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DC Field | Value | Language |
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dc.contributor | Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP | |
dc.contributor.author | SANDRI, Silvana | |
dc.contributor.author | WATANABE, Luis R. M. | |
dc.contributor.author | OLIVEIRA, Erica Aparecida de | |
dc.contributor.author | FAIAO-FLORES, Fernanda | |
dc.contributor.author | MIGLIORINI, Silene | |
dc.contributor.author | TIAGO, Manoela | |
dc.contributor.author | FELIPE-SILVA, Aloisio | |
dc.contributor.author | VAZQUEZ, Vinicius de Lima | |
dc.contributor.author | SOUZA, Paola da Costa | |
dc.contributor.author | CONSOLARO, Marcia Edilaine Lopes | |
dc.contributor.author | CAMPA, Ana | |
dc.contributor.author | MARIA-ENGLER, Silvya Stuchi | |
dc.date.accessioned | 2020-10-15T14:38:40Z | - |
dc.date.available | 2020-10-15T14:38:40Z | - |
dc.date.issued | 2020 | |
dc.identifier.citation | PHARMACOLOGICAL RESEARCH, v.159, article ID 104998, 10p, 2020 | |
dc.identifier.issn | 1043-6618 | |
dc.identifier.uri | https://observatorio.fm.usp.br/handle/OPI/37904 | - |
dc.description.abstract | Indoleamine 2,3-dioxygenase (IDO) is associated with the progression of many types of tumors, including melanoma. However, there is limited information about IDO modulation on tumor cell itself and the effect of BRAF inhibitor (BRAFi) treatment and resistance. Herein, IDO expression was analyzed in different stages of melanoma development and progression linked to BRAFi resistance. IDO expression was increased in primary and metastatic melanomas from patients' biopsies, especially in the immune cells infiltrate. Using a bioinformatics approach, we also identified an increase in the IDO mRNA in the vertical growth and metastatic phases of melanoma. Using in silico analyses, we found that IDO mRNA was increased in BRAFi resistance. In an in vitro model, IDO expression and activity induced by interferon-gamma (IFN gamma) in sensitive melanoma cells was decreased by BRAFi treatment. However, cells that became resistant to BRAFi presented random IDO expression levels. Also, we identified that treatment with the IDO inhibitor, 1-methyltryptophan (1-MT), was able to reduce clonogenicity for parental and BRAFi-resistant cells. In conclusion, our results support the hypothesis that the decreased IDO expression in tumor cells is one of the many additional outcomes contributing to the therapeutic effects of BRAFi. Still, the IDO production changeability by the BRAFi-resistant cells reiterates the complexity of the response arising from resistance, making it not possible, at this stage, to associate IDO expression in tumor cells with resistance. On the other hand, the maintenance of 1-MT off-target effect endorses its use as an adjuvant treatment of melanoma that has become BRAFi-resistant. | eng |
dc.description.sponsorship | Sao Paulo Research FoundationFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2017/04926-6, 2016/16554-3, 2017/26148-5 2011/19045-9, 2012/05910-2, 2013/05172-4, 2015/10821-7] | |
dc.description.sponsorship | Coordination for the Improvement of Higher Education Personnel (CAPES)CAPES [1569289] | |
dc.description.sponsorship | Brazilian National Council for Scientific and Technological Development (CNPq)National Council for Scientific and Technological Development (CNPq) [304339/2017-2, 408769/2018-1] | |
dc.language.iso | eng | |
dc.publisher | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | eng |
dc.relation.ispartof | Pharmacological Research | |
dc.rights | restrictedAccess | eng |
dc.subject | Indoleamine 2,3 dioxygenase activity | eng |
dc.subject | Kynurenine | eng |
dc.subject | BRAFi | eng |
dc.subject | Immune effects | eng |
dc.subject | 1-Methyl tryptophan (1-MT) | eng |
dc.subject | Antiproliferative effects | eng |
dc.subject | Melanoma resistance | eng |
dc.subject.other | tumor microenvironment | eng |
dc.subject.other | antitumor-activity | eng |
dc.subject.other | pd-l1 expression | eng |
dc.subject.other | mek inhibitors | eng |
dc.subject.other | vemurafenib | eng |
dc.subject.other | cells | eng |
dc.subject.other | mapk | eng |
dc.subject.other | ido | eng |
dc.subject.other | mechanisms | eng |
dc.subject.other | kynurenine | eng |
dc.title | Indoleamine 2,3-dioxygenase in melanoma progression and BRAF inhibitor resistance | eng |
dc.type | article | eng |
dc.rights.holder | Copyright ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | eng |
dc.identifier.doi | 10.1016/j.phrs.2020.104998 | |
dc.identifier.pmid | 32535222 | |
dc.subject.wos | Pharmacology & Pharmacy | eng |
dc.type.category | original article | eng |
dc.type.version | publishedVersion | eng |
hcfmusp.author.external | SANDRI, Silvana:Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol Anal, Skin Biol Grp, Sao Paulo, Brazil | |
hcfmusp.author.external | WATANABE, Luis R. M.:Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol Anal, Skin Biol Grp, Sao Paulo, Brazil | |
hcfmusp.author.external | OLIVEIRA, Erica Aparecida de:Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol Anal, Skin Biol Grp, Sao Paulo, Brazil | |
hcfmusp.author.external | FAIAO-FLORES, Fernanda:Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol Anal, Skin Biol Grp, Sao Paulo, Brazil | |
hcfmusp.author.external | MIGLIORINI, Silene:Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol Anal, Skin Biol Grp, Sao Paulo, Brazil | |
hcfmusp.author.external | TIAGO, Manoela:Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol Anal, Skin Biol Grp, Sao Paulo, Brazil | |
hcfmusp.author.external | VAZQUEZ, Vinicius de Lima:Barretos Canc Hosp, Inst Res & Educ & Melanoma Sarcoma Surg, Barretos, SP, Brazil | |
hcfmusp.author.external | SOUZA, Paola da Costa:Lab Souza Patol, Maringa, Parana, Brazil | |
hcfmusp.author.external | CONSOLARO, Marcia Edilaine Lopes:Univ Estadual Maringa, Dept Clin Anal & Biomed, Maringa, Parana, Brazil | |
hcfmusp.author.external | CAMPA, Ana:Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol Anal, Skin Biol Grp, Sao Paulo, Brazil | |
hcfmusp.author.external | MARIA-ENGLER, Silvya Stuchi:Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol Anal, Skin Biol Grp, Sao Paulo, Brazil | |
hcfmusp.description.articlenumber | 104998 | |
hcfmusp.description.volume | 159 | |
hcfmusp.origem | WOS | |
hcfmusp.origem.id | WOS:000566435200007 | |
hcfmusp.origem.id | 2-s2.0-85086985023 | |
hcfmusp.publisher.city | LONDON | eng |
hcfmusp.publisher.country | ENGLAND | eng |
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dc.description.index | MEDLINE | eng |
hcfmusp.citation.scopus | 9 | - |
hcfmusp.scopus.lastupdate | 2024-03-29 | - |
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