6533b831fe1ef96bd12997c2

RESEARCH PRODUCT

Tetrachlorodecaoxide Improves the Oxygenation Status of Multicellular Tumor Spheroids

subject

description

Insufficient O2 supply to solid tumors has been recognized since many years to be a crucial problem in cancer therapy. Hypoxia and anoxia may increase the resistance of tumor cells to certain antiproliferative drugs or to ionizing radiation. Numerous approaches to overcoming this problem have been reported in the literature. Efforts have been made in mainly two basic directions: (1) the development of therapeutic means which are particularly efficient in hypoxic and nutrient-deprived tissue areas or which are at least independent of the tissue oxygenation, and (2) the development of methods for improving the oxygenation status of solid tumors. Among the former approaches, the cytotoxicity of radiosensitizers against hypoxic cells, the cytocidal effect of hyperthermia on energy-deprived cells and the absence of an “oxygen effect” when using high LET-radiation are to be mentioned here. In addition,pathophysiological mechanisms may be utilized to further enhance the efficacy of such a treatment, e.g., the decrease of tumor blood flow during hyperthermia at high thermal doses (Mueller-Klieser and Vaupel, 1984). Improvement of the tumor tissue oxygenation can be achieved either through the inhibition of the cellular respiration (Durand and Biaglow, 1974; Durand and Olive, 1981; Vaupel and Mueller-Klieser, 1985) or by increasing the O2 delivery to the tumor tissue. The latter effect may result from an increase in nutritive tumor blood flow and/or from an elevation of the O2 transport capacity in the arterial blood. Tumor blood flow may be increased during low-dose hyperthermia (Mueller-Klieser and Vaupel, 1984), during hemodilution (Vaupel and MuellerKlieser, 1984) or upon application of vasoactive drugs (Jirtle et al.,1978; Suzuki et al.,1981; Kaelin et al.,1982). The O2 transport via blood to tumor tissue may be enhanced by breath-ing pure O2, by hyperbaric oxygenation (Mueller-Klieser and Vaupel, 1983; Mueller-Klieser et al.,1984) or by the use of perfluorochemical emulsions (Goodman et al.,1984; Teicher and Rose, 1984; Rockwell, 1985).