Enhancement effect of an anti-angiogenic agent, TNP-470, on hyperthermia-induced growth suppression of human esophageal and gastric cancers transplantable to nude mice.

The effect of a combination of TNP-470 (AGM-1470, an anti-angiogenic agent) and hyperthermia on tumor growth was examined using human esophageal (ESO-2) and gastric (NSC-8) cancers transplantable to nude mice. TNP-470 alone at a dose of 30 mg/kg three times a week for 2 weeks was sufficient to obtain an antitumor effect. A combination of this dose of TNP-470 and 43 degrees C hyperthermia for 30 min inhibited tumor growth markedly in comparison with either treatment alone. It was considered that angiogenesis after hyperthermia was inhibited by TNP-470, and then regrowth of the tumor cells was potently suppressed by reduction of O2 pressure, pH and nutrient supply in the tumor tissue.