The combined treatment of transplantable solid mammary carcinoma in Wistar rats by use of photodynamic therapy and cysteine proteinase inhibitor.

Yousif Saleh1, B.S., Piotr Ziólkowski1, M.D. PhD, Maciej Siewinski1,2, PhD, Jerzy Milach1, M.D., Piotr Marszalik1, M.D., Jacek Rybka3

1 Department of Pathology, Medical University of Wroclaw, 1 Marcinkowskiego St.,PL- 50-368 Wroclaw, tel. 4871-3209974, fax: 4871-3281029, E-mail: 2 Department of Obstetrics an Gynaecology, Medical University of Wroclaw, Chalubinskiego 3; PL-50-368 Wroclaw, tel. 4871-3209741 3-Institute of Immunology and Experimental Therapy, Wroclaw, 12 Weigla St., PL- 53-114 Wroclaw, tel. 4871-3732274, fax:4871-3732587;

Numerous studies showed that lysosomal proteinases play important role in carcinogenesis. Enzymatic activity of tumor-associated proteases is counter-balanced by specific inhibitors. PDT is technique which involves photoexcitation of sensitizing drug retained in neoplastic tissue that is subsequently destroyed. Intraperitoneal injections of hematoporphyrin derivative (HpD) were made in dose 20 mg/kg in rats transplanted with mammary carcinoma. Halogen lamp was used 24 hrs later at 630+/-20 nm and total dose - 200 J/sq. cm. Cysteine proteinase inhibitor (CPI) was dissolved in saline and injected subcutaneously in doses 50 mg and 200 mg per animal. Effectiveness of treatment was evaluated with regard to survival time and tumor response and to depth of necrosis. In several cases tumors completely disappeared following HpD-PDT+CPI. Number of complete tumor responses was higher when PDT+200 mg of CPI was used, i.e. 6/10 rats. Promising results have also been obtained with regard to survival time of treated animals and to induction of tumor necrosis.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Carcinogenesis.