MORPHOFUNCTIONAL CHARACTERISTICS OF RAT SARCOMA M-1 AFTER PHOTODYNAMIC THERAPY WITH THE BACTERIOCHLOROPHYLL A DERIVATIVE

The study of the functional morphology of rat sarcoma M-1 after photodynamic therapy using bacteriopurpurinimide disulfide derivative (disulfide-BPI) as a photosensitizer is described. 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. Photoinduced antitumor effect was shown to be due to the destruction of sarcoma M-1 vascular bed, the rapid inhibition of proliferative activity and devitalization of tumor cells by apoptosis and necrosis. It is reasonable to suppose that in the early stages after photodynamic therapy destruction of the microvasculature and photocytostatic shock of tumor cells with subsequent development of necrosis are caused by direct influence of the light flux on sensitized cellular elements in parenchyma and stroma of tumors. The efficiency of photodynamic therapy with the novel photosensitizer is determined by the sequence of destructive and inflammatory changes in tumor parenchyma and surrounding tissues, as well as repopulation potential of tumor cells survived after treatment.

1. Kaplan M.A., Kapinus V.N., Popuchiev V.V., Romanko Yu.S., Yaroslavtseva-Isaeva E.V., Spichenkova I.S., Shubina A.M., Borgul O.V., Goranskaya E.V. Photodynamic therapy: results and prospects, Radiatsiya i risk, 2013, Vol. 22, No. 3, pp. 115-123. (in Russian).

2. Filonenko E.V., Serova L.G. Photodynamic therapy in clinical practice, Biomedical Photonics, 2016, Vol. 5, No. 2, pp. 26-37. (in Russian).

3. Pervaiz S. Reactive oxygen-dependent production of novel photochemotherapeutic agents, FASEB J., 2001, Vol. 15, No. 3, pp. 612-617.

4. Sibata C.H., Colussi V.C., Oleinick N.L., Kinsella T.J. Photodynamic therapy in oncology, Expert Opin. Pharmacother., 2001, Vol. 2, No. 6, pp. 917-927.

5. Kaplan M.A., Romanko Yu.S., Popuchiev V.V., Yuzhakov V.V., Bandurko L.N., Fomina N.K., Mikhina L.N., Malygina A.I., Ingel' I.E. Action of photodynamic therapy with Photoditazin on the growth and functional morphology of sarcoma M-1, Lazernaya meditsina, 2005, Vol. 9, No. 4, pp. 41-47. (in Russian).

6. Kaplan M.A., Romanko Yu.S., Popuchiev V.V., Yuzhakov V.V., Bandurko L.N., Mikhina L.N., Fomina N.K., Malygina A.I., Ingel' I.E. Influence of the density of light energy on the antitumor efficiency of photodynamic therapy with Photoditazin, Lazernaya meditsina, 2005, Vol. 9, No. 2, pp. 46-54. (in Russian).

7. Filonenko E.V. Fluorescence diagnostics and photodynamic therapy: justification of applications and opportunities in oncology, Biomedical Photonics, 2014, Vol. 3, No. 1, pp. 3-7. (in Russian).

8. Akopov A.L., Kazakov N.V., Rusanov A.A., Karlson A. The mechanisms of photodynamic action for treating of cancer patients, Biomedical Photonics, 2015, Vol. 4, No. 2, pp. 9-16. (in Russian).

9. Dougherty T.J., Gomer C.J., Henderson B.W., Jori G., Kessel D., Korbelik M., Moan J., Peng Q. Photodynamic therapy, J. Natl. Cancer Inst., 1998, Vol. 90, No. 12, pp. 889-905.

10. Rak J.W., St. Croix B.D., Kerbel R.S. Consequences of angiogenesis for tumor progression, metastasis and cancer therapy, Anticancer Drugs, 1995, Vol. 6, No. 1, pp. 3-18.

11. Goel S., Duda D.G., Xu L., Munn L.L., Boucher Y., Fukumura D., Jain R.K. Normalization of the vasculature for treatment of cancer and other diseases, Physiol Rev., 2011, Vol. 91, No. 3, pp. 1071-1121.

12. Grin M.A., Mironov A.F., Shtil A.A. Bacteriochlorophyll a and its derivatives: Сhemistry and perspectives for cancer therapy, Anti-Cancer Agents in Med. Chem., 2008, Vol. 8, No. 6, pp. 683-697.

13. Pantyushenko I.V., Grin M.A., Yakubovskaya R.I., Plotnikova E.A., Morozova N.B., Tsygankov A.A. Mironov A.F. The novel highly effective IRphotosensitized for photodynamic therapy of cancer, Tonkiye khimicheskiye tekhnologii, 2014, Vol. 9, No. 3, pp. 3-10. (in Russian).

14. Chissov V.I., Jakubovskaja R.I., Mironov A.F., Grin M.A., Plotnikova E.A., Morozova N.B., Tsygankov A.A. The drug for photodynamic therapy and method of photodynamic therapy for cancer, Patent RF No. 2521327, 2014.

15. Iuzhakov V.V., Khavinson V.Kh., Kvetnoĭ I.M., Fomina N.K., Kuznetsova M.N. Growth kinetics and functional morphology of M-1 sarcoma in rats before and after gamma-irradiation, Vopr. Onkol., 2001, Vol. 47, No. 3, pp. 328-334. (in Russian).

16. 1Yuzhakov V.V., Sevan'kaeva L.E., Konoplyannikov A.G., Bandurko L.N., Konoplyannikov M.A., Ingel I.E., Fomina N.K., Tsyganova M.G.,. Kal'sina S.Sh. A morphofunctional study of mesenchymal stem cells’ effects on sarcoma M-1, Molekulyarnaya meditsina, 2015, No. 1, pp. 39-45. (in Russian).

17. Iuzhakov V.V., Sevan'kaeva L.E., Ul'ianenko S.E., Iakovleva N.D., Kuznetsova M.N., Tsyganova M.G., Fomina N.K., Ingel' I.E., Lychagin A.A. The effectiveness of fractionated exposure of sarcoma M-1 to gamma-radiation and fast neutrons, Radiats. Biol. Radioecol., 2013, Vol. 53, No. 3, pp. 267-279. (in Russian).

18. Weidner N., Semple J.P., Welch W.R., Folkman J. Tumor angiogenesis and metastasis — correlation in invasive breast carcinoma, N. Engl. J. Med., 1991, Vol. 324, No. 1, pp. 1-8.

19. Al-Najar A., Al-Sanabani S., Korda J.B., Hegele A., Bolenz C., Herbst H., Jönemann K.P. Naumann C.M. Microvessel density as a prognostic factor in penile squamous cell carcinoma, Urol. Oncol., 2012, Vol. 30, No. 3, pp. 325-329.

20. Yuzhakov V.V., Kaplan M.A., Kvetnoy I.M. Functional morphology of tumors exposed to laser and ionizing radiation. Prospects of the low level laser applications in complex antitumor therapy, Fizicheskaya meditsina, 1993, Vol. 3, No. 1-2, pp. 5-13. (in Russian).

21. Plate K.H., Scholz A., Dumont D.J. Tumor angiogenesis and antiangiogenic therapy in malignant gliomas revisited, Acta Neuropathol., 2012, Vol. 124, No. 6, pp. 763- 775.

22. Ferrario A., von Tiehl K.F., Rucker N, Schwarz M.A., Gill P.S., Gomer C.J. Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma, Cancer Res., 2000, Vol. 60, No. 15, pp. 4066-4069.

23. Gomer C.J., Ferrario A., Luna M., Rucker N., Wong S. Photodynamic therapy: combined modality approaches targeting the tumor microenvironment, Lasers Surg. Med., 2006, Vol. 38, No. 5, pp. 516-521.