BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost import...BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost importance. Circulating diagnostic and prognostic biomarkers could be used in proper postoperative treatment of patients at an early stage of HCC development. This review summarizes recent studies of the specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. DATA SOURCES: An English-language literature search was conducted using MEDLINE (June 1998 to Spetember 2006) on researches of some valuable specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. RESULTS: Hepatoma tissues can synthesize various tumor-related proteins, polypeptides, and isoenzymes, such as alpha-fetoprotein (AFP), hepatoma-specific gamma-glutamyl transpeptidase (HS-GGT), etc, and then secrete into blood. The valuable early diagnostic and prognostic biomarkers could predict the development an metastases of HCC. Recent researches have confirmed that circulating hepatoma-specific AFP subfraction, transforming growth factor (TGF)-beta 1, HS-GGT, and free insulin-like growth factor (IGF)-II may be more specific markers than total AFP level for early diagnosis for HCC. The circulating genetic markers such as AFP-mRNA, TGF-beta 1-mRNA, IGF-II-mRNA, etc from peripheral blood mononuclear cells of HCC patients have been most extensively used in monitoring distal metastasis or postoperative recurrence of HCC. CONCLUSIONS: Hepatoma tissues synthesize and secrete valuable molecular markers into blood. The analyses of circulating hepatoma-specific biomarkers are useful to early diagnosis of HCC or monitoring metastasis or postoperative recurrence of HCC.展开更多
BACKGROUND: The active form of nuclear factor-kappa B (NF-kappa B) is involved in the initiation, generation, and development of hepatocellular carcinoma (HCC), and is up-regulated in inflammation-associated malignanc...BACKGROUND: The active form of nuclear factor-kappa B (NF-kappa B) is involved in the initiation, generation, and development of hepatocellular carcinoma (HCC), and is up-regulated in inflammation-associated malignancies. We investigated the dynamic expression of NF-kappa B and its influences on the occurrence of HCC through antiangiogenic (thalidomide) intervention in NF-kappa B activation. METHODS : Hepatoma models were induced with 2-fluorenylacetamide (2-FAA, 0.05%) in male Sprague-Dawley rats, and thalidomide (100 mg/kg body weight) was administered intragastrically to intervene in NF-kappa B activation. The pathological changes in the liver of sacrificed rats were assessed after hematoxylin and eosin staining. NF-kappa B mRNA was amplified by RT-nested PCR. The alterations of NF-kappa B and vascular endothelial growth factor (VEGF) expression were analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blotting. RESULTS: Rat hepatocytes showed denatured, precancerous, and cancerous stages in hepatocarcinogenesis, with an increasing tendency of hepatic NF-kappa B, NF-kappa B mRNA, and VEGF expression, and their values in the HCC group were higher than those in controls (P<0.001). In the thalidomide-treated group, the morphologic changes generated only punctiform denaturation and necrosis at the early or middle stages, and nodular hyperplasia or a little atypical hyperplasia at the final stages, with the expression of NF-kappa B (chi(2)=9.93, P<0.001) and VEGF (chi(2)=8.024, P<0.001) lower than that in the 2-FAA group. CONCLUSION: NF-kappa B is overexpressed in hepatocarcinogenesis and antiangiogenic treatment down-regulates the expression of NF-kappa B and VEGF, and delays the occurrence of HCC. (Hepatobiliary Pancreat Dis Int 2010; 9: 169-174)展开更多
基金This study was supported by grants from the Key Project of Medical Science from Jiangsu Province (RC2003100)the Project of Medical Science from Department of Health, Jiangsu Province (H200523), China.
文摘BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost importance. Circulating diagnostic and prognostic biomarkers could be used in proper postoperative treatment of patients at an early stage of HCC development. This review summarizes recent studies of the specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. DATA SOURCES: An English-language literature search was conducted using MEDLINE (June 1998 to Spetember 2006) on researches of some valuable specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. RESULTS: Hepatoma tissues can synthesize various tumor-related proteins, polypeptides, and isoenzymes, such as alpha-fetoprotein (AFP), hepatoma-specific gamma-glutamyl transpeptidase (HS-GGT), etc, and then secrete into blood. The valuable early diagnostic and prognostic biomarkers could predict the development an metastases of HCC. Recent researches have confirmed that circulating hepatoma-specific AFP subfraction, transforming growth factor (TGF)-beta 1, HS-GGT, and free insulin-like growth factor (IGF)-II may be more specific markers than total AFP level for early diagnosis for HCC. The circulating genetic markers such as AFP-mRNA, TGF-beta 1-mRNA, IGF-II-mRNA, etc from peripheral blood mononuclear cells of HCC patients have been most extensively used in monitoring distal metastasis or postoperative recurrence of HCC. CONCLUSIONS: Hepatoma tissues synthesize and secrete valuable molecular markers into blood. The analyses of circulating hepatoma-specific biomarkers are useful to early diagnosis of HCC or monitoring metastasis or postoperative recurrence of HCC.
基金supported by grants from the Project of Elitist Peak in Six Fields(No.2006-B-063)the Project of Medical Sciences(H200727),the Bureau of Health,Jiangsu Province,China
文摘BACKGROUND: The active form of nuclear factor-kappa B (NF-kappa B) is involved in the initiation, generation, and development of hepatocellular carcinoma (HCC), and is up-regulated in inflammation-associated malignancies. We investigated the dynamic expression of NF-kappa B and its influences on the occurrence of HCC through antiangiogenic (thalidomide) intervention in NF-kappa B activation. METHODS : Hepatoma models were induced with 2-fluorenylacetamide (2-FAA, 0.05%) in male Sprague-Dawley rats, and thalidomide (100 mg/kg body weight) was administered intragastrically to intervene in NF-kappa B activation. The pathological changes in the liver of sacrificed rats were assessed after hematoxylin and eosin staining. NF-kappa B mRNA was amplified by RT-nested PCR. The alterations of NF-kappa B and vascular endothelial growth factor (VEGF) expression were analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blotting. RESULTS: Rat hepatocytes showed denatured, precancerous, and cancerous stages in hepatocarcinogenesis, with an increasing tendency of hepatic NF-kappa B, NF-kappa B mRNA, and VEGF expression, and their values in the HCC group were higher than those in controls (P<0.001). In the thalidomide-treated group, the morphologic changes generated only punctiform denaturation and necrosis at the early or middle stages, and nodular hyperplasia or a little atypical hyperplasia at the final stages, with the expression of NF-kappa B (chi(2)=9.93, P<0.001) and VEGF (chi(2)=8.024, P<0.001) lower than that in the 2-FAA group. CONCLUSION: NF-kappa B is overexpressed in hepatocarcinogenesis and antiangiogenic treatment down-regulates the expression of NF-kappa B and VEGF, and delays the occurrence of HCC. (Hepatobiliary Pancreat Dis Int 2010; 9: 169-174)
