Alʹmanah Kliničeskoj Mediciny (Aug 2017)
Effect of photodynamic therapy with the bacteriochlorophyll a derivative on growth and functional morphology of rat sarcoma M-1
Abstract
Background: In recent years, the method of photodynamic therapy (PDT) has been increasingly used in clinical oncology. Three non-toxic components play a key role in realization of the anti- tumor effect of PDT: a photosensitizer (PS), local irradiation of the tumor with light/laser of a certain wavelength corresponding to the sensitizer absorption peak, and oxygen. The highly reactive biological oxidants formed during photochemical reactions exert a destructive effect on cells and tumor vasculature with subsequent activation of the immune response. Efficiency of PDT is determined by the level of PS accumulation in tumors, as well as by its photophysical parameters and photochemical activity. To create a new PS, natural chlorophylls and their derivatives with intense absorption in the long-wave region of the spectrum are of particular interest.Aim: To study the efficacy and mechanism of PDT action (using a conjugate containing two molecules of dipropoxy-bacteriopurpurinimide with a cystamine residue as a PS) on the growth and functional morphology of transplanted solid connective tissue tumor.Materials and methods: The study was carried out in female white outbred rats with subcutaneously implanted sarcoma M-1. PS was injected to rats of the experimental group intraperitoneally. PDT was performed during the maximal index of tumor/ healthy tissue contrast after the administration of the PS. The criterion of PDT efficacy was a change in the tumor growth/regression coefficient. The research methods included immunohistochemistry for PCNA and CD31, evaluation of mitotic activity and apoptosis of tumor cells, as well as computer analysis of microscopic images.Results: After PDT with the new PS, a 16-fold decrease of growth coefficient of tumor nodes was registered. The photo-induced antitumor effect was shown to be due to destruction of sarcoma M-1 vascular bed, rapid inhibition of proliferative activity and devitalization of tumor cells. At early stages after PDT, destruction of the microvasculature and photo-cytostatic shock of tumor cells with subsequent development of necrosis appears to be caused by direct influence of the light flux on sensitized cellular elements in tumor parenchyma and stroma. Conclusion: The final result of PDT is determined by the sequence of destructive and inflammatory changes in the tumor parenchyma and surrounding tissues, as well as by a proliferative potential of malignant cells surviving after treatment. The surviving tumor cells, which determine the recurrent growth of neoplasms after PDT, are still present, maybe due to an insufficient concentration of the sensitizer in certain weakly vascularized areas of sarcoma M-1.
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