Contributions of Fibroblasts, Extracellular Matrix, Stiffness, and Mechanosensing to Hepatocarcinogenesis

Semin Liver Dis DOI: 10.1055/s-0039-1685539Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. A unique feature of liver cancer is its close association with liver fibrosis. About 90% of HCCs develop in advanced liver fibrosis or cirrhosis, suggesting an important role for the fibrotic microenvironment in driving HCC development. Here, the authors will discuss functional contributions of liver fibrosis to the development of HCC, focusing on mechanisms through which fibrosis may promote HCC development such as hepatic stellate cell-derived extracellular matrix, growth factors, and cytokines, stiffness-induced signaling pathways, and immunosuppression. Better understanding of these factors in HCC development and progression may provide the basis for novel stromal-based therapies for tumor prevention or therapy. [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Seminars in Liver Disease - Category: Gastroenterology Authors: Tags: Review Article Source Type: research

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Abstract Several researchers have analyzed the alterations of the methionine cycle associated with liver disease to clarify the pathogenesis of human hepatocellular carcinoma (HCC) and improve the preventive and the therapeutic approaches to this tumor. Different alterations of the methionine cycle leading to a decrease of S-adenosylmethionine (SAM) occur in hepatitis, liver steatosis, liver cirrhosis, and HCC. The reproduction of these changes in MAT1A-KO mice, prone to develop hepatitis and HCC, demonstrates the pathogenetic role of MAT1A gene under-regulation associated with up-regulation of the MAT2A gene (MAT...
Source: Medicina (Kaunas) - Category: Universities & Medical Training Authors: Tags: Medicina (Kaunas) Source Type: research
CONCLUSION: SNP rs10945859 in the PARK2 gene could prove useful in predicting the clinical outcome in HCV-infected patients. PMID: 31208654 [PubMed]
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
Conclusion: Our data reveal molecular epigenetic signatures within this mutationally homogeneous group that point to ways to stratify patients for liver disease risk.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by array Homo sapiens Source Type: research
ConclusionOur study suggested that 25-OHD deficiency at baseline is a prognostic indicator for a poor tumor response in hepatocellular carcinoma treated with TACE.
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
lico Silymarin, a mixture of flavonolignan and flavonoid polyphenolic compounds extractable from milk thistle (Silybum marianum) seeds, has anti-oxidant, anti-inflammatory, anti-cancer and anti-viral activities potentially useful in the treatment of several liver disorders, such as chronic liver diseases, cirrhosis and hepatocellular carcinoma. Equally promising are the effects of silymarin in protecting the brain from the inflammatory and oxidative stress effects by which metabolic syndrome contributes to neurodegenerative diseases. However, although clinical trials have proved that silymarin is safe at high doses (&a...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
Conclusion Massive SI and immune cell paralysis associated with ACLF represent the extreme severity of CAID in response to an infectious or sterile challenge. The severe immune disturbance plays a pivotal role in the pathogenesis of the distinctive features of ACLF: organ failure and bacterial infection susceptibility. Excessive SI in ACLF results from the massive activation and dysfunction of an innate immune system challenged by increased PAMPs and DAMPs. SI leads to cell and tissue immunopathology contributing to hepatic and extrahepatic organ failure. Concomitantly, the course of ACLF is associated with a disproportio...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: While there is a certain overlap between the results of the current study and published transcriptomic profiles of non-transplanted livers with steatosis, we have identified discrete characteristics of the non-alcoholic fatty liver disease in liver grafts potentially utilizable for the establishment of predictive signature. Introduction Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries, its prevalence being estimated at 19–31.3% (1). It encompasses a range of conditions that are thought to arise from fatty liver (simple steatosis) throu...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Joanna Mikulak1,2, Elena Bruni1,2, Ferdinando Oriolo1,2, Clara Di Vito1 and Domenico Mavilio1,2* 1Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy 2Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy The liver is considered a preferential tissue for NK cells residency. In humans, almost 50% of all intrahepatic lymphocytes are NK cells that are strongly imprinted in a liver-specific manner and show a broad spectrum of cellular heterogeneity. Hepatic NK (he-NK) cells play key roles in tuning liver immune response in b...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Ali Mahzari1, Songpei Li1, Xiu Zhou1,2, Dongli Li2, Sherouk Fouda1, Majid Alhomrani1, Wala Alzahrani1, Stephen R. Robinson1 and Ji-Ming Ye1,2* 1Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia 2School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China The present study investigated the effects of matrine on non-alcoholic steatohepatitis (NASH) in mice induced by a methionine choline-deficient (MCD) diet and the mechanism involved. The study was performed in C57B/6J mice fed a MCD diet for 6 weeks to induce NAS...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion: In conclusion, Baishouwu extract exhibited potent effect on the development of HCC by altering TLR4/MyD88/ NF-κB signaling pathway in the sequence of hepatic inflammation-fibrosis-cancer, which provided novel insights into the mechanism of Baishouwu extract as a candidate for the pretreatment of HCC in the future. Introduction Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third cause of cancer-related deaths (Jemal et al., 2011). Chronic inflammation, caused by chemical, biological and physical factors, is found to be related to certain human cancers. The effe...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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