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

Hepatocellular carcinoma (HCC) is associated with a high morbidity and mortality due to its high rate of recurrence. However, little is known about the biological characteristics of recurrent HCC cells. A single patient's primary and recurrent HCC-derived cell lines, Hep-11 and Hep-12, respectively, were established by primary culture. These two cell lines have the same hepatitis B virus integration site and share many common amplifications and deletions, which suggest that they have the same clonal origin. While Hep-11 cells were non-tumorigenic at 16 weeks following injection of up to 10 000 cells, injection of only 100 Hep-12 cells was sufficient to initiate tumor growth, and all single Hep-12 clones were tumorigenic in immunodeficient mice. Compared with Hep-11, Hep-12 cells expressed the oval cell markers AFP, NCAM/CD56, c-kit/CD117, as well as multiple stem cell markers such as Nanog, OCT4 and SOX2. In addition, >90% of Hep-12 cells were aldehyde dehydrogenase positive. They were also less resistant to paclitaxel, but more resistant to doxorubicin, cisplatin and hydroxycamptothecin (HCPT), which had been administrated to the patient. Furthermore, Hep-12 cells expressed higher levels of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) than Hep-11, and PARP-1 inhibition potentiated the sensitivity to HCPT in Hep-12 cells but not in Hep-11 cells. These results indicate that a large population of the recurrent HCC-derived Hep-12 cells were tumor-initiating cells and that elevated expression of PARP-1 was related to their resistance to HCPT.
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PMID:The properties of tumor-initiating cells from a hepatocellular carcinoma patient's primary and recurrent tumor. 1989 2

Neoplasms contain distinct subpopulations of cells known as tumor-initiating stem-like cells (TICs) that have been identified as key drivers of tumor growth and malignant progression with drug resistance. Stem cells normally proliferate through self-renewing divisions in which the two daughter cells differ markedly in their proliferative potential, with one displaying the differentiation phenotypes and another retaining self-renewing activity. Therefore, understanding the molecular mechanisms of hepatocarcinogenesis will be required for the eventual development of improved therapeutic modalities for treating hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) and hepatitis B virus is a major cause of HCC. Compelling epidemiologic evidence identifies obesity and alcohol as co-morbidity factors that can increase the risk of HCV patients for HCC, especially in alcoholics or obese patients. The mechanisms underlying liver oncogenesis, and how environmental factors contribute to this process, are not yet understood. The HCV-Toll-like receptor 4 (TLR4)-Nanog signaling network is established since alcohol/obesity-associated endotoxemia then activates TLR4 signaling, resulting in the induction of the stem cell marker Nanog expression and liver tumors. Liver TICs are highly sensitized to leptin and exposure of TICs to leptin increases the expression and activity of an intrinsic pluripotency-associated transcriptional network comprised of signal transducer and activator of transcription 3, SOX2, OCT4, and Nanog. Stimulation of the pluripotency network may have significant implications for hepatocellular oncogenesis via genesis and maintenance of TICs. It is important to understand how HCV induces liver cancer through genesis of TICs so that better prevention and treatment can be found. This article reviews the oncogenic pathways to generate TICs.
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PMID:Tumor-initiating stem-like cells and drug resistance: carcinogenesis through Toll-like receptors, environmental factors, and virus. 2578 83

Significance: Neoplasms contain tumor-initiating stem-like cells (TICs) that drive malignant progression and tumor growth with drug resistance. TICs proliferate through a self-renewal process in which the two daughter cells differ in their proliferative potential, with one retaining the self-renewing phenotype and another displaying the differentiated phenotype. Recent Advances: Cancer traits (hepatocellular carcinoma) are triggered by alcoholism, obesity, and hepatitis B or C virus (HBV and HCV), including genetic changes, angiogenesis, defective tumor immunity, immortalization, metabolic reprogramming, excessive and prolonged inflammation, migration/invasion/metastasis, evasion of cell cycle arrest, anticell death, and compensatory regeneration/proliferation. Critical Issues: This review describes how metabolic reprogramming in mitochondria promotes self-renewal and oncogenicity of TICs. Pluripotency transcription factors (TFs), NANOG, OCT4, MYC, and SOX2, contribute to cancer progression by mitochondrial reprogramming, leading to the genesis of TICs and cancer. For example, oxidative phosphorylation (OXPHOS) and fatty acid metabolism are identified as major pathways contributing to pluripotency TF-mediated oncogenesis. Future Directions: Identification of novel metabolic pathways provides potential drug targets for neutralizing the activity of highly malignant TICs found in cancer patients. Antioxid. Redox Signal. 28, 1080-1089.
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PMID:Pluripotency Transcription Factors and Metabolic Reprogramming of Mitochondria in Tumor-Initiating Stem-like Cells. 2925 36

Human hepatocytes are a primary site of infection and replication of the hepatitis B virus (HBV). It is tempting to conclude that tissue specificity is controlled via virus-hepatocyte specific interactions at various steps during the viral lifecycle. However, the molecular mechanisms underlying hepatotropism of HBV are not fully clear. To address this issue, this study aims to identify hepatic factors that contribute to the regulation of the lifecycles of hepatitis viruses- especially HBV- and to clarify their regulatory mechanisms. We established oval-like cell lines (Hdo cells) by introducing a set of reprogramming factors (OCT3/4, SOX2, KLF4, LIN28, and NANOG) into human hepatoma HuH7 cells that are susceptible to HBV. Hdo cells exhibit a bi-directional differentiation potential. We found that Hdo cells maintained support for the replication of HBV but not of HCV. The level of particle-associated HBV DNA secreted into the culture medium was higher in the Hdo cells. Still, the HBs antigen level was lower than in parental HuH7 cells, suggesting that the regulation of HBV gene expression was affected by the reprogramming of HuH7 cells. A microarray analysis determined that the expression of host factors was largely comparable among of HuH7 and Hdo cells. In contrast, Hdo cells lost their susceptibility to HCV infection and to replication of the viral subgenome replicon RNA. Our results suggest that epigenetic reprogramming of human hepatoma cells potentially changes their permissivity to HBV. Furthermore, Hdo cells can be used as powerful tools to identify cellular determinants that change their expression during reprogramming or hepatic differentiation.
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PMID:The susceptibility of human hepatoma-derived oval-like cells to hepatitis B virus infection. 3194 38