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Preclinical studies of the novel vascular disrupting agent MN-029.

AbstractBACKGROUND:
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.
AuthorsWenyin Shi, Dietmar W Siemann
JournalAnticancer research (Anticancer Res) 2005 Nov-Dec Vol. 25 Issue 6B Pg. 3899-904 ISSN: 0250-7005 [Print] Greece
PMID16309177 (Publication Type: Journal Article)
Chemical References
  • Angiogenesis Inhibitors
  • Benzimidazoles
  • denibulin
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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