Effect and safety of sorafenib in patients with intermediate hepatocellular carcinoma who received transarterial chemoembolization: A retrospective comparative study

AIM To evaluate the safety and efficacy of sorafenib plus transarterial chemoembolization(TACE) treatment for intermediate hepatocellular carcinoma(HCC).METHODS Sixty-seven patients with intermediate-stage [Barcelona Clinic liver cancer stage B(BCLC-B)] HCC who were treated with sorafenib plus TACE or TACE alone between 2009 and 2011 were included in the study. Follow-up was until 2014 or patient death. Two groups were defined in the experiment: The experimental group, treated with sorafenib plus TACE, and the control group, treated with standard TACE alone.RESULTS The Kaplan-Meier survival analysis showed that the median overall survival(m OS) of the experimental group was 35.2 mo, while that of the control group was 22.0 mo(P < 0.05). Sorafenib plus TACE showed higher incidence rates of rash, hand-foot syndrome(HFS), and hypertension(P < 0.05) than TACE treatment alone.CONCLUSION Sorafenib plus TACE treatment for BCLC-B HCC significantly prolonged the m OS of patients compared to TACE treatment alone. The most common toxicities with sorafenib were rash(31.6%), HFS(39.5%) and hypertension(31.6%), but there were no intolerable adverse events. The Cox multivariate analysis showed that the survival of patients with BCLC-B HCC depended on the Child-Pugh classification, tumor diameter, and treatment with sorafenib plus TACE compared to TACE alone.

Spontaneous running wheel improves neuroprotection efficacy of ischemic postconditioning in mice following ischemia/reperfusion injury

Ischemic postconditioning(IP)has been shown to provide protection for ischemia/reperfusion(IR)injury,but its efficacy is limited.In this study we hypothesized that spontaneous running wheel(RW)could improve neuroprotection efficacy of IP for IR.We established mouse models of IR and showed that compared to Sham group,IR group had obvious brain infract and neurological dysfunction.In IR+IP group,brain infract and neurological dysfunction improved compared to IR group.However,in IR+IP+RW group brain infract and neurological dysfunction improved much better.TUNEL assay showed that IP but not RW significantly reduced the number of apoptotic cells after IR.However,the number of apoptotic cells was significantly reduced in RW+IP group.In addition,the levels of pro-apoptotic factors increased in IR group but significantly reduced in IR+IP+RW group,while the levels of antiapoptotic factors decreased in IR group but significantly increased in IR+IP+RW group.Moreover,in IR+IP+RW group,MDA level was further decreased and SOD level was further increased compared to IR+IP group.Finally,both PI3K inhibitor and STAT3 inhibitor significantly worsened brain infract and neurological dysfunction and promoted apoptosis in IR mice.In conclusion,RW combined with IP reduces brain infract and neurological dysfunction in mice after IR,and this is associated with enhanced anti-apoptotic and anti-oxidant benefits via the activation of PI3K and STAT3 pathways.