{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T06:33:25Z","timestamp":1793428405086,"version":"4.5.0"},"reference-count":33,"publisher":"Radiation Research Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2023,4,22]]},"abstract":"<jats:p>This study conducted fundamental research to develop a more effective BNCT targeting cancer stem cells. We constructed plasmids that induced the overexpression of L-type amino acid transporter 1 (LAT1) tagged with tdTomato on the cytoplasmic membranes of CD133 expressing cancer cells. After transfection of the plasmids into a glioblastoma cell line (T98G), several clones overexpressing LAT1-tdTomato in the hypoxic microenvironment of the spheroids formed from each clone were obtained. Confocal laser microscopic observation confirmed that signals from LAT1-tdTomato overlapped with immunofluorescence signals from the second antibody binding to CD133 in the hypoxic microenvironment of the spheroids. As CD133-positive cells in the hypoxic microenvironment of T98G spheroids have cancer stem cell characteristics, LAT1 seems to be selectively overexpressed in cancer stem cell-like cells. An RI tracer method showed that cells overexpressing LAT1-tdTomato in the hypoxic microenvironment of spheroids incorporate 14C-BPA much more than cells that do not overexpress LAT1-tdTomato. Neutron radiation experiments showed a more significant regression in spheroids formed with clones than in spheroids formed with parental cells when spheroids were treated with 10BPA. These results suggest that BNCT combined with gene therapy targeting cancer stem cells is more effective in glioblastoma therapy.<\/jats:p>","DOI":"10.1667\/rade-22-00195.1","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T10:15:50Z","timestamp":1684750550000},"page":"21-31","source":"Crossref","is-referenced-by-count":2,"title":["Advanced Boron Neutron Capture Therapy Targeting Cancer Stem Cells by Selective Induction of LAT1 Overexpression"],"prefix":"10.1667","volume":"200","author":[{"given":"Toshiaki","family":"Tani","sequence":"first","affiliation":[{"name":"National Institutes for Quantum and Radiological Science and Technology Hospital, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Fujita","sequence":"additional","affiliation":[{"name":"Departments of Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Misawa","sequence":"additional","affiliation":[{"name":"Departments of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Tojo","sequence":"additional","affiliation":[{"name":"National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Shikano","sequence":"additional","affiliation":[{"name":"Departments of Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Research Reactor Institute, Kyoto University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"R Stupp, ME Hegi, WP Mason, et al.  \"Lancet Oncol.\"  10, \"Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.\" 459 (2009)","DOI":"10.1016\/S1470-2045(09)70025-7"},{"key":"3","doi-asserted-by":"crossref","unstructured":"R Stupp, WP Mason, MJ van den Bent, et al.  \"N Engl J Med.\"  352, \"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.\" 987 (2005)","DOI":"10.1056\/NEJMoa043330"},{"key":"12","unstructured":"GL. Locher,  \"Am J Reontgenol Radium Ther.\"  36, \"Biological effects and therapeutic possibilities of neutrons.\" 1 (1936)"},{"key":"2","doi-asserted-by":"crossref","unstructured":"JL Fisher, JA Schwartzbaum, M Wrensch, et al.  \"Neurol Clin.\"  25, \"Epidemiology of brain tumors.\" 867 (2007)","DOI":"10.1016\/j.ncl.2007.07.002"},{"key":"4","doi-asserted-by":"crossref","unstructured":"SY. Lee,  \"Genes Dis.\"  3, \"Temozolomide resistance in glioblastoma multiforme.\" 198 (2016)","DOI":"10.1016\/j.gendis.2016.04.007"},{"key":"5","doi-asserted-by":"crossref","unstructured":"A Sharma, DN Sharma, PK Julka, et al.  \"Lancet Oncol.\"  13, \"Treatment options in elderly patients with glioblastoma.\" 460 (2012)","DOI":"10.1016\/S1470-2045(12)70459-X"},{"key":"6","doi-asserted-by":"crossref","unstructured":"S Bao, Q Wu, RE Mclendon,  \"Nature.\"  444, \"Glioma stem cells promote radioresistance by preferential activation of the DNA damage response.\" 756 (2006)","DOI":"10.1038\/nature05236"},{"key":"7","doi-asserted-by":"crossref","unstructured":"SK Singh, C Hawkins, ID Clarke, et al.  \"Nature.\"  432, \"Identification of human brain tumour initiating cells.\" 396 (2004)","DOI":"10.1038\/nature03128"},{"key":"8","doi-asserted-by":"crossref","unstructured":"D Beier, JB Schulz, CP Beier,  \"Mol Cancer.\"  128, \"Chemoresistance of glioblastoma cancer stem cells-much more complex than expected.\" (2011)","DOI":"10.1186\/1476-4598-10-128"},{"key":"9","doi-asserted-by":"crossref","unstructured":"B Paola, O Barbara, F Lorenzo, et al.  \"Stem Cells.\"  31, \"CD133 is essential for glioblastoma stem cell maintenance.\" 857 (2013)","DOI":"10.1002\/stem.1317"},{"key":"10","doi-asserted-by":"crossref","unstructured":"Y Murota, K Tabu, T Taga,  \"Cells.\"  11, \"Cancer stem cell-associated immune microenvironment in recurrent glioblastomas.\" 2054 (2022)","DOI":"10.3390\/cells11132054"},{"key":"11","doi-asserted-by":"crossref","unstructured":"H Cerecetto  and M Couto  \"Medicinal chemistry of boron-bearing compounds for BNCT in glioma treatment: current challenges and perspectives in glioma contemporary diagnostic and therapeutic approaches.\" (2018)","DOI":"10.5772\/intechopen.76369"},{"key":"13","doi-asserted-by":"crossref","unstructured":"FB Rolf, M Graca, KH Otto, et al.  \"Radiat Oncol.\"  7, \"Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer.\" 146 (2012)","DOI":"10.1186\/1748-717X-7-146"},{"key":"14","doi-asserted-by":"crossref","unstructured":"RF Barth, P Mi, W Yang,  \"Cancer Commun.\"  38, \"Boron delivery agents for neutron capture therapy of cancer.\" 35 (2018)","DOI":"10.1186\/s40880-018-0299-7"},{"key":"15","doi-asserted-by":"crossref","unstructured":"M Yoshimoto, N Honda, H Kurihara, et al.  \"Cancer Sci.\"  109, \"Non-invasive estimation of 10B-4-borono-L-phenylala-ninederived boron concentration in tumors by PET using 4-borono-2-18F-fluoro-phenylalanine.\" 1617 (2018)","DOI":"10.1111\/cas.13553"},{"key":"16","doi-asserted-by":"crossref","unstructured":"N Kondo, M Hikida, M Nakada, et al.  \"Cancers.\"  12, \"Glioma stem-like cells can be targeted in boron neutron capture therapy with boronophenylalanine.\" 3040 (2020)","DOI":"10.3390\/cancers12103040"},{"key":"17","doi-asserted-by":"crossref","unstructured":"T Nomoto, Y Inoue, Y Yao, et al.  \"Sci. Adv.\"  6, \"Poly (vinyl alcohol) boosting therapeutic potential of p-boronophenylalanine in neutron capture therapy by modulating metabolism.\" eaaz1722 (2020)","DOI":"10.1126\/sciadv.aaz1722"},{"key":"18","doi-asserted-by":"crossref","unstructured":"D Allah  and SC Garth  \"Cancer Res.\"  69, \"L-Amino acid transporter-1 and boronophenylalanine -based boron neutron capture therapy of human brain tumors.\" 2126 (2009)","DOI":"10.1158\/0008-5472.CAN-08-2345"},{"key":"19","doi-asserted-by":"crossref","unstructured":"S Miyatake, S Kawabata, K Yokoyama, et al.  \"J. Neurooncol.\"  91, \"Survival benefit of boron neutron capture therapy for recurrent malignant gliomas.\" 199 (2009)","DOI":"10.1007\/s11060-008-9699-x"},{"key":"20","doi-asserted-by":"crossref","unstructured":"F Yoshida, T Kurita, K Endo, et al.  \"Appl Radiat Isot.\"  164, \"Difference in BPA uptake between glioma stem-like cells and their cancerous cells.\" 109234 (2020)","DOI":"10.1016\/j.apradiso.2020.109234"},{"key":"21","doi-asserted-by":"crossref","unstructured":"S Ting, Z Youxin, X Xueshun, et al.  \"Appl Radiat Isot.\"  70, \"Selective uptake of boronophenylalanine by glioma stem\/progenitor cells.\" 1512 (2021)","DOI":"10.1016\/j.apradiso.2012.04.005"},{"key":"22","doi-asserted-by":"crossref","unstructured":"Y Wada, K Hirose, T Harada, et al.  \"J Radiat Res.\"  59, \"Impact of oxygen status on 10B-BPA uptake into human glioblastoma cells, referring to significance in boron neutron capture therapy.\" 122 (2018)","DOI":"10.1093\/jrr\/rrx080"},{"key":"23","doi-asserted-by":"crossref","unstructured":"K Ohnishi, T Tani, S Bando, et al.  \"Int J Oncol.\"  45, \"Plastic induction of CD133AC133-positive cells in the microenvironment of glioblastoma spheroid.\" 581 (2014)","DOI":"10.3892\/ijo.2014.2483"},{"key":"24","doi-asserted-by":"crossref","unstructured":"K Ohnishi, T Tani, N Tojo, et al.  \"Biochemi Biophys Res Commu.\"  546, \"Glioblastoma cell line shows phenotypes of cancer stem cells in hypoxic microenvironment of spheroids.\" 150 (2021)","DOI":"10.1016\/j.bbrc.2021.02.009"},{"key":"25","doi-asserted-by":"crossref","unstructured":"T Tani, N Tojo, K Ohnishi,  \"Oncol Lett.\"  23, \"Preferential radiosensitization to glioblastoma cancer stem cell-like cells by a Hsp90 inhibitor, N-vinylpyrrolidone-AUY-922\" 102 (2022)","DOI":"10.3892\/ol.2022.13222"},{"key":"26","doi-asserted-by":"crossref","unstructured":"M Yamaguchi, A Ito, N Okamoto, et al.  \"J Biosci Bioengi.\"  114, \"Heat-inducible transgene expression system incorporating a positive feedback loop of transcriptional amplification for hyperthermiainduced gene therapy.\" 460 (2012)","DOI":"10.1016\/j.jbiosc.2012.05.006"},{"key":"27","doi-asserted-by":"crossref","unstructured":"H Iida, M Suzuki, R Goitsuka, et al.  \"Int J Oncol.\"  40, \"Hypoxia induces CD133 expression in human lung cancer cells by up-regulation of OCT3\/4 and SOX2.\" 71 (2011)","DOI":"10.3892\/ijo.2011.1207"},{"key":"28","doi-asserted-by":"crossref","unstructured":"K Ohnishi, M Misawa, N Sikano, et al.  \"Radiat Res.\"  196, \"Enhancement of cancer cell-killing effects of boron neutron capture therapy by manipulating the expression of L-type amino acid transporter 1.\" 17 (2021)","DOI":"10.1667\/RADE-20-00214.1"},{"key":"29","doi-asserted-by":"crossref","unstructured":"N Nozawa-Suzuki, H Nagasawa, K Ohnishi, et al.  \"Biochemi Biophys Res Commu.\"  457, \"The inhibitory effect of hypoxic cytotoxin on the expansion of cancer stem cells in ovarian cancer.\" 706 (2015)","DOI":"10.1016\/j.bbrc.2015.01.053"},{"key":"30","doi-asserted-by":"crossref","unstructured":"K Kusamori, M Nishikawa, Y Takahashi, et al.  \"Drug Deliv Syst.\"  28, \"Development of multicellular spheroid for cell-based therapy.\" 45 (2013)","DOI":"10.2745\/dds.28.45"},{"key":"31","doi-asserted-by":"crossref","unstructured":"B Wei, XY Han, CL Qi, et al.  \"Plos One.\"  7, \"Coaction of spheroid-derived stem-like cells and endothelial progenitor cells promotes development of colon cancer.\" e39069 (2012)","DOI":"10.1371\/journal.pone.0039069"},{"key":"32","doi-asserted-by":"crossref","unstructured":"T Watabe, K Kaneda-Nakashima, Y Shirakami, et al.  \"Oncotarget.\"  11, \"Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice.\" 1388 (2020)","DOI":"10.18632\/oncotarget.27552"},{"key":"33","doi-asserted-by":"crossref","unstructured":"K Kaneda-Nakashima, Z Zhang, Y Manabe, et al.  \"Cancer Sci.\"  112, \"\u03b1-Emitting cancer therapy using 211At-AAMT targeting LAT1.\" 1132 (2021)","DOI":"10.1111\/cas.14761"}],"container-title":["Radiation Research"],"original-title":[],"link":[{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-22-00195.1\/3238720\/10.1667_rade-22-00195.1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-22-00195.1\/3238720\/10.1667_rade-22-00195.1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T06:00:50Z","timestamp":1793426450000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-200\/issue-1\/RADE-22-00195.1\/Advanced-Boron-Neutron-Capture-Therapy-Targeting-Cancer-Stem-Cells-by\/10.1667\/RADE-22-00195.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,22]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,7,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-22-00195.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,22]]}}}