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Hepatocellular Carcinoma

发布时间 2018-01-31
点击次数 76
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     Hepatocellular Carcinoma  

     

     Introduction


          Hepatocellular Carcinoma

     Aflatoxin or chronic infection with hepatitis B and C virus is the predominant risk factor for HCC in Southeast Asia and Africa,

     while chronic infection with hepatitis C virus and hepatic cirrhosis (mostly alcoholism) are the predominant risk factors for HCC in Western countries and Japan.

     Hepatocarcinogenesis is a complex process associated with accumulation of genetic and epigenetic changes that occur during initiation, promotion and progression of the disease. Some important cellular signaling pathways such as Wnt, P53, Jak/STAT, pRB, Ras/Raf Akt/ mTOR and growth factor are involved in HCC progression.

     Systemic cytotoxic therapies have demonstrated a very limited impact on advancing HCC. Recently, the strategy of using specific inhibitors targeting tyrosine kinase and associated pathways has been tested in HCC clinical trials, such as Sorafenib, Bevacizumab and Sunitinib.


     PharmaLegacy Models and Research Tools


HCC tumor models:

     *Human HCC s.c. xenograft model in nude mice (> 10 tumor cells lines, > 5 Asian HCC lines)

     *Human HCC s.c. xenograft model in nude Rats (Combinational study of PK-PD and local drug delivery)

     *Human HCC orthotopic implantation models, both in mice and rats (Liver orthotopic modeling)

     *Human primary tumor derived HCC models in nude mice (representing human HCC)

     *Luciferase-reporter based HCC imaging model (growth and metastasis following orthotopic implantation)

Hepatocarcinogenesis, Biomarkers and Molecular Pharmacology:

     *HCC cell culture based assays (MTT, invasion, etc.)

     *Hematology and liver chemistry

     *Cytokines / chemokine / biomarker analysis (ELISA)

     *Drug target levels in liver/tumor (Real Time PCR and Western Blot)

     *Drug target activities in liver/tumor (kinase assays and phosphorylation)

Histopathology:

     *Histology

     *Immunohistochemistry (proliferation, apoptosis, angiogenesis)


Case Study - Inhibition of Tumor Growth



          Hepatocellular Carcinoma

          Hepatocellular Carcinoma

     

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