Document Detail

Metronomic chemotherapy in combination with antiangiogenic treatment induces mosaic vascular reduction and tumor growth inhibition in hepatocellular carcinoma xenografts.
MedLine Citation:
PMID:  22736027     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: In addition to sprouting angiogenesis, other mechanisms, such as mosaic tumor vessel formation, have been recognized to contribute to tumor vascularization. We sought to examine vascular alteration as well as tumor growth inhibition after treatment with antiangiogenic therapy, chemotherapy alone or in combination.
METHODS: Hepatocellular carcinoma cells (Hep3B) expressed green fluorescent protein were utilized to establish orthotopic xenograft model in nude mice. The formation and distribution of mosaic vessels was analyzed quantitatively by immunolabeling. Next, changes in tumor microcirculation and therapeutic effects on tumor growth were evaluated in several different treatment groups: control, conventional doxorubicin, metronomic doxorubicin, bevacizumab, bevacizumab plus conventional doxorubicin, and bevacizumab plus metronomic doxorubicin. In addition, we examined the effects of combined regimens on lung metastasis using a highly metastatic human hepatocellular carcinoma (HCCLM3) mouse model.
RESULTS: Approximately 62 % of the vessels were present in the central part or near the midsection of the tumor and were mosaic. Only the combined antiangiogenic treatment and chemotherapy (metronomic schedule, P = 0.00; conventional schedule, P = 0.02) had a significant effect on the degree of mosaic vasculature. Metronomic doxorubicin in combination with bevacizumab had an even more profound effect than bevacizumab plus conventional doxorubicin (P < 0.05) on tumor growth inhibition and survival. However, bevacizumab plus metronomic doxorubicin failed to inhibit lung metastasis compared with antiangiogenic monotherapy.
CONCLUSIONS: Metronomic chemotherapy in combination with antiangiogenic treatment results in the reduction of mosaic tumor vasculature, inhibition of tumor growth, and enhanced survival of mice. Further investigation of drug scheduling is required to optimize antitumor activity.
Fan Zhou; Juan Hu; Jiang-Hua Shao; Shu-Bing Zou; Shun-Li Shen; Zhi-Qiang Luo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-27
Journal Detail:
Title:  Journal of cancer research and clinical oncology     Volume:  138     ISSN:  1432-1335     ISO Abbreviation:  J. Cancer Res. Clin. Oncol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-26     Completed Date:  2013-01-23     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  7902060     Medline TA:  J Cancer Res Clin Oncol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1879-90     Citation Subset:  IM    
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, 1 Mingde Road, Nanchang 330006, China.
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MeSH Terms
Administration, Metronomic
Angiogenesis Inhibitors / administration & dosage
Antibodies, Monoclonal, Humanized / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Carcinoma, Hepatocellular / drug therapy*,  pathology
Cell Line, Tumor
Doxorubicin / administration & dosage
Drug Administration Schedule
Injections, Intravenous
Liver Neoplasms / drug therapy*,  pathology
Lung Neoplasms / prevention & control,  secondary
Mice, Inbred BALB C
Mice, Nude
Neovascularization, Pathologic / pathology,  prevention & control*
Survival Analysis
Treatment Outcome
Tumor Burden / drug effects
Xenograft Model Antitumor Assays*
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal, Humanized; 23214-92-8/Doxorubicin; 2S9ZZM9Q9V/bevacizumab

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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