We present experimental results obtained by combining photodynamic therapy (PDT) with tumor chemotherapy or radiotherapy. Dimethoxyhematoporphyrin (DMHp) and photosan (PS) were used as photosensitizers, pharanoxi and vincristine as antitumor drugs. The therapeutic effect of the combination of PDT and antitumor drugs (pharanoxi, vincristine) slightly increases as compared to the treatment of PDT or antitumor drug alone. The additive therapeutic effect is achieved under the combination of PDT and 60Co irradiation. It seems that the sensitizers DMHp and PS regulate lipid peroxidation in blood serum of experimental animals, which becomes more active under the influence of alkylating antitumor drugs. Therefore, they could protect an organism from negative influence of tumor chemotherapy.
Efficiency of cell radiosensitization by porphyrins is a function of the irradiation dose, the nature of the cell and physico-chemical properties of the sensitizer. The maximal radio- sensitization for E. ascites tumor cells was reached at 2 Gy, for Saccharomyces cerevisiae- 25Gy. The radiosensitization by different porphyrins in E.ascites tumor cells increases their cytotoxicity by a factor of 3, in Saccharomyces cerevisae --inhibition of growth 0.5 - 2.5 time.
The new hematoporphyrin derivatives--HpD-1 and dimethoxyhematoporphyrin--DMHp were studied. Their physico-chemical properties, activity in tumor PDT and influence on therapeutic effect of tumor radiation therapy and on toxicity of chemotherapeutic agents were investigated. Hematoporphyrin--Hp was used as control. Data, obtained by absorption spectroscopy, indicated that HpD-1 and DMHp strongly aggregates in aqueous solution and HpD-1 has many covalently bound structures. HpD-1 and DMHp effects in tumor PDT and radiation therapy were studied using 8 species of transplantable tumors. The sensitizers were injected to the animals intraperitoneally in a dosage of 5 - 20 mg/kg. In 48-76 hours after sensitizers were injected, the tumors were irradiated by the pulsed Raman laser pumped by the SHG of YAG:Nd3+ laser. The parameters of this laser system are as follows: the wavelength 630 nm, the pulse duration (tau) equals 1 ns, energy E equals 10 mJ, the repetition rate f equals 10 Hz, average power P equals 100 mW. The goal of our investigation was to attempt to optimize tumor radiation therapy and chemotherapy.
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