| 1 | Indicators of sorafenib efficacy in patients with advanced hepatocellular carcinoma显示文摘AIM:To determine significant indicators for the efficacy of sorafenib in patients with advanced hepatocellular carcinoma(HCC).METHODS:A total of 46 patients with Barcelona Clinic Liver Cancer stage C who received sorafenib for more than 30 d at the Iizuka Hospital from June 2009 to December 2012 were enrolled in this study.Multivariate and univariate analyses were performed to evaluate the associations of hepatic function according to Child-Pugh grade,location and size of the largest tumor and adverse events of sorafenib treatment,such as hand-foot syndrome(HFS),hypertension,diarrhea,and alopecia,with the efficacy of treatment,as measured by overall survival(OS)and time to progression(TTP).RESULTS:Patients included 39 men and 7 women whose ages ranged from 48 to 85 years(70.6±9.6years).HCC was classified according to etiology as follows:hepatitis C virus(n=26),hepatitis B virus(n=9),and other(n=11).Liver function in patients was categorized as Child-Pugh grade A(n=30)or B(n=16).Tumors were categorized by size[<5 cm(n=33)or>5 cm(n=13)]and the location of the largest tumor was used to categorize patients with intrahepatic(n=28)or extrahepatic(n=18)HCC.HFS,hypertension,diarrhea,and alopecia were present in22(47.8%),19(41.3%),15(32.6%)and 7 patients(15.2%),respectively.The median OS of all patients was 373 d and the median TTP was 112 d.The etiology of HCC did not correlate with the median OS and TPP.The median OS of patients with tumors<5 cm was significantly longer than those with larger tumors(496 vs 245 d;HR=0.19,95%CI:0.07-0.48;P<0.01).According to the results of a multivariate analysis,the size of the largest tumor affected OS(HR=0.22,95%CI:0.08-0.59;P<0.01).The median TTP was significantly longer in patients with extrahepatic compared to intrahepatic major HCC(224 vs 98 d;HR=0.32;95%CI:0.14-0.67;P<0.01).The median TTP of patients with HFS was significantly longer than those without it(195 d vs 83 d;HR=0.41,95%CI:0.20-0.82;P<0.05),and the median TTP was significantly longer in patients with hypertension(195 d vs84 d;HR=0.43,95%CI:0.21-0.84;P<0.05).According to the results of the multivariate analysis,extrahepatic major HCC(HR=0.36,P<0.01)and HFS(HR=0.44,P<0.05)prolonged TTP.CONCLUSION:Extrahepatic major HCC and HFS are associated with prolonged TTP and are useful indicators for judging the efficacy of sorafenib treatment. | Masayoshi Yada Akihide Masumoto Kenta Motomura Hirotaka Tajiri Yusuke Morita Hideo Suzuki Takeshi Senju Toshimasa Koyanagi | 2014 | World Journal of Gastroenterology2014，20，35： | 7 |
| 2 | Distinct antifibrogenic effects of erlotinib,sunitinib and sorafenib on rat pancreatic stellate cells显示文摘AIM:To study if three clinically available small molecule kinase inhibitors(SMI),erlotinib,sunitinib and sorafenib,exert antifibrogenic effects on pancreatic stellate cells(PSC)and analyze the basis of their action.METHODS:Cultured rat PSC were exposed to SMI.Cell proliferation and viability were assessed employing 5-bromo-2’-deoxyuridine incorporation assay and flow cytometry,respectively.2-Deoxy-2-[18F]fluoroglucose(18F-FDG)uptake was measured to study metabolic activity.Exhibition of the myofibroblastic PSC phenotype was monitored by immunofluorescence analysis ofα-smooth muscle actin(α-SMA)expression.Levels of mRNA were determined by real-time PCR,while protein expression and phosphorylation were analyzed by immunoblotting.Transforming growth factor-β1 (TGF-β1)levels in culture supernatants were quantified by ELISA.RESULTS:All three SMI inhibited cell proliferation and18F-FDG uptake in a dose-dependent manner and without significant cytotoxic effects.Furthermore,additive effects of the drugs were observed.Immunoblot analysis showed that sorafenib and sunitib,but not erlotinib,efficiently blocked activation of the AKT pathway,while all three drugs displayed little effect on phosphorylation of ERK1/2.Cells treated with sorafenib or sunitinib expressed less interleukin-6 mRNA as well as less collagen type 1 mRNA and protein.Sorafenib was the only drug that also upregulated the expression of matrix metalloproteinase-2 and reduced the secretion of TGF-β1 protein.All three drugs showed insignificant or discordant effects on the mRNA and protein levels ofα-SMA.CONCLUSION:The tested SMI,especially sorafenib,exert inhibitory effects on activated PSC,which should be further evaluated in preclinical studies. | Anne Elsner Falko Lange Brit Fitzner Martin Heuschkel Bernd Joachim Krause Robert Jaster | 2014 | World Journal of Gastroenterology2014，20，24： | 2 |
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