Cancers, Vol. 12, Pages 286: Smad Phospho-Isoforms for Hepatocellular Carcinoma Risk Assessment in Patients with Nonalcoholic Steatohepatitis

Cancers, Vol. 12, Pages 286: Smad Phospho-Isoforms for Hepatocellular Carcinoma Risk Assessment in Patients with Nonalcoholic Steatohepatitis Cancers doi: 10.3390/cancers12020286 Authors: Suwa Yamaguchi Yoshida Murata Ichimura Tsuneyama Seki Okazaki Nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) sometimes occurs in mildly fibrotic livers, while HCC incidence in NASH-related cirrhosis is lower than and less predictable than in hepatitis C virus (HCV)-related cirrhosis. Transforming growth factor (TGF)-β signaling in hepatocytic nuclei is implicated in fibrosis and carcinogenesis. TGF-βtype I receptor (TβRI) and c-Jun N-terminal kinase (JNK) differentially phosphorylate the mediator Smad3, resulting in 2 distinct phospho-isoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). In mature hepatocytes, oncogenic signaling via the JNK/pSmad3L pathway antagonizes signaling via the tumor-suppressive TβRI/pSmad3C pathway. We immunohistochemically examined domain-specific Smad3 phosphorylation in liver biopsy specimens from 30 NASH patients representing different fibrotic stages and 20 chronically infected hepatitis C patients as controls, correlating Smad3 phosphorylation with clinical course. HCC occurred during follow-up in 11 of 12 NASH patients with abundant pSmad3L and limited pSmad3C but in only 2 of 18 with limited pSmad3L. In contrast, HCC devel...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

Related Links:

ConclusionA substantial further reduction in cases of HCC requires a wider application of universal HBV vaccination and effective treatment of HBV- and HCV-related chronic hepatitis and cirrhosis, more effective campaigns to favor correct dietary habits and reduce alcohol consumption and the intensification of studies on HCC pathogenesis for future optimized prevention strategies.
Source: Infection - Category: Infectious Diseases Source Type: research
Authors: Zappulo E, Scotto R, Buonomo AR, Maraolo AE, Pinchera B, Gentile I Abstract Introduction: Hepatitis C virus (HCV) is estimated to infect approximately 70 million people worldwide. If left untreated, chronic infection can progress to cirrhosis, liver failure or hepatocellular carcinoma. The advent of new direct-acting antivirals (DAA) has revolutionized patients' chances of treatment and viral elimination. Currently, several DAA options are available on the market.Areas covered: This review focuses on the pharmacokinetics, efficacy, tolerability and safety profile of DCV-TRIO, a twice-daily fixed-dose combi...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
k A Abstract BACKGROUND: There is ongoing search for new noninvasive biomarkers to improve management of patients with hepatocellular carcinoma (HCC). Studies, mostly from the Asian-Pacific region, demonstrated differential expression of liver-specific microRNA-122 (miR-122) in tissue as well as in sera of patients with hepatitis B virus- and hepatitis C virus-induced HCC. AIM: To evaluate prognostic value of miR-122 in patients with HCC in a European population and determine potential factors related to alteration of miR-122 in sera. METHODS: Patients with confirmed HCC (n = 91) were included in the stu...
Source: World Journal of Gastroenterology : WJG - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
ConclusionsThe additive risk of T2DM for HCC development was highest in patients with NASH. HCC risk may vary depending on the underlying etiology.
Source: Journal of Clinical and Experimental Hepatology - Category: Gastroenterology Source Type: research
Background/Aims: The course of hepatitis C infection (HCV) in patients with thalassemia has not been adequately studied and management has not been optimized. The current prospective longitudinal study assessed the clinical course, outcome, progression and management of recently acquired HCV in patients with transfusion dependent thalassemia major versus acute HCV without thalassemia.Methods: A well-characterized cohort of patients with thalassemia and recent HCV infection or recent HCV without thalassemia were enrolled and prospectively followed. The blood transfusion needs and chelating agents were determined. Liver func...
Source: Mediterranean Journal of Hematology and Infectious Diseases - Category: Hematology Source Type: research
CONCLUSIONS: The six serum miRNAs can be utilized as a surrogate and non-invasive biomarker for HCV-related HCC diagnosis. PMID: 31658041 [PubMed - as supplied by publisher]
Source: Cancer Biomarkers - Category: Cancer & Oncology Tags: Cancer Biomark Source Type: research
Conclusions: The constantly increasing prevalence of NAFLD in the general population can contribute to a growing role of NAFLD/NASH in HCC epidemiology. Moreover, some particular challenges specific for patients with liver steatosis may impede proper HCC diagnosis, treatment and follow-up. PMID: 31631714 [PubMed - as supplied by publisher]
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
In conclusion, our data indicate that hepatic pro-survival UPR signaling suppresses the liver-specific HNF4A and its downstream target miR-122 in cirrhosis. These results provide an explanation as to why cirrhosis is a risk factor for the development of HCC in chronic HCV infection.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract Hepatocellular carcinoma (HCC) is a serious consequence of persistent hepatitis C virus (HCV) infection and represents one of the most aggressive neoplasms globally. The implication of microRNA-301 (miR-301) in the initiation and progression of different types of cancers has been proved. We aimed to assess circulating microRNA-301 as possible biomarker for the early detection of HCC in patients with chronic HCV infection. miR-301 expression levels were estimated in plasma samples of 42 patients with newly diagnosed HCV-related HCC, 48 chronically HCV infected patients with liver cirrhosis and 40 healthy i...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
This study examined two miRNAs which are miRNA-122 and miRNA-224 if it could serve as biomarkers for diagnosis of HCC. Methods: This study included 20 patients with HCV-induced HCC and 20 patients with HCV-induced liver cirrhosis for comparison. As well as 20 healthy volunteers as controls. All participants were subjected to history taking, clinical examination, and determination of serum alpha-fetoprotein. Quantification of plasma miRNA-122 and miRNA-224 was done by real-time quantitative PCR. Results: Our results showed that levels of miRNA-122 were significantly lower in HCC group compared to the cirrhosis group and con...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
More News: Cancer | Cancer & Oncology | Carcinoma | Cirrhosis | Hepatitis | Hepatitis C | Hepatocellular Carcinoma | Liver | Liver Cancer | Urology & Nephrology