Photolon enhanccement of ultrasound cytotoxicity

Objective: To evaluate the impact of Photolon on cytostatic and cytotoxic effects of therapeutic range ultrasound in C6 glioma cells. Methods: C6 glioma cells in suspension or monolayer cell culture were exposed to ultrasound (880 kHz, 0.2-0.7 W/cm2) in the presence or absence of Photolon at the concentration of 1 µg/ml in the culture medium, and then cell viability was evaluated. Results: Photolon increased the cytotoxic effect of ultrasound by 1.5-2.3-fold but had no effect on its cytostatic activity. Conclusion: Photolon produces a pronounced sonosensitizing effect on glioma C6 cells and is a promising drug for sonodynamic treatment of malignant tumors

Effects of combined sonodynamic and photodynamic therapies with photolon on a glioma C6 tumor model

The aim of this study was to investigate the low-power density sonication, sonodynamic therapy (SDT) with Photolon and combination of SDT and photodynamic therapy (PDT) with Photolon for the ablation of glioma C6 tumor model in rats. Methods: The study was performed on 50 rats bearing glioma C6. The tumors were sonicated with/without prior intravenous injection of photosensitizer (PS) Photolon (2.5 mg/kg b.w). Sonication was performed with 0.4; 0.7 and 1.0 W/cm² power density at 1 MHz frequency for 10 min, 2.0 h after Photolon administration using BTL-5710 Sono (BTL Industries Limited, Great Britain). PDT was carried out 2.5 h after Photolon administration using diode laser with 661 nm wavelength (IMAF-AXICON, Minsk, Republic of Belarus) at doses of 50 and 100 J/cm² with 0,17 W/cm² fluence rate. Assessment of tumor response was performed by vital staining with Evans blue and pathologic examination. Results: The maximal tumor necrosis area that underwent sonication (1 MHz; 0.7 W/cm²; 10 min.) followed by PDT at a dose of 100 J/cm² was 100%. Conclusion: This is the first report to demonstrate the benefits of sono-photodynamic therapy (SPDT) consisting of low-power density ultrasound and PDT for the treatment of malignant glioma models

Dose enhancement effect of anticaner drugs associated with increased temperature in vitro

Aim: To evaluate in vitro the influence of elevated temperature (42 °C for 60 min) on the action of anticancer drugs doxorubicin, vinorelbine, carboplatin, ifosfamide, etoposide, oxaliplatin, docetaxel and gemcitabine. Methods: HeLa tumor cell cultures, 24 h after seeding, were incubated for 60 min with different concentrations of chemotherapeutical drugs at a temperature of 37 °C or 42 °C. 48 h later the number of viable cells in the flasks were counted using trypan-blue exclusion on a hemacytometer. Results: Hyperthermia alone caused only 10–20% growth inhibition of cell culture. All the chemotherapeutic drugs used demonstrated a dose enhancement effect at elevated temperature. Thermal enhancement ratio for cell proliferation for oxaliplatin, vinorelbine, carboplatin and ifosfamide exceeded 4, for doxorubicin and gemcitabine exceeded 2. Thermal enhancement ratio for cell death did not exceed 1.4. Conclusion: Synergism of hyperthermia and chemotherapeutical drugs was clearly demonstrated for oxaliplatin, vinorelbine, carboplatin, ifosfamide and to a lesser extent for doxorubicin and gemcitabine. Enhancement of the cytostatic effect of anticancer drugs by hyperthermia was more prominent than their cytotoxic effect.Цель: изучить in vitro влияние повышенной температуры (42 °C в течение 60 мин) на действие противоопухолевых препаратов: доксорубицина, винорельбина, карбоплатина, ифосфамида, этопозида, оксалиплатина, доцетаксела и гемцитабина. Методы: культуру опухолевых клеток HeLa через 24 ч после рассева инкубировали в течение 60 мин с различными концентрациями химиотерапевтических препаратов при температуре 37 °C или 42 °C. Спустя 48 ч подсчитывали количество живых клеток во флаконах, используя гемоцитометр и метод исключения красителя трипанового синего. Результаты: гипертермия сама по себе вызывала 10–20% угнетение роста культуры клеток. У всех исследованных химиотерапевтических препаратов отмечали эффект усиления при повышенной температуре. Коэффициент теплового усиления в отношении клеточной пролиферации для оксалиплатина, винорельбина, карбоплатина и ифосфамида превысил 4,0, для доксорубицина и гемцитабина — 2,0. Коэффициент теплового усиления в отношении гибели клеток не превышал 1,4. Выводы: синергизм гипертермии и химиотерапевтических препаратов продемонстрирован для оксалиплатина, винорельбина, карбоплатина, ифосфамида, в меньшей степени — для доксорубицина и гемцитабина. Усиление цитостатического эффекта противоопухолевых препаратов под действием гипертермии было более выраженным, чем их цитотоксического эффекта