| Beneficial effect of metronomic chemotherapy on tumor suppression and survival in a rat model of hepatocellular carcinoma with liver cirrhosis. | |
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MedLine Citation:
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PMID: 19701751 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Recent studies have demonstrated that frequent, low-dose metronomic (MET) dosing of cytotoxic agents may not only be as efficient as conventional maximum tolerated dose (MTD) chemotherapy but also less toxic. In this study, we investigated the therapeutic effect and safety of MET chemotherapy using cyclophosphamide (CTX) in rats with chemically induced hepatocellular carcinoma (HCC). METHODS: Rats received weekly intraperitoneal (i.p.) injections of diethylnitrosamine during 16 weeks for induction of HCC. The rats were divided into three groups: MTD group received 40 mg/kg CTX i.p. injection on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received saline and 20 mg/kg CTX i.p. injection twice a week, respectively. The growth-modulating effects and overall survival were compared between the groups. Anti-angiogenic effects were evaluated by a measurement of endothelial cell and VEGFR-2 expression. RESULTS: At 6 weeks of therapy, MTD and MET chemotherapy resulted in a significant reduction in tumor number and size compared with Control group. MET chemotherapy showed more prolonged survival than MTD chemotherapy and Control groups (P < 0.05). MET chemotherapy resulted in a significant decrease in both the micro-vessel density and endothelial proliferation index (P < 0.01). Furthermore, MET chemotherapy led to a greater decrease in VEGFR-2 expression at the mRNA and protein levels (P < 0.01). CONCLUSIONS: MET scheduling not only exhibits anti-tumor and anti-angiogenic effects, but also prolongs survival without major toxicities in a rat model of HCC. Our results suggest that MET chemotherapy has a high therapeutic value and should be considered for future clinical trials. |
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Authors:
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Seong Tae Park; Jeong Won Jang; Gi Dae Kim; Joung Ah Park; Wonhee Hur; Hyun Young Woo; Jin Dong Kim; Jeong Hyun Kwon; Chan Ran Yoo; Si Hyun Bae; Jong Young Choi; Seung Kew Yoon |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-08-23 |
Journal Detail:
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Title: Cancer chemotherapy and pharmacology Volume: 65 ISSN: 1432-0843 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-03-16 Completed Date: 2010-05-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 1029-37 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine and WHO Collaborating for Reference and Research on Viral Hepatitis, The Catholic University of Korea, Seoul, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents, Alkylating / administration & dosage, therapeutic use Apoptosis / drug effects Body Weight / drug effects Cell Proliferation / drug effects Cyclophosphamide / administration & dosage, therapeutic use* Diethylnitrosamine Dose-Response Relationship, Drug Drug Administration Schedule Endothelial Cells / cytology, drug effects, metabolism Immunoblotting Kaplan-Meiers Estimate Liver / drug effects*, metabolism, pathology Liver Cirrhosis / chemically induced, drug therapy* Liver Neoplasms, Experimental / chemically induced, drug therapy* Proliferating Cell Nuclear Antigen / metabolism Random Allocation Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction Tumor Burden / drug effects Vascular Endothelial Growth Factor Receptor-2 / genetics, metabolism von Willebrand Factor / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Alkylating; 0/Proliferating Cell Nuclear Antigen; 0/von Willebrand Factor; 50-18-0/Cyclophosphamide; 55-18-5/Diethylnitrosamine; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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