| Angiogenesis inhibitor TNP-470 suppresses the progression of experimentally-induced hepatocellular carcinoma in rats. | |
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MedLine Citation:
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PMID: 10639583 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We evaluated the effects of angiogenesis inhibitor, TNP-470, on hepatocellular carcinoma (HCCs) induced by a choline-deficient L-amino acid defined (CDAA) diet in rats. Male Fisher 344 rats were fed CDAA for 68 weeks. Rats were treated by subcutaneous injection of TNP-470 (15 mg/kg) or saline (control) three times per week from 53 to 68 weeks. At the end of the experiment, we determined the frequency and size of HCCs and glutathione S-transferase placental form (GSTP)-positive lesions, histology of liver cirrhosis, liver function, and liver weight per body weight. We also determined, using histologic and immunohistochemical semiquantification analyses, the degree of vascularity, apoptosis and proliferation in HCC and adjacent tissues. Treatment with TNP-470 resulted in a reduction of the size and frequency of HCC compared to untreated rats. However, TNP-470 did not influence the histology of liver cirrhosis and liver function. The liver weight per body weight of TNP-470-treated rats was slightly heavier in comparison with that of the controls. Treatment with TNP-470 significantly reduced tumor vascularity relative to the controls. There were no significant differences in the Ki-67 labeling index of HCCs between TNP-470 treated and control rats. The frequency of apoptotic hepatoma cells in TNP-470-treated rats was higher than in control rats. Our results indicate that TNP-470 suppresses the progression of CDAA-induced HCCs in rats through inhibition of angiogenesis, and suggest that TNP-470 might be useful clinically for HCCs. |
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Authors:
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M Kin; T Torimura; T Ueno; T Nakamura; R Ogata; M Sakamoto; S Tamaki; M Sata |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of oncology Volume: 16 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2000 Feb |
Date Detail:
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Created Date: 2000-03-07 Completed Date: 2000-03-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: GREECE |
Other Details:
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Languages: eng Pagination: 375-82 Citation Subset: IM |
Affiliation:
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The Second Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inhibitors
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therapeutic use* Animals Apoptosis / drug effects Carcinoma, Hepatocellular / drug therapy*, pathology Choline / administration & dosage Cyclohexanes Diet Fatty Acids, Unsaturated / therapeutic use* Liver Neoplasms, Experimental / drug therapy*, pathology Lung Neoplasms / secondary Male Neovascularization, Pathologic / drug therapy Rats Rats, Inbred F344 Sesquiterpenes / therapeutic use* |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inhibitors; 0/Cyclohexanes; 0/Fatty Acids, Unsaturated; 0/Sesquiterpenes; 129298-91-5/O-(chloroacetylcarbamoyl)fumagillol; 23110-15-8/fumagillin; 62-49-7/Choline |
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