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Biomedical subjects

I Schepetkin

Publications and source records attributed to I Schepetkin.

4 recordsLinked to original sources

Immune response to haptenized tumor antigen as possible mechanism of anticancer action of hypoxic bioreductive agents at low doses.

Possible anticancer effect mechanism of hypoxic bioreductive agents (HBA) at low nongenotoxic doses are reviewed. Experimental and clinical investigations show the process which can develop step-by-step when injecting HBA into the tumor-bearing organism resulting in the stimulation of antitumor immunity: HBA activation in hypoxic tumor tissue, conjugation of activated HBA with proteins of tumor cells, antigen processing, presentation of neoantigen epitops in association with major histocompatibility complex-I and cytolysis of these tumor cells by T-killers. The present process can be a variant of the delayed-type hypersensitivity reaction in the tumor region. The direct regulating influence of HBA on immunocompetent and/or tumor cells as a result of interaction of these drugs with superficial or intercellular receptors is supposed to be realized additively with this process. It is concluded that the ability of HBA to selective activation in tumor tissue and formation of immunogenic conjugates with tumor proteins can be a starting-point for developing drugs with immuno-modulation anticancer properties.

Adjuvants, Immunologic↗

The luminol-amplified chemiluminescence of neutrophils and monocytes in patients with gastric cancer after intraoperative radiotherapy using radiosensitizer sanazole.

The effect of electron-beam intraoperative radiotherapy (IORT) with radiosensitizer sanazole (drug AK-2123) on the functional activity of neutrophils and monocytes in patients with gastric cancer was studied with the use of luminol-amplified chemiluminescence. Sanazole was administered intravenously in a dose of 1.2 g/m2, 30 min before IORT. After resection of the tumor a single dose of 10 Gy was given to the field of regional lymph collectors and the bed of the removed tumor applying a small-size betatron MIB-6E. Cells were separated and chemiluminescence was estimated on the 1-st day before and on the 3-d day and 2-d week after IORT with sanazole. Insignificant effect on the zymosan- or phorbol-12 -myristate-13-acetate (PMA)-stimulated chemiluminescence was observed in this group, although there was found a considerable increase of chemiluminescence of neutrophils in response to zymosan and PMA in 5 from 8 patients, and chemiluminescence of monocytes--in 3 from 8 patients. Correlation between individual indices of zymosan- and PMA-stimulated chemiluminescence of neutrophils before IORT with sanazole was not high, r = 0.71, but it increased significantly to r = 0.91 on the 3-d day and to r = 0.96 on 2-d week after treatment. Correlation between individual indices of stimulated chemiluminescence of monocytes before IORT with sanazole was r = 0.90, and increased to r = 0.99 on the 3-d day and to r = 0.96 on the 2-d week after treatment. So, it is indicative of a correcting effect of the combined treatment including IORT with sanazole administration on the functional activity of neutrophils and monocytes, and the absence of functional disturbances of these cells.

Adenocarcinoma↗

Suppression by radiosensitizer AK-2123 of early phorbol myristate acetate-stimulated chemiluminescence response of human neutrophils induced by gamma-irradiation (short communication).

The influence of gamma-irradiation and radiosensitizer AK-2123 on secretion of reactive oxygen species (ROS) of human neutrophils was studied. gamma-Irradiation (from 5 to 25 Gy) of the neutrophil suspension inhibited spontaneous chemiluminescence and activated phorbol-12-myristate-13-acetate (PMA)-stimulated chemiluminescence. The time of maximum PMA-stimulated chemiluminescence amplitude was decreased with the dose range from 2 to 25 Gy. The addition of radiosensitizer AK-2123 depressed the early PMA-stimulated chemiluminescence response to gamma-irradiation. The obtained results suggest that this effect is connected with influence of AK-2123 on ion canals of neutrophils and may prevent the radiation-induced damage of blood cells.

Dose-Response Relationship, Radiation↗