@article{oai:repo.qst.go.jp:00080478,
 author = {Sai, Sei and Ho Kim, Eun and Vares, Guillaume and Suzuki, Masao and Yu, Dong and Horimoto, Yoshiya and Hayashi, Mitsuhiro and Sai, Sei and Ho Kim, Eun and Vares, Guillaume and Suzuki, Masao and Yu, Dong and Horimoto, Yoshiya},
 issue = {8},
 journal = {American journal of cancer research},
 month = {Aug},
 note = {To investigate whether carbon-ion beam alone, or in combination with lapatinib, has a beneficial effect in targeting HER2-positive breast cancer stem-like cells (CSCs) compared to that of X-rays, human breast CSCs derived from BT474 and SKBR3 cell lines were treated with a carbon-ion beam or X-rays irradiation alone or in combination with lapatinib, and then cell viability, spheroid formation assays, apoptotic analyses, gene expression analysis of related genes, and -H2AX foci  were performed. Spheroid formation assays confirmed that ESA+/CD24- cells have CSC properties compared to ESA-/CD24+ cells. CSCs were more highly enriched after X-ray irradiation combined with lapatinib, whereas carbon-ion beam combined with lapatinib significantly decreased the proportion of CSCs. Carbon-ion beam combined with lapatinib significantly suppressed spheroid formation compared to X-rays combined with lapatinib or carbon ion beam alone. Cell cycle analysis showed that carbon ion beam combined with lapatinib predominantly enhanced sub-G1 and G2/M arrested population compared to that of carbon-ion beam, X-ray treatments alone. Carbon-ion beam combined with lapatinib significantly enhanced apoptosis and carbon-ion beam alone dose-dependently increased autophagy-related expression of Beclin1 and in combination with lapatinib greatly enhanced ATG7 expression at protein levels. In addition, a large-sized H2AX foci in CSCs were induced by carbon ion beam combined with lapatinib treatment in CSCs compared to cells receiving X-rays or carbon-ion beam alone. Altogether, combination of carbon-ion beam irradiation and lapatinib has a high potential to kill HER2-positive breast CSCs, causing severe irreparable DNA damage, enhanced autophagy, and apoptosis.},
 pages = {2371--2386},
 title = {Combination of carbon-ion beam and dual tyrosine kinase inhibitor, lapatinib, effectively destroys HER2 positive breast cancer stem-like cells.},
 volume = {10},
 year = {2020}
}