[Fundamentals of thermochemotherapy of cancer]

Different activation energy for heat cell killing is observed between ranges of temperatures at above and below 43 degrees C, i.e. ca. 150 and 360 kcal/mol, respectively, resulting in the different concept and mode of application in clinical heating for oncotherapy. Cell phase response to heat is characterized in more thermosensitivity of S-phase cells rather than G2, M and G1 phases, while less radiosensitive of S-phase. Reduced partial Oxygen tension (pO2), nutrition and pH as the cell-extrinsic circumstances result in enhanced thermosensitivity, respectively. Not synthesis but cellular content of heat shock proteins (HSPs) as part of physiological stress proteins, which are produced by the cells principally after and occasionally even during the sublethal heating with the contrary reduction of the other proteogeneses or otherwise which are produced constitutively, concern development of thermotolerance. Among the combined thermotherapy with anticancer drug(s), that with MMC or BLM showed interactive, or more than additive, cell killing effect, while that with ADR occasionally showed less than additive effect up to the modality of the combination. Benzaldehyde showed no appreciable cytotoxicity at 37 degrees C while enhanced thermosensitivity and inhibited development of thermotolerance. Study on therapeutic ratio in in vitro cells enables that effect of each of the above-mentioned extrinsic factors on the cellular thermosensitivity is investigated independently, while study on that in vivo may not distinguish the effect of the each factor since those are given by a single cause of inadequate vascularization of tumor tissue rather than the normal counter part.