Thermal enhancement of melphalan and oxaliplatin cytotoxicity in vitro Journal Article
| Authors: | Urano, M.; Ling, C. C. |
| Article Title: | Thermal enhancement of melphalan and oxaliplatin cytotoxicity in vitro |
| Abstract: | It has been established that hyperthermia can enhance cytotoxicity of some chemotherapeutic agents. This has led to various clinical trials of thermochemotherapy, although many questions remain unanswered. The effects of various agents have been studied on animal tumours with different histopathology at elevated temperatures. These studies indicated that alkylating agents were most effective to all tumours at a moderately elevated temperature. Cisplatin was also effective to all tumours, but its effectiveness at 41.5°C was less than that of alkylating agents. To quantitatively study these findings, the magnitude of thermal enhancement of melphalan, an alkylating agent, and that of oxaliplatin, a new platinum compound, were studied at 37-44.5°C by the colony formation assay. The dose of each agent was kept constant, and cell survival was determined as a function of treatment time. The cell survival curve was exponentially related with treatment time at all test temperatures, and the T0 (the time to reduce survival from 1 to 0.37) decreased with an increasing temperature. These results suggested that the cytotoxic effect of these agents occurred with a constant rate at 37°C, and the rate was facilitated with an increasing temperature. This suggests that heat can accelerate the cytotoxic chemical reaction, leading to substantial thermal enhancement. The thermal enhancement ratio (TER, the ratio of the T0 at 37°C to the T0 at an elevated temperature) increased with an increase in the temperature. The activation energy for melphalan at moderately elevated temperatures was largest among the agents tested in the laboratory and that for oxaliplatin was approximately half of the melphalan activation energy. This suggests that the thermal enhancement for the cytotoxicity of melphalan or alkylating agents might be the greatest. Potential mechanisms of thermal enhancement of cytotoxicity were discussed. |
| Keywords: | controlled study; histopathology; cisplatin; fluorouracil; drug efficacy; nonhuman; antineoplastic agents; combined modality therapy; animal cell; animals; cell survival; alkylating agent; melphalan; cytotoxicity; in vitro study; drug effect; tumor cells, cultured; carmustine; drug mechanism; quantitative analysis; laboratory test; antineoplastic agents, alkylating; tumor cell; bleomycin; mitomycin c; platinum; temperature; hyperthermic therapy; hyperthermia, induced; oxaliplatin; organoplatinum compounds; chemical reaction; colony formation; heat; high temperature; thermal enhancement; thermochemotherapy; article; platinum compound; ter |
| Journal Title: | International Journal of Hyperthermia |
| Volume: | 18 |
| Issue: | 4 |
| ISSN: | 0265-6736 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2002-07-01 |
| Start Page: | 307 |
| End Page: | 315 |
| Language: | English |
| DOI: | 10.1080/02656730210123534 |
| PUBMED: | 12079586 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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