{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:15:50Z","timestamp":1790036150148,"version":"4.0.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:00:00Z","timestamp":1604966400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:00:00Z","timestamp":1604966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008907","name":"Oklahoma Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008907","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Children's Hospital Foundation"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1S10OD023508"],"award-info":[{"award-number":["1S10OD023508"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30 CA225520"],"award-info":[{"award-number":["P30 CA225520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P20 GM103639"],"award-info":[{"award-number":["P20 GM103639"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Oblato, Inc."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diffuse intrinsic pontine glioma (DIPG) is the most common brainstem cancer in childhood. This rapidly progressing brainstem glioma holds a very dismal prognosis with median survival of less than 1\u00a0year. Despite extensive research, no significant therapeutic advancements have been made to improve overall survival in DIPG patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we used an orthotopic xenograft pediatric DIPG (HSJD-DIPG-007) mouse model to monitor the effects of anti-cancer agent, OKlahoma Nitrone-007 (OKN-007), as an inhibitor of tumor growth after 28\u00a0days of treatment. Using magnetic resonance imaging (MRI), we confirmed the previously described efficacy of LDN-193189, a known activin A receptor, type I (ACVR1) inhibitor, in decreasing tumor burden and found that OKN-007 was equally efficacious.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After 28\u00a0days of treatment, the tumor volumes were significantly decreased in OKN-007 treated mice (p\u2009&lt;\u20090.01). The apparent diffusion coefficient (ADC), as a measure of tissue structural alterations, was significantly decreased in OKN-007 treated tumor-bearing mice (p\u2009&lt;\u20090.0001). Histological analysis also showed a significant decrease in CD34 expression, essential for angiogenesis, of OKN-007 treated mice (p\u2009&lt;\u20090.05) compared to LDN-193189 treated mice. OKN-007-treated mice also significantly decreased protein expression of the human nuclear antigen (HNA) (p\u2009&lt;\u20090.001), ACVR1 (p\u2009&lt;\u20090.0001), and c-MET (p\u2009&lt;\u20090.05), as well as significantly increased expression of cleaved caspase 3 (p\u2009&lt;\u20090.001) and histone H3 K27-trimethylation (p\u2009&lt;\u20090.01), compared to untreated mouse tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>With the dismal prognosis and limited effective chemotherapy available for DIPG, there is significant room for continued research studies, and OKN-007 merits further exploration as a therapeutic agent.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-020-02593-5","type":"journal-article","created":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T22:02:33Z","timestamp":1604959353000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["OKlahoma Nitrone-007: novel treatment for diffuse intrinsic pontine glioma"],"prefix":"10.1186","volume":"18","author":[{"given":"Lincy","family":"Thomas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Zalles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Gulej","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Lerner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kar-Ming","family":"Fung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel M.","family":"Carcaboso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-8983","authenticated-orcid":false,"given":"Rheal A.","family":"Towner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,10]]},"reference":[{"issue":"S7","key":"2593_CR1","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1002\/cncr.23741","volume":"113","author":"ML Bondy","year":"2008","unstructured":"Bondy ML, Scheurer ME, Malmer B, Barnholtz-Sloan JS, Davis FG, Il\u2019Yasova D, et al. Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium. Cancer. 2008;113(S7):1953\u201368.","journal-title":"Cancer"},{"issue":"1\u20132","key":"2593_CR2","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/pr.2013.194","volume":"75","author":"KM Schroeder","year":"2014","unstructured":"Schroeder KM, Hoeman CM, Becher OJ. Children are not just little adults: recent advances in understanding of diffuse intrinsic pontine glioma biology. Pediatr Res. 2014;75(1\u20132):205\u20139.","journal-title":"Pediatr Res"},{"issue":"6","key":"2593_CR3","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s00401-015-1478-0","volume":"130","author":"D Castel","year":"2015","unstructured":"Castel D, Philippe C, Calmon R, Le Dret L, Truffaux N, Boddaert N, et al. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol. 2015;130(6):815\u201327.","journal-title":"Acta Neuropathol"},{"issue":"6","key":"2593_CR4","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","volume":"131","author":"DN Louis","year":"2016","unstructured":"Louis DN, Perry A, Reifenberger G, Von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803\u201320.","journal-title":"Acta Neuropathol"},{"key":"2593_CR5","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s42003-019-0420-8","volume":"2","author":"D Carvalho","year":"2019","unstructured":"Carvalho D, Taylor KR, Olaciregui NG, Molinari V, Clarke M, Mackay A, et al. ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma. Commun Biol. 2019;2:156.","journal-title":"Commun Biol"},{"issue":"8","key":"2593_CR6","doi-asserted-by":"publisher","first-page":"e0134276","DOI":"10.1371\/journal.pone.0134276","volume":"10","author":"P Coutinho de Souza","year":"2015","unstructured":"Coutinho de Souza P, Mallory S, Smith N, Saunders D, Li X-N, McNall-Knapp RY, et al. Inhibition of pediatric glioblastoma tumor growth by the anti-cancer agent OKN-007 in orthotopic mouse xenografts. PLoS ONE. 2015;10(8):e0134276.","journal-title":"PLoS ONE"},{"issue":"2","key":"2593_CR7","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.tranon.2018.10.002","volume":"12","author":"RA Towner","year":"2019","unstructured":"Towner RA, Smith N, Saunders D, Brown CA, Cai X, Ziegler J, et al. OKN-007 increases temozolomide (TMZ) sensitivity and suppresses TMZ-resistant glioblastoma (GBM) tumor growth. Transl Oncol. 2019;12(2):320\u201335.","journal-title":"Transl Oncol"},{"issue":"4","key":"2593_CR8","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1002\/jmri.22106","volume":"31","author":"P Garteiser","year":"2010","unstructured":"Garteiser P, Doblas S, Watanabe Y, Saunders D, Hoyle J, Lerner M, et al. Multiparametric assessment of the anti-glioma properties of OKN007 by magnetic resonance imaging. J Magn Imaging. 2010;31(4):796\u2013806.","journal-title":"J Magn Imaging"},{"issue":"3","key":"2593_CR9","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1093\/neuonc\/nos337","volume":"15","author":"RA Towner","year":"2013","unstructured":"Towner RA, Gillespie DL, Schwager A, Saunders DG, Smith N, Njoku CE, et al. Regression of glioma tumor growth in F98 and U87 rat glioma models by the Nitrone OKN-007. Neuro Oncology. 2013;15(3):330\u201340.","journal-title":"Neuro Oncology"},{"issue":"3","key":"2593_CR10","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1002\/gcc.22022","volume":"52","author":"X Zheng","year":"2013","unstructured":"Zheng X, Gai X, Han S, Moser CD, Hu C, Shire AM, et al. The human sulfatase 2 inhibitor 2, 4-disulfonylphenyl-tert-butylnitrone (OKN-007) has an antitumor effect in hepatocellular carcinoma mediated via suppression of TGFB1\/SMAD2 and Hedgehog\/GLI1 signaling. Genes Chromosomes Cancer. 2013;52(3):225\u201336.","journal-title":"Genes Chromosomes Cancer"},{"key":"2593_CR11","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.freeradbiomed.2015.06.026","volume":"87","author":"P Coutinho de Souza","year":"2015","unstructured":"Coutinho de Souza P, Smith N, Atolagbe O, Ziegler J, Njoku C, Lerner M, et al. OKN-007 decreases free radical levels in a preclinical F98 rat glioma model. Free Radic Biol Med. 2015;87:157\u201368.","journal-title":"Free Radic Biol Med."},{"issue":"4","key":"2593_CR12","first-page":"363","volume":"5","author":"PC de Souza","year":"2015","unstructured":"de Souza PC, Smith N, Pody R, He T, Njoku C, Silasi-Mansat R, et al. OKN-007 decreases VEGFR-2 levels in a preclinical GL261 mouse glioma model. Am J Nucl Med Mol Imaging. 2015;5(4):363.","journal-title":"Am J Nucl Med Mol Imaging"},{"issue":"5","key":"2593_CR13","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/ng.2925","volume":"46","author":"KR Taylor","year":"2014","unstructured":"Taylor KR, Mackay A, Truffaux N, Butterfield YS, Morozova O, Philippe C, et al. Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet. 2014;46(5):457\u201361.","journal-title":"Nat Genet"},{"issue":"8","key":"2593_CR14","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1038\/s41591-018-0086-7","volume":"24","author":"M Vinci","year":"2018","unstructured":"Vinci M, Burford A, Molinari V, Kessler K, Popov S, Clarke M, et al. Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells. Nat Med. 2018;24(8):1204\u201315.","journal-title":"Nat Med"},{"issue":"9","key":"2593_CR15","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1158\/1535-7163.MCT-15-0558","volume":"15","author":"MH Jansen","year":"2016","unstructured":"Jansen MH, Lagerweij T, Sewing AC, Vugts DJ, van Vuurden DG, Molthoff CF, et al. Bevacizumab targeting diffuse intrinsic pontine glioma: results of 89Zr-bevacizumab PET imaging in brain tumor models. Mol Cancer Ther. 2016;15(9):2166\u201374.","journal-title":"Mol Cancer Ther"},{"key":"2593_CR16","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.mex.2018.02.006","volume":"5","author":"MH Meel","year":"2018","unstructured":"Meel MH, Metselaar DS, Waranecki P, Kaspers GJ, Hulleman EJM. An efficient method for the transduction of primary pediatric glioma neurospheres. MethodsX. 2018;5:173\u201383.","journal-title":"MethodsX"},{"key":"2593_CR17","doi-asserted-by":"publisher","first-page":"172","DOI":"10.3389\/fonc.2015.00172","volume":"5","author":"KL Misuraca","year":"2015","unstructured":"Misuraca KL, Cordero FJ, Becher OJ. Pre-clinical models of diffuse intrinsic pontine glioma. Front Oncol. 2015;5:172.","journal-title":"Front Oncol"},{"issue":"1","key":"2593_CR18","doi-asserted-by":"publisher","first-page":"e0169485","DOI":"10.1371\/journal.pone.0169485","volume":"12","author":"T Hennika","year":"2017","unstructured":"Hennika T, Hu G, Olaciregui NG, Barton KL, Ehteda A, Chitranjan A, et al. Pre-clinical study of panobinostat in xenograft and genetically engineered murine diffuse intrinsic pontine glioma models. PLoS ONE. 2017;12(1):e0169485.","journal-title":"PLoS ONE"},{"key":"2593_CR19","doi-asserted-by":"publisher","first-page":"101510","DOI":"10.1016\/j.redox.2020.101510","volume":"36","author":"MA Rodriguez-Hernandez","year":"2020","unstructured":"Rodriguez-Hernandez MA, de la Cruz-Ojeda P, Lopez-Grueso MJ, Navarro-Villaran E, Requejo-Aguilar R, Castejon-Vega B, et al. Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer. Redox Biol. 2020;36:101510.","journal-title":"Redox Biol"},{"issue":"1","key":"2593_CR20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ctrv.2011.06.007","volume":"38","author":"M Jansen","year":"2012","unstructured":"Jansen M, Van Vuurden D, Vandertop W, Kaspers GJ. Diffuse intrinsic pontine gliomas: a systematic update on clinical trials and biology. Cancer Treat Rev. 2012;38(1):27\u201335.","journal-title":"Cancer Treat Rev"},{"issue":"3","key":"2593_CR21","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S1470-2045(06)70615-5","volume":"7","author":"D Hargrave","year":"2006","unstructured":"Hargrave D, Bartels U, Bouffet EJT. Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol. 2006;7(3):241\u20138.","journal-title":"Lancet Oncol"},{"issue":"44","key":"2593_CR22","doi-asserted-by":"publisher","first-page":"76644","DOI":"10.18632\/oncotarget.19656","volume":"8","author":"C Xu","year":"2017","unstructured":"Xu C, Liu X, Geng Y, Bai Q, Pan C, Sun Y, et al. Patient-derived DIPG cells preserve stem-like characteristics and generate orthotopic tumors. Oncotarget. 2017;8(44):76644\u201355.","journal-title":"Oncotarget"},{"issue":"2","key":"2593_CR23","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s11548-016-1483-3","volume":"12","author":"M Soltaninejad","year":"2017","unstructured":"Soltaninejad M, Yang G, Lambrou T, Allinson N, Jones TL, Barrick TR, et al. Automated brain tumour detection and segmentation using superpixel-based extremely randomized trees in FLAIR MRI. Int J Comput Assist Radiol Surg. 2017;12(2):183\u2013203.","journal-title":"Int J Comput Assist Radiol Surg"},{"issue":"4","key":"2593_CR24","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1007\/s00401-014-1319-6","volume":"128","author":"P Buczkowicz","year":"2014","unstructured":"Buczkowicz P, Bartels U, Bouffet E, Becher O, Hawkins CJ. Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications. Acta Neuropathol. 2014;128(4):573\u201381.","journal-title":"Acta Neuropathol"},{"issue":"6","key":"2593_CR25","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.2214\/AJR.06.1403","volume":"188","author":"DM Koh","year":"2007","unstructured":"Koh DM, Collins DJ. Diffusion-weighted MRI in the body: applications and challenges in oncology. Am J Roentgenol. 2007;188(6):1622\u201335.","journal-title":"Am J Roentgenol"},{"issue":"1","key":"2593_CR26","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s11060-014-1375-8","volume":"117","author":"RM Lober","year":"2014","unstructured":"Lober RM, Cho YJ, Tang Y, Barnes PD, Edwards MS, Vogel H, et al. Diffusion-weighted MRI derived apparent diffusion coefficient identifies prognostically distinct subgroups of pediatric diffuse intrinsic pontine glioma. J Neuro-Oncol. 2014;117(1):175\u201382.","journal-title":"J Neuro-Oncol"},{"issue":"9","key":"2593_CR27","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1158\/1541-7786.MCR-16-0389","volume":"15","author":"FJ Cordero","year":"2017","unstructured":"Cordero FJ, Huang Z, Grenier C, He X, Hu G, McLendon RE, et al. Histone H3 3K27M represses p16 to accelerate gliomagenesis in a murine model of DIPG. Mol Cancer Res. 2017;15(9):1243\u201354.","journal-title":"Mol Cancer Res"},{"issue":"3","key":"2593_CR28","doi-asserted-by":"publisher","first-page":"343","DOI":"10.3340\/jkns.2018.0008","volume":"61","author":"RK Mathew","year":"2018","unstructured":"Mathew RK, Rutka JT. Diffuse intrinsic pontine glioma\u202f: clinical features, molecular genetics, and novel targeted therapeutics. J Korean Neurosurg Soc. 2018;61(3):343\u201351.","journal-title":"J Korean Neurosurg Soc"},{"issue":"6","key":"2593_CR29","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1002\/jmri.24935","volume":"42","author":"PC de Souza","year":"2015","unstructured":"de Souza PC, Balasubramanian K, Njoku C, Smith N, Gillespie DL, Schwager A, et al. OKN-007 decreases tumor necrosis and tumor cell proliferation and increases apoptosis in a preclinical F98 rat glioma model. J Magn Reson Imaging. 2015;42(6):1582\u201391.","journal-title":"J Magn Reson Imaging"},{"issue":"5","key":"2593_CR30","doi-asserted-by":"publisher","first-page":"E455","DOI":"10.1002\/ijc.29220","volume":"136","author":"JL Ali","year":"2015","unstructured":"Ali JL, Lagasse BJ, Minuk AJ, Love AJ, Moraya AI, Lam L, et al. Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells. Int J Cancer. 2015;136(5):E455\u201369.","journal-title":"Int J Cancer"},{"issue":"11","key":"2593_CR31","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1016\/j.cellsig.2011.06.019","volume":"23","author":"J Vogt","year":"2011","unstructured":"Vogt J, Traynor R, Sapkota GP. The specificities of small molecule inhibitors of the TGFss and BMP pathways. Cell Signal. 2011;23(11):1831\u201342.","journal-title":"Cell Signal"},{"issue":"6","key":"2593_CR32","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1056\/NEJMoa070240","volume":"357","author":"A Shuaib","year":"2007","unstructured":"Shuaib A, Lees KR, Lyden P, Grotta J, Davalos A, Davis SM, et al. NXY-059 for the treatment of acute ischemic stroke. N Engl J Med. 2007;357(6):562\u201371.","journal-title":"N Engl J Med"},{"issue":"4","key":"2593_CR33","doi-asserted-by":"publisher","first-page":"373","DOI":"10.2174\/187152011795677517","volume":"11","author":"R Floyd","year":"2011","unstructured":"Floyd R, Chandru KH, He T, Towner RA. Anti-cancer activity of nitrones and observations on mechanism of action. Anticancer Agents Med Chem. 2011;11(4):373\u20139.","journal-title":"Anticancer Agents Med Chem"},{"key":"2593_CR34","doi-asserted-by":"publisher","first-page":"4443","DOI":"10.1038\/s41388-018-0291-3","volume":"37","author":"S Yoon","year":"2018","unstructured":"Yoon S, Lee E-J, Choi J-H, Chung T, Im J-Y, Bae M-H, et al. Recapitulation of pharmacogenomic data reveals that invalidation of SULF2 enhance sorafenib susceptibility in liver cancer. Oncogene. 2018;37:4443\u201354.","journal-title":"Oncogene"},{"issue":"98","key":"2593_CR35","doi-asserted-by":"publisher","first-page":"37112","DOI":"10.18632\/oncotarget.26430","volume":"9","author":"T Huang","year":"2018","unstructured":"Huang T, Garcia R, Qi J, Lulla R, Horbinski C, Behdad A, et al. Detection of histone H3 K27M mutation and post-translational modifications in pediatric diffuse midline glioma via tissue immunohistochemistry informs diagnosis and clinical outcomes. Oncotarget. 2018;9(98):37112\u201324.","journal-title":"Oncotarget"},{"issue":"7","key":"2593_CR36","doi-asserted-by":"publisher","first-page":"e2830","DOI":"10.1097\/MD.0000000000002830","volume":"95","author":"X Kong","year":"2016","unstructured":"Kong X, Guan J, Ma W, Li Y, Xing B, Yang Y, et al. CD34 over-expression is associated with gliomas\u2019 higher WHO grade. Medicine (Baltimore). 2016;95(7):e2830.","journal-title":"Medicine (Baltimore)"},{"issue":"3","key":"2593_CR37","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/s11060-011-0778-z","volume":"107","author":"NN Rahmah","year":"2012","unstructured":"Rahmah NN, Sakai K, Sano K, Hongo KJ. Expression of RECK in endothelial cells of glioma: comparison with CD34 and VEGF expressions. J Neurooncol. 2012;107(3):559\u201364.","journal-title":"J Neurooncol"},{"issue":"13","key":"2593_CR38","doi-asserted-by":"publisher","first-page":"3868","DOI":"10.1158\/1078-0432.CCR-06-2730","volume":"13","author":"T Kobayashi","year":"2007","unstructured":"Kobayashi T, Masumoto J, Tada T, Nomiyama T, Hongo K, Nakayama JJ. Prognostic significance of the immunohistochemical staining of cleaved caspase-3, an activated form of caspase-3, in gliomas. Clin Cancer Res. 2007;13(13):3868\u201374.","journal-title":"Clin Cancer Res"},{"issue":"5","key":"2593_CR39","first-page":"962","volume":"58","author":"S Kondo","year":"1998","unstructured":"Kondo S, Tanaka Y, Kondo Y, Ishizaka Y, Hitomi M, Haqqi T, et al. Retroviral transfer of CPP32\u03b2 gene into malignant gliomas in vitro and in vivo. Cancer Res. 1998;58(5):962\u20137.","journal-title":"Cancer Res"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-020-02593-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12967-020-02593-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-020-02593-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T22:10:31Z","timestamp":1604959831000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-020-02593-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,10]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2593"],"URL":"https:\/\/doi.org\/10.1186\/s12967-020-02593-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-48362\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-48362\/v2","asserted-by":"object"}]},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,10]]},"assertion":[{"value":"30 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Human cells used in this study were obtained under a protocol (M-1608) approved by the Institutional Review Board (IRB) at Hospital Sant Joan de D\u00e9u (Barcelona, Spain). Acquisition of human tissue samples were obtained after signed informed consent from legal guardians. The Institutional Animal Care and Use Committee (IACUC) of the Oklahoma Medical Research Foundation approved the animal protocol [\n                      \n                      \u2013\n                      \n                      ].","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"RAT holds patents for OKN-007 as a treatment for gliomas. The remaining authors have declared no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"424"}}