Differential cytotoxic activity of pharmacological inhibitors of IGF1R-related pathways in JAK2(V617F) driven cells

Página do item simplificado
dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorFERNANDES, Jaqueline Cristina
dc.contributor.authorFENERICH, Bruna Alves
dc.contributor.authorALVES-SILVA, Antonio Bruno
dc.contributor.authorFONSECA, Natasha Peixoto
dc.contributor.authorCOELHO-SILVA, Juan Luiz
dc.contributor.authorSCHEUCHER, Priscila Santos
dc.contributor.authorREGO, Eduardo Magalhaes
dc.contributor.authorFIGUEIREDO-PONTES, Lorena Lobo
dc.contributor.authorMACHADO-NETO, Joao Agostinho
dc.contributor.authorTRAINA, Fabiola
dc.date.accessioned2022-12-21T13:17:58Z
dc.date.available2022-12-21T13:17:58Z
dc.date.issued2022
dc.description.abstractMyeloproliferative neoplasms (MPN) belong to a group of clonal diseases of hematopoietic stem cells characterized by aberrant proliferation of mature myeloid lineages. The constitutive activation of the JAK2/STAT signaling pathway is now well established to play a central role in MPN pathogenesis; however, accumulating evidence now indicates that the IGF1R-mediated signaling pathway contributes to the maintenance of the malignant phenotype. Studies using inhibitors of IGF1-mediated signaling have reported cytotoxic effects in cellular and murine models of MPN, but no consensus has been reached regarding the potency and efficacy of inhibitors of the IGF1R-related pathway in this context. In the present study, we compared the potency and efficacy of three inhibitors of IGF1R-related pathways in a JAK2(V617F)-driven cellular model. These inhibitors (NT157, OSI-906, and NVP-AEW54) present antineoplastic activity with similar efficacy in Ba/F3 JAK2(V617F) cells, with NT157 showing the greatest potency. Both the induction of apoptosis and reduction in cell proliferation were associated with the observed reduction in cell viability. Downregulation of JAK2/STAT signaling was an advantageous off-target effect of all three inhibitors. These preclinical studies reinforce the potential of the IGF1R-related pathway as a therapeutic target in MPN.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil [2013/08135-2, 2015/02200-2, 2016/14049-0, 2017/19864-6, 2019/23864-7]
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) [001]
dc.identifier.citationTOXICOLOGY IN VITRO, v.83, article ID 105384, 7p, 2022
dc.identifier.doi10.1016/j.tiv.2022.105384
dc.identifier.eissn1879-3177
dc.identifier.issn0887-2333
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/50423
dc.language.isoeng
dc.publisherPERGAMON-ELSEVIER SCIENCE LTDeng
dc.relation.ispartofToxicology in Vitro
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright PERGAMON-ELSEVIER SCIENCE LTDeng
dc.subjectMyeloproliferative neoplasmseng
dc.subjectInsulin-like growth factor 1 receptoreng
dc.subjectJAK2V617Feng
dc.subjectPharmacological inhibitorseng
dc.subjectAntineoplastic activityeng
dc.subject.othergrowth-factor-ieng
dc.subject.otherinsulin-receptorseng
dc.subject.otherdual inhibitoreng
dc.subject.otherphase-ieng
dc.subject.otherosi-906eng
dc.subject.otheractivationeng
dc.subject.othermutationeng
dc.subject.othertargeteng
dc.subject.othernt157eng
dc.subject.otherigf1reng
dc.subject.wosToxicologyeng
dc.titleDifferential cytotoxic activity of pharmacological inhibitors of IGF1R-related pathways in JAK2(V617F) driven cellseng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalFERNANDES, Jaqueline Cristina:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Haematol & Oncol, Av Bandeirante 3900, BR-14048900 Ribeirao Preto, SP, Brazil; Sao Paulo Res Fdn, Ctr Cell Based Therapy, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalFENERICH, Bruna Alves:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Haematol & Oncol, Av Bandeirante 3900, BR-14048900 Ribeirao Preto, SP, Brazil; Sao Paulo Res Fdn, Ctr Cell Based Therapy, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalALVES-SILVA, Antonio Bruno:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Haematol & Oncol, Av Bandeirante 3900, BR-14048900 Ribeirao Preto, SP, Brazil; Sao Paulo Res Fdn, Ctr Cell Based Therapy, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalFONSECA, Natasha Peixoto:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Haematol & Oncol, Av Bandeirante 3900, BR-14048900 Ribeirao Preto, SP, Brazil; Sao Paulo Res Fdn, Ctr Cell Based Therapy, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalCOELHO-SILVA, Juan Luiz:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Haematol & Oncol, Av Bandeirante 3900, BR-14048900 Ribeirao Preto, SP, Brazil; Sao Paulo Res Fdn, Ctr Cell Based Therapy, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalSCHEUCHER, Priscila Santos:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Haematol & Oncol, Av Bandeirante 3900, BR-14048900 Ribeirao Preto, SP, Brazil
hcfmusp.author.externalFIGUEIREDO-PONTES, Lorena Lobo:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Haematol & Oncol, Av Bandeirante 3900, BR-14048900 Ribeirao Preto, SP, Brazil; Sao Paulo Res Fdn, Ctr Cell Based Therapy, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalMACHADO-NETO, Joao Agostinho:Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalTRAINA, Fabiola:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Haematol & Oncol, Av Bandeirante 3900, BR-14048900 Ribeirao Preto, SP, Brazil; Sao Paulo Res Fdn, Ctr Cell Based Therapy, Ribeirao Preto, SP, Brazil
hcfmusp.citation.scopus1
hcfmusp.contributor.author-fmusphcEDUARDO MAGALHAES REGO
hcfmusp.description.articlenumber105384
hcfmusp.description.volume83
hcfmusp.origemWOS
hcfmusp.origem.pubmed35568132
hcfmusp.origem.scopus2-s2.0-85130940536
hcfmusp.origem.wosWOS:000833395200005
hcfmusp.publisher.cityOXFORDeng
hcfmusp.publisher.countryENGLANDeng
hcfmusp.relation.referenceArber DA, 2016, BLOOD, V127, P2391, DOI 10.1182/blood-2016-03-643544eng
hcfmusp.relation.referenceCampos PD, 2016, ONCOTARGET, V7, P6948, DOI 10.18632/oncotarget.6851eng
hcfmusp.relation.referenceChapuis N, 2010, HAEMATOL-HEMATOL J, V95, P415, DOI 10.3324/haematol.2009.010785eng
hcfmusp.relation.referenceChen E, 2014, HEMATOL-AM SOC HEMAT, P268, DOI 10.1182/asheducation-2014.1.268eng
hcfmusp.relation.referenceFassnacht M, 2015, LANCET ONCOL, V16, P426, DOI 10.1016/S1470-2045(15)70081-1eng
hcfmusp.relation.referenceFenerich BA, 2020, SIGNAL TRANSDUCT TAR, V5, DOI 10.1038/s41392-019-0102-5eng
hcfmusp.relation.referenceFlashner-Abramson E, 2016, ONCOGENE, V35, P2675, DOI 10.1038/onc.2015.229eng
hcfmusp.relation.referenceGarofalo C, 2015, FRONT ENDOCRINOL, V6, DOI 10.3389/fendo.2015.00074eng
hcfmusp.relation.referenceIbuki N, 2014, MOL CANCER THER, V13, P2827, DOI 10.1158/1535-7163.MCT-13-0842eng
hcfmusp.relation.referenceJi QS, 2007, MOL CANCER THER, V6, P2158, DOI 10.1158/1535-7163.MCT-07-0070eng
hcfmusp.relation.referenceJones RL, 2015, CLIN CANCER RES, V21, P693, DOI 10.1158/1078-0432.CCR-14-0265eng
hcfmusp.relation.referenceKralovics R, 2005, NEW ENGL J MED, V352, P1779, DOI 10.1056/NEJMoa051113eng
hcfmusp.relation.referenceKuhn DJ, 2012, BLOOD, V120, P3260, DOI 10.1182/blood-2011-10-386789eng
hcfmusp.relation.referenceMulvihill MJ, 2009, FUTURE MED CHEM, V1, P1153, DOI 10.4155/FMC.09.89eng
hcfmusp.relation.referenceAlves APNR, 2019, CANCER LETT, V456, P59, DOI 10.1016/j.canlet.2019.04.030eng
hcfmusp.relation.referenceOsorio FG, 2016, NAT MED, V22, P91, DOI 10.1038/nm.4013eng
hcfmusp.relation.referencePardanani A, 2011, LEUKEMIA, V25, P218, DOI 10.1038/leu.2010.269eng
hcfmusp.relation.referencePetrelli A, 2008, CURR MED CHEM, V15, P422eng
hcfmusp.relation.referencePuzanov I, 2015, CLIN CANCER RES, V21, P701, DOI 10.1158/1078-0432.CCR-14-0303eng
hcfmusp.relation.referenceQuintas-Cardama A, 2010, BLOOD, V115, P3109, DOI 10.1182/blood-2009-04-214957eng
hcfmusp.relation.referenceRamsay RR, 2018, CLIN TRANSL MED, V7, DOI 10.1186/s40169-017-0181-2eng
hcfmusp.relation.referenceReuveni H, 2013, CANCER RES, V73, P4383, DOI 10.1158/0008-5472.CAN-12-3385eng
hcfmusp.relation.referenceScopim-Ribeiro R, 2021, INVEST NEW DRUG, V39, P736, DOI 10.1007/s10637-020-01028-8eng
hcfmusp.relation.referenceStaerk J, 2005, J BIOL CHEM, V280, P41893, DOI 10.1074/jbc.C500358200eng
hcfmusp.relation.referenceSu SP, 2018, MOL CANCER THER, V17, P931, DOI 10.1158/1535-7163.MCT-17-0377eng
hcfmusp.relation.referenceWarmuth M, 2007, CURR OPIN ONCOL, V19, P55, DOI 10.1097/CCO.0b013e328011a25feng
hcfmusp.relation.referenceYaktapour N, 2013, BLOOD, V122, P1621, DOI 10.1182/blood-2013-02-484386eng
hcfmusp.relation.referenceYan DQ, 2012, BLOOD, V119, P3539, DOI 10.1182/blood-2011-03-345215eng
hcfmusp.scopus.lastupdate2024-05-10
relation.isAuthorOfPublication98f9f342-22fe-4b3b-a069-69b76a59958f
relation.isAuthorOfPublication.latestForDiscovery98f9f342-22fe-4b3b-a069-69b76a59958f
Arquivos
Pacote Original
Agora exibindo 1 - 1 de 1
Nenhuma Miniatura disponível
Nome:
art_FERNANDES_Differential_cytotoxic_activity_of_pharmacological_inhibitors_of_IGF1Rrelated_2022.PDF
Tamanho:
5.31 MB
Formato:
Adobe Portable Document Format
Descrição:
publishedVersion (English)
Baixar
Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/31
Artigos e Materiais de Revistas Científicas - ODS/03