib Mesylate 62-70 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 125-145 12678420-5 2003 Lately reports of efficacy of a specific anticancer drug with imatinib (ST1571) based on specific molecular abnormalities of proto-oncogene c-kit present in gastrointestinal stromal tumors induced us to identify the c-kit phenotype also in uterine leiomyosarcomas. Imatinib Mesylate 62-70 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 140-145 12616857-1 2003 Imatinib mesilate (Glivec) is a protein-tyrosine kinase inhibitor that potently inhibits the Bcr-Abl tyrosine kinase as well as the receptors for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, at in vitro and cellular kinase assay levels. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 212-217 12616857-1 2003 Imatinib mesilate (Glivec) is a protein-tyrosine kinase inhibitor that potently inhibits the Bcr-Abl tyrosine kinase as well as the receptors for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, at in vitro and cellular kinase assay levels. Imatinib Mesylate 19-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 212-217 12952023-1 2003 BACKGROUND: Imatinib mesylate is an inhibitor of a few tyrosine kinases including KIT, which is an important growth factor receptor of mast cells. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-85 12952023-11 2003 The mechanism of action is not known, but one possible target for the action of imatinib is inhibition of the KIT receptor on mast cells. Imatinib Mesylate 80-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 14657531-7 2003 STI571 also inhibits other TKs, including the receptor TK c-kit, which is expressed in gastrointestinal stromal tumors. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-63 12538164-8 2002 Inhibition of c-Kit activity with the pharmacological inhibitor of c-Kit signaling STI571 reversed the KSHV-induced morphological transformation of DMVEC. Imatinib Mesylate 83-89 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-19 12538164-8 2002 Inhibition of c-Kit activity with the pharmacological inhibitor of c-Kit signaling STI571 reversed the KSHV-induced morphological transformation of DMVEC. Imatinib Mesylate 83-89 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-72 12436445-5 2002 Imatinib mesylate appears to demonstrate inhibitory activity against multiple class 3 receptor tyrosine kinases, including platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta, as well as c-kit. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 204-209 12436445-9 2002 CONCLUSIONS: Imatinib mesylate has been reported to have activity against desmoid tumor, most likely because of c-kit and PDGFR receptor tyrosine kinase activity inhibition, and warrants further study. Imatinib Mesylate 13-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 112-117 12514786-2 2002 Studies have shown that the tyrosine kinase inhibitor STI-571 (Gleevec) is used successfully against tumors expressing the c-kit oncogene, such as gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 54-61 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-128 12417503-5 2002 STI571 is an oral agent that selectively inhibits Kit. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-53 12414661-3 2002 In vitro, the inhibition of c-Kit tyrosine kinase activity by the small molecule tyrosine kinase inhibitor STI571 (Gleevec) abrogates cell growth. Imatinib Mesylate 107-113 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-33 12414661-11 2002 Treatment of NCI-H69 cells with STI571 specifically inhibited the c-Kit signaling events of Akt and p70 S6 kinase, whereas SDF-1alpha-mediated activation of Akt or p70 S6 kinase was normal. Imatinib Mesylate 32-38 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 66-71 12424067-9 2002 Imatinib mesylate is an orally administered selective inhibitor of certain tyrosine kinases including KIT. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-105 12429808-9 2002 Nonetheless, the growth of TAKA-1 cells and pancreatic cancer cells was inhibited by the c-kit tyrosine kinase inhibitor STI571. Imatinib Mesylate 121-127 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-94 12360044-2 2002 In the STI571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Imatinib Mesylate 24-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 111-116 12360044-2 2002 In the STI571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Imatinib Mesylate 24-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 118-123 12512386-7 2002 The improved understanding of the molecular pathophysiology of GIST, a disease that was previously untreatable with any available systemic therapy, has led to the development of imatinib, a well-tolerated agent that can inhibit the dysregulated KIT signaling pathways in GIST. Imatinib Mesylate 178-186 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 245-248 12208734-0 2002 The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy. Imatinib Mesylate 36-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-9 12208734-1 2002 The c-kit tyrosine kinase inhibitor STI571 exhibits a substantial therapeutic activity in patients with chronic myeloid leukemia and gastrointestinal stromal tumors respectively associated with constitutive activation of the BCR-ABL and c-kit tyrosine kinases. Imatinib Mesylate 36-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-9 12208734-1 2002 The c-kit tyrosine kinase inhibitor STI571 exhibits a substantial therapeutic activity in patients with chronic myeloid leukemia and gastrointestinal stromal tumors respectively associated with constitutive activation of the BCR-ABL and c-kit tyrosine kinases. Imatinib Mesylate 36-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 237-242 12208734-9 2002 These encouraging results warrant further preclinical investigations and clinical trials on the use of the c-kit inhibitor STI571 as a chemotherapeutic agent in colon cancer prevention and in treatment of advanced colorectal cancers associated with liver metastases. Imatinib Mesylate 123-129 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 107-112 12528772-2 2002 The specific identification of GIST has become increasingly important because a Kit-selective tyrosine kinase inhibitor, imatinib (Glivec, formerly known as STI571, Novartis Pharma AG, Basel, Switzerland), has shown promise as an effective adjuvant therapy treatment. Imatinib Mesylate 157-163 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-83 12528773-10 2002 Imatinib was subsequently shown to block activity of the KIT tyrosine kinase as well, and in laboratory studies this led to apoptotic death of GIST cells. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-60 12209733-1 2002 STI571 (imatinib mesylate; Gleevec) is a selective inhibitor of the bcr-abl, c-kit, and platelet-derived growth factor receptor tyrosine kinases. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-82 12209733-1 2002 STI571 (imatinib mesylate; Gleevec) is a selective inhibitor of the bcr-abl, c-kit, and platelet-derived growth factor receptor tyrosine kinases. Imatinib Mesylate 8-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-82 12134042-7 2002 Inhibition of c-Kit activity with either a pharmacological inhibitor of c-Kit (STI 571) or a dominant-negative c-Kit protein reversed SCF-dependent proliferation. Imatinib Mesylate 79-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-19 12134042-7 2002 Inhibition of c-Kit activity with either a pharmacological inhibitor of c-Kit (STI 571) or a dominant-negative c-Kit protein reversed SCF-dependent proliferation. Imatinib Mesylate 79-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-77 12134042-7 2002 Inhibition of c-Kit activity with either a pharmacological inhibitor of c-Kit (STI 571) or a dominant-negative c-Kit protein reversed SCF-dependent proliferation. Imatinib Mesylate 79-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-77 12094371-7 2002 STI-571 is a small molecule that selectively inhibits the enzymatic activity of the ABL, platelet-derived growth factor receptor, and KIT tyrosine kinases and the BCR-ABL fusion protein and is a landmark development in cancer therapy. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-137 12094372-5 2002 A KIT tyrosine kinase inhibitor, STI-571 (imatinib [Gleevec]; Novartis, Basel, Switzerland), has recently shown promise in the treatment of metastatic GISTs. Imatinib Mesylate 33-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 2-5 11953894-1 2002 STI571 is a selective tyrosine kinase inhibitor with proven therapeutic potential in malignancies expressing c-kit. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 109-114 11914627-2 2002 Studies using the oral agent STI-571 (Gleevec, Novartis), an inhibitor of the tyrosine kinases bcr-abl, c-kit, and PDGFR, have shown significant responses in patients with chronic myelogenous leukemia and gastrointestinal stromal tumor. Imatinib Mesylate 29-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 104-109 11861291-0 2002 The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations. Imatinib Mesylate 62-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-9 11861291-0 2002 The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations. Imatinib Mesylate 62-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 6-9 12094372-5 2002 A KIT tyrosine kinase inhibitor, STI-571 (imatinib [Gleevec]; Novartis, Basel, Switzerland), has recently shown promise in the treatment of metastatic GISTs. Imatinib Mesylate 42-50 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 2-5 12094372-5 2002 A KIT tyrosine kinase inhibitor, STI-571 (imatinib [Gleevec]; Novartis, Basel, Switzerland), has recently shown promise in the treatment of metastatic GISTs. Imatinib Mesylate 52-59 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 2-5 11790564-3 2002 STI-571, a small molecule inhibitor of the Bcr-Abl, c-kit and platelet derived growth factor receptor tyrosine kinases, produced dramatic clinical responses in patients with Bcr-Abl positive chronic myeloid leukemia and c-kit positive gastrointestinal stromal tumors. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-57 11790564-3 2002 STI-571, a small molecule inhibitor of the Bcr-Abl, c-kit and platelet derived growth factor receptor tyrosine kinases, produced dramatic clinical responses in patients with Bcr-Abl positive chronic myeloid leukemia and c-kit positive gastrointestinal stromal tumors. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 220-225 11831067-6 2002 STI571 was shown to be a competitive inhibitor at the ATP-binding site of the Bcr-Abl tyrosine kinase, the platelet-derived growth factor receptor and c-kit tyrosine kinases. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 151-156 12191602-9 2002 In a preclinical model, STI571 (Glivec(R), Gleevec) showed potent in vitro and in vivo antitumor activity that was selective for Abl, c-Kit, and the platelet-derived growth factor-receptor. Imatinib Mesylate 24-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-139 12191602-10 2002 Phase I/II studies demonstrated that STI571 is well tolerated, and that it showed promising hematological and cytogenetic responses in CML and clinical responses in the c-Kit-driven gastrointestinal tumors. Imatinib Mesylate 37-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 169-174 11831067-14 2002 According to its pharmacological profile, STI571 could also be useful in the treatment of tumors with deregulated PDGF receptor or c-kit signaling, e.g., in chronic myelomonocytic leukemia with a t(5;12) chromosomal translocation or in cases with gastrointestinal stromal tumors (GIST). Imatinib Mesylate 42-48 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 131-136 11831069-1 2002 BACKGROUND: Imatinib (STI571 or Glivec, Novartis) is a new type of tyrosine kinase inhibitor that selectively inhibits various tyrosine kinases including ABL, BCR-ABL, KIT and PDGF receptors. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 168-171 11831069-1 2002 BACKGROUND: Imatinib (STI571 or Glivec, Novartis) is a new type of tyrosine kinase inhibitor that selectively inhibits various tyrosine kinases including ABL, BCR-ABL, KIT and PDGF receptors. Imatinib Mesylate 22-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 168-171 11831069-5 2002 IMATINIB IN GIST: Gastrointestinal stromal tumors (GIST) are also suitable indications for treatment with Imatinib, the prerequisite being overexpression by the tumor of c-KIT (CD117). Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-175 11831069-5 2002 IMATINIB IN GIST: Gastrointestinal stromal tumors (GIST) are also suitable indications for treatment with Imatinib, the prerequisite being overexpression by the tumor of c-KIT (CD117). Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 177-182 11831069-5 2002 IMATINIB IN GIST: Gastrointestinal stromal tumors (GIST) are also suitable indications for treatment with Imatinib, the prerequisite being overexpression by the tumor of c-KIT (CD117). Imatinib Mesylate 106-114 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-175 11831069-5 2002 IMATINIB IN GIST: Gastrointestinal stromal tumors (GIST) are also suitable indications for treatment with Imatinib, the prerequisite being overexpression by the tumor of c-KIT (CD117). Imatinib Mesylate 106-114 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 177-182 11751479-9 2001 SCF-induced phosphorylation of c-kit in MO7e cells was inhibited by STI571. Imatinib Mesylate 68-74 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 31-36 12122963-3 2002 Imatinib mesylate is indicated for the treatment of patients with Kit (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors and patients with Philadelphia chromosome-positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alfa. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-76 10955819-5 2000 Pretreatment of the H526 small cell lung cancer (SCLC) cell line with STI571 inhibited SCF-mediated Kit activation with an IC50 of 0.1 microM as measured by inhibition of receptor tyrosine phosphorylation and 0.2 microM as measured by immune complex kinase assay. Imatinib Mesylate 70-76 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-103 11705489-3 2001 Imatinib (STI571) inhibits a similar tyrosine kinase, BCR-ABL, leading to responses in chronic myeloid leukaemia, and has also been shown to inhibit KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 149-152 11705489-3 2001 Imatinib (STI571) inhibits a similar tyrosine kinase, BCR-ABL, leading to responses in chronic myeloid leukaemia, and has also been shown to inhibit KIT. Imatinib Mesylate 10-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 149-152 11680792-1 2001 Imatinib mesylate, also known as STI571 or CGP57148, is a competitive inhibitor of a few tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 131-134 11680792-1 2001 Imatinib mesylate, also known as STI571 or CGP57148, is a competitive inhibitor of a few tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). Imatinib Mesylate 33-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 131-134 11680792-1 2001 Imatinib mesylate, also known as STI571 or CGP57148, is a competitive inhibitor of a few tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). Imatinib Mesylate 43-51 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 131-134 11740801-7 2001 The success of imatinib mesylate in CML led rapidly to clinical trials in other cancers associated with activation of two other tyrosine kinases known to be sensitive to imatinib mesylate, c-Kit and the platelet-derived growth factor receptor. Imatinib Mesylate 15-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 189-194 11740802-9 2001 Additional trials are planned to investigate the efficacy of imatinib mesylate to treat a variety of solid tumors whose pathogenesis is driven by the other tyrosine kinase targets, c-Kit and platelet-derived growth factor receptor. Imatinib Mesylate 61-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 181-186 11740803-8 2001 This hypothesis became testable with the identification of the signal transduction inhibitor imatinib mesylate (formerly STI571, [Gleevec]; Novartis Pharmaceuticals Corp, East Hanover, NJ), which blocks the tyrosine kinase activity of KIT as well as the kinase activity of the normal c-abl gene product, the oncogenic Bcr-Abl chimeric fusion protein of chronic myeloid leukemia, and the platelet-derived growth factor receptor. Imatinib Mesylate 93-110 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 235-238 11740803-8 2001 This hypothesis became testable with the identification of the signal transduction inhibitor imatinib mesylate (formerly STI571, [Gleevec]; Novartis Pharmaceuticals Corp, East Hanover, NJ), which blocks the tyrosine kinase activity of KIT as well as the kinase activity of the normal c-abl gene product, the oncogenic Bcr-Abl chimeric fusion protein of chronic myeloid leukemia, and the platelet-derived growth factor receptor. Imatinib Mesylate 121-127 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 235-238 11740803-9 2001 Preclinical experiments showed rapid inhibition of ligand-independent KIT phosphorylation, decreased cellular proliferation, and induction of apoptosis after exposure of GIST cells to imatinib mesylate in vitro. Imatinib Mesylate 184-201 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-73 11526490-5 2001 GIST882 c-KIT protein is constitutively tyrosine phosphorylated, but tyrosine phosphorylation was rapidly and completely abolished after incubating the cells with the selective tyrosine kinase inhibitor STI571. Imatinib Mesylate 203-209 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 8-13 11526490-7 2001 Similar results were obtained after administering STI571 to a primary GIST cell culture that expressed a c-KIT exon 11 juxtamembrane mutation (K558NP). Imatinib Mesylate 50-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 105-110 11495816-4 2001 Produced from the 2-phenylaminopyrimidine class, a novel synthetic inhibitor, identified as CGP57148 (STI571), inhibits tyrosine kinase activity of c-ABL, BCR-ABL, PDGF-R and c-kit at micromolar concentrations. Imatinib Mesylate 92-100 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 175-180 11342454-1 2001 The 2-phenylaminopyrimidine derivative STI571 is a selective inhibitor of c-Abl, c-kit, and platelet-derived growth factor-receptor tyrosine kinases and is presently in phase II-III clinical studies. Imatinib Mesylate 39-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-86 11378651-8 2001 The remarkable clinical response of tumors that express c-kit to treatment with the tyrosine kinase inhibitor STI571 is a triumph of molecular pharmacology. Imatinib Mesylate 110-116 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 56-61 11512149-2 2001 Glivec is an aminopyrimidine derivative that interacts with the ATP-binding site within the kinase domain of ABL and several other tyrosine kinases, including c-KIT, PDGF beta receptor, and ARG. Imatinib Mesylate 0-6 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 159-164 10910906-0 2000 Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Imatinib Mesylate 57-64 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-19 10910906-5 2000 STI 571 inhibited c-kit autophosphorylation, activation of mitogen-activated protein (MAP) kinase, and activation of Akt without altering total protein levels of c-kit, MAP kinase, or Akt. Imatinib Mesylate 0-7 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-23 10910906-11 2000 These findings show that STI 571 selectively inhibits c-kit tyrosine kinase activity and downstream activation of target proteins involved in cellular proliferation and survival. Imatinib Mesylate 25-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 54-59 11600816-10 2001 Since c-kit overexpression is inhibited in small-cell lung cancer cell lines, a study with STI571 as second-line therapy of c-kit-positive small-cell lung cancer is in progress. Imatinib Mesylate 91-97 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-129 10991971-0 2000 Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. Imatinib Mesylate 38-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-100 10918610-11 2000 These data imply that STI 571 inhibits growth of SCLC cells through a mechanism that involves inactivation of the tyrosine kinase c-Kit. Imatinib Mesylate 22-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 130-135 21893472-3 2011 The aim of this study was to investigate the effects of imatinib as a c-kit receptor antagonist on the spontaneous or oxytocin (OT) induced contractions of human non-pregnant myometrium in vitro. Imatinib Mesylate 56-64 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-75 34889232-4 2021 Imatinib mesylate, a small-molecule inhibitor of the KIT tyrosine kinase, provides a rapid but not durable clinical response in KIT-mutant melanoma. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-56 34709443-2 2022 The treatment of GISTs has been revolutionized since imatinib and other tyrosine kinase inhibitors were introduced for the treatment of GISTs, which inhibit the tyrosine kinases c-KIT and platelet-derived growth factor receptor (PDGFR) alpha. Imatinib Mesylate 53-61 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 178-183 34889232-4 2021 Imatinib mesylate, a small-molecule inhibitor of the KIT tyrosine kinase, provides a rapid but not durable clinical response in KIT-mutant melanoma. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 128-131 34398495-13 2021 The clinical benefit with KIT inhibitors, such as imatinib, remains to be determined. Imatinib Mesylate 50-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 34621020-7 2021 Buttressed on these findings, we established in vitro and in vivo the preclinical proof-of-concept for co-targeting KIT and the ubiquitin pathway to maximize the therapeutic response to first-line imatinib treatment. Imatinib Mesylate 197-205 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 116-119 34917498-0 2021 Case Report: Evolution of KIT D816V-Positive Systemic Mastocytosis to Myeloid Neoplasm With PDGFRA Rearrangement Responsive to Imatinib. Imatinib Mesylate 127-135 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 34236401-2 2021 KIT inhibitors commonly used to treat GIST (eg, imatinib and sunitinib) are inactive-state (type II) inhibitors. Imatinib Mesylate 48-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 34944576-5 2021 Imatinib block the binding site of ATP in the BCR/ABL protein and is also a platelet-derived growth factor receptor (PDGFR) and a KIT (CD117) kinase inhibitor. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 130-133 34944576-5 2021 Imatinib block the binding site of ATP in the BCR/ABL protein and is also a platelet-derived growth factor receptor (PDGFR) and a KIT (CD117) kinase inhibitor. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 135-140 34775854-14 2022 DISCUSSION: Imatinib is an oral signal inhibitor that targets tyrosine kinase for BCR/ABL, platelet-derived growth factor, stem cell factor, and c-kit (CD117). Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 145-150 34775854-14 2022 DISCUSSION: Imatinib is an oral signal inhibitor that targets tyrosine kinase for BCR/ABL, platelet-derived growth factor, stem cell factor, and c-kit (CD117). Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 152-157 34775854-15 2022 The conjunctiva and sclera have a large amount of c-kit positive mast cells which are inhibited by imatinib. Imatinib Mesylate 99-107 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-55 34775854-16 2022 The inhibition of c-kit positive mast cells by imatinib may be responsible for further exposure of the conjunctival mucosa to injuries. Imatinib Mesylate 47-55 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-23 34376580-0 2021 KIT Low Cells Mediate Imatinib Resistance in Gastrointestinal Stromal Tumor. Imatinib Mesylate 22-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 34376580-1 2021 Gastrointestinal stromal tumor (GIST) is commonly driven by oncogenic KIT mutations that are effectively targeted by imatinib, a tyrosine kinase inhibitor (TKI). Imatinib Mesylate 117-125 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-73 34446510-0 2021 Sustained response to imatinib in patient with extraskeletal myxoid chondrosarcoma and novel KIT mutation. Imatinib Mesylate 22-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-96 34589354-3 2021 Imatinib mesylate, a tyrosine kinase inhibitor with activity against ABL, BCR-ABL, platelet-derived growth factor receptor-alpha (PDGFRA), and c-KIT (CD117), constitutes the cornerstone of treatment for inoperable or metastatic GIST. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 143-148 34589354-3 2021 Imatinib mesylate, a tyrosine kinase inhibitor with activity against ABL, BCR-ABL, platelet-derived growth factor receptor-alpha (PDGFRA), and c-KIT (CD117), constitutes the cornerstone of treatment for inoperable or metastatic GIST. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 150-155 34489967-6 2021 In addition to inhibiting the KIT oncogene, imatinib appears to act by promoting cytotoxic T-cell activity, interacting with natural killer cells, and inhibiting the expression of PD-L1. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-33 34322383-2 2021 Approval of imatinib, a KIT/PDGFRA tyrosine kinase inhibitor (TKI), meaningfully improved the treatment of advanced GIST. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 34324512-2 2021 KIT/PDGFRA inhibitors, such as imatinib do not evoke an effective cytocidal response, leaving room for quiescence and development of multiple secondary resistance mutations. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 34359600-1 2021 The majority of gastrointestinal stromal tumor (GIST) patients develop resistance to the first-line KIT inhibitor, imatinib mesylate (IM), through acquisition of secondary mutations in KIT or bypass signaling pathway activation. Imatinib Mesylate 115-132 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-103 34359600-1 2021 The majority of gastrointestinal stromal tumor (GIST) patients develop resistance to the first-line KIT inhibitor, imatinib mesylate (IM), through acquisition of secondary mutations in KIT or bypass signaling pathway activation. Imatinib Mesylate 115-132 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 185-188 34359600-1 2021 The majority of gastrointestinal stromal tumor (GIST) patients develop resistance to the first-line KIT inhibitor, imatinib mesylate (IM), through acquisition of secondary mutations in KIT or bypass signaling pathway activation. Imatinib Mesylate 134-136 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-103 34359600-1 2021 The majority of gastrointestinal stromal tumor (GIST) patients develop resistance to the first-line KIT inhibitor, imatinib mesylate (IM), through acquisition of secondary mutations in KIT or bypass signaling pathway activation. Imatinib Mesylate 134-136 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 185-188 34298737-2 2021 The management of locally advanced or metastatic unresectable GIST involves detecting KIT, PDGFR, or other molecular alterations targeted by imatinib and other tyrosine kinase inhibitors. Imatinib Mesylate 141-149 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 86-89 34065883-6 2021 The KIT inhibitors (Tyrosine kinase inhibitors: TKIs) imatinib and nilotinib could be the treatment options. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-7 34089444-1 2021 BACKGROUND: Retrospective analyses suggest that patients with advanced KIT exon 9-mutated gastrointestinal stromal tumors (GISTs) receiving imatinib 800 mg (rather than 400 mg) daily have better outcomes. Imatinib Mesylate 140-148 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-74 35487307-9 2022 Other KIT-targeting drugs, such as imatinib or masitinib, are less effective or even non-effective against KIT D816V and are thus only recommended for use in patients with other KIT mutant forms (non codon 816 mutations) or with wild type KIT. Imatinib Mesylate 35-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 6-9 35585158-1 2022 Although KIT-mutant GISTs can be effectively treated with tyrosine kinase inhibitors (TKIs), many patients develop resistance to imatinib mesylate (IM) as well as the FDA-approved later-line agents sunitinib, regorafenib and ripretinib. Imatinib Mesylate 129-146 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 9-12 35585158-1 2022 Although KIT-mutant GISTs can be effectively treated with tyrosine kinase inhibitors (TKIs), many patients develop resistance to imatinib mesylate (IM) as well as the FDA-approved later-line agents sunitinib, regorafenib and ripretinib. Imatinib Mesylate 148-150 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 9-12 35349049-3 2022 Imatinib is first-line treatment for unresectable gastrointestinal stromal tumors (GISTs) unless they harbor a PDGFRA D842V mutation; it is recommended to escalate imatinib to twice daily dosing for KIT exon 9 mutant tumors. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 199-202 34983047-7 2022 These characteristics may explain the limited activity of the tyrosine kinase inhibitor imatinib in the adjuvant setting in KIT exon 9-mutant GISTs, as well as their lower sensitivity to standard dose imatinib in the advanced setting. Imatinib Mesylate 88-96 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-127 35217782-2 2022 The discovery of KIT mutations as the first and most prevalent drivers of GIST and the subsequent development of the first KIT tyrosine kinase inhibitor (TKI), imatinib, revolutionized the treatment of patients with this disease. Imatinib Mesylate 160-168 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-20 35217782-2 2022 The discovery of KIT mutations as the first and most prevalent drivers of GIST and the subsequent development of the first KIT tyrosine kinase inhibitor (TKI), imatinib, revolutionized the treatment of patients with this disease. Imatinib Mesylate 160-168 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-126 35120552-12 2022 Inhibiting the activation of c-kit by imatinib remarkably suppressed the proliferation and promoted the apoptosis of ESCs. Imatinib Mesylate 38-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-34 35174150-1 2022 Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tracts and a model for the targeted therapy of solid tumors because of the oncogenic driver mutations in KIT and PDGDRA genes, which could be effectively inhibited by the very first targeted agent, imatinib mesylate. Imatinib Mesylate 297-305 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 204-207 35053574-7 2022 Since c-Kit is targeted by the FDA-approved drug imatinib, we tested the ability of imatinib on the phenotype of the vascular malformations in vivo. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 6-11 35053574-9 2022 Imatinib may be useful in the treatment of human vascular malformations that express c-Kit, including Sturge-Weber syndrome. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-90 35194937-0 2022 Nintedanib overcomes drug resistance from upregulation of FGFR signalling and imatinib-induced KIT mutations in gastrointestinal stromal tumours. Imatinib Mesylate 78-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-98 33848847-9 2021 c-Kit inhibition with both imatinib and monoclonal blocking antibody reduced expression of ARG-1, iNOS, PD-L1, and SAA3. Imatinib Mesylate 27-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 33783002-1 2021 Imatinib (IM) is a pharmaceutical drug that inhibits tyrosine kinase enzymes that are responsible for the activation of many proteins by signal transduction cascades as c-Abl, c-Kit and the platelet-derived growth factor (PDGF) receptor. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 176-181 33783002-1 2021 Imatinib (IM) is a pharmaceutical drug that inhibits tyrosine kinase enzymes that are responsible for the activation of many proteins by signal transduction cascades as c-Abl, c-Kit and the platelet-derived growth factor (PDGF) receptor. Imatinib Mesylate 10-12 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 176-181 33947686-2 2021 Imatinib, sunitinib, and regorafenib are available as first, second, and third-line targeted therapies, respectively, for metastatic or unresectable KIT-driven GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 149-152 33247506-9 2021 Blocking c-KIT signaling using Imatinib or ISCK03 reduced p-ELK1 expression and consequently decreased CEA levels in CRC cells, as did blocking the ERK1/2 pathway by U0126. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 9-14 33524167-14 2021 Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib-sensitive KIT mutations. Imatinib Mesylate 96-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-118 33743084-2 2021 Unfortunately, acquired c-kit mutations cause secondary resistance to imatinib in a median of 18-24 months. Imatinib Mesylate 70-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-29 33737510-5 2021 Patients with GIST with KIT or PDGFRA mutations sensitive to the tyrosine kinase inhibitor (TKI) imatinib that are at high risk of relapse have improved survival with adjuvant imatinib treatment. Imatinib Mesylate 97-105 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 33737510-5 2021 Patients with GIST with KIT or PDGFRA mutations sensitive to the tyrosine kinase inhibitor (TKI) imatinib that are at high risk of relapse have improved survival with adjuvant imatinib treatment. Imatinib Mesylate 176-184 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 33641024-4 2021 Interestingly, KIT/PDGFRA genotype predicts the response to first-line imatinib and to all tyrosine kinase inhibitors (TKIs) approved or in investigation after imatinib failure. Imatinib Mesylate 71-79 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 15-18 33641024-4 2021 Interestingly, KIT/PDGFRA genotype predicts the response to first-line imatinib and to all tyrosine kinase inhibitors (TKIs) approved or in investigation after imatinib failure. Imatinib Mesylate 160-168 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 15-18 33673554-0 2021 Type and Gene Location of KIT Mutations Predict Progression-Free Survival to First-Line Imatinib in Gastrointestinal Stromal Tumors: A Look into the Exon. Imatinib Mesylate 88-96 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 33673554-5 2021 Our data showed a predictive impact of KIT exon 11 pathogenic variant on PFS to imatinib treatment: patients with deletion or insertion/deletion (delins) in 557/558 codons had a shorter PFS (median PFS: 24 months) compared to the patients with a deletion in other codons, or duplication/insertion/SNV (median PFS: 43 and 49 months, respectively) (p < 0.001). Imatinib Mesylate 80-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 39-42 33422470-0 2021 A Phase II Trial of Imatinib Mesylate as Maintenance Therapy for Patients With Newly Diagnosed C-kit-positive Acute Myeloid Leukemia. Imatinib Mesylate 20-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-100 33727226-1 2021 Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling therapeutic targets in gastrointestinal stromal tumor (GIST), and treatment with the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with advanced GIST. Imatinib Mesylate 180-188 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-13 33727226-1 2021 Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling therapeutic targets in gastrointestinal stromal tumor (GIST), and treatment with the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with advanced GIST. Imatinib Mesylate 180-188 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 159-162 33727226-2 2021 Polyclonal emergence of KIT/PDGFRA secondary mutations is the main mechanism of imatinib progression, making it challenging to overcome KIT/PDGFRA-inhibitor resistance. Imatinib Mesylate 80-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 33727226-2 2021 Polyclonal emergence of KIT/PDGFRA secondary mutations is the main mechanism of imatinib progression, making it challenging to overcome KIT/PDGFRA-inhibitor resistance. Imatinib Mesylate 80-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 136-139 33389076-3 2021 The aim of our study was to explore the feasibility of blocking KIT dimerisation upstream of the phosphorylation in imatinib-resistant GIST. Imatinib Mesylate 116-124 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-67 33307872-1 2021 INTRODUCTION: 90% of gastrointestinal stromal tumors (GISTs) harbor an activating mutation in the KIT or PDGFRalpha oncogene, and these are known to confer imatinib sensitivity. Imatinib Mesylate 156-164 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-101 33307872-3 2021 EXPERT OPINION: Several studies have shown that the response to imatinib in GIST patients mainly depends on the mutational status of KIT or PDGFRalpha. Imatinib Mesylate 64-72 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 133-136 33030616-11 2021 Imatinib and apatinib augmented the sensitivity of pyrotinib-resistant cells and xenografts to pyrotinib, by blocking SCF/c-kit signaling. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 122-127 33670651-5 2021 KIT exon 11 mutant patients were more favorable in responding to imatinib than those with exon 9 mutant or wild-type GISTs, and compared to non-KIT exon 11 mutant GISTs (p = 0.041). Imatinib Mesylate 65-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 33402214-4 2021 The management of GIST was revolutionized by the introduction of imatinib, a KIT inhibitor, which has become the standard first line treatment for metastatic GIST. Imatinib Mesylate 65-73 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-80 32615108-1 2020 BACKGROUND: Targeting of KIT and PDGFRA with imatinib revolutionised treatment in gastrointestinal stromal tumour; however, PDGFRA Asp842Val (D842V)-mutated gastrointestinal stromal tumour is highly resistant to tyrosine kinase inhibitors. Imatinib Mesylate 45-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 25-28 32836055-2 2020 BRAF mutated GISTs usually do not respond to imatinib treatment, even more GISTs with imatinib sensitive KIT mutation. Imatinib Mesylate 86-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 105-108 33116851-1 2020 Purpose: KIT/PDGFRA wild-type (WT) gastrointestinal stromal tumors (GISTs) represent a heterogeneous subgroup of GISTs that lack KIT or PDGFRA mutations and possess distinct genetic alterations and primary resistance to imatinib. Imatinib Mesylate 220-228 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 9-12 32619820-2 2020 Tyrosine kinase inhibitors (TKIs) such as imatinib have proven effective since the discovery of KIT and PDGFRA. Imatinib Mesylate 42-50 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-99 32697050-2 2020 This study aimed to evaluate the prognostic value of mutations in KIT and PDGFRA in a large-scale cohort of GIST patients with current therapy including surgery and imatinib. Imatinib Mesylate 165-173 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 66-69 32697050-7 2020 In high-risk GISTs treated with R0 resection and imatinib, patients with KIT exon 11 homozygous mutations and KIT intron 10/exon 11 junction deletions demonstrated the highest recurrence rate, indicating that these mutations can be independent prognostic factors of DFS. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 32697050-9 2020 CONCLUSION: Low-incidence mutations such as KIT exon 11 homozygous mutations or intron 10/exon 11 junction deletions in GISTs should be carefully evaluated to explore novel treatment strategies, as tumors with these mutations have a high recurrence rate and a very poor prognosis after surgery followed by imatinib adjuvant treatment. Imatinib Mesylate 306-314 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 32291709-2 2020 Imatinib and sunitinib are approved KIT-inhibiting therapies. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 36-39 32291709-9 2020 Our data show that dasatinib is more potent than imatinib or sunitinib at inhibiting the activity of drug-resistant KIT mutants. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 116-119 32843387-0 2020 Chronic mast cell leukaemia with exon 9 KIT mutation A502_Y503dup: a rare imatinib responsive variant. Imatinib Mesylate 74-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 40-43 33468755-7 2020 Histopathological examination showed c-kit positivity and she was diagnosed with small intestinal GIST; as a result, a course of imatinib was started. Imatinib Mesylate 129-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-42 33024275-3 2020 The small molecule imatinib inhibits KIT and has been a mainstay of therapy in GIST. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-40 33024275-4 2020 Unfortunately, imatinib-treated patients typically relapse, most often due to clonal emergence of the resistance-associated KIT V654A mutation. Imatinib Mesylate 15-23 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-127 33212994-8 2020 However, when compared to a classical imatinib-resistant KIT mutation (T670I), N655K was slightly more sensitive to imatinib, and encouraging responses were observed with last-generation TKIs. Imatinib Mesylate 38-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-60 33212994-8 2020 However, when compared to a classical imatinib-resistant KIT mutation (T670I), N655K was slightly more sensitive to imatinib, and encouraging responses were observed with last-generation TKIs. Imatinib Mesylate 116-124 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-60 33195674-5 2020 Mutational analysis showed secondary mutation in KIT exon 13 (V564A), which is resistant to imatinib treatment. Imatinib Mesylate 92-100 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 32999756-0 2020 Expression differences of miR-142-5p between treatment-naive chronic myeloid leukemia patients responding and non-responding to imatinib therapy suggest a link to oncogenic ABL2, SRI, cKIT and MCL1 signaling pathways critical for development of therapy resistance. Imatinib Mesylate 128-136 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 184-188 32753885-10 2020 Detection of KIT and PDGFRA gene mutations in the transplanted imatinib-resistant GIST was done by denaturing high performance liquid chromatography (DHPLC) and direct sequencing. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 13-16 32005261-2 2020 The events that drive GIST oncogenesis are primarily KIT or PDGFRA mutations, which lead to the susceptibility of these tumors to small-molecule tyrosine kinase inhibitors such as imatinib and sunitinib. Imatinib Mesylate 180-188 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-56 32371592-5 2020 Simultaneous PI3K and KIT inhibition with copanlisib and imatinib resulted in enhanced impairment of cell viability in both imatinib-sensitive and -resistant GIST cell models, although apoptosis was mostly triggered in GIST-T1. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 32371592-5 2020 Simultaneous PI3K and KIT inhibition with copanlisib and imatinib resulted in enhanced impairment of cell viability in both imatinib-sensitive and -resistant GIST cell models, although apoptosis was mostly triggered in GIST-T1. Imatinib Mesylate 124-132 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 32371592-9 2020 Effective KIT inhibition is necessary in order to achieve synergistic or additive effects with the combination of imatinib and any given PI3K/mTOR pathway inhibition. Imatinib Mesylate 114-122 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-13 32457834-17 2020 Finally, targeted therapy with imatinib was induced in presence of a druggable c-KIT mutation, leading to a considerable response of all tumor sites that is still ongoing. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 79-84 32350132-2 2020 Although first-line treatment, imatinib, has revolutionized GIST treatment, drug resistance due to acquisition of secondary KIT/PDGFRalpha mutations develops in a majority of patients. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-127 32350132-5 2020 Here, we report the discovery and pharmacological characterization of AZD3229, a potent and selective small-molecule inhibitor of KIT and PDGFRalpha designed to inhibit a broad range of primary and imatinib-resistant secondary mutations seen in GIST. Imatinib Mesylate 198-206 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 130-133 31702819-3 2020 Previous reports have found success with sunitinib in imatinib-resistant GIST, but we report a certain wild-type KIT mutation GIST with cutaneous and subcutaneous metastasis that was unresponsive to multiple tyrosine kinase inhibitor (TKI) treatments. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 113-116 32198455-1 2020 The majority of gastrointestinal stromal tumors (GISTs) are driven by oncogenic KIT signaling and can therefore be effectively treated with the tyrosine kinase inhibitor (TKI) imatinib mesylate. Imatinib Mesylate 176-184 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-83 32198455-2 2020 However, most GISTs develop imatinib resistance through secondary KIT mutations. Imatinib Mesylate 28-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 66-69 32082541-0 2020 Loss of PI3 kinase association improves the sensitivity of secondary mutation of KIT to Imatinib. Imatinib Mesylate 88-96 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 32082541-3 2020 Results: In this study, we found that secondary mutation of KIT dramatically increases the ligand-independent activation of the receptor and their resistance to the often used KIT inhibitor Imatinib in the treatment of GISTs. Imatinib Mesylate 190-198 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 32082541-3 2020 Results: In this study, we found that secondary mutation of KIT dramatically increases the ligand-independent activation of the receptor and their resistance to the often used KIT inhibitor Imatinib in the treatment of GISTs. Imatinib Mesylate 190-198 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 176-179 32082541-6 2020 The in vivo assay further showed that the growth of tumors carrying secondary mutations of KIT is more sensitive to Imatinib when PI3 kinase association is blocked while inhibition of the lipid kinase activity of PI3 kinase cannot inhibit tumor growth, indicating that PI3 kinase is important for the drug resistance of secondary mutation of KIT independent of the lipid kinase activity of PI3 kinase. Imatinib Mesylate 116-124 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 91-94 31776458-8 2020 Coordinated inhibition of CK2 and KIT by CX4945 (or CK2 shRNA) and imatinib, respectively, leads to increased apoptosis, anti-proliferative effects and cell cycle arrest and decreased p-AKT and p-S6 expression, migration and invasiveness in all GIST cell lines compared with either intervention alone, indicating additive effects of inhibiting these two important regulators of GIST biology. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 31776458-9 2020 CONCLUSION: Our findings suggest that combinatorial inhibition of CK2 and KIT warrants evaluation as a novel therapeutic strategy in GIST, especially in imatinib-resistant GIST. Imatinib Mesylate 153-161 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-77 32099073-11 2020 In conclusion, our study indicates that DTF may harbor a broader mutational spectrum beyond CTNNB1 mutations, comprising targetable alterations including the herewith first reported imatinib-sensitive KIT V559D mutation in DTF. Imatinib Mesylate 182-190 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 201-204 32116712-0 2020 Clonal Selection of a Novel Deleterious TP53 Somatic Mutation Discovered in ctDNA of a KIT/PDGFRA Wild-Type Gastrointestinal Stromal Tumor Resistant to Imatinib. Imatinib Mesylate 152-160 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-90 32560620-0 2020 Encapsulation of Imatinib in Targeted KIT-5 Nanoparticles for Reducing its Cardiotoxicity and Hepatotoxicity. Imatinib Mesylate 17-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 38-41 31892598-1 2020 AIM: The purpose of the Imadje study was to confirm the efficacy and safety of imatinib, following resection of kit-positive gastrointestinal stromal tumour (GIST), in the adjuvant setting in the Greek population. Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 112-115 31758409-13 2020 Secondary mutations of KIT/PDGFRA were the most important contributors in GISTs developing resistance to imatinib treatment. Imatinib Mesylate 105-113 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-26 31197522-0 2020 Targeting the WEE1 kinase strengthens the antitumor activity of imatinib via promoting KIT autophagic degradation in gastrointestinal stromal tumors. Imatinib Mesylate 64-72 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-90 32640452-6 2020 A spectacular response to empirical imatinib treatment triggered further genetic analysis and led to the identification of a 45-bp duplication in KIT exon 11 undetectable by routine NGS. Imatinib Mesylate 36-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 146-149 32053767-2 2019 The use of targeted therapy against these mutations in GISTs is one of the most successful examples of precision medicine in solid tumors, beginning in 2002 with the development of imatinib, a small molecule tyrosine kinase inhibitor (TKI) of KIT. Imatinib Mesylate 181-189 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 243-246 31471313-1 2019 PURPOSE: Polyclonal emergence of KIT secondary mutations is a main mechanism of imatinib progression in gastrointestinal stromal tumor (GIST). Imatinib Mesylate 80-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 33-36 31236647-2 2019 Desmoid is a tumour with a local aggressiveness; GIST with KIT mutation responds massively to target treatment as IMATINIB, whereas soft tissue sarcoma and leiomyosarcoma are very aggressive with poor response to systemic therapies. Imatinib Mesylate 114-122 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 59-62 31363162-9 2019 Taken together, these results demonstrate the existence of a nuclear KIT-driven NFKBIB-RELA-KIT autoregulatory loop in GIST tumorigenesis, which are potential targets for developing combination therapy to overcome imatinib-resistant of KIT-expressing GISTs. Imatinib Mesylate 214-222 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-95 30079802-2 2019 Imatinib, a small molecule tyrosine kinase inhibitor, induces rapid and sustained clinical benefit by inhibiting a number of signaling pathways, including BCR-ABL and c-KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 167-172 31363162-0 2019 Nuclear KIT induces a NFKBIB-RELA-KIT autoregulatory loop in imatinib-resistant gastrointestinal stromal tumors. Imatinib Mesylate 61-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 8-11 31363162-0 2019 Nuclear KIT induces a NFKBIB-RELA-KIT autoregulatory loop in imatinib-resistant gastrointestinal stromal tumors. Imatinib Mesylate 61-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 31363162-7 2019 These findings were further confirmed by either RELA overexpression or NFKB/RELA inducer, valproic acid, treatment to result in reduced KIT expression and relative cell viability of imatinib-resistant GIST cells. Imatinib Mesylate 182-190 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 136-139 31363162-9 2019 Taken together, these results demonstrate the existence of a nuclear KIT-driven NFKBIB-RELA-KIT autoregulatory loop in GIST tumorigenesis, which are potential targets for developing combination therapy to overcome imatinib-resistant of KIT-expressing GISTs. Imatinib Mesylate 214-222 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-72 31363162-9 2019 Taken together, these results demonstrate the existence of a nuclear KIT-driven NFKBIB-RELA-KIT autoregulatory loop in GIST tumorigenesis, which are potential targets for developing combination therapy to overcome imatinib-resistant of KIT-expressing GISTs. Imatinib Mesylate 214-222 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-95 31371779-1 2019 Oncogenic KIT or PDGFRA tyrosine kinase mutations are compelling therapeutic targets in most gastrointestinal stromal tumors (GISTs), and the KIT inhibitor, imatinib, is therefore standard of care for patients with metastatic GIST. Imatinib Mesylate 157-165 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-13 31371779-1 2019 Oncogenic KIT or PDGFRA tyrosine kinase mutations are compelling therapeutic targets in most gastrointestinal stromal tumors (GISTs), and the KIT inhibitor, imatinib, is therefore standard of care for patients with metastatic GIST. Imatinib Mesylate 157-165 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 142-145 30707374-6 2019 KIT inhibitors that have been investigated in relevant clinical trials in advanced melanoma include imatinib, sunitinib, dasatinib, and nilotinib. Imatinib Mesylate 100-108 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 31372066-5 2019 Several approved tyrosine kinase inhibitors (TKIs), such as imatinib and nilotinib, have activity against wild-type KIT but lack activity against KITD816V. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 116-119 31308690-8 2019 Currently, the main strategy to combat imatinib resistance is to switch to another tyrosine kinase inhibitor, because imatinib-resistant GIST is usually still oncogenically addicted to KIT/PDGFRA signaling. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 185-188 31308690-8 2019 Currently, the main strategy to combat imatinib resistance is to switch to another tyrosine kinase inhibitor, because imatinib-resistant GIST is usually still oncogenically addicted to KIT/PDGFRA signaling. Imatinib Mesylate 118-126 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 185-188 30614559-0 2019 Response to imatinib in vaginal melanoma with KIT p.Val559Gly mutation previously treated with nivolumab, pembrolizumab and ipilimumab. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-49 30864679-0 2019 [Corrigendum] Antiproliferative effects of imatinib mesylate on ZR-75-1 and MDA-MB-231 cell lines via PDGFR-beta, PDGF-BB, c-Kit and SCF expression. Imatinib Mesylate 43-60 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-128 31138788-9 2019 In vitro, both SCF isoforms were able to activate the Akt pathway in c-Kit+ cells, and this effect was counteracted by the tyrosine kinase inhibitor imatinib. Imatinib Mesylate 149-157 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-74 31046271-2 2019 Despite the success of imatinib as the first-line treatment of GISTs, dozens of drug-acquired resistant mutations emerge, and c-KIT T670I is one of the most common mutants among them. Imatinib Mesylate 23-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 126-131 31205499-1 2019 The tyrosine kinase inhibitor (TKI) imatinib has radically changed the natural history of KIT-driven gastrointestinal stromal tumours (GISTs). Imatinib Mesylate 36-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-93 31205508-0 2019 Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors. Imatinib Mesylate 28-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-51 31205508-9 2019 In addition, it could inhibit imatinib resistant cKIT T670I and V654A mutants in vitro and in vivo GIST preclinical models. Imatinib Mesylate 30-38 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-53 30523507-2 2019 Imatinib, a potent inhibitor of mutated KIT, has revolutionized the clinical management of advanced, metastatic GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 40-43 30396570-1 2018 Imatinib mesylate, commercially known as Gleevec/Glivec, is the first targeted anticancer drug that inhibits activity of the tyrosine kinases, c-ABL, c-KIT, and PDGFR. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 150-155 31083182-0 2019 Relationship between efficacy of sunitinib and KIT mutation of patients with advanced gastrointestinal stromal tumors after failure of imatinib: A systematic review. Imatinib Mesylate 135-143 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-50 30126859-1 2019 BACKGROUND: Oncogenic KIT/PDGFRA signaling inhibition with imatinib achieves disease control in most patients with advanced/metastatic gastrointestinal stromal tumor (GIST), but resistance eventually develops after 20-24 months. Imatinib Mesylate 59-67 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 30902661-2 2019 Being tyrosine kinase inhibitor, imatinib modulates the activities of Abelson gene (c-Abl), Abelson related gene (ARG), platelet-derived growth factor receptor (PDGFR), FMS-like tyrosine kinase 3 (FLT3), lymphocyte-specific protein (Lck), mitogen activated protein kinase (MAPK), amyloid precursor protein intracellular domain (AICD), alpha-synuclein and the stem-cell factor receptor (c-kit). Imatinib Mesylate 33-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 386-391 30684595-0 2019 Repurposing cabozantinib to GISTs: Overcoming multiple imatinib-resistant cKIT mutations including gatekeeper and activation loop mutants in GISTs preclinical models. Imatinib Mesylate 55-63 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-78 30684595-1 2019 Despite of the great success of imatinib as the first-line treatment for GISTs, the majority of patients will develop drug-acquired resistance due to secondary mutations in the cKIT kinase. Imatinib Mesylate 32-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 177-181 30684595-3 2019 Through a drug repositioning approach, we found that cabozantinib exhibited higher potency than imatinib against primary gain-of-function mutations of cKIT. Imatinib Mesylate 96-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 151-155 30984366-10 2019 Our data also support the hypothesis that the use of KIT/PDGFRA inhibitors, including non-approved agents, has improved OS for patients with imatinib- and sunitinib-resistant GIST. Imatinib Mesylate 141-149 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-56 31037149-2 2019 At present, imatinib is the only targeted drug for KIT-mutation-bearing melanomas that is recommended by the National Comprehensive Cancer Network (NCCN) Clinical Practice guidelines. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-54 31037149-3 2019 Patients with KIT mutations, however, are either insensitive or rapidly progress to imatinib insensitivity, which restricts its clinical use. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 31037149-6 2019 Results: Ponatinib was more potent than imatinib against cells bearing KIT mutations. Imatinib Mesylate 40-48 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-74 30536695-14 2019 Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib-sensitive KIT mutations. Imatinib Mesylate 96-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-118 30530703-2 2019 Imatinib, an inhibitor of KIT, platelet-derived growth factor receptor alpha (PDGFRA), and a few other tyrosine kinases, is highly effective for GIST, but advanced GISTs frequently progress on imatinib and other approved tyrosine kinase inhibitors. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 30880826-5 2019 The benefit of radio- and chemotherapies is not clear and a small number of treatment attempts with imatinib have been made in cases of CD117 positivity or treatment attempts on an endocrine basis. Imatinib Mesylate 100-108 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 136-141 30612056-0 2019 Molecular response to imatinib in KIT F522C-mutated systemic mastocytosis. Imatinib Mesylate 22-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 28777148-2 2019 KIT tyrosine kinase inhibitor, imatinib mesylate, has been successfully used for the treatment of primary, advanced, and disseminated GISTs. Imatinib Mesylate 31-48 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 30567202-1 2018 Imatinib is a specific tyrosine kinase inhibitor which has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukaemia and c-KIT (CD117)-positive gastrointestinal stromal tumours. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 157-162 30567202-1 2018 Imatinib is a specific tyrosine kinase inhibitor which has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukaemia and c-KIT (CD117)-positive gastrointestinal stromal tumours. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 164-169 30311036-1 2018 Background Imatinib mesylate is a potent inhibitor of the Abl, KIT and platelet derived growth factor (PDGF) receptor tyrosine kinases. Imatinib Mesylate 11-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-66 30253992-11 2018 Subsequent KIT-targeting tyrosine kinase inhibitor therapy with imatinib was administered for a short time. Imatinib Mesylate 64-72 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 11-14 30500954-7 2018 Notably, upregulation of c-KIT expression by FUBP1 and RUNX1 promotes cell proliferation and renders cells more resistant to the c-KIT inhibitor imatinib mesylate, a common therapeutic drug. Imatinib Mesylate 145-162 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 25-30 30500954-7 2018 Notably, upregulation of c-KIT expression by FUBP1 and RUNX1 promotes cell proliferation and renders cells more resistant to the c-KIT inhibitor imatinib mesylate, a common therapeutic drug. Imatinib Mesylate 145-162 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 129-134 30101284-2 2018 Mutations in these type III receptor tyrosine kinases (RTKs) account for over 85% of GIST cases, and the majority of KIT primary mutations respond to treatment with the tyrosine kinase inhibitor (TKI) imatinib. Imatinib Mesylate 201-209 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-120 30268485-4 2018 Amino acid sequence alignment confirmed homology to the imatinib-sensitive KIT N822 K activation loop mutation observed in GIST. Imatinib Mesylate 56-64 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-78 30075827-2 2019 Current studies show that imatinib treatment is a promising approach in treating advanced melanoma patients harboring c-Kit mutations or amplifications. Imatinib Mesylate 26-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 118-123 30075827-10 2019 Our study, combined with those studies targeting patients with a c-Kit alteration, validates the role of imatinib as an important and promising therapeutic agent in the treatment of patients with advanced melanoma. Imatinib Mesylate 105-113 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 65-70 30792533-0 2019 Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours. Imatinib Mesylate 88-96 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-74 30792533-1 2019 BACKGROUND: Most patients with KIT-mutant gastrointestinal stromal tumours (GISTs) benefit from imatinib, but treatment resistance results from outgrowth of heterogeneous subclones with KIT secondary mutations. Imatinib Mesylate 96-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 31-34 30792533-8 2019 CONCLUSIONS: Our data highlight that heterogeneity of KIT secondary mutations is the main mechanism of tumour progression to KIT inhibitors in imatinib-resistant GIST patients. Imatinib Mesylate 143-151 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 54-57 30792533-8 2019 CONCLUSIONS: Our data highlight that heterogeneity of KIT secondary mutations is the main mechanism of tumour progression to KIT inhibitors in imatinib-resistant GIST patients. Imatinib Mesylate 143-151 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 125-128 30199578-0 2019 Successful treatment of metastatic mucosal melanoma with a Del579 c-KIT mutation by imatinib after treatment of anti-PD-1 antibody. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-71 30569109-1 2019 Imatinib is a powerful tyrosine kinase inhibitor that specifically targets BCR-ABL, c-KIT, and PDGFR kinases, and is used in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and other types of cancers. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-89 31043947-0 2019 Lack of Response to Imatinib in Melanoma Carrying Rare KIT Mutation p.T632I. Imatinib Mesylate 20-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 55-58 31043947-2 2019 There is a diversity of spectrum of KIT mutations, with some of them rendering tumors responsive to imatinib, while others being imatinib-resistant or not studied yet. Imatinib Mesylate 100-108 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 36-39 31043947-2 2019 There is a diversity of spectrum of KIT mutations, with some of them rendering tumors responsive to imatinib, while others being imatinib-resistant or not studied yet. Imatinib Mesylate 129-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 36-39 30311036-0 2018 A phase II study of imatinib mesylate and letrozole in patients with hormone receptor-positive metastatic breast cancer expressing c-kit or PDGFR-beta. Imatinib Mesylate 20-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 131-136 30545989-6 2018 The tumor harbored a KIT exon 11 deletion mutation in codon 558, which predicts a favorable response to imatinib. Imatinib Mesylate 104-112 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-24 30396237-4 2018 The inhibition of SCF signaling via treatment with a c-KIT antagonist (imatinib) during hPSC-derived hematopoiesis resulted in reductions in the yield and multi-lineage potential of hematopoietic progenitors. Imatinib Mesylate 71-79 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-58 29623544-3 2018 Despite the revolutionary effects of imatinib, some patients are primarily resistant to imatinib and many become resistant because of acquisition of secondary mutations in KIT. Imatinib Mesylate 37-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 172-175 30697609-5 2019 The tyrosine kinase inhibitor imatinib, which selectively inhibits tyrosine kinase KIT, has shown substantial clinical benefit for patients with GIST. Imatinib Mesylate 30-38 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 83-86 30697609-6 2019 In clinical trials, imatinib treatment resulted in response rates of 40%-55% and longer progression-free survival for patients with a KIT-positive unresectable or metastatic GIST. Imatinib Mesylate 20-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-137 30298093-3 2018 Drug resistance to Imatinib Mesylate (c-KIT inhibitor) has emerged. Imatinib Mesylate 19-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 38-43 29764854-2 2018 Treatment with the small-molecule inhibitors imatinib, sunitinib, and regorafenib resulted in resistance (c-KIT mutant tumors) or limited activity (c-KIT wild-type tumors). Imatinib Mesylate 45-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-111 29764854-2 2018 Treatment with the small-molecule inhibitors imatinib, sunitinib, and regorafenib resulted in resistance (c-KIT mutant tumors) or limited activity (c-KIT wild-type tumors). Imatinib Mesylate 45-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 148-153 30224936-1 2018 Objectives: Sunitinib (a second-line chemotherapeutic agent that inhibits multiple kinases, including KIT and PDGFR) is widely used in imatinib-resistant patients with gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 135-143 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-105 30159192-5 2018 In addition, histological analysis of the tumor for macroscopic and microscopic characteristics including mitotic index and c-Kit/CD117 status should be obtained to guide adjuvant therapy with imatinib mesylate. Imatinib Mesylate 193-210 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-129 30159192-5 2018 In addition, histological analysis of the tumor for macroscopic and microscopic characteristics including mitotic index and c-Kit/CD117 status should be obtained to guide adjuvant therapy with imatinib mesylate. Imatinib Mesylate 193-210 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 130-135 30007460-4 2018 The discovery of KIT mutations as central to the pathobiology of mastocytosis has prompted development of KIT-targeted agents, including imatinib and midostaurin (approved medications for patients with advanced systemic mastocytosis), and drugs in development, like KIT D816V-specific inhibitor avapritinib. Imatinib Mesylate 137-145 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-20 28736245-5 2018 Imatinib has the desirable effect of attacking multiple targets involved in the early hypoxic and inflammatory stages of FOP flare-ups, including HIF1-alpha, PDGFRalpha, c-KIT, and multiple MAP kinases. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-175 29724653-2 2018 They can be effectively treated by the kinase inhibitor imatinib, which locks the c-KIT kinase domain into an inactive conformation. Imatinib Mesylate 56-64 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-87 29724653-3 2018 However resistance to imatinib, driven by active-site mutations, is a recurrent clinical challenge, which has been only partly met by the subsequent development of second and third-generation c-KIT inhibitors. Imatinib Mesylate 22-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 192-197 29969914-6 2018 CONCLUSION: Adjuvant imatinib improves RFS of GIST with intermediate risk of recurrence, particularly in GIST with intestinal and rectal location or c-kit gene exon 11 deletion mutation. Imatinib Mesylate 21-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 149-154 29620139-9 2018 In addition, PDGFR-beta, PDGF-BB, c-Kit and SCF were expressed in both breast carcinoma cell lines; PDGFR-beta and c-Kit, as imatinib targets, were downregulated in response to imatinib mesylate treatment. Imatinib Mesylate 125-133 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-120 29620139-9 2018 In addition, PDGFR-beta, PDGF-BB, c-Kit and SCF were expressed in both breast carcinoma cell lines; PDGFR-beta and c-Kit, as imatinib targets, were downregulated in response to imatinib mesylate treatment. Imatinib Mesylate 177-194 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 115-120 29620139-11 2018 In conclusion, the antiproliferative, cytostatic and proapoptotic effects of imatinib mesylate may be the result of a reduction in the expression of c-Kit and PDGFR tyrosine kinase receptors, thus resulting in suppression of the corresponding ligand PDGF-BB. Imatinib Mesylate 77-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 149-154 29704617-7 2018 An activation segment exon 17 D816V mutation is one of the more common resistance mutations in Kit and this mutant is resistant to imatinib and sorafenib. Imatinib Mesylate 131-139 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-98 29704617-10 2018 Based upon the X-ray crystallographic structures, imatinib, sunitinib, and ponatinib are Type II Kit inhibitors. Imatinib Mesylate 50-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 97-100 29620139-0 2018 Antiproliferative effects of imatinib mesylate on ZR-75-1 and MDA-MB-231 cell lines via PDGFR-beta, PDGF-BB, c-Kit and SCF expression. Imatinib Mesylate 29-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 109-114 29620139-1 2018 Imatinib mesylate is an anti-neoplastic targeted chemotherapeutic agent, which can inhibit tyrosine kinase receptors, including BCR-ABL, platelet-derived growth factor receptors (PDGFRs) and c-Kit. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 191-196 29494307-13 2018 Our cell death assay revealed that SpCC cell death was induced by the anticancer drug imatinib, which is known to inhibit protein tyrosine kinase activity of ABL, platelet-derived growth factor receptor alpha (PDGFRalpha), and KIT. Imatinib Mesylate 86-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 227-230 29600692-4 2018 Imatinib was shown to achieve high response rates in c-kit mutated melanoma. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-58 29998023-3 2018 Advances in immunopathology have identified a mutation in the c-KIT proto-oncogene, leading to the development of the tyrosine-kinase inhibitor Imatinib as targeted therapy for advanced disease. Imatinib Mesylate 144-152 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-67 29439183-2 2018 Most patients exhibit a D816V-mutated variant of KIT, which confers resistance against imatinib. Imatinib Mesylate 87-95 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 28710566-0 2018 Remarkable effects of imatinib in a family with young onset gastrointestinal stromal tumors and cutaneous hyperpigmentation associated with a germline KIT-Trp557Arg mutation: case report and literature overview. Imatinib Mesylate 22-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 151-154 28710566-5 2018 The effect of imatinib in patients harboring a germline KIT mutation has been rarely described. Imatinib Mesylate 14-22 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 56-59 28710566-13 2018 Imatinib treatment in GIST patients harboring a germline KIT mutation shows favorable and long-term responses in both the tumor and the phenotypical hyperpigmentation. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-60 29523662-2 2018 Adjuvant imatinib therapy, which targets the most common driver mutations in GIST (KIT and PDGFRA), is recommended for patients with high-risk GIST, but it has known teratogenicity in the first trimester. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 83-86 27384439-0 2018 Two different KIT mutations may lead to different responses to imatinib in metastatic gastrointestinal stromal tumor. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 29682621-1 2018 Although imatinib is a standard treatment for metastatic or recurrent gastrointestinal stromal tumors (GISTs), acquired c-kit mutations reportedly cause secondary resistance to imatinib. Imatinib Mesylate 177-185 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-125 29552659-9 2018 Imatinib mesylate (IM) is indicated as first-line treatment of metastatic or unresectable GIST, and clinical outcomes are correlated with KIT mutation genotype. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-141 29552659-9 2018 Imatinib mesylate (IM) is indicated as first-line treatment of metastatic or unresectable GIST, and clinical outcomes are correlated with KIT mutation genotype. Imatinib Mesylate 19-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-141 30488756-2 2018 However, approximately 10% of KIT-positive GIST metastases lose KIT expression at the time of clinical progression during imatinib therapy. Imatinib Mesylate 122-130 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-33 29423012-0 2018 CCDC26 knockdown enhances resistance of gastrointestinal stromal tumor cells to imatinib by interacting with c-KIT. Imatinib Mesylate 80-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 109-114 29423012-8 2018 We also found that inhibiting c-KIT induced resistance to imatinib. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-35 29423012-9 2018 Lastly, we proved that inhibiting c-KIT can reverse CCDC26 knockdown-mediated imatinib resistance in GIST. Imatinib Mesylate 78-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-39 29423012-10 2018 We suggest that CCDC26 knockdown can induce imatinib resistance in GIST cells by downregulating c-KIT expression. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-101 29334307-0 2018 Regorafenib regresses an imatinib-resistant recurrent gastrointestinal stromal tumor (GIST) with a mutation in exons 11 and 17 of c-kit in a patient-derived orthotopic xenograft (PDOX) nude mouse model. Imatinib Mesylate 25-33 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 130-135 30488756-2 2018 However, approximately 10% of KIT-positive GIST metastases lose KIT expression at the time of clinical progression during imatinib therapy. Imatinib Mesylate 122-130 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-67 28988501-6 2017 The first effective systemic therapy in clinical practice in GIST and DFSP was imatinib - tyrosine kinase inhibitor acting on KIT and PDGFR alpha/beta. Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 126-129 29143894-1 2018 Imatinib has revolutionized the treatment of GIST since this drug is able to inhibit tumoral growth by blocking the activity of receptor tyrosine kinases, KIT or PDGFRA, that in these tumors are constitutively activated because of the presence of mutations that alters their catalytic activity. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 155-158 30286478-10 2018 In 3 patients KIT mutations (e.g. pM541L, pV654A) known to be tissue-based biomarkers with level 1 evidence for the treatment with imatinib and sunitinib were found. Imatinib Mesylate 131-139 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 30069623-3 2018 Imatinib is a rationally designed oral signal transduction inhibitor that specifically targets several protein tyrosine kinases, Abl, Arg (Abl-related gene), the stem cell factor receptor (c-KIT), platelet-derived growth factor receptor (PDGF-R), and their oncogenic forms, most notably BCR-ABL. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 189-194 29043985-11 2017 Lack of therapeutic response and absence of the KIT D816V mutation led to switch to imatinib, following the latest scientific recommendations. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-51 29245294-4 2017 However, imatinib mesylate, a specific inhibitor of KIT tyrosine kinase, frequently involves changes in the morphology and IHC staining of GIST, impeding the diagnosis. Imatinib Mesylate 9-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 29245294-14 2017 A molecular analysis found a mutation in exon 11 of KIT gene before and after imatinib therapy in both patients, confirming the diagnosis of GIST. Imatinib Mesylate 78-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 28765927-10 2017 It may be possible that a similar mechanism of KIT overexpression underlies the acquisition of imatinib resistance in some human tumors that are driven by KIT mutation. Imatinib Mesylate 95-103 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-50 29113157-3 2017 Gastrointestinal stromal tumor (GIST) development is associated with activating mutations of KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA), which are oncogenes that predict the response to imatinib mesylate. Imatinib Mesylate 251-268 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-136 29113157-3 2017 Gastrointestinal stromal tumor (GIST) development is associated with activating mutations of KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA), which are oncogenes that predict the response to imatinib mesylate. Imatinib Mesylate 251-268 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-96 28790106-2 2017 Imatinib treatment, which inhibits KIT signaling, depletes mast cells in vivo. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 35-38 28421416-1 2017 PURPOSE: The KIT inhibitor, imatinib, has shown promising efficacy in patients with KIT-mutated melanoma; however, acquisition of resistance to imatinib occurs rapidly in the majority of patients. Imatinib Mesylate 28-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 13-16 28421416-1 2017 PURPOSE: The KIT inhibitor, imatinib, has shown promising efficacy in patients with KIT-mutated melanoma; however, acquisition of resistance to imatinib occurs rapidly in the majority of patients. Imatinib Mesylate 28-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 28421416-1 2017 PURPOSE: The KIT inhibitor, imatinib, has shown promising efficacy in patients with KIT-mutated melanoma; however, acquisition of resistance to imatinib occurs rapidly in the majority of patients. Imatinib Mesylate 144-152 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 13-16 28421416-3 2017 METHODS: We analyzed biopsy samples from paired baseline and post-treatment tumor lesions in one patient with KIT-mutated melanoma who had had an initial objective tumor regression in response to imatinib treatment followed by disease progression 8 months later. Imatinib Mesylate 196-204 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 28421416-8 2017 Further investigation into the causes of acquired resistance to imatinib will be essential to improve the prognosis for patients with KIT-mutated melanoma. Imatinib Mesylate 64-72 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-137 28765927-10 2017 It may be possible that a similar mechanism of KIT overexpression underlies the acquisition of imatinib resistance in some human tumors that are driven by KIT mutation. Imatinib Mesylate 95-103 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 155-158 29098070-0 2017 Imatinib response of gastrointestinal stromal tumor patients with germline mutation on KIT exon 13: A family report. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-90 29098070-5 2017 We describe here clinical, imaging, pathological and genetic findings of a family with four affected members; grandmother, his son and two grand-sons having a germline gain-of-function mutation of KIT in exon 13 and discuss the imatinib mesylate treatment surveillance outcomes towards disease management. Imatinib Mesylate 228-245 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 197-200 28760855-0 2017 Dual Targeting of Insulin Receptor and KIT in Imatinib-Resistant Gastrointestinal Stromal Tumors. Imatinib Mesylate 46-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 39-42 28760855-7 2017 Our findings suggest that combinatorial inhibition of IR and KIT warrants clinical evaluation as a novel therapeutic strategy in imatinib-resistant GISTs. Imatinib Mesylate 129-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-64 28760855-1 2017 Oncogenic KIT or PDGFRA receptor tyrosine kinase (RTK) mutations are compelling therapeutic targets in gastrointestinal stromal tumors (GIST), and treatment with the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with metastatic GIST. Imatinib Mesylate 187-195 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-13 28760855-1 2017 Oncogenic KIT or PDGFRA receptor tyrosine kinase (RTK) mutations are compelling therapeutic targets in gastrointestinal stromal tumors (GIST), and treatment with the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with metastatic GIST. Imatinib Mesylate 187-195 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 166-169 28760855-3 2017 Using phospho-RTK and immunoblot assays, we demonstrate activation of KIT and insulin receptor (IR) in imatinib-resistant GIST cell lines (GIST430 and GIST48) and biopsies with acquisition of KIT secondary mutations, but not in imatinib-sensitive GIST cells (GIST882 and GIST-T1). Imatinib Mesylate 103-111 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-73 28760855-3 2017 Using phospho-RTK and immunoblot assays, we demonstrate activation of KIT and insulin receptor (IR) in imatinib-resistant GIST cell lines (GIST430 and GIST48) and biopsies with acquisition of KIT secondary mutations, but not in imatinib-sensitive GIST cells (GIST882 and GIST-T1). Imatinib Mesylate 228-236 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-73 28760855-5 2017 Additive effects showing increased apoptosis, antiproliferative effects, cell-cycle arrest, and decreased pAKT and pS6 expression, tumor growth, migration, and invasiveness were observed in imatinib-resistant GIST cells with IR activation after coordinated inhibition of IR and KIT by linsitinib (or IR shRNA) and imatinib, respectively, compared with either intervention alone. Imatinib Mesylate 190-198 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 278-281 28915580-0 2017 Molecular and functional characterization of a new 3" end KIT juxtamembrane deletion in a duodenal GIST treated with neoadjuvant Imatinib. Imatinib Mesylate 129-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-61 28410286-0 2017 Successful treatment with imatinib after nilotinib and ipilimumab in a c-kit-mutated advanced melanoma patient: a case report. Imatinib Mesylate 26-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-76 28410286-3 2017 Different trials show that imatinib or nilotinib lead to meaningful responses in c-kit-mutated melanoma patients. Imatinib Mesylate 27-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-86 28410286-5 2017 We describe the sequential use of imatinib after nilotinib in a c-kit-mutated melanoma patient, who progressed on interferon, Allovectin, dacarbazine, nilotinib and ipilimumab, and was finally treated with the c-kit inhibitor imatinib. Imatinib Mesylate 34-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-69 29137292-9 2017 The Kit inhibitor imatinib could benefit metastatic OMM patients with c-Kit mutations. Imatinib Mesylate 18-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-75 28334439-1 2017 BACKGROUND: KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-15 28334439-1 2017 BACKGROUND: KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-102 28334439-1 2017 BACKGROUND: KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-102 28334439-19 2017 In view of its clinical activity, it is recommended that imatinib remain the KIT tyrosine kinase inhibitor of choice for unresectable KIT+ melanoma. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-80 28334439-19 2017 In view of its clinical activity, it is recommended that imatinib remain the KIT tyrosine kinase inhibitor of choice for unresectable KIT+ melanoma. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 134-137 28487491-2 2017 Imatinib selectively inhibits KIT and PDGFR, leading to disease control for 80%-90% of patients with metastatic GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-33 28487491-3 2017 Imatinib resistance can occur within a median of 2-3 years due to secondary mutations in KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-92 29100343-6 2017 Imatinib inhibited the KIT pathway in imatinib-sensitive GIST-T1 but not GIST-RX1, RX2, and RX4. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-26 29100343-6 2017 Imatinib inhibited the KIT pathway in imatinib-sensitive GIST-T1 but not GIST-RX1, RX2, and RX4. Imatinib Mesylate 38-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-26 28442505-8 2017 Compared with both monotherapies, the C75/imatinib combination more effectively suppressed the growth of xenografts, exhibiting decreased KIT phosphorylation, Ki-67, and phosphorylated PI3K/AKT/mTOR levels and increased TUNEL labeling.Conclusions: We have characterized the prognostic, biological, and therapeutic implications of overexpressed FASN in GISTs. Imatinib Mesylate 42-50 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-141 28410286-5 2017 We describe the sequential use of imatinib after nilotinib in a c-kit-mutated melanoma patient, who progressed on interferon, Allovectin, dacarbazine, nilotinib and ipilimumab, and was finally treated with the c-kit inhibitor imatinib. Imatinib Mesylate 34-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 210-215 28915580-6 2017 In line with these clinical evidences computer simulations, biophysical techniques and in vitro experiments demonstrated that the receptor tyrosine kinase KIT carrying the Delta574-580 mutation displays constitutive phosphorylation, which can be switched-off upon Imatinib treatment. Imatinib Mesylate 264-272 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 155-158 28196207-1 2017 Importance: After identification of activating mutations of the KIT gene in gastrointestinal stromal tumor (GIST)-the most common sarcomaof the gastrointestinal tract-a phase 2 study demonstrated efficacy of imatinib mesylate in patients with metastatic GIST harboring a KIT exon 11 mutation. Imatinib Mesylate 208-225 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-67 28196207-1 2017 Importance: After identification of activating mutations of the KIT gene in gastrointestinal stromal tumor (GIST)-the most common sarcomaof the gastrointestinal tract-a phase 2 study demonstrated efficacy of imatinib mesylate in patients with metastatic GIST harboring a KIT exon 11 mutation. Imatinib Mesylate 208-225 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 271-274 28403213-2 2017 The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 28514613-0 2017 KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma. Imatinib Mesylate 18-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 28514613-3 2017 We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma. Imatinib Mesylate 66-74 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 78-81 28192400-2 2017 Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. Imatinib Mesylate 56-64 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-45 28192400-3 2017 The characteristic intracellular accumulation of imatinib-sensitive and -resistant Kit protein is well documented, but its relationship to oncogenic signaling remains unknown. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 83-86 28192400-5 2017 In imatinib-resistant GIST with a secondary Kit mutation, Kit localizes predominantly on the Golgi apparatus. Imatinib Mesylate 3-11 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 28192400-5 2017 In imatinib-resistant GIST with a secondary Kit mutation, Kit localizes predominantly on the Golgi apparatus. Imatinib Mesylate 3-11 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 58-61 28192400-6 2017 Both imatinib-sensitive and imatinib-resistant Kit (Kit(mut)) become fully auto-phosphorylated only on the Golgi and only if in a complex-glycosylated form. Imatinib Mesylate 5-13 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-50 28192400-6 2017 Both imatinib-sensitive and imatinib-resistant Kit (Kit(mut)) become fully auto-phosphorylated only on the Golgi and only if in a complex-glycosylated form. Imatinib Mesylate 28-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-50 28541695-0 2017 Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRalpha) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs). Imatinib Mesylate 158-166 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 104-109 28478525-3 2017 Three tyrosine kinase inhibitors (TKIs) with KIT inhibitory activity - imatinib, sunitinib, and regorafenib - are approved to treat advanced GIST and have successfully exploited this addiction to KIT oncogenic signaling, demonstrating remarkable activity in a disease that historically had no successful systemic therapy options. Imatinib Mesylate 71-79 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-48 28478525-3 2017 Three tyrosine kinase inhibitors (TKIs) with KIT inhibitory activity - imatinib, sunitinib, and regorafenib - are approved to treat advanced GIST and have successfully exploited this addiction to KIT oncogenic signaling, demonstrating remarkable activity in a disease that historically had no successful systemic therapy options. Imatinib Mesylate 71-79 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 196-199 28334365-16 2017 Conclusions and Relevance: Patients with KIT exon 11 deletion mutations benefit most from the longer duration of adjuvant imatinib. Imatinib Mesylate 122-130 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 41-44 28334365-17 2017 The duration of adjuvant imatinib modifies the risk of GIST recurrence associated with some KIT mutations, including deletions that affect exon 11 codons 557 and/or 558. Imatinib Mesylate 25-33 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 92-95 28403213-2 2017 The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 28403213-3 2017 However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Imatinib Mesylate 108-116 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 28403213-3 2017 However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Imatinib Mesylate 199-207 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 28403213-4 2017 Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the signal transducer and activator of transcription 5 (STAT5) but only on endolysosomes and on the endoplasmic reticulum (ER), respectively. Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-101 28403213-4 2017 Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the signal transducer and activator of transcription 5 (STAT5) but only on endolysosomes and on the endoplasmic reticulum (ER), respectively. Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 27997714-2 2017 Despite its proven benefits, half of the patients treated with imatinib show disease progression within 2 years due to secondary resistance mutations in KIT. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 153-156 27997714-10 2017 Pre-existing cancer cells with genetic alterations promoting apoptosis resistance may serve as a basis whereby cancer cells with critical mutations, such as secondary KIT mutations, can establish full imatinib resistance. Imatinib Mesylate 201-209 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 167-170 27864817-12 2016 Moreover, secondary mutations in the KIT gene, similar to those involved in resistance to imatinib, might be involved in resistance to nilotinib. Imatinib Mesylate 90-98 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-40 28260860-0 2017 Antiproliferation effect of imatinib mesylate on MCF7, T-47D tumorigenic and MCF 10A nontumorigenic breast cell lines via PDGFR-beta, PDGF-BB, c-Kit and SCF genes. Imatinib Mesylate 28-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 143-148 28260860-3 2017 Imatinib mesylate is a selective inhibitor of receptor tyrosine kinase, including PDGFR-beta and c-Kit. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 97-102 28074523-0 2017 Familial gastrointestinal stromal tumors, lentigines, and cafe-au-lait macules associated with germline c-kit mutation treated with imatinib. Imatinib Mesylate 132-140 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 104-109 27965460-0 2017 Opposing roles of KIT and ABL1 in the therapeutic response of gastrointestinal stromal tumor (GIST) cells to imatinib mesylate. Imatinib Mesylate 109-126 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 27965460-3 2017 Because of cross-reactivity of imatinib against the KIT kinase, the drug is also successfully used for the treatment of GIST. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 27965460-4 2017 Although inhibition of KIT clearly has a major role in the therapeutic response of GIST to imatinib, the contribution of concomitant inhibition of ABL in this context has never been explored. Imatinib Mesylate 91-99 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-26 27965460-6 2017 Using siRNA-mediated knockdown, we demonstrate that depletion of KIT in conjunction with ABL1 - hence mimicking imatinib treatment - leads to reduced apoptosis induction and attenuated inhibition of cellular proliferation when compared to depletion of KIT alone. Imatinib Mesylate 112-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 65-68 27470968-11 2017 PD-1 and PD-L1 blockade in vivo each had no efficacy alone but enhanced the antitumor effects of imatinib by increasing T-cell effector function in the presence of KIT and IDO inhibition. Imatinib Mesylate 97-105 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 164-167 27687311-0 2017 Mutant KIT as imatinib-sensitive target in metastatic sinonasal carcinoma. Imatinib Mesylate 14-22 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 7-10 27687311-6 2017 Results: Molecularly guided treatment with imatinib in analogy to the management of gastrointestinal stromal tumor (GIST) resulted in a dramatic and durable response with remission of nearly all tumor manifestations, indicating a dominant driver function of mutant KIT in this tumor. Imatinib Mesylate 43-51 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 265-268 27793025-12 2016 Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST. Imatinib Mesylate 112-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-32 27928806-6 2016 More than half of metastatic GISTs patients receiving imatinib treatment can develop to c-kit secondary mutations, which are responsible for secondary resistance. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 88-93 26416414-6 2016 In imatinib arm, KIT exon 11 deletions was associated with a shorter TTP (7 vs 17 months; P = 0.02), with a trend in OS (54 vs 71 months P = 0.063). Imatinib Mesylate 3-11 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-20 27762455-10 2016 Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 27762455-10 2016 Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 27793952-2 2016 Specifically, the consistent dependence of GISTs on proto-oncogene c-KIT signaling led to the development and successful implementation of imatinib, a small-molecule c-KIT inhibitor. Imatinib Mesylate 139-147 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-72 27793952-2 2016 Specifically, the consistent dependence of GISTs on proto-oncogene c-KIT signaling led to the development and successful implementation of imatinib, a small-molecule c-KIT inhibitor. Imatinib Mesylate 139-147 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-72 27793952-3 2016 Imatinib induces, rapid and sustained clinical benefit by blocking the signaling via c-KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-90 26416414-7 2016 No difference was found in patients treated with sunitinib (P = 0.370).A second line with sunitinib was associated with an improved TTP in KIT exon 11 mutated patients progressing on imatinib 400 mg/die. Imatinib Mesylate 183-191 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 139-142 27527414-4 2016 GISTs are known to be refractory to conventional therapies but the introduction of Imatinib, a selective inhibitor of tyrosine kinases Abl and Kit, significantly ameliorated the treatment options of GISTs patients. Imatinib Mesylate 83-91 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 143-146 27467080-4 2016 In particular, the mutation V560G in KIT increases its sensitivity to Imatinib, while the D816V in KIT, and D802V in CSF-1R, triggers resistance to the drug. Imatinib Mesylate 70-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-40 28195260-2 2016 The discovery of the occurrence of activating KIT mutations and KIT expression in GISTs opened the way to the unequivocal diagnosis of these tumors and to their successful treatment with imatinib, a tyrosin kinase inhibitor. Imatinib Mesylate 187-195 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-49 28195260-2 2016 The discovery of the occurrence of activating KIT mutations and KIT expression in GISTs opened the way to the unequivocal diagnosis of these tumors and to their successful treatment with imatinib, a tyrosin kinase inhibitor. Imatinib Mesylate 187-195 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-67 27482095-5 2016 A second class of KIT mutants, including a mutant resistant to imatinib treatment, responded well to a combination of TKI with anti-KIT antibodies or to anti-KIT toxin conjugates, respectively. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 27515884-0 2016 Successful treatment of c-kit-positive metastatic Adenoid Cystic Carcinoma (ACC) with a combination of curcumin plus imatinib: A case report. Imatinib Mesylate 117-125 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-29 27515884-5 2016 Imatinib is monoclonal antibody with specific activity against c-kit but has not been found to be effective in treating patients with ACC in which c-kit is overexpressed and activated. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-68 27515884-15 2016 To our knowledge, this is the first report of a patient with a c-kit-positive ACC that is successfully treated with the combination of imatinib and curcumin in an integrative approach. Imatinib Mesylate 135-143 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-68 27512117-4 2016 Tyrosine kinase inhibitors (TKI) targeting c-KIT, such as imatinib, has been used successfully to treat c-KIT driven gastrointestinal stromal tumors. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-48 27512117-4 2016 Tyrosine kinase inhibitors (TKI) targeting c-KIT, such as imatinib, has been used successfully to treat c-KIT driven gastrointestinal stromal tumors. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 104-109 28978170-1 2017 Resistance to imatinib has been recurrently reported in systemic mastocytosis (SM) carrying exon 17 KIT mutations. Imatinib Mesylate 14-22 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 100-103 28978170-10 2017 These results together with previous data from the literature support the relevance of the KIT mutational status in selecting SM patients who are candidates for imatinib therapy. Imatinib Mesylate 161-169 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 91-94 27467080-5 2016 We analyzed the Imatinib binding affinity to the native and mutated KIT (mutations V560G, S628N and D816V) and CSF-1R (mutation D802V) by using molecular dynamics simulations and energy calculations of Imatinib target complexes. Imatinib Mesylate 16-24 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-71 27467080-6 2016 Further, we evaluated the sensitivity of the studied KIT receptors to Imatinib by measuring the inhibition of KIT phosphorylation. Imatinib Mesylate 70-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-56 27467080-6 2016 Further, we evaluated the sensitivity of the studied KIT receptors to Imatinib by measuring the inhibition of KIT phosphorylation. Imatinib Mesylate 70-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 27467080-7 2016 Our study showed that (i) the binding free energy of Imatinib to the targets is highly correlated with their experimentally measured sensitivity; (ii) the electrostatic interactions are a decisive factor affecting the binding energy; (iii) the most deleterious impact to the Imatinib sensitivity is promoted by D802V (CSF-1R) and D816V (KIT) mutations; (iv) the role of the juxtamembrane region, JMR, in the imatinib binding is accessory. Imatinib Mesylate 53-61 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 337-340 27467080-7 2016 Our study showed that (i) the binding free energy of Imatinib to the targets is highly correlated with their experimentally measured sensitivity; (ii) the electrostatic interactions are a decisive factor affecting the binding energy; (iii) the most deleterious impact to the Imatinib sensitivity is promoted by D802V (CSF-1R) and D816V (KIT) mutations; (iv) the role of the juxtamembrane region, JMR, in the imatinib binding is accessory. Imatinib Mesylate 275-283 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 337-340 27467080-7 2016 Our study showed that (i) the binding free energy of Imatinib to the targets is highly correlated with their experimentally measured sensitivity; (ii) the electrostatic interactions are a decisive factor affecting the binding energy; (iii) the most deleterious impact to the Imatinib sensitivity is promoted by D802V (CSF-1R) and D816V (KIT) mutations; (iv) the role of the juxtamembrane region, JMR, in the imatinib binding is accessory. Imatinib Mesylate 408-416 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 337-340 27077705-2 2016 Clinically used c-KIT kinase inhibitors, i.e., Imatinib and Sunitinib, bear other important targets such as ABL or FLT3 kinases. Imatinib Mesylate 47-55 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 16-21 26982239-5 2016 During treatment with the c-KIT inhibitor imatinib, she developed severe therapy-limiting skin toxicity. Imatinib Mesylate 42-50 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-31 27272772-3 2016 In the early 2000s, the ability of imatinib mesylate, a tyrosine kinase inhibitor, to inhibit KIT established a new paradigm for cancer treatment. Imatinib Mesylate 35-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 94-97 26848617-8 2016 Eleven patients treated with imatinib were evaluable for clinical response, and 2 of 3 patients with KIT mutations achieved partial response (PR), while only 1 of 8 patients without KIT mutations reached PR. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 101-104 27097112-2 2016 A recent description of KIT and BRAF mutations co-occurring in an untreated GIST has challenged the concept of their being mutually exclusive and may account for ab initio resistance to Imatinib, even in the presence of Imatinib-sensitive KIT mutations. Imatinib Mesylate 186-194 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 27097112-2 2016 A recent description of KIT and BRAF mutations co-occurring in an untreated GIST has challenged the concept of their being mutually exclusive and may account for ab initio resistance to Imatinib, even in the presence of Imatinib-sensitive KIT mutations. Imatinib Mesylate 220-228 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 27123048-9 2016 Imatinib, a tyrosine kinase inhibitor, may be an effective treatment against standard chemotherapy-resistant CNS germinoma patients exhibiting c-Kit mutations. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 143-148 27167336-11 2016 Combinational treatment with KIT inhibitors (imatinib, regorafenib) enhanced the proapoptotic effect. Imatinib Mesylate 45-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-32 27156227-1 2016 BACKGROUND: Gastrointestinal stromal tumours (GIST) treated with the tyrosine kinase inhibitor (TKI) imatinib can become resistant when additional mutations in the receptor tyrosine kinases KIT or PDGFRA block imatinib activity. Imatinib Mesylate 101-109 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 190-193 27156227-1 2016 BACKGROUND: Gastrointestinal stromal tumours (GIST) treated with the tyrosine kinase inhibitor (TKI) imatinib can become resistant when additional mutations in the receptor tyrosine kinases KIT or PDGFRA block imatinib activity. Imatinib Mesylate 210-218 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 190-193 27156227-10 2016 Nine patients (35%) had a best response of stable disease, including two patients who had KIT mutations known to be associated with resistance to imatinib and sunitinib. Imatinib Mesylate 146-154 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-93 27097112-1 2016 AIM: The BRAF mutation is a rare pathogenetic alternative to KIT/PDGFRA mutation in GIST and causes Imatinib resistance. Imatinib Mesylate 100-108 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-64 26942271-0 2016 p.(L576P) -KIT mutation in GIST: Favorable prognosis and sensitive to imatinib? Imatinib Mesylate 70-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 11-14 26942271-1 2016 Exon 11 KIT mutations are found in a majority of gastrointestinal stromal tumors (GIST) and are usually predictive of response to imatinib, a KIT, PDGFRA and ABL inhibitor. Imatinib Mesylate 130-138 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 8-11 26942271-1 2016 Exon 11 KIT mutations are found in a majority of gastrointestinal stromal tumors (GIST) and are usually predictive of response to imatinib, a KIT, PDGFRA and ABL inhibitor. Imatinib Mesylate 130-138 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 142-145 26942271-3 2016 In silico and in vitro studies suggested a decreased binding affinity for imatinib in p.(L576P) KIT mutations, thereby offering an explanation for their poor outcome and poor response to standard therapy. Imatinib Mesylate 74-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-99 26942271-5 2016 However, we describe the favorable response to imatinib and outcome in 5 p.(L576P)-KIT mutant GIST patients treated at a tertiary sarcoma referral center. Imatinib Mesylate 47-55 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 83-86 26942271-6 2016 The sensitivity of p.(L576P)-KIT mutations to imatinib, and the prognostic impact of this mutation need to be further evaluated in a larger cohort. Imatinib Mesylate 46-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-32 27080051-6 2016 RESULTS: For large GIST at unfavorable anatomical locations, which are not amenable to organ-sparing resection, neoadjuvant imatinib therapy is the standard upfront treatment prior to surgery in the case of imatinib-sensitive mutations in the c-KIT protooncogene. Imatinib Mesylate 124-132 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 243-248 25547508-0 2016 Imatinib-Sensitizing KIT Mutation in a Carney-Stratakis-Associated GI Stromal Tumor. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-24 26885657-2 2016 Imatinib (IM) a selective inhibitor of C-KIT, is indicated for the treatment of KIT-positive unresectable and/or metastatic GIST, and has tripled the survival time of patients with metastatic GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 39-44 26130666-3 2016 RESULTS: KIT and PDGFRA genotyping in 823 patients identified 18 patients (2%) with PDGFRA mutations who were treated with first-line imatinib. Imatinib Mesylate 134-142 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 9-12 27073655-4 2016 A patient with a c-kit mutation-positive thymic carcinoma received imatinib followed by sunitinib consecutively, which are both c-Kit inhibitors. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-22 27073655-4 2016 A patient with a c-kit mutation-positive thymic carcinoma received imatinib followed by sunitinib consecutively, which are both c-Kit inhibitors. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 128-133 26457546-2 2016 Imatinib mesylate is approved for the adjuvant treatment of KIT-positive gastrointestinal stromal tumor (GIST) following surgical resection. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 26893362-1 2016 Although treatment with imatinib, which inhibits KIT and PDGFR, controls advanced disease in about 80% of gastrointestinal stromal tumor (GIST) patients, resistance to imatinib often develops. Imatinib Mesylate 24-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 26893362-4 2016 Imatinib treatment inhibits c-KIT activity and prevents RACK1 degradation, and RACK1 is upregulated in imatinib-resistant GIST cells compared to non-resistant parental cells. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-33 26893362-7 2016 Combined inhibition of KIT and RACK1 inhibited growth in imatinib-resistant GIST cell lines and reduced tumor relapse in GIST xenografts. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-26 26990482-4 2016 KIT is an established therapeutic target in cancers with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and considerable efficacy has been achieved with various small molecule inhibitors of KIT including imatinib mesylate. Imatinib Mesylate 234-251 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 26990482-4 2016 KIT is an established therapeutic target in cancers with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and considerable efficacy has been achieved with various small molecule inhibitors of KIT including imatinib mesylate. Imatinib Mesylate 234-251 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 26990482-4 2016 KIT is an established therapeutic target in cancers with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and considerable efficacy has been achieved with various small molecule inhibitors of KIT including imatinib mesylate. Imatinib Mesylate 234-251 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 26587973-0 2016 KIT over-expression by p55PIK-PI3K leads to Imatinib-resistance in patients with gastrointestinal stromal tumors. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 26587973-1 2016 Imatinib is the first-line drug for gastrointestinal stromal tumors (GISTs), as mutated KIT is closely associated with the occurrence of GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 88-91 26428235-2 2016 Although targeted therapy involving tyrosine kinase inhibitors (TKIs) such as imatinib mesylate is highly effective for gastrointestinal stromal tumor carrying V560G c-kit mutation, it does not show much potential for targeting wild-type KIT (WT-KIT). Imatinib Mesylate 78-95 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 166-171 27516199-10 2016 Considering that imatinib, a PDGF receptor inhibitor, entered the clinical trials for the treatment of pulmonary hypertension, the first patents were devoted to inhibitors of tyrosine kinase receptors, such as PDGFR and c-Kit. Imatinib Mesylate 17-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 220-225 26779618-0 2016 Detecting Secondary C-KIT Mutations in the Peripheral Blood of Patients with Imatinib-Resistant Gastrointestinal Stromal Tumor. Imatinib Mesylate 77-85 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-25 26779618-2 2016 Imatinib resistance is mostly caused by secondary mutations in C-KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-68 26779618-9 2016 RESULTS: Imatinib-resistant lesions had single-nucleotide substitutions in C-KIT exon 13 in 3 patients and exon 18 in 1 patient. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-80 26779618-11 2016 One patient had growth of an imatinib-resistant tumor containing a C-KIT exon 13 mutation, and the fraction of ctDNA decreased after initiation of sunitinib. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-72 26779374-5 2015 In recent years, imatinib, a PDGFbetaR, ABL and KIT inhibitor, has revolutionized systemic therapy in DFSP. Imatinib Mesylate 17-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-51 28031906-2 2015 Mutually exclusive KIT and PDGFRA mutations are central events in GIST pathogenesis, and their understanding is crucial because specific treatment targeting oncogenic KIT and PDGFRA activation (especially imatinib) has become available. Imatinib Mesylate 205-213 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 19-22 26730054-27 2015 Tyrosine kinase receptor (KIT) inhibitor like imatinib is used for adjuvant treatment. Imatinib Mesylate 46-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-29 26819809-4 2015 C-kit-negative GISTs could be treated by complete resection and/or imatinib, which is the same treatment for c-kit-positive GISTs. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 26644081-1 2015 Imatinib, a multitargeted tyrosine kinase inhibitor, exhibits potent anticancer activity against leukemia harboring the Bcr-Abl oncogene and some solid tumors overexpressing c-kit and PDGFR. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 174-179 26576593-2 2015 BACKGROUND: Imatinib mesylate, a potent inhibitor of the KIT and PDGFR tyrosine kinases, is highly effective in the treatment of advanced gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-60 25941032-4 2015 The design of a specific quantitative PCR assay to monitor the molecular response during treatment with imatinib, a multitargeted tyrosine kinase inhibitor (TKI) with activity against ABL, c-Kit, and PDGFRA revealed an outstanding disease control with durably undetectable BCR-PDGFRA transcripts. Imatinib Mesylate 104-112 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 189-194 26474484-7 2015 Furthermore, the pro-survival and pro-migratory effects of SCF were augmented by c-kit overexpression and abrogated by c-kit inhibition with imatinib. Imatinib Mesylate 141-149 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 119-124 26355082-9 2015 The use of imatinib or dasatinib as a c-Kit inhibitor reduced the level of sphere-forming cells in culture. Imatinib Mesylate 11-19 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 38-43 26067856-5 2015 RESULTS: Sunitinib, which targets the imatinib-inhibited tyrosine kinases of VEGFR, KIT, PDGFR, and FLT-3, was without effect in COV434 and KGN cell lines. Imatinib Mesylate 38-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 25182956-0 2015 KIT and BRAF heterogeneous mutations in gastrointestinal stromal tumors after secondary imatinib resistance. Imatinib Mesylate 88-96 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 25182956-4 2015 The most frequent mechanism of imatinib resistance in GIST is the acquisition of secondary mutations in either KIT or PDGFRA. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 111-114 25182956-9 2015 RESULTS: The imatinib-resistant tumor showed not only heterogeneous mutations of KIT and BRAF besides the primary mutation, but also transdifferentiation into a rhabdomyosarcoma phenotype. Imatinib Mesylate 13-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 25182956-10 2015 According to Western blot analysis, in imatinib-resistant GIST with both KIT V559D and BRAF V600E mutations, the inhibition of KIT V559D by imatinib caused a strong decrease of AKT phosphorylation, while ERK1/2 phosphorylation was not affected. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 25182956-10 2015 According to Western blot analysis, in imatinib-resistant GIST with both KIT V559D and BRAF V600E mutations, the inhibition of KIT V559D by imatinib caused a strong decrease of AKT phosphorylation, while ERK1/2 phosphorylation was not affected. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 127-130 25182956-10 2015 According to Western blot analysis, in imatinib-resistant GIST with both KIT V559D and BRAF V600E mutations, the inhibition of KIT V559D by imatinib caused a strong decrease of AKT phosphorylation, while ERK1/2 phosphorylation was not affected. Imatinib Mesylate 140-148 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 25182956-10 2015 According to Western blot analysis, in imatinib-resistant GIST with both KIT V559D and BRAF V600E mutations, the inhibition of KIT V559D by imatinib caused a strong decrease of AKT phosphorylation, while ERK1/2 phosphorylation was not affected. Imatinib Mesylate 140-148 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 127-130 25985771-0 2015 Predicting Effectiveness of Imatinib Mesylate in Tumors Expressing Platelet-Derived Growth Factors (PDGF-AA, PDGF-BB), Stem Cell Factor Ligands and Their Respective Receptors (PDGFR-alpha, PDGFR-beta, and c-kit). Imatinib Mesylate 28-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 205-210 25985771-1 2015 INTRODUCTION: This research aims to optimize and predict the effectiveness of imatinib mesylate (imatinib) in tumors expressing platelet-derived growth factors (PDGF-AA, BB), kit/stem cell factor (SCF) ligands and their respective receptors (PDGFR-alpha, PDGFR-beta, and c-kit). Imatinib Mesylate 78-95 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 271-276 25985771-1 2015 INTRODUCTION: This research aims to optimize and predict the effectiveness of imatinib mesylate (imatinib) in tumors expressing platelet-derived growth factors (PDGF-AA, BB), kit/stem cell factor (SCF) ligands and their respective receptors (PDGFR-alpha, PDGFR-beta, and c-kit). Imatinib Mesylate 78-86 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 271-276 25985771-9 2015 CONCLUSION: The effect of imatinib is transient and reversible, reduces tyrosine phosphorylation of tumor-derived PDGFR-alpha, PDGFR-beta, and c-kit without affecting their levels of expression. Imatinib Mesylate 26-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 143-148 26240289-1 2015 In the June 1, 2005, issue of Clinical Cancer Research, Antonescu and colleagues defined second-site KIT mutations in gastrointestinal stromal tumor (GIST) as the leading mechanism of acquired resistance to imatinib. Imatinib Mesylate 207-215 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 101-104 25865047-6 2015 In human GIST cells carrying imatinib-sensitive and imatinib-resistant mutations in KIT, PDGFRA was reduced by RNA interference (knockdown) or inhibited with crenolanib besylate (a selective inhibitor of PDGFRA and PDGFRB). Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 25865047-6 2015 In human GIST cells carrying imatinib-sensitive and imatinib-resistant mutations in KIT, PDGFRA was reduced by RNA interference (knockdown) or inhibited with crenolanib besylate (a selective inhibitor of PDGFRA and PDGFRB). Imatinib Mesylate 52-60 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 26316776-0 2015 Inactivity of imatinib in gastrointestinal stromal tumors (GISTs) harboring a KIT activation-loop domain mutation (exon 17 mutation pN822K). Imatinib Mesylate 14-22 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 78-81 26316776-2 2015 Imatinib mesylate is an oral small molecular tyrosine kinase inhibitor that mainly targets abl, c-KIT, and PDGFRalpha. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-101 26316776-7 2015 In this article, we focus on a case of a patient suffering from GIST, harboring an extremely rare KIT activation-loop domain mutation (exon 17 mutation pN822K) treated with imatinib. Imatinib Mesylate 173-181 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-101 26185540-6 2015 The C-Kit inhibitor, imatinib mesylate, was administrated to confirm the effect of stromal cells on the tumorigenesis. Imatinib Mesylate 21-38 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-9 25970686-0 2015 KIT, PDGFRA, and BRAF mutational spectrum impacts on the natural history of imatinib-naive localized GIST: a population-based study. Imatinib Mesylate 76-84 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 25810235-2 2015 Imatinib is an inhibitor of the proto-oncogene tyrosine kinase (c-kit) and the first-line agent in patients with locally advanced and metastatic GIST. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-69 25934947-3 2015 The introduction of molecularly targeted therapy (e.g., with imatinib mesylate) following the discovery of the role of oncogenic mutations in the receptor tyrosine kinases KIT and platelet-derived growth factor alpha (PDGFRA) significantly increased patient survival. Imatinib Mesylate 61-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 172-175 25964201-7 2015 Interestingly, cross-resistance to imatinib and enzastaurin (selective inhibitors of c-Kit and PKC-beta, respectively), was observed and the use of YK-4-279 with enzastaurin in vitro led to marked drug synergy, suggesting a potential role for combination therapies in the future. Imatinib Mesylate 35-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-90 25786656-14 2015 The paradoxical effect of imatinib in PC3 cells may be related with the differential expression of c-KIT protein variants. Imatinib Mesylate 26-34 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-104 25786656-1 2015 BACKGROUND: Imatinib mesylate is a chemotherapeutic drug that inhibits the tyrosine kinase activity of c-KIT and has been successfully used to treat leukemias and some solid tumors. Imatinib Mesylate 12-29 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-108 25432174-4 2015 Addition of the FGFR3 ligand FGF2 to GIST cells restored KIT phosphorylation during imatinib treatment, allowing sensitive cells to proliferate in the presence of the drug. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-60 25673643-4 2015 The combination of KIT and FGFR inhibition showed increased growth inhibition in imatinib-sensitive GIST cell lines and improved efficacy in patient-derived GIST xenografts. Imatinib Mesylate 81-89 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 19-22 25673643-9 2015 The imatinib-induced ERK rebound can be repressed by the FGFR inhibitor BGJ398, and combined KIT and FGFR inhibition leads to increased efficacy in vitro and in patient-derived xenografts. Imatinib Mesylate 4-12 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-96 25688753-10 2015 Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 25688753-10 2015 Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 25695690-1 2015 PURPOSE: Although durable responses can be achieved with tyrosine kinase inhibitors such as imatinib in melanomas harboring KIT mutations, the efficacy of alternative inhibitors after progression to imatinib and the activity of these agents on brain metastases are unknown. Imatinib Mesylate 92-100 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-127 25781619-2 2015 Dramatic metabolic responses following imatinib treatment indicate a high, KIT-dependent glucose turnover which has been particularly helpful for predicting tumor response to imatinib. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-78 25781619-2 2015 Dramatic metabolic responses following imatinib treatment indicate a high, KIT-dependent glucose turnover which has been particularly helpful for predicting tumor response to imatinib. Imatinib Mesylate 175-183 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-78 25042176-6 2015 c-KIT mutations are more common than in other types of melanoma and this has led to significant advances in the use of imatinib for the treatment of metastatic mucosal melanoma. Imatinib Mesylate 119-127 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 25572173-2 2015 Despite the clinical success of imatinib, which targets KIT, most patients with advanced GIST develop resistance and eventually die of the disease. Imatinib Mesylate 32-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 56-59 25432174-6 2015 Moreover, combining KIT and FGFR3 inhibitors synergized to block the growth of imatinib-resistant cells. Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-23 25432174-7 2015 Signaling crosstalk between KIT and FGFR3 activated the MAPK pathway to promote resistance to imatinib. Imatinib Mesylate 94-102 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-31 25557174-2 2015 METHODS: RTK expression (c-Kit, c-Met, AXL, HER-1, HER-2, IGF-1R) in pre-/post-imatinib (IM) GIST patient samples (n=16) and 4 GIST cell lines were examined for RTK inhibitor activity. Imatinib Mesylate 79-87 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 25-30 25605011-4 2015 We examined the in vitro- and in vivo effects of the KIT-targeting drug imatinib on growth and development of human MC. Imatinib Mesylate 72-80 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-56 29147422-5 2015 The presence of activating mutations of C-KIT has prompted use of C-KIT inhibitors such as imatinib and sunitini. Imatinib Mesylate 91-99 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 40-45 25554490-2 2015 Imatinib, a targeted anticancer drug, exerts a therapeutic effect against GISTs by repressing the kinase activity of KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 117-120 25554490-10 2015 The goal of the study was to investigate the mechanism of acquired resistance in GISTs against imatinib, a molecularly targeted drug that inhibits kinase activity of the KIT protein and that has been approved for the treatment of GISTs. Imatinib Mesylate 95-103 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-173 25554490-11 2015 In imatinib-resistant GIST cells, we observed elevated expression of KIT and restoration of its kinase activity, as well as activation of multiple proliferative signaling pathways. Imatinib Mesylate 3-11 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-72 25594139-2 2015 The c-kit inhibitor STI571 represents one of the most important treatments for patients with mastocytosis. Imatinib Mesylate 20-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-9 29147422-5 2015 The presence of activating mutations of C-KIT has prompted use of C-KIT inhibitors such as imatinib and sunitini. Imatinib Mesylate 91-99 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 66-71 24997326-1 2015 Gastric gastrointestinal stromal tumors (GISTs) usually contain the mast/stem cell growth factor receptor Kit gene (KIT) or platelet-derived growth factor receptor A (PDGFRA) mutations that can be targeted by, or mediate resistance to, imatinib. Imatinib Mesylate 236-244 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-109 26658996-3 2015 Molecular studies on GIST have improved our understanding of the biology of the disease and have led to the use of targeted therapy approach, such as imatinib for KIT/PDGFRA-mutated GIST. Imatinib Mesylate 150-158 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 163-166 24997326-1 2015 Gastric gastrointestinal stromal tumors (GISTs) usually contain the mast/stem cell growth factor receptor Kit gene (KIT) or platelet-derived growth factor receptor A (PDGFRA) mutations that can be targeted by, or mediate resistance to, imatinib. Imatinib Mesylate 236-244 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 116-119 24997326-7 2015 We predicted that 32% of patients would have primary resistance to imatinib, based on mutations in exon 17 of KIT, exon 18 of PDGFRA (D842V), or no mutation in either gene. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 26098203-3 2015 Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST. Imatinib Mesylate 39-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-127 25682460-3 2015 Recently, Imatinib mesylate has shown a significantly prolonged progression-free survival and overall survival in metastatic and locally advanced c-Kit positive gastro-intestinal stromal tumors (GISTs) and more recently a prolonged disease-free survival in operated high risk GIST. Imatinib Mesylate 10-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 146-151 26372795-2 2015 Since it also inhibits platelet derived growth factor receptor (PDGFR) and c-Kit, imatinib is used for various other tumors caused by abnormalities of one or both these two enzymes. Imatinib Mesylate 82-90 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-80 25481675-1 2015 KIT and PDGFRA gene mutations are the major genetic alterations seen in gastrointestinal stromal tumors (GISTs) and are being used clinically for predicting response to imatinib therapy. Imatinib Mesylate 169-177 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 25882020-2 2015 Since its launch to the market, imatinib has proven to be very valuable in the treatment of Philadelphia chromosome (BCR/ ABL) - positive (Ph+) chronic myeloid leukemia and Kit (CD117) positive gastrointestinal stromal tumors. Imatinib Mesylate 32-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 174-177 25882020-2 2015 Since its launch to the market, imatinib has proven to be very valuable in the treatment of Philadelphia chromosome (BCR/ ABL) - positive (Ph+) chronic myeloid leukemia and Kit (CD117) positive gastrointestinal stromal tumors. Imatinib Mesylate 32-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 179-184 25349971-8 2014 Functionally, miR-125a-5p expression modulated imatinib sensitivity in GIST882 cells with a homozygous KIT mutation but not in GIST48 cells with double KIT mutations. Imatinib Mesylate 47-55 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-106 25621775-6 2015 Imatinib mesilate is a selective inhibitor of KIT and PDGFRA with an antityrosine kinase activity (TKI) used in advanced or metastatic GIST as well as in adjuvant setting after complete resection of neoplasm. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-49 25755909-0 2014 Long-lasting complete response to imatinib in a patient with systemic mastocytosis exhibiting wild type KIT. Imatinib Mesylate 34-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 104-107 25755909-3 2014 In adult patients the transforming KIT mutation D816V is usually present and confers resistance against imatinib. Imatinib Mesylate 104-112 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 35-38 25755909-5 2014 Nonetheless, imatinib may work in patients with SM lacking KIT D816V. Imatinib Mesylate 13-21 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 59-62 25755909-13 2014 This case-study confirms the long-term efficacy and safety of imatinib in patients with SM lacking activating KIT mutations. Imatinib Mesylate 62-70 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 25755909-14 2014 Imatinib should be considered in select cases of SM in whom MCs exhibit wild-type KIT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-85 25488584-11 2014 Systemic treatment with imatinib for unresectable or recurrent tumors with positive c-KIT could be the best therapeutic option. Imatinib Mesylate 24-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-89 25317746-6 2014 Furthermore,we evaluated the sensitivity of the mutant to imatinib and dasatinib.CONCLUSIONS AND RELEVANCE We report a novel KIT gain-of-function mutation with S628N substitution (exon 13) and show that it is sensitive to imatinib in vitro. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 125-128 25317746-6 2014 Furthermore,we evaluated the sensitivity of the mutant to imatinib and dasatinib.CONCLUSIONS AND RELEVANCE We report a novel KIT gain-of-function mutation with S628N substitution (exon 13) and show that it is sensitive to imatinib in vitro. Imatinib Mesylate 222-230 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 125-128 25239608-2 2014 Imatinib, sunitinib, and regorafenib are approved therapies; however, efficacy is often limited by the acquisition of polyclonal secondary resistance mutations in KIT, with those located in the activation (A) loop (exons 17/18) being particularly problematic. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 163-166 25264277-1 2014 Imatinib mesylate is a tyrosine kinase inhibitor with selectivity for abelson tyrosine-protein kinase 1 (c-Abl), breakpoint cluster region (Bcr)-Abl fusion protein (Bcr-Abl), mast/stem cell growth factor receptor Kit (c-Kit), and platelet-derived growth factor receptor (PDGFR). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 218-223 25264277-3 2014 However, although neuroblastoma cells express c-Kit and PDGFR, the imatinib concentrations required to achieve significant growth inhibitory effects (>= 10 muM) are substantially higher than those required for inhibition of ligand-induced phosphorylation of wild type c-Kit and PDGFR (<= 1 muM), suggesting that additional mechanisms are responsible for the antitumor activity of imatinib on these cells. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 271-276 25239608-4 2014 EXPERIMENTAL DESIGN: The cellular and in vivo activities of ponatinib, imatinib, sunitinib, and regorafenib against mutant KIT were evaluated using an accelerated mutagenesis assay and a panel of engineered and GIST-derived cell lines. Imatinib Mesylate 71-79 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-126 25609545-0 2014 Metabolic response by FDG-PET to imatinib correlates with exon 11 KIT mutation and predicts outcome in patients with mucosal melanoma. Imatinib Mesylate 33-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 66-69 25609545-1 2014 BACKGROUND: In patients with metastatic melanoma and KIT amplifications and/or mutations, therapy with imatinib mesylate may prolong survival. Imatinib Mesylate 103-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-56 24743220-15 2014 Novel therapies targeting multiple components of the integrated KIT receptor signaling pathways in imatinib-resistant GIST warrant further studies. Imatinib Mesylate 99-107 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-67 25088577-2 2014 D816V KIT mutation, found in ~80% of SM, is resistant to the currently available tyrosine kinase inhibitors (TKIs) (e.g. imatinib mesylate). Imatinib Mesylate 121-138 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 6-9 25550846-12 2014 Since the exon 8 mutations appeared to be really sensitive to imatinib as shown in the present case study, accurate genotyping including exon 8 of the c-kit gene is necessary in GISTs to predict response to imatinib in both the unresectable/metastatic and adjuvant settings. Imatinib Mesylate 62-70 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 151-156 25550846-12 2014 Since the exon 8 mutations appeared to be really sensitive to imatinib as shown in the present case study, accurate genotyping including exon 8 of the c-kit gene is necessary in GISTs to predict response to imatinib in both the unresectable/metastatic and adjuvant settings. Imatinib Mesylate 207-215 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 151-156 25139846-0 2014 Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412. Imatinib Mesylate 95-103 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-48 25003536-0 2014 Novel somatic KIT exon 8 mutation with dramatic response to imatinib in a patient with mucosal melanoma: a case report. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 25003536-4 2014 Tumor response to imatinib mesylate has been reported in about half of the patients with tumors harboring KIT mutations. Imatinib Mesylate 18-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-109 25003536-10 2014 This biology may explain the successful application of imatinib in animals with tumors harboring exon 8 KIT mutations and in our patient with mucosal melanoma. Imatinib Mesylate 55-63 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 104-107 25003536-11 2014 This report expands the population of patients with melanoma who might benefit from imatinib to those with somatic exon 8 KIT mutations. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 122-125 25139846-3 2014 In vitro treatment with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells harboring KIT K509I mutation. Imatinib Mesylate 24-32 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 25139846-5 2014 Both patients with familial systemic mastocytosis had remarkable hematological and skin improvement after three months of imatinib treatment, suggesting that it may be an effective front line therapy for patients harboring KIT K509I mutation. Imatinib Mesylate 122-130 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 223-226 25324906-7 2014 Imatinib may be effective for patients with with c-Kit gene mutations. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-54 23642471-1 2014 Imatinib mesylate is a tyrosine kinase inhibitor that targets the BCR-ABL, c-kit, and PDGF (platelet-derived growth factor) receptors. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-80 25841461-5 2014 KIT inhibitors, most notably imatinib, have shown promising clinical activity in KIT-mutant advanced melanoma, including mucosal melanoma, with clinical response rates exceeding 35% in patients with hot-spot mutations in exon 11 or 13 and/or a high mutant/wild-type allelic ratio. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 25841461-5 2014 KIT inhibitors, most notably imatinib, have shown promising clinical activity in KIT-mutant advanced melanoma, including mucosal melanoma, with clinical response rates exceeding 35% in patients with hot-spot mutations in exon 11 or 13 and/or a high mutant/wild-type allelic ratio. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-84 25015329-0 2014 Identification of kit(M541L) somatic mutation in chronic eosinophilic leukemia, not otherwise specified and its implication in low-dose imatinib response. Imatinib Mesylate 136-144 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 25174682-0 2014 Impact of KIT exon 10 M541L allelic variant on the response to imatinib in aggressive fibromatosis: analysis of the desminib series by competitive allele specific Taqman PCR technology. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-13 25621158-0 2014 Imatinib in pulmonary arterial hypertension: c-Kit inhibition. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-50 25621158-4 2014 Imatinib, a tyrosine kinase inhibitor that targets c-Kit, has been shown to be beneficial for patients with PAH. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-56 25621158-5 2014 Here we hypothesize that the clinical benefit of imatinib in PAH could be related to c-Kit inhibition of progenitor cell mobilization and maturation into mast cells. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-90 25621158-9 2014 Circulating CD34(+)CD133(+) and c-Kit(+) progenitor cells as well as c-Kit(+)/CD34(+)CD133(+) decreased with imatinib therapy (all P < 0.05). Imatinib Mesylate 109-117 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 32-37 25621158-9 2014 Circulating CD34(+)CD133(+) and c-Kit(+) progenitor cells as well as c-Kit(+)/CD34(+)CD133(+) decreased with imatinib therapy (all P < 0.05). Imatinib Mesylate 109-117 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-74 25621158-11 2014 The findings support c-Kit inhibition as a potential mechanism of action of imatinib in PAH and suggest that tryptase is a potential biomarker of response to therapy. Imatinib Mesylate 76-84 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-26 24890748-6 2014 Imatinib blocks the PTK receptor c-kit and forestalls its PTK activity. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 33-38 25015329-2 2014 The M541L KIT substitution (KIT(M541L)) has been described to be associated with pediatric mastocytosis, to enhance growth rate of the affected cells and to confer higher sensitivity to imatinib therapy. Imatinib Mesylate 186-194 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-13 25015329-2 2014 The M541L KIT substitution (KIT(M541L)) has been described to be associated with pediatric mastocytosis, to enhance growth rate of the affected cells and to confer higher sensitivity to imatinib therapy. Imatinib Mesylate 186-194 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-31 25015329-8 2014 Our study strongly suggests to search for the KIT(M541L) in patients with CEL, NOS, negative for PDGFRalpha and PDGFRbeta abnormalities, to identify a subgroup of cases who may benefit from low dose imatinib therapy. Imatinib Mesylate 199-207 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-49 25313780-2 2014 Tyrosine kinase inhibitors (TKIs), such as imatinibmesylate, have been used for the adjuvant treatment of KIT-positive GISTs. Imatinib Mesylate 43-59 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-109 25222580-12 2014 CONCLUSIONS: The ratio of overall survival of patients with advanced GIST with a mutation other than exon 11 KIT mutation treated with imatinib is similar to the ratio of overall survival of patients with GIST with exon 11 KIT mutation. Imatinib Mesylate 135-143 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 109-112 24662807-4 2014 We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit but also Abl1, PDFGFRalpha, and PDFGFRbeta, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. Imatinib Mesylate 43-51 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 114-119 24885658-9 2014 These trends predict sensitivity to agents such as paclitaxel (ABCB1 substrate) and imatinib (c-KIT inhibitor) would be altered with extended passage. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 94-99 25669042-10 2014 Most gastrointestinal stromal tumors (GISTs) have KIT or platelet-derived growth factor receptor a mutations, related to the effectiveness of imatinib. Imatinib Mesylate 142-150 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-53 25120810-6 2014 C-kit expression is a frequent finding in triple negative breast cancers; 1 activating mutation which was also found in gastrointestinal stromal tumors was detected; a few cases might benefit from imatinib. Imatinib Mesylate 197-205 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 24652072-0 2014 Mechanisms of resistance to imatinib mesylate in KIT-positive metastatic uveal melanoma. Imatinib Mesylate 28-45 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 24652072-1 2014 Imatinib mesylate is used in targeted therapy of cancer to inhibit type III tyrosine kinase receptors, such as KIT and platelet-derived growth factor receptors (PDGFRs). Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 111-114 24652072-2 2014 Expression of KIT in uveal melanoma (UM) suggests that this receptor may be the target of imatinib mesylate therapy. Imatinib Mesylate 90-98 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 24925195-0 2014 Successful imatinib therapy for neuroendocrine carcinoma with activating Kit mutation: a case study. Imatinib Mesylate 11-19 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 24925195-8 2014 Despite previously reported KIT expression in NET, this is the first documented case of an activating KIT mutation in NET and of successful treatment with both a KIF11 inhibitor and imatinib, each of which was elucidated through molecular profiling of the patient"s tumor. Imatinib Mesylate 182-190 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 28-31 24925195-8 2014 Despite previously reported KIT expression in NET, this is the first documented case of an activating KIT mutation in NET and of successful treatment with both a KIF11 inhibitor and imatinib, each of which was elucidated through molecular profiling of the patient"s tumor. Imatinib Mesylate 182-190 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 102-105 24925195-9 2014 Imatinib may be a valuable therapy in NET harboring activating KIT mutations. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-66 24674454-4 2014 Different CD117 expression patterns could be related to different KIT mutational status in the two lesions: gastric GIST showed a dot-like pattern and lacked KIT mutations; duodenal GIST had a strong membranous expression pattern, likely due to KIT exon 9 duplication, which is associated with lower response to imatinib. Imatinib Mesylate 312-320 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-15 24638003-9 2014 When comparing the two arms, imatinib therapy was associated with higher RFS in patients with a KIT exon 11 deletion of any type, but not a KIT exon 11 insertion or point mutation, KIT exon 9 mutation, PDGFRA mutation, or wild-type tumor, although some of these patient groups were small. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-99 24638003-12 2014 Patients with KIT exon 11 deletions assigned to 1 year of adjuvant imatinib had a longer RFS. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 24317392-0 2014 A new KIT mutation (N505I) in acral melanoma confers constitutive signaling, favors tumorigenic properties, and is sensitive to imatinib. Imatinib Mesylate 128-136 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 6-9 24855380-0 2014 Antitumor activity of sorafenib and imatinib in a patient with thymic carcinoma harboring c-KIT exon 13 missense mutation K642E. Imatinib Mesylate 36-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-95 24788138-4 2014 An imatinib-resistant activating mutation of the receptor tyrosine kinase KIT (KIT D816V) is most frequently present in transformed mast cells and is associated with all clinical forms of the disease. Imatinib Mesylate 3-11 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-77 24788138-4 2014 An imatinib-resistant activating mutation of the receptor tyrosine kinase KIT (KIT D816V) is most frequently present in transformed mast cells and is associated with all clinical forms of the disease. Imatinib Mesylate 3-11 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 79-82 24552773-0 2014 Ponatinib induces apoptosis in imatinib-resistant human mast cells by dephosphorylating mutant D816V KIT and silencing beta-catenin signaling. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 101-104 24552773-4 2014 We discovered that ponatinib abrogated the phosphorylation of KIT harboring either V560G (sensitive to imatinib) or D816V mutation (resistant to imatinib) and the downstream signaling transduction. Imatinib Mesylate 103-111 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-65 24552773-4 2014 We discovered that ponatinib abrogated the phosphorylation of KIT harboring either V560G (sensitive to imatinib) or D816V mutation (resistant to imatinib) and the downstream signaling transduction. Imatinib Mesylate 145-153 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 62-65 24783183-2 2014 Several recent findings that there are activating mutations in the KIT and PDGFRA (platelet-derived growth factor receptor-alpha) genes of GISTs provide the rationale for using targeted therapies such as imatinib or sunitinib. Imatinib Mesylate 204-212 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-70 24790651-3 2014 However, most advanced GISTs responding to imatinib progress within 2-3 years due to heterogeneous subclones harboring a range of imatinib-resistant secondary KIT mutations. Imatinib Mesylate 130-138 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 159-162 24333732-0 2014 Imatinib sensitizes endometrial cancer cells to cisplatin by targeting CD117-positive growth-competent cells. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-76 24333732-7 2014 Imatinib was confirmed to selectively target CD117(+) cells in vitro, and synergistically enhanced the anti-tumor effect of low dose cisplatin in vivo, which showed only modest effects when used as a single use. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-50 24333732-9 2014 Targeting of the SCF/CD117 axis by imatinib sensitized endometrial cancer cells to cisplatin, proposing a novel therapeutic strategy for this tumor type. Imatinib Mesylate 35-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-26 25674429-2 2014 Imatinib mesylate, a tyrosine kinase inhibitor of platelet derived growth factor receptor-alpha and -beta, c-fms, c-kit, abl and arg kinase (imatinib targets), has been shown to prevent tumor progression in early studies of recurrent gliomas, but has shown weak activity in randomized controlled trials. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 114-119 24484970-2 2014 Anaplastic GIST, with pleomorphic cells and loss of CD117, until recently have only been reported in patients with chronic imatinib mesylate treatment. Imatinib Mesylate 123-140 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-57 24479586-7 2014 Furthermore, stem cell factor (SCF)-stimulated c-Kit activation and melanocyte proliferation were completely abrogated by imatinib. Imatinib Mesylate 122-130 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-52 24479586-8 2014 CONCLUSIONS: Inactivation of c-Kit signalling by imatinib has inhibitory effects on melanocyte survival, proliferation and melanogenesis, which explains the clinical hypopigmentation seen in patients with CML. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-34 24385214-1 2014 Most gastrointestinal stromal tumors (GIST) are caused by oncogenic KIT or platelet-derived growth factor receptor activation, and the small molecule kinase inhibitor imatinib mesylate is an effective first-line therapy for metastatic or unresectable GIST. Imatinib Mesylate 167-184 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-71 24727986-1 2014 In gastrointestinal stromal tumors (GIST), molecularly targeted therapies, starting with imatinib, are directed against an activating mutation of KIT or PDGFRA, which drives the disease. Imatinib Mesylate 89-97 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 146-149 24378417-3 2014 In a pilot study, imatinib, a c-kit/PDGF-receptor inhibitor, induced partial regression of AIDS-associated KS (AIDS-KS) in five of 10 patients. Imatinib Mesylate 18-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-35 24300419-7 2014 Treatment of dendritic cells with inhibitors of c-kit activation such as imatinib mesylate (Gleevec) induces breach of T-cell tolerance, skewing of responses toward Th1, and activation of natural killer cells. Imatinib Mesylate 73-90 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-53 24384849-5 2014 Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib, sunitinib, and regorafenib is effective in controlling unresectable disease; however, drug resistance caused by secondary KIT or PDGFRA mutations eventually develops in 90% of cases. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 189-192 24756783-3 2014 Imatinib is a rationally designed oral signal transduction inhibitor that specifically targets several protein tyrosine kinases, Abl, Arg (Abl-related gene), the stem cell factor receptor (c-KIT), platelet-derived growth factor receptor (PDGF-R), and their oncogenic forms, most notably BCR-ABL. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 189-194 24300419-7 2014 Treatment of dendritic cells with inhibitors of c-kit activation such as imatinib mesylate (Gleevec) induces breach of T-cell tolerance, skewing of responses toward Th1, and activation of natural killer cells. Imatinib Mesylate 92-99 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-53 24490049-0 2014 Durable response with a combination of imatinib and sorafenib in KIT exon 17 mutant gastrointestinal stromal tumor. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 65-68 24490049-1 2014 Imatinib, a selective KIT tyrosine-kinase inhibitor is considered standard first line therapy in metastatic gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 24577437-0 2014 CD117 (c-kit) expression on CD34+ cells participates in the cytogenetic response to imatinib in patients with chronic myeloid leukemia in the first chronic phase. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 24577437-0 2014 CD117 (c-kit) expression on CD34+ cells participates in the cytogenetic response to imatinib in patients with chronic myeloid leukemia in the first chronic phase. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 7-12 24577437-6 2014 RESULTS: The percentage of CD34+ cells expressing c-kit (CD117) isolated from bone marrow samples of 54 CML patients treated with standard-dose imatinib was significantly lower among imatinib responders. Imatinib Mesylate 144-152 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-55 24577437-6 2014 RESULTS: The percentage of CD34+ cells expressing c-kit (CD117) isolated from bone marrow samples of 54 CML patients treated with standard-dose imatinib was significantly lower among imatinib responders. Imatinib Mesylate 144-152 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-62 24577437-6 2014 RESULTS: The percentage of CD34+ cells expressing c-kit (CD117) isolated from bone marrow samples of 54 CML patients treated with standard-dose imatinib was significantly lower among imatinib responders. Imatinib Mesylate 183-191 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-55 24577437-6 2014 RESULTS: The percentage of CD34+ cells expressing c-kit (CD117) isolated from bone marrow samples of 54 CML patients treated with standard-dose imatinib was significantly lower among imatinib responders. Imatinib Mesylate 183-191 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-62 24280068-0 2014 Imatinib analogs as potential agents for PET imaging of Bcr-Abl and c-KIT expression at a kinase level. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-73 24280068-1 2014 We synthesized two series of imatinib mesylate (STI-571) analogs to develop a Bcr-Abl and c-KIT receptor-specific labeling agent for positron emission tomography (PET) imaging to measure Bcr-Abl and c-KIT expression levels in a mouse model. Imatinib Mesylate 29-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-95 24963404-4 2014 Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-89 24963404-5 2014 Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT. Imatinib Mesylate 51-59 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 145-150 24963404-5 2014 Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT. Imatinib Mesylate 100-108 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 145-150 24635438-0 2014 Significant antitumor effectiveness of imatinib in c- kit negative gastrointestinal stromal tumor - case report. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-57 24635438-6 2014 We therefore consider imatinib mesylate an appropriate therapy for c- kit negative GIST bearing PDGFRA mutations. Imatinib Mesylate 22-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-73 24323358-5 2013 In both mice and humans, the KIT oncoprotein inhibitor imatinib polarized TAMs to become M2-like, a process which involved TAM interaction with apoptotic tumor cells leading to the induction of CCAAT/enhancer binding protein (C/EBP) transcription factors. Imatinib Mesylate 55-63 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-32 24839736-1 2013 BACKGROUND: To assess the response and the impact on the overall survival (OS) on c-KIT-positive (CD117+) gastrointestinal stromal tumours (GISTs) patients treated with imatinib mesylate. Imatinib Mesylate 169-186 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-87 23659595-8 2013 CONCLUSION: Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KIT816-unmutated patients with aggressive SM. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-88 23659595-3 2013 Here, the authors report significant symptomatic, cutaneous and systemic response to imatinib in a case of childhood onset indolent D816V KIT unmutated systemic mastocytosis (SM). Imatinib Mesylate 85-93 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-141 24369323-0 2013 Correlation of imatinib resistance with the mutational status of KIT and PDGFRA genes in gastrointestinal stromal tumors: a meta-analysis. Imatinib Mesylate 15-23 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 65-68 24369323-3 2013 Our meta-analysis aimed to investigate the association between imatinib resistance and KIT and PDGFRA mutations in GIST. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 87-90 24369323-9 2013 Total imatinib resistance was found in 35.5 % of PDGFRA-mutant tumors (OR = 2.9, P = 0.038), 33.7% of wild-type tumors (KIT and PDGFRA non-mutant tumors; OR = 2.8, P = 0.002), and 27.4% of KIT-mutant tumors (OR = 0.3, P = 0.001). Imatinib Mesylate 6-14 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-123 24369323-9 2013 Total imatinib resistance was found in 35.5 % of PDGFRA-mutant tumors (OR = 2.9, P = 0.038), 33.7% of wild-type tumors (KIT and PDGFRA non-mutant tumors; OR = 2.8, P = 0.002), and 27.4% of KIT-mutant tumors (OR = 0.3, P = 0.001). Imatinib Mesylate 6-14 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 189-192 24369323-10 2013 Primary imatinib resistance was found in 50.0% of PDGFRA-mutant tumors (OR = 10.9, P = 0.031), 33.4% of wild-type tumors (OR = 5.9, P = 0.060), and 8.9% of KIT-mutant tumors (OR = 0.2, P = 0.025). Imatinib Mesylate 8-16 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 156-159 24369323-14 2013 Our meta-analysis indicates that imatinib resistance is closely associated with KIT and PDGFRA genotypes in GIST. Imatinib Mesylate 33-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-83 24369323-15 2013 Thus, the mutational status of KIT and PDGFRA might predict response to imatinib in GIST patients. Imatinib Mesylate 72-80 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 31-34 23659595-8 2013 CONCLUSION: Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KIT816-unmutated patients with aggressive SM. Imatinib Mesylate 66-74 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 85-88 23659595-10 2013 However, the authors have demonstrated the usefulness of imatinib in the treatment of c-KIT-negative indolent SM with extensive cutaneous involvement. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 86-91 24124608-7 2013 Surprisingly, all four malignant GISTs with KIT exon 11 deletion mutations with primary resistance to imatinib had an increased GSTT1 CN and mRNA expression level of GSTT1. Imatinib Mesylate 102-110 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 44-47 24223922-12 2013 CONCLUSION: Patients with advanced GIST harboring a KIT exon 11 mutation have the best response rate and long-term survival with imatinib treatment. Imatinib Mesylate 129-137 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 23775094-1 2013 INTRODUCTION: The discovery of activating KIT and PDGFRalpha mutations in gastrointestinal stromal tumors (GISTs) represented a milestone as it allowed clinicians to use tyrosine kinase inhibitors, like imatinib, to treat this sarcoma. Imatinib Mesylate 203-211 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-45 23702733-6 2013 Moreover, in in vitro experiments, KIT mutants with concurrent KRAS mutation showed resistance to imatinib, a receptor tyrosine kinase inhibitor used in GIST treatment. Imatinib Mesylate 98-106 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 35-38 23755839-9 2013 Of the 19 R0-resected young adult patients, one patient with small intestinal GIST harboring KIT exon 11 deletion mutation developed recurrence and showed partial responses for imatinib. Imatinib Mesylate 177-185 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 93-96 23975171-2 2013 They have represented a paradigm of molecular-targeted therapies for solid tumors since the discovery of KIT mutations and KIT expression in GIST in 1998, which opened the way to the use of imatinib, a tyrosine kinase inhibitor able to inhibit the growth of cells expressing KIT-mutant isoforms. Imatinib Mesylate 190-198 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 105-108 24457249-0 2013 A new KIT gene mutation in thymic cancer and a promising response to imatinib. Imatinib Mesylate 69-77 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 6-9 24052062-4 2013 Imatinib, a TKI with targets that include the breakpoint cluster region-Abelson (bcr-abl) fusion protein kinase and mast/stem cell growth factor receptor kinase (c-Kit), was the first clinically successful drug of this type and revolutionized the treatment and prognosis of chronic myeloid leukemia and gastrointestinal stromal tumors. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 162-167 23975171-2 2013 They have represented a paradigm of molecular-targeted therapies for solid tumors since the discovery of KIT mutations and KIT expression in GIST in 1998, which opened the way to the use of imatinib, a tyrosine kinase inhibitor able to inhibit the growth of cells expressing KIT-mutant isoforms. Imatinib Mesylate 190-198 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-126 23975171-2 2013 They have represented a paradigm of molecular-targeted therapies for solid tumors since the discovery of KIT mutations and KIT expression in GIST in 1998, which opened the way to the use of imatinib, a tyrosine kinase inhibitor able to inhibit the growth of cells expressing KIT-mutant isoforms. Imatinib Mesylate 190-198 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-126 23860199-4 2013 The KIT protooncogene or, less frequently, platelet-derived growth factor receptor alpha is mutated in GIST; the gene products of both are inhibited by imatinib mesylate. Imatinib Mesylate 152-169 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-7 23775962-0 2013 Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-72 23775962-2 2013 PATIENTS AND METHODS: We conducted a multicenter phase II trial of imatinib in metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with KIT amplifications and/or mutations. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 153-156 23775962-15 2013 Imatinib can be effective when tumors harbor KIT mutations, but not if KIT is amplified only. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-48 23775962-16 2013 NRAS mutations and KIT copy number gain may be mechanisms of therapeutic resistance to imatinib. Imatinib Mesylate 87-95 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 19-22 23198834-4 2013 Moreover, there is reported a small proportion of wild-type GISTs for both KIT and PDGFRA genes, and tumors more often acquire secondary mutations on KIT, that results into imatinib resistance. Imatinib Mesylate 173-181 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 150-153 23198834-3 2013 The presence and type of KIT/PDGFRA mutations help to predict the imatinib mesylate therapy, a selective tyrosine kinase inhibitor. Imatinib Mesylate 66-74 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 25-28 23198834-4 2013 Moreover, there is reported a small proportion of wild-type GISTs for both KIT and PDGFRA genes, and tumors more often acquire secondary mutations on KIT, that results into imatinib resistance. Imatinib Mesylate 173-181 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-78 23947692-1 2013 Imatinib mesylate is a selective protein tyrosine kinase inhibitor, which can inhibit BCR/Abl, PDGF-R, c-KIT, c-fms, TCR/Abl, Lck, FLT-3 and MAPKs activities on various cell types. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-108 23681919-2 2013 We have recently produced a mouse model for imatinib resistant gastrointestinal stromal tumor (GIST) carrying the Kit(V558Delta) and Kit(T669I) (human KIT(T670I) ) mutations found in imatinib-resistant GIST. Imatinib Mesylate 44-52 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-100 23904774-5 2013 The Kit inhibitor imatinib mesylate is approved for aggressive sm. Imatinib Mesylate 18-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-7 23567324-1 2013 A novel double-mutant KIT in GIST that responds to Imatinib. Imatinib Mesylate 51-59 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 23567324-3 2013 Generally only one KIT mutation is found in primary tumors and the majority of mutations affecting KIT exon 11 is sensitive to Imatinib. Imatinib Mesylate 127-135 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-102 23567324-5 2013 The relative affinities for ATP and Imatinib of each single (W557G, Y578C) and double (W557G/Y578C) mutant KITs were predicted by in silico studies (computer-based molecular simulations), and compared with those obtained for known Imatinib sensitive and resistant KIT mutants. Imatinib Mesylate 36-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 107-110 23720340-10 2013 Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 23935374-2 2013 Successful targeting of c-KIT and PDGFRA with imatinib, a tyrosine kinase inhibitor (TKI), has had a major impact in advanced GIST and as an adjuvant and neoadjuvant treatment. Imatinib Mesylate 46-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-29 23720340-10 2013 Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 23749045-4 2013 Imatinib or a blocking anti-stem cell factor (SCF) mAb also inhibited colony formation of two cell lines expressing C-KIT and SCF, and decreased P-AKT. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 116-121 23648119-5 2013 Efficacy of imatinib in GISTs with KIT exon 13 was evaluated and compared with published data. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 35-38 23582185-2 2013 Many activating c-Kit mutations have been shown to be highly sensitive to imatinib mesylate, although the majority of patients with c-Kit mutant melanoma eventually progress on this inhibitor. Imatinib Mesylate 74-91 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 16-21 23582185-4 2013 Four imatinib-resistant and six nilotinib-resistant sublines had acquired additional, secondary c-Kit mutations. Imatinib Mesylate 5-13 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-101 23582185-5 2013 The secondary A829P c-Kit mutation rendered cells resistant to imatinib, but did not suppress the activity of the tyrosine kinase inhibitors nilotinib and dasatinib. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-25 23582185-6 2013 Sublines with an additional T670I c-Kit mutation showed resistance to imatinib, nilotinib and dasatinib, but responded to sunitinib. Imatinib Mesylate 70-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-39 23840364-1 2013 Advanced gastrointestinal stromal tumors (GIST), a KIT oncogene-driven tumor, on imatinib mesylate (IM) treatment may develop secondary KIT mutations to confer IM-resistant phenotype. Imatinib Mesylate 81-98 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-54 23840364-1 2013 Advanced gastrointestinal stromal tumors (GIST), a KIT oncogene-driven tumor, on imatinib mesylate (IM) treatment may develop secondary KIT mutations to confer IM-resistant phenotype. Imatinib Mesylate 81-98 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 136-139 23576565-8 2013 Similar results were obtained after selection of imatinib-resistant DOG1- and KIT-negative cells derived from parental DOG1 and KIT-positive GIST cells, where a 5,000-fold increase in IGFBP5 mRNA transcripts were documented. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 78-81 23576565-8 2013 Similar results were obtained after selection of imatinib-resistant DOG1- and KIT-negative cells derived from parental DOG1 and KIT-positive GIST cells, where a 5,000-fold increase in IGFBP5 mRNA transcripts were documented. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 128-131 23722018-8 2013 Reactivity for DOG1 may aid in the diagnosis of GISTs, which fail to express c-kit antigen, and lead to appropriate treatment with imatinib mesylate, an inhibitor of the KIT tyrosine kinase. Imatinib Mesylate 131-148 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 170-173 23576565-1 2013 Gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT or platelet-derived growth factor receptor alpha(PDGFRA), which can be therapeutically targeted by tyrosine kinase inhibitors (TKI) such as imatinib. Imatinib Mesylate 228-236 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 23592754-3 2013 The KIT tyrosine kinase inhibitor imatinib mesylate markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects on tumor cells as well as by indirect immunostimulatory effects on T and NK cells. Imatinib Mesylate 34-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 4-7 23610110-0 2013 Rare, germline mutation of KIT with imatinib-resistant multiple GI stromal tumors and mastocytosis. Imatinib Mesylate 36-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 27-30 23420410-7 2013 Additionally, imatinib is a promising targeted therapy for patients whose tumors harbor a KIT mutation in exons 11 and 13. Imatinib Mesylate 14-22 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-93 23375402-3 2013 Here, we present a case report of TC with c-Kit mutation, who has relapsed after exposure to multiple lines of combination chemotherapy, but he has shown an impressive and long lasting response to sunitinib after imatinib failure. Imatinib Mesylate 213-221 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 42-47 23894705-0 2013 Use of a KIT-specific monoclonal antibody to bypass imatinib resistance in gastrointestinal stromal tumors. Imatinib Mesylate 52-60 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 9-12 23894705-2 2013 We have recently demonstrated that a monoclonal antibody targeting KIT could potentially bypass imatinib resistance in preclinical models of GIST. Imatinib Mesylate 96-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 67-70 23459373-0 2013 Extracellular domain c-kit mutation with duplication of Ser501Ala502 found in gastrointestinal stromal tumors is more imatinib- and nilotinib-sensitive than that with duplication of Ala502Tyr503. Imatinib Mesylate 118-126 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 21-26 23459373-8 2013 The inhibitory effect of selective tyrosine kinase inhibitors, imatinib and nilotinib, on KIT-Dup-Ser501Ala502 was examined and compared with that of KIT-Dup-Ala502Tyr503. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 90-93 23459373-12 2013 In fact, a patient with KIT-Dup-Ser501Ala502 showed long-term stable disease with administration of the usual dose of 400 mg imatinib. Imatinib Mesylate 125-133 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-27 23456621-0 2013 Secondary mutations of c-KIT contribute to acquired resistance to imatinib and decrease efficacy of sunitinib in Chinese patients with gastrointestinal stromal tumors. Imatinib Mesylate 66-74 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-28 23456621-1 2013 The aim of this study was to investigate the associations between secondary mutations of c-KIT/PDGFRalpha and acquired imatinib resistance or efficacy of sunitinib in Chinese patients with gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 119-127 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-94 23456621-6 2013 After imatinib treatment, 25 of 38 (65.8 %) resistant tumors had secondary mutations in c-KIT exon 13 (n = 10), exon 14 (n = 1), exon 17 (n = 12) and exon 18 (n = 2), while no secondary mutations of c-KIT were found in 14 sensitive tumors (P < 0.001), indicating the close association of c-KIT secondary mutations with imatinib-acquired resistance. Imatinib Mesylate 6-14 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 88-93 23456621-6 2013 After imatinib treatment, 25 of 38 (65.8 %) resistant tumors had secondary mutations in c-KIT exon 13 (n = 10), exon 14 (n = 1), exon 17 (n = 12) and exon 18 (n = 2), while no secondary mutations of c-KIT were found in 14 sensitive tumors (P < 0.001), indicating the close association of c-KIT secondary mutations with imatinib-acquired resistance. Imatinib Mesylate 322-330 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 88-93 23456621-8 2013 Secondary mutations of c-KIT were significantly associated with acquired resistance to imatinib in Chinese GIST patients, and whether secondary mutations of c-KIT could influence the efficacy of sunitinib needed to be further investigated. Imatinib Mesylate 87-95 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-28 23859518-8 2013 Indeed patients with metastatic GIST and duplication within exon 9 of KIT deserve to receive twice the dose of imatinib, while GIST with PDGFRA p.D842 V mutation are resistant to this drug. Imatinib Mesylate 111-119 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 70-73 22797058-7 2013 Imatinib (Gleevec), a clinical drug that blocks c-Kit kinase activity, also demonstrated its inhibition potency on OTICs. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-53 23480638-1 2013 BACKGROUND: Acquired resistance to imatinib is frequently caused by secondary KIT mutations. Imatinib Mesylate 35-43 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 78-81 23459373-13 2013 Although mutation sites of KIT-Dup-Ser501Ala502 and KIT-Dup-Ala502Tyr503 are closely located, imatinib- and nilotinib-sensitive KIT-Dup-Ser501Ala502 are distinguishable from KIT-Dup-Ala502Tyr503. Imatinib Mesylate 94-102 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 27-30 23459373-13 2013 Although mutation sites of KIT-Dup-Ser501Ala502 and KIT-Dup-Ala502Tyr503 are closely located, imatinib- and nilotinib-sensitive KIT-Dup-Ser501Ala502 are distinguishable from KIT-Dup-Ala502Tyr503. Imatinib Mesylate 94-102 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 23459373-13 2013 Although mutation sites of KIT-Dup-Ser501Ala502 and KIT-Dup-Ala502Tyr503 are closely located, imatinib- and nilotinib-sensitive KIT-Dup-Ser501Ala502 are distinguishable from KIT-Dup-Ala502Tyr503. Imatinib Mesylate 94-102 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 23459373-13 2013 Although mutation sites of KIT-Dup-Ser501Ala502 and KIT-Dup-Ala502Tyr503 are closely located, imatinib- and nilotinib-sensitive KIT-Dup-Ser501Ala502 are distinguishable from KIT-Dup-Ala502Tyr503. Imatinib Mesylate 94-102 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-55 23637779-3 2013 We initially observed that imatinib (IM), an inhibitor targeting the tyrosine kinase activity of c-Kit concomitantly down-regulated the expression of c-Kit and accelerated the Epo-driven differentiation of erythroblasts in the absence of SCF. Imatinib Mesylate 27-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 97-102 23637779-3 2013 We initially observed that imatinib (IM), an inhibitor targeting the tyrosine kinase activity of c-Kit concomitantly down-regulated the expression of c-Kit and accelerated the Epo-driven differentiation of erythroblasts in the absence of SCF. Imatinib Mesylate 27-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 150-155 23637779-3 2013 We initially observed that imatinib (IM), an inhibitor targeting the tyrosine kinase activity of c-Kit concomitantly down-regulated the expression of c-Kit and accelerated the Epo-driven differentiation of erythroblasts in the absence of SCF. Imatinib Mesylate 37-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 97-102 23637779-3 2013 We initially observed that imatinib (IM), an inhibitor targeting the tyrosine kinase activity of c-Kit concomitantly down-regulated the expression of c-Kit and accelerated the Epo-driven differentiation of erythroblasts in the absence of SCF. Imatinib Mesylate 37-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 150-155 23196876-5 2013 In this study, we demonstrated that NVP-AUY922 (AUY922), a new class of HSP90AA1 inhibitor, is effective in inhibiting the growth of GIST cells expressing mutant KIT protein, the imatinib-sensitive GIST882 and imatinib-resistant GIST48 cells. Imatinib Mesylate 210-218 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 162-165 23348204-2 2013 Altered morphology and loss of CD117 reactivity has been described previously after chronic imatinib treatment; however, this phenomenon has not been reported in imatinib-naive tumors. Imatinib Mesylate 92-100 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 31-36 23348204-12 2013 However, 2 imatinib-resistant tumors showed coexistence of KIT exon 11 and exon 13 mutations. Imatinib Mesylate 11-19 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 59-62 23299198-6 2013 Imatinib, a selective inhibitor targeting Abl as well as c-kit and the platelet-derived growth factor receptor, has been tested for the efficacy and toxicities in metastatic melanoma patients, suggesting that imatinib may increase the progression-free survival and overall survival in selected melanoma patients harboring mutations in c-kit gene. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-62 23299198-6 2013 Imatinib, a selective inhibitor targeting Abl as well as c-kit and the platelet-derived growth factor receptor, has been tested for the efficacy and toxicities in metastatic melanoma patients, suggesting that imatinib may increase the progression-free survival and overall survival in selected melanoma patients harboring mutations in c-kit gene. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 335-340 23299198-6 2013 Imatinib, a selective inhibitor targeting Abl as well as c-kit and the platelet-derived growth factor receptor, has been tested for the efficacy and toxicities in metastatic melanoma patients, suggesting that imatinib may increase the progression-free survival and overall survival in selected melanoma patients harboring mutations in c-kit gene. Imatinib Mesylate 209-217 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-62 23299198-6 2013 Imatinib, a selective inhibitor targeting Abl as well as c-kit and the platelet-derived growth factor receptor, has been tested for the efficacy and toxicities in metastatic melanoma patients, suggesting that imatinib may increase the progression-free survival and overall survival in selected melanoma patients harboring mutations in c-kit gene. Imatinib Mesylate 209-217 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 335-340 23299198-7 2013 The current status of c-kit mutation and the standard for selection of imatinib-sensitive patients have been tentatively established. Imatinib Mesylate 71-79 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-27 23299198-10 2013 In selected subsets of melanoma patients harboring genetic alterations of c-kit, imatinib may be a promising agent. Imatinib Mesylate 81-89 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-79 23206668-7 2013 Patients on imatinib whose tumours harbour mutations in exon 11 of the KIT gene tend to have superior RFS compared with patients with exon 9 mutations. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 71-74 23536354-4 2013 In recent years, targeted therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. Imatinib Mesylate 39-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 23382202-0 2013 Anti-KIT monoclonal antibody inhibits imatinib-resistant gastrointestinal stromal tumor growth. Imatinib Mesylate 38-46 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 5-8 23382202-4 2013 Treatment of GIST with imatinib, a small-molecule tyrosine kinase inhibitor, inhibits KIT-mediated signaling and initially results in disease control in 70-85% of patients with KIT-positive GIST. Imatinib Mesylate 23-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 86-89 23382202-4 2013 Treatment of GIST with imatinib, a small-molecule tyrosine kinase inhibitor, inhibits KIT-mediated signaling and initially results in disease control in 70-85% of patients with KIT-positive GIST. Imatinib Mesylate 23-31 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 177-180 23277171-2 2013 Coupled with the development of tyrosine kinase inhibitors such as imatinib, c-kit has emerged as a viable drug target in what seems to be a validated therapeutic concept. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-82 23420128-4 2013 However, primary resistance to imatinib in GISTs with wild-type KIT and acquired resistance in GISTs with mutant KIT are becoming increasingly significant problems. Imatinib Mesylate 31-39 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-67 23127916-2 2013 Response to imatinib mainly depends from KIT and PDGFRalpha mutational status. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 41-44 23053257-0 2013 Two-year adjuvant imatinib mesylate after complete resection of localized, high-risk GIST with KIT exon 11 mutation. Imatinib Mesylate 18-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-98 23326179-6 2013 Imatinib mesylate is an oral agent that is a selective protein tyrosine kinase inhibitor of the KIT protein tyrosine kinase, and it has demonstrated clinical benefit and objective tumor responses in most GIST patients in phase II and III trials. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 96-99 23326179-7 2013 The presence and the type of KIT or PDGFRA mutation are predictive of response to imatinib therapy in patients with advanced and metastatic disease. Imatinib Mesylate 82-90 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-32 23983708-8 2013 Since pediatric GISTs are typically resistant to imatinib, we performed genotype analysis of the operative specimen that revealed KIT mutations associated with imatinib sensitivity and resistance. Imatinib Mesylate 160-168 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 130-133 23053257-1 2013 PURPOSE: To evaluate the efficacy and safety of 2-year adjuvant imatinib for patients at high risk of recurrence after complete resection of localized gastrointestinal stromal tumor with KIT exon 11 mutation. Imatinib Mesylate 64-72 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 187-190 23053257-12 2013 CONCLUSIONS: Postoperative adjuvant imatinib for 2 years was safe and could prolong the recurrence-free survival in patients with a high risk of recurrence after complete resection of localized KIT exon 11 mutated gastrointestinal stromal tumor. Imatinib Mesylate 36-44 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 194-197 23278880-14 2013 The effects of SCF on mediator release from mast cells were reversed by the c-kit inhibitor imatinib. Imatinib Mesylate 92-100 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 76-81 24136010-1 2013 The oral tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of gastrointestinal stromal tumors (GISTs), most of which harbor oncogenic mutation in genes that encode the receptor tyrosine kinases KIT or PDGFA. Imatinib Mesylate 41-49 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 218-221 23092343-6 2013 Imatinib, a KIT receptor inhibitor, was developed to treat GIST patients by inactivating signaling pathways. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-15 23092343-7 2013 However, some GISTs, especially cases with mutations in exon 13 and 17 of KIT, are resistant to imatinib treatment. Imatinib Mesylate 96-104 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-77 23423603-7 2013 Two patients with a KIT stop codon mutation did not respond to imatinib therapy and died shortly after treatment. Imatinib Mesylate 63-71 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-23 23221606-11 2013 CONCLUSIONS: In patients with LGESS, c-kit and PDGFR were expressed in higher portions of patients, suggesting that imatinib mesylate should be investigated as a potential targeting agent. Imatinib Mesylate 116-133 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 37-42 23069194-3 2013 Treatment with imatinib, a KIT inhibitor, resulted in resolution of the lesions and were well tolerated by the patients. Imatinib Mesylate 15-23 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 27-30 23127174-2 2013 While benefits have been obtained from use of inhibitors of KIT kinase activity such as imatinib, especially in gastrointestinal stromal tumours (GIST), primary resistance occurs with certain oncogenic mutations. Imatinib Mesylate 88-96 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 23127174-6 2013 The action of KIT kinase inhibitors, especially imatinib, sunitinib, dasatinib and PKC412, on different primary and secondary mutants is discussed. Imatinib Mesylate 48-56 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 22712835-0 2013 Hyperpigmentation of the hard palate associated with imatinib therapy for chronic myeloid leukemia with a genetic variation in the proto-oncogene c-KIT. Imatinib Mesylate 53-61 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 131-151 24136010-8 2013 In the adjuvant setting, final results of the trial by the Scandinavian Sarcoma Group and the Sarcoma Group of the Arbeitsgemeinschaft Internistische Onkologie demonstrate that 3 years of adjuvant imatinib, compared with 1 year, significantly reduces the risk of recurrence and improves overall survival of patients with KIT-positive GIST at high risk of recurrence. Imatinib Mesylate 197-205 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 321-324 22736149-6 2012 In addition, a CD117 (c-kit) gene mutation has been identified in cutaneous melanomas, indicating that there may be potential therapeutic benefits of tyrosine kinase inhibitors, such as Imatinib. Imatinib Mesylate 186-194 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 15-20 22748304-4 2012 Recently, some cases of Langerhans cell histiocytosis were reported to express platelet-derived growth factor receptors alpha and beta or c-KIT by immunohistochemistry, and some of these patients had a clinical response to imatinib mesylate. Imatinib Mesylate 223-240 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 138-143 22736149-6 2012 In addition, a CD117 (c-kit) gene mutation has been identified in cutaneous melanomas, indicating that there may be potential therapeutic benefits of tyrosine kinase inhibitors, such as Imatinib. Imatinib Mesylate 186-194 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-27 22795573-0 2012 KIT mutations in a series of melanomas and their impact on treatment with imatinib. Imatinib Mesylate 74-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 22815156-0 2012 C-KIT mutations were closely associated with the response to Imatinib in Chinese advanced gastrointestinal stromal tumor patients. Imatinib Mesylate 61-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 22815156-1 2012 To investigate the correlation between C-KIT/PDGFRalpha mutations and Imatinib response or survival in Chinese advanced gastrointestinal stromal tumor (GIST) patients. Imatinib Mesylate 70-78 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 39-44 22815156-9 2012 C-KIT mutations were closely associated with Imatinib response and progression-free survival of Chinese advanced GIST patients. Imatinib Mesylate 45-53 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 23257463-3 2012 It has been confirmed that imatinib not only inhibits BCR-ABL mutations, but also suppresses other tyrosine kinase receptor genes such as PDGFR, JAK2V617F and C-KIT mutations, providing an important potential of targeted therapy for myeloproliferative disease. Imatinib Mesylate 27-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 159-164 23257463-4 2012 As the PDGFR, JAK2 and C-KIT play important roles in the regulation of hematopoiesis, suggesting that imatinib may block the phosphorylation of PDGFR, JAK2V617F and C-KIT receptors, interrupt the signal transduction cascades, disrupt cell differentiation and proliferation. Imatinib Mesylate 102-110 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-28 23257463-4 2012 As the PDGFR, JAK2 and C-KIT play important roles in the regulation of hematopoiesis, suggesting that imatinib may block the phosphorylation of PDGFR, JAK2V617F and C-KIT receptors, interrupt the signal transduction cascades, disrupt cell differentiation and proliferation. Imatinib Mesylate 102-110 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 165-170 23267948-6 2012 Because a duplication mutation in KIT exon 9 was found in the primary tumor, we decided to increase the dose of imatinib to 800 mg/day. Imatinib Mesylate 112-120 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 22829019-3 2012 This study demonstrated that long-term culture with imatinib mesylate, the tyrosine kinase inhibitor against PDGFR and c-Kit resulted in reduced cancer stem cell ability in glioblastoma cells through cell differentiation. Imatinib Mesylate 52-69 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 119-124 23036227-2 2012 Small molecule inhibitors such as imatinib and sunitinib are known to inhibit the aberrantly activated KIT and PDGFRA receptor signaling and can lead to excellent clinical outcomes for patients with GIST. Imatinib Mesylate 34-42 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-106 22968735-8 2012 In KIT exon 9 mutations, a doubled daily dose of 800 mg imatinib is now standard. Imatinib Mesylate 56-64 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 3-6 22743761-9 2012 Targeted therapies such as vemurafenib or imatinib can be offered to patients whose melanomas express the BRAF V600E or C-Kit mutations. Imatinib Mesylate 42-50 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 120-125 22998385-0 2012 C-kit-positive acute myelogenous leukemia effectively treated with imatinib: a case report and review of the literature. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 23073628-7 2012 The observation that gain-of-function mutations in c-Kit can promote tumor formation and progression has stimulated the development of therapeutics agents targeting this receptor, e.g., the clinically used inhibitor imatinib mesylate. Imatinib Mesylate 216-233 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-56 22314612-7 2012 Administration of imatinib mesylate dose-dependently inhibited cell proliferation of PrSC with downregulation of JAK2 and STAT1, which are the main pathways downstream of SCF/KIT signal. Imatinib Mesylate 18-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 175-178 22665524-7 2012 Notably our data indicate that sorafenib is more effective than imatinib or sunitinib for inhibiting the kinase activity of drug-resistant KIT mutants (as assessed by biochemical IC(50)). Imatinib Mesylate 64-72 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 139-142 22161019-1 2012 Imatinib is a powerful protein tyrosine kinase (PTK) inhibitor that specifically targets BCR-ABL, KIT, and PDGFR kinases, has become the current first-line therapy for all newly diagnosed chronic myeloid leukemia (CML). Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 98-101 22942908-1 2012 Since its approval by the US Food and Drug Administration in February 2002, the tyrosine kinase inhibitor, imatinib, has become the standard of care for patients with metastatic or unresectable KIT-positive gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 107-115 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 194-197 22942908-2 2012 Imatinib functions by blocking the adenosine triphosphate binding site of the constitutively activated mutant KIT or platelet-derived growth factor receptor alpha, effectively shutting down the oncogenic signal that drives up to 90% of these tumors. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-113 22855146-0 2012 Tyrosine-kinase mutations in c-KIT and PDGFR-alpha genes of imatinib naive adult patients with gastrointestinal stromal tumours (GISTs) of the stomach and small intestine: relation to tumour-biological risk-profile and long-term outcome. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 29-34 22855146-2 2012 The aim of this study was to investigate the role of c-KIT and PDGFRA gene mutations in primary resectable, imatinib naive GISTs located in the stomach and small intestine. Imatinib Mesylate 108-116 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-58 22714264-2 2012 Further secondary resistance mutations within KIT limit clinical responses to tyrosine kinase inhibitors, such as imatinib. Imatinib Mesylate 114-122 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-49 22714264-3 2012 The dependence of KIT and its mutated forms on HSP90 suggests that HSP90 inhibition might be a valuable treatment option for GIST, which would be equally effective on imatinib-sensitive and -resistant clones. Imatinib Mesylate 167-175 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 18-21 22807968-4 2012 The activity of imatinib mesylate is correlated with the mutation of c-kit gene exons 9 and 11 in gastrointestinal stromal tumors. Imatinib Mesylate 16-33 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 69-74 22807968-3 2012 With the success of imatinib mesylate in the treatment of gastrointestinal stromal tumors expressing c-kit, its use in SCLC serves as a novel molecular therapeutic approach. Imatinib Mesylate 20-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 101-106 22301675-0 2012 Ponatinib is active against imatinib-resistant mutants of FIP1L1-PDGFRA and KIT, and against FGFR1-derived fusion kinases. Imatinib Mesylate 28-36 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 76-79 22154054-10 2012 These results indicate that a subset of anorectal melanomas have activating c-kit mutations, which suggests that kinase inhibitors such as imatinib may be used to treat this subset of melanoma patients. Imatinib Mesylate 139-147 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 76-81 22713591-7 2012 A radical surgery was rejected by the patient and adjuvant therapy with imatinib at an initial dose of 400 mg/day was considered, with the intention of increasing the dose to 800 mg/day because of the presence of mutation in c-KIT exon 9 related to a poor response to imatinib. Imatinib Mesylate 72-80 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 225-230 22713591-7 2012 A radical surgery was rejected by the patient and adjuvant therapy with imatinib at an initial dose of 400 mg/day was considered, with the intention of increasing the dose to 800 mg/day because of the presence of mutation in c-KIT exon 9 related to a poor response to imatinib. Imatinib Mesylate 268-276 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 225-230 22430048-1 2012 KIT/PDGFRA wild-type (WT) gastrointestinal stromal tumours (GISTs) showed a response rate to imatinib ranging from 0 to 25%. Imatinib Mesylate 93-101 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 22124674-3 2012 DISCUSSION: Besides surgery, therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. Imatinib Mesylate 42-59 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 76-79 22643209-1 2012 BACKGROUND: Imatinib therapy has been successful in gastrointestinal stromal tumours containing mutation of the KIT gene. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 112-115 22643209-2 2012 However, there are few reported cases of successful imatinib therapy in patients with melanoma containing KIT gene mutation or c-kit protein expression. Imatinib Mesylate 52-60 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 106-109 22643209-2 2012 However, there are few reported cases of successful imatinib therapy in patients with melanoma containing KIT gene mutation or c-kit protein expression. Imatinib Mesylate 52-60 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 127-132 22932406-0 2012 [Secondary mutation of c-kit/PDGFRalpha genotypes after imatinib mesylate therapy and its relationship with efficacy of sunitinib]. Imatinib Mesylate 56-64 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-28 22932406-1 2012 OBJECTIVE: To investigate the relationship between secondary mutations of c-kit/PDGFRalpha resistance to imatinib mesylate and the efficacy of sunitinib in patients with gastrointestinal stromal tumor (GIST). Imatinib Mesylate 105-122 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 74-79 22932406-6 2012 C-kit exon 11 mutations were detected in 3 patients, which were all acquired mutations, including c-kit exon 13 V654A, c-kit exon 13 V654E and c-kit exon 17 N822K, after imatinib mesylate resistance. Imatinib Mesylate 170-187 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 22932406-8 2012 C-kit exon 9 mutations were detected in 2 patients with no acquired mutations after imatinib mesylate resistance. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-5 22932406-10 2012 CONCLUSION: The c-kit/PDGFRalpha genotypes after imatinib mesylate resistance may both relate to primary mutations and efficacy of sunitinib treatment. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 16-21 22410759-10 2012 Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 22229850-7 2012 Patients whose tumors harbor a KIT exon 11 mutation benefit the most from imatinib mesylate therapy, in terms of response rate, progression-free survival, and overall survival. Imatinib Mesylate 74-91 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 31-34 22203182-1 2012 BACKGROUND: Imatinib inhibits the KIT and PDGFR tyrosine kinases, resulting in its notable antitumor activity in gastrointestinal stromal tumor (GIST). Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 22493373-2 2012 Imatinib mesylate (Gleevec( ), ST1571, Novartis Pharmaceuticals, Basel, Switzerland) is a selective inhibitor of break point cluster-Ableson (BCR-ABL), c-Kit, and platelet-derived growth factor receptor alpha (PDGFRalpha) tyrosine kinases. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 152-157 22493373-3 2012 Imatinib has been approved in the U.S. for the treatment of Philadelphia-chromosome positive chronic myeloid leukemia, KIT (CD117)-positive unresectable and metastatic malignant GIST and adjuvant treatment of adult patients following resection. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 119-122 22493373-3 2012 Imatinib has been approved in the U.S. for the treatment of Philadelphia-chromosome positive chronic myeloid leukemia, KIT (CD117)-positive unresectable and metastatic malignant GIST and adjuvant treatment of adult patients following resection. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 124-129 22410759-10 2012 Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 23550446-8 2012 For example, patients with metastatic GIST and a duplication of KIT exon 9 should receive twice the usual dose of imatinib, while GIST with the PDGFRA p. D842 V mutation are resistant to imatinib. Imatinib Mesylate 114-122 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-67 22453014-5 2012 Nevertheless, case reports continued to surface that demonstrated the remarkable efficacy of imatinib for patients with specific KIT genetic aberrations. Imatinib Mesylate 93-101 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 129-132 22282465-1 2012 PURPOSE: Gastrointestinal stromal tumors (GIST) are characterized by gain-of-function mutations in KIT/PDGFRA genes leading to a constitutive receptor activation which is well counteracted by imatinib. Imatinib Mesylate 192-200 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 99-102 22282465-5 2012 Cell lines expressing a constitutively activated and imatinib-responding KIT, alone or in combination with activated KRAS and BRAF, were produced and treated with imatinib. Imatinib Mesylate 53-61 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 22282465-5 2012 Cell lines expressing a constitutively activated and imatinib-responding KIT, alone or in combination with activated KRAS and BRAF, were produced and treated with imatinib. Imatinib Mesylate 163-171 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 22282465-8 2012 In vitro experiments showed that imatinib was able to switch off the mutated receptor KIT but not the downstream signaling triggered by RAS-RAF effectors. Imatinib Mesylate 33-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 86-89 22880266-8 2012 Biological therapy with imatinib mesylate is recommended in patients with newly diagnosed, locally advanced, inoperable, or metastasizing gastrointestinal GISTs that express the c-KIT protein. Imatinib Mesylate 24-41 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 178-183 22369443-6 2012 In addition, patients with documented KIT exon 9 mutations are likely to derive benefit from initial treatment with high-dose imatinib to improve clinical outcomes. Imatinib Mesylate 126-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 38-41 22369443-8 2012 However, the decision to use either high-dose imatinib or sunitinib should be based on the underlying cause of failure on imatinib, KIT mutational status and on whether the patient is intolerant of or has developed a resistance to imatinib. Imatinib Mesylate 46-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 132-135 22453014-6 2012 Recently, trials of imatinib have selected patients with KIT genetic aberrations and have shown promising results. Imatinib Mesylate 20-28 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 57-60 22083669-8 2012 These findings indicate that the novel type human KIT-Tyr553Cys mutation is the cause of the present familial and multiple GISTs, and that both imatinib and nilotinib might effectively inhibit the growth of GISTs developing in the patients of this family. Imatinib Mesylate 144-152 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-53 21221851-1 2012 Imatinib, a small molecule inhibitor of ABL, PDGFR and C-KIT, has revolutionized treatment of chronic myeloid leukaemia (CML). Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 55-60 22678007-0 2012 High-risk CD117-positive gastrointestinal stromal tumor of the colon in a 12-year-old girl: adjuvant treatment with imatinib mesylate. Imatinib Mesylate 117-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 10-15 23264790-3 2012 Treatment with thyrosin kinase inhibitors (e.g., Imatinib) is useful in CD117- positive GISTs. Imatinib Mesylate 49-57 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-77 22454169-10 2012 CONCLUSION: Imatinib is effective in treating patients with advanced GIST, c-kit exon 9 mutations and poor performance status predict an adverse survival benefit of imatinib therapy. Imatinib Mesylate 165-173 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 75-80 22800481-10 2012 CONCLUSIONS: Human GIST xenografts with mutation in c-kit have been established from imatinib-resistant GIST lines. Imatinib Mesylate 85-93 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 52-57 21710245-3 2012 On the basis of the radiographic response obtained with imatinib (Novartis Pharma, Basel, Switzerland) in a patient with thymic carcinoma harboring the V560del c-KIT mutation, a phase II trial was initiated at the Department of Molecular and Clinical Oncology and Endocrinology of University "Federico II of Naples" with the purpose to test imatinib in TETs. Imatinib Mesylate 56-64 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 160-165 21710245-19 2012 Nevertheless, imatinib may represent a valuable option in selected patients with TETs, such as those harboring the V560del c-KIT mutation. Imatinib Mesylate 14-22 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-128 22173128-6 2012 Treatment of HMC-cells with the c-Kit inhibitor STI571 blocked the IL-1beta-induced activation of Erk1/2 and JNK1/2 but not p38 and NFkappaB. Imatinib Mesylate 48-54 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 32-37 22213031-1 2012 KIT protein expression and mutational status of KIT gene in different types of tumours have been intensively studied since Imatinib Mesylate, KIT/PDGFRA tyrosine kinase inhibitor became available. Imatinib Mesylate 123-131 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 22213031-11 2012 Our results may suggest a role of KIT in the pathogenesis of a subset of pituitary adenomas and point out the need for further research to find out if KIT-reactive adenomas could be sensitive to Imatinib Mesylate. Imatinib Mesylate 195-212 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 151-154 21968742-10 2012 Ex vivo targeting of synovial mast cells with the c-Kit inhibitor imatinib mesylate significantly decreased the production of IL-17 as well as other proinflammatory cytokines in synovial tissue cultures. Imatinib Mesylate 66-83 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-55 24451733-6 2012 Positron Emission Tomography in patients with GI stromal tumors or genotyping of c-kit in chronic myelogenous leukemia cells can guide the use of imatinib, these scenarios represent a minority of patients. Imatinib Mesylate 146-154 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 81-86 24451813-1 2012 The identification of KIT as a critical driver in the pathogenesis of GI stromal tumor (GIST), and its subsequent inhibition with imatinib, have resulted in tremendous efforts to identify other potential therapeutic targets for the heterogeneous group of diseases known as sarcomas. Imatinib Mesylate 130-138 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 22855636-2 2012 Early events in GIST development are activating mutations in KIT or PDGFRA, which occur in most GISTs and encode for mutated tyrosine receptor kinases that are therapeutic targets for tyrosine kinase inhibitors, including imatinib and sunitinib. Imatinib Mesylate 222-230 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-64 22346278-1 2011 Imatinib mesylate (Gleevec , STI571), a selective inhibitor of BCR-ABL, c-Kit, and platelet-derived factor receptor, has been used to treat chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-77 22846208-2 2012 Its product, CD117, is a specific immunohistochemical (IHQ) marker that is associated with response to a potent tyrosine kinase inhibitor therapy with STI-571 (Gleevec ) in chronic myelogenous leukemia and GISTs. Imatinib Mesylate 151-158 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 13-18 23102192-5 2012 Tumors with C-KIT mutation respond to therapy with C-KIT kinase inhibitor imatinib and the ones characterized by BRAF mutations respond to BRAF kinase inhibitor vemurafenib. Imatinib Mesylate 74-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 12-17 23102192-5 2012 Tumors with C-KIT mutation respond to therapy with C-KIT kinase inhibitor imatinib and the ones characterized by BRAF mutations respond to BRAF kinase inhibitor vemurafenib. Imatinib Mesylate 74-82 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 51-56 21993766-0 2012 Chemotherapeutic alteration of beta-catenin and c-kit expression by imatinib in p16-positive squamous cell carcinoma compared to HPV-negative HNSCC cells in vitro. Imatinib Mesylate 68-76 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 48-53 23285214-6 2012 The effect of imatinib on CD117(high)/KIT+ tumors was determined on first passage cells; absolute cell counts and flow cytometry were readouts for drug sensitivity of cell subsets. Imatinib Mesylate 14-22 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 26-31 23285214-6 2012 The effect of imatinib on CD117(high)/KIT+ tumors was determined on first passage cells; absolute cell counts and flow cytometry were readouts for drug sensitivity of cell subsets. Imatinib Mesylate 14-22 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 38-41 23285214-10 2012 Primary cultures of CD117(high) tumors were sensitive to imatinib (5 microM) in short term culture. Imatinib Mesylate 57-65 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 20-25 22101339-5 2011 Either blocking the functional activity of the KIT protein with imatinib or knocking-down oncogene expression using lentiviral vectors producing shRNA against AML1-ETO or KIT eliminated the sensitivity of Kasumi-1 cells to binase toxic action and promoted their survival, even in the absence of KIT-dependent proliferation and antiapoptotic pathways. Imatinib Mesylate 64-72 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 47-50 22015552-4 2012 Indeed, imatinib mesylate inhibits KIT kinase activity and represents the front line drug for the treatment of unresectable and advanced GISTs, achieving a partial response or stable disease in about 80% of patients with metastatic GIST. Imatinib Mesylate 8-25 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 35-38 22015552-6 2012 Patients with the most common exon 11 mutation experience higher rates of tumor shrinkage and prolonged survival, as tumors with an exon 9 mutation or wild-type KIT are less likely to respond to imatinib. Imatinib Mesylate 195-203 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 161-164 23285088-2 2012 The BCR-ABL inhibitor imatinib is also known to inhibit the tyrosine kinase of the stem cell factor receptor, c-Kit. Imatinib Mesylate 22-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-115 22788088-1 2012 Gastrointestinal stromal tumors (GISTs) have been a topic of increasing interest since the discovery of their cellular activation pathway via the receptor for tyrosine kinase (KIT) leading to the possibility of targeted molecular therapy in the form of imatinib mesylate. Imatinib Mesylate 253-270 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 176-179 22204765-6 2011 Unfortunately, TKIs have not been shown to be particularly active in the case of mastocytosis, although the majority of patients with mastocytosis carry a c-KIT alteration, a target of agents such as imatinib. Imatinib Mesylate 200-208 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 155-160 22346278-1 2011 Imatinib mesylate (Gleevec , STI571), a selective inhibitor of BCR-ABL, c-Kit, and platelet-derived factor receptor, has been used to treat chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors. Imatinib Mesylate 19-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-77 22346278-1 2011 Imatinib mesylate (Gleevec , STI571), a selective inhibitor of BCR-ABL, c-Kit, and platelet-derived factor receptor, has been used to treat chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors. Imatinib Mesylate 29-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 72-77 21955167-5 2011 We report a case of a 60-year-old woman with a heavily pretreated recurrent, c-kit positive, GCT of the ovary who underwent an experimental therapy with imatinib, a tyrosine kinase inhibitor. Imatinib Mesylate 153-161 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 77-82 22069175-1 2011 Progression on first-line therapy with imatinib in gastrointestinal stromal tumors (GIST) is caused by either initial resistance or more often a secondary mutation in tyrosine kinases KIT or PDGFR. Imatinib Mesylate 39-47 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 184-187 22069175-2 2011 Therapies in development for imatinib-resistant GIST include agents that target KIT/PDGFR with greater potency or possess broader kinase inhibition profiles including VEGFR. Imatinib Mesylate 29-37 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-83 21970485-2 2011 They harbor specific activating mutations in the KIT or platelet-derived growth factor receptor alpha ( PDGFRA ) receptor tyrosine kinases, which makes them responsive to pharmacologic inhibitors, such as imatinib mesylate and sunitinib malate. Imatinib Mesylate 205-222 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 49-52 20799000-1 2011 Gastrointestinal stromal tumors lacking mutations in KIT or PDGFRalpha are known as wild type (WT) and are less responsive to imatinib. Imatinib Mesylate 126-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 53-56 22190996-0 2011 Imatinib Mesylate for Patients with Recurrent or Metastatic Gastrointestinal Stromal Tumors Expressing KIT: A Decade Experience from Taiwan. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-106 21969494-0 2011 Impressive response with imatinib in a heavily pretreated patient with metastatic c-KIT mutated thymic carcinoma. Imatinib Mesylate 25-33 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 82-87 21641899-2 2011 Indeed imatinib mesylate (Gleevec( )) treatment has dramatically improved the management of these tumors as they frequently express the c-kit oncogene. Imatinib Mesylate 7-24 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 136-141 21934616-8 2011 Furthermore these tumors frequently harbor KIT exon 9 mutations for which the adequate dose of adjuvant imatinib is debated. Imatinib Mesylate 104-112 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 43-46 22052279-1 2011 Imatinib mesylate (STI 571; Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) is an orally available tyrosine kinase inhibitor that targets a constitutively activated BCR-ABL tyrosine kinase with additional inhibitory effects on platelet derived growth factor (PDGF) receptors alpha and beta, and KIT. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 302-305 21737509-2 2011 Imatinib (IMA) and sunitinib (SUN) are very effective KIT-inhibitors in patients with advanced GIST but have no curative potential. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 54-57 21737509-2 2011 Imatinib (IMA) and sunitinib (SUN) are very effective KIT-inhibitors in patients with advanced GIST but have no curative potential. Imatinib Mesylate 10-13 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 54-57 21641642-8 2011 Imatinib is effective in patients with increased mast cells and eosinophils associated with FIP1L1/PDGFRA+ (e.g., myeloid neoplasm with eosinophilia and rearrangement of PDGFRA) or rare patients with SM associated with KIT mutations outside of exon 17. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 219-222 21874433-7 2011 We speculate that the treatment might have triggered development of the imatinib mesylate-resistant clone, which may have existed in the primary lesion as a KIT gene mutant. Imatinib Mesylate 72-89 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 157-160 21279555-3 2011 The initial response to kinase inhibitors (imatinib mesylate, Gleevec, Novartis) usually is partial and depend on the mutational KIT or PDGFRA state. Imatinib Mesylate 43-60 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 129-132 21495997-1 2011 A comparison of in vitro and in vivo characteristics of tumour cells derived from patients with mucosal melanoma treated with imatinib was performed with respect to KIT mutations. Imatinib Mesylate 126-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 165-168 21873989-1 2011 Imatinib mesylate targets mutated KIT oncoproteins in gastrointestinal stromal tumor (GIST) and produces a clinical response in 80% of patients. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 21495997-6 2011 Expression of KIT protein and KIT mutation was shown in two patients who responded to imatinib in vivo. Imatinib Mesylate 86-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 21495997-6 2011 Expression of KIT protein and KIT mutation was shown in two patients who responded to imatinib in vivo. Imatinib Mesylate 86-94 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 30-33 21561667-8 2011 The mutant KIT expressed on 293 cells showed ligand-independent phosphorylation and imatinib suppressed this phosphorylation in a dose-dependent manner. Imatinib Mesylate 84-92 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 11-14 21690468-0 2011 Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. Imatinib Mesylate 42-59 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 107-112 21690468-2 2011 We tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring c-Kit mutations or amplifications. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 123-128 21690468-14 2011 CONCLUSION: Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 23.3%. Imatinib Mesylate 12-20 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 110-115 21689725-10 2011 In vitro assays on KIT-N822I-expressing Ba/F3 cells confirmed that the N822I mutant is resistant to imatinib mesylate. Imatinib Mesylate 100-117 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 19-22 21689725-13 2011 In addition, we demonstrated that KIT-N822I is resistant to imatinib and sensitive to dasatinib. Imatinib Mesylate 60-68 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-37 21863513-12 2011 Patients with mutations in KIT exon 9 should be treated with 800 mg imatinib/day, since they profit from a significantly longer progression-free survival. Imatinib Mesylate 68-76 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 27-30 21599631-3 2011 Imatinib, first designed to competitively inhibit the ATP-binding pocket of the BCR-ABL tyrosin kinase exhibits inhibition also in the KIT and PDGFRalpha tyrosine kinases, which revolutionized the therapy of gastrointestinal stromal tumors, a disease without any systemic treatment options prior to imatinib. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 135-138 21666577-13 2011 KIT and PDGFRalpha mutational analyses are important in confirming a diagnosis of GIST and predicting its response to imatinib therapy. Imatinib Mesylate 118-126 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 21462307-2 2011 Imatinib mesylate, which targets KIT and PDGFRA, is effective in treating GISTs, but 90% of GIST patients become imatinib-resistant as a result of acquiring secondary KIT mutations. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 33-36 21462307-2 2011 Imatinib mesylate, which targets KIT and PDGFRA, is effective in treating GISTs, but 90% of GIST patients become imatinib-resistant as a result of acquiring secondary KIT mutations. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 167-170 21462307-2 2011 Imatinib mesylate, which targets KIT and PDGFRA, is effective in treating GISTs, but 90% of GIST patients become imatinib-resistant as a result of acquiring secondary KIT mutations. Imatinib Mesylate 113-121 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 167-170 21462307-4 2011 It is therefore possible that the acquisition of secondary KIT mutations during imatinib treatment may occur in putative GIST CSCs. Imatinib Mesylate 80-88 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 59-62 21519258-4 2011 RECENT FINDINGS: The major mechanism of resistance toward imatinib and sunitinib is the development of secondary resistance mutations in the kinase domain of KIT. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 158-161 21677482-2 2011 Imatinib mesylate, a tyrosine kinase inhibitor of KIT and platelet-derived growth factor receptor(PDGFR), has dramatically improved the prognosis ofpatients with advanced, recurrent, and/or metastatic GISTs. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 50-53 21323568-0 2011 Placental growth factor and soluble c-kit receptor dynamics characterize the cytokine signature of imatinib in prostate cancer and bone metastases. Imatinib Mesylate 99-107 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 36-41 21323568-2 2011 After adjusting for multiple tests, significantly different declines in placental growth factor (PIGF), soluble vascular endothelial growth factor receptor-1 (VEGFR1), VEGF, and soluble c-kit were observed with docetaxel plus imatinib (n=41) compared to docetaxel alone (n=47). Imatinib Mesylate 226-234 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 186-191 21323568-6 2011 Plasma PIGF and soluble c-kit kinetics are candidate biomarkers of imatinib effect. Imatinib Mesylate 67-75 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-29 21642685-3 2011 OBJECTIVE: To assess clinical effects of imatinib mesylate in patients with melanoma harboring KIT alterations. Imatinib Mesylate 41-58 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 95-98 21642685-11 2011 CONCLUSIONS: Among patients with advanced melanoma harboring KIT alterations, treatment with imatinib mesylate results in significant clinical responses in a subset of patients. Imatinib Mesylate 93-101 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-64 21244632-4 2011 An example of targeted therapies is the successful treatment of KIT-mutant melanoma with the kinase inhibitor imatinib. Imatinib Mesylate 110-118 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 64-67 20622642-11 2011 Concomitant treatment of CD117 positive tumors with imatinib leads to long-term survival. Imatinib Mesylate 52-60 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 25-30 21677482-4 2011 Sunitinib malate, a multi-targeted tyrosine kinase inhibitor that shows activity against KIT and other receptor tyrosine kinases, including PDGFR and vascular endothelial growth factor receptor, is the only treatment for imatinib-resistant GISTs that is covered by national health insurance in Japan as ofthis writing. Imatinib Mesylate 221-229 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-92 21403650-0 2011 A phase I/II study of imatinib plus reinduction therapy for c-kit-positive relapsed/refractory acute myeloid leukemia: inhibition of Akt activation correlates with complete response. Imatinib Mesylate 22-30 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-65 21403650-1 2011 This phase I/II study evaluated imatinib as a c-kit inhibitor combined with mitoxantrone, etoposide and cytarabine therapy for patients with primary refractory or relapsed c-kit+ acute myeloid leukemia (AML). Imatinib Mesylate 32-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 46-51 21403650-1 2011 This phase I/II study evaluated imatinib as a c-kit inhibitor combined with mitoxantrone, etoposide and cytarabine therapy for patients with primary refractory or relapsed c-kit+ acute myeloid leukemia (AML). Imatinib Mesylate 32-40 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 172-177 21698178-3 2011 D816V-mutated KIT is constitutively active, and resistant to treatment with the anti-cancer drug Imatinib. Imatinib Mesylate 97-105 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 14-17 21310803-2 2011 Using a whole orbital tissue culture system, we tested the potential efficacy of imatinib mesylate (a tyrosine kinase inhibitor that blocks platelet-derived growth factor (PDGF)-receptor, c-Abl and c-Kit activity) and adalimumab (an anti-TNF-alpha antibody) for the treatment of Graves" ophthalmopathy (GO). Imatinib Mesylate 81-98 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 198-203 21600007-7 2011 Recently, it has been confirmed that the kinase genotype of KIT and platelet-derived growth factor receptor alpha can accurately predict a good response to imatinib mesylate therapy. Imatinib Mesylate 156-164 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 60-63 21566432-2 2011 Imatinib mesylate has shown significant safety and great effectiveness for patients with KIT-positive unresectable, advanced, or metastatic GIST. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 89-92 21566429-7 2011 Activated mutant c-kit or platelet-derived growth factor receptor alpha (PDGFRA), which are potential therapeutic targets for imatinib, are constitutively expressed in most GIST. Imatinib Mesylate 126-134 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 17-22 21566433-3 2011 The cause of resistance to imatinib is the low sensitivity of gene mutations in the KIT gene or PDGFRalpha, or an acquisition of additional mutations, and a low plasma level of imatinib. Imatinib Mesylate 27-35 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 84-87 21330162-1 2011 Imatinib mesylate is a tyrosine kinase inhibitor which targets Bcr-Abl-protein, c-Kit, and platelet-derived growth factor receptor. Imatinib Mesylate 0-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 80-85 21387287-2 2011 This review evaluates the clinical efficacy and safety of imatinib for adjuvant treatment of localized KIT (CD117)-positive resected GIST. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 103-106 21387287-2 2011 This review evaluates the clinical efficacy and safety of imatinib for adjuvant treatment of localized KIT (CD117)-positive resected GIST. Imatinib Mesylate 58-66 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 108-113 21387287-11 2011 This study adds to the evidence (based on one RCT and a number of observational studies) that GIST patients treated with adjuvant imatinib therapy show an improvement in recurrence-free survival compared to placebo or no treatment after resection of KIT-positive localized GIST with tolerable toxicity. Imatinib Mesylate 130-138 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 250-253 21442641-10 2011 Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Imatinib Mesylate 0-8 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 21501463-6 2011 NGF rescues HMC-1(V560G c-Kit) cells from imatinib mediated cell death and promotes proliferation. Imatinib Mesylate 42-50 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 24-29 21501463-7 2011 To examine the NGF mediated proliferation and survival in these cells, we compared the NGF mediated upregulated genes (30 and 120 min after stimulation) to the downregulated genes by imatinib treatment (downregulation of c-Kit activity for 4 h) by transcriptome analysis. Imatinib Mesylate 183-191 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 221-226 21295132-3 2011 The imatinib targets, KIT and platelet derived growth factor receptor beta (PDGFRB), were shown here to be expressed in "germline stem" (GS) cell cultures that contain spermatogonia, including spermatogonial stem cells (SSCs). Imatinib Mesylate 4-12 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 22-25 21295132-6 2011 However, growth in imatinib led to decreased numbers of differentiated spermatogonia and reduced culture growth consistent with the known requirement for KIT in survival and proliferation of spermatogonia. Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 154-157 21442641-10 2011 Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Imatinib Mesylate 54-62 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 73-76 21249321-8 2011 But imatinib also has an inhibitory impact on the PTK receptor c-kit and on its PTK activity. Imatinib Mesylate 4-12 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 63-68 20596710-1 2011 PURPOSE: Imatinib mesylate (Imatinib), clinically employed for chronic myeloid leukemia and gastrointestinal stromal tumors, is a selective inhibitor of the tyrosine kinases, c-abl, c-kit and PDGFRs. Imatinib Mesylate 9-26 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 182-187 20596710-1 2011 PURPOSE: Imatinib mesylate (Imatinib), clinically employed for chronic myeloid leukemia and gastrointestinal stromal tumors, is a selective inhibitor of the tyrosine kinases, c-abl, c-kit and PDGFRs. Imatinib Mesylate 9-17 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 182-187 20857409-6 2011 On the contrary, an inhibitory antibody that neutralized the KIT ligand binding site, reduced growth of MCC-1 cells, as did high doses of the KIT kinase inhibitors imatinib and nilotinib. Imatinib Mesylate 164-172 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 61-64 20857409-6 2011 On the contrary, an inhibitory antibody that neutralized the KIT ligand binding site, reduced growth of MCC-1 cells, as did high doses of the KIT kinase inhibitors imatinib and nilotinib. Imatinib Mesylate 164-172 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 142-145 21159146-0 2011 V559A and N822I double KIT mutant melanoma with predictable response to imatinib? Imatinib Mesylate 72-80 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 23-26 21479127-6 2011 KIT and PDGFRA-wild type tumors are expected to have lesser response to imatinib treatment. Imatinib Mesylate 72-80 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 0-3 21419931-2 2011 Recognition of the key role played by the receptor tyrosine kinases KIT and platelet-derived growth factor receptor alpha (PDGFRalpha) in the pathogenesis of GIST led to the development of imatinib, the first TKI for this indication and the current first-line standard of care for unresectable or metastatic GIST. Imatinib Mesylate 189-197 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 68-71 21419934-2 2011 The prototype TKI, imatinib, selectively inhibits BCR-ABL, as well as several other kinases, including stem cell factor receptor (KIT), discoidin domain receptor (DDR), platelet-derived growth factor receptor (PDGFR), and colony-stimulating factor receptor-1 (CSF-1R). Imatinib Mesylate 19-27 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 130-133 21421113-3 2011 Activating mutations in B-Raf and c-kit are associated with clinical response to the specific kinase inhibitors PLX4032 and imatinib, respectively. Imatinib Mesylate 124-132 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 34-39 20846303-13 2011 CONCLUSION: These data indicate that the SCF/c-KIT system plays an important role in scar pathogenesis, and underscore the role of imatinib as a key therapeutic agent in keloid scars. Imatinib Mesylate 131-139 KIT proto-oncogene, receptor tyrosine kinase Homo sapiens 45-50