Please use this identifier to cite or link to this item:
https://observatorio.fm.usp.br/handle/OPI/40565
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor | Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP | |
dc.contributor.author | SCOPIM-RIBEIRO, Renata | |
dc.contributor.author | MACHADO-NETO, Joao Agostinho | |
dc.contributor.author | EIDE, Christopher A. | |
dc.contributor.author | COELHO-SILVA, Juan Luiz | |
dc.contributor.author | FENERICH, Bruna Alves | |
dc.contributor.author | FERNANDES, Jaqueline Cristina | |
dc.contributor.author | SCHEUCHER, Priscila Santos | |
dc.contributor.author | STEVENS, Samantha L. Savage | |
dc.contributor.author | CAMPOS, Paula de Melo | |
dc.contributor.author | SAAD, Sara T. Olalla | |
dc.contributor.author | PALMA, Leonardo de Carvalho | |
dc.contributor.author | FIGUEIREDO-PONTES, Lorena Lobo de | |
dc.contributor.author | SIMOES, Belinda Pinto | |
dc.contributor.author | REGO, Eduardo Magalhaes | |
dc.contributor.author | TOGNON, Cristina E. | |
dc.contributor.author | DRUKER, Brian J. | |
dc.contributor.author | TRAINA, Fabiola | |
dc.date.accessioned | 2021-06-17T13:50:32Z | - |
dc.date.available | 2021-06-17T13:50:32Z | - |
dc.date.issued | 2021 | |
dc.identifier.citation | INVESTIGATIONAL NEW DRUGS, v.39, n.3, p.736-746, 2021 | |
dc.identifier.issn | 0167-6997 | |
dc.identifier.uri | https://observatorio.fm.usp.br/handle/OPI/40565 | - |
dc.description.abstract | Chronic myeloid leukemia (CML) is successfully treated with BCR-ABL1 tyrosine kinase inhibitors, but a significant percentage of patients develop resistance. Insulin receptor substrate 1 (IRS1) has been shown to constitutively associate with BCR-ABL1, and IRS1-specific silencing leads to antineoplastic effects in CML cell lines. Here, we characterized the efficacy of NT157, a pharmacological inhibitor of IGF1R-IRS1/2, in CML cells and observed significantly reduced cell viability and proliferation, accompanied by induction of apoptosis. In human K562 cells and in murine Ba/F3 cells, engineered to express either wild-type BCR-ABL1 or the imatinib-resistant BCR-ABL1(T315I) mutant, NT157 inhibited BCR-ABL1, IGF1R, IRS1/2, PI3K/AKT/mTOR, and STAT3/5 signaling, increased CDKN1A, FOS and JUN tumor suppressor gene expression, and reduced MYC and BCL2 oncogenes. NT157 significantly reduced colony formation of human primary CML cells with minimal effect on normal hematopoietic cells. Exposure of primary CML cells harboring BCR-ABL1(T315I) to NT157 resulted in increased apoptosis, reduced cell proliferation and decreased phospho-CRKL levels. In conclusion, NT157 has antineoplastic effects on BCR-ABL1 leukemogenesis, independent of T315I mutational status. | eng |
dc.description.sponsorship | Sao Paulo Research Foundation (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [14/06037-6, 16/01639-3, 14/509477, 13/08135-2] | |
dc.description.sponsorship | Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) | |
dc.description.sponsorship | National Counsel of Technological and Scientific Development (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [460750/2014-3, 305158/2013-9] | |
dc.language.iso | eng | |
dc.publisher | SPRINGER | eng |
dc.relation.ispartof | Investigational New Drugs | |
dc.rights | restrictedAccess | eng |
dc.subject | Insulin receptor substrate 1 | eng |
dc.subject | NT157 | eng |
dc.subject | BCR-ABL1 | eng |
dc.subject | Leukemogenesis | eng |
dc.subject.other | insulin-receptor substrate | eng |
dc.subject.other | gene-expression | eng |
dc.subject.other | ponatinib | eng |
dc.subject.other | imatinib | eng |
dc.subject.other | cancer | eng |
dc.subject.other | stat3 | eng |
dc.subject.other | irs-1 | eng |
dc.title | NT157, an IGF1R-IRS1/2 inhibitor, exhibits antineoplastic effects in pre-clinical models of chronic myeloid leukemia | eng |
dc.type | article | eng |
dc.rights.holder | Copyright SPRINGER | eng |
dc.identifier.doi | 10.1007/s10637-020-01028-8 | |
dc.identifier.pmid | 33403501 | |
dc.subject.wos | Oncology | eng |
dc.subject.wos | Pharmacology & Pharmacy | eng |
dc.type.category | original article | eng |
dc.type.version | publishedVersion | eng |
hcfmusp.author.external | SCOPIM-RIBEIRO, Renata:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Oncol, Av Bandeirante 3900, Ribeirao Preto, SP, Brazil; Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA | |
hcfmusp.author.external | MACHADO-NETO, Joao Agostinho:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Oncol, Av Bandeirante 3900, Ribeirao Preto, SP, Brazil; Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo, Brazil | |
hcfmusp.author.external | EIDE, Christopher A.:Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA; Howard Hughes Med Inst, Portland, OR USA | |
hcfmusp.author.external | COELHO-SILVA, Juan Luiz:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Oncol, Av Bandeirante 3900, Ribeirao Preto, SP, Brazil | |
hcfmusp.author.external | FENERICH, Bruna Alves:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Oncol, Av Bandeirante 3900, Ribeirao Preto, SP, Brazil | |
hcfmusp.author.external | FERNANDES, Jaqueline Cristina:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Oncol, Av Bandeirante 3900, Ribeirao Preto, SP, Brazil | |
hcfmusp.author.external | SCHEUCHER, Priscila Santos:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Oncol, Av Bandeirante 3900, Ribeirao Preto, SP, Brazil | |
hcfmusp.author.external | STEVENS, Samantha L. Savage:Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA | |
hcfmusp.author.external | CAMPOS, Paula de Melo:Univ Estadual Campinas, Hematol & Transfus Med Ctr, Hemoctr, UNICAMP, Campinas, SP, Brazil | |
hcfmusp.author.external | SAAD, Sara T. Olalla:Univ Estadual Campinas, Hematol & Transfus Med Ctr, Hemoctr, UNICAMP, Campinas, SP, Brazil | |
hcfmusp.author.external | PALMA, Leonardo de Carvalho:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Oncol, Av Bandeirante 3900, Ribeirao Preto, SP, Brazil | |
hcfmusp.author.external | FIGUEIREDO-PONTES, Lorena Lobo de:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Oncol, Av Bandeirante 3900, Ribeirao Preto, SP, Brazil | |
hcfmusp.author.external | SIMOES, Belinda Pinto:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Oncol, Av Bandeirante 3900, Ribeirao Preto, SP, Brazil | |
hcfmusp.author.external | TOGNON, Cristina E.:Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA; Howard Hughes Med Inst, Portland, OR USA | |
hcfmusp.author.external | DRUKER, Brian J.:Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA; Howard Hughes Med Inst, Portland, OR USA | |
hcfmusp.author.external | TRAINA, Fabiola:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Oncol, Av Bandeirante 3900, Ribeirao Preto, SP, Brazil | |
hcfmusp.description.beginpage | 736 | |
hcfmusp.description.endpage | 746 | |
hcfmusp.description.issue | 3 | |
hcfmusp.description.volume | 39 | |
hcfmusp.origem | WOS | |
hcfmusp.origem.id | WOS:000605108600001 | |
hcfmusp.origem.id | 2-s2.0-85098727034 | |
hcfmusp.publisher.city | DORDRECHT | eng |
hcfmusp.publisher.country | NETHERLANDS | eng |
hcfmusp.relation.reference | Abraham SA, 2016, NATURE, V534, P341, DOI 10.1038/nature18288 | eng |
hcfmusp.relation.reference | Apperley JF, 2015, LANCET, V385, P1447, DOI 10.1016/S0140-6736(13)62120-0 | eng |
hcfmusp.relation.reference | Carter BZ, 2016, SCI TRANSL MED, V8, DOI 10.1126/scitranslmed.aag1180 | eng |
hcfmusp.relation.reference | Chou TC, 2006, PHARMACOL REV, V58, P621, DOI 10.1124/pr.58.3.10 | eng |
hcfmusp.relation.reference | Cortes JE, 2013, NEW ENGL J MED, V369, P1783, DOI 10.1056/NEJMoa1306494 | eng |
hcfmusp.relation.reference | Cortes JE, 2012, NEW ENGL J MED, V367, P2075, DOI 10.1056/NEJMoa1205127 | eng |
hcfmusp.relation.reference | Deininger MWN, 2000, BLOOD, V96, P3343, DOI 10.1182/blood.V96.10.3343 | eng |
hcfmusp.relation.reference | Fenerich BA, 2020, SIGNAL TRANSDUCT TAR, V5, DOI 10.1038/s41392-019-0102-5 | eng |
hcfmusp.relation.reference | Flashner-Abramson E, 2016, ONCOGENE, V35, P2675, DOI 10.1038/onc.2015.229 | eng |
hcfmusp.relation.reference | FOLLI F, 1992, J BIOL CHEM, V267, P22171 | eng |
hcfmusp.relation.reference | Garofalo C, 2015, FRONT ENDOCRINOL, V6, DOI 10.3389/fendo.2015.00074 | eng |
hcfmusp.relation.reference | Hoshino K, 2009, LEUKEMIA RES, V33, P1361, DOI 10.1016/j.leukres.2009.03.044 | eng |
hcfmusp.relation.reference | Hughes TP, 2015, LEUKEMIA, V29, P1832, DOI 10.1038/leu.2015.168 | eng |
hcfmusp.relation.reference | Ibuki N, 2014, MOL CANCER THER, V13, P2827, DOI 10.1158/1535-7163.MCT-13-0842 | eng |
hcfmusp.relation.reference | Juric D, 2007, J CLIN ONCOL, V25, P1341, DOI 10.1200/JCO.2006.09.3534 | eng |
hcfmusp.relation.reference | Lakshmikuttyamma A, 2008, ONCOGENE, V27, P3831, DOI 10.1038/onc.2008.8 | eng |
hcfmusp.relation.reference | Machado-Neto JA, 2011, BBA-MOL CELL RES, V1813, P1404, DOI 10.1016/j.bbamcr.2011.04.002 | eng |
hcfmusp.relation.reference | Moslehi JJ, 2015, J CLIN ONCOL, V33, P4210, DOI 10.1200/JCO.2015.62.4718 | eng |
hcfmusp.relation.reference | Mulvihill MJ, 2009, FUTURE MED CHEM, V1, P1153, DOI 10.4155/FMC.09.89 | eng |
hcfmusp.relation.reference | O'Hare T, 2007, BLOOD, V110, P2242, DOI 10.1182/blood-2007-03-066936 | eng |
hcfmusp.relation.reference | O'Hare T, 2009, CANCER CELL, V16, P401, DOI 10.1016/j.ccr.2009.09.028 | eng |
hcfmusp.relation.reference | Passegue E, 2004, CELL, V119, P431, DOI 10.1016/j.cell.2004.10.010 | eng |
hcfmusp.relation.reference | Reuveni H, 2013, CANCER RES, V73, P4383, DOI 10.1158/0008-5472.CAN-12-3385 | eng |
hcfmusp.relation.reference | Sanchez-Lopez E, 2016, ONCOGENE, V35, P2634, DOI 10.1038/onc.2015.326 | eng |
hcfmusp.relation.reference | SKOLNIK EY, 1993, SCIENCE, V260, P1953, DOI 10.1126/science.8316835 | eng |
hcfmusp.relation.reference | Traina F, 2003, FEBS LETT, V535, P17, DOI 10.1016/S0014-5793(02)03845-0 | eng |
hcfmusp.relation.reference | Vardiman J, 2017, WHO CLASSIFICATION T, V4th, P30 | eng |
hcfmusp.relation.reference | WANG LM, 1993, SCIENCE, V261, P1591, DOI 10.1126/science.8372354 | eng |
hcfmusp.relation.reference | Xie JJ, 2015, J HEMATOL ONCOL, V8, DOI 10.1186/s13045-015-0106-8 | eng |
hcfmusp.relation.reference | Yang MY, 2003, BLOOD, V101, P3205, DOI 10.1182/blood-2002-05-1598 | eng |
hcfmusp.relation.reference | Yang YZ, 2018, HORM CANCER-US, V9, P371, DOI 10.1007/s12672-018-0343-8 | eng |
dc.description.index | MEDLINE | eng |
dc.identifier.eissn | 1573-0646 | |
hcfmusp.citation.scopus | 6 | - |
hcfmusp.scopus.lastupdate | 2024-03-29 | - |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MCM Artigos e Materiais de Revistas Científicas - LIM/31 Artigos e Materiais de Revistas Científicas - ODS/03 |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
art_SCOPIM-RIBEIRO_NT157_an_IGF1RIRS12_inhibitor_exhibits_antineoplastic_effects_in_2021.PDF Restricted Access | publishedVersion (English) | 1.37 MB | Adobe PDF | View/Open Request a copy |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.