Abstract

Abstract Radiotherapy is an effective locoregional control modality for many types of tumors. However, sometimes treatment failures occur due to radioresistance of cancer cells. To reduce treatment failure, elucidating the epigenetic mechanism of radioresistance is very important. Nucleotides associated with radioresistance could be promising treatment targets or prognostic markers. The cancer stem cells (CSCs) theory helps us to understand the resistance mechanism. CSCs are small population of cells in cancer with stem cell properties such as self-renewal, cell proliferation and multiple-differentiation. CSCs are very important clinical target, because they induce tumor metastasis and recurrence. Targeting CSCs would be promising therapy to reduce treatment failure. X-ray induces DNA damages mostly through reactive oxygen species (ROS). Since CSCs have the low levels of ROS and high DNA repair capacity, and exist under hypoxia condition, CSCs are resistant to X-ray radiotherapy. Therefore, it is difficult to eliminate CSCs with X-ray. Carbon ion beam is known to be effective to cancer cells in hypoxic condition, since it is high linear energy transfer (LET) beam inducing direct damage to DNA rather than mediating ROS. Therefore, carbon ion beam radiotherapy is more effective than x-ray radiotherapy against CSCs. However, even with carbon ion beam, there are treatment failures, indicating that there could be some protection mechanism other than ROS, associated in carbon ion beam resistance. Our purpose is to elucidate the mechanism of radioresistance and to identify the difference between X-ray resistance and carbon-ion beam resistance by nucleotides profiling analysis. We analyzed X-ray resistant (total 60Gy irradiated, 6fraction) and carbon ion beam resistant (total 30Gy irradiated, 6fraction) mouse squamous cell line NR-S1 by micro array. Total 23474 cDNA, 1265 micro RNA (miR) data was obtained and each cell lines expression pattern was totally different. We listed up all the cDNA and miR which specifically expressed in X-ray resistant cells (64 cDNA, 20 miR) and carbon ion beam resistant cells (34 cDNA, 16 miR). This data would be a basis in elucidating the mechanism of radioresistance, and our next step is to identify which cDNA or miR is related with the resistance. Note: This abstract was not presented at the meeting. Citation Format: Sungjae Baek, Hideshi Ishii, Katsutoshi Sato, Naohiro Nishida, Keisuke Tamari, Kazuhiko Hayashi, Yuji Seo, Koichi Kawamoto, Jun Koseki, Masamitsu Konno, Yuichiro Doki, Masaki Mori, Kazuhiko Ogawa. Microarray analysis of radioresistant mouse squamous cell carcinoma: comparison of x-ray resistance and carbon-ion beam resistance. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3334. doi:10.1158/1538-7445.AM2015-3334

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