@misc{oai:repo.qst.go.jp:00068770,
 author = {Nojiri, Kazunori and Imadome, Kaori and Sakai, Minako and Gotou, Miyako and Matsumoto, Yoshitaka and Ishikawa, Atsuko and Iwakawa, Mayumi and 野尻 和典 and 今留 香織 and 酒井 美奈子 and 中渡 美也子 and 松本 孔貴 and 石川 敦子 and 岩川 眞由美},
 month = {Nov},
 note = {Purpose/Objective(s):The purpose of this study was to identify molecular mechanism induced by carbon ion radiotherapy in order to provide information on potential targets for prediction of its effectiveness.
Materials/Methods:Murine squamous cell carcinomas, NR-S1 (resistant to gamma-irradiation), and SCCVII (sensitive), were transplanted in hind legs of C3H/He male mice and established solid tumors (7.5-8.5 mm in diameter) were locally irradiated with carbon ion beam at 30Gy. Carbon-12 ions were accelerated by the Heavy Ion Medical Accelerator in Chiba or HIMAC synchrotron up to 290 MeV/u with a dose rate of approximately 3 Gy /min. Tumor growth delay (TGD) time, reduction rate of tumor, and recurrence rate of tumor were investigated as parameters of radiosensitivity of tumors. The mice were sacrificed and immediately dissected before irradiation and after different time points, such as 6,12,18h, 1, 3, 5, 7, 10, 15, 20 days after irradiation or recurrence for transcriptome assays and pathological investigation. Expression analyses were performed using single-color analysis microarrays consisting of 55k genes. Principal Compornent Analysis (PCA) was used to investigate similarity of comprehensive overview of the changes in gene expression between expression profiles of two tumors. Analysis of variance (ANOVA) was applied to the intensity of each tumor at different time point to evaluate significant differences.
Results:TGD time of NR-S1 and SCCVII was 30 days and 56 days, reduction rate of NR-S1 and SCCVII was 40% and 100%, and recurrence rate of NR-S1 and SCCVII was 75% and 50%, respectively.PCA showed that all expression profiles of NR-S1 were identified as a group, while those of SCCVII were identified as another group. Recurred tumors showed different profiles from non-irradiation control tumors. We detected genes, whose expressions were significantly up-regulated or down regulated at each time point after carbon-irradiation (p value< 0.0001). At 6 hours after irradiation, fourteen genes, which were related with cell cycle regulation, were differentially expressed in both tumors. Eleven genes, which were related with inflammation or extracellular matrix, were up-regulated at 6 hours in both tumors, however, their expression changes on time-course were different. Pathological specimen showed duplet cells in both tumors 1 day after irradiation and continuous infiltration of inflammatory cells in SCCVII.
Conclusions:Tumor growth assays revealed that two murine tumors, which have different radiosensitivity to gamma irradiation, kept their intrinsic radiosensitivity to carbon-ion irradiation. Transcriptional profiling of two tumors identified a number of carbon-ion irradiation response genes in murine tumors. We have also identified genes as being candidates for predictive markers of radiosensitivity to carbon-ion therapy., 48th Annual Meeting of the American Society for Therapeutic Radiology and Oncology},
 title = {Microarray Analysis Of The Transcriptional Response To Carbon Ion Irradiation In Murine Tumors},
 year = {2006}
}