{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T03:45:01Z","timestamp":1782704701786,"version":"3.54.5"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Br J Cancer"],"published-print":{"date-parts":[[2026,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To investigate the antitumoral and pro-inflammatory effect of Boron Neutron Capture Therapy (BNCT) following systemic or intravesical borophenilalanine administration, and to compare it with conventional radiotherapy (cRT) in an experimental bladder cancer (BC) model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty-four Wistar rats were used, of which half were exposed to carcinogen to induce BC. Radiation therapy (RT) was performed both in the MARK TRIGA-II reactor for BNCT and in the Radiation Oncology divison for cRT. After necropsy, bladder and perivesical tissues were collected. Tumour staging, tumour burden, proliferative, and apoptotic indexes were evaluated for bladder samples. Bladder and perivesical tissues (colon, uterus, and anterior abdominal wall) were also assessed for inflammatory changes in H&amp;E-stained sections, and also bladder TNF-\u03b1 expressions was examined by immunohistochemistry and Western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The animals with cancer had a 15\u201330% decrease in tumour burden after RT. The incidence of persistent papillary urothelial carcinoma was 100% in the Cancer-cRT group and 87.5% in the Cancer-BNCT-Sys group, whereas a lower incidence was observed in the Cancer-BNCT-IV group (71.4%). A lower proliferative and a higher apoptotic indexes were observed in \u00a0Cancer-BNCT-IV group compared to Cancer-cRT. Immunohistochemistry and Western blot for TNF-\u03b1 expression showed that pro-inflammatory response in bladder was lower in BNCT-IV group\u00a0among cancer treated groups. Moreover, there were lower proinflammatory adverse findings in perivesical tissues, including colon and uterus, in animals receiving BNCT-IV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Similar to cRT, systemic or intravesical BNCT resulted in a partial decrease in tumour burden, but fewer adverse findings by intravesical borophenilalanine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03418-w","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:45:29Z","timestamp":1776408329000},"page":"223-231","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Boron neutron capture therapy (BNCT) for experimental bladder cancer: systemic or intravesical approach"],"prefix":"10.1038","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-4662","authenticated-orcid":false,"given":"Kerem","family":"Teke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00fcneyt","family":"\u00d6zer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00fc\u015fra","family":"Yaprak Bayrak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130skender Atilla","family":"Reyhancan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7i\u011fdem","family":"Vural","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Kasap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015feg\u00fcl \u00dcnal","family":"Karabey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcrler","family":"Akp\u0131nar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efe","family":"Bosnal\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neslihan","family":"Koyuncu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130brahim Erkut","family":"Avc\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"Erbay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammet","family":"Sahip K\u0131z\u0131lta\u015f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Hun\u00e7","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyneb","family":"Camtakan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6nder","family":"Kara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6rkem","family":"Aksu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zdal","family":"Dillio\u011flugil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"3418_CR1","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.eururo.2019.08.016","volume":"76","author":"M Babjuk","year":"2019","unstructured":"Babjuk M, Burger M, Comperat EM, Gontero P, Mostafid AH, Palou J, et al. European Association of Urology guidelines on non-muscle-invasive bladder cancer (TaT1 and carcinoma in situ) - 2019 update. Eur Urol. 2019;76:639.","journal-title":"Eur Urol"},{"key":"3418_CR2","doi-asserted-by":"publisher","first-page":"786.e1","DOI":"10.1016\/j.urolonc.2021.03.009","volume":"39","author":"R Rodrigues Pessoa","year":"2021","unstructured":"Rodrigues Pessoa R, Mueller AC, Boxley P, Flaig TW, Piper C, Konety B, et al. Systematic review and meta-analysis of radiation therapy for high-risk non-muscle invasive bladder cancer. Urol Oncol. 2021;39:786.e1.","journal-title":"Urol Oncol"},{"key":"3418_CR3","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1111\/j.1464-410X.2010.09564.x","volume":"107","author":"AM Maarouf","year":"2011","unstructured":"Maarouf AM, Khalil S, Salem EA, ElAdl M, Nawar N, Zaiton F. Bladder preservation multimodality therapy as an alternative to radical cystectomy for treatment of muscle invasive bladder cancer. BJU Int. 2011;107:1605.","journal-title":"BJU Int"},{"key":"3418_CR4","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1007\/s00345-019-02982-6","volume":"38","author":"P Gontero","year":"2020","unstructured":"Gontero P, Pisano F, Palou J, Joniau S, Albersen M, Colombo R, et al. Complication rate after cystectomy following pelvic radiotherapy: an international, multicenter, retrospective series of 682 cases. World J Urol. 2020;38:1959.","journal-title":"World J Urol"},{"key":"3418_CR5","doi-asserted-by":"publisher","first-page":"71","DOI":"10.14338\/IJPT-22-00002.1","volume":"9","author":"WH Jin","year":"2022","unstructured":"Jin WH, Seldon C, Butkus M, Sauerwein W, Giap HB. A review of boron neutron capture therapy: its history and current challenges. Int J Part Ther. 2022;9:71.","journal-title":"Int J Part Ther"},{"key":"3418_CR6","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s10147-019-01480-4","volume":"25","author":"M Suzuki","year":"2020","unstructured":"Suzuki M. Boron neutron capture therapy (BNCT): a unique role in radiotherapy with a view to entering the accelerator-based BNCT era. Int J Clin Oncol. 2020;25:43.","journal-title":"Int J Clin Oncol"},{"key":"3418_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2913-x","volume":"16","author":"T Watanabe","year":"2016","unstructured":"Watanabe T, Hattori Y, Ohta Y, Ishimura M, Nakagawa Y, Sanada Y, et al. Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [(18)F]-L-FBPA positron emission tomography in boron neutron capture therapy. BMC Cancer. 2016;16:859.","journal-title":"BMC Cancer"},{"key":"3418_CR8","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1046\/j.1442-2042.1999.00623.x","volume":"6","author":"O Yaman","year":"1999","unstructured":"Yaman O, Ozdiler E, Sozen S, Gogus O. Transmurally absorbed intravesical chemotherapy with dimethylsulfoxide in an animal model. Int J Urol. 1999;6:87.","journal-title":"Int J Urol"},{"key":"3418_CR9","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.addr.2012.02.011","volume":"65","author":"R Notman","year":"2013","unstructured":"Notman R, Anwar J. Breaching the skin barrier-insights from molecular simulation of model membranes. Adv Drug Deliv Rev. 2013;65:237.","journal-title":"Adv Drug Deliv Rev"},{"key":"3418_CR10","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1002\/nau.23204","volume":"36","author":"WF Rawls","year":"2017","unstructured":"Rawls WF, Cox L, Rovner ES. Dimethyl sulfoxide (DMSO) as intravesical therapy for interstitial cystitis\/bladder pain syndrome: a review. Neurourol Urodyn. 2017;36:1677.","journal-title":"Neurourol Urodyn"},{"key":"3418_CR11","first-page":"13","volume":"102","author":"RA Vanderpool","year":"1994","unstructured":"Vanderpool RA, Hoff D, Johnson PE. Use of inductively coupled plasma-mass spectrometry in boron-10 stable isotope experiments with plants, rats, and humans. Environ Health Perspect. 1994;102:13.","journal-title":"Environ Health Perspect"},{"key":"3418_CR12","doi-asserted-by":"crossref","unstructured":"Landberg T, Chavaudra J, Dobbs J, Gerard JP, Hanks G, Horiot JC, et al. International Commission on Radiation Units and Measurements. ICRU Report 62: Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50). Bethesda: ICRU Publications (1999).","DOI":"10.1093\/jicru_os32.1.48"},{"key":"3418_CR13","doi-asserted-by":"publisher","first-page":"7683","DOI":"10.7150\/thno.45358","volume":"10","author":"T Lin","year":"2020","unstructured":"Lin T, Zhang Q, Yuan A, Wang B, Zhang F, Ding Y, et al. Synergy of tumor microenvironment remodeling and autophagy inhibition to sensitize radiation for bladder cancer treatment. Theranostics. 2020;10:7683.","journal-title":"Theranostics"},{"key":"3418_CR14","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1016\/S0360-3016(03)00214-1","volume":"56","author":"AK Gupta","year":"2003","unstructured":"Gupta AK, Cerniglia GJ, Mick R, Ahmed MS, Bakanauskas VJ, Muschel RJ, et al. Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002. Int J Radiat Oncol Biol Phys. 2003;56:846.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"3418_CR15","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.meddos.2013.02.007","volume":"38","author":"V Vyas","year":"2013","unstructured":"Vyas V, Palmer L, Mudge R, Jiang R, Fleck A, Schaly B, et al. On bolus for megavoltage photon and electron radiation therapy. Med Dosim. 2013;38:268.","journal-title":"Med Dosim"},{"key":"3418_CR16","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s00418-024-02306-9","volume":"162","author":"F Naselli","year":"2024","unstructured":"Naselli F, Cardinale PS, Volpes S, Martino C, Cruciata I, Valenti R, et al. An alternative approach of TUNEL assay to specifically characterize DNA fragmentation in cell model systems. Histochem Cell Biol. 2024;162:429.","journal-title":"Histochem Cell Biol"},{"key":"3418_CR17","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3892\/ol.2023.14167","volume":"27","author":"T Simsek","year":"2024","unstructured":"Simsek T, Bal Albayrak MG, Akpinar G, Canturk NZ, Kasap M. Downregulated GPD1 and MAGL protein levels as potential biomarkers for the metastasis of triple\u2011negative breast tumors to axillary lymph nodes. Oncol Lett. 2024;27:34.","journal-title":"Oncol Lett"},{"key":"3418_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-07760-x","volume":"21","author":"T Yoneyama","year":"2021","unstructured":"Yoneyama T, Hatakeyama S, Sutoh Yoneyama M, Yoshiya T, Uemura T, Ishizu T, et al. Tumor vasculature-targeted (10)B delivery by an Annexin A1-binding peptide boosts effects of boron neutron capture therapy. BMC Cancer. 2021;21:72.","journal-title":"BMC Cancer"},{"key":"3418_CR19","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1016\/j.ijrobp.2006.07.1373","volume":"66","author":"M Suzuki","year":"2006","unstructured":"Suzuki M, Sakurai Y, Nagata K, Kinashi Y, Masunaga S, Ono K, et al. Impact of intra-arterial administration of boron compounds on dose-volume histograms in boron neutron capture therapy for recurrent head-and-neck tumors. Int J Radiat Oncol Biol Phys. 2006;66:1523.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"3418_CR20","doi-asserted-by":"publisher","first-page":"e67","DOI":"10.1016\/j.ijrobp.2010.09.057","volume":"82","author":"L Kankaanranta","year":"2012","unstructured":"Kankaanranta L, Seppala T, Koivunoro H, Saarilahti K, Atula T, Collan J, et al. Boron neutron capture therapy in the treatment of locally recurred head-and-neck cancer: final analysis of a phase I\/II trial. Int J Radiat Oncol Biol Phys. 2012;82:e67.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"3418_CR21","doi-asserted-by":"crossref","unstructured":"Fukuda H. Boron neutron capture therapy (BNCT) for cutaneous malignant melanoma using (10)B-p-Boronophenylalanine (BPA) with special reference to the radiobiological basis and clinical results. Cells. 2021;10.","DOI":"10.3390\/cells10112881"},{"key":"3418_CR22","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1002\/cac2.12089","volume":"40","author":"MA Dymova","year":"2020","unstructured":"Dymova MA, Taskaev SY, Richter VA, Kuligina EV. Boron neutron capture therapy: Current status and future perspectives. Cancer Commun (Lond). 2020;40:406.","journal-title":"Cancer Commun (Lond)"},{"key":"3418_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.925671","volume":"12","author":"F Tang","year":"2022","unstructured":"Tang F, Wei Y, Zhang S, Wang J, Gu W, Tang F, et al. Evaluation of pharmacokinetics of boronophenylalanine and its uptake in gastric cancer. Front Oncol. 2022;12:925671.","journal-title":"Front Oncol"},{"key":"3418_CR24","doi-asserted-by":"publisher","first-page":"817","DOI":"10.3109\/0284186X.2011.582516","volume":"50","author":"T Schmitz","year":"2011","unstructured":"Schmitz T, Blaickner M, Ziegner M, Bassler N, Grunewald C, Kratz JV, et al. Dose determination using alanine detectors in a mixed neutron and gamma field for boron neutron capture therapy of liver malignancies. Acta Oncol. 2011;50:817.","journal-title":"Acta Oncol"},{"key":"3418_CR25","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1093\/rpd\/ncq466","volume":"143","author":"F Ballarini","year":"2011","unstructured":"Ballarini F, Bortolussi S, Clerici AM, Ferrari C, Protti N, Altieri S. From radiation-induced chromosome damage to cell death: modelling basic mechanisms and applications to boron neutron capture therapy. Radiat Prot Dosim. 2011;143:523.","journal-title":"Radiat Prot Dosim"},{"key":"3418_CR26","first-page":"600","volume":"4","author":"H Tomoe","year":"2015","unstructured":"Tomoe H. In what type of interstitial cystitis\/bladder pain syndrome is DMSO intravesical instillation therapy effective? Transl Androl Urol. 2015;4:600\u20134.","journal-title":"Transl Androl Urol"},{"key":"3418_CR27","doi-asserted-by":"publisher","first-page":"4603","DOI":"10.3390\/molecules27144603","volume":"27","author":"Y Liu","year":"2022","unstructured":"Liu Y, Chen W, Zheng F, Yu H, Wei K. Xanthatin alleviates LPS-induced inflammatory response in RAW264.7 macrophages by inhibiting NF-\u03baB, MAPK and STATs activation. Molecules. 2022;27:4603.","journal-title":"Molecules"},{"key":"3418_CR28","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1007\/s00192-020-04490-3","volume":"32","author":"S Liu","year":"2021","unstructured":"Liu S, Zhang C, Peng L, Lu Y, Luo D. Comparative effectiveness and safety of intravesical instillation treatment of interstitial cystitis\/bladder pain syndrome: a systematic review and network meta-analysis of randomized controlled trials. Int Urogynecol J. 2021;32:1061\u201371.","journal-title":"Int Urogynecol J"},{"key":"3418_CR29","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1006\/jsre.1998.5527","volume":"82","author":"CK Chang","year":"1999","unstructured":"Chang CK, Llanes S, Schumer W. Inhibitory effect of dimethyl sulfoxide on nuclear factor-\u03baB activation and intercellular adhesion molecule-1 gene expression in septic rats. J Surg Res. 1999;82:294\u20139.","journal-title":"J Surg Res"},{"key":"3418_CR30","doi-asserted-by":"publisher","first-page":"3122","DOI":"10.1128\/iai.62.8.3122-3128.1994","volume":"62","author":"KA Kelly","year":"1994","unstructured":"Kelly KA, Hill MR, Youkhana K, Wanker F, Gimble JM. Dimethyl sulfoxide modulates NF-\u03baB and cytokine activation in lipopolysaccharide-treated murine macrophages. Infect Immun. 1994;62:3122\u20138.","journal-title":"Infect Immun"}],"container-title":["British Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03418-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03418-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03418-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T03:01:43Z","timestamp":1782702103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03418-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,7,20]]}},"alternative-id":["3418"],"URL":"https:\/\/doi.org\/10.1038\/s41416-026-03418-w","relation":{},"ISSN":["0007-0920","1532-1827"],"issn-type":[{"value":"0007-0920","type":"print"},{"value":"1532-1827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,17]]},"assertion":[{"value":"30 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All experiments adhered to ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"No generative AI tools were used in the design, analysis, or writing of this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Use of AI tools"}}]}}