Mechanism of Action of Shoulder-Modifying Anoxic Radiosensitizers and Their Use in Combination with Other Treatment Modalities. Coordinated Programme on Improvement in Radiotherapy of Cancer Using Modifiers of Radiosensitivity of

摘要

Research focused on four approaches to increased killing of tumor cells: hypoxic sensitizers, protective agents, hyperthermia and chemotherapeutic drugs. Emphasis was on the basic mechanisms involved. Results are summarized as follows. Chemical sensitization: Results with the glutathione-oxidant ''diamide'' confirmed the importance of cellular GSH in the oxygen effect. Moreover, the possibility of combining agents like diamide with the nitroimidazole agents (e.g. misonidazole) was examined. Perhaps the most fundamental observation was the decrease in survival curve shoulder for hypoxic cells when irradiated in the presence of diamide. Chemical protection: The thio-phosphate WR2721, with respect to protection of various tissues and to the basis for its differential protection of normal tissues vs tumors was tested. Other studies examined the mechanism by which thiols protect against X-ray damage and the effects of certain chemotherapy drugs (e.g. Cis-platinum). Hyperthermia: Heat has been studied in conjunction with neutron irradiation (there is no differential effect on hypoxic cells) and at lower temperatures (40 exp 0 ). The latter treatment (4. (Atomindex citation 14:727694)