PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33970400-0 2021 The Role of p53 Expression in Patients with RAS/BRAF Wild-Type Metastatic Colorectal Cancer Receiving Irinotecan and Cetuximab as Later Line Treatment. Irinotecan 102-112 tumor protein p53 Homo sapiens 12-15 32743640-0 2021 Irinotecan and vandetanib create synergies for treatment of pancreatic cancer patients with concomitant TP53 and KRAS mutations. Irinotecan 0-10 tumor protein p53 Homo sapiens 104-108 32743640-8 2021 Irinotecan and vandetanib are prospective drugs for PAAD patients with KRASG12Dmutation and TP53 mutation. Irinotecan 0-10 tumor protein p53 Homo sapiens 92-96 33970400-3 2021 OBJECTIVE: In our study, we evaluated the role of p53 expression in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) receiving irinotecan/cetuximab in an exploratory and a validation cohort. Irinotecan 147-157 tumor protein p53 Homo sapiens 50-53 33970400-4 2021 PATIENTS AND METHODS: p53 expression was analysed in patients with RAS/BRAF wild-type mCRC receiving second-line or third-line irinotecan/cetuximab. Irinotecan 127-137 tumor protein p53 Homo sapiens 22-25 32961616-2 2020 Here, we explore enhancement of the effect of irinotecan [camptothecin-11 (CPT-11)] by the p53-dependent induction of carboxylesterase 2 (CES2), a CPT-11-activating enzyme, in MM. Irinotecan 46-56 tumor protein p53 Homo sapiens 91-94 33869031-10 2021 In PDX models with mutated p53 status, there was significant tumor growth inhibition from the combination of AZD1775 with irinotecan or capecitabine (P <= 0.03), while PDX models with wild type p53 did not show anti-tumor synergy from the same combinations (P >= 0.08). Irinotecan 122-132 tumor protein p53 Homo sapiens 27-30 32961616-2 2020 Here, we explore enhancement of the effect of irinotecan [camptothecin-11 (CPT-11)] by the p53-dependent induction of carboxylesterase 2 (CES2), a CPT-11-activating enzyme, in MM. Irinotecan 58-73 tumor protein p53 Homo sapiens 91-94 32961616-2 2020 Here, we explore enhancement of the effect of irinotecan [camptothecin-11 (CPT-11)] by the p53-dependent induction of carboxylesterase 2 (CES2), a CPT-11-activating enzyme, in MM. Irinotecan 75-81 tumor protein p53 Homo sapiens 91-94 32961616-2 2020 Here, we explore enhancement of the effect of irinotecan [camptothecin-11 (CPT-11)] by the p53-dependent induction of carboxylesterase 2 (CES2), a CPT-11-activating enzyme, in MM. Irinotecan 147-153 tumor protein p53 Homo sapiens 91-94 31056264-2 2019 In this study, we present a new mechanism of Irinotecan which inhibits the activities of MDM2, an E3 ligase of tumour suppressor p53, and Bcl-xL, an anti-apoptotic protein, through direct binding. Irinotecan 45-55 tumor protein p53 Homo sapiens 129-132 32502622-0 2020 P53 activation suppresses irinotecan metabolite SN-38-induced cell damage in non-malignant but not malignant epithelial colonic cells. Irinotecan 26-36 tumor protein p53 Homo sapiens 0-3 32502622-0 2020 P53 activation suppresses irinotecan metabolite SN-38-induced cell damage in non-malignant but not malignant epithelial colonic cells. Irinotecan 48-53 tumor protein p53 Homo sapiens 0-3 32502622-5 2020 SN-38 treatment induced significant apoptosis in all cell lines after 48 h. Nutlin-3a unexpectedly increased cell death in the p53 wild-type CRC cell line, HCT116+/+, while Nutlin-3a pre-treatment provided protection from SN-38 in the p53 wild-type normal cell line, FHS 74. Irinotecan 0-5 tumor protein p53 Homo sapiens 127-130 32502622-5 2020 SN-38 treatment induced significant apoptosis in all cell lines after 48 h. Nutlin-3a unexpectedly increased cell death in the p53 wild-type CRC cell line, HCT116+/+, while Nutlin-3a pre-treatment provided protection from SN-38 in the p53 wild-type normal cell line, FHS 74. Irinotecan 0-5 tumor protein p53 Homo sapiens 235-238 32084420-6 2020 Interestingly, p53 expression was elevated by the SN-38 mono-treatment, and was not further increased after the co-treatment; besides, knockdown of p53 could only reduce the expression of cleaved-PARP partially, and weaken the enhanced proliferation inhibition induced by SN-38 plus imatinib, indicating that there might be other factors involved in the synergistic effects besides p53. Irinotecan 50-55 tumor protein p53 Homo sapiens 15-18 32084420-6 2020 Interestingly, p53 expression was elevated by the SN-38 mono-treatment, and was not further increased after the co-treatment; besides, knockdown of p53 could only reduce the expression of cleaved-PARP partially, and weaken the enhanced proliferation inhibition induced by SN-38 plus imatinib, indicating that there might be other factors involved in the synergistic effects besides p53. Irinotecan 272-277 tumor protein p53 Homo sapiens 15-18 32084420-6 2020 Interestingly, p53 expression was elevated by the SN-38 mono-treatment, and was not further increased after the co-treatment; besides, knockdown of p53 could only reduce the expression of cleaved-PARP partially, and weaken the enhanced proliferation inhibition induced by SN-38 plus imatinib, indicating that there might be other factors involved in the synergistic effects besides p53. Irinotecan 272-277 tumor protein p53 Homo sapiens 148-151 32084420-6 2020 Interestingly, p53 expression was elevated by the SN-38 mono-treatment, and was not further increased after the co-treatment; besides, knockdown of p53 could only reduce the expression of cleaved-PARP partially, and weaken the enhanced proliferation inhibition induced by SN-38 plus imatinib, indicating that there might be other factors involved in the synergistic effects besides p53. Irinotecan 272-277 tumor protein p53 Homo sapiens 148-151 31289894-0 2019 Functional mismatch repair and inactive p53 drive sensitization of colorectal cancer cells to irinotecan via the IAP antagonist BV6. Irinotecan 94-104 tumor protein p53 Homo sapiens 40-43 31289894-2 2019 The purpose of this study was to analyze the cytostatic/cytotoxic response of colorectal carcinoma (CRC) cells to irinotecan, depending on the mismatch repair (MMR) and p53 status and to examine the impact of BV6, a bivalent antagonist of inhibitors of apoptosis c-IAP1/c-IAP2, alone or combined with irinotecan. Irinotecan 114-124 tumor protein p53 Homo sapiens 169-172 31289894-4 2019 Upon irinotecan, MMR-deficient/p53-mutated lines repaired DNA double-strand breaks by homologous recombination less efficiently than MMR-proficient/p53-mutated lines and underwent elevated caspase-9-dependent apoptosis. Irinotecan 5-15 tumor protein p53 Homo sapiens 31-34 31289894-8 2019 Therefore, the particular MMR+/p53mt signature, often found in non-metastasizing (stage II) CRC might be used as a prognostic factor for an adjuvant therapy using low-dose irinotecan combined with a bivalent IAP antagonist. Irinotecan 172-182 tumor protein p53 Homo sapiens 31-34 31056264-5 2019 We further showed that Irinotecan increased the amount of p53 only in the presence of MDM2 and inhibited the physical interaction of Bcl-xL with Bim, a core pro-apoptotic protein. Irinotecan 23-33 tumor protein p53 Homo sapiens 58-61 31056264-7 2019 Collectively, we suggest a new mechanism of action for Irinotecan as a dual target inhibitor of MDM2 and Bcl-xL facilitating the anticancer activities mediated by p53 and Bcl-xL interaction partners. Irinotecan 55-65 tumor protein p53 Homo sapiens 163-166 30898612-6 2019 Interestingly, co-treatment with nutlin-3a and certain chemotherapeutic drug such as irinotecan and oxaliplatin resulted in antagonistic effects in cells both lacking and containing WT-TP53 activity. Irinotecan 85-95 tumor protein p53 Homo sapiens 185-189 30085332-0 2018 Radiosensitization by irinotecan is attributed to G2/M phase arrest, followed by enhanced apoptosis, probably through the ATM/Chk/Cdc25C/Cdc2 pathway in p53-mutant colorectal cancer cells. Irinotecan 22-32 tumor protein p53 Homo sapiens 153-156 30120489-0 2018 Replica to the Opinion Letter regarding the article "Sensitization of colorectal cancer cells to irinotecan by the Survivin inhibitor LLP3 depends on XAF1 proficiency in the context of mutated p53" (Arch Toxicol https://doi.org/10.1007/s00204-018-240-x). Irinotecan 97-107 tumor protein p53 Homo sapiens 193-196 30085332-4 2018 In the present study, we examined the radiosensitizing effects of irinotecan on the p53-mutant colorectal cancer cell lines, HT29 and SW620, and explored the potential underlying mechanisms. Irinotecan 66-76 tumor protein p53 Homo sapiens 84-87 30085332-11 2018 In addition, the expression of Ser216p-Cdc25C was also increased in the combined group, indicating that irinotecan likely radiosensitized the p53-mutant HT29 and SW620 cells through the ATM/Chk/Cdc25C/Cdc2 pathway. Irinotecan 104-114 tumor protein p53 Homo sapiens 142-145 29963241-3 2018 Here we demonstrate that CPT-11 stalls such cells in the G2/M phase of the cell cycle, induces an accumulation of the tumor suppressor p53, the replicative stress/DNA damage marker gammaH2AX, phosphorylation of the checkpoint kinases ATM and ATR, and an ATR-dependent accumulation of the pro-survival molecule survivin. Irinotecan 25-31 tumor protein p53 Homo sapiens 135-138 29980405-5 2018 Upon introduction of the WT-TP53 gene into the MIA-PaCa-2 pancreatic cancer cell line, the sensitivity to drugs used to treat pancreatic cancer cells such as: gemcitabine, fluorouracil (5FU), cisplatin, irinotecan, oxaliplatin, and paclitaxel increased significantly. Irinotecan 203-213 tumor protein p53 Homo sapiens 28-32 29947891-0 2018 Sensitization of colorectal cancer cells to irinotecan by the Survivin inhibitor LLP3 depends on XAF1 proficiency in the context of mutated p53. Irinotecan 44-54 tumor protein p53 Homo sapiens 140-143 29257266-0 2018 Wee1 inhibition can suppress tumor proliferation and sensitize p53 mutant colonic cancer cells to the anticancer effect of irinotecan. Irinotecan 123-133 tumor protein p53 Homo sapiens 63-66 29138869-3 2018 Mutated p53 in CRC was reported to be associated with resistance to commonly used chemotherapeutic agents including, 5-fluorouracil, oxaliplatin and irinotecan. Irinotecan 149-159 tumor protein p53 Homo sapiens 8-11 28000054-11 2017 Furthermore, 5-FU retains its ability to cause nuclear accumulation of p53 in the presence of irinotecan or topotecan. Irinotecan 94-104 tumor protein p53 Homo sapiens 71-74 22721392-0 2013 The role of autophagic cell death and apoptosis in irinotecan-treated p53 null colon cancer cells. Irinotecan 51-61 tumor protein p53 Homo sapiens 70-73 28131902-0 2017 CQ synergistically sensitizes human colorectal cancer cells to SN-38/CPT-11 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk. Irinotecan 63-68 tumor protein p53 Homo sapiens 134-137 28131902-0 2017 CQ synergistically sensitizes human colorectal cancer cells to SN-38/CPT-11 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk. Irinotecan 69-75 tumor protein p53 Homo sapiens 134-137 28131902-4 2017 Notably, another autophagy inhibitor chloroquine (CQ) synergistically enhanced the anti-tumor activity of SN-38 in CRC cells with wild type (WT) p53. Irinotecan 106-111 tumor protein p53 Homo sapiens 145-148 28131902-5 2017 Subsequently, we identified a potential mechanism of this cooperative interaction by showing that CQ and SN-38 acted together to trigger reactive oxygen species (ROS) burst, upregulate p53 expression, elicit the loss of lysosomal membrane potential (LMP) and mitochondrial membrane potential ( psim). Irinotecan 105-110 tumor protein p53 Homo sapiens 185-188 28131902-6 2017 In addition, ROS induced by CQ plus SN-38 upregulated p53 levels by activating p38, conversely, p53 stimulated ROS. Irinotecan 36-41 tumor protein p53 Homo sapiens 54-57 28131902-9 2017 Altogether, all results suggested that CQ synergistically sensitized human CRC cells with WT p53 to SN-38 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk. Irinotecan 100-105 tumor protein p53 Homo sapiens 93-96 25833236-2 2015 The present study investigated the anticancer effect of irinotecan on p53-negative Caco-2 and p53-positive CW2 human colorectal cancer cell lines. Irinotecan 56-66 tumor protein p53 Homo sapiens 70-73 25474278-9 2014 The post-progression survival (PPS) of p53-positive patients undergoing 2nd and/or 3rd line chemotherapy with irinotecan and/or cetuximab was significantly longer compared to p53-negative patients. Irinotecan 110-120 tumor protein p53 Homo sapiens 39-42 25474278-11 2014 mCRC patients with p53 overexpression undergoing an irinotecan containing second- or third-line chemotherapy after oxaliplatin failure have a significantly longer post-progression survival compared to patients without p53 overexpression. Irinotecan 52-62 tumor protein p53 Homo sapiens 19-22 25474278-12 2014 To validate the clinical impact of p53 in patients with mCRC treated with irinotecan- and/or cetuximab further studies are needed. Irinotecan 74-84 tumor protein p53 Homo sapiens 35-38 25738310-12 2015 Sorafenib suppressed p53 expression at both mRNA and protein levels, which might contribute to cell cycle arrest and sensitize tumor cells to irinotecan. Irinotecan 142-152 tumor protein p53 Homo sapiens 21-24 25064805-5 2014 The combination of Nano Se and irinotecan showed increased cytotoxic effect with HCT-8 tumor cells likely by p53 mediated apoptosis. Irinotecan 31-41 tumor protein p53 Homo sapiens 109-112 24968890-13 2014 Co-administration of CFZ and CPT-11 induced G2/M arrest, increased p21WAF1/CIP, and decreased mutant p53 and cdc25c expression. Irinotecan 29-35 tumor protein p53 Homo sapiens 101-104 23653048-6 2013 In the MLH1-proficient cells SN-38, the active metabolite of irinotecan, induced lower levels of DNA damage than in MLH1-deficient cells, as shown by the weaker induction of gamma-H2AX and p53 phosphorylation. Irinotecan 29-34 tumor protein p53 Homo sapiens 189-192 23653048-6 2013 In the MLH1-proficient cells SN-38, the active metabolite of irinotecan, induced lower levels of DNA damage than in MLH1-deficient cells, as shown by the weaker induction of gamma-H2AX and p53 phosphorylation. Irinotecan 61-71 tumor protein p53 Homo sapiens 189-192 22721392-1 2013 The roles of autophagic cell death and apoptosis induced by topoisomerase inhibitor irinotecan in colon cancer cells with deleted p53 were investigated during 48 h. We report that irinotecan-dependent cytotoxicity and proapoptotic activity were reduced in the present model while autophagy levels significantly increased. Irinotecan 180-190 tumor protein p53 Homo sapiens 130-133 22721392-4 2013 These results suggest that different modes of cell death in p53 null colon cancer cells treated with cytostatics (irinotecan) may be activated simultaneously. Irinotecan 114-124 tumor protein p53 Homo sapiens 60-63 22665525-1 2012 The topoisomerase I inhibitor irinotecan is used to treat advanced colorectal cancer and has been shown to have p53-independent anticancer activity. Irinotecan 30-40 tumor protein p53 Homo sapiens 112-115 22270257-10 2012 Conversely potency of PP242 and the combination index for PP242 + irinotecan were unrelated, but synergy exists across all dose levels in PP242 and irinotecan sensitive, p53 wild-type cell lines. Irinotecan 148-158 tumor protein p53 Homo sapiens 170-173 22898888-6 2012 Further analyses showed that CPT-11 induced in both types of cells DNA damage and activated stress response pathways including p53 and p16 but with varying activity of stress kinase p38 and selected stress-associated microRNAs. Irinotecan 29-35 tumor protein p53 Homo sapiens 127-130 23373735-0 2013 Regulation of carboxylesterase-2 expression by p53 family proteins and enhanced anti-cancer activities among 5-fluorouracil, irinotecan and doxazolidine prodrug. Irinotecan 125-135 tumor protein p53 Homo sapiens 47-50 22665525-2 2012 The aim of this study was to identify the p53-independent signaling mechanisms activated by irinotecan. Irinotecan 92-102 tumor protein p53 Homo sapiens 42-45 22665525-3 2012 Transcriptional profiling of isogenic HCT116 p53 wild-type and p53 null cells was carried out following treatment with the active metabolite of irinotecan, SN38. Irinotecan 144-154 tumor protein p53 Homo sapiens 45-48 22665525-3 2012 Transcriptional profiling of isogenic HCT116 p53 wild-type and p53 null cells was carried out following treatment with the active metabolite of irinotecan, SN38. Irinotecan 144-154 tumor protein p53 Homo sapiens 63-66 22647487-0 2012 MAPK14/p38alpha confers irinotecan resistance to TP53-defective cells by inducing survival autophagy. Irinotecan 24-34 tumor protein p53 Homo sapiens 49-53 21372224-7 2011 Exposure of cells to the ADC demonstrated signaling pathways leading to PARP cleavage, but differences versus free SN-38 in p53 and p21 upregulation were noted. Irinotecan 115-120 tumor protein p53 Homo sapiens 124-127 20467885-10 2011 Irinotecan and simvastatin combination treatment of A549 and H460 cells increased G(1) phase arrest, which was associated with up-regulation of p21(WAF1/CIP) and p53 compared with irinotecan alone. Irinotecan 0-10 tumor protein p53 Homo sapiens 162-165 21286718-6 2011 The effects of cetuximab or irinotecan as single agents or the combination on the expression of p53, p16, and EGFR signaling pathways were also studied. Irinotecan 28-38 tumor protein p53 Homo sapiens 96-99 19491654-11 2009 These results support the combination of p53 gene therapy with topoisomerase I inhibitors SN-38/CPT-11 when tumour cells contain mutated p53. Irinotecan 90-95 tumor protein p53 Homo sapiens 137-140 19491654-5 2009 In OVCAR-3 cells, p53 gene therapy inhibited the cell growth and sensitized cells to CPT-11/SN-38, but not to docetaxel. Irinotecan 85-91 tumor protein p53 Homo sapiens 18-21 19491654-5 2009 In OVCAR-3 cells, p53 gene therapy inhibited the cell growth and sensitized cells to CPT-11/SN-38, but not to docetaxel. Irinotecan 92-97 tumor protein p53 Homo sapiens 18-21 20164124-0 2010 Secreted protein acidic and rich in cysteine-induced cellular senescence in colorectal cancers in response to irinotecan is mediated by P53. Irinotecan 110-120 tumor protein p53 Homo sapiens 136-139 19653336-6 2009 Irinotecan sensitizes p53 wild type, mutant and null cells to Fas-mediated cell apoptosis in CRC cells. Irinotecan 0-10 tumor protein p53 Homo sapiens 22-25 19653336-7 2009 Wild type p53 cells were more sensitive to irinotecan than mutated p53. Irinotecan 43-53 tumor protein p53 Homo sapiens 10-13 19653336-10 2009 p53 and VEGF status of the patients" tumour is likely to affect the responsiveness of CRC to irinotecan. Irinotecan 93-103 tumor protein p53 Homo sapiens 0-3 19491654-11 2009 These results support the combination of p53 gene therapy with topoisomerase I inhibitors SN-38/CPT-11 when tumour cells contain mutated p53. Irinotecan 96-102 tumor protein p53 Homo sapiens 137-140 19531575-13 2009 If confirmed in other models, these results suggest that p16 and p53 status affects the 5-aza-irinotecan interaction. Irinotecan 94-104 tumor protein p53 Homo sapiens 65-68 18929442-6 2009 Western Blot showed that SN-38 down-regulated protein expression of p-Akt and increased protein expression of p53 and p21, but it had no effects on protein expression of Bax, Bcl-2 and Akt. Irinotecan 25-30 tumor protein p53 Homo sapiens 110-113 18929442-7 2009 Transfection of the full-length Akt cDNA into HeLa and SiHa cells resulted in the reduction of apoptosis induced by SN-38, and Akt kinase activity regulated the p53 pathway, indicating that inhibition of the Akt pathway played an important role in exhibition of SN-38-mediated cytotoxic effect. Irinotecan 262-267 tumor protein p53 Homo sapiens 161-164 18929442-8 2009 Our data suggested that SN-38 could induce apoptosis through a p53 pathway and that activation of p53 in response to S-38 is governed by Akt. Irinotecan 24-29 tumor protein p53 Homo sapiens 63-66 18929442-8 2009 Our data suggested that SN-38 could induce apoptosis through a p53 pathway and that activation of p53 in response to S-38 is governed by Akt. Irinotecan 24-29 tumor protein p53 Homo sapiens 98-101 17487378-7 2007 The ITAI was also correlated with CPT-11 response among cell lines derived from a variety of tissues that had inactivating p53 mutations or deletions, supporting its applicability for predicting response to camptothecins in other tissues regardless of p53 status. Irinotecan 34-40 tumor protein p53 Homo sapiens 123-126 18820127-9 2009 The combination of SN-38 and 17AAG was shown to be synergistic in p53-null but not in parental HCT116 cells by median effect/combination index analysis. Irinotecan 19-24 tumor protein p53 Homo sapiens 66-69 18381438-3 2008 With the combination therapy of SN-38 (the active metabolite of CPT-11) followed by flavopiridol, the induction of apoptosis was 5-fold greater in the p53+/+ cells compared with the p53-/- cells. Irinotecan 64-70 tumor protein p53 Homo sapiens 151-154 18381438-3 2008 With the combination therapy of SN-38 (the active metabolite of CPT-11) followed by flavopiridol, the induction of apoptosis was 5-fold greater in the p53+/+ cells compared with the p53-/- cells. Irinotecan 64-70 tumor protein p53 Homo sapiens 182-185 18381438-7 2008 Depletion of Rad51 by small interfering RNA (siRNA) sensitized both p53+/+ and p53-/- cells to SN-38-induced apoptosis with increase of gamma H2AX, a marker of DNA damage. Irinotecan 95-100 tumor protein p53 Homo sapiens 79-82 17666793-0 2007 Irinotecan-induced apoptosis is inhibited by increased P-glycoprotein expression and decreased p53 in human hepatocellular carcinoma cells. Irinotecan 0-10 tumor protein p53 Homo sapiens 95-98 17666793-7 2007 SN-38 significantly induced apoptosis in Huh7 cells at 24 h. SN-38 also increased the expression of p53, Bax, and caspase-9 and decreased Bcl-xL expression in Huh7 cells. Irinotecan 0-5 tumor protein p53 Homo sapiens 100-103 17666793-7 2007 SN-38 significantly induced apoptosis in Huh7 cells at 24 h. SN-38 also increased the expression of p53, Bax, and caspase-9 and decreased Bcl-xL expression in Huh7 cells. Irinotecan 61-66 tumor protein p53 Homo sapiens 100-103 17666793-8 2007 SN-38 decreased p53 expression and increased P-gp expression after 120 h, resulting in inhibition of apoptosis. Irinotecan 0-5 tumor protein p53 Homo sapiens 16-19 17666793-10 2007 SN-38-induced P-gp expression was additionally enhanced by p53 decoy oligodeoxynucleotide. Irinotecan 0-5 tumor protein p53 Homo sapiens 59-62 17609585-6 2007 SN-38 binding motifs were detected in the proximal promoter of p53 (bases -433 to -317 and -814 to -711). Irinotecan 0-5 tumor protein p53 Homo sapiens 63-66 17609585-7 2007 These results suggest that the p53-mediated apoptosis pathway is important in the anticancer effects of irinotecan in hepatocellular carcinoma. Irinotecan 104-114 tumor protein p53 Homo sapiens 31-34 18381438-3 2008 With the combination therapy of SN-38 (the active metabolite of CPT-11) followed by flavopiridol, the induction of apoptosis was 5-fold greater in the p53+/+ cells compared with the p53-/- cells. Irinotecan 32-37 tumor protein p53 Homo sapiens 151-154 18381438-3 2008 With the combination therapy of SN-38 (the active metabolite of CPT-11) followed by flavopiridol, the induction of apoptosis was 5-fold greater in the p53+/+ cells compared with the p53-/- cells. Irinotecan 32-37 tumor protein p53 Homo sapiens 182-185 17609585-0 2007 Irinotecan activates p53 with its active metabolite, resulting in human hepatocellular carcinoma apoptosis. Irinotecan 0-10 tumor protein p53 Homo sapiens 21-24 17609585-4 2007 SN-38 significantly increased the expression of p53 protein and its phosphorylation at Ser(15) in the nucleus and apoptosis-inducing proteins Bax, caspase-9, and caspase-3, while it significantly decreased the antiapoptosis protein Bcl-xL of Huh7 cells. Irinotecan 0-5 tumor protein p53 Homo sapiens 48-51 17609585-5 2007 SN-38-induced apoptosis was recovered after p53 antisense oligodeoxynucleotide (AS ODN) pretreatment, while Huh7 cells were precultured with p53 AS ODN, followed by the addition of SN-38 for 24 h. Furthermore, increases in p53 DNA-binding activity were observed in the nuclei of Huh7 cells after SN-38 treatment as shown by electrophoretic mobility shift analysis. Irinotecan 0-5 tumor protein p53 Homo sapiens 44-47 17609585-5 2007 SN-38-induced apoptosis was recovered after p53 antisense oligodeoxynucleotide (AS ODN) pretreatment, while Huh7 cells were precultured with p53 AS ODN, followed by the addition of SN-38 for 24 h. Furthermore, increases in p53 DNA-binding activity were observed in the nuclei of Huh7 cells after SN-38 treatment as shown by electrophoretic mobility shift analysis. Irinotecan 0-5 tumor protein p53 Homo sapiens 141-144 17609585-5 2007 SN-38-induced apoptosis was recovered after p53 antisense oligodeoxynucleotide (AS ODN) pretreatment, while Huh7 cells were precultured with p53 AS ODN, followed by the addition of SN-38 for 24 h. Furthermore, increases in p53 DNA-binding activity were observed in the nuclei of Huh7 cells after SN-38 treatment as shown by electrophoretic mobility shift analysis. Irinotecan 0-5 tumor protein p53 Homo sapiens 141-144 16446370-1 2006 DNA damage induced by the topoisomerase I inhibitor irinotecan (CPT-11) triggers in p53(WT) colorectal carcinoma cells a long term cell cycle arrest and in p53MUT cells a transient arrest followed by apoptosis (Magrini, R., Bhonde, M. R., Hanski, M. L., Notter, M., Scherubl, H., Boland, C. R., Zeitz, M., and Hanski, C. (2002) Int. Irinotecan 52-62 tumor protein p53 Homo sapiens 84-87 17725105-0 2007 Schedule-dependent cytotoxicity of 5-fluorouracil and irinotecan in p53 mutant human colon cancer. Irinotecan 54-64 tumor protein p53 Homo sapiens 68-71 17725105-2 2007 We evaluated cytotoxic effects of a sequentially administered a combination of 5-FU with CPT-11 in human p53 mutant colon cancer. Irinotecan 89-95 tumor protein p53 Homo sapiens 105-108 17255282-6 2007 CHIR-124 interacts synergistically with topoisomerase poisons (e.g., camptothecin or SN-38) in causing growth inhibition in several p53-mutant solid tumor cell lines as determined by isobologram or response surface analysis. Irinotecan 85-90 tumor protein p53 Homo sapiens 132-135 16518418-3 2006 In FaDu xenografts, a poorly differentiated tumor-expressing mutant p53, the cure rate was increased from 30% with irinotecan alone to 100% with the combination of irinotecan and MSC. Irinotecan 115-125 tumor protein p53 Homo sapiens 68-71 16518418-3 2006 In FaDu xenografts, a poorly differentiated tumor-expressing mutant p53, the cure rate was increased from 30% with irinotecan alone to 100% with the combination of irinotecan and MSC. Irinotecan 164-174 tumor protein p53 Homo sapiens 68-71 16446370-1 2006 DNA damage induced by the topoisomerase I inhibitor irinotecan (CPT-11) triggers in p53(WT) colorectal carcinoma cells a long term cell cycle arrest and in p53MUT cells a transient arrest followed by apoptosis (Magrini, R., Bhonde, M. R., Hanski, M. L., Notter, M., Scherubl, H., Boland, C. R., Zeitz, M., and Hanski, C. (2002) Int. Irinotecan 52-62 tumor protein p53 Homo sapiens 156-159 16446370-1 2006 DNA damage induced by the topoisomerase I inhibitor irinotecan (CPT-11) triggers in p53(WT) colorectal carcinoma cells a long term cell cycle arrest and in p53MUT cells a transient arrest followed by apoptosis (Magrini, R., Bhonde, M. R., Hanski, M. L., Notter, M., Scherubl, H., Boland, C. R., Zeitz, M., and Hanski, C. (2002) Int. Irinotecan 64-70 tumor protein p53 Homo sapiens 84-87 16446370-1 2006 DNA damage induced by the topoisomerase I inhibitor irinotecan (CPT-11) triggers in p53(WT) colorectal carcinoma cells a long term cell cycle arrest and in p53MUT cells a transient arrest followed by apoptosis (Magrini, R., Bhonde, M. R., Hanski, M. L., Notter, M., Scherubl, H., Boland, C. R., Zeitz, M., and Hanski, C. (2002) Int. Irinotecan 64-70 tumor protein p53 Homo sapiens 156-159 16446370-5 2006 Here we used five p53WT and five p53MUT established colon carcinoma cell lines to identify gene expression alterations associated with apoptosis in p53MUT cells after treatment with SN-38, the irinotecan metabolite. Irinotecan 182-187 tumor protein p53 Homo sapiens 18-21 16446370-5 2006 Here we used five p53WT and five p53MUT established colon carcinoma cell lines to identify gene expression alterations associated with apoptosis in p53MUT cells after treatment with SN-38, the irinotecan metabolite. Irinotecan 182-187 tumor protein p53 Homo sapiens 33-36 16446370-10 2006 Together, these data indicate that the high expression of mitotic genes in p53MUT cells after SN-38 treatment contributes to DNA damage-induced apoptosis, whereas their suppression in p53WT cells acts as a safeguard mechanism preventing mitosis initiation and the subsequent apoptosis. Irinotecan 94-99 tumor protein p53 Homo sapiens 75-78 15604280-0 2004 Elimination of hepatic metastases of colon cancer cells via p53-independent cross-talk between irinotecan and Apo2 ligand/TRAIL. Irinotecan 95-105 tumor protein p53 Homo sapiens 60-63 16204068-3 2005 In contrast, irinotecan (CPT-11) and tomudex sensitized p53 WT, mutant, and null cells to Fas-mediated cell death. Irinotecan 13-23 tumor protein p53 Homo sapiens 56-59 16204068-3 2005 In contrast, irinotecan (CPT-11) and tomudex sensitized p53 WT, mutant, and null cells to Fas-mediated cell death. Irinotecan 25-31 tumor protein p53 Homo sapiens 56-59 16204068-4 2005 Furthermore, CPT-11 and tomudex, but not 5-FU or oxaliplatin, up-regulated Fas cell surface expression in a p53-independent manner. Irinotecan 13-19 tumor protein p53 Homo sapiens 108-111 16204068-5 2005 In addition, increased Fas cell surface expression in p53 mutant and null cell lines in response to CPT-11 and tomudex was accompanied by only a slight increase in total Fas mRNA and protein expression, suggesting that these agents trigger p53-independent trafficking of Fas to the plasma membrane. Irinotecan 100-106 tumor protein p53 Homo sapiens 54-57 16204068-6 2005 Treatment with CPT-11 or tomudex induced STAT1 phosphorylation (Ser727) in the p53-null HCT116 cell line but not the p53 WT cell line. Irinotecan 15-21 tumor protein p53 Homo sapiens 79-82 16204068-10 2005 We conclude that CPT-11 and tomudex may be more effective than 5-FU and oxaliplatin in the treatment of p53 mutant colorectal cancer tumors by sensitizing them to Fas-mediated apoptosis in a STAT1-dependent manner. Irinotecan 17-23 tumor protein p53 Homo sapiens 104-107 15604280-3 2004 Whereas irinotecan-induced up-regulation of the proapoptotic proteins PUMA and Noxa requires p53, we find that irinotecan inhibits Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 and 5 (STAT3/5) signaling in both p53-proficient and p53-deficient tumor cells. Irinotecan 111-121 tumor protein p53 Homo sapiens 238-241 15604280-4 2004 We show that irinotecan inhibits JAK2-STAT3/5-dependent expression of survival proteins (Bcl-x(L) and XIAP) and cooperates with Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) to facilitate p53-independent apoptosis of colon cancer cells. Irinotecan 13-23 tumor protein p53 Homo sapiens 224-227 15604280-5 2004 Whereas xenografts of p53-deficient colon cancer cells are relatively resistant to irinotecan compared with their p53-proficient counterparts, combined treatment with irinotecan and Apo2L/TRAIL eliminates hepatic metastases of both p53-proficient and p53-deficient cancer cells in vivo and significantly improves the survival of animals relative to treatment with either agent alone. Irinotecan 83-93 tumor protein p53 Homo sapiens 22-25 15604280-5 2004 Whereas xenografts of p53-deficient colon cancer cells are relatively resistant to irinotecan compared with their p53-proficient counterparts, combined treatment with irinotecan and Apo2L/TRAIL eliminates hepatic metastases of both p53-proficient and p53-deficient cancer cells in vivo and significantly improves the survival of animals relative to treatment with either agent alone. Irinotecan 167-177 tumor protein p53 Homo sapiens 114-117 15604280-6 2004 Although the synergy between chemotherapy and Apo2L/TRAIL has been ascribed to p53, our data demonstrate that irinotecan enhances Apo2L/TRAIL-induced apoptosis of tumor cells via a distinct p53-independent mechanism involving inhibition of JAK2-STAT3/5 signaling. Irinotecan 110-120 tumor protein p53 Homo sapiens 190-193 15604280-7 2004 These findings identify a novel p53-independent channel of cross-talk between topoisomerase I inhibitors and Apo2L/TRAIL and suggest that the addition of Apo2L/TRAIL can improve the therapeutic index of irinotecan against both p53-proficient and p53-deficient colorectal cancers, including those that have metastasized to the liver. Irinotecan 203-213 tumor protein p53 Homo sapiens 32-35 15604280-7 2004 These findings identify a novel p53-independent channel of cross-talk between topoisomerase I inhibitors and Apo2L/TRAIL and suggest that the addition of Apo2L/TRAIL can improve the therapeutic index of irinotecan against both p53-proficient and p53-deficient colorectal cancers, including those that have metastasized to the liver. Irinotecan 203-213 tumor protein p53 Homo sapiens 227-230 15604280-7 2004 These findings identify a novel p53-independent channel of cross-talk between topoisomerase I inhibitors and Apo2L/TRAIL and suggest that the addition of Apo2L/TRAIL can improve the therapeutic index of irinotecan against both p53-proficient and p53-deficient colorectal cancers, including those that have metastasized to the liver. Irinotecan 203-213 tumor protein p53 Homo sapiens 227-230 15604280-2 2004 Using isogenic human colon cancer cells that differ only in their p53 status, we demonstrate that loss of p53 renders tumor cells relatively resistant to the topoisomerase I inhibitor, irinotecan. Irinotecan 185-195 tumor protein p53 Homo sapiens 106-109 15604280-3 2004 Whereas irinotecan-induced up-regulation of the proapoptotic proteins PUMA and Noxa requires p53, we find that irinotecan inhibits Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 and 5 (STAT3/5) signaling in both p53-proficient and p53-deficient tumor cells. Irinotecan 8-18 tumor protein p53 Homo sapiens 93-96 15604280-3 2004 Whereas irinotecan-induced up-regulation of the proapoptotic proteins PUMA and Noxa requires p53, we find that irinotecan inhibits Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 and 5 (STAT3/5) signaling in both p53-proficient and p53-deficient tumor cells. Irinotecan 8-18 tumor protein p53 Homo sapiens 238-241 15604280-3 2004 Whereas irinotecan-induced up-regulation of the proapoptotic proteins PUMA and Noxa requires p53, we find that irinotecan inhibits Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 and 5 (STAT3/5) signaling in both p53-proficient and p53-deficient tumor cells. Irinotecan 8-18 tumor protein p53 Homo sapiens 238-241 15604280-3 2004 Whereas irinotecan-induced up-regulation of the proapoptotic proteins PUMA and Noxa requires p53, we find that irinotecan inhibits Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 and 5 (STAT3/5) signaling in both p53-proficient and p53-deficient tumor cells. Irinotecan 111-121 tumor protein p53 Homo sapiens 238-241 15041737-0 2004 Characterization of p53 wild-type and null isogenic colorectal cancer cell lines resistant to 5-fluorouracil, oxaliplatin, and irinotecan. Irinotecan 127-137 tumor protein p53 Homo sapiens 20-23 15213307-2 2004 We found that methioninase-activated MSC potentiates 7-ethyl-10-hydroxycamptothecin (SN-38)-induced cell lethality in vitro in the p53-defective human head and neck carcinoma A253 cells. Irinotecan 53-83 tumor protein p53 Homo sapiens 131-134 15213307-2 2004 We found that methioninase-activated MSC potentiates 7-ethyl-10-hydroxycamptothecin (SN-38)-induced cell lethality in vitro in the p53-defective human head and neck carcinoma A253 cells. Irinotecan 85-90 tumor protein p53 Homo sapiens 131-134 15143945-6 2004 MKN45 that has wild-type p53 showed severe inhibition by irinotecan compared with MKN28, which has mutated p53. Irinotecan 57-67 tumor protein p53 Homo sapiens 25-28 15374978-8 2004 Conversely, concurrent treatment with SN-38 and UCN-01 resulted in S-phase checkpoint override, an amplified DNA damage response including increased phosphorylation of the DNA double-strand breakage marker H2AX and augmentation of clonogenic inhibition, which was independent of p53. Irinotecan 38-43 tumor protein p53 Homo sapiens 279-282 15001986-6 2004 Activated wt-p53 increased apoptosis and enhanced sensitivity to CPT-11. Irinotecan 65-71 tumor protein p53 Homo sapiens 13-16 15001986-10 2004 We demonstrate a gain of sensitivity to CPT-11 in a p53-mutated colon cancer model either by restoring wild-type p53 function or by sequential treatment with cdk-Is. Irinotecan 40-46 tumor protein p53 Homo sapiens 52-55 15001986-0 2004 Enhanced sensitivity to irinotecan by Cdk1 inhibition in the p53-deficient HT29 human colon cancer cell line. Irinotecan 24-34 tumor protein p53 Homo sapiens 61-64 15001986-3 2004 Since the DNA-damage checkpoint depends on p53 activation, the status of p53 might critically influence the response to CPT-11. Irinotecan 120-126 tumor protein p53 Homo sapiens 43-46 15001986-10 2004 We demonstrate a gain of sensitivity to CPT-11 in a p53-mutated colon cancer model either by restoring wild-type p53 function or by sequential treatment with cdk-Is. Irinotecan 40-46 tumor protein p53 Homo sapiens 113-116 15001986-3 2004 Since the DNA-damage checkpoint depends on p53 activation, the status of p53 might critically influence the response to CPT-11. Irinotecan 120-126 tumor protein p53 Homo sapiens 73-76 14961077-4 2004 Using 19 glioblastoma cell lines, including 15 low-passage ex vivo cell lines derived from patients, as well as isogenic glioblastoma cells varying in p53 status, we show that clinically relevant levels of SN-38 potently induce cell cycle arrest and temporary senescence in glioblastoma cells with wild-type p53 while causing massive apoptosis in p53-deficient cells (P<0.0002). Irinotecan 206-211 tumor protein p53 Homo sapiens 151-154 14961077-4 2004 Using 19 glioblastoma cell lines, including 15 low-passage ex vivo cell lines derived from patients, as well as isogenic glioblastoma cells varying in p53 status, we show that clinically relevant levels of SN-38 potently induce cell cycle arrest and temporary senescence in glioblastoma cells with wild-type p53 while causing massive apoptosis in p53-deficient cells (P<0.0002). Irinotecan 206-211 tumor protein p53 Homo sapiens 308-311 14961077-4 2004 Using 19 glioblastoma cell lines, including 15 low-passage ex vivo cell lines derived from patients, as well as isogenic glioblastoma cells varying in p53 status, we show that clinically relevant levels of SN-38 potently induce cell cycle arrest and temporary senescence in glioblastoma cells with wild-type p53 while causing massive apoptosis in p53-deficient cells (P<0.0002). Irinotecan 206-211 tumor protein p53 Homo sapiens 308-311 12538824-0 2003 p53-mediated regulation of expression of a rabbit liver carboxylesterase confers sensitivity to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11). Irinotecan 96-161 tumor protein p53 Homo sapiens 0-3 14645705-4 2003 Here, we imaged p53 transcriptional activity in Bax-/- carcinomas by using bioluminescence, in vivo, and find that p53 is required for sensitization to TRAIL by CPT-11. Irinotecan 161-167 tumor protein p53 Homo sapiens 115-118 12538824-0 2003 p53-mediated regulation of expression of a rabbit liver carboxylesterase confers sensitivity to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11). Irinotecan 163-169 tumor protein p53 Homo sapiens 0-3 12538824-3 2003 Upon transfection of these plasmids into cells expressing either wt or mutant p53, differential expression of the CE has been observed, resulting in sensitization of the cells expressing the latter protein to the anticancer prodrug irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carb- onyloxycamptothecin (CPT-11). Irinotecan 232-242 tumor protein p53 Homo sapiens 78-81 12538824-3 2003 Upon transfection of these plasmids into cells expressing either wt or mutant p53, differential expression of the CE has been observed, resulting in sensitization of the cells expressing the latter protein to the anticancer prodrug irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carb- onyloxycamptothecin (CPT-11). Irinotecan 244-312 tumor protein p53 Homo sapiens 78-81 12538824-3 2003 Upon transfection of these plasmids into cells expressing either wt or mutant p53, differential expression of the CE has been observed, resulting in sensitization of the cells expressing the latter protein to the anticancer prodrug irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carb- onyloxycamptothecin (CPT-11). Irinotecan 314-320 tumor protein p53 Homo sapiens 78-81 12538824-5 2003 These studies indicate that the inactivation of wtp53 by mutant p53 in human tumor cells may be sufficient enough to generate a therapeutic window for enhanced cytotoxicity with CPT-11. Irinotecan 178-184 tumor protein p53 Homo sapiens 50-53 12209584-0 2002 Cellular effects of CPT-11 on colon carcinoma cells: dependence on p53 and hMLH1 status. Irinotecan 20-26 tumor protein p53 Homo sapiens 67-70 11894120-5 2002 In LS174T cells, the antisense oligonucleotide, but not the mismatch oligonucleotide, specifically inhibited MDM2 expression, resulting in a significant increase in irinotecan-associated p53 activation and p21 induction. Irinotecan 165-175 tumor protein p53 Homo sapiens 187-190 10770640-11 2000 These findings suggest that CPT-11 and 5-FU may thus be useful as possible anticancer agents for use in a combination therapy regimen using wt p53 gene transfer. Irinotecan 28-34 tumor protein p53 Homo sapiens 143-146 10732766-0 2000 Sensitivity to CPT-11 of xenografted human colorectal cancers as a function of microsatellite instability and p53 status. Irinotecan 15-21 tumor protein p53 Homo sapiens 110-113 10732766-16 2000 Taken together, these observations indicate that MSI and p53 alterations could be associated with different CPT-11 sensitivities; MSI phenotype moderately influences the CPT-11 sensitivity, MSI+ being more sensitive than MSI(-)CRC freshly obtained from patients, mutp53 status being associated with a poor response to CPT-11. Irinotecan 108-114 tumor protein p53 Homo sapiens 57-60 10604724-0 1999 Schedule-dependent cytotoxicity of SN-38 in p53 wild-type and mutant colon adenocarcinoma cell lines. Irinotecan 35-40 tumor protein p53 Homo sapiens 44-47 10604724-10 1999 Dose-dependent p53-associated G1 arrest, in the absence of DNA synthesis indicates an additional cytotoxic mechanism for SN-38, which requires higher concentrations than the S phase mechanism, and detection of which seems to involve p53. Irinotecan 121-126 tumor protein p53 Homo sapiens 15-18 10604724-12 1999 Although expression of wild-type p53 leads to a more rapid induction of apoptosis, SN-38 cytotoxicity was generally greater in cells with mutant p53, as wild-type cells escaped apoptosis by p53 associated prolonged cell cycle arrest. Irinotecan 83-88 tumor protein p53 Homo sapiens 145-148 10604724-12 1999 Although expression of wild-type p53 leads to a more rapid induction of apoptosis, SN-38 cytotoxicity was generally greater in cells with mutant p53, as wild-type cells escaped apoptosis by p53 associated prolonged cell cycle arrest. Irinotecan 83-88 tumor protein p53 Homo sapiens 145-148 9506540-3 1998 When p53 was expressed at sublethal levels, it sensitized cells to the DNA-damaging drugs Adriamycin, mitomycin C, actinomycin D, etoposide (VP16), cisplatin and CPT11. Irinotecan 162-167 tumor protein p53 Homo sapiens 5-8 9743293-8 1998 Thus, although p53-dependent apoptosis is induced by camptothecin, topotecan and SN-38 in this human ovarian carcinoma cell line, these drugs induce p53-independent death, as measured by clonogenic assay. Irinotecan 81-86 tumor protein p53 Homo sapiens 15-18 34258881-0 2021 Mechanistic insights into p53-regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells. Irinotecan 80-90 tumor protein p53 Homo sapiens 26-29 34667024-12 2022 These include irinotecan, which induces apoptosis of DDLS cells in a C/EBPalpha-dependent, p53-independent manner and should be clinically evaluated in patients with advanced DDLS. Irinotecan 14-24 tumor protein p53 Homo sapiens 91-94 35192728-4 2022 Together with extended tumor exposure to therapeutically effective drug levels via reversible conjugation to Pluronic F-108 (PF108), these features translated into rapid tumor regression and long-term survival in models of both ABCG2-overexpressing and p53-mutant high-risk neuroblastomas, in contrast to a marginal effect of the clinically used camptothecin derivative, irinotecan. Irinotecan 371-381 tumor protein p53 Homo sapiens 253-256 35197630-7 2022 Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or KRAS-TP53 double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. Irinotecan 22-32 tumor protein p53 Homo sapiens 112-116