CYP genes in osteosarcoma: Their role in tumorigenesis, pulmonary metastatic microenvironment and treatment response

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dc.contributor.author Trujillo-Paolillo, Alini [UNIFESP]
dc.contributor.author Tesser-Gamba, Francine [UNIFESP]
dc.contributor.author Petrilli, Antonio Sergio [UNIFESP]
dc.contributor.author de Seixas Alves, Maria Teresa [UNIFESP]
dc.contributor.author Garcia Filho, Reynaldo Jesus [UNIFESP]
dc.contributor.author de Oliveira, Renato [UNIFESP]
dc.contributor.author Caminada de Toledo, Silvia Regina [UNIFESP]
dc.date.accessioned 2020-06-26T16:30:36Z
dc.date.available 2020-06-26T16:30:36Z
dc.date.issued 2017
dc.identifier http://dx.doi.org/10.18632/oncotarget.15869 ]
dc.identifier.citation Oncotarget. Orchard Park, v. 8, n. 24, p. 38530-38540, 2017.
dc.identifier.issn 1949-2553
dc.identifier.uri https://repositorio.unifesp.br/handle/11600/53660
dc.description.abstract Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The present study investigated the expression of Cytochrome P-450 (CYP) genes: CYP1A2, CYP3A4 and CYP3A5 by qRT-PCR in 135 specimens obtained from OS patients, including biopsy (pre-chemotherapy), tumor resected in surgery (post-chemotherapy), adjacent bone to tumor (nonmalignant tissue), pulmonary metastasis and adjacent lung to metastasis (nonmalignant tissue). Normal bone and normal lung tissues were used as control. We also investigated in five OS cell lines the modulation of CYPs expression by cisplatin, doxorubicin and methotrexate. As result, the adjacent lung specimens presented CYP1A2 overexpression compared to the normal lung (p=0.0256). Biopsy specimens presented lower CYP3A4 expression than normal bone (p=0.0314). The overexpression of both CYP1A2 and CYP3A4 in post-chemotherapy specimens were correlated with better event free-survival (p=0.0244) and good response (p=0.0484), respectively. Furthermore, in vitro assays revealed that CYP1A2 was upregulated by doxorubicin (p=0.0034) en
dc.description.abstract CYP3A4 was upregulated by cisplatin, doxorubicin and methotrexate (p=0.0004, p=0.0024, p<0.0001, respectively) en
dc.description.abstract and CYP3A5 was downregulated by doxorubicin (p=0.0285) and upregulated in time-dependent manner by methotrexate (p=0.0239). In conclusion, our findings suggest that CYP genes play an important role in OS tumorigenesis, at primary and metastatic sites, as well in treatment response. en
dc.description.sponsorship Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
dc.description.sponsorship Grupo de Apoio ao Adolescente e a Crianca com Cancer (GRAACC/UNIFESP)
dc.format.extent 38530-38540
dc.language.iso eng
dc.publisher Impact Journals Llc
dc.relation.ispartof Oncotarget
dc.rights ACESSO ABERTO
dc.subject osteosarcoma en
dc.subject cytochrome P-450 en
dc.subject osteosarcoma cell line en
dc.subject tumor microenvironment en
dc.subject treatment response en
dc.title CYP genes in osteosarcoma: Their role in tumorigenesis, pulmonary metastatic microenvironment and treatment response en
dc.type Artigo
dc.description.affiliation Univ Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC, Genet Lab, Rua Botucatu, BR-04023062 Sao Paulo, SP, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Clin & Expt Oncol, Rua Dr Diogo de Faria, BR-04037003 Sao Paulo, SP, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Pathol, Rua Botucatu, BR-04023062 Sao Paulo, SP, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Orthoped Surg & Traumatol, Rua Borges Lagoa, BR-04038031 Sao Paulo, SP, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Thorac Surg, Rua Napoleao Barros, BR-04024002 Vila Clementino, SP, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Morphol & Genet, Rua Botucatu, BR-04023062 Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC, Genet Lab, Rua Botucatu, BR-04023062 Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Clin & Expt Oncol, Rua Dr Diogo de Faria, BR-04037003 Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp |Univ Fed Sao Paulo, Dept Pathol, Rua Botucatu, BR-04023062 Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Orthoped Surg & Traumatol, Rua Borges Lagoa, BR-04038031 Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Thorac Surg, Rua Napoleao Barros, BR-04024002 Vila Clementino, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Morphol & Genet, Rua Botucatu, BR-04023062 Sao Paulo, SP, Brazil
dc.description.sponsorshipID FAPESP: 2013/19166-6
dc.description.sponsorshipID Grupo de Apoio ao Adolescente e a Crianca com Cancer (GRAACC/UNIFESP)
dc.identifier.file WOS000403311900040.pdf
dc.identifier.doi 10.18632/oncotarget.15869
dc.description.source Web of Science
dc.identifier.wos WOS:000403311900040
dc.coverage Orchard Park
dc.citation.volume 8 ]
dc.citation.issue 24 ]



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