The current management therapies for hepatocellular carcinoma(HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a "difficult to treat" cancer because HCC typic...The current management therapies for hepatocellular carcinoma(HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a "difficult to treat" cancer because HCC typically occurs in advanced liver disease or hepatic cirrhosis. The progression of multistep and multicentric HCC hampers the prevention of the recurrence of HCC. Many HCC patients are treated with surgical resection and radiofrequency ablation(RFA), although these modalities should be considered in only selected cases with a certain HCC number and size. Although there is a shortage of grafts, liver transplantation has the highest survival rates for HCC. Several modalities are salvage treatments; however, intensive care in combination with other modalities or in combination with surgical resection or RFA might offer a better prognosis. Sorafenib is useful for patients with advanced HCC. In the near future, HCC treatment will include stronger molecular targeted drugs, which will have greater potency and fewer adverse events. Further studies will be ongoing.展开更多
Similar to other cancers, a multistep process of carcinogenesis is observed in hepatocellular carcinoma(HCC). Although the mechanisms underlying the development of HCC have been investigated in terms of oncology, viro...Similar to other cancers, a multistep process of carcinogenesis is observed in hepatocellular carcinoma(HCC). Although the mechanisms underlying the development of HCC have been investigated in terms of oncology, virology, and stem cell biology, the whole picture of hepatocarcinogenesis remains to be elucidated. Recent progress in molecular biology has provided clues to the underlying cause of various diseases. In particular, sequencing technologies, such as whole genome and exome sequencing analyses, have made an impact on genomic research on a variety of cancers including HCC. Comprehensive genomic analyses have detected numerous abnormal genetic alterations, such as mutations and copy number alterations. Based on these findings, signaling pathways and cancer-related genes involved in hepatocarcinogenesis could be analyzed in detail. Simultaneously, a number of novel biomarkers, both from tissue and blood samples, have been recently reported. These biomarkers have been successfully applied to early diagnosis and prognostic prediction of patients with HCC. In this review, we focus on the recent developments in molecular cancer research on HCC and explain the biological features and novel biomarkers.展开更多
AIM: To elucidate anticancer effects of transcatheter arterial infusion chemotherapy(TAI) in patients with hepatocellular carcinoma(HCC). METHODS: Data from a total of 95 patients with HCC who received TAI were analyz...AIM: To elucidate anticancer effects of transcatheter arterial infusion chemotherapy(TAI) in patients with hepatocellular carcinoma(HCC). METHODS: Data from a total of 95 patients with HCC who received TAI were analyzed retrospectively. The efficacy of TAI was evaluated according to the Response Evaluation Criteria in Cancer of the Liver. Overall survival was calculated from the date of initial treatment to the date of death or last follow-up. Survival curves were calculated by the Kaplan-Meier method, and differences in survival were evaluated by the log rank test. Clinical variables that were identified as statistically different by a univariate analysis were included into the Cox proportional hazard regression model for multivariate analysis. A prognostic index based on the regression coefficients derived from variables identified by the multivariate analysis was constructed. Stratification of the patients was conducted using this prognostic index. RESULTS: The patient group was comprised of 76 men and 19 women with an average age of 68 years(range: 37-82 years). Six patients(6.3%) showedcomplete response and 18 patients(18.9%) showed partial response, for an overall response rate of 25.2%. The median overall survival was 27.6 mo, and the proportions of survivors at 1, 2, and 5 years were 67.4%, 54.0%, and 17.4%, respectively. Multivariate analysis demonstrated that no prior transcatheter arterial chemoembolization, lactate dehydrogenase < 230 IU/L, and performance status of 0 were the independent favorable prognostic factors. The development of a 0-3-point prognostic score index was based on the sum of these three prognostic factors. Subsequently, the patients were categorized into three groups: those with a good(prognostic index = 0-1; n = 54), intermediate(prognostic index = 2; n = 26), or poor(prognostic index = 3; n = 15) prognosis. The median survival times in these three groups were 41.0, 21.2, and 6.8 mo, respectively(P < 0.01). CONCLUSION: Our simple prognostic index may be helpful for management of patients in determining treatment strategies for advanced HCC in the era of molecularly targeted therapy.展开更多
BACKGROUND Hepatitis B virus(HBV)is a major cause of hepatocellular carcinoma(HCC).HBV DNA can get integrated into the hepatocyte genome to promote carcinogenesis.However,the precise mechanism by which the integrated ...BACKGROUND Hepatitis B virus(HBV)is a major cause of hepatocellular carcinoma(HCC).HBV DNA can get integrated into the hepatocyte genome to promote carcinogenesis.However,the precise mechanism by which the integrated HBV genome promotes HCC has not been elucidated.AIM To analyze the features of HBV integration in HCC using a new reference database and integration detection method.METHODS Published data,consisting of 426 Liver tumor samples and 426 paired adjacent non-tumor samples,were re-analyzed to identify the integration sites.Genome Reference Consortium Human Build 38(GRCh38)and Telomere-to-Telomere Consortium CHM13(T2T-CHM13(v2.0))were used as the human reference genomes.In contrast,human genome 19(hg19)was used in the original study.In addition,GRIDSS VIRUSBreakend was used to detect HBV integration sites,whereas high-throughput viral integration detection(HIVID)was applied in the original study(HIVID-hg19).RESULTS A total of 5361 integration sites were detected using T2T-CHM13.In the tumor samples,integration hotspots in the cancer driver genes,such as TERT and KMT2B,were consistent with those in the original study.GRIDSS VIRUSBreakend detected integrations in more samples than by HIVID-hg19.Enrichment of integration was observed at chromosome 11q13.3,including the CCND1 pro-moter,in tumor samples.Recurrent integration sites were observed in mitochondrial genes.CONCLUSION GRIDSS VIRUSBreakend using T2T-CHM13 is accurate and sensitive in detecting HBV integration.Re-analysis provides new insights into the regions of HBV integration and their potential roles in HCC development.展开更多
文摘The current management therapies for hepatocellular carcinoma(HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a "difficult to treat" cancer because HCC typically occurs in advanced liver disease or hepatic cirrhosis. The progression of multistep and multicentric HCC hampers the prevention of the recurrence of HCC. Many HCC patients are treated with surgical resection and radiofrequency ablation(RFA), although these modalities should be considered in only selected cases with a certain HCC number and size. Although there is a shortage of grafts, liver transplantation has the highest survival rates for HCC. Several modalities are salvage treatments; however, intensive care in combination with other modalities or in combination with surgical resection or RFA might offer a better prognosis. Sorafenib is useful for patients with advanced HCC. In the near future, HCC treatment will include stronger molecular targeted drugs, which will have greater potency and fewer adverse events. Further studies will be ongoing.
文摘Similar to other cancers, a multistep process of carcinogenesis is observed in hepatocellular carcinoma(HCC). Although the mechanisms underlying the development of HCC have been investigated in terms of oncology, virology, and stem cell biology, the whole picture of hepatocarcinogenesis remains to be elucidated. Recent progress in molecular biology has provided clues to the underlying cause of various diseases. In particular, sequencing technologies, such as whole genome and exome sequencing analyses, have made an impact on genomic research on a variety of cancers including HCC. Comprehensive genomic analyses have detected numerous abnormal genetic alterations, such as mutations and copy number alterations. Based on these findings, signaling pathways and cancer-related genes involved in hepatocarcinogenesis could be analyzed in detail. Simultaneously, a number of novel biomarkers, both from tissue and blood samples, have been recently reported. These biomarkers have been successfully applied to early diagnosis and prognostic prediction of patients with HCC. In this review, we focus on the recent developments in molecular cancer research on HCC and explain the biological features and novel biomarkers.
文摘AIM: To elucidate anticancer effects of transcatheter arterial infusion chemotherapy(TAI) in patients with hepatocellular carcinoma(HCC). METHODS: Data from a total of 95 patients with HCC who received TAI were analyzed retrospectively. The efficacy of TAI was evaluated according to the Response Evaluation Criteria in Cancer of the Liver. Overall survival was calculated from the date of initial treatment to the date of death or last follow-up. Survival curves were calculated by the Kaplan-Meier method, and differences in survival were evaluated by the log rank test. Clinical variables that were identified as statistically different by a univariate analysis were included into the Cox proportional hazard regression model for multivariate analysis. A prognostic index based on the regression coefficients derived from variables identified by the multivariate analysis was constructed. Stratification of the patients was conducted using this prognostic index. RESULTS: The patient group was comprised of 76 men and 19 women with an average age of 68 years(range: 37-82 years). Six patients(6.3%) showedcomplete response and 18 patients(18.9%) showed partial response, for an overall response rate of 25.2%. The median overall survival was 27.6 mo, and the proportions of survivors at 1, 2, and 5 years were 67.4%, 54.0%, and 17.4%, respectively. Multivariate analysis demonstrated that no prior transcatheter arterial chemoembolization, lactate dehydrogenase < 230 IU/L, and performance status of 0 were the independent favorable prognostic factors. The development of a 0-3-point prognostic score index was based on the sum of these three prognostic factors. Subsequently, the patients were categorized into three groups: those with a good(prognostic index = 0-1; n = 54), intermediate(prognostic index = 2; n = 26), or poor(prognostic index = 3; n = 15) prognosis. The median survival times in these three groups were 41.0, 21.2, and 6.8 mo, respectively(P < 0.01). CONCLUSION: Our simple prognostic index may be helpful for management of patients in determining treatment strategies for advanced HCC in the era of molecularly targeted therapy.
文摘BACKGROUND Hepatitis B virus(HBV)is a major cause of hepatocellular carcinoma(HCC).HBV DNA can get integrated into the hepatocyte genome to promote carcinogenesis.However,the precise mechanism by which the integrated HBV genome promotes HCC has not been elucidated.AIM To analyze the features of HBV integration in HCC using a new reference database and integration detection method.METHODS Published data,consisting of 426 Liver tumor samples and 426 paired adjacent non-tumor samples,were re-analyzed to identify the integration sites.Genome Reference Consortium Human Build 38(GRCh38)and Telomere-to-Telomere Consortium CHM13(T2T-CHM13(v2.0))were used as the human reference genomes.In contrast,human genome 19(hg19)was used in the original study.In addition,GRIDSS VIRUSBreakend was used to detect HBV integration sites,whereas high-throughput viral integration detection(HIVID)was applied in the original study(HIVID-hg19).RESULTS A total of 5361 integration sites were detected using T2T-CHM13.In the tumor samples,integration hotspots in the cancer driver genes,such as TERT and KMT2B,were consistent with those in the original study.GRIDSS VIRUSBreakend detected integrations in more samples than by HIVID-hg19.Enrichment of integration was observed at chromosome 11q13.3,including the CCND1 pro-moter,in tumor samples.Recurrent integration sites were observed in mitochondrial genes.CONCLUSION GRIDSS VIRUSBreakend using T2T-CHM13 is accurate and sensitive in detecting HBV integration.Re-analysis provides new insights into the regions of HBV integration and their potential roles in HCC development.
