HCC, Hepatocellular Carcinoma

Abbreviations AFP, a-fetoprotein CK, cytokeratin ECM, extracellular matrix EMT, epithelial to mesenchymal transition HCC, hepatocellular carcinoma HNF, hepatocyte nuclear factor, HSC, hepatic stellate cell MFB, myofibroblast M2-PK, M2-pyruvate kinase PDGF, platelet-derived growth factor TGF, transforming growth factor. 

Fig. 3.2.1. Barcelona Clinic Liver Cancer (BCLC) stage-dependent treatment of HCC. (HCC Hepatocellular carcinoma, LTx liver transplantation, Rx liver resection)...

Fig. 17.1 Schematic representation of the production of nitric oxide and peroxynitrite anion and their possible effects on hepatocarcinogenesis. HCC, hepatocellular carcinoma...

Hepatocellular carcinoma (HCC) develops in patients with chronic liver diseases associated with hepatitis B and hepatitis C vims infections with high incidences. Here, an acyclic retinoid has been shown to suppress the posttherapeutic recurrence after interferon-y or glycerrhicin treatment in cirrhotic patients who underwent curative treatment of preceding tumors. The retinoid induced the disappearance of serum lectin-reactive a-fetoprotein (AFP-L3), a tumor marker indicating the presence of unrecognizable tumors in the remnant liver, suggesting a deletion of such minute (pre)malignant clones (clonal deletion). As a molecular mechanism of the clonal deletion, a novel mechanism of... 

Seow TK et al. Two-dimensional electrophoresis map of the human hepatocellular carcinoma cell line, HCC-M, and identification of the separated proteins by... 

The protein profiling approach also provides the use of pattern recognition for discrimination of disease states. Biomarkers for prostate cancer were profiled and a panel assembled that could differentiate cancer patients from noncancer populations (see Fung et al., 2001, Reference 11). Poon et al. (2003) utilized the ProteinChip to obtain tumor-specific proteomic signatures to detect hepatocellular carcinoma (HCC) in patients having chronic liver disease (CLD). 

Approximately 350 million people worldwide are chronic carriers of HBV, with the majority living in Asia and Africa. In the United States approximately one million people have chronic HBV infection. Although chronically infected, individuals may remain asymptomatic for long periods. Spontaneous loss of HBeAg occurs in 7% to 20% of patients each year, but spontaneous loss of HBsAg occurs in only 1% to 2% per year [14]. Health experts estimate that 2% of patients with chronic HBV infection develop cirrhosis each year, and that 15% to 25% of patients with chronic HBV infection will die prematurely from cirrhosis or hepatocellular carcinoma (HCC). 

The other program involves systemic administration of the gene-laden adenovirus via a hepatic artery catheter to treat hepatocellular carcinoma (HCC). The hepatic artery supplies the normal liver with 25% of its blood supply. However, it is the sole blood supply for the carcinoma. Preclinical results demonstrated efficacy in a rat HCC model. In a small, open-label clinical trial of patients positive for HCC, but also having post-hepatitis cirrhosis, patient response was marginal [22]. 

In the present study, we analyzed proteome in hepatocellular carcinoma (HCC), esophageal cancer, and pancreatic cancer tissues. We identified many proteins whose expression in cancer tissues was different from corresponding non-cancerous tissues by using 2-DE and MS. Furthermore, we identified some auto-antibodies reacting to proteins in HCC cancer tissues. In this chapter, we will describe the method, our experimental result, and reports from other researchers about proteomic analysis in cancer patients. 

Key Words Proteomics hepatocellular carcinoma HCC esophageal cancer pancreatic cancer auto-antibody... 

Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly cancer. One million patients with HCC die each year. One of the major causes of HCC is infection with the hepatitis C virus (HCV), and the pathogenesis of HCV-related HCC in its incipient stage from the infection to the onset of cancer is being researched. 

In another tumor study, C3H mice bearing s.c. hepatocellular carcinoma (HCC) were injected intratumorally with 100 pg IL-12 encoding pDNA, followed by electroporation into the tumor (Yamashita et al., 2001). Remarkably a single injection of IL-12 pDNA followed by electroporation resulted in measurable serum levels of IL-12. By day five after pDNA injection, a mean of 4pg/ml of IL-12 was detected in the serum and 2pg/ml of IL-12 was detected as late as 28 days after pDNA injection. 

Infection by human hepatitis B or C virus is a major risk factor for the development of liver cirrhosis and hepatocellular carcinoma (HCC) (Brechot, et al., 2000, Colombo, et al., 2003). Although they act via different mechanisms, both viruses directly influence the control of Ca2+ homeostasis in human hepatocytes. One of the proteins encoded by the HBV genome, the hepatitis virus X protein... 

Brechot, C., Gozuacik, D., Murakami, Y. and Paterlini-Brechot, P., 2000, Molecular bases for die development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Semin Cancer Biol 10, 211-31. 

PIVKA-II, tumor marker of hepatocellular carcinoma (HCC) 1995 B Factor 1,000,000,000 (IPCR 10-10 dilution sample of PIVKA antigen) Tsujii et al. [97]... 

Hepatic stellate cell activation is also associated with the induction of other liver diseases. In livers of patients with chronic hepatitis, an increased number of activated HSC were detected [87], Recently, an interaction of hepatitis C virus (HCV) with HSC was reported [88], Furthermore, HSC activation is associated with the development of liver tumors, for instance, hepatocellular carcinomas (HCC). Mediators like TGF-a and TGF-P derived from dysplastic hepatocytes... 

Sorafenib (l)11 is a multikinase inhibitor marketed by Bayer and Onyx. Sorafenib blocks tyrosine kinases as well as serine/threonine kinases. Its story began in 1994 when Bayer and Onyx entered a collaboration to discover novel Raf/MEK/ERK inhibitors. They first discovered a very mildly active compound 8 (/C50 17 pM) against Rafl kinase in 1995 from screening a collection of 200,000 compounds. The optimization of its potency and its ADMET profile using medicinal chemistry and combinatorial chemistry methods led to the identification of sorafenib (1) in 1999 as a preclinical development candidate. Multiple phase I studies started in 2000, when sorafenib tosylate (19) was evaluated in patents with advanced solid tumors of different types. In December 2005, Sorafenib tosylate (19) received U.S. FDA approval for the treatment of advanced renal cell carcinoma (RCC). Two years later, it was approved for the treatment of unresectable hepatocellular carcinoma (HCC). 

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