AIM To detect the expression of caspase 3gene in primary human hepatocellular carcinoma(HCC)and investigate its relationship to p21<sup>WAF1</sup>gene expression and HCC apoptosis.METHODS In situ hybridi...AIM To detect the expression of caspase 3gene in primary human hepatocellular carcinoma(HCC)and investigate its relationship to p21<sup>WAF1</sup>gene expression and HCC apoptosis.METHODS In situ hybridization was employedto determine caspase 3 and p21<sup>WAF1</sup>expression inHCC.In situ end-labeling was used to detecthepatocytic apoptosis in HCC.RESULTS Twenty-one of 39(53.8%)cases ofHCC were found to express caspase 3transcripts,while 45.2% of HCC failed toexpress caspase 3.Non-cancerous adjacent livertissues showed more positive caspase 3(87.5%,7/8)as compared with HCC(P【0.05).The expression of caspase 3 is correlated withHCC differentiation,72.2%(13/18)ofmoderately to highly differentiated HCC showedcaspase 3 transcripts positive,while only 38.1%of poorly differentiated HCC harbored caspase 3transcripts(P【0.05).No relationship wasfound between caspase 3 expression and tumorsize or grade or metastasis,although 52.5%(5/8)of HCC with metastasis were caspase 3positive and a little higher than that with nometastasis(51.6%,P】0.05).Expression of caspase 3 alone did not affect the apoptosisindex(AI)of HCC.The AI was 7.12%o in caspase3-positive tumors(n=21),while in caspase 3-negative cases(n=18)6.59%0(P】0.05).Expression of caspase 3 clearly segregated withp21<sup>WAF1</sup>positive tumors as compared withp21<sup>WAF1</sup>-negative cases(16 of 23,69.6% versus5 of 16,31.3%)with statistical significance(P=0.017).In the cases with positive caspase 3and negative p21<sup>WAF1</sup>,the Al was found slightlyhigher,but with no statistical significance,thanthat with expression of p21<sup>WAF1</sup>and caspase 3(7.21‰ vs 6.98‰,P】0.05).CONCLUSION Loss of caspase 3 expressionmay contribute to HCC carcinogenesis,althoughthe expression of caspase 3 does not correlatewell with cell apoptosis in HCC.p21<sup>WAF1</sup>may bemerely one of the inhibitors which can reducecaspase 3 mediated cell apoptosis in HCCs.展开更多
BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is poor and its early diagnosis is of the utmost importance. This study aimed to investigate the values of glypican-3 (GPC-3) expression in the liver and ser...BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is poor and its early diagnosis is of the utmost importance. This study aimed to investigate the values of glypican-3 (GPC-3) expression in the liver and sera and its gene transcription for diagnosis and monitoring of metastasis of HCC. METHODS: Liver GPC-3 was analyzed in HCC tissues from 36 patients by immunohistochemistry and Western blotting. GPC-3 mRNA from circulating peripheral blood mononuclear cells from 123 HCC patients or 246 patients with other diseases or 36 HCC tissues was amplified by RT-PCR, quantitative realtime PCR, and confirmed by DNA sequencing. Circulating GPC-3 level was detected by ELISA. RESULTS: The increasing expression of GPC-3 was observed from non-cancerous to cancerous tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation. The positive rate of GPC-3 was 80.6% in HCC, 41.7% in their paracancerous tissues, and none in distal cancerous tissues (P【0.001), with no significant difference in differentiation grade and tumor number except for size (Z=2.941, P=0.003). Serum GPC-3 was detected only in HCC (52.8%) and significant difference was found between GPC-3 and tumor size (χ2 =6.318, P=0.012) or HBV infection (χ2 =23.362, P【0.001). Circulating GPC-3 mRNA was detected in 70.7% of HCC tissues, with relation to TNM stage, periportal cancerous embolus, and extra-hepatic metastasis (P【0.001). The combination ofcirculating GPC-3, GPC-3 mRNA and alpha-fetoprotein is of complementary value for HCC diagnosis (94.3%). CONCLUSION: Both GPC-3 overexpression and GPC-3 mRNA abnormality could be used as markers for the diagnosis of HCC and monitoring its metastasis.展开更多
Hepatocellular carcinoma(HCC)is a malignant tumor with a fairly poor prognosis(5-year survival of less than 50%).Using sorafenib,the only food and drug administration(FDA)-approved drug,HCC cannot be effectively treat...Hepatocellular carcinoma(HCC)is a malignant tumor with a fairly poor prognosis(5-year survival of less than 50%).Using sorafenib,the only food and drug administration(FDA)-approved drug,HCC cannot be effectively treated;it can only be controlled at most for a couple of months.There is a great need to develop efficacious treatment against this debilitating disease.Glypican-3(GPC3),a member of the glypican family that attaches to the cell surface by a glycosylphosphatidylinositol anchor,is overex-pressed in HCC cases and is elevated in the serum of a large proportion of patients with HCC.GPC3 expression contributes to HCC growth and metastasis.Furthermore,several different types of antibodies targeting GPC3 have been developed.The aim of this review is to summarize the current literatures on the GPC3 expression in human HCC,molecular mechanisms of GPC3 regulation and antibodies targeting GPC3.展开更多
CDV3 is correlated with tumorigenesis and may affect some biological process in cancer.In this study,we explore the role of CDV3 in HCC.According to the TCGA data base,CDV3 is over-expressed in HCC tissues.Up-regulati...CDV3 is correlated with tumorigenesis and may affect some biological process in cancer.In this study,we explore the role of CDV3 in HCC.According to the TCGA data base,CDV3 is over-expressed in HCC tissues.Up-regulation of CDV3 is correlated with lower over-all survival rate in HCC patients.In HCC samples from our hospital,CDV3 is also enriched in cancer tissues and CDV3 expression associated with HCC pathological T stage.What is more,higher CDV3 expression could forecast poor survival rate in HCC patients.In conclusion,CDV3 is a biomarker of HCC and could be a potential therapeutic target.展开更多
文摘AIM To detect the expression of caspase 3gene in primary human hepatocellular carcinoma(HCC)and investigate its relationship to p21<sup>WAF1</sup>gene expression and HCC apoptosis.METHODS In situ hybridization was employedto determine caspase 3 and p21<sup>WAF1</sup>expression inHCC.In situ end-labeling was used to detecthepatocytic apoptosis in HCC.RESULTS Twenty-one of 39(53.8%)cases ofHCC were found to express caspase 3transcripts,while 45.2% of HCC failed toexpress caspase 3.Non-cancerous adjacent livertissues showed more positive caspase 3(87.5%,7/8)as compared with HCC(P【0.05).The expression of caspase 3 is correlated withHCC differentiation,72.2%(13/18)ofmoderately to highly differentiated HCC showedcaspase 3 transcripts positive,while only 38.1%of poorly differentiated HCC harbored caspase 3transcripts(P【0.05).No relationship wasfound between caspase 3 expression and tumorsize or grade or metastasis,although 52.5%(5/8)of HCC with metastasis were caspase 3positive and a little higher than that with nometastasis(51.6%,P】0.05).Expression of caspase 3 alone did not affect the apoptosisindex(AI)of HCC.The AI was 7.12%o in caspase3-positive tumors(n=21),while in caspase 3-negative cases(n=18)6.59%0(P】0.05).Expression of caspase 3 clearly segregated withp21<sup>WAF1</sup>positive tumors as compared withp21<sup>WAF1</sup>-negative cases(16 of 23,69.6% versus5 of 16,31.3%)with statistical significance(P=0.017).In the cases with positive caspase 3and negative p21<sup>WAF1</sup>,the Al was found slightlyhigher,but with no statistical significance,thanthat with expression of p21<sup>WAF1</sup>and caspase 3(7.21‰ vs 6.98‰,P】0.05).CONCLUSION Loss of caspase 3 expressionmay contribute to HCC carcinogenesis,althoughthe expression of caspase 3 does not correlatewell with cell apoptosis in HCC.p21<sup>WAF1</sup>may bemerely one of the inhibitors which can reducecaspase 3 mediated cell apoptosis in HCCs.
基金supported in part by grants-in-Aid from the Projects of Jiangsu Medical Science (HK201102, H200925)the Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD)the Program of Nantong Society Undertaking and Technological Innovation (HS2011012),China
文摘BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is poor and its early diagnosis is of the utmost importance. This study aimed to investigate the values of glypican-3 (GPC-3) expression in the liver and sera and its gene transcription for diagnosis and monitoring of metastasis of HCC. METHODS: Liver GPC-3 was analyzed in HCC tissues from 36 patients by immunohistochemistry and Western blotting. GPC-3 mRNA from circulating peripheral blood mononuclear cells from 123 HCC patients or 246 patients with other diseases or 36 HCC tissues was amplified by RT-PCR, quantitative realtime PCR, and confirmed by DNA sequencing. Circulating GPC-3 level was detected by ELISA. RESULTS: The increasing expression of GPC-3 was observed from non-cancerous to cancerous tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation. The positive rate of GPC-3 was 80.6% in HCC, 41.7% in their paracancerous tissues, and none in distal cancerous tissues (P【0.001), with no significant difference in differentiation grade and tumor number except for size (Z=2.941, P=0.003). Serum GPC-3 was detected only in HCC (52.8%) and significant difference was found between GPC-3 and tumor size (χ2 =6.318, P=0.012) or HBV infection (χ2 =23.362, P【0.001). Circulating GPC-3 mRNA was detected in 70.7% of HCC tissues, with relation to TNM stage, periportal cancerous embolus, and extra-hepatic metastasis (P【0.001). The combination ofcirculating GPC-3, GPC-3 mRNA and alpha-fetoprotein is of complementary value for HCC diagnosis (94.3%). CONCLUSION: Both GPC-3 overexpression and GPC-3 mRNA abnormality could be used as markers for the diagnosis of HCC and monitoring its metastasis.
基金This work was supported in part by grants from the State Key Basic Research Program (No.39825114) and the NationalNatural Science Foundation of China (No.39770379).
基金This study was supported by grants funded by the USA National Institutes of Health R01CA222490 to Y.-J.Y.Wanthe UC Davis Comprehensive Cancer Center seed grants to Y.-J.Y.Wan and T.-C.Shih.
文摘Hepatocellular carcinoma(HCC)is a malignant tumor with a fairly poor prognosis(5-year survival of less than 50%).Using sorafenib,the only food and drug administration(FDA)-approved drug,HCC cannot be effectively treated;it can only be controlled at most for a couple of months.There is a great need to develop efficacious treatment against this debilitating disease.Glypican-3(GPC3),a member of the glypican family that attaches to the cell surface by a glycosylphosphatidylinositol anchor,is overex-pressed in HCC cases and is elevated in the serum of a large proportion of patients with HCC.GPC3 expression contributes to HCC growth and metastasis.Furthermore,several different types of antibodies targeting GPC3 have been developed.The aim of this review is to summarize the current literatures on the GPC3 expression in human HCC,molecular mechanisms of GPC3 regulation and antibodies targeting GPC3.
基金This study was funded by The National Natural Science Foundation of China(Grant No.81702408)the Science Foundation for Fostering Talents of The First Affiliated Hospital of Chongqing Medical University(Grant No.PYJJ2017-08)The Medical research program from Board of Health in Chongqing(Grant No.2013-2-009).
文摘CDV3 is correlated with tumorigenesis and may affect some biological process in cancer.In this study,we explore the role of CDV3 in HCC.According to the TCGA data base,CDV3 is over-expressed in HCC tissues.Up-regulation of CDV3 is correlated with lower over-all survival rate in HCC patients.In HCC samples from our hospital,CDV3 is also enriched in cancer tissues and CDV3 expression associated with HCC pathological T stage.What is more,higher CDV3 expression could forecast poor survival rate in HCC patients.In conclusion,CDV3 is a biomarker of HCC and could be a potential therapeutic target.