Abstract | BACKGROUND: Vascular disrupting agents (VDAs) are designed to cause a rapid and selective shutdown of the established tumor vasculature, which leads to secondary ischemic tumor cell death. MATERIALS AND METHODS: We examined the efficacy of a novel VDA, MN-029, in the rodent KHT sarcoma model. RESULTS: A significant reduction in the functional vessel number was observed after intraperitoneal injection of MN-029 at a dose of 100 mg/kg. Histological evaluation showed extensive necrosis (approximately 90%) by 24 h. MN-029 treatment to the tumor-bearing mice also resulted in a dose-dependent tumor cell killing. When used in combination with radiation or cisplatin chemotherapy, a 100 mg/kg dose of MN-029 significantly enhanced tumor killing compared to that seen with radiation or cisplatin alone. CONCLUSION: The results demonstrated that MN-029 could cause rapid vascular shutdown in solid tumors, dose-dependent secondary tumor cell killing, and effective enhancement of the antitumor effects of radiation and cisplatin chemotherapy.
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Authors | Wenyin Shi, Dietmar W Siemann |
Journal | Anticancer research
(Anticancer Res)
2005 Nov-Dec
Vol. 25
Issue 6B
Pg. 3899-904
ISSN: 0250-7005 [Print] Greece |
PMID | 16309177
(Publication Type: Journal Article)
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Chemical References |
- Angiogenesis Inhibitors
- Benzimidazoles
- denibulin
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Topics |
- Angiogenesis Inhibitors
(pharmacology)
- Animals
- Benzimidazoles
(pharmacology)
- Combined Modality Therapy
- Dose-Response Relationship, Drug
- Female
- Mice
- Mice, Inbred C3H
- Necrosis
- Neovascularization, Pathologic
(drug therapy)
- Sarcoma, Experimental
(blood supply, drug therapy, pathology, radiotherapy)
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