Development of therapy for pancreatic cancers which targets adaptation response to hypoxia.

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1)We found that the expression of adrenomedullin, which has been reported to be a vasodilater, is enhanced by hypoxia.2)We found that the administration of adrenomedullin antagonist peptides into tumor tissues induced the disappearance of tumors through the suppression of angiogenesis.3)We found that dominant negative HIF-1α decreased the resistance to apoptosis induced by hypoglycemia.4) We also found that dominant negative HIF-1α decreased the tumorigenicity of a pancreatic cancer cell line.5)We demonstrated that dominant negative HIF-1α decreased the expression of Glut-1 enhanced by hypoxia and that dominant negative HIF-1α decreased the uptake of FDG in tumor tissues.