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Experimental and Clinical Therapeutics

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP183) Effect of high-dose spatially fractionated GRID radiation on regression of distant human lung tumor xenografts.

Sultanov, Marianna*,1, Mohiuddin, Mohammed1, Ahmed, Mansoor1, 1 Radiation Medicine, Lexington, KY, USA

ABSTRACT- The purpose of this study is to evaluate and compare the tumor regressing effects of low energy high-dose spatially fractionated GRID radiation (SFGRT) with conventional ionizing radiation therapy (IRT). A549 lung adenocarcinoma tumor cell line was injected in both right (RT) and left (LT) flanks of 86 nude mice. Mice were randomized into 7 groups: I: No treatment in either LT or RT tumors; II: 15 Gy SFGRT as a single dose to the LT tumor only; III: 15 Gy SFGRT plus 5 fractions of 2 Gy IRT to the LT tumor only; IV: 15 Gy SFGRT as a single dose to the LT tumor and 5 fractions of 2 Gy IRT to the RT tumor; V: 7.5 Gy IRT as a single dose to the LT tumor only; VI: 7.5 Gy IRT plus 5 fractions of 2 Gy IRT to the LT tumor only; VII: 7.5 Gy IRT as a single dose to LT tumor and 5 fractions of 2 Gy IRT to the RT tumor. Tumor regression was monitored weekly twice for 90 days beginning from the 1st day of treatment. Two mice from each group were euthanized at 3 hours after high-dose and 24 hours after the end of treatment for the tumor tissue harvest. Protein kinetics of bax, bcl-2, and cytochrome C release were assessed using Western blot and immunofluorescence. Tumor regression was observed in all treated groups compared to the untreated group. Initial regression of both LT and RT tumors was less pronounced in Group II versus Group V. However, in Group II both LT and RT tumors showed a stable and sustained tumor growth delay compared to Group V. No significant differences in tumor regression and delay (in both RT and LT tumors) between Group III and Group VI were observed. RT and LT tumors of Group IV regressed significantly with a prolonged growth delay. This effect was not observed in corresponding Group VII where the tumor growth delay was very short. Increased cell death was observed in the RT tumors of Group II, III and IV compared to RT tumors in Groups V, VI and VII. Further, the RT tumors of Group II and III showed increased bax induction with concomitant down-regulation of bcl-2 associated with enhanced Cytochrome C release compared to Groups V and VI. These findings strongly suggest that SFGRT is a potent inducer of pro-apoptotic abscopal factors than the high-dose open-field radiation. Studies are underway to assess whether the abscopal factors induced by SFGRT have effects in the death of endothelial cells in the RT and LT tumor compartments.

Key words: SFGRT, tumor regression, lung cancer, abscopal


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2005 RRS