Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.
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PMID:The prognostic molecular markers in hepatocellular carcinoma. 1204 56

The objective of this study was to determine in a rat model of hepatocellular carcinoma (HCC) the effects of the antiangiogenic agent TNP-470 on cell proliferation and effectors of the apoptotic pathway, including p53, p21WAF1/CIP1, cyclin D, and cyclin E. Tumor was induced in male Wistar rats by diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene administration. Experiments were carried out at 28 weeks after initiating the treatment. TNP-470 was administered at 30 mg/kg, 3 times per week from 20 to 28 weeks. Serum levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor beta (HGFbeta) liver expression were increased by hepatocarcinogenesis (+38% and +183%, respectively), and treatment with TNP-470 was able to prevent the increase in these angiogenic factors induced by HCC. HCC coursed with reduced expression of p21WAF1/CIP1 and p53 (-63% and -60%, respectively). Hepatic expression of cyclin D and cyclin E were significantly increased in rats with HCC (+108% and +115%, respectively). In animals with experimental carcinogenesis, a significant increase in the expression of Cdk4 and CdK2 was also observed (+119% and +187%, respectively). These effects were prevented by TNP-470 administration. In conclusion, cell-cycle inhibition by TNP-470 is mediated at least in part by an activation of p21WAF1/CIP1 because of a p53-dependent mechanism, with reduction of the cyclin D-Cdk4 and cyclin E-Cdk 2 expression. These cytostatic effects should be considered when assessing the efficacy of TNP-470 for anti-angiogenic therapy. These findings may prove useful for the development of therapies for the treatment of human HCC.
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PMID:Cell-cycle inhibition by TNP-470 in an in vivo model of hepatocarcinoma is mediated by a p53 and p21WAF1/CIP1 mechanism. 1719 22