6533b7d2fe1ef96bd125f3d8

RESEARCH PRODUCT

Microcirculatory and pH Alterations in Isotransplanted Rat and Xenotransplanted Human Tumors Associated with Hyperthermia

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The rationale for considering the use of hyperthermia as an antitumor agent is based on three different mechanisms of action depending on the hyperthermia levels chosen: At moderate hyperthermia levels (40°–42.5° C) heat can increase the radiosensitivity and/or the chemosensitivity. At higher tissue temperatures ( > 42.5° C) hyperthermia acts as a cytotoxic agent since mammalian cells die after heating in a temperature-, time-, and cell cycle-dependent manner. Besides direct effects on the cell membranes, on the cytoskeleton, on metabolic processes, on DNA replication, and on RNA and protein synthesis, indirect effects distinctly modulating the anticancer action of heat have to be considered. These indirect effects are mostly mediated through the cellular microenvironment, both for in vitro and for in vivo conditions. In most solid tumors, this microenvironment is characterized by hypoxia and even anoxia, acidosis, and energy deprivation, which are known to enhance the heat effect even under in vitro conditions. These characteristic features of the cellular microenvironment are mostly determined by tumor microcirculation. It is generally accepted that nutritive blood flow in most tumors is heterogeneously distributed and on the average insufficient at larger tumor sizes. This flow pattern in solid tumors has two relevant consequences: 1. It induces the hostile microenvironment described, thus rendering the tumor cells in vivo more heat sensitive as compared with normal tissues. 2. It limits the heat dissipation from the tumor tissue and thus the energy input required to reach a therapeutic tissue temperature level. The latter fact often implies the possibility of a relatively selective heating of the tumor tissue.