Wenyin Shi1, Dietmar W Siemann. 1. Department of Radiation Oncology, Shands Cancer Center, University of Florida, Gainesville, FL 32610, USA.
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.
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.
Authors: Roben G Gieling; Richard J Fitzmaurice; Brian A Telfer; Muhammad Babur; Kaye J Williams Journal: Clin Exp Metastasis Date: 2015-06-26 Impact factor: 5.150
Authors: Anne M Traynor; Michael S Gordon; Dona Alberti; David S Mendelson; Mark S Munsey; George Wilding; Richard E Gammans; William L Read Journal: Invest New Drugs Date: 2009-05-13 Impact factor: 3.850