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Hepatocellular carcinoma: From bedside to proteomics

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Title: Hepatocellular carcinoma: From bedside to proteomics


1
Hepatocellular carcinomaFrom bedside to
proteomics
  • Proteomics 2001, 1, 12491263
  • ?????
  • ? ? ?

2
Contents
  • 1 Introduction
  • 2 Hepatocellular carcinoma clinical aspects
  • 2.1 Occurrence and distribution
  • 2.2 Aetiological factors
  • 2.3 Screening and diagnosis
  • 2.4 Treatment and prevention
  • 3 Hepatocellular carcinoma proteomics
  • 3.1 Early work
  • 3.2 Proteome analysis of HCC
  • 3.3 Protein database of hepatocellular carcinoma
  • 4 Concluding remarks

3
1. Introduction
  • Proteomics the study of the proteome, which is
    the total protein complement of a genome.
  • The disease that has been studied most widely by
    proteomics is cancer.
  • In this paper, we review recent progress made in
    the study of hepatocellular carcinoma (HCC).

4
2 Hepatocellular carcinoma clinical aspects
  • 2.1 Epidemiology
  • Hepatocellular carcinoma(HCC) is the most common
    primary cancer of the liver in Africa and Asia.
  • HCC is four to eight times more common in males
    than in females.
  • HCCs occurrence increases progressively with age.

5
2.2 Aetiological factors
  • Hepatitis B virus (70)
  • Hepatitis C virus (20)
  • Aflatoxins
  • Liver cirrhosis(90) -gt HCC
  • Others

6
2.3 Screening and diagnosis
  • Ultrasound scan of the liver to detect for the
    presence of tumor nodule(s)
  • Measurement of the serum tumor marker
    a-feto-protein(AFP)- gt500ng/ml
  • AFP, serum ferritin, ?-glutamyltranspeptidase
    isozyme, alkaline phosphatase, des- ?-carboxy
    prothrombin, a-1-antitrypsin, aldolase A,
    a-1-fucosidase

7
2.4 Treatment and prevention
  • Treatment
  • Surgery- liver resection or liver transplantation
  • Systemic chemotherapy, selective internal
    irradiation with yittrium-90
  • -gt can only palliate but not cure the disease.
  • Prevention
  • Reducing and removing environmental carcinogens
  • The use of Interferon(IFN) alone or in
    combination antiviral agents (HBV or HCV chronic
    infection)

8
3 Hepatocellular carcinoma proteomics
  • Proteome analysis of liver proteins
  • -gt to understand better the underlying process of
    hepatocarcinogenesis
  • 3.1 Hepatoma cell lines
  • (HepG2, Huh-7, FOCUS, SK-Hep1, Chang, WRL-68,
    BEL7404, L-2, and HCC-M)
  • -gt analysed and compared the 2DE maps

9
  • cDNA microarray analysis of hepatoma cell lines
  • Human liver tumor tissue
  • Hepatic stellate cells
  • -gt play an important role in the development
    of liver fibrosis.
  • Protein database of hepatocellular carcinoma
  • -gt One of the major goals of proteomics is to
    establish a protein database for tissue, cell or
    model organism
  • -gt SWISS-2DPAGE database

10
4 Concluding remarks
  • One of the major goals of proteomics is to
    establish a protein database for tissue, cell or
    model organism
  • The screening for novel diagnostic markers for
    early detection and therapeutic targets for
    treatment of HCC
  • New technology (ICAT, protein chip)

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12
Flowchart of the integrated Approach utilised in
the proteomics analysis of the HCC-M cell line.
13
Analytical 2-DE map of the HCC-M
14
Novel HCC-1 protein
15
Early stage
Tumorous tissue
Advanced stage
Normal tissue
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