Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The patients with hepatitis B or C based liver cirrhosis are at high risk for developing Hepatocellular carcinoma (HCC), and HCC patients treated surgically or by other therapies are also at high risk for recurrence. As a result, the prognosis of HCC remains poor, and new therapies for the prevention of cancer development and recurrence are urgently needed. We previously reported that glypican 3 (GPC3) was over expressed specifically in HCC. In this report, we found the HLA-A2 or HLA-A24 restricted GPC3 epitope peptide, and investigated whether these peptides could induce GPC3 reactive CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A2+ or HLA-A24+ HCC patients. We used HLA-A2.1 (HHD) transgenic mice (Tgm) to identify the HLA-A2-restricted GPC3 epitopes. We found that these epitope peptides could induce peptide-reactive CTLs in about 50% of HLA A2+ or HLA-A24+, and GPC3+ HCC patients. Our study raises the possibility that these GPC3 peptides may therefore be applicable to cancer immunotherapy for prevention of cancer development and recurrence of HCC.
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PMID:[Possibilities of glypican-3-specific immunotherapy for hepatocellular carcinoma]. 1721 93

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. HCC occurs mainly in chronically diseased livers, e.g. following hepatitis B and C infection. These high-risk patients are closely followed up, and increasing numbers of small equivocal lesions are detected by imaging diagnosis. They are now widely recognized as precursor or early-stage HCCs and are classified as dysplastic nodule or early HCC. These lesions lack typical imaging and histology of ordinary HCC and do not show elevated serum markers of alpha-fetoprotein and PIVKA-II, for example. Molecular analysis of these lesions would help to develop molecular markers for objective histological diagnosis of early HCC and possibly new serum markers for early detection of HCC. It has been reported that HSP70, CAP2, glypican 3 and glutamine synthetase could serve as molecular markers for early HCC. Further analysis is expected to evaluate their usefulness in routine pathological diagnosis including biopsy diagnosis and also as serum markers for early detection of HCC.
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PMID:Candidate molecular markers for histological diagnosis of early hepatocellular carcinoma. 1854 47

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. HCC occurs mainly in patients with chronic liver disease such as in hepatitis B and C infection. These high-risk patients are closely followed up, and increasing numbers of small equivocal lesions are detected by imaging diagnosis. They are now widely recognized as a precursor or early stage of HCC and are classified as dysplastic nodules or early HCC. It is considered that early HCC is a key step in the process of HCC development and progression. However, the molecular mechanisms of early hepatocarcinogenesis are far from clear. Specific mutations of classical oncogenes or tumor suppressor genes have not been identified in early HCC so far. Recent progress in comprehensive analysis of gene expression is shedding some light on this issue. It has been reported that HSP70, CAP2, glypican 3, and glutamine synthetase could serve as molecular markers for early HCC. Further analysis is expected to evaluate their usefulness in routine pathological diagnosis including biopsy diagnosis and also as serum markers for early detection of HCC.
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PMID:Early HCC: diagnosis and molecular markers. 1914 3

There is a significant sex disparity favoring males among hepatocellular carcinoma (HCC) patients. Although various risk factors have been identified, the exact etiology of such sexual dimorphism(s) in HCC is uncertain. Previous studies showed that overexpression of the Y-located protooncogene, testis-specific protein Y encoded (TSPY), promotes cell proliferation and oncogenesis whereas its X-located homologue, TSPYhomologue X (TSPX), retards cell cycle and oncogenic progression. Furthermore, TSPX promotes proteasomal degradation of hepatitis B virus-encoded X oncoprotein and hence could serve as a tumor suppressor in virus-associated HCC. Using immunohistochemistry and reverse-transcription polymerase chain reaction analysis, we had examined the expression of TSPY and TSPX with reference to other established biomarkers in HCC and related liver cancers. Our results demonstrated that 55 (19.2%) of 287 male cases were TSPY positive in immunohistochemistry of tissue arrays, and 15 (46.9%) of 32 male cases were TSPY positive in reverse-transcription polymerase chain reaction analysis of clinical samples. TSPY expression was closely associated with the expression of HCC biomarkers, such as glypican 3. In contrast, TSPX expression was down-regulated in 54.5% of total tumor/nontumorous paired samples (18/33) and negatively associated with those of TSPY, glypican 3, and forkhead box M1 (FOXM1) and was positively associated with that of a tumor suppressor, insulin-like growth factor binding protein 3. The present findings support the hypothesis that the oncogenic events leading to an ectopic activation of the Y-located protooncogene TSPY and/or inactivating mutation/epigenetic silencing of the X-located tumor suppressor gene TSPX could collectively contribute to the sexual dimorphism(s) in HCC and related liver cancers in male-biased manners.
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PMID:The potential contributions of a Y-located protooncogene and its X homologue in sexual dimorphisms in hepatocellular carcinoma. 2501 35

A major etiological risk factor for hepatocellular carcinoma (HCC) is infection by Hepatitis viruses, especially hepatitis B virus and hepatitis C virus. Hepatitis B virus and hepatitis C virus do not cause aggressive activation of an oncogenic pathway, but they transactivate a broad array of genes, cause chronic inflammation, and, through interference with mitotic processes, lead to mitotic error-induced chromosome instability (ME-CIN). However, how ME-CIN is involved in the development of HCC remains unclear. Delineating the effect of ME-CIN on HCC development should help in identifying measures to combat HCC. In this study, we used ME-CIN model mice haploinsufficient in Shugoshin 1 (Sgo1(-/+)) to assess the role of ME-CIN in HCC development. Treatment with the carcinogen azoxymethane caused Sgo1(-/+) ME-CIN model mice to develop HCCs within 6 months, whereas control mice developed no HCC (P < 0.003). The HCC development was associated with expression of early HCC markers (glutamine synthetase, glypican 3, heat shock protein 70, and the serum marker alpha fetoprotein), although without fibrosis. ME-CIN preceded the expression of HCC markers, suggesting that ME-CIN is an important early event in HCC development. In 12-month-old untreated Sgo1 mice, persistent DNA damage, altered gene expression, and spontaneous HCCs were observed. Sgo1 protein accumulated in response to DNA damage in vitro. Overall, Sgo1(-/+)-mediated ME-CIN strongly promoted/progressed development of HCC in the presence of an initiator carcinogen, and it had a mild initiator effect by itself. Use of the ME-CIN model mice should help in identifying drugs to counteract the effects of ME-CIN and should accelerate anti-HCC drug development.
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PMID:Tumor-promoting/progressing role of additional chromosome instability in hepatic carcinogenesis in Sgo1 (Shugoshin 1) haploinsufficient mice. 2574 Aug 22