AIM: To identify the prognostic value of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections in patients with intrahepatic cholangiocarcinoma.METHODS: A search was performed for relevant publications in Pub M...AIM: To identify the prognostic value of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections in patients with intrahepatic cholangiocarcinoma.METHODS: A search was performed for relevant publications in Pub Med, EMBASE and Web of Science databases. The pooled effects were calculated from the available information to identify the relationship between HBV or HCV infection and the prognosis and clinicopathological features. The χ2 and I2 tests were used to evaluate heterogeneity between studies. Pooled hazard ratios(HRs) with 95% confidence intervals(CIs) were calculated by a fixed-effects model, if no heterogeneity existed. If there was heterogeneity, a random-effects model was applied.RESULTS: In total, 14 studies involving 2842 cases were enrolled in this meta-analysis. The patients with HBV infection presented better overall and diseasefree survival, and the pooled HRs were significant at 0.76(95%CI: 0.70-0.83) and 0.78(95%CI: 0.66-0.94), respectively. Additionally, our study revealed that HCV infection was correlated with shortened overall survival in comparison with the control group(HR = 2.64, 95%CI: 1.77-3.93). We also found that HBV infection occurred more frequently in male patients [odds ratio(OR) = 1.91, 95%CI: 1.06-3.44] and was correlated with higher levels of serum aspartate transaminase(AST) and alpha-fetoprotein(AFP)(OR = 1.93, 95%CI: 1.11-3.35; OR = 3.86, 95%CI: 2.58-5.78) and a lower level of serum carbohydrate antigen 19-9(CA19-9)(OR = 0.47, 95%CI: 0.34-0.65). Moreover, HBV infection was associated with cirrhosis(OR = 6.44, 95%CI: 4.33-9.56), a higher proportion of capsule formation(OR = 6.04, 95%CI: 3.56-10.26), and a lower rate of lymph node metastasis(OR = 0.39, 95%CI: 0.25-0.58). No significant publication bias was seen in any of the enrolled studies.CONCLUSION: HBV infection may indicate a favorable prognosis in patients with intrahepatic cholangiocarcinoma, while HCV infection suggests a poor prognosis.展开更多
Background The efficacy of immune checkpoint inhibitors(ICIs),such as programmed cell death protein-1(PD-1)or its ligand 1(PD-L1)antibody,in hepatocellular carcinoma(HCC)is limited,and it is recommended that they be c...Background The efficacy of immune checkpoint inhibitors(ICIs),such as programmed cell death protein-1(PD-1)or its ligand 1(PD-L1)antibody,in hepatocellular carcinoma(HCC)is limited,and it is recommended that they be combined with other therapies.We evaluated the combination of pegylated interferon-α(Peg-IFNα)with PD-1 blockade in HCC mouse models.Methods We analyzed the effects of Peg-IFNαon tumor-infiltrating immune cells and PD-1 expression in the HCC immune microenvironment and examined the underlying mechanism of its unique effect on the PD-1 pathway.The in vivo efficacy of anti-PD-1 and Peg-IFNαwas evaluated in both subcutaneous and orthotopic mouse models of HCC.Results The combination of Peg-IFNαwith PD-1 blockade dramatically enhanced T-cell infiltration,improved the efficacy of PD-1 antibody and prolonged mouse survival compared with PD-1 antibody monotherapy.Mechanistically,Peg-IFNαcould recruit cytotoxic CD8+T cells to infiltrate the HCC microenvironment by inducing tumor cells to secrete the chemokine CCL4.Nevertheless,the HCC microenvironment quickly overcame the immune responses by upregulating PD-1 expression in CD8+T cells via the IFNα-IFNAR1-JAK1-STAT3 signaling pathway.The combination of PD-1 blockade with Peg-IFNαcould restore the cytotoxic capacity of CD8+T cells and exerted a significant synergistic effect on HCC.Conclusion These results indicate that in addition to initiating the antitumor immune response itself,Peg-IFNαcan also generate a microenvironment favoring PD-1 blockade.Thus,the combination of Peg-IFNαand PD-1 blockade can be a promising strategy for HCC.展开更多
Objective: The expression of B-cell lymphoma 2(Bcl-2) seems to be influenced by the endocrine environment. Numerous reports demonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With...Objective: The expression of B-cell lymphoma 2(Bcl-2) seems to be influenced by the endocrine environment. Numerous reports demonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With the exception of estrogen-related tumors, androgen-related tumors have shown their characteristics in Bcl-2 expression. In this study, the status of Bcl-2 expression in male hepatocellular carcinoma(HCC) patients was examined to verify the high incidence of HCC in males.Methods: Tumor tissue microarray was used to examine Bcl-2 expression levels in 374 HCC cases including 306 males and 68 females. Kaplan-Meier method, log-rank test, and Cox proportional hazards model were applied to investigate the predictive value of Bcl-2 in HCC patients.Results: Immunohistochemistry analysis showed that male patients with higher Bcl-2 levels had significantly longer median survival time and recurrence time than those with lower levels. However, no significant differences in outcomes were found between different Bcl-2 levels in female patients. When the male patients were stratified into several age points, the level of Bcl-2expression showed poorer predictive efficiency in the 45–49 and 55–60 age groups in andropause-age patients compared with other age groups. Bcl-2 was an independent prognostic factor for both overall survival(P < 0.0001) and recurrence time(P =0.0001) in male patients. After excluding male patients in the 45–60 age group, the predictive efficiency was enhanced(n = 147,OS, P = 0.0002, TTR, P < 0.0001).Conclusions: Bcl-2 expression is an independent predictor of survival and recurrence in male HCC. Bcl-2 levels may also be regulated by androgens or androgen receptors in male HCC patients. Bcl-2 levels change and exhibit poor predictive efficiency when androgen levels vary dramatically(andropause age).展开更多
基金Supported by National Key Projects for Infectious Diseases of ChinaNo.2012ZX10002-012+3 种基金National Key Basic Research Program of ChinaNo.2013CB910500NSFC Program of International Cooperation and ExchangesNo.81120108016
文摘AIM: To identify the prognostic value of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections in patients with intrahepatic cholangiocarcinoma.METHODS: A search was performed for relevant publications in Pub Med, EMBASE and Web of Science databases. The pooled effects were calculated from the available information to identify the relationship between HBV or HCV infection and the prognosis and clinicopathological features. The χ2 and I2 tests were used to evaluate heterogeneity between studies. Pooled hazard ratios(HRs) with 95% confidence intervals(CIs) were calculated by a fixed-effects model, if no heterogeneity existed. If there was heterogeneity, a random-effects model was applied.RESULTS: In total, 14 studies involving 2842 cases were enrolled in this meta-analysis. The patients with HBV infection presented better overall and diseasefree survival, and the pooled HRs were significant at 0.76(95%CI: 0.70-0.83) and 0.78(95%CI: 0.66-0.94), respectively. Additionally, our study revealed that HCV infection was correlated with shortened overall survival in comparison with the control group(HR = 2.64, 95%CI: 1.77-3.93). We also found that HBV infection occurred more frequently in male patients [odds ratio(OR) = 1.91, 95%CI: 1.06-3.44] and was correlated with higher levels of serum aspartate transaminase(AST) and alpha-fetoprotein(AFP)(OR = 1.93, 95%CI: 1.11-3.35; OR = 3.86, 95%CI: 2.58-5.78) and a lower level of serum carbohydrate antigen 19-9(CA19-9)(OR = 0.47, 95%CI: 0.34-0.65). Moreover, HBV infection was associated with cirrhosis(OR = 6.44, 95%CI: 4.33-9.56), a higher proportion of capsule formation(OR = 6.04, 95%CI: 3.56-10.26), and a lower rate of lymph node metastasis(OR = 0.39, 95%CI: 0.25-0.58). No significant publication bias was seen in any of the enrolled studies.CONCLUSION: HBV infection may indicate a favorable prognosis in patients with intrahepatic cholangiocarcinoma, while HCV infection suggests a poor prognosis.
基金This work was supported by the National Natural Science Foundation of China(81902390 and 81902952)the National Key Research and Development Program of China(2017YFC1308604).
文摘Background The efficacy of immune checkpoint inhibitors(ICIs),such as programmed cell death protein-1(PD-1)or its ligand 1(PD-L1)antibody,in hepatocellular carcinoma(HCC)is limited,and it is recommended that they be combined with other therapies.We evaluated the combination of pegylated interferon-α(Peg-IFNα)with PD-1 blockade in HCC mouse models.Methods We analyzed the effects of Peg-IFNαon tumor-infiltrating immune cells and PD-1 expression in the HCC immune microenvironment and examined the underlying mechanism of its unique effect on the PD-1 pathway.The in vivo efficacy of anti-PD-1 and Peg-IFNαwas evaluated in both subcutaneous and orthotopic mouse models of HCC.Results The combination of Peg-IFNαwith PD-1 blockade dramatically enhanced T-cell infiltration,improved the efficacy of PD-1 antibody and prolonged mouse survival compared with PD-1 antibody monotherapy.Mechanistically,Peg-IFNαcould recruit cytotoxic CD8+T cells to infiltrate the HCC microenvironment by inducing tumor cells to secrete the chemokine CCL4.Nevertheless,the HCC microenvironment quickly overcame the immune responses by upregulating PD-1 expression in CD8+T cells via the IFNα-IFNAR1-JAK1-STAT3 signaling pathway.The combination of PD-1 blockade with Peg-IFNαcould restore the cytotoxic capacity of CD8+T cells and exerted a significant synergistic effect on HCC.Conclusion These results indicate that in addition to initiating the antitumor immune response itself,Peg-IFNαcan also generate a microenvironment favoring PD-1 blockade.Thus,the combination of Peg-IFNαand PD-1 blockade can be a promising strategy for HCC.
文摘Objective: The expression of B-cell lymphoma 2(Bcl-2) seems to be influenced by the endocrine environment. Numerous reports demonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With the exception of estrogen-related tumors, androgen-related tumors have shown their characteristics in Bcl-2 expression. In this study, the status of Bcl-2 expression in male hepatocellular carcinoma(HCC) patients was examined to verify the high incidence of HCC in males.Methods: Tumor tissue microarray was used to examine Bcl-2 expression levels in 374 HCC cases including 306 males and 68 females. Kaplan-Meier method, log-rank test, and Cox proportional hazards model were applied to investigate the predictive value of Bcl-2 in HCC patients.Results: Immunohistochemistry analysis showed that male patients with higher Bcl-2 levels had significantly longer median survival time and recurrence time than those with lower levels. However, no significant differences in outcomes were found between different Bcl-2 levels in female patients. When the male patients were stratified into several age points, the level of Bcl-2expression showed poorer predictive efficiency in the 45–49 and 55–60 age groups in andropause-age patients compared with other age groups. Bcl-2 was an independent prognostic factor for both overall survival(P < 0.0001) and recurrence time(P =0.0001) in male patients. After excluding male patients in the 45–60 age group, the predictive efficiency was enhanced(n = 147,OS, P = 0.0002, TTR, P < 0.0001).Conclusions: Bcl-2 expression is an independent predictor of survival and recurrence in male HCC. Bcl-2 levels may also be regulated by androgens or androgen receptors in male HCC patients. Bcl-2 levels change and exhibit poor predictive efficiency when androgen levels vary dramatically(andropause age).
