Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma (HCC) is one of the major cancers in the world. There is a striking variation in HCC incidence rates between various countries, with a highest-to-lowest ratio of 112.5 for males and 54.7 for females. The high-risk populations are clustered in sub-Saharan Africa and eastern Asia. The male-to-female ratio for HCC ranges from < 1 to 6.4 and mostly from 2 to 4. There exist significant variations in the incidence of HCC among different ethnic groups living in the same area and among migrants of the same ethnic groups living in different areas. The age curves of HCC are significantly different in various countries, suggesting variability in exposure to risk factors. Chronic carriers of hepatitis B and C viruses (HBV and HCV, respectively) have an increased risk of HCC. The relative and attributable HCC risk of HBV and HCV carrier status varies in different countries. There exists a synergistic interaction on HCC between the two viruses. Aflatoxin exposure, cigarette smoking, heavy alcohol consumption, low vegetable intake, inorganic arsenic ingestion, radioactive thorium dioxide exposure, iron overload and the use of oral contraceptives and anabolic steroids have been documented as HCC risk factors. Recent molecular epidemiological studies have shown that low serum retinol levels as well as elevated serum levels of testosterone, neu oncoprotein and aflatoxin B1-albumin adduct are associated with an increased HCC risk. There is a synergistic interaction on HCC between chronic HBV infection and aflatoxin exposure. Familial aggregation of HCC exists and a major susceptibility gene of HCC has been hypothesized. Patients of some genetic diseases are at an increased risk of HCC. The genetic polymorphisms of cytochrome P450 2E1 and 2D6 and arylamine N-acetyltransferase 2 are associated with the development of HCC. A dose-response relationship between aflatoxin exposure and HCC has been observed among chronic HBV carriers who have null genotypes of glutathione S-transferase M1 or T1, but not among those who have non-null genotypes. Human hepatocarcinogenesis is a multistage process with the involvement of a multifactorial aetiology. Gene-environment interactions are involved in the development of HCC in humans.
 ...
PMID:Epidemiological characteristics and risk factors of hepatocellular carcinoma. 940 50

Transforming growth factor beta (TGF-beta), a pro-fibrogenic cytokine, has several polymorphism in humans with difference in activity levels. Hepato-carcinogenesis involves alterations in the action of protooncogenes such as the; neu (C-erb-B2) oncogene. Overexpression of the neu-oncogene has been implicated in experimental cellular transformation and tumorigenesis in a wide range of human cancer. We examined TGF-beta1 and C-erb-B2 mRNA expression and their protein levels in hepatitis C virus (HCV) patients and those developing Hepatocellular carcinoma (HCC). Sixty patients (30 HCV and 30 HCC) and 30 controls were enrolled. HCV patients were classified into mild, moderate, marked and no fibrosis. HCC patients were categorized into grade I, II, Ill. TGP-beta1 and C-erb-B2 expression were studied. Messenger RNA was extracted using the guanidinum thiocyanate phenol chloroform method, and used of RT-PCR. Protein serum levels were estimated by (EIA). Significant difference were obtained when comparing TGF-bet1 and C-erb-B2 mRNA in HCV and HCC P = 0.0076, and controls. The HCV group revealed significant difference with C-erb-B2 but not TGF-B1 mRNA as compared to controls P < 0.005 and P > 0.05 respectively. Serum protein levels demonstrated difference increase significance shown when comparing their levels in both studied groups P < 0.001, P < 0.05 respectively and when compared to controls (P < 0.001). TGF-beta1 serum levels in HCV patients showed increase with degree of fibrosis (P = 0.003) while, C-erbB-2 serum levels showed no significance (P = 0.089). In different grades of HCC patients, TGF-beta1 levels showed no significant difference (P = 0.769). However, C-erb-B2 levels revealed significant difference (P = 0.002) between grade I & III and grade II &. Ill (P < 0.001). Positive correlations to protein serum level were obtained with TGF beta1mRNA in HCV group, while, C-erb-B2 mRNA in HCC patients. In conclusion, TGF-beta1 upregulation in HCC suggests its role in hepatic carcinogenesis. Elevated expression of C-erb-B2 may reflect pre-neoplastic liver cell proliferation, cellular necrosis associated with chronic liver disease and alternatively from HCV carcinogens which enhance malignant transformation. Correlation of both parameters with their protein levels might rise using their antibodies in immunotherapy for HCC.
 ...
PMID:TGF-beta1 and C-erb-B2 neu oncoprotein in Egyptian HCV related chronic liver disease and hepatocellular carcinoma patients. 2030 68