[Hypoxic bioreductive agents: the possible immune and receptor-mediated mechanisms of antitumor action].
The article discusses the possible mechanisms of the antineoplastic effect of hypoxic bioreducing agents (HBA) when they are used in low nonhypoxic doses. Experimental and clinical studies provide evidence of the occurrence of stages which in administration of HBA into the organisms of the tumor-carrier may develop in succession, leading to stimulation of antineoplastic immunity: GBA activation in the hypoxic neoplastic tissue, conjugation of HBA metabolites with the macromolecules of the tumor cells, and presentation of the epitopes of neoantigens in association with the main complex of class I histocompatibility (MCH) cytolysis of these cells by T-killers. This process may be similar to that in contact sensitivity to low-molecular compounds (a variant of the reaction of delayed hypersensitivity [DH]) in the neoplastic focus. It is suggested that direct control of the effect of HBA on the immunocompetent and/or tumor cells may occur additively to or synergically with this process as the result of interaction of these compounds with the surface or intracellular receptors. It cannot be excluded that the activated HBA may force the endogenic ligands out of the nucleophilic centers of these receptors and realize receptor-mediated control of gene expression.
Shchepetkin
I A
IA
Experimental Department of Oncology, Tomsk Research Center, Siberian Branch, Russian Academy of Medical Sciences, Russia.
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology; D010084:Oxidation-Reduction / Q000187:drug effects; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D011956:Receptors, Cell Surface
Gipoksicheskie bioreduktivnye agenty: vozmozhnye immunnye i retseptoroposredovannye mekhanizmy protivoopukholevogo deĭstviia.