APOPTOSIS IN THE LYMPH NODES OF THE ABDOMINAL LYMPHODISSECTION ZONE AFTER LOCAL INTRAOPERATIVE PHOTODYNAMIC THERAPY OF GASTROINTESTINAL CANCERS

The method of DNA-electrophoresis was used to study apoptosis in the lymph nodes of the abdominal lymphodissection zone after local intraoperative photodynamic therapy (PDT) for the gastrointestinal cancers. Apoptosis (apoptotic ladder) was determined in the four cell populations of lymph nodes:

– in the lymph nodes with metastases that have not been irradiated;

– in the irradiated during PDT lymph nodes with metastases;

– in the lymph nodes without metastases that have not been irradiated;

– in the irradiated during PDT lymph nodes without metastases.

The implementation of this study was possible due to intraoperative division of lymph nodes into two parts, one of which was removed while another one intentionally wasn’t removed and was irradiated (in human). It was also removed 60-90 minutes after PDT treatment and examined for apoptosis. As a result, it was found that apoptosis is detected in the irradiated during PDT lymph nodes with metastases. The obtained results show the fact that in the lymph nodes of the abdominal lymphodissection zone tumor cells selectively die by apoptosis as a result of the local intraoperative photodynamic therapy (PDT) for the gastrointestinal cancers while in non-malignant cells apoptosis doesn’t occur after PDT (p <0.01). Thus, the obtained clinical and experimental data made it possible to evaluate the target PDT effect and confirm the safety of the photodynamic effect on healthy tissues of the lymphoid system located in the irradiation zone.

1. Dougherty T.J. Photodynamic therapy, Photochemistry and Photobiology, 1993, Vol. 58, pp. 895-900.

2. Dougherty T.J., Gomer C.J., Henderson B.W., Jori G., Kessel D., Korbelik M., Moan J., Peng Q. Photodynamic therapy, Journal of the National Cancer Institute, 1998, Vol. 90, pp. 889-905.

3. Reynolds T. Photodynamic therapy expands its horizons, Journal of the National Cancer Institute, 1997, Vol. 89, pp. 112-114.

4. Rowe P.M. Photodynamic therapy begins to shine, Lancet, 1998, Vol. 351, pp. 1496.

5. Mroz P., Yaroslavsky A., Kharkwal G.B., Hamblin M.R. Cell death pathways in photodynamic therapy of cancer, Cancers (Basel), 2011, Vol. 3(2), pp. 2516-2539.

6. Serbin M.E., Shcherbak E.V. Apoptosis and its molecular effectors, in Aktual'nye problemy biologii, meditsiny i ekologii, Sbornik [Actual problems of biology, medicine and ecology, Collection], by ed Il’inskih N.N. Tomsk, Sibirskii gosudarstvennyi meditsinskii universitet Publ., 2004, Is. 1. (in Russian).

7. Wen L.Y., Bae S.-M., Do J.H., Park K.-S., Ahn W.S. The effects of photodynamic therapy with Photodithazine on HPV 16 E6/ E7 associated cervical cancer model, Journal of Porphyrins and Phthalocyanines, 2011, Vol. 15(3), pp. 174-180.

8. Mirzaei H., Djavid G.E., Hadizadeh M., Jahanshiri-Moghadam M., Hajian P. The efficacy of Radachlorin-mediated photodynamic therapy in human hepatocellular carcinoma cells, Photochemistry and Photobiology, 2015, Vol. 142, pp. 86-91.

9. Ajani J.A., Bentrem D.J., Besh S., D’Amico T.A., Das P., Denlinger C., Fakih M.G., Fuchs C.S., Gerdes H., Glasgow R.E., Hayman J.A., Hofstetter W.L., Ilson D.H., Keswani R.N., Kleinberg L.R. Gastric Cancer, Version 2.2013: featured updates to the NCCN Guidelines, Journal of the National Comprehensive Cancer Network, 2013, Vol. 11(5), pp. 531-546.

10. Ajani J.A., D’Amico Th.A., Almhanna K., Bentrem D.J., Besh S., Chao J., Das P., Denlinger C., Fanta P., Fuchs C.S., Gerdes H., Glasgow R.E., Hayman J.A., Hochwald S., Hofstetter W.L., Ilson D.H., Jaroszewski D. , Jasperson K. Keswani R.N.,. Kleinberg L.R, Korn W. M., Leong S., Lockhart A.C., Mulcahy M.F., Orringer M.B., Posey J.A., Poultsides G.A., Sasson A.R., Scott W.J., Strong V.E., Varghese T.K.Jr, Washington M.K., Willett C.G., Wright C.D., Zelman D., McMillian N., Sundar H. Esophageal and Esophagogastric Junction Cancers, version 1.2015., Journal of the National Comprehensive Cancer Network, 2015, Vol. 13(2), pp. 194-227.

11. Tempero M. Active Systemic Treatment of Pancreatic Cancer, Journal of the National Comprehensive Cancer Network, 2017, Vol. 15, pp. 723-725.

12. Messersmith W.A. Systemic Management of Colorectal Cancer, Journal of the National Comprehensive Cancer Network, 2017, Vol. 15, pp. 699-670.

13. Sokolov V.V., Filonenko E.V. Combined treatment of obstructing esophageal cancer: recanalization, endoprosthetics and photodynamic therapy, Palliativnaya meditsina i reabilitatsiya, 2004, No. 2, pp. 49b-49. (in Russian).