Optimizing radiotherapy of @entity1313 by a combination of @entity2903 _ XXXX .

@entity1 @entity137 @entity1313 @entity5 @entity2904 @entity3733 @entity11 @entity3460 @entity19981 @entity2903 @entity236
BACKGROUND _ OBJECTIVE: @entity2903 ( @entity2904 ), a second generation alkylating drug, an effective cytotoxic agent as well as radiosensitizer for malignant @entity1313 , has side effects like myelosuppression. @entity19981 (LND) increases the effectiveness of several experimental multiple chemotherapy protocols, without increasing @entity236 and is effective in @entity1313 @entity1 . The objective of the present studies was to investigate whether combining clinically relevant doses of LND and @entity2904 could increase the proliferation and radiation response of malignant @entity1 @entity1313 cells in vitro. METHODS: A malignant @entity1 @entity11 (U373MG) cell line was used in these studies. @entity2904 (20, 40 or 60 microM) or LND (100, 150 or 200 microM), or the combination of both (20 and 100 microM, respectively) in 0.1 per cent @entity3733 ( @entity3733 ) were added three days after setting up cultures, in six well plates (5 x 10(4) cells/ well). The effects of continuous treatment for two days on proliferation response and @entity137 were studied after trypsinization; by cell counts and the uptake of @entity3460 dye (0.5%). For the study of radiation (60Co-Gamma-rays, 2 Gy) response, drugs were removed 4 h after irradiation and cultures were grown further in drug free, normal growth medium for another 20 h or 44 h. RESULTS: Continuous presence of @entity2904 or LND for two days significantly inhibited cell proliferation in a concentration dependent manner. The frequencies of non viable cells increased significantly only at higher concentrations of LND. Combination of 20 microM @entity2904 with 100 microM LND had additive effects on proliferation response, without affecting cell viability. Short-term drug treatments without irradiation did not induce micronuclei formation. Cell proliferation and viability were also not affected. However, post-irradiation presence of either of these drugs for 4 h significantly reduced the proliferation response, 24 and 48 h after treatments. It was further inhibited by the combination treatment. On the contrary, radiation induced micronuclei formation was enhanced by either of the drugs; which was significantly increased by the combined treatment, 24 h as well as 48 h after irradiation. No effects on cell viability were observed, immediately after these treatments as well as at later time points. INTERPRETATION _ CONCLUSION: Our findings showed that combination of @entity2904 and LND at clinically achievable, low plasma concentrations could inhibit @entity5 growth, and @entity19981 could reduce the dose of @entity2903 required for radiosensitization of @entity1313 .
