engleski

The role of macrophages in photodynamic therapy of tumors

THE ROLE OF MACROPHAGES IN PHOTODYNAMIC THERAPY OF TUMORS Marko Doko, Suzana Borović, Alfred Švarc, and Mislav Jurin Clinical Hospital Sestre Milosrdnice, Zagreb and Ruđer Bošković Institute, Zagreb, Croatia Photodynamic therapy was recently introduced in clinical practice of several countries. However, the main problems still are a possible toxicity of a photosensitive drug and its sensitivity to the light of particular wavelength, the limited light penetration in bigger tumor, as well as a possible role of macrophages in tumor elimination during photodynamic therapy. The dose of 25 mg/kg of Photofrin (Quadra Logic Technologies, Canada) used in our experiments, was without any toxic effects on the organism and was very successful in eradicating methilcholanthrene induced fibrosarcoma transplanted in syngeneic CBA/HZgr mice, if red light ( strength 260 mW/cm2) was applied during 20 minutes and if the tumor was under 5 mm in diameter. The influence of Photofrin and light on tumor cells and on macrophages was of particular interest and importance. Namely, if fibrosarcoma cells and macrophages, isolated from the spleen of normal mice, were cultivated together (25 macrophages per each tumor cell), about 20% of tumor cells were destroyed. However if macrophages were cultivated with Photofrin (25 mg/mL , during 1 hour) and exposed to red light (strength 130 mW/cm2, during 40 seconds) they were not able to destroy tumor cells. Further, about 40% of tumor cells were destroyed if cultivated with Photofrin (25 mg/mL, during 1 hour) and exposed to red light (strength 260 mW/cm2 during 20 seconds). Finally, if the macrophages from normal mice were added to these pretreated fibrosarcoma cells, the destruction was more pronounced and about 80% of tumor cells were destroyed. These data point to the macrophages as an important factor involved in photodynamic therapy. Tumor cells undergoing a limited destruction during photodynamic therapy could recover and get involved in tumor regrowth if the macrophages were not active. However, both, the tumor cells and the macrophages, are sensitive to Photofrin and light application. So, the successful photodynamic therapy is in balance between tumor cell destruction and the efficacy of the macrophages which escaped the destruction.

tumor; photodynamic therapy; macrophages

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