1,721,099 research outputs found
Multifocal hepatocellular carcinoma: intrahepatic metastasis or multicentric carcinogenesis?
No full textMultifocal Hepatocellular carcinoma (HCC) may be multiple HCCs of multicentric origin (MO) or intrahepatic metastases (IM) arising from a primary HCC. Numerous attempts to differentiate the two types of multifocal HCC have been made including the valuation of the clinicopathologic characteristics of MO and IM patients and the recurrence time, loss-of-heterozygosity analysis of specific DNA microsatellite loci to distinguish multiclonal MO from IM of monoclonal origin, and the research of diagnostic and progression markers through genomic and proteomic analyses. These approaches, however, have been unsatisfactory hitherto. Recently, a multi-omic analysis of HBV-related multifocal HCCs, including intergraded genomics and transcriptomics, was performed and the results, validated by a cohort of 174 HCC patients, were correlated with HCC clinicopathological data. The two multifocal HCC types were effectively discerned by multi-omics profiling that could predict HCC clonality and aggressiveness. Further, the dual-specificity protein kinase TTK was recognized as a prognostic marker for HCC. Multi-omics strategy potentially opens new perspectives for the diagnosis, prognosis and personalized treatment of multi-focal HCC. Further work aimed at extending this strategy to HCC with other etiology, simplifying the analysis, and reducing its costs is necessary for its routine clinical application
INTERACTION OF MAJOR GENES PREDISPOSING TO HEPATOCELLULAR CARCINOMA WITH GENES ENCODING SIGNAL TRANSDUCTION PATHWAYS INFLUENCES TUMOR PHENOTYPE AND PROGNOSIS
No full textExpression of N-acetylglucosaminyltransferase III in hepatic nodules generated by different models of rat liver carcinogenesis.
No full textGenomic abnormalities in hepatocarcinogenesis. Implications for a chemopreventive strategy.
No full textFocal loss of long non-coding RNA-PRAL, as determinant of cell function and phenotype of hepatocellular carcinoma
No full textlncRNA-PRAL down-regulation may be responsible for p53 inactivation in p53-wild type HCC. Indeed apoptosis is absent in p53-deficient (Hep3B) or p53-mutant (Huh7) cells cultured in presence of lncRNA-PRAL
Dissection of signal transduction pathways as a tool for the development of targeted therapies of hepatocellular carcinoma
No full textPrognostic markers and putative therapeutic targets for hepatocellular carcinoma.
No full textMol Aspects Med. 2010 Apr;31(2):179-93. Epub 2010 Feb 20.
Prognostic markers and putative therapeutic targets for hepatocellular carcinoma.
Frau M, Biasi F, Feo F, Pascale RM.
Source
Department of Biomedical Sciences, Division of Experimental Pathology and Oncology, University of Sassari, 07100 Sassari, Italy.
Abstract
Hepatocellular carcinoma (HCC) is the fifth most frequent human cancer and a fatal disease. Therapies with pharmacological agents do not improve the prognosis of patients with unresectable HCC. This emphasizes the need to identify new targets for early diagnosis, chemoprevention, and treatment of the disease. Available evidence indicates that clinical outcome of HCC could reflect the genetic predisposition to cancer development and progression. Numerous loci controlling HCC progression have been identified in rodents. In this review, we describe results of recent studies on effector mechanisms of susceptibility/resistance genes, responsible for HCC progression, aimed at identifying new putative prognostic markers and therapeutic targets of this tumor. Highest c-myc amplification and overexpression, alterations of iNOS crosstalk with IKK/NF-kB and RAS/ERK signaling, ubiquitination of ERK and cell cycle inhibitors, and deregulation of FOXM1 and cell cycle key genes occur in rapidly progressing dysplastic nodules and HCC, induced in genetic susceptible rat strains, compared to the lesions of resistant rats. Notably, alterations of these mechanisms in human HCC subtypes with poorer or better prognosis, are similar to those present in genetically susceptible and resistant rats, respectively, and function as prognostic markers and therapeutic targets. Attempts to cure advanced HCC by molecular therapy directed against specific targets led to modest survival benefit. Thus, efforts are necessary to identify and test, in pre-clinical and clinical studies, new therapeutic targets for combined molecular treatments of HCC. They may take advantage from the comparative analysis of signal transduction in HCCs differently prone to progress, in rats and humans
An infernal cross‐talk between oncogenic β‐catenin and c‐Met in hepatocellular carcinoma: Evidence from mouse modeling
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