@article{oai:oist.repo.nii.ac.jp:00001719, author = {Vares, Guillaume and Ahire, Vidhula and Sunada, Shigeaki and Ho Kim, Eun and Sai, Sei and Chevalier, François and Romeo, Paul-Henri and Yamamoto, Tadashi and Nakajima, Tetsuo and Saintigny, Yannick}, journal = {Radiotherapy and Oncology}, month = {Jul}, note = {Background and purpose High-grade chondrosarcomas are chemo- and radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new therapeutic strategies are urgently needed. Material and methods Chondrosarcoma cells (CH-2879) were exposed to carbon-ion irradiation, combined with miR-34 mimic and/or rapamycin administration. The effects of treatment on cancer stem cells, stemness-associated phenotype, radioresistance and tumor-initiating properties were evaluated. Results We show that high-grade chondrosarcoma cells contain a population of radioresistant cancer stem cells that can be targeted by a combination of carbon-ion therapy, miR-34 mimic administration and/or rapamycin treatment that triggers FOXO3 and miR-34 over-expression. mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression. Conclusion Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment resistance of high-grade chondrosarcoma.}, pages = {253--261}, title = {A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells}, volume = {150}, year = {2020} }