PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33839325-10 2021 In summary, we show that increased TRERNA1 expression induced by HBx reduces HCC cell sensitivity to sorafenib by activating the RAS/Raf/MEK/ERK signaling pathway. Sorafenib 101-110 mitogen-activated protein kinase 1 Homo sapiens 141-144 33948974-7 2021 Hormonal pharmaceuticals, including melatonin, exerts proapoptotic via regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib exerts antiproliferative effect via MAPK/ERK pathway and antiangiogenesis activity via VEGF/VEGFR pathway. Sorafenib 148-157 mitogen-activated protein kinase 1 Homo sapiens 194-198 33948974-7 2021 Hormonal pharmaceuticals, including melatonin, exerts proapoptotic via regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib exerts antiproliferative effect via MAPK/ERK pathway and antiangiogenesis activity via VEGF/VEGFR pathway. Sorafenib 148-157 mitogen-activated protein kinase 1 Homo sapiens 199-202 33674622-6 2021 Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Sorafenib 51-60 mitogen-activated protein kinase 1 Homo sapiens 86-89 33628103-2 2021 However, the benefit of sorafenib is often diminished because of acquired resistance through the reactivation of ERK signaling in sorafenib-resistant HCC cells. Sorafenib 24-33 mitogen-activated protein kinase 1 Homo sapiens 113-116 33628103-2 2021 However, the benefit of sorafenib is often diminished because of acquired resistance through the reactivation of ERK signaling in sorafenib-resistant HCC cells. Sorafenib 130-139 mitogen-activated protein kinase 1 Homo sapiens 113-116 33021963-4 2020 miR-216a-3p overexpression significantly increases the sorafenib sensitivity of HCC cells by suppressing MAPK14 expression and reducing the subsequent activation of the MEK/ERK and ATF2 signaling pathways. Sorafenib 55-64 mitogen-activated protein kinase 1 Homo sapiens 173-176 32300243-8 2020 We further revealed that sorafenib dose-dependently decreased the levels of p-ERK and p-STAT3, whereas artesunate markedly increased the levels of p-ERK and p-STAT3 in HuH7 and Hep3B cells. Sorafenib 25-34 mitogen-activated protein kinase 1 Homo sapiens 78-81 32300243-9 2020 When used in combination, sorafenib abolished artesunate-elevated levels of p-STAT3 and p-ERK. Sorafenib 26-35 mitogen-activated protein kinase 1 Homo sapiens 90-93 32300243-10 2020 Moreover, pharmacological inhibition of ERK by inhibitor PD0325901 or STAT3 by inhibitor Stattic markedly enhanced the anticancer activity of artesunate, suggesting that suppression of ERK and STAT3 signaling by sorafenib contributes to the synergistic anticancer activity against HCC caused by combination of sorafenib and artesunate. Sorafenib 212-221 mitogen-activated protein kinase 1 Homo sapiens 40-43 32300243-10 2020 Moreover, pharmacological inhibition of ERK by inhibitor PD0325901 or STAT3 by inhibitor Stattic markedly enhanced the anticancer activity of artesunate, suggesting that suppression of ERK and STAT3 signaling by sorafenib contributes to the synergistic anticancer activity against HCC caused by combination of sorafenib and artesunate. Sorafenib 212-221 mitogen-activated protein kinase 1 Homo sapiens 185-188 32776632-15 2020 Phosphorylated-ERK was evaluated as a pharmacodynamic marker, and sorafenib plus trametinib inhibited phosphorylated-ERK up to 98.1% (median: 81.2%) in peripheral blood mononuclear cells.. Sorafenib 66-75 mitogen-activated protein kinase 1 Homo sapiens 117-120 33553331-16 2021 Mechanistically, our results suggested that miR-126-3p promoted sorafenib resistance via targeting SPRED1 and activating the ERK signaling pathway. Sorafenib 64-73 mitogen-activated protein kinase 1 Homo sapiens 125-128 33209885-6 2020 Sorafenib was another widely applicated target drug in HCC which could inhibit multiple kinases including MAPK/ERK. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 111-114 33209885-8 2020 Methods: In HCC cells, MAPK/ERK signaling pathway was blocked by U0126 and sorafenib. Sorafenib 75-84 mitogen-activated protein kinase 1 Homo sapiens 28-31 31469916-8 2020 CONCLUSION: Our findings indicate that the PRMT6-ERK-PKM2 regulatory axis is an important determinant of the Warburg effect in tumor cells and provide a mechanistic link between tumorigenicity, sorafenib resistance and glucose metabolism. Sorafenib 194-203 mitogen-activated protein kinase 1 Homo sapiens 49-52 32391926-6 2022 Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 45-48 32391926-6 2022 Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 131-134 32391926-6 2022 Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. Sorafenib 66-75 mitogen-activated protein kinase 1 Homo sapiens 45-48 32391926-6 2022 Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. Sorafenib 66-75 mitogen-activated protein kinase 1 Homo sapiens 131-134 32187962-10 2020 PI3K and p-ERK pathway were involved in the anti-tumor functions of BZG alone and when combined with sorafenib. Sorafenib 101-110 mitogen-activated protein kinase 1 Homo sapiens 11-14 32354204-6 2020 We showed that GLI transcript levels were down-regulated by the MEK inhibitor U0126 and the Raf inhibitor sorafenib, suggesting that non-canonical signaling including the Ras-Raf-MEK-ERK pathway is involved. Sorafenib 106-115 mitogen-activated protein kinase 1 Homo sapiens 183-186 29782854-0 2018 Combined treatment with sorafenib and silibinin synergistically targets both HCC cells and cancer stem cells by enhanced inhibition of the phosphorylation of STAT3/ERK/AKT. Sorafenib 24-33 mitogen-activated protein kinase 1 Homo sapiens 164-167 32181767-9 2020 Finally, in non-V600 BRAF mutant cell lines combined inhibition of pan-RAF and MEK with sorafenib/AZ628 and selumetinib showed significantly stronger cell growth, cell migration and Erk activation inhibition and also increased apoptosis induction compared to single treatments. Sorafenib 88-97 mitogen-activated protein kinase 1 Homo sapiens 182-185 31233204-0 2019 Synergistic antitumor effect of BRMS1 and sorafenib via inhibition of the PI3K/AKT/mTOR/ERK signaling pathway. Sorafenib 42-51 mitogen-activated protein kinase 1 Homo sapiens 88-91 31233204-7 2019 In addition, expression of inflammatory response-related genes was increased, while secretion of angiogenesis-related molecules was decreased, and apoptosis was also activated after sorafenib treatment using qPCR method, and it was further demonstrated that this effect was mediated by inhibition of the PI3K/AKT/mTOR/ERK signaling pathway using western blot analysis. Sorafenib 182-191 mitogen-activated protein kinase 1 Homo sapiens 318-321 31233204-8 2019 In conclusion, overexpression of BRMS1 potentiated the effect of sorafenib via PI3K/AKT/mTOR/ERK signaling, while knockdown of BRMS1 expression attenuated this effect. Sorafenib 65-74 mitogen-activated protein kinase 1 Homo sapiens 93-96 30426981-9 2018 In addition, the western blot and real-time cell analysis in vitro assays revealed that the ERK phosphorylation and the cellular proliferation of cells are inhibited, respectively, in the sorafenib-treated cells. Sorafenib 188-197 mitogen-activated protein kinase 1 Homo sapiens 92-95 30030148-8 2018 RESULT: We found that suppression of ERK2 (MAPK1) sensitizes several liver cancer cell lines to sorafenib. Sorafenib 96-105 mitogen-activated protein kinase 1 Homo sapiens 37-41 30030148-8 2018 RESULT: We found that suppression of ERK2 (MAPK1) sensitizes several liver cancer cell lines to sorafenib. Sorafenib 96-105 mitogen-activated protein kinase 1 Homo sapiens 43-48 30030148-9 2018 Drugs inhibiting the MEK (MEK1/2 [MAP2K1/2]) or ERK (ERK1/2 [MAPK1/3]) kinases reverse unresponsiveness to sorafenib in vitro and in vivo in a subset of liver cancer cell lines characterized by high levels of active p-ERK, through synergistic inhibition of ERK kinase activity. Sorafenib 107-116 mitogen-activated protein kinase 1 Homo sapiens 48-51 30030148-9 2018 Drugs inhibiting the MEK (MEK1/2 [MAP2K1/2]) or ERK (ERK1/2 [MAPK1/3]) kinases reverse unresponsiveness to sorafenib in vitro and in vivo in a subset of liver cancer cell lines characterized by high levels of active p-ERK, through synergistic inhibition of ERK kinase activity. Sorafenib 107-116 mitogen-activated protein kinase 1 Homo sapiens 53-56 30030148-9 2018 Drugs inhibiting the MEK (MEK1/2 [MAP2K1/2]) or ERK (ERK1/2 [MAPK1/3]) kinases reverse unresponsiveness to sorafenib in vitro and in vivo in a subset of liver cancer cell lines characterized by high levels of active p-ERK, through synergistic inhibition of ERK kinase activity. Sorafenib 107-116 mitogen-activated protein kinase 1 Homo sapiens 53-56 30030148-12 2018 Herein, we found that inhibition of the kinase ERK2 increases the response to sorafenib in liver cancer. Sorafenib 78-87 mitogen-activated protein kinase 1 Homo sapiens 47-51 30126548-9 2018 Rat and human hepatoma cells expressing Lsp1 shRNA displayed increased sensitivity to sorafenib, as evidenced by decreased cell numbers and phosphorylated ERK expression compared with control. Sorafenib 86-95 mitogen-activated protein kinase 1 Homo sapiens 155-158 30456603-6 2019 We further revealed that S1 mainly inhibited the Akt/S6 phosphorylation while sorafenib mostly decreased the phosphorylation of ERK. Sorafenib 78-87 mitogen-activated protein kinase 1 Homo sapiens 128-131 30456603-8 2019 The combination of S1 and sorafenib exerts potentiated anti-tumor effects, in which the underlying mechanisms may involve their differential modulation of the phosphorylation of Akt and S6 in the PI3K/Akt/mTOR cascades and ERK phosphorylation in the Raf/MEK/ERK pathways. Sorafenib 26-35 mitogen-activated protein kinase 1 Homo sapiens 223-226 30456603-8 2019 The combination of S1 and sorafenib exerts potentiated anti-tumor effects, in which the underlying mechanisms may involve their differential modulation of the phosphorylation of Akt and S6 in the PI3K/Akt/mTOR cascades and ERK phosphorylation in the Raf/MEK/ERK pathways. Sorafenib 26-35 mitogen-activated protein kinase 1 Homo sapiens 258-261 30761258-6 2019 Notably, we also found that regorafenib reversed HGF-induced sorafenib resistance by inhibiting ERK and STAT3, and subsequently down-regulating Snail and EMT. Sorafenib 61-70 mitogen-activated protein kinase 1 Homo sapiens 96-99 30761258-7 2019 Taken together, our results indicate that HGF induces sorafenib resistance by activating phosporylated (P)-ERK/Snail/EMT and P-STAT3/Snail/EMT pathways. Sorafenib 54-63 mitogen-activated protein kinase 1 Homo sapiens 107-110 30655811-7 2019 The results of the present study indicated that pre-treatment with sorafenib followed by TSA inhibited the cell viability compared with other treatment modalities, and prevented TSA-induced extracellular-signal-regulated kinase (ERK)/NF-kappaB activity and expression of downstream effector proteins. Sorafenib 67-76 mitogen-activated protein kinase 1 Homo sapiens 190-227 30655811-7 2019 The results of the present study indicated that pre-treatment with sorafenib followed by TSA inhibited the cell viability compared with other treatment modalities, and prevented TSA-induced extracellular-signal-regulated kinase (ERK)/NF-kappaB activity and expression of downstream effector proteins. Sorafenib 67-76 mitogen-activated protein kinase 1 Homo sapiens 229-232 30655811-10 2019 Furthermore, sorafenib pre-treatment is hypothesized to sensitize HCC to TSA via the inhibition of the MEK/ERK/NF-kappaB signal transduction pathway. Sorafenib 13-22 mitogen-activated protein kinase 1 Homo sapiens 107-110 30106087-0 2018 Synergistic effect of ursodeoxycholic acid on the antitumor activity of sorafenib in hepatocellular carcinoma cells via modulation of STAT3 and ERK. Sorafenib 72-81 mitogen-activated protein kinase 1 Homo sapiens 144-147 30106087-6 2018 Thus, chemotherapy with sorafenib and ursodeoxycholic combination may be efficacious in hepatocellular carcinoma by inhibiting cell proliferation and inducing apoptosis through reactive oxygen species-dependent activation of ERK and dephosphorylation of STAT3. Sorafenib 24-33 mitogen-activated protein kinase 1 Homo sapiens 225-228 29702736-4 2018 The relationship between sorafenib exposure and target modulation of kinase targets (FMS-like tyrosine kinase 3 (FLT3)-ITD and extracellular signal-regulated kinase (ERK)) were described by an inhibitory maximum effect (Emax ) model. Sorafenib 25-34 mitogen-activated protein kinase 1 Homo sapiens 127-164 29858683-8 2018 RESULTS: Sorafenib activated the Raf/MEK/ERK pathway and caused sorafenib resistance in HCC cell lines and patient-derived HCC primary cells. Sorafenib 9-18 mitogen-activated protein kinase 1 Homo sapiens 41-44 29858683-9 2018 Sorafenib reactivated the MAPK pathway by down-regulating RKIP at the post-translational level. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 26-30 29858683-11 2018 We also found that sorafenib-reactivated ERK maybe an attractive target for second-line therapy for patients with sorafenib resistance. Sorafenib 19-28 mitogen-activated protein kinase 1 Homo sapiens 41-44 29858683-11 2018 We also found that sorafenib-reactivated ERK maybe an attractive target for second-line therapy for patients with sorafenib resistance. Sorafenib 114-123 mitogen-activated protein kinase 1 Homo sapiens 41-44 29858683-13 2018 CONCLUSION: Reactivation of the Raf/MEK/ERK pathway through aberrant expression of RKIP is one of the mechanisms behind sorafenib resistance in HCC. Sorafenib 120-129 mitogen-activated protein kinase 1 Homo sapiens 40-43 29573266-0 2018 Sorafenib paradoxically activates the RAS/RAF/ERK pathway in polyclonal human NK cells during expansion and thereby enhances effector functions in a dose- and time-dependent manner. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 46-49 29702736-4 2018 The relationship between sorafenib exposure and target modulation of kinase targets (FMS-like tyrosine kinase 3 (FLT3)-ITD and extracellular signal-regulated kinase (ERK)) were described by an inhibitory maximum effect (Emax ) model. Sorafenib 25-34 mitogen-activated protein kinase 1 Homo sapiens 166-169 29538717-0 2018 Sorafenib inhibits proliferation and invasion in desmoid-derived cells by targeting Ras/MEK/ERK and PI3K/Akt/mTOR pathways. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 92-95 29538717-7 2018 Signaling arrays identified multiple potential targets of sorafenib in the Ras/MEK/ERK and PI3K/Akt/mTOR signaling cascades. Sorafenib 58-67 mitogen-activated protein kinase 1 Homo sapiens 83-86 29538717-8 2018 Immunoblot analysis revealed that sorafenib inhibited Akt, MEK and ERK phosphorylation, and this effect correlated with inhibition of total Akt and total MEK, while total ERK levels remained unchanged. Sorafenib 34-43 mitogen-activated protein kinase 1 Homo sapiens 67-70 29538717-11 2018 Taken together, our results suggest that sorafenib suppresses DT proliferation and invasion via inhibition of Ras/MEK/ERK and PI3K/Akt/mTOR signaling pathways with additional effects on translation. Sorafenib 41-50 mitogen-activated protein kinase 1 Homo sapiens 118-121 29156516-1 2018 Sorafenib, a multikinase inhibitor for hepatocellular carcinoma treatment, inhibits the Raf/MAPK/ERK signaling pathway. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 92-96 29552199-0 2018 Sorafenib inhibited cell growth through the MEK/ERK signaling pathway in acute promyelocytic leukemia cells. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 48-51 29552199-7 2018 Furthermore, the phosphorylation of MEK and ERK was inhibited in sorafenib-treated NB4 cells compared with untreated cells. Sorafenib 65-74 mitogen-activated protein kinase 1 Homo sapiens 44-47 29251327-0 2018 Survival pathway of cholangiocarcinoma via AKT/mTOR signaling to escape RAF/MEK/ERK pathway inhibition by sorafenib. Sorafenib 106-115 mitogen-activated protein kinase 1 Homo sapiens 80-83 29251327-2 2018 Sorafenib, a multikinase inhibitor of the RAF/MEK/ERK pathway, is a molecular-targeted drug that is approved for hepatocellular carcinoma (HCC) but not for CCC. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 50-53 29251327-4 2018 Sorafenib inhibited cell growth significantly less in CCC cells than in HCC cells, with lower suppression of ERK phosphorylation. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 109-112 29251327-9 2018 Prevention of escape by AKT/mTOR signaling from the RAF/MEK/ERK pathway in sorafenib treatment by suppressing mTORC2 activity may lead to promising new approaches in CCC therapy. Sorafenib 75-84 mitogen-activated protein kinase 1 Homo sapiens 60-63 29156516-1 2018 Sorafenib, a multikinase inhibitor for hepatocellular carcinoma treatment, inhibits the Raf/MAPK/ERK signaling pathway. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 97-100 29156516-2 2018 However, PI3K/Akt signaling pathway is activated by Sorafenib and cross-talks with the Raf/MAPK/ERK signaling pathway, leading to drug resistance. Sorafenib 52-61 mitogen-activated protein kinase 1 Homo sapiens 91-95 29156516-2 2018 However, PI3K/Akt signaling pathway is activated by Sorafenib and cross-talks with the Raf/MAPK/ERK signaling pathway, leading to drug resistance. Sorafenib 52-61 mitogen-activated protein kinase 1 Homo sapiens 96-99 28687354-7 2017 Additionally, the combination of aspirin and sorafenib showed synergetic effects via inhibiting mTORC1 signaling and the PI3K/AKT, MAPK/ERK pathways. Sorafenib 45-54 mitogen-activated protein kinase 1 Homo sapiens 136-139 29423069-1 2018 Inhibition of RAS-RAF-ERK-signaling is a major mechanism mediated by the multi-kinase inhibitors sorafenib and regorafenib, the only effective therapeutic approaches for advanced hepatocellular carcinoma (HCC). Sorafenib 97-106 mitogen-activated protein kinase 1 Homo sapiens 22-25 29030911-0 2017 Phosphorylated ERK is a potential prognostic biomarker for Sorafenib response in hepatocellular carcinoma. Sorafenib 59-68 mitogen-activated protein kinase 1 Homo sapiens 15-18 28808038-6 2017 Pictilisib activated the compensatory MEK/ERK pathway that likely contributed to pictilisib resistance, which was reversed by cotreatment with the RAF inhibitor sorafenib. Sorafenib 161-170 mitogen-activated protein kinase 1 Homo sapiens 42-45 29113345-4 2017 The Raf inhibitor sorafenib (SFN) or the Mek inhibitor U0126 suppressed MAPK signaling to a greater extent than LPN; which correlated with greater cytotoxic potency of SFN, but not U0126. Sorafenib 18-27 mitogen-activated protein kinase 1 Homo sapiens 72-76 28161506-0 2017 Mathematical modelling unveils the essential role of cellular phosphatases in the inhibition of RAF-MEK-ERK signalling by sorafenib in hepatocellular carcinoma cells. Sorafenib 122-131 mitogen-activated protein kinase 1 Homo sapiens 104-107 28693200-9 2017 There was a reduction in the expression of Ets-1 and ERK phosphorylation in sorafenib or 1,4-Diamino-2,3-dicyano-1,4-bis (2-aminophenylthio) butadiene treated cells suggesting that sorafenib may reduce the expression levels of Ets-1 by blocking the Ras/Raf/mitogen activated protein kinase signaling pathway. Sorafenib 76-85 mitogen-activated protein kinase 1 Homo sapiens 53-56 29113345-4 2017 The Raf inhibitor sorafenib (SFN) or the Mek inhibitor U0126 suppressed MAPK signaling to a greater extent than LPN; which correlated with greater cytotoxic potency of SFN, but not U0126. Sorafenib 29-32 mitogen-activated protein kinase 1 Homo sapiens 72-76 29113345-4 2017 The Raf inhibitor sorafenib (SFN) or the Mek inhibitor U0126 suppressed MAPK signaling to a greater extent than LPN; which correlated with greater cytotoxic potency of SFN, but not U0126. Sorafenib 168-171 mitogen-activated protein kinase 1 Homo sapiens 72-76 28693200-9 2017 There was a reduction in the expression of Ets-1 and ERK phosphorylation in sorafenib or 1,4-Diamino-2,3-dicyano-1,4-bis (2-aminophenylthio) butadiene treated cells suggesting that sorafenib may reduce the expression levels of Ets-1 by blocking the Ras/Raf/mitogen activated protein kinase signaling pathway. Sorafenib 181-190 mitogen-activated protein kinase 1 Homo sapiens 53-56 28161506-2 2017 Sorafenib, the medical treatment of reference against advanced stages of hepatocellular carcinoma (HCC), inhibits the RAF-MEK-ERK cascade in HCC cells. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 126-129 28161506-5 2017 In silico predictions derived from our mathematical model suggested that the disappearance of phosphorylated MEK and ERK proteins catalysed by cellular phosphatases is an essential mechanism underlying the anti-ERK efficacy of sorafenib in HCC cells. Sorafenib 227-236 mitogen-activated protein kinase 1 Homo sapiens 117-120 28161506-5 2017 In silico predictions derived from our mathematical model suggested that the disappearance of phosphorylated MEK and ERK proteins catalysed by cellular phosphatases is an essential mechanism underlying the anti-ERK efficacy of sorafenib in HCC cells. Sorafenib 227-236 mitogen-activated protein kinase 1 Homo sapiens 211-214 28161506-7 2017 These findings highlight an unexpected mode of action of sorafenib on the kinome of HCC cells, and open new perspectives regarding the therapeutic targeting of the RAF-MEK-ERK cascade in this context. Sorafenib 57-66 mitogen-activated protein kinase 1 Homo sapiens 172-175 28276530-4 2017 Here, we demonstrate that RAF inhibition by sorafenib rapidly leads to RAF dimerization and ERK activation in HCCs, which contributes to treatment evasion. Sorafenib 44-53 mitogen-activated protein kinase 1 Homo sapiens 92-95 28260092-5 2017 Sorafenib treatment effectively suppressed the expression of angiogenic factors and activation of the Raf/MEK/ERK pathway in HOXB9-expressing HCC cell lines. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 110-113 28276530-9 2017 Thus, this nano-delivery strategy to selectively target tumors and prevent the paradoxical ERK activation could increase the feasibility of dual RAF/MEK inhibition to overcome sorafenib treatment escape in HCC. Sorafenib 176-185 mitogen-activated protein kinase 1 Homo sapiens 91-94 28035421-6 2017 Digitoxin and sorafenib synergistically inhibited cell viability, but did not inhibit migration, which was potentially mediated by suppression of ERK and hypoxia signaling. Sorafenib 14-23 mitogen-activated protein kinase 1 Homo sapiens 146-149 28164434-5 2017 In this study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways. Sorafenib 15-24 mitogen-activated protein kinase 1 Homo sapiens 248-251 28164434-5 2017 In this study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways. Sorafenib 15-24 mitogen-activated protein kinase 1 Homo sapiens 253-293 28164434-5 2017 In this study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways. Sorafenib 60-69 mitogen-activated protein kinase 1 Homo sapiens 248-251 28164434-5 2017 In this study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways. Sorafenib 60-69 mitogen-activated protein kinase 1 Homo sapiens 253-293 27807662-0 2017 C2-ceramide enhances sorafenib-induced caspase-dependent apoptosis via PI3K/AKT/mTOR and Erk signaling pathways in HCC cells. Sorafenib 21-30 mitogen-activated protein kinase 1 Homo sapiens 89-92 27807662-7 2017 Combination treatment of sorafenib and C2-ceramide inhibited obviously cell growth and proliferation via PI3K/AKT/mTOR and Erk signaling pathways. Sorafenib 25-34 mitogen-activated protein kinase 1 Homo sapiens 123-126 28035421-7 2017 In downstream signaling pathways, the activity of ERK was synergistically suppressed by combinatorial treatment of HepG2 and BEL-7402 cells with sorafenib and digitoxin. Sorafenib 145-154 mitogen-activated protein kinase 1 Homo sapiens 50-53 27863838-2 2016 Present study is aimed to preliminarily evaluate our hypothesis that the combination of resveratrol (RSV), a natural antioxidant, and lower dose of sorafenib (SF), a multi-kinase inhibitor and a component of ERK1/2 (extracellular signal-regulated kinase 1/2) pathway, would augment apoptosis in human breast cancer MCF7 cells. Sorafenib 148-157 mitogen-activated protein kinase 1 Homo sapiens 216-257 27840968-7 2017 Sorafenib inhibited the expression of phospho-ERK and -4EBP1 in 769-P cells; sunitinib, phospho-ERK and -4EBP1 in 786-O and 769-P cells; and everolimus, phospho-p70 in 786-O and 769-P cells. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 46-49 27840968-8 2017 Knockdown of ERK reduced sensitivity to sorafenib in both cell lines, knockdown of ERK and 4EBP1 reduced sensitivity to sunitinib in 769-P cells, and knockdown of 4EBP1 and p70 reduced sensitivity to everolimus in 786-O cells. Sorafenib 40-49 mitogen-activated protein kinase 1 Homo sapiens 13-16 27840968-9 2017 High expression of phospho-ERK, -4EBP1 and -p70 correlated with better progression-free survival in patients treated with sorafenib, sunitinib and everolimus, respectively. Sorafenib 122-131 mitogen-activated protein kinase 1 Homo sapiens 27-30 27840968-10 2017 Our results indicate that phospho-ERK, -4EBP1 and/or -ERK, and phospho-p70 can be used as biomarkers for the therapeutic efficacy of sorafenib, sunitinib and everolimus, respectively. Sorafenib 133-142 mitogen-activated protein kinase 1 Homo sapiens 34-37 27840968-10 2017 Our results indicate that phospho-ERK, -4EBP1 and/or -ERK, and phospho-p70 can be used as biomarkers for the therapeutic efficacy of sorafenib, sunitinib and everolimus, respectively. Sorafenib 133-142 mitogen-activated protein kinase 1 Homo sapiens 54-57 27863427-0 2016 Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-kappaB pathway in human hepatocellular carcinoma-bearing mouse model. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 67-70 27530187-7 2016 CONCLUSION: ANGPTL1 inhibits sorafenib resistance and cancer stemness in HCC cells by repressing EMT through inhibition of the MET receptor-AKT/ERK-Egr-1-Slug signaling cascade. Sorafenib 29-38 mitogen-activated protein kinase 1 Homo sapiens 144-147 27129180-0 2016 Sorafenib-resistant hepatocellular carcinoma stratified by phosphorylated ERK activates PD-1 immune checkpoint. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 74-77 27853648-8 2016 Our findings support that the evaluation of both the circulating EPC frequency and the level of ERK phosphorylation in EPCs may serve as potential non-invasive biomarkers of sorafenib efficacy, both as predictor of treatment outcome and efficacy during drug treatment. Sorafenib 174-183 mitogen-activated protein kinase 1 Homo sapiens 96-99 27853648-0 2016 Endothelial progenitor cell number and ERK phosphorylation serve as predictive and prognostic biomarkers in advanced hepatocellular carcinoma patients treated with sorafenib. Sorafenib 164-173 mitogen-activated protein kinase 1 Homo sapiens 39-42 27853648-2 2016 An earlier study conducted with HCC tumor tissue suggested that ERK phosphorylation (pERK), a downstream target of sorafenib, may serve as a potential biomarker for therapeutic efficacy of sorafenib. Sorafenib 115-124 mitogen-activated protein kinase 1 Homo sapiens 64-67 27853648-2 2016 An earlier study conducted with HCC tumor tissue suggested that ERK phosphorylation (pERK), a downstream target of sorafenib, may serve as a potential biomarker for therapeutic efficacy of sorafenib. Sorafenib 189-198 mitogen-activated protein kinase 1 Homo sapiens 64-67 27853648-5 2016 A statistically significant reduction in the level of ERK phosphorylation and in the absolute number of EPCs was detected following in vivo sorafenib treatment (p < 0 .01 for both). Sorafenib 140-149 mitogen-activated protein kinase 1 Homo sapiens 54-57 27853648-7 2016 In vitro sorafenib treatment of pre- and post-samples from the same patient cohort inhibited ERK phosphorylation levels in EPCs and decreased the number of EPCs at all doses tested (p = 0.01). Sorafenib 9-18 mitogen-activated protein kinase 1 Homo sapiens 93-96 26299635-0 2016 Combinatorial anticancer effects of curcumin and sorafenib towards thyroid cancer cells via PI3K/Akt and ERK pathways. Sorafenib 49-58 mitogen-activated protein kinase 1 Homo sapiens 105-108 27167344-0 2016 Des-gamma-carboxy prothrombin antagonizes the effects of Sorafenib on human hepatocellular carcinoma through activation of the Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways. Sorafenib 57-66 mitogen-activated protein kinase 1 Homo sapiens 135-138 27167344-8 2016 Our results indicate that DCP antagonizes the inhibitory effects of Sorafenib on HCC through activation of the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR signaling pathways. Sorafenib 68-77 mitogen-activated protein kinase 1 Homo sapiens 123-126 26097571-5 2015 Dual luciferase analysis confirmed that Raf/MEK/ERK pathway could directly be regulated by SOX9, and sequential experiments demonstrated that, renal carcinoma cells could sensitize to Sorafenib/Sunitinib through Raf/MEK/ERK signaling pathway inhibition regulated by SOX9 down-regulation. Sorafenib 184-193 mitogen-activated protein kinase 1 Homo sapiens 48-51 26998658-1 2016 INTRODUCTION: Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor (VEGF). Sorafenib 14-23 mitogen-activated protein kinase 1 Homo sapiens 109-112 26998658-2 2016 Since the Ras/Raf/MEK/ERK pathway is implicated in the proliferation of multiple myeloma (MM) cells and VEGF in bone marrow neovascularization, sorafenib is a drug offering the potential for targeting two important pathogenetic mechanisms involved in MM. Sorafenib 144-153 mitogen-activated protein kinase 1 Homo sapiens 22-25 26711788-8 2016 Based on these results, we conclude that resistance to sorafenib is associated with weak ERK signaling and strong Akt signaling in LCSCs. Sorafenib 55-64 mitogen-activated protein kinase 1 Homo sapiens 89-92 27152946-4 2016 The synergistic effects of alpha-Mangostin and Sorafenib were associated with enhanced inhibition of activated AKT and ERK, induced ER stress, and reduced autophagy, eventually leading to apoptosis. Sorafenib 47-56 mitogen-activated protein kinase 1 Homo sapiens 119-122 26655273-0 2016 MicroRNA-122 confers sorafenib resistance to hepatocellular carcinoma cells by targeting IGF-1R to regulate RAS/RAF/ERK signaling pathways. Sorafenib 21-30 mitogen-activated protein kinase 1 Homo sapiens 116-119 26544731-3 2016 Here we present a novel system to provide quantitative information concerning sorafenib-related targets by simultaneous detection of phosphorylated ERK (pERK) and pAkt expressions in circulating tumor cells (CTCs) isolated from HCC patients. Sorafenib 78-87 mitogen-activated protein kinase 1 Homo sapiens 148-151 27095937-7 2016 Moreover, sorafenib and pemetrexed demonstrated stronger synergism, demonstrating that inhibiting the Ras/Raf/Mek/Erk and Ras/PI3K/Akt pathways concurrently may achieve improved antitumor effects. Sorafenib 10-19 mitogen-activated protein kinase 1 Homo sapiens 114-117 26324075-3 2015 In other types of cancer, paradoxical ERK activation has emerged as a potential resistance mechanism to RAF-inhibiting drugs including MKIs such as sorafenib and pazopanib. Sorafenib 148-157 mitogen-activated protein kinase 1 Homo sapiens 38-41 26488287-5 2015 The anti-tumor activity of sorafenib is largely attributed to the blockade of the signals from growth factors, such as vascular endothelial growth factor receptor and platelet-derived growth factor receptor, and the downstream RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade. Sorafenib 27-36 mitogen-activated protein kinase 1 Homo sapiens 296-299 26488287-5 2015 The anti-tumor activity of sorafenib is largely attributed to the blockade of the signals from growth factors, such as vascular endothelial growth factor receptor and platelet-derived growth factor receptor, and the downstream RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade. Sorafenib 27-36 mitogen-activated protein kinase 1 Homo sapiens 314-317 26097571-5 2015 Dual luciferase analysis confirmed that Raf/MEK/ERK pathway could directly be regulated by SOX9, and sequential experiments demonstrated that, renal carcinoma cells could sensitize to Sorafenib/Sunitinib through Raf/MEK/ERK signaling pathway inhibition regulated by SOX9 down-regulation. Sorafenib 184-193 mitogen-activated protein kinase 1 Homo sapiens 220-223 25451688-5 2015 While inhibitors targeting JNK, ERK or PI3K reduce PTMA expression, only ERK activation is suppressed by sorafenib. Sorafenib 105-114 mitogen-activated protein kinase 1 Homo sapiens 73-76 25614335-2 2015 The aim of this study was to assess the effects of the multi-target drug, sorafenib, on clear cell-renal cell carcinoma (ccRCC) necrosis by regulating CypD expression and to explore whether this effect was related to the phosphorylation of extracellular signal-regulated kinases (ERKs). Sorafenib 74-83 mitogen-activated protein kinase 1 Homo sapiens 280-284 25614335-9 2015 Epidermal growth factor (EGF, the activator of ERK) and ERK overexpression inhibited the effect of sorafenib on CypD expression, apoptosis-induced 786-O and mitochondrial membrane potential depolarization. Sorafenib 99-108 mitogen-activated protein kinase 1 Homo sapiens 47-50 25614335-9 2015 Epidermal growth factor (EGF, the activator of ERK) and ERK overexpression inhibited the effect of sorafenib on CypD expression, apoptosis-induced 786-O and mitochondrial membrane potential depolarization. Sorafenib 99-108 mitogen-activated protein kinase 1 Homo sapiens 56-59 25451688-8 2015 We also identify a sorafenib-responsive segment lying 1000-1500-bp upstream of the PTMA transcription start site and observe that it is controlled by c-Myc and ERK. Sorafenib 19-28 mitogen-activated protein kinase 1 Homo sapiens 160-163 25245054-0 2014 Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-kappaB-dependent pathway that reduces uPA and MMP-9 expression. Sorafenib 109-118 mitogen-activated protein kinase 1 Homo sapiens 151-154 25665465-5 2015 In FLT3-ITD positive cells sorafenib blocks Erk activity and cell proliferation, and triggers apoptosis. Sorafenib 27-36 mitogen-activated protein kinase 1 Homo sapiens 44-47 25665465-6 2015 However, in cells lacking FLT3-ITD, sorafenib paradoxically activates Erk2, and stimulates cellular proliferation and metabolic activity. Sorafenib 36-45 mitogen-activated protein kinase 1 Homo sapiens 70-74 24375110-5 2014 In the present study, we performed assays of cell proliferation, RT-PCR, and western blot to investigate the effect of sorafenib on OS MG63 cells and to elucidate the molecular actions of sorafenib against RTKs VEGFR2 and RET, as well as MEK/ERK signaling pathway. Sorafenib 188-197 mitogen-activated protein kinase 1 Homo sapiens 242-245 24803676-14 2014 In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Sorafenib 22-31 mitogen-activated protein kinase 1 Homo sapiens 91-94 25136776-0 2014 Sorafenib regulating ERK signals pathway in gastric cancer cell. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 21-24 25136776-3 2014 Treatment of sorafenib significantly decreased phosphorylation activation of ERK protein in a dose-dependent manner. Sorafenib 13-22 mitogen-activated protein kinase 1 Homo sapiens 77-80 25136776-6 2014 Deactivation of phosphorylation of ERK protein is one of the mechanisms of sorafenib inhibiting gastric cancer. Sorafenib 75-84 mitogen-activated protein kinase 1 Homo sapiens 35-38 24486412-6 2014 Blocking the TGF-alpha/EGFR pathway by gefitinib, a specific EGFR inhibitor, reduced the activation of STAT (signal transducer and activator of transcription) 3, AKT and ERK (extracellular signal-regulated kinase), and synergized with sorafenib to inhibit proliferation and induce apoptosis of hypoxic HCC cells. Sorafenib 235-244 mitogen-activated protein kinase 1 Homo sapiens 175-212 25219752-0 2014 The regulation of ERK and p-ERK expression by cisplatin and sorafenib in gastric cancer cells. Sorafenib 60-69 mitogen-activated protein kinase 1 Homo sapiens 18-21 25219752-7 2014 These results suggested that the antitumor mechanism of cisplatin and sorafenib involved altering the cell cycle and stimulating ERK phosphorylation in the ERK signaling pathway. Sorafenib 70-79 mitogen-activated protein kinase 1 Homo sapiens 129-132 25219752-7 2014 These results suggested that the antitumor mechanism of cisplatin and sorafenib involved altering the cell cycle and stimulating ERK phosphorylation in the ERK signaling pathway. Sorafenib 70-79 mitogen-activated protein kinase 1 Homo sapiens 156-159 24807012-0 2014 Sorafenib increases efficacy of vorinostat against human hepatocellular carcinoma through transduction inhibition of vorinostat-induced ERK/NF-kappaB signaling. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 136-139 24807012-10 2014 The mechanism of sorafenib to enhance SAHA efficacy on HCC is through the suppression of ERK/NF-kappaB pathway, which induces extrinsic and intrinsic apoptosis. Sorafenib 17-26 mitogen-activated protein kinase 1 Homo sapiens 89-92 27508178-6 2014 An increasing number of studies have reported that sorafenib exerts "off-target" effects, including the modulation of signaling pathways other than Raf/MEK/ERK pathway, nonapoptotic cell death mechanisms, and even immune modulation. Sorafenib 51-60 mitogen-activated protein kinase 1 Homo sapiens 156-159 24375110-0 2014 VEGFR, RET, and RAF/MEK/ERK pathway take part in the inhibition of osteosarcoma MG63 cells with sorafenib treatment. Sorafenib 96-105 mitogen-activated protein kinase 1 Homo sapiens 24-27 24375110-6 2014 The present study confirmed that sorafenib could inhibit the proliferation of OS MG63 cells and caused a series of biomolecule effects, including the change of VEGFR2 and ERK gene expression, and the phosphorylation alteration of VEGFR2, RET, and MEK1 proteins. Sorafenib 33-42 mitogen-activated protein kinase 1 Homo sapiens 171-174 24375110-7 2014 VEGFR2, RET, and MEK/ERK signaling pathway are involved in the pharmacological mechanism of sorafenib. Sorafenib 92-101 mitogen-activated protein kinase 1 Homo sapiens 21-24 24520095-7 2014 However, sorafenib blocked MPT0E028-induced Erk activation and its downstream signaling cascades, such as Stat3 phosphorylation (Ser(727)) and Mcl-1 upregulation. Sorafenib 9-18 mitogen-activated protein kinase 1 Homo sapiens 44-47 24817927-6 2014 The decreased anti-tumor effect of sorafenib was rescued by chemical inhibition of ERK and AKT. Sorafenib 35-44 mitogen-activated protein kinase 1 Homo sapiens 83-86 24817927-7 2014 When TGF-beta-sensitized cells were treated with sorafenib plus VPA, the levels of phosphorylated ERK and AKT were considerably suppressed and the numbers of dead cells were increased by 3.7-5.7-fold compared with those exposed to sorafenib alone (P<0.05). Sorafenib 49-58 mitogen-activated protein kinase 1 Homo sapiens 98-101 24817927-9 2014 Collectively, TGF-beta/ERK/AKT signaling might play a critical role in sorafenib resistance in hepatoma cells, and combination treatment with VPA may be effective against this drug resistance. Sorafenib 71-80 mitogen-activated protein kinase 1 Homo sapiens 23-26 24520095-9 2014 Pharmacologic inhibition of Mek by PD98059 potentiated MPT0E028-induced apoptosis, suggesting that the synergistic interaction between MPT0E028 and sorafenib occurs at least partly through inhibition of Erk signaling. Sorafenib 148-157 mitogen-activated protein kinase 1 Homo sapiens 203-206 24378831-2 2014 Sorafenib, an inhibitor of a number of kinases targeting the Raf/MEK/ERK pathway, is a promising new chemotherapeutic agent in human medicine that has been approved since 2006 for the therapy of renal cell carcinoma and since 2007 for the treatment of hepatocellular carcinoma. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 69-72 24213303-0 2014 Stimulatory effects of sorafenib on human non-small cell lung cancer cells in vitro by regulating MAPK/ERK activation. Sorafenib 23-32 mitogen-activated protein kinase 1 Homo sapiens 103-106 24096267-2 2014 The anti-tumor effect of sorafenib is thought to be mediated through its inhibition of the RAS-Raf-Erk pathway, as well as its inhibition of VEGFR and PDGFR. Sorafenib 25-34 mitogen-activated protein kinase 1 Homo sapiens 99-102 24696725-7 2014 Western blotting results showed that those 3 HMT genes knockdown alone or sorafenib treatments alone both induce AKT/ERK activation. Sorafenib 74-83 mitogen-activated protein kinase 1 Homo sapiens 117-120 24213303-7 2014 Furthermore, sorafenib was confirmed to regulate the expression of cyclin D1 and apoptosis-associated proteins through the regulation of extracellular signal-regulated kinase 1/2 phosphorylation in A549 cells. Sorafenib 13-22 mitogen-activated protein kinase 1 Homo sapiens 137-176 23732299-8 2013 Sorafenib and its metabolites, again with the exception of N"-hydroxymethylsorafenib N-oxide, impaired MEK/ERK signaling in MDA-MB-231 cells and modulated the expression of cyclin D1 and myeloid cell leukemia sequence-1, which regulate cell viability. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 107-110 23682582-0 2013 Radiosensitivity enhancement of human hepatocellular carcinoma cell line SMMC-7721 by sorafenib through the MEK/ERK signal pathway. Sorafenib 86-95 mitogen-activated protein kinase 1 Homo sapiens 112-115 23682582-8 2013 Furthermore, sorafenib pretreatment led to decreased phosphorylation levels of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in SMMC-7721 cells. Sorafenib 13-22 mitogen-activated protein kinase 1 Homo sapiens 79-116 23682582-8 2013 Furthermore, sorafenib pretreatment led to decreased phosphorylation levels of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in SMMC-7721 cells. Sorafenib 13-22 mitogen-activated protein kinase 1 Homo sapiens 118-121 23682582-9 2013 Interestingly, pretreatment of mitogen-activated protein kinase kinases/extracellular signal-regulated kinase (MEK/ERK) signaling inhibitor U0126 had a similar effect as that of sorafenib pretreatment in hepatocellular carcinoma cells, whereas pretreatment of phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling inhibitor LY294002 in the same cells had no effect on radiosensitization. Sorafenib 178-187 mitogen-activated protein kinase 1 Homo sapiens 72-109 23682582-13 2013 The MEK/ERK signaling pathway may be a pathway responsible for the radiosensitivity enhancement of sorafenib. Sorafenib 99-108 mitogen-activated protein kinase 1 Homo sapiens 8-11 24405594-5 2014 Whereas, RAD001 combined with c-Raf inhibitor sorafenib eliminated RAD001-induced activation of c-Raf-ERK pathway and reversed pancreatic cancer cell resistance to RAD001; compared with the RAD001 alone, sorafenib had a synergistical inhibitory effect with RAD001. Sorafenib 46-55 mitogen-activated protein kinase 1 Homo sapiens 102-105 24331695-11 2013 Moreover, sorafenib alone significantly inhibited the RAF/MEK/ERK and STAT3 pathways, with the fold-changes of p-C-RAF, p-ERK1/2 and p-STAT3 being 0.56 +/- 0.05, 0.54 +/- 0.02 and 0.36 +/- 0.02, respectively (all P less than 0.01); 5-FU alone produced no significant effects on these pathways. Sorafenib 10-19 mitogen-activated protein kinase 1 Homo sapiens 62-65 24331695-14 2013 Sorafenib-inhibited RAF/MEK/ERK and STAT3 signaling and cyclinD1 expression may have induced the observed G1phase arrest and S phase reduction, thereby reducing the cells" sensitivity to 5-FU. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 28-31 23960095-7 2013 Moreover, we found that sorafenib improved the efficacy of irinotecan by inhibiting the irinotecan-mediated p38 and ERK activation. Sorafenib 24-33 mitogen-activated protein kinase 1 Homo sapiens 116-119 23845703-3 2013 Thus, this study was designed to investigate whether phosphorylated ERK (pERK) and members of the sorafenib target or PI3K/Akt/mTOR signaling pathway predict the efficacy of sorafenib in advanced HCC patients. Sorafenib 174-183 mitogen-activated protein kinase 1 Homo sapiens 68-71 23732299-10 2013 Thus, it emerges that, by targeting the MEK/ERK pathway, multiple sorafenib metabolites may contribute to the actions of sorafenib in breast cancer. Sorafenib 66-75 mitogen-activated protein kinase 1 Homo sapiens 44-47 23732299-10 2013 Thus, it emerges that, by targeting the MEK/ERK pathway, multiple sorafenib metabolites may contribute to the actions of sorafenib in breast cancer. Sorafenib 121-130 mitogen-activated protein kinase 1 Homo sapiens 44-47 23467984-5 2013 Of note, sorafenib sensitized K562 to DNR by inhibiting proliferation and inducing apoptosis in a dose-dependent manner which was through blocking the RAF/MEK/ERK pathway. Sorafenib 9-18 mitogen-activated protein kinase 1 Homo sapiens 159-162 23463670-6 2013 Sorafenib suppressed Mcl-1 at the gene transactivation level by inactivating the ERK/Elk-1 pathway. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 81-84 23463670-9 2013 Furthermore, sorafenib reduced the stability of the Mcl-1 protein by enhancing its ubiquitination and degradation by the proteasome via the AKT/GSK3beta and the ERK pathways. Sorafenib 13-22 mitogen-activated protein kinase 1 Homo sapiens 161-164 23591401-1 2013 OBJECTIVES: Sorafenib, an oral multikinase inhibitor of the VEGFR/PDGFR/Raf/MEK/ERK pathway, has shown potential activity in patients with recurrent ovarian cancer (OC). Sorafenib 12-21 mitogen-activated protein kinase 1 Homo sapiens 80-83 23316005-5 2013 We demonstrate that alphaB-Crystallin overexpression fosters HCC progression by inducing epithelial-mesenchymal transition (EMT) in HCC cells through activation of the extracellular-regulated protein kinase (ERK) cascade, which can counteract the effect of sorafenib. Sorafenib 257-266 mitogen-activated protein kinase 1 Homo sapiens 168-206 23316005-5 2013 We demonstrate that alphaB-Crystallin overexpression fosters HCC progression by inducing epithelial-mesenchymal transition (EMT) in HCC cells through activation of the extracellular-regulated protein kinase (ERK) cascade, which can counteract the effect of sorafenib. Sorafenib 257-266 mitogen-activated protein kinase 1 Homo sapiens 208-211 23497499-3 2013 Sorafenib is a multikinase inhibitor of the Ras/Raf/MEK/ERK pathway and of tumor angiogenesis. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 56-59 23620775-0 2013 Sorafenib inhibits lymphoma xenografts by targeting MAPK/ERK and AKT pathways in tumor and vascular cells. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 57-60 23620775-5 2013 Upon sorafenib treatment, endothelial and tumor cells from SU-DHL-4V, Granta-519, and KMS-11 nodules showed a potent inhibition of either phospho-ERK or phospho-AKT, whereas a concomitant inhibition of phospho-ERK and phospho-AKT was only observed in HD-MyZ nodules. Sorafenib 5-14 mitogen-activated protein kinase 1 Homo sapiens 146-149 23620775-5 2013 Upon sorafenib treatment, endothelial and tumor cells from SU-DHL-4V, Granta-519, and KMS-11 nodules showed a potent inhibition of either phospho-ERK or phospho-AKT, whereas a concomitant inhibition of phospho-ERK and phospho-AKT was only observed in HD-MyZ nodules. Sorafenib 5-14 mitogen-activated protein kinase 1 Homo sapiens 210-213 23564781-6 2013 RESULTS: HCC fragments in culture retain their morphology and viability for at least 48 h, permitting an in vitro analysis of the effect of sorafenib on the Extracellular signal-regulated kinase (ERK) cascade. Sorafenib 140-149 mitogen-activated protein kinase 1 Homo sapiens 157-194 23564781-6 2013 RESULTS: HCC fragments in culture retain their morphology and viability for at least 48 h, permitting an in vitro analysis of the effect of sorafenib on the Extracellular signal-regulated kinase (ERK) cascade. Sorafenib 140-149 mitogen-activated protein kinase 1 Homo sapiens 196-199 22821509-6 2012 Increased proliferation due to strong activation of extracellular-signal-regulated kinase 1/2 (ERK1/2) is caused by overexpression/activation of platelet-derived growth factor receptor-beta (PDGFR-beta) and ErbB2/3 which we successfully blocked with AZD6244, sorafenib, or lapatinib. Sorafenib 259-268 mitogen-activated protein kinase 1 Homo sapiens 52-93 23142289-4 2013 Sorafenib selectively inhibited radiation-induced activation of vascular endothelial growth factor receptor-2 (VEGFR2) and downstream extracellular signal-regulated kinase (ERK) pathway, induced DNA damage and suppressed DNA repair capacity, decreased radiation-activated NF-kappaB and increased radiation-induced apoptosis. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 134-171 23142289-4 2013 Sorafenib selectively inhibited radiation-induced activation of vascular endothelial growth factor receptor-2 (VEGFR2) and downstream extracellular signal-regulated kinase (ERK) pathway, induced DNA damage and suppressed DNA repair capacity, decreased radiation-activated NF-kappaB and increased radiation-induced apoptosis. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 173-176 22973961-8 2013 Moreover, sorafenib reduced Akt/ERK phosphorylation in erlotinib-resistant cells, associated with significant RKIP up-regulation. Sorafenib 10-19 mitogen-activated protein kinase 1 Homo sapiens 32-35 22941213-7 2013 Moreover, MEK/ERK signaling was hyperactivated by the selective mutant B-Raf inhibitor PLX4720 and inhibited by the pan-Raf inhibitor sorafenib. Sorafenib 134-143 mitogen-activated protein kinase 1 Homo sapiens 14-17 22941213-8 2013 Our data suggest that sorafenib sensitivity in MDR cells is mediated through the inhibition of P-glycoprotein activity following strong inhibition of Raf/MEK/ERK signaling. Sorafenib 22-31 mitogen-activated protein kinase 1 Homo sapiens 158-161 22929805-10 2012 Moreover, the phosphorylation levels of mTOR, extracellular signal-regulated kinase (ERK), p70S6K, RP-S6, 4E-BP1, and eIF4E were significantly suppressed by sorafenib. Sorafenib 157-166 mitogen-activated protein kinase 1 Homo sapiens 46-83 22929805-10 2012 Moreover, the phosphorylation levels of mTOR, extracellular signal-regulated kinase (ERK), p70S6K, RP-S6, 4E-BP1, and eIF4E were significantly suppressed by sorafenib. Sorafenib 157-166 mitogen-activated protein kinase 1 Homo sapiens 85-88 22929805-12 2012 CONCLUSIONS: Sorafenib-mediated inhibition of HIF-1alpha synthesis is associated with previously undefined pathways in which mTOR/p70S6K/4E-BP1 and ERK phosphorylation are downregulated. Sorafenib 13-22 mitogen-activated protein kinase 1 Homo sapiens 148-151 22773582-0 2012 Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK/NF-kappaB pathway in hepatocellular carcinoma cells. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 76-79 22843888-5 2012 Moreover, pre-treatment of Caki-1 (wild-type VHL) and 786-O (mutant VHL) with HDACIs followed by sorafenib reduced cell viability synergistically via activation of caspases and downregulation of the levels of myeloid leukemia cell differentiation protein (MCL1), phospho-extracellular signal-regulated kinase (ERK), and secreted vascular endothelial growth factor (VEGF). Sorafenib 97-106 mitogen-activated protein kinase 1 Homo sapiens 263-308 22843888-5 2012 Moreover, pre-treatment of Caki-1 (wild-type VHL) and 786-O (mutant VHL) with HDACIs followed by sorafenib reduced cell viability synergistically via activation of caspases and downregulation of the levels of myeloid leukemia cell differentiation protein (MCL1), phospho-extracellular signal-regulated kinase (ERK), and secreted vascular endothelial growth factor (VEGF). Sorafenib 97-106 mitogen-activated protein kinase 1 Homo sapiens 310-313 22641227-10 2012 Sorafenib/AZD6244 potently inhibited angiogenesis and phosphorylation of VEGFR-2, PDGFR-beta and ERK, p90RSK, p70S6K, cdk-2 and retinoblastoma. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 109-112 22773582-7 2012 Sorafenib inhibits TPA-induced MMP-9 and VEGF expressions via the suppression of ERK/NF-kappaB pathway in HCC cells. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 81-84 22634008-6 2012 Moreover, sorafenib inhibited IFN-alpha induced oncogenic signaling of STAT3, AKT and ERK but not the activation of the tumor suppressor STAT1. Sorafenib 10-19 mitogen-activated protein kinase 1 Homo sapiens 86-89 22414764-9 2012 In cell lines cultured in 10% serum or treated with EGF, sorafenib alone inhibited phospho-STAT3 while it maintained or even increased phospho-ERK and/or phospho-AKT. Sorafenib 57-66 mitogen-activated protein kinase 1 Homo sapiens 143-146 22520038-0 2012 Vitamin K1 enhances sorafenib-induced growth inhibition and apoptosis of human malignant glioma cells by blocking the Raf/MEK/ERK pathway. Sorafenib 20-29 mitogen-activated protein kinase 1 Homo sapiens 126-129 22787432-9 2012 Mechanistically, the combination could more noticeably downregulate the phosphorylation of constitutively active extracellular signal-regulated kinase (ERK), Akt (Thr308), and signal transducer and activator of transcription 3 (STAT3) than sorafenib alone. Sorafenib 240-249 mitogen-activated protein kinase 1 Homo sapiens 113-150 22787432-9 2012 Mechanistically, the combination could more noticeably downregulate the phosphorylation of constitutively active extracellular signal-regulated kinase (ERK), Akt (Thr308), and signal transducer and activator of transcription 3 (STAT3) than sorafenib alone. Sorafenib 240-249 mitogen-activated protein kinase 1 Homo sapiens 152-155 22787432-10 2012 Collectively, these findings demonstrate that CH12 interacts additively with sorafenib to strongly inhibit the tumor growth of HCC xenografts expressing EGFRvIII by enhancing the sorafenib-mediated inhibition of the MEK/ERK, phosphoinositide 3-kinase/AKT, and STAT3 pathways. Sorafenib 179-188 mitogen-activated protein kinase 1 Homo sapiens 220-223 22519770-2 2012 sorafenib is an oral multikinase inhibitor that targets Raf/mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase (ERK) (Raf/MEK/ERK) and several tyrosine kinases (VEGFR-2, VEGFR-3, PDGFR-beta) that has shown efficacy in hepatocellular carcinoma (HCC). Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 138-141 22519770-2 2012 sorafenib is an oral multikinase inhibitor that targets Raf/mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase (ERK) (Raf/MEK/ERK) and several tyrosine kinases (VEGFR-2, VEGFR-3, PDGFR-beta) that has shown efficacy in hepatocellular carcinoma (HCC). Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 152-155 22520038-6 2012 Sorafenib in combination with VK1 treatment produced marked potentiation of growth inhibition and apoptosis, and reduced expression of phospho-mitogen-activated protein kinase kinase (MEK) and phospho-extracellular signal-regulated kinase (ERK). Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 193-238 22176637-8 2012 RESULTS: Treatment with sorafenib led to decreased ERK phosphorylation, reduced cell viability and induction of apoptosis in HepT1 and HUH6 cells. Sorafenib 24-33 mitogen-activated protein kinase 1 Homo sapiens 51-54 22520038-6 2012 Sorafenib in combination with VK1 treatment produced marked potentiation of growth inhibition and apoptosis, and reduced expression of phospho-mitogen-activated protein kinase kinase (MEK) and phospho-extracellular signal-regulated kinase (ERK). Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 240-243 22520038-8 2012 CONCLUSIONS: Our findings indicated that VK1 enhanced the cytotoxicity effect of sorafenib through inhibiting the Raf/MEK/ERK signaling pathway in glioma cells, and suggested that sorafenib in combination with VK1 maybe a new therapeutic option for patients with gliomas. Sorafenib 81-90 mitogen-activated protein kinase 1 Homo sapiens 122-125 22176637-13 2012 ERK phosphorylation was reduced in tumours tissues after sorafenib treatment. Sorafenib 57-66 mitogen-activated protein kinase 1 Homo sapiens 0-3 21979753-4 2012 One single dose of 10 mumol/L or the repeated addition of 1 mumol/L sorafenib caused caspase-dependent apoptosis and reduced levels of phosphorylated B-RAF, C-RAF, extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3) and myeloid cell leukemia sequence 1 (Mcl-1) in CLL cells in the presence of the microenvironment. Sorafenib 68-77 mitogen-activated protein kinase 1 Homo sapiens 164-201 21979753-5 2012 We show that the RAF/mitogen-activated protein kinase kinase (MEK)/ERK pathway can modulate Mcl-1 expression and contribute to CLL cell viability, thereby associating so-rafenib cytotoxicity to its impact on RAF and Mcl-1. Sorafenib 167-177 mitogen-activated protein kinase 1 Homo sapiens 67-70 21979753-8 2012 Taken together, our data suggest that sorafenib exerts its cytotoxic effect likely via inhibition of the VEGFR and RAF/MEK/ERK pathways, both of which can modulate Mcl-1 expression in CLL cells. Sorafenib 38-47 mitogen-activated protein kinase 1 Homo sapiens 123-126 21979753-4 2012 One single dose of 10 mumol/L or the repeated addition of 1 mumol/L sorafenib caused caspase-dependent apoptosis and reduced levels of phosphorylated B-RAF, C-RAF, extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3) and myeloid cell leukemia sequence 1 (Mcl-1) in CLL cells in the presence of the microenvironment. Sorafenib 68-77 mitogen-activated protein kinase 1 Homo sapiens 203-206 22109971-8 2012 At concentrations below its IC(50), sorafenib-treated TT and MZ-CRC-1 cells demonstrated transient inhibition and then re-activation of Erk over 6 h. In concordance, synergistic effects were only identified using sorafenib in combination with the Mek inhibitor AZD6244 (P<0.001 for each cell line). Sorafenib 36-45 mitogen-activated protein kinase 1 Homo sapiens 136-139 21529991-2 2011 Therefore, research effort has focused on target-specific agents, such as sorafenib, which blocks both the RAF/MEK/ERK signalling pathways and receptors involved in neovascularization and tumor progression, including VEGFR-2 and c-Kit. Sorafenib 74-83 mitogen-activated protein kinase 1 Homo sapiens 115-118 20552299-2 2011 Sorafenib is an orally administered multikinase inhibitor that blocks intracellular kinases in the Raf/MEK/ERK pathway involved in tumor proliferation, and also kinases responsible for angiogenesis, including VEGFr-2, VEGFr-3, Flt-3, PDGFr-beta and c-KIT. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 107-110 21529991-9 2011 Sorafenib reduced c-Kit and ERK activation and gemcitabine inhibited Akt phosphorylation. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 28-31 21529991-11 2011 CONCLUSIONS: These data demonstrate that sorafenib and gemcitabine synergistically interact against NSCLC cells, through suppression of Akt, c-Kit and ERK phosphorylation, induction of apoptosis and modulation of dCK, RRM1, RRM2 and RKIP gene expression. Sorafenib 41-50 mitogen-activated protein kinase 1 Homo sapiens 151-154 20810616-0 2010 Sorafenib inhibits cAMP-dependent ERK activation, cell proliferation, and in vitro cyst growth of human ADPKD cyst epithelial cells. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 34-37 21689083-5 2011 Previously described sorafenib targets within the RAF kinase family were found to be expressed and phosphorylated in all cell lines, and sorafenib perturbed the activation of classical RAF/MEK/ERK pathway targets. Sorafenib 137-146 mitogen-activated protein kinase 1 Homo sapiens 193-196 20926530-7 2011 Similarly, although the RAF inhibitor sorafenib effectively inhibited MEK/ERK activation, it did not block the mitochondrial localization of BRAF(V600E). Sorafenib 38-47 mitogen-activated protein kinase 1 Homo sapiens 74-77 20812347-0 2010 Sorafenib induces growth inhibition and apoptosis of human chondrosarcoma cells by blocking the RAF/ERK/MEK pathway. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 100-103 20812347-6 2010 RESULTS: The results showed that sorafenib effectively inhibited cell growth and induced apoptosis in chondrosarcoma cells, which was concurrent with inhibition of the expression of phospho-MEK and phospho-ERK. Sorafenib 33-42 mitogen-activated protein kinase 1 Homo sapiens 206-209 21102438-3 2010 Signalling through this ERK cascade is frequently amplified in cancers, and drugs such as sorafenib (which is prescribed to treat renal and hepatic carcinomas) and PLX4720 (which targets melanomas) inhibit RAF kinases. Sorafenib 90-99 mitogen-activated protein kinase 1 Homo sapiens 24-27 20191303-1 2011 BACKGROUND: Sorafenib is an oral multikinase inhibitor that blocks cell proliferation via the ERK pathway and angiogenesis via the VEGF pathway. Sorafenib 12-21 mitogen-activated protein kinase 1 Homo sapiens 94-97 21790999-1 2011 A multikinase inhibitor of the Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, sorafenib, is increasingly being used in the management of hepatocellular carcinoma, and its combination with conventional chemotherapeutics has stimulated particular interest. Sorafenib 134-143 mitogen-activated protein kinase 1 Homo sapiens 120-123 21289252-13 2011 CONCLUSIONS: Inhibiting the Ras/Raf/MAPK kinase/ERK and RET kinase pathways with sorafenib and tipifarnib is well tolerated and active against thyroid cancer. Sorafenib 81-90 mitogen-activated protein kinase 1 Homo sapiens 48-51 21258214-6 2011 Combining ABC294640 and sorafenib led to a decrease in the levels of phosphorylated ERK in SK-HEP-1 cells, indicating that the antitumor effect of this drug combination is likely mediated through a suppression of the MAPK pathway in hepatocellular models. Sorafenib 24-33 mitogen-activated protein kinase 1 Homo sapiens 84-87 21258214-6 2011 Combining ABC294640 and sorafenib led to a decrease in the levels of phosphorylated ERK in SK-HEP-1 cells, indicating that the antitumor effect of this drug combination is likely mediated through a suppression of the MAPK pathway in hepatocellular models. Sorafenib 24-33 mitogen-activated protein kinase 1 Homo sapiens 217-221 21079155-4 2011 The CXCL12-induced phosphorylation of ERK and MEK in ZAP-70(+) CLL cells was blocked by sorafenib, a small molecule inhibitor of RAF. Sorafenib 88-97 mitogen-activated protein kinase 1 Homo sapiens 38-41 21351273-11 2010 Thus, combination of VK1 plus sorafenib strongly induced growth inhibition and apoptosis in rodent and human HCC and inhibited the RAF/mitogen-activated protein kinase kinase/ERK pathway. Sorafenib 30-39 mitogen-activated protein kinase 1 Homo sapiens 175-178 21187475-6 2010 EGF increased phosphorylation of MEK and ERK, key Ras/Raf downstream signaling proteins; this activation was inhibited by sorafenib. Sorafenib 122-131 mitogen-activated protein kinase 1 Homo sapiens 41-44 20810616-5 2010 We found that nanomolar concentrations of Sorafenib reduced the basal activity of ERK, inhibited cAMP-dependent activation of B-Raf and MEK/ERK signaling, and caused a concentration-dependent inhibition of cell proliferation induced by cAMP, epidermal growth factor, or the combination of the two agonists. Sorafenib 42-51 mitogen-activated protein kinase 1 Homo sapiens 82-85 20810616-5 2010 We found that nanomolar concentrations of Sorafenib reduced the basal activity of ERK, inhibited cAMP-dependent activation of B-Raf and MEK/ERK signaling, and caused a concentration-dependent inhibition of cell proliferation induced by cAMP, epidermal growth factor, or the combination of the two agonists. Sorafenib 42-51 mitogen-activated protein kinase 1 Homo sapiens 140-143 20301194-0 2010 Sorafenib combined vitamin K induces apoptosis in human pancreatic cancer cell lines through RAF/MEK/ERK and c-Jun NH2-terminal kinase pathways. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 101-104 20301194-11 2010 Thus, combination VK1 plus Sorafenib strongly induced growth inhibition and apoptosis in pancreas cancer cells, involving both inhibition of the RAF/MEK/ERK pathway as well as activation of the JNK, c-Jun and FasL apoptotic pathway. Sorafenib 27-36 mitogen-activated protein kinase 1 Homo sapiens 153-156 19890601-4 2010 The sole systemic therapy that has shown efficacy in improving the survival of HCC patients is sorafenib, an oral kinase inhibitor that blocks the Raf/MEK/ERK pathway and the receptor for VEGFR 2 and PDGFR-beta. Sorafenib 95-104 mitogen-activated protein kinase 1 Homo sapiens 155-158 20071162-5 2010 However, Raf/MEK/ERK inhibition by Sorafenib was not responsible for Sorafenib cell death or TRAIL sensitisation of endometrial cancer cells. Sorafenib 35-44 mitogen-activated protein kinase 1 Homo sapiens 17-20 20571072-7 2010 Response to sorafenib significantly correlated with extracellular signal-regulated kinase (ERK) downregulation and loss of Mcl-1 expression (P < 0.05). Sorafenib 12-21 mitogen-activated protein kinase 1 Homo sapiens 52-89 20571072-7 2010 Response to sorafenib significantly correlated with extracellular signal-regulated kinase (ERK) downregulation and loss of Mcl-1 expression (P < 0.05). Sorafenib 12-21 mitogen-activated protein kinase 1 Homo sapiens 91-94 20698202-10 2010 Sorafenib, a multikinase inhibitor, which can competitively inhibit RAF/MEK/ERK pathway, human vascular endothelial growth factor receptors (VEGFR2, VEGFR3) platelet-derived growth factor receptor beta (PDGFR), Flt3, and C-kit receptors, has been successfully applied for solid tumors such as renal cancer and hepatocellular carcinoma. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 76-79 20490331-0 2010 Sorafenib downregulates ERK/Akt and STAT3 survival pathways and induces apoptosis in a human neuroblastoma cell line. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 24-27 19638574-1 2009 Sorafenib is a multikinase inhibitor whose targets include B-RAF and C-RAF, both of which function in the extracellular signal-regulated kinase (ERK) signaling pathway but which also have distinct downstream targets. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 106-143 20109071-8 2010 Flow cytometry studies suggest that sorafenib inhibits ERK phosphorylation via c-KIT. Sorafenib 36-45 mitogen-activated protein kinase 1 Homo sapiens 55-58 19737956-2 2009 This study explored whether the efficacy of sorafenib can be improved by adding the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor CI-1040 to vertically block the Raf/MEK/ERK pathway. Sorafenib 44-53 mitogen-activated protein kinase 1 Homo sapiens 156-159 19737956-2 2009 This study explored whether the efficacy of sorafenib can be improved by adding the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor CI-1040 to vertically block the Raf/MEK/ERK pathway. Sorafenib 44-53 mitogen-activated protein kinase 1 Homo sapiens 224-227 19737956-8 2009 RESULTS: Combination of sorafenib and CI-1040 synergistically inhibited ERK phosphorylation and cell growth and induced apoptosis in both HCC cells and HUVECs. Sorafenib 24-33 mitogen-activated protein kinase 1 Homo sapiens 72-75 19737956-12 2009 CONCLUSION: The antitumor effects of sorafenib in HCC can be improved by vertical blockade of Raf/MEK/ERK signaling with CI-1040. Sorafenib 37-46 mitogen-activated protein kinase 1 Homo sapiens 102-105 19633425-0 2009 Sorafenib induces growth inhibition and apoptosis in human synovial sarcoma cells via inhibiting the RAF/MEK/ERK signaling pathway. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 109-112 19633425-7 2009 Sorafenib inhibited the phosphorylation of MEK and ERK, downregulated cyclin D1 and Rb levels, caused G(1) arrest and S phase decrease, and induced apoptosis as confirmed by flow cytometry and the TUNEL assay. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 51-54 20714148-5 2010 Sorafenib reduced c-Kit, ERK and VEGFR2 activation and on the other hand, gemcitabine inhibited Akt phosphorylation. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 25-28 19910069-6 2010 Sorafenib-induced elevation of the insulin-like growth factor receptor 1 (IGF-1R), phospho-c-Raf Ser338, phospho-MEK Ser217/221 and phospho-ERK Thr202/Tyr204 was attenuated by co-treating cells with anti-human IGF-1R antibody or over-expression of activated mutant p70S6K. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 140-143 19910069-7 2010 Pharmacological inhibition of the MEK/ERK pathway by AZD6244 enhanced the anti-tumor effect of sorafenib in both orthotopic and ectopic models of HCC. Sorafenib 95-104 mitogen-activated protein kinase 1 Homo sapiens 38-41 19783865-4 2009 Pharmacological experiments showed that the responses (ERK phosphorylation and AA release) induced by EGF and PMA were mediated by a mitogen-activated protein kinase/ERK kinase (MEK)-ERK-alpha-type cytosolic phospholipase A(2) (cPLA(2)alpha) pathway and that EGFR couples with the pathway in a manner insensitive to sorafenib, an inhibitor of B- and C-Raf, enzymes upstream of MEK. Sorafenib 316-325 mitogen-activated protein kinase 1 Homo sapiens 55-58 19783865-4 2009 Pharmacological experiments showed that the responses (ERK phosphorylation and AA release) induced by EGF and PMA were mediated by a mitogen-activated protein kinase/ERK kinase (MEK)-ERK-alpha-type cytosolic phospholipase A(2) (cPLA(2)alpha) pathway and that EGFR couples with the pathway in a manner insensitive to sorafenib, an inhibitor of B- and C-Raf, enzymes upstream of MEK. Sorafenib 316-325 mitogen-activated protein kinase 1 Homo sapiens 166-169 19783865-4 2009 Pharmacological experiments showed that the responses (ERK phosphorylation and AA release) induced by EGF and PMA were mediated by a mitogen-activated protein kinase/ERK kinase (MEK)-ERK-alpha-type cytosolic phospholipase A(2) (cPLA(2)alpha) pathway and that EGFR couples with the pathway in a manner insensitive to sorafenib, an inhibitor of B- and C-Raf, enzymes upstream of MEK. Sorafenib 316-325 mitogen-activated protein kinase 1 Homo sapiens 166-169 19698189-0 2009 Phosphorylated ERK is a potential predictor of sensitivity to sorafenib when treating hepatocellular carcinoma: evidence from an in vitro study. Sorafenib 62-71 mitogen-activated protein kinase 1 Homo sapiens 15-18 19698189-9 2009 Sorafenib inhibited ERK phosphorylation in a dose-dependent manner in all four cell lines at a concentration between 5 and 20 microM, but the degree of inhibition was significantly different according to their basal pERK expression level (P < 0.0001). Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 20-23 19698189-13 2009 After the basal ERK phosphorylation level in MHCC97-H cells was reduced with U0126, they were significantly less sensitive to sorafenib-mediated growth inhibition, with an IC50 of 17.31 +/- 1.62 microM versus 10.81 +/- 1.24 microM (P = 0.0281). Sorafenib 126-135 mitogen-activated protein kinase 1 Homo sapiens 16-19 19638574-1 2009 Sorafenib is a multikinase inhibitor whose targets include B-RAF and C-RAF, both of which function in the extracellular signal-regulated kinase (ERK) signaling pathway but which also have distinct downstream targets. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 145-148 19638574-4 2009 Sorafenib inhibited ERK phosphorylation in cells with wild-type KRAS but not in those with mutant KRAS. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 20-23 17178882-0 2006 Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 29-32 18808443-10 2008 Sorafenib blocks tumour cell proliferation by targeting Raf/MEK/ERK signalling and exerts an antiangiogenic effect by targeting VEGF receptors-2/3 and platelet derived growth factor receptor beta tyrosine kinases. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 64-67 18676833-0 2008 Down-regulation of myeloid cell leukemia-1 through inhibiting Erk/Pin 1 pathway by sorafenib facilitates chemosensitization in breast cancer. Sorafenib 83-92 mitogen-activated protein kinase 1 Homo sapiens 62-65 18676833-8 2008 Based on this newly identified mechanism of Mcl-1 stabilization, two strategies were used to overcome Mcl-1-mediated chemoresistance: inhibiting Erk by Sorafenib, an approved clinical anticancer drug, or knocking down Pin1 by using a SiRNA technique. Sorafenib 152-161 mitogen-activated protein kinase 1 Homo sapiens 145-148 18676833-9 2008 In conclusion, the current report not only unravels a novel mechanism to link Erk/Pin1 pathway and Mcl-1-mediated chemoresistance but also provides a plausible combination therapy, Taxol (Paclitaxel) plus Sorafenib, which was shown to be effective in killing breast cancer cells. Sorafenib 205-214 mitogen-activated protein kinase 1 Homo sapiens 78-81 18200035-3 2008 Our studies demonstrated that sorafenib significantly inhibited the phosphorylation levels of Raf downstream target proteins MEK1/2 and Erk, induced apoptosis and inhibited colony formation in AML cell lines and in primary AML samples. Sorafenib 30-39 mitogen-activated protein kinase 1 Homo sapiens 136-139 18200035-6 2008 Importantly, sorafenib also modulated phospho-Erk, Bim, Bax and Mcl-1 levels in samples procured from patients in an ongoing Phase I clinical trial of sorafenib in AML. Sorafenib 13-22 mitogen-activated protein kinase 1 Homo sapiens 46-49 17655513-6 2007 Sorafenib and sunitinib are novel therapies that target growth factor receptors known to be activated by the hypoxia-inducible factor and the Ras-Raf/MEK/ERK pathways. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 154-157 17178882-4 2006 Sorafenib inhibited the phosphorylation of MEK and ERK and down-regulated cyclin D1 levels in these two cell lines. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 51-54 17178882-5 2006 Sorafenib also reduced the phosphorylation level of eIF4E and down-regulated the antiapoptotic protein Mcl-1 in a MEK/ERK-independent manner. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 118-121 17178882-6 2006 Consistent with the effects on both MEK/ERK-dependent and MEK/ERK-independent signaling pathways, sorafenib inhibited proliferation and induced apoptosis in both HCC cell lines. Sorafenib 98-107 mitogen-activated protein kinase 1 Homo sapiens 40-43 17178882-6 2006 Consistent with the effects on both MEK/ERK-dependent and MEK/ERK-independent signaling pathways, sorafenib inhibited proliferation and induced apoptosis in both HCC cell lines. Sorafenib 98-107 mitogen-activated protein kinase 1 Homo sapiens 62-65 17178882-10 2006 In mechanism of action studies, sorafenib inhibited the phosphorylation of both ERK and eIF4E, reduced the microvessel area (assessed by CD34 immunohistochemistry), and induced tumor cell apoptosis (assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling) in PLC/PRF/5 tumor xenografts. Sorafenib 32-41 mitogen-activated protein kinase 1 Homo sapiens 80-83 16498671-5 2006 RESULTS: At all dose levels of BAY 43-9006 used to treat solid tumor patients, ERK could be activated by PMA in peripheral T-cells and we were not able to show inhibition of raf kinase. Sorafenib 31-42 mitogen-activated protein kinase 1 Homo sapiens 79-82 17071608-0 2006 Inhibition of tumor endothelial ERK activation, angiogenesis, and tumor growth by sorafenib (BAY43-9006). Sorafenib 82-91 mitogen-activated protein kinase 1 Homo sapiens 32-35 17071608-0 2006 Inhibition of tumor endothelial ERK activation, angiogenesis, and tumor growth by sorafenib (BAY43-9006). Sorafenib 93-103 mitogen-activated protein kinase 1 Homo sapiens 32-35 17071608-6 2006 Extracellular signal-regulated kinase (ERK) activation in tumor endothelial cells, revealed by immunostaining for phospho-ERK and CD34, was inhibited, whereas AKT activation, revealed by phospho-AKT immunostaining, was not inhibited in K1735 and two other tumor types treated with sorafenib. Sorafenib 281-290 mitogen-activated protein kinase 1 Homo sapiens 0-37 17071608-6 2006 Extracellular signal-regulated kinase (ERK) activation in tumor endothelial cells, revealed by immunostaining for phospho-ERK and CD34, was inhibited, whereas AKT activation, revealed by phospho-AKT immunostaining, was not inhibited in K1735 and two other tumor types treated with sorafenib. Sorafenib 281-290 mitogen-activated protein kinase 1 Homo sapiens 39-42 17071608-8 2006 These data indicate that sorafenib"s anti-tumor efficacy may be primarily attributable to angiogenesis inhibition resulting from its inhibition of Raf-MEK-ERK signaling in endothelial cells. Sorafenib 25-34 mitogen-activated protein kinase 1 Homo sapiens 155-158 17071608-9 2006 Assessing endothelial cell ERK activation in tumor bio-psies may provide mechanistic insights into and allow monitoring of sorafenib"s activity in patients in clinical trials. Sorafenib 123-132 mitogen-activated protein kinase 1 Homo sapiens 27-30 16498671-1 2006 BACKGROUND: We previously reported a flow cytometry technique to monitor pharmacodynamic effects of the raf kinase inhibitor BAY 43-9006 based on the ability of phorbol ester (PMA) to phosphorylate extracellular-regulated kinase (ERK) in peripheral blood (Chow et al., Cytometry 2001;46:72-78). Sorafenib 125-136 mitogen-activated protein kinase 1 Homo sapiens 198-228 16498671-1 2006 BACKGROUND: We previously reported a flow cytometry technique to monitor pharmacodynamic effects of the raf kinase inhibitor BAY 43-9006 based on the ability of phorbol ester (PMA) to phosphorylate extracellular-regulated kinase (ERK) in peripheral blood (Chow et al., Cytometry 2001;46:72-78). Sorafenib 125-136 mitogen-activated protein kinase 1 Homo sapiens 230-233 16498671-8 2006 Furthermore, normal donor CD34+ve stem cells were much more sensitive to BAY 43-9006 when ERK was activated by SCF, compared to PMA. Sorafenib 73-84 mitogen-activated protein kinase 1 Homo sapiens 90-93 16452220-4 2006 BAY 43-9006 (sorafenib) down-modulates the levels of Bcl-2 and Bcl-X(L) in a MAPK-independent manner in A2058 and SKMEL5 melanoma cells but not in the more resistant A375 cells. Sorafenib 0-11 mitogen-activated protein kinase 1 Homo sapiens 77-81 16452220-4 2006 BAY 43-9006 (sorafenib) down-modulates the levels of Bcl-2 and Bcl-X(L) in a MAPK-independent manner in A2058 and SKMEL5 melanoma cells but not in the more resistant A375 cells. Sorafenib 13-22 mitogen-activated protein kinase 1 Homo sapiens 77-81 15613696-5 2005 The effect of BAY 43-9006 on phorbol myristate acetate-stimulated ERK phosphorylation in peripheral blood lymphocytes was studied using flow cytometry. Sorafenib 14-25 mitogen-activated protein kinase 1 Homo sapiens 66-69 15850570-5 2005 Activation of MEK-ERK by peroxynitrite was related to the upstream activation of Raf-1 kinase, as ERK and MEK phosphorylation were prevented by the Raf-1 inhibitor BAY43-9006. Sorafenib 164-174 mitogen-activated protein kinase 1 Homo sapiens 18-21 15850570-5 2005 Activation of MEK-ERK by peroxynitrite was related to the upstream activation of Raf-1 kinase, as ERK and MEK phosphorylation were prevented by the Raf-1 inhibitor BAY43-9006. Sorafenib 164-174 mitogen-activated protein kinase 1 Homo sapiens 98-101 15466206-0 2004 BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Sorafenib 0-11 mitogen-activated protein kinase 1 Homo sapiens 84-87 15598034-0 2004 Correlation of ERK-phosphorylation and toxicities in patients treated with the Raf kinase inhibitor BAY 43-9006. Sorafenib 100-111 mitogen-activated protein kinase 1 Homo sapiens 15-18 15466206-2 2004 The novel bi-aryl urea BAY 43-9006 is a potent inhibitor of Raf-1, a member of the RAF/MEK/ERK signaling pathway. Sorafenib 23-34 mitogen-activated protein kinase 1 Homo sapiens 91-94 33803354-5 2021 The MAPK14-ATF2-axis represents a collateral pathway ensuring persisting ERK-activation in the presence of sorafenib-mediated RAF-inhibition. Sorafenib 107-116 mitogen-activated protein kinase 1 Homo sapiens 73-76 15208680-5 2004 B-RAF depletion inhibits DNA synthesis and induces apoptosis in three melanoma cell lines and we show that the RAF inhibitor BAY43-9006 also blocks ERK activity, inhibits DNA synthesis and induces cell death in these cells. Sorafenib 125-135 mitogen-activated protein kinase 1 Homo sapiens 148-151 34377232-0 2021 Phenformin synergistically sensitizes liver cancer cells to sorafenib by downregulating CRAF/ERK and PI3K/AKT/mTOR pathways. Sorafenib 60-69 mitogen-activated protein kinase 1 Homo sapiens 93-96 34377232-7 2021 Phenformin further bolstered the ability of sorafenib to inhibit the CRAF/ERK and PI3K/AKT/mTOR pathways. Sorafenib 44-53 mitogen-activated protein kinase 1 Homo sapiens 74-77 34377232-9 2021 Sorafenib and phenformin can synergistically suppress CRAF/ERK and PI3K/AKT/mTOR pathway activation in HCC cells, and may thus represent a promising approach to treating this deadly cancer. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 59-62 35478108-6 2022 CONCLUSION: Amentoflavone may sensitize OS to sorafenib treatment by inducing intrinsic and extrinsic apoptosis and inhibiting ERK/NF-kappaB signaling transduction. Sorafenib 46-55 mitogen-activated protein kinase 1 Homo sapiens 127-130 34069373-9 2021 In Huh7 and Hep3B cells, FGL1 knockdown significantly increased colony formation by 61% (p = 0.0013) and 99% (p = 0.0002), respectively, compared to that in controls and abolished sorafenib-induced suppression of colony formation, possibly by modulating ERK and autophagy signals. Sorafenib 180-189 mitogen-activated protein kinase 1 Homo sapiens 254-257 35121728-8 2022 Moreover, PGK1 promotes sorafenib resistance via increasing CXCR4-mediated ERK phosphorylation. Sorafenib 24-33 mitogen-activated protein kinase 1 Homo sapiens 75-78 35196602-0 2022 PDE4D targeting enhances anti-tumor effects of sorafenib in clear cell renal cell carcinoma and attenuates MAPK/ERK signaling in a CRAF-dependent manner. Sorafenib 47-56 mitogen-activated protein kinase 1 Homo sapiens 112-115 35121728-9 2022 In conclusion, PGK1-invovled metabolic reprogramming and activation of CXCR4/ERK signaling pathway contributes to tumor growth and sorafenib resistance of KIRC. Sorafenib 131-140 mitogen-activated protein kinase 1 Homo sapiens 77-80 35142429-5 2022 Sorafenib showed obvious downregulation of RAF/MEK/ERK signaling pathways and dose-dependent anti-proliferative effects only on s003 parent cell line, which showed the lowest expression of NANOG among all tested cell lines except one downregulated NANOG with upregulated POU5F1 s020 subgroup. Sorafenib 0-9 mitogen-activated protein kinase 1 Homo sapiens 51-54