{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:44:52Z","timestamp":1784907892815,"version":"3.55.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Fundacion Alfonso Moreno Jaramillo","award":["2020-31631"],"award-info":[{"award-number":["2020-31631"]}]},{"DOI":"10.13039\/501100005278","name":"University of Antioquia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005278","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Oncol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acute lymphoblastic leukemia (ALL) is hematological neoplasia that affects human beings from early life to adulthood. Although ALL treatment has been effective, an important percentage of ALL patients are resilient to treatment. Therefore, there is an urgent need for testing a new combination of compounds for the treatment of this disease. Recently, combined TPEN and TPGS (T2 combo) have shown selective cytotoxic effects in vitro leukemia cells such as Jurkat, K562, and Ba\/F3 cells. In this study, we aimed to test the effect of combined TPEN and TPGS agents (T2 combo) at a fixed dose (TPEN 5\u00a0mg\/kg: TPGS 100\u00a0mg\/kg) on leukemic Ba\/F3-BCR-ABL P210 BALB-c mice model. We found that 4 successive 2-day apart intravenous injections of T2 combo showed a statistically significant reduction of Ba\/F3 BCR-ABL leukemia cells (\u2212\u00a069%) in leukemia BALB\/c mice (<jats:italic>n<\/jats:italic>\u2009=\u20096) compared to untreated leukemia group (<jats:italic>n<\/jats:italic>\u2009=\u20096). Moreover, the T2 combo was innocuous to non-leukemia BALB\/c mice (<jats:italic>n<\/jats:italic>\u2009=\u20093) compared to untreated non-leukemia mice (control, <jats:italic>n<\/jats:italic>\u2009=\u20093). After treatments (day 42), all mice were left to rest until day 50. Outstandingly, the leukemia BALB\/c mice treated with the T2 combo showed a lower percentage of Ba\/F3-BCR-ABL P210 cells (\u2212\u00a084%) than untreated leukemia BALB\/c mice. Furthermore, treatment of leukemia and non-leukemia mice with T2 combo showed no significant tissue alteration\/damage according to the histopathological analysis of brain, heart, liver, kidney, and spleen samples; however, T2 combo significantly reduced the number of leukocytes in the bone marrow of treated leukemia mice. We conclude that the T2 combo specifically affects leukemia cells but no other tissue\/organs. Therefore, we anticipate that the T2 combo might be a potential pro-oxidant combination for the treatment of leukemia patients.<\/jats:p>","DOI":"10.1007\/s12032-022-01873-y","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T21:20:20Z","timestamp":1668028820000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TPEN\/TPGS (T2) combo dramatically reduces Philadelphia chromosome-positive pro-lymphoblastic B leukemia in BALB\/c mice"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8824-379X","authenticated-orcid":false,"given":"Miguel","family":"Mendivil-Perez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3477-2386","authenticated-orcid":false,"given":"Marlene","family":"Jimenez-Del-Rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0557-0411","authenticated-orcid":false,"given":"Carlos","family":"Velez-Pardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"1873_CR1","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1016\/S0140-6736(19)33018-1","volume":"395","author":"F Malard","year":"2020","unstructured":"Malard F, Mohty M. Acute lymphoblastic leukaemia. Lancet. 2020;395:1146\u201362. https:\/\/doi.org\/10.1016\/S0140-6736(19)33018-1.","journal-title":"Lancet"},{"key":"1873_CR2","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.cll.2021.04.003","volume":"41","author":"DC Luca","year":"2021","unstructured":"Luca DC. Update on lymphoblastic leukemia\/lymphoma. Clin Lab Med. 2021;41:405\u201316. https:\/\/doi.org\/10.1016\/j.cll.2021.04.003.","journal-title":"Clin Lab Med"},{"key":"1873_CR3","doi-asserted-by":"publisher","DOI":"10.4084\/MJHID.2014.073","volume":"6","author":"S Chiaretti","year":"2014","unstructured":"Chiaretti S, Zini G, Bassan R. Diagnosis and subclassification of acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis. 2014;6: e2014073. https:\/\/doi.org\/10.4084\/MJHID.2014.073.","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"1873_CR4","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1080\/14656566.2022.2033725","volume":"23","author":"A Grunenberg","year":"2022","unstructured":"Grunenberg A, Sala E, Kapp-Schwoerer S, Viardot A. Pharmacotherapeutic management of T-cell acute lymphoblastic leukemia in adults: an update of the literature. Expert Opin Pharmacother. 2022;23:561\u201371. https:\/\/doi.org\/10.1080\/14656566.2022.2033725.","journal-title":"Expert Opin Pharmacother"},{"key":"1873_CR5","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1182\/blood-2018-08-832105","volume":"133","author":"F Ravandi","year":"2019","unstructured":"Ravandi F. How I treat Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2019;133:130\u20136. https:\/\/doi.org\/10.1182\/blood-2018-08-832105.","journal-title":"Blood"},{"key":"1873_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14071805","author":"K Saleh","year":"2022","unstructured":"Saleh K, Fernandez A, Pasquier F. Treatment of philadelphia chromosome-positive acute lymphoblastic leukemia in adults. Cancers. 2022. https:\/\/doi.org\/10.3390\/cancers14071805.","journal-title":"Cancers"},{"key":"1873_CR7","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10091926","author":"H Inaba","year":"2021","unstructured":"Inaba H, Pui CH. Advances in the diagnosis and treatment of pediatric acute lymphoblastic leukemia. J Clin Med. 2021. https:\/\/doi.org\/10.3390\/jcm10091926.","journal-title":"J Clin Med"},{"key":"1873_CR8","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/s41408-021-00516-1","volume":"11","author":"I Aldoss","year":"2021","unstructured":"Aldoss I, Pillai R, Yang D, Yang L, Arslan S, Mokhtari S, Malki MMA, Salhotra A, Shahani S, Ali H, et al. Late and very late relapsed acute lymphoblastic leukemia: clinical and molecular features, and treatment outcomes. Blood Cancer J. 2021;11:125. https:\/\/doi.org\/10.1038\/s41408-021-00516-1.","journal-title":"Blood Cancer J"},{"key":"1873_CR9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063067","author":"K J\u0119draszek","year":"2022","unstructured":"J\u0119draszek K, Malczewska M, Parysek-W\u00f3jcik K, Lejman M. Resistance mechanisms in pediatric B-cell acute lymphoblastic leukemia. Int J Mol Sci. 2022. https:\/\/doi.org\/10.3390\/ijms23063067.","journal-title":"Int J Mol Sci"},{"key":"1873_CR10","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1158\/2326-6066.CIR-19-0058","volume":"7","author":"Y Vicioso","year":"2019","unstructured":"Vicioso Y, Gram H, Beck R, Asthana A, Zhang K, Wong DP, Letterio J, Parameswaran R. Combination therapy for treating advanced drug-resistant acute lymphoblastic leukemia. Cancer Immunol Res. 2019;7:1106\u201319. https:\/\/doi.org\/10.1158\/2326-6066.CIR-19-0058.","journal-title":"Cancer Immunol Res"},{"key":"1873_CR11","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s12032-022-01697-w","volume":"39","author":"M Mendivil-Perez","year":"2022","unstructured":"Mendivil-Perez M, Jimenez-Del-Rio M, Velez-Pardo C. Combinational treatment of TPEN and TPGS induces apoptosis in acute lymphoblastic and chronic myeloid leukemia cells in vitro and ex vivo. Med Oncol. 2022;39:109. https:\/\/doi.org\/10.1007\/s12032-022-01697-w.","journal-title":"Med Oncol"},{"key":"1873_CR12","doi-asserted-by":"publisher","first-page":"121","DOI":"10.4103\/0253-7176.116232","volume":"35","author":"J Charan","year":"2013","unstructured":"Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian J Psychol Med. 2013;35:121\u20136. https:\/\/doi.org\/10.4103\/0253-7176.116232.","journal-title":"Indian J Psychol Med"},{"key":"1873_CR13","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.863","author":"SB Gorzalczany","year":"2021","unstructured":"Gorzalczany SB, Rodriguez Basso AG. Strategies to apply 3Rs in preclinical testing. Pharmacol Res Perspect. 2021. https:\/\/doi.org\/10.1002\/prp2.863.","journal-title":"Pharmacol Res Perspect"},{"key":"1873_CR14","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1016\/j.intimp.2011.04.011","volume":"11","author":"XH Huyan","year":"2011","unstructured":"Huyan XH, Lin YP, Gao T, Chen RY, Fan YM. Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb\/c mice. Int Immunopharmacol. 2011;11:1293\u20137. https:\/\/doi.org\/10.1016\/j.intimp.2011.04.011.","journal-title":"Int Immunopharmacol"},{"key":"1873_CR15","doi-asserted-by":"publisher","first-page":"3023","DOI":"10.1074\/jbc.M705513200","volume":"283","author":"SM Kweon","year":"2008","unstructured":"Kweon SM, Cho YJ, Minoo P, Groffen J, Heisterkamp N. Activity of the Bcr GTPase-activating domain is regulated through direct protein\/protein interaction with the Rho guanine nucleotide dissociation inhibitor. J Biol Chem. 2008;283:3023\u201330. https:\/\/doi.org\/10.1074\/jbc.M705513200.","journal-title":"J Biol Chem"},{"key":"1873_CR16","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1590\/s0037-86822003000400002","volume":"36","author":"SG Andrade","year":"2003","unstructured":"Andrade SG, Mesquita IM, Jambeiro JF, Santos IF, Portella RS. Treatment with benznidazole in association with immunosuppressive drugs in mice chronically infected with Trypanosoma cruzi: investigation into the possible development of neoplasias. Rev Soc Bras Med Trop. 2003;36:441\u20137. https:\/\/doi.org\/10.1590\/s0037-86822003000400002.","journal-title":"Rev Soc Bras Med Trop"},{"key":"1873_CR17","doi-asserted-by":"publisher","first-page":"3971","DOI":"10.1200\/JCO.2008.16.1414","volume":"26","author":"EA Raetz","year":"2008","unstructured":"Raetz EA, Borowitz MJ, Devidas M, Linda SB, Hunger SP, Winick NJ, Camitta BM, Gaynon PS, Carroll WL. Reinduction platform for children with first marrow relapse of acute lymphoblastic leukemia: a Children\u2019s Oncology Group Study [corrected]. J Clin Oncol. 2008;26:3971\u20138. https:\/\/doi.org\/10.1200\/JCO.2008.16.1414.","journal-title":"J Clin Oncol"},{"key":"1873_CR18","doi-asserted-by":"publisher","first-page":"3702","DOI":"10.1182\/blood-2014-11-551481","volume":"125","author":"E Curran","year":"2015","unstructured":"Curran E, Stock W. How I treat acute lymphoblastic leukemia in older adolescents and young adults. Blood. 2015;125:3702\u201310. https:\/\/doi.org\/10.1182\/blood-2014-11-551481.","journal-title":"Blood"},{"key":"1873_CR19","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1097\/CCO.0b013e328011a25f","volume":"19","author":"M Warmuth","year":"2007","unstructured":"Warmuth M, Kim S, Gu XJ, Xia G, Adrian F. Ba\/F3 cells and their use in kinase drug discovery. Curr Opin Oncol. 2007;19:55\u201360. https:\/\/doi.org\/10.1097\/CCO.0b013e328011a25f.","journal-title":"Curr Opin Oncol"},{"key":"1873_CR20","doi-asserted-by":"publisher","first-page":"35488","DOI":"10.18632\/oncotarget.17828","volume":"8","author":"K Kong","year":"2017","unstructured":"Kong K, Ng PK, Scott KL. Ba\/F3 transformation assays. Oncotarget. 2017;8:35488\u20139. https:\/\/doi.org\/10.18632\/oncotarget.17828.","journal-title":"Oncotarget"},{"key":"1873_CR21","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.1016\/j.apsb.2022.01.014","volume":"12","author":"T Ren","year":"2022","unstructured":"Ren T, Li R, Zhao L, Fawcett JP, Sun D, Gu J. Biological fate and interaction with cytochromes P450 of the nanocarrier material, d-. Acta Pharm Sin B. 2022;12:3156\u201366. https:\/\/doi.org\/10.1016\/j.apsb.2022.01.014.","journal-title":"Acta Pharm Sin B"},{"key":"1873_CR22","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/s0041-0101(96)00215-2","volume":"35","author":"M Adler","year":"1997","unstructured":"Adler M, Dinterman RE, Wannemacher RW. Protection by the heavy metal chelator N, N, N\u2032, N\u2032-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) against the lethal action of botulinum neurotoxin A and B. Toxicon. 1997;35:1089\u2013100. https:\/\/doi.org\/10.1016\/s0041-0101(96)00215-2.","journal-title":"Toxicon"},{"key":"1873_CR23","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1186\/1471-2407-14-527","volume":"14","author":"M Fatfat","year":"2014","unstructured":"Fatfat M, Merhi RA, Rahal O, Stoyanovsky DA, Zaki A, Haidar H, Kagan VE, Gali-Muhtasib H, Machaca K. Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species. BMC Cancer. 2014;14:527. https:\/\/doi.org\/10.1186\/1471-2407-14-527.","journal-title":"BMC Cancer"},{"key":"1873_CR24","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1038\/leu.2011.76","volume":"25","author":"R Parameswaran","year":"2011","unstructured":"Parameswaran R, Yu M, Lim M, Groffen J, Heisterkamp N. Combination of drug therapy in acute lymphoblastic leukemia with a CXCR4 antagonist. Leukemia. 2011;25:1314\u201323. https:\/\/doi.org\/10.1038\/leu.2011.76.","journal-title":"Leukemia"},{"key":"1873_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/cells10112833","author":"SM Bolandi","year":"2021","unstructured":"Bolandi SM, Pakjoo M, Beigi P, Kiani M, Allahgholipour A, Goudarzi N, Khorashad JS, Eiring AM. A role for the bone marrow microenvironment in drug resistance of acute myeloid Leukemia. Cells. 2021. https:\/\/doi.org\/10.3390\/cells10112833.","journal-title":"Cells"},{"key":"1873_CR26","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/313275","volume":"2012","author":"M Mendivil-Perez","year":"2012","unstructured":"Mendivil-Perez M, Velez-Pardo C, Jimenez-Del-Rio M. TPEN induces apoptosis independently of zinc chelator activity in a model of acute lymphoblastic leukemia and ex vivo acute leukemia cells through oxidative stress and mitochondria caspase-3- and AIF-dependent pathways. Oxid Med Cell Longev. 2012;2012: 313275. https:\/\/doi.org\/10.1155\/2012\/313275.","journal-title":"Oxid Med Cell Longev"},{"key":"1873_CR27","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1007\/s10495-016-1266-x","volume":"21","author":"C Ruiz-Moreno","year":"2016","unstructured":"Ruiz-Moreno C, Jimenez-Del-Rio M, Sierra-Garcia L, Lopez-Osorio B, Velez-Pardo C. Vitamin E synthetic derivate-TPGS-selectively induces apoptosis in jurkat t cells via oxidative stress signaling pathways: implications for acute lymphoblastic leukemia. Apoptosis. 2016;21:1019\u201332. https:\/\/doi.org\/10.1007\/s10495-016-1266-x.","journal-title":"Apoptosis"},{"key":"1873_CR28","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1007\/s10495-017-1424-9","volume":"22","author":"Z Zou","year":"2017","unstructured":"Zou Z, Chang H, Li H, Wang S. Induction of reactive oxygen species: an emerging approach for cancer therapy. Apoptosis. 2017;22:1321\u201335. https:\/\/doi.org\/10.1007\/s10495-017-1424-9.","journal-title":"Apoptosis"},{"key":"1873_CR29","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s13046-018-0797-0","volume":"37","author":"R Prieto-Bermejo","year":"2018","unstructured":"Prieto-Bermejo R, Romo-Gonzalez M, Perez-Fernandez A, Ijurko C, Hernandez-Hernandez A. Reactive oxygen species in haematopoiesis: leukaemic cells take a walk on the wild side. J Exp Clin Cancer Res. 2018;37:125. https:\/\/doi.org\/10.1186\/s13046-018-0797-0.","journal-title":"J Exp Clin Cancer Res"},{"key":"1873_CR30","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/s12276-020-0384-2","volume":"52","author":"B Perillo","year":"2020","unstructured":"Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, Castoria G, Migliaccio A. ROS in cancer therapy: the bright side of the moon. Exp Mol Med. 2020;52:192\u2013203. https:\/\/doi.org\/10.1038\/s12276-020-0384-2.","journal-title":"Exp Mol Med"},{"key":"1873_CR31","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3389\/fonc.2014.00095","volume":"4","author":"E Jacoby","year":"2014","unstructured":"Jacoby E, Chien CD, Fry TJ. Murine models of acute leukemia: important tools in current pediatric leukemia research. Front Oncol. 2014;4:95. https:\/\/doi.org\/10.3389\/fonc.2014.00095.","journal-title":"Front Oncol"},{"key":"1873_CR32","doi-asserted-by":"publisher","first-page":"2836","DOI":"10.4161\/15384101.2014.949137","volume":"13","author":"J Hauer","year":"2014","unstructured":"Hauer J, Borkhardt A, S\u00e1nchez-Garc\u00eda I, Cobaleda C. Genetically engineered mouse models of human B-cell precursor leukemias. Cell Cycle. 2014;13:2836\u201346. https:\/\/doi.org\/10.4161\/15384101.2014.949137.","journal-title":"Cell Cycle"},{"key":"1873_CR33","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1080\/17460441.2016.1229297","volume":"11","author":"S Bhatia","year":"2016","unstructured":"Bhatia S, Daschkey S, Lang F, Borkhardt A, Hauer J. Mouse models for pre-clinical drug testing in leukemia. Expert Opin Drug Discov. 2016;11:1081\u201391. https:\/\/doi.org\/10.1080\/17460441.2016.1229297.","journal-title":"Expert Opin Drug Discov"},{"key":"1873_CR34","doi-asserted-by":"publisher","DOI":"10.3791\/54624","author":"TK Nguyen","year":"2016","unstructured":"Nguyen TK, Morse SJ, Fleischman AG. Transduction-transplantation mouse model of myeloproliferative neoplasm. J Vis Exp. 2016. https:\/\/doi.org\/10.3791\/54624.","journal-title":"J Vis Exp"},{"key":"1873_CR35","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/cmi.2016.39","volume":"14","author":"R Diehl","year":"2017","unstructured":"Diehl R, Ferrara F, M\u00fcller C, Dreyer AY, McLeod DD, Fricke S, Boltze J. Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches. Cell Mol Immunol. 2017;14:146\u201379. https:\/\/doi.org\/10.1038\/cmi.2016.39.","journal-title":"Cell Mol Immunol"},{"key":"1873_CR36","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1124\/dmd.118.083766","volume":"47","author":"DA Ramirez","year":"2019","unstructured":"Ramirez DA, Collins KP, Aradi AE, Conger KA, Gustafson DL. Kinetics of cyclophosphamide metabolism in humans, dogs, cats, and mice and relationship to cytotoxic activity and pharmacokinetics. Drug Metab Dispos. 2019;47:257\u201368. https:\/\/doi.org\/10.1124\/dmd.118.083766.","journal-title":"Drug Metab Dispos"},{"key":"1873_CR37","first-page":"596","volume":"13","author":"YM Wei","year":"2005","unstructured":"Wei YM, Lin JH, Xia R, Lan JC. Establishment of a transplantable human myeloid BALB\/c nude mouse model. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005;13:596\u2013600.","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"}],"container-title":["Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-022-01873-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12032-022-01873-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-022-01873-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T03:32:20Z","timestamp":1673839940000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12032-022-01873-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,9]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["1873"],"URL":"https:\/\/doi.org\/10.1007\/s12032-022-01873-y","relation":{},"ISSN":["1559-131X"],"issn-type":[{"value":"1559-131X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,9]]},"assertion":[{"value":"26 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal study was reviewed and approved by the Ethical Committee for Animal Experimentation from UdeA Acta# 127 (2019\/09\/04).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare that they have no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"15"}}