Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical

Bibliographic Details
Main Author: TIRONE, Nelson Rannieri
Publication Date: 2008
Format: Master thesis
Language: por
Source: Biblioteca Digital de Teses e Dissertações da UFTM
Download full: http://localhost:8080/tede/handle/tede/43
Summary: Interferor-alfa (IFN-α) is a glicoprotein belonged to a family of cytokines which participate in the control and cell replication in the defence of hostess against strange organisms, as vírus or bacteria. Although the IFN-α has been known by antiviral property, numerous investigations afterward showed that the IFN is involved on regulation cell growth and on immunomodulatory effect. The IFN-α engage with the receptors of interferon alpha (IFNAR 1 and 2 ) with are expresses many types of cells of organism including growth cells and immune system. The synthesis of protein involved in intracellular resistance against vírus includes the production of 2.5. OAS. This enzyme binds with high affinity to RNase L and endoribonuclease that bunch the signs of single stranded of RNA taking the inhibition of viral proteins. In the literature there aren´t reports about evaluation of expression of genes receptors of interferon alpha and enzyme 2.,5. OAS in cells of cervical intraepithelial neoplasia wake up us to the intention of study and corelation themselves to expression of receivers, or a possible disfunction in translate of sign intracell, that consequence will take a minus ativation of enzyme, factors would be contribute to difficult the extintion of HPV or will act as a facilitator in evolution of epithelials cells to neoplasics injuries. The present work evaluated for RT-PCR the expression of mRNA of IFN-α, the receptors of Interferon alpha ( IFNAR 1 and IFNAR 2 ) and the expression of one of responsible elements encouragement of interferon ( ISRE ) to be present in regions of genes induced by IFN-α; through of the expression of mRNA of enzyme 2. 5. oligoadenilato synthetase ( 2.,5. OAS ) in biopsies of patients in different levels of cervical intraepithelial neoplasia ( CIN I, II and III ). Biopsies of uterine cervix was collected in women with CIN I, II and III ( n=28 ) and controls ( n= 17 ) without injury or infection by HPV. The presence of DNA of HPV with high and low risk was determined by hybrid capture. Levels of mRNA of IFNAR 1, IFNAR 2, IFN-α and 2.5.OAS were determined by RT-PCR. After the transcription the cDNA was submitted to amplification with specifics primers. In the research of expression of the interferon receptor alpha 1 ( IFNAR 1 ) the sample controls showed greater expression of the receptor 58,3% ( 10/17 ), while in the sample CIN 14,2% ( 4/28 ) expressed the mRNA of the receptor; p=0.0018. The expression of IFNAR2 was bigger also in the sample controls 64,7% ( 11/17 ) than in the patients with injuries 7,1% ( 2/28 ), p=0.0018. The simultaneous expression of two receptor was observed only in the control group 47,0% ( 8/17 ), p=0.0001. The results for the IFN-α show the presence of the fragment in 14,2% ( 4/28 ) of sample of CIN, without expression in the control group and the expression of levels of enzyme 2.5.OAS was 28,5% ( 8/28 ) in the samples of CIN and 11,7% ( 2/17 ) in the samples of control group, p=n.s. With the present study we can conclude that the samples of CIN showed the DNA of HPV in 50% ( 14/28 ), the samples have gotten of patients with cervical intraepithelial neoplasia showed one low expression of RNA messanger of the receptor of interferon subunit 1 and 2. The simultaneous expression of two subunits of receptors were found only in control group. There wasn.t significant difference of expression of RNA messanger of IFN-α and of enzyme 2.5.OAS between the control groups and CIN.
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spelling MICHELIN, Márcia Antoniazihttp://lattes.cnpq.br/2599409028588669MURTA, Eddie Fernando CândidoMURTA, Eddie Fernando Cândidohttp://lattes.cnpq.br/5535116611578084TIRONE, Nelson Rannieri2015-11-27T18:50:18Z2009-02-132008-08-14TIRONE, Nelson Rannieri. Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical. 2008. 75 f. Dissertação (Mestrado em Patologia Clínica) - Universidade Federal do Triângulo Mineiro, Uberaba, 2008.http://localhost:8080/tede/handle/tede/43Interferor-alfa (IFN-α) is a glicoprotein belonged to a family of cytokines which participate in the control and cell replication in the defence of hostess against strange organisms, as vírus or bacteria. Although the IFN-α has been known by antiviral property, numerous investigations afterward showed that the IFN is involved on regulation cell growth and on immunomodulatory effect. The IFN-α engage with the receptors of interferon alpha (IFNAR 1 and 2 ) with are expresses many types of cells of organism including growth cells and immune system. The synthesis of protein involved in intracellular resistance against vírus includes the production of 2.5. OAS. This enzyme binds with high affinity to RNase L and endoribonuclease that bunch the signs of single stranded of RNA taking the inhibition of viral proteins. In the literature there aren´t reports about evaluation of expression of genes receptors of interferon alpha and enzyme 2.,5. OAS in cells of cervical intraepithelial neoplasia wake up us to the intention of study and corelation themselves to expression of receivers, or a possible disfunction in translate of sign intracell, that consequence will take a minus ativation of enzyme, factors would be contribute to difficult the extintion of HPV or will act as a facilitator in evolution of epithelials cells to neoplasics injuries. The present work evaluated for RT-PCR the expression of mRNA of IFN-α, the receptors of Interferon alpha ( IFNAR 1 and IFNAR 2 ) and the expression of one of responsible elements encouragement of interferon ( ISRE ) to be present in regions of genes induced by IFN-α; through of the expression of mRNA of enzyme 2. 5. oligoadenilato synthetase ( 2.,5. OAS ) in biopsies of patients in different levels of cervical intraepithelial neoplasia ( CIN I, II and III ). Biopsies of uterine cervix was collected in women with CIN I, II and III ( n=28 ) and controls ( n= 17 ) without injury or infection by HPV. The presence of DNA of HPV with high and low risk was determined by hybrid capture. Levels of mRNA of IFNAR 1, IFNAR 2, IFN-α and 2.5.OAS were determined by RT-PCR. After the transcription the cDNA was submitted to amplification with specifics primers. In the research of expression of the interferon receptor alpha 1 ( IFNAR 1 ) the sample controls showed greater expression of the receptor 58,3% ( 10/17 ), while in the sample CIN 14,2% ( 4/28 ) expressed the mRNA of the receptor; p=0.0018. The expression of IFNAR2 was bigger also in the sample controls 64,7% ( 11/17 ) than in the patients with injuries 7,1% ( 2/28 ), p=0.0018. The simultaneous expression of two receptor was observed only in the control group 47,0% ( 8/17 ), p=0.0001. The results for the IFN-α show the presence of the fragment in 14,2% ( 4/28 ) of sample of CIN, without expression in the control group and the expression of levels of enzyme 2.5.OAS was 28,5% ( 8/28 ) in the samples of CIN and 11,7% ( 2/17 ) in the samples of control group, p=n.s. With the present study we can conclude that the samples of CIN showed the DNA of HPV in 50% ( 14/28 ), the samples have gotten of patients with cervical intraepithelial neoplasia showed one low expression of RNA messanger of the receptor of interferon subunit 1 and 2. The simultaneous expression of two subunits of receptors were found only in control group. There wasn.t significant difference of expression of RNA messanger of IFN-α and of enzyme 2.5.OAS between the control groups and CIN.O interferon - alfa (IFN-α) é uma glicoproteínas pertencente à família das citocinas que participa no controle e na replicação celular, na defesa do hospedeiro contra organismos estranhos, como vírus ou bactérias. Embora o IFN-á tenha sido inicialmente conhecido pela propriedade antiviral, numerosas investigações posteriores mostraram que o IFN está envolvido na regulação do crescimento celular e no efeito imunomodulatório. O IFN-α interage com os receptores de interferon alfa (IFNAR 1 e 2) que são expressos em vários tipos de células do organismo incluindo células tumorais e do sistema imune. A síntese de proteínas envolvidas na resistência intracelular contra vírus inclui a produção de 2´5´OAS. Esta enzima se liga com alta afinidade a uma RNase L e endoribonuclease que catalisa a clivagem das fitas simples de RNA levando a inibição das proteínas virais. Na literatura não existem relatos de avaliação da expressão dos genes do receptor de interferon alfa e da enzima 2´,5´OAS em células de neoplasia intraepitelial cervical, despertando-nos a intenção de estudar e correlacionar se a expressão dos receptores, ou uma possível disfunção na transdução do sinal intracelular, que por conseqüência levaria a uma diminuição da ativação da enzima, seriam fatores que contribuem para dificultar a eliminação do HPV ou atuariam como facilitador na evolução das células epiteliais para lesões neoplásicas. O presente trabalho avaliou por RT-PCR a expressão do RNAm do IFN-α, dos receptores de Interferon alfa (IFNAR1 e IFNAR2) e a expressão de um dos elementos responsivos pelo estimulo de interferon (ISRE) presente nas regiões dos genes induzidos pelo IFN-; através da expressão do RNAm da enzima 2´5´ Oligoadenilato sintetase (2´,5´OAS) em biopsias de pacientes em diferentes graus de neoplasia intraepitelial cervical (NIC I, II e III). Biopsia do colo uterino era coletada em mulheres com NIC I, II E III (n=28) e controles (n=17) sem lesão ou infecção por HPV. A presença do DNA do HPV de alto e baixo risco foi determinada por Captura hibrida. Níveis de mRNA do IFNAR1, IFNAR2, IFN-α e 2´5´OAS eram determinados por RT-PCR. Após a transcrição o cDNA foi submetido à amplificação com primers específicos. Na pesquisa da expressão do receptor de interferon alfa 1 (IFNAR1) as amostras controles apresentaram uma maior expressão do receptor 58,3%(10/17), enquanto nas amostras NIC 14,2% (4/28) expressavam o RNAm do receptor; p=0.0018. A expressão do IFNAR2 foi maior também nas amostras controles 64,7% (11/17) que nos pacientes com lesões 7,1% (2/28), p=0.0018. A expressão simultânea dos dois receptores foi observada apenas no grupo controle 47,0% (8/17), p=0.0001. Os resultados para o IFN-α mostram a presença do fragmento em 14,2% (4/28) das amostras de NIC, sem expressão no grupo controle e a expressão dos níveis da enzima 2´5´OAS foi de 28,5% (8/28) nas amostras de NIC e de 11,7% (2/17) nas amostras do grupo controle, p=n.s. Com o presente estudo podemos concluir que as amostras de NIC apresentavam o DNA do HPV em 50% (14/28), as amostras obtidas de pacientes com neoplasia intraepitelial cervical apresentam uma baixa expressão do RNA mensageiro do receptor de interferon subunidade 1 e 2. A expressão simultânea das duas subunidades dos receptores foi encontrada apenas no grupo controle. Não houve diferença significativa da expressão do RNA mensageiro do IFN-α e da enzima 2´5´OAS entre os grupos controle e NIC.Fundação de Amparo a Pesquisa do Estado de Minas Geraisapplication/pdfhttp://localhost:8080/tede/retrieve/282/Tese_NelsonRironeME.pdf.jpgporUniversidade Federal do Triângulo MineiroPrograma de Pós-Graduação em PatologiaUFTMBRPatologia ClínicaNeoplasia intraepitelial cervicalInterferon alfaReceptores de interferonCervical intraepithelial neoplasiaInterferon alphaInterferon alpha receptor2´5´Oligoadenylate SynthetaseCNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICAExpressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervicalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFTMinstname:Universidade Federal do Triangulo Mineiro (UFTM)instacron:UFTMORIGINALTese_NelsonRironeME.pdfapplication/pdf986343http://bdtd.uftm.edu.br/bitstream/tede/43/1/Tese_NelsonRironeME.pdf5f7926b17e24660eeb885773bb21c9e2MD51TEXTTese_NelsonRironeME.pdf.txtTese_NelsonRironeME.pdf.txtExtracted Texttext/plain128000http://bdtd.uftm.edu.br/bitstream/tede/43/2/Tese_NelsonRironeME.pdf.txt67405d33392b180b151ade0286ca9f0fMD52THUMBNAILTese_NelsonRironeME.pdf.jpgTese_NelsonRironeME.pdf.jpgGenerated Thumbnailimage/jpeg3775http://bdtd.uftm.edu.br/bitstream/tede/43/3/Tese_NelsonRironeME.pdf.jpg55a9fb8b53f0cef2979a7bc80e31fc20MD53tede/432019-07-22 15:13:36.708oai:bdtd.uftm.edu.br:tede/43Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.uftm.edu.br/PUBhttp://bdtd.uftm.edu.br/oai/requestbdtd@uftm.edu.br||bdtd@uftm.edu.bropendoar:2019-07-22T18:13:36Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)false
dc.title.por.fl_str_mv Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical
title Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical
spellingShingle Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical
TIRONE, Nelson Rannieri
Neoplasia intraepitelial cervical
Interferon alfa
Receptores de interferon
Cervical intraepithelial neoplasia
Interferon alpha
Interferon alpha receptor
2´5´Oligoadenylate Synthetase
CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
title_short Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical
title_full Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical
title_fullStr Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical
title_full_unstemmed Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical
title_sort Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical
author TIRONE, Nelson Rannieri
author_facet TIRONE, Nelson Rannieri
author_role author
dc.contributor.advisor1.fl_str_mv MICHELIN, Márcia Antoniazi
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2599409028588669
dc.contributor.advisor-co1.fl_str_mv MURTA, Eddie Fernando Cândido
dc.contributor.advisor-co1Lattes.fl_str_mv MURTA, Eddie Fernando Cândido
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5535116611578084
dc.contributor.author.fl_str_mv TIRONE, Nelson Rannieri
contributor_str_mv MICHELIN, Márcia Antoniazi
MURTA, Eddie Fernando Cândido
dc.subject.por.fl_str_mv Neoplasia intraepitelial cervical
Interferon alfa
Receptores de interferon
topic Neoplasia intraepitelial cervical
Interferon alfa
Receptores de interferon
Cervical intraepithelial neoplasia
Interferon alpha
Interferon alpha receptor
2´5´Oligoadenylate Synthetase
CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
dc.subject.eng.fl_str_mv Cervical intraepithelial neoplasia
Interferon alpha
Interferon alpha receptor
2´5´Oligoadenylate Synthetase
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
description Interferor-alfa (IFN-α) is a glicoprotein belonged to a family of cytokines which participate in the control and cell replication in the defence of hostess against strange organisms, as vírus or bacteria. Although the IFN-α has been known by antiviral property, numerous investigations afterward showed that the IFN is involved on regulation cell growth and on immunomodulatory effect. The IFN-α engage with the receptors of interferon alpha (IFNAR 1 and 2 ) with are expresses many types of cells of organism including growth cells and immune system. The synthesis of protein involved in intracellular resistance against vírus includes the production of 2.5. OAS. This enzyme binds with high affinity to RNase L and endoribonuclease that bunch the signs of single stranded of RNA taking the inhibition of viral proteins. In the literature there aren´t reports about evaluation of expression of genes receptors of interferon alpha and enzyme 2.,5. OAS in cells of cervical intraepithelial neoplasia wake up us to the intention of study and corelation themselves to expression of receivers, or a possible disfunction in translate of sign intracell, that consequence will take a minus ativation of enzyme, factors would be contribute to difficult the extintion of HPV or will act as a facilitator in evolution of epithelials cells to neoplasics injuries. The present work evaluated for RT-PCR the expression of mRNA of IFN-α, the receptors of Interferon alpha ( IFNAR 1 and IFNAR 2 ) and the expression of one of responsible elements encouragement of interferon ( ISRE ) to be present in regions of genes induced by IFN-α; through of the expression of mRNA of enzyme 2. 5. oligoadenilato synthetase ( 2.,5. OAS ) in biopsies of patients in different levels of cervical intraepithelial neoplasia ( CIN I, II and III ). Biopsies of uterine cervix was collected in women with CIN I, II and III ( n=28 ) and controls ( n= 17 ) without injury or infection by HPV. The presence of DNA of HPV with high and low risk was determined by hybrid capture. Levels of mRNA of IFNAR 1, IFNAR 2, IFN-α and 2.5.OAS were determined by RT-PCR. After the transcription the cDNA was submitted to amplification with specifics primers. In the research of expression of the interferon receptor alpha 1 ( IFNAR 1 ) the sample controls showed greater expression of the receptor 58,3% ( 10/17 ), while in the sample CIN 14,2% ( 4/28 ) expressed the mRNA of the receptor; p=0.0018. The expression of IFNAR2 was bigger also in the sample controls 64,7% ( 11/17 ) than in the patients with injuries 7,1% ( 2/28 ), p=0.0018. The simultaneous expression of two receptor was observed only in the control group 47,0% ( 8/17 ), p=0.0001. The results for the IFN-α show the presence of the fragment in 14,2% ( 4/28 ) of sample of CIN, without expression in the control group and the expression of levels of enzyme 2.5.OAS was 28,5% ( 8/28 ) in the samples of CIN and 11,7% ( 2/17 ) in the samples of control group, p=n.s. With the present study we can conclude that the samples of CIN showed the DNA of HPV in 50% ( 14/28 ), the samples have gotten of patients with cervical intraepithelial neoplasia showed one low expression of RNA messanger of the receptor of interferon subunit 1 and 2. The simultaneous expression of two subunits of receptors were found only in control group. There wasn.t significant difference of expression of RNA messanger of IFN-α and of enzyme 2.5.OAS between the control groups and CIN.
publishDate 2008
dc.date.issued.fl_str_mv 2008-08-14
dc.date.available.fl_str_mv 2009-02-13
dc.date.accessioned.fl_str_mv 2015-11-27T18:50:18Z
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dc.identifier.citation.fl_str_mv TIRONE, Nelson Rannieri. Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical. 2008. 75 f. Dissertação (Mestrado em Patologia Clínica) - Universidade Federal do Triângulo Mineiro, Uberaba, 2008.
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identifier_str_mv TIRONE, Nelson Rannieri. Expressão local de interferon alfa, dos receptores de interferon alfa (IFNAR) e da enzima 2´5´Oligoadenilato sintetase em pacientes com neoplasia intraepitelial cervical. 2008. 75 f. Dissertação (Mestrado em Patologia Clínica) - Universidade Federal do Triângulo Mineiro, Uberaba, 2008.
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