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Morphological and molecular features of the hepatocellular carcinoma developed in cirrhotic microenvironment: a new experimental paradigm in the study of human hepatocarcinogenesis

Grant number: 10/51719-7
Support type:Regular Research Grants
Duration: November 01, 2010 - May 31, 2013
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:José Roberto Machado Cunha da Silva
Grantee:José Roberto Machado Cunha da Silva
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Hepatocellular carcinoma (HCC) is the 5th most common tumor in humans. About 90% of HCC cases are associated with liver cirrhosis and its development is preceded by preneoplastic lesions (PNLs) and molecular changes in cirrhotic tissue. The experimental models are important tools to study the mechanisms and molecular pathways involved in carcinogenesis, besides helping in the search for new therapies. However, current models of hepatocarcinogenesis are developed in non-cirrhotic liver, which can not reproduce the same characteristics of human HCC. In a recent work by our group, we found that thioacetamide (TAA), a substance commonly used in models of fibrosis and cirrhosis, produced PNLs in the hepatic tissue of cirrhotic rats, mimicking the pattern of human hepatocarcinogenesis. Thus, we believe this model will be useful and extremely important in characterizing the transition of PNLs to the HCC in cirrhotic environment, validating the possible "triggers" involved and opening possibilities for diagnosis and orientated therapies for human HCC. Thus, this work aims to establish an experimental model for hepatocarcinogenesis in cirrhotic environment, based on anatomo-pathological, biochemical, cellular and molecular mechanisms. Understanding the factors involved in the transition of PNLs of cirrhosis for HCC will provide tools for early diagnosis of human HCC, as well as support in the development of therapeutic targets in cirrhotic patients. (AU)