Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic hepatitis C virus (HCV) infection has been clearly established as a major risk factor in the development of hepatocellular carcinoma. In the present study we have attempted to identify the HCV genotypes associated with hepatocellular carcinoma in patients from the USA and Japan. RNAs from tumorous and non-tumorous tissues from 11 HCV seropositive Japanese patients, and plasma from 4 American patients were analysed by reverse transcription-polymerase chain reaction (RT-PCR) methods employing primers specific for the 5'UTR, the NS5 and E2/NS1 regions. Amplified products were cloned and compared by nucleotide sequencing and phylogenetic analysis. The 5'UTR region could be successfully amplified and sequenced from all samples, and phylogenetic analysis of the nucleotide sequences demonstrated with the exception of two of Japanese viruses were closely related to HCV type 1. Type 2 was detected in these two cases. In addition, two of the Japanese patients who were found to have cholangiocarcinoma were also found to be infected with type 1. HCV amplification of the NS5 was successful in 7 of the Japanese and 1 USA sample and clearly demonstrated that genotype 1b was predominant. Amplification of the E2/NS1 regions proved to be extremely difficult and was unsuccessful in all HCC patients despite the fact that these regions could be consistently amplified in samples from patients with both acute and chronic HCV infection. These findings might suggest that with long term persistent HCV infection, there may be marked heterogeneity in both the structural and non-structural regions of the virus, and/or possibly that the viral genomes may be defective.
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PMID:[Analysis of hepatitis C virus (HCV) genotypes in hepatocellular carcinoma]. 899 37

AIM:To study hepatocarcinogenesis of hepatitis C virus (HCV).METHODS: Expression of HCV antigens (CP10, NS3 and NS5) and several cancer-associated gene products (ras p21, c-myc, c-erbB-2, mutated p53 and p16 protein) in the tissues of hepatocellular carcinoma (HCC, n = 46) and its surrounding liver tissue were studied by the ABC(avidin-biotin complex) immunohistochemical method. The effect of HCV infection on expression of those gene products in HCC was analyzed by comparing HCV antigen positive group with HCV antigen negative group.RESULTS:Positive immunostaining with one, two or three HCV antigens was found in 20 (43.5%) cases,with either of two or three HCV antigens in 16 (34.8%) cases, and with three HCV antigens in 9 (19.6%) cases.Deletion rate of p16 protein expression in HCC with positive HCV antigen (80%, 16/20)was significantly higher than that in HCC with negative HCV antigen. Whereas no significant difference of the other gene product expression was observed between the two groups.CONCLUSION:HCV appears related to about one third of cases of HCC in Chongqing, the southwest of China, and it may be involved in hepatocarcinogenesis by inhibi ting the function of p16 gene, which acts as a negative regulator of cell cycle.
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PMID:Effect of HCV infection on expression of several cancer-associated gene products in HCC. 1181 78

We recently establish that aspafilioside B, a steroidal saponin extracted from Asparagus filicinus, is an active cytotoxic component. However, its antitumor activity is till unknown. In this study, the anticancer effect of aspafilioside B against HCC cells and the underlying mechanisms were investigated. Our results showed that aspafilioside B inhibited the growth and proliferation of HCC cell lines. Further study revealed that aspafilioside B could significantly induce G2 phase cell cycle arrest and apoptosis, accompanying the accumulation of reactive oxygen species (ROS), but blocking ROS generation with N-acetyl-l-cysteine (NAC) could not prevent G2/M arrest and apoptosis. Additionally, treatment with aspafilioside B induced phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase. Moreover, both ERK inhibitor PD98059 and p38 inhibitor SB203580 almost abolished the G2/M phase arrest and apoptosis induced by aspafilioside B, and reversed the expression of cell cycle- and apoptosis-related proteins. We also found that aspafilioside B treatment increased both Ras and Raf activation, and transfection of cells with H-Ras and N-Ras shRNA almost attenuated aspafilioside B-induced G2 phase arrest and apoptosis as well as the ERK and p38 activation. Finally, in vivo, aspafilioside B suppressed tumor growth in mouse xenograft models, and the mechanism was the same as in vitro study. Collectively, these findings indicated that aspafilioside B may up-regulate H-Ras and N-Ras, causing c-Raf phosphorylation, and lead to ERK and p38 activation, which consequently induced the G2 phase arrest and apoptosis. This study provides the evidence that aspafilioside B is a promising therapeutic agent against HCC.
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PMID:Aspafilioside B induces G2/M cell cycle arrest and apoptosis by up-regulating H-Ras and N-Ras via ERK and p38 MAPK signaling pathways in human hepatoma HepG2 cells. 2568 3