The combined treatment of transplantable solid mammary carcinoma in Wistar rats by use of photodynamic therapy and cysteine proteinase inhibitor.
Numerous studies have shown that lysosomal proteinases play an important role in carcinogenesis. The enzymatic activity of tumor-associated proteases is counter-balanced by specific inhibitors. Photodynamic therapy (PDT) is a technique which involves photoexcitation of sensitizing drugs retained in neoplastic tissue that is subsequently destroyed. Intraperitoneal injections of hematoporphyrin derivative (HpD) were given at a dose of 20 mg/kg in rats transplanted with mammary carcinoma. A halogen lamp was used 24 hours 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 of 50 mg and 200 mg per animal. The effectiveness of the 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. The number of complete tumor responses was higher when PDT + 200 mg of CPI was used, i.e. 6 out of 10 rats. Promising results have also been obtained with regard to survival time of treated animals and to induction of tumor necrosis. We may presume that a combination of PDT and proteinase inhibitors could be a useful tool in further anticancer studies and, hopefully, in anticancer therapy.
Saleh
Y
Y
Department of Medical Biochemistry, Medical University of Wroclaw, 10 Chalubinskiego PL-50-368 Wroclaw, Poland.
Ziolkowski
P
P
Siewinski
M
M
Milach
J
J
Marszalik
P
P
Rybka
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D003131:Combined Modality Therapy; D015853:Cysteine Proteinase Inhibitors / Q000302:isolation & purification / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D017324:Hematoporphyrin Derivative / Q000528:radiation effects / Q000627:therapeutic use; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D010206:Papain / Q000037:antagonists & inhibitors; D010777:Photochemistry; D010778:Photochemotherapy; D010920:Placenta / Q000201:enzymology; D051381:Rats
D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D009363:Neoplasm Proteins; D017324:Hematoporphyrin Derivative; D002401:Cathepsin B; D010206:Papain