Visualizar Tese - Instituto de Biociências - Unesp

Visualizar Tese - Instituto de Biociências - Unesp Visualizar Tese - Instituto de Biociências - Unesp

10.07.2015 Views

Cirilo, PDRCONCLUSÕES DISCUSSÃO207cromossômica, reparo a danos no DNA e indução da apoptose, enquanto que genescom expressão aumentada (34%) atuam na proliferação e acúmulo da matrizextracelular. A ação conjunta destes grupos de genes pode contribuir para atransformação de células normais do miométrio em células neoplásicas. A integração dos dados genômicos e transcriptômicos aplicada neste estudodetectou 75 genes, classificados como potenciais modulares do fenótipo tumoral,entre os quais 26 tiveram correlação positiva e três apresentaram correlaçãonegativa. A análise de enriquecimento de genes revelou que 32 dos 75 genes estavamassociados a câncer. Os genes FGFR1, DBN1, NUPR1, COL3A1, AOC3, IFITM1,CALCRL, NOVA2, MVP, MFAP5, DIP2C apresentaram correlação positiva e CENPF,RHOH e BICD1 apresentaram correlação negativa (P < 0,05). A análise funcional dos 75 genes moduladores demonstrou que COL3A1, IGFBP5 eFGFR1 atuam em vias de proliferação e da matriz extracelular, exibindo atividadesindiretas na transcrição de genes alvos. Em adição, FGFR1 foi previamenteassociado a outras doenças humanas. Este gene pode ser um importante alvoterapêutico para o tratamento dos Leiomiomas Uterinos.

Cirilo, PDRREFERÊNCIAS2087. Referências BibliográficasAcevedo VD and Ittmann M. Paths of FGFR-driven tumorigenesis. Cell Cycle, 8, 580-588, 2009.Ahn WS, Kim KW, Bae SM et al. Targeted cellular process profiling approach for uterine leiomyomausing cDNA microarray, proteomics and gene ontology analysis. Int J Exp Path, 84, 267–279,2003.Akavia UD, Litvin O, Kim J et al. An integrated approach to uncover drivers of cancer. Cell, 143,1005–1017, 2010.Alderton GK. Common disease pathogenesis pathways. Nat Rev Caner, 10, Research Highlights,2010.Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large β-cell lymphoma identified bygene expression profiling. Nature, 403, 503–511, 2000.Alizadeh AA, Ross DT, Perou CM et al. Towards a novel classification of human malignancies basedon gene expression patterns. J Pathol, 195, 41–52, 2001.Alvarez H, Opalinska J, Zhou L et al. Widespread Hypomethylation Occurs Early and Synergizes withGene Amplification during Esophageal Carcinogenesis. PLoS Genet, 7, e1001356, 2011.Anania CA, Stewart EA, Quade BJ et al. Expression of the fibroblast growth factor receptor in womenwith leiomyomas and abnormal uterine bleeding. Mol Hum Reprod, 3, 685-691, 1997.Annereau JP, Szakacs G, Tucker CJ et al. Analysis of ATPbinding cassette transporter expression indrug-selected cell lines by a microarray dedicated to multidrug resistance. Mol Pharmacol,66, 1397-1405, 2004.Arslan AA, Gold LI, Mittal K et al. Gene expression studies provide clues to the pathogenesis ofuterine leiomyoma: new evidence and a systematic review. Human Reproduction, 20, 852-863, 2005.Arvanitis DA and Spandidos DA. Deregulation of the G1/S phase transition in cancer and squamousintraepithelial lesions of the uterine cervix: a case control study. Oncol Rep, 20, 751-760,2008.Asaoka Y, Ikenoue T, Koike K. New targeted therapies for gastric cancer. Expert Opin InvestigDrugs. May;20, 595-604, 2011.Aspenström P, Ruusala A, Pacholsky D Taking Rho GTPases to the next level: the cellular functionsof atypical Rho GTPases. Exp Cell Res, 15, 313, 3673-3679, 2007.Bahamondes L, Bahamondes MV, Monteiro I. Levonorgestrel-releasing intrauterine system: usesand controversies. Expert Rev Med Devices, 5, 437-445, 2008.Bakas P, Liapis A, Vlahopoulos S et al. Estrogen receptor alpha and beta in uterine fibroids: a basisfor altered estrogen responsiveness. Fertil Steril, 90, 1878-1885, 2008.

Cirilo, PDRREFERÊNCIAS2087. Referências BibliográficasAcevedo VD and Ittmann M. Paths of FGFR-driven tumorigenesis. Cell Cycle, 8, 580-588, 2009.Ahn WS, Kim KW, Bae SM et al. Targeted cellular process profiling approach for uterine leiomyomausing cDNA microarray, proteomics and gene ontology analysis. Int J Exp Path, 84, 267–279,2003.Akavia UD, Litvin O, Kim J et al. An integrated approach to uncover drivers of cancer. Cell, 143,1005–1017, 2010.Al<strong>de</strong>rton GK. Common disease pathogenesis pathways. Nat Rev Caner, 10, Research Highlights,2010.Aliza<strong>de</strong>h AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large β-cell lymphoma i<strong>de</strong>ntified bygene expression profiling. Nature, 403, 503–511, 2000.Aliza<strong>de</strong>h AA, Ross DT, Perou CM et al. Towards a novel classification of human malignancies basedon gene expression patterns. J Pathol, 195, 41–52, 2001.Alvarez H, Opalinska J, Zhou L et al. Wi<strong>de</strong>spread Hypomethylation Occurs Early and Synergizes withGene Amplification during Esophageal Carcinogenesis. PLoS Genet, 7, e1001356, 2011.Anania CA, Stewart EA, Qua<strong>de</strong> BJ et al. Expression of the fibroblast growth factor receptor in womenwith leiomyomas and abnormal uterine bleeding. Mol Hum Reprod, 3, 685-691, 1997.Annereau JP, Szakacs G, Tucker CJ et al. Analysis of ATPbinding cassette transporter expression indrug-selected cell lines by a microarray <strong>de</strong>dicated to multidrug resistance. Mol Pharmacol,66, 1397-1405, 2004.Arslan AA, Gold LI, Mittal K et al. Gene expression studies provi<strong>de</strong> clues to the pathogenesis ofuterine leiomyoma: new evi<strong>de</strong>nce and a systematic review. Human Reproduction, 20, 852-863, 2005.Arvanitis DA and Spandidos DA. Deregulation of the G1/S phase transition in cancer and squamousintraepithelial lesions of the uterine cervix: a case control study. Oncol Rep, 20, 751-760,2008.Asaoka Y, Ikenoue T, Koike K. New targeted therapies for gastric cancer. Expert Opin InvestigDrugs. May;20, 595-604, 2011.Aspenström P, Ruusala A, Pacholsky D Taking Rho GTPases to the next level: the cellular functionsof atypical Rho GTPases. Exp Cell Res, 15, 313, 3673-3679, 2007.Bahamon<strong>de</strong>s L, Bahamon<strong>de</strong>s MV, Monteiro I. Levonorgestrel-releasing intrauterine system: usesand controversies. Expert Rev Med Devices, 5, 437-445, 2008.Bakas P, Liapis A, Vlahopoulos S et al. Estrogen receptor alpha and beta in uterine fibroids: a basisfor altered estrogen responsiveness. Fertil Steril, 90, 1878-1885, 2008.

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