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J Didziapetriene

Publications and source records attributed to J Didziapetriene.

5 recordsLinked to original sources

Evaluation of cytotoxic effect of photodynamic therapy in combination with electroporation in vitro.

Under the influence of electric pulses cells undergo membrane electroporation (EP), which results in increased permeability of the membrane to exogenous compounds. EP is applied in oncology as a method to enhance delivery of anticancer drugs. For that reason it was essential to combine photodynamic tumor therapy (PDT)--the cancer treatment method based on the use of photosensitizers that localize selectively in malignant tumors and become cytotoxic when exposed to light, and EP, with the aim to enhance the delivery of photosensitizers into the tumor and therefore to increase the efficacy of PDT. Thus, the aim of study was to evaluate the cytotoxic effect of PDT in combination with EP. A Chinese hamster lung fibroblast cell line (DC-3F) was used. The cells were affected by photosensitizers chlorin e(6) (C e(6)) at the dose of 10 mug/ml and aluminium phthalocyanine tetrasulfonate (AlPcS4) at the dose of 50 microg/ml. Immediately after adding of photosensitizers the cells were electroporated with 8 electric pulses at 1200 V/cm intensity, 0.1 ms duration, 1 Hz frequency. Then, after 20 min of incubation the cells were irradiated using a light source--a visible light passing through a filter (KC 14, emitted light from 660 nm). The fluence rate at the level of the cells was 3 mW/m(2). Cytotoxic effect on cells viability was evaluated using MTT assay. Our in vitro data showed that the cytotoxicity of PDT in combination with EP increases fourfold on the average. Based on the results we suggest that EP could enhance the effect of PDT.

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Schedule-dependent interaction between Doxorubicin and mTHPC-mediated photodynamic therapy in murine hepatoma in vitro and in vivo.

PURPOSE: To evaluate cytotoxic and antitumor effects of a conventional anticancer drug Doxorubicin (Dox) and photodynamic therapy (PDT) mediated by a promising photosensitizer of second generation meta-tetra (3-hydroxyphenyl)-chlorin (mTHPC) in combination. METHODS: Murine hepatoma MH-22A was used for investigation in vitro and in vivo. In vitro, the cells were incubated with 0.15 microg/ml mTHPC for 18 h and exposed to light from LED array (lambda = 660+/-20 nm) at 0.6-2.4 kJ/m2. 0.05-0.2 microg/ml Dox was administered either 24 h prior to or immediately after light exposure (Dox-->PDT or PDT + Dox, respectively). The cytotoxicity was tested by staining with crystal violet. The character of the combined effect was assessed by multiple regression analysis. In vivo, the antitumor activity was estimated by monitoring the tumor volume over time, in mice transplanted subcutaneously with MH-22A and treated with Dox and/or PDT. For PDT, mice were exposed to light from diode laser (lambda = 650+/-2 nm) at 12 kJ/m2 following 24 h after administration of 0.15 mg/kg mTHPC. A 3 mg/kg Dox was administered either within 15 min prior to mTHPC or within 15 min after light exposure (Dox-->PDT or PDT + Dox, respectively). RESULTS: Both in vitro and in vivo, the combination of mTHPC-mediated PDT and Dox was evaluated to be more effective than each treatment alone. In vitro, the difference between cell viability curves after photodynamic treatment as a single modality and after combination of photodynamic treatment with Dox was statistically significant under most of the applied conditions (P < or = 0.02). In the case of PDT + Dox, the combination had an additive character, and the sequence Dox-->PDT caused a sub-additive interaction. In vivo, both regimens of combination were more effective in inhibiting tumor growth than any single treatment (P < 0.09). The antitumor activity of PDT + Dox regimen was more prominent than that of Dox-->PDT; however, significance of the difference was not high (P = 0.08). CONCLUSIONS: These results indicate that Dox potentiates therapeutic efficacy of mTHPC-mediated PDT and vice versa, and the degree of potentiation is influenced by the combination schedule: administration of Dox immediately after light exposure is preferable to administration of Dox at 24 h prior to light exposure.

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Electroporation of transplantable tumour for the enhanced accumulation of photosensitizers.

The aim of this study was to verify whether electroporation could increase the accumulation of the hydrophilic photosensitizers: aluminium phthalocyanine tetrasulphonate (AlPcS(4)) and chlorin e(6) (C e(6)) in tumour tissue. The experiment was performed in vivo using hybrid mice (C57Bl/CBA) bearing hepatoma A22 (MH-A22) tumours transplanted in the right haunch. The time dependence of the fluorescence intensity of administered photosensitizers was measured after the ordinary and electrically stimulated delivery. The obtained fluorescence spectroscopy results implied the tumour being affected by an electrical field in a way, which led to a higher accumulation of both photosensitizers (AlPcS(4) and C e(6)) in the periphery of the tumour and it superficial layer. Our pilot study suggests that electroporation could be considered as a useful procedure seeking for the more effective application of photodynamic tumour treatment.

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Effects of photodynamic therapy in combination with Adriamycin.

The combination of photodynamic therapy (PDT) and Adriamycin (ADM) was studied in the animal model system. Photohem (PH) was used as a photosensitizer. Mice bearing carcinoma epidermoides LL of the lung received PH once at a dose 10 mg/kg and after 24 h ADM was injected i.p. at a dose 3 mg/kg and tumors were illuminated with laser light after three different time intervals, 15 min, 3 and 24 h. To evaluate the effect of PDT and PDT combined with ADM the intensity of lipid peroxidation in tumor tissue and in blood serum was determined using the thiobarbituric acid assay. PDT induces an increase of malondialdehyde (MDA) concentration in tumor tissue as well as in blood serum. When PDT is combined with ADM, the MDA level in tumor tissue is similar to the level of this product as in the PDT alone. No enhancement of the efficiency of the combined treatment was observed at these experimental conditions. This is also confirmed by the tumor growth dynamics, survival time of animals and flow cytometric DNA analysis of tumor cells. For the successful combination of PDT with chemotherapy it is suggested to apply the drugs at the regimen which will allow to avoid the interaction between two agents since the ground state interaction between PH and ADM is stated spectroscopically. It should lead to the conclusion that the sequence of the combination of two treatment modalities is an important factor for synergistic effect.

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Faranoxi-a new antitumor agent.

The aim of the present study was to evaluate the antitumor activity of faranoxi experimentally and clinically. Faranoxi is a derivative of chloroethylaminophenylacetic acid containing a cytostatic group modified by oxygen in its structure. It has a broad spectrum of antitumor activity in experimental studies. One hundred eighty-eight patients with different types of malignancies were included in clinical studies. At a dosage of 90-120 mg/m2 a day for 12-15 days faranoxi is relatively well tolerated. Clinical studies demonstrate the antitumor activity of faranoxi against melanoma, lymphoma and rectal cancer. It should be noted that primary melanoma was less responsive to faranoxi compared to lymphoid metastases. Using the combination regimen FDV (faranoxi, deticene, vincristine) as treatment of melanoma, partial remission was achieved in up to 50% of the cases. Clinical trials are ongoing.

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