Avaliação da expressão da granzima b e sua relação com o prognóstico do carcinoma espinocelular de boca

Detalhes bibliográficos
Ano de defesa: 2010
Autor(a) principal: COSTA, Nádia do Lago lattes
Orientador(a): BATISTA, Aline Carvalho lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Goiás
Programa de Pós-Graduação: Mestrado em Odontologia
Departamento: Ciência da Saúde
País: BR
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tde/1363
Resumo: The cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are more effective in fighting cancer because these cells recognize tumor cells and release cytotoxic granules rich in perforin and granzyme B (GB). The perforin form pores in tumor cells allowing the influx of GB. When inside the cell, the GB promotes tumor cell death through apoptosis. In this context, high expression of GB into the microenvironment of different types of cancers has been considered a key event for effective antitumor immunity. Therefore, the objective of this study was to identify and quantify GB+ cells, peri- and intratumoral, and its relationship with clinical prognostic parameters (size of the primary lesion, location, metastasis and survival) and microscopic (microscopic grading and cell proliferation index and apoptosis of neoplastic cells) of squamous cell carcinoma (SCC) of the oral cavity. GB+ cells were identified by the technique of immunohistochemistry, a method of polymer, in 20 samples from patients with SCC of the oral cavity that had metastasized to cervical lymph nodes and in 35 samples from patients with SCC of the oral cavity without metastasis to cervical lymph nodes. Our results showed that the density of peritumoral GB+ cells was significantly higher in the non-metastatic SCC when compared with metastatic group (p=0.03). In addition, patients with high expression of peritumoral GB had a longer survival than those with low expression of this protease (Kaplan Meier, Log Rank p=0.02). We showed also that patients with high density of peritumoral GB+ cells showed a low percentage of neoplastic cells bcl2+ (antiapoptotic protein) (P=0.004) and high density of neoplastic cells Bax+ (apoptotic protein) (p=0.031) when compared to the group of low density of peritumoral GB+ cells. In agreement with these data, patients who had a high density of peritumoral GB+ cells showed high expression of Annexin V by neoplastic cells. Additionally, the density of GB+ cells intratumoral and peritumoral was significantly higher in the T1 and T2 (39.44±7.21 and 14.61±3.60, respectively) when compared to T3 and T4 (31.03±3.76 and 11.90±1.88, respectively), however these results were not statistically significant (p>0.05). The association between the density of cells GB+ and other characteristics of SCC of the oral cavity, such as location, tumor proliferation and tumor grading was not observed. Our findings suggest that the increased of expression of GB in tumor microenvironment of SCC of the oral cavity may have beneficial effect against neoplastics cells, contributing to apoptosis of these cells, lower lymph node involvement and increased survival time of patients.
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spelling BATISTA, Aline Carvalhohttp://lattes.cnpq.br/0199082642322002http://lattes.cnpq.br/9120865567187887COSTA, Nádia do Lago2014-07-29T15:21:56Z2011-01-062010-02-26COSTA, Nádia do Lago. Evaluation of the expression of granzyme b and its relationship with the prognosis of carcinoma of the mouth. 2010. 45 f. Dissertação (Mestrado em Ciência da Saúde) - Universidade Federal de Goiás, Goiânia, 2010.http://repositorio.bc.ufg.br/tede/handle/tde/1363The cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are more effective in fighting cancer because these cells recognize tumor cells and release cytotoxic granules rich in perforin and granzyme B (GB). The perforin form pores in tumor cells allowing the influx of GB. When inside the cell, the GB promotes tumor cell death through apoptosis. In this context, high expression of GB into the microenvironment of different types of cancers has been considered a key event for effective antitumor immunity. Therefore, the objective of this study was to identify and quantify GB+ cells, peri- and intratumoral, and its relationship with clinical prognostic parameters (size of the primary lesion, location, metastasis and survival) and microscopic (microscopic grading and cell proliferation index and apoptosis of neoplastic cells) of squamous cell carcinoma (SCC) of the oral cavity. GB+ cells were identified by the technique of immunohistochemistry, a method of polymer, in 20 samples from patients with SCC of the oral cavity that had metastasized to cervical lymph nodes and in 35 samples from patients with SCC of the oral cavity without metastasis to cervical lymph nodes. Our results showed that the density of peritumoral GB+ cells was significantly higher in the non-metastatic SCC when compared with metastatic group (p=0.03). In addition, patients with high expression of peritumoral GB had a longer survival than those with low expression of this protease (Kaplan Meier, Log Rank p=0.02). We showed also that patients with high density of peritumoral GB+ cells showed a low percentage of neoplastic cells bcl2+ (antiapoptotic protein) (P=0.004) and high density of neoplastic cells Bax+ (apoptotic protein) (p=0.031) when compared to the group of low density of peritumoral GB+ cells. In agreement with these data, patients who had a high density of peritumoral GB+ cells showed high expression of Annexin V by neoplastic cells. Additionally, the density of GB+ cells intratumoral and peritumoral was significantly higher in the T1 and T2 (39.44±7.21 and 14.61±3.60, respectively) when compared to T3 and T4 (31.03±3.76 and 11.90±1.88, respectively), however these results were not statistically significant (p>0.05). The association between the density of cells GB+ and other characteristics of SCC of the oral cavity, such as location, tumor proliferation and tumor grading was not observed. Our findings suggest that the increased of expression of GB in tumor microenvironment of SCC of the oral cavity may have beneficial effect against neoplastics cells, contributing to apoptosis of these cells, lower lymph node involvement and increased survival time of patients.Os Linfócitos T Citotóxicos (LTC) e as células Natural Killer (NK) são as células mais efetivas no combate ao câncer, pois essas células reconhecem células tumorais e liberam grânulos citotóxicos ricos em perforina e granzima B (GB). A perforina forma poros nas células tumorais permitindo o influxo da GB. Quando no interior da célula, a GB promove a morte da célula tumoral através da apoptose. Neste contexto, a alta expressão de GB no microambiente de diferentes tipos de cânceres tem sido considerado um evento fundamental para uma efetiva imunidade antitumoral. Portanto, o objetivo do presente estudo foi identificar e quantificar células GB+, peri- e intratumoral, e sua relação com parâmetros de prognóstico clínicos (tamanho da lesão primária, localização, metástase e sobrevida) e microscópicos (gradação microscópica e índices de proliferação celular e de apoptose das células neoplásicas) do carcimoma espinocelular (CEC) de cavidade oral. As células GB+ foram identificadas pela técnica da imunoistoquímica, método do polímero, em 20 amostras de pacientes com CEC de cavidade oral que apresentaram metástase para linfonodos cervicais e em 35 amostras de pacientes com CEC de cavidade oral sem metástase para linfonodos cervicais. Nossos resultados demonstraram que a densidade de células GB+ peritumoral foi significativamente maior no grupo de CEC não metastático quando comparado com o metastático (p=0,03). Além disso, os pacientes com alta expressão de GB peritumoral apresentaram um maior tempo de sobrevida do que aqueles com baixa expressão dessa protease (Kaplan Meier, Log Rank p=0,02). Evidenciamos, também, que os pacientes com alta densidade de células GB+ peritumoral apresentaram baixa porcentagem de células neoplásicas bcl2+ (proteína anti-apoptótica) (P=0.004) e alta densidade de células neoplásicas Bax+ (proteína pró-apoptótica) (p=0,031) quando comparado ao grupo de baixa densidade de células GB+ peritumoral. Em concordância com esses dados, os pacientes que apresentaram alta densidade de células GB+ peritumoral apresentaram alta expressão de Anexina V por células neoplásicas. Adicionalmente, a densidade de células GB+ peritumoral e intratumoral foi significativamente maior no grupo T1 e T2 (39,44±7,21 e 14,61±3,60, respectivamente) quando comparado a T3 e T4 (31,03±3,76 e 11,90±1,88, respectivamente), no entanto esses resultados não foram estatisticamente significativo (p>0,05). A associação entre a densidade de células GB+ e outras características do CEC de cavidade oral, como localização, proliferação tumoral e gradação tumoral não foi observada. Nossos achados sugerem que a alta expressão da GB no microambiente do CEC de cavidade oral pode ter um efeito benéfico contra células neoplásicas, contribuindo para apoptose dessas células, baixa metástase linfonodal e maior tempo sobrevida desses pacientesapplication/pdfhttp://repositorio.bc.ufg.br/TEDE/retrieve/3544/DISSERTACAO%20NADIA%20DO%20L%20COSTA.pdf.jpgporUniversidade Federal de GoiásMestrado em OdontologiaUFGBRCiência da SaúdeCâncer de bocacarcinoma espinocelular de bocagranzima Bapoptoseoral canceroral squamous cell carcinomagranzyme BapoptosisCNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA::CLINICA ODONTOLOGICAAvaliação da expressão da granzima b e sua relação com o prognóstico do carcinoma espinocelular de bocaEvaluation of the expression of granzyme b and its relationship with the prognosis of carcinoma of the mouthinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGORIGINALDISSERTACAO NADIA DO L COSTA.pdfapplication/pdf215211http://repositorio.bc.ufg.br/tede/bitstreams/799d8be8-2281-4cd9-9a93-45087ca932a6/download98b2cf88b4766dae4e25cfa06b0970d4MD51THUMBNAILDISSERTACAO NADIA DO L COSTA.pdf.jpgDISSERTACAO NADIA DO L COSTA.pdf.jpgGenerated Thumbnailimage/jpeg1943http://repositorio.bc.ufg.br/tede/bitstreams/42f47013-bb34-4506-a774-e7884adca2aa/downloadcc73c4c239a4c332d642ba1e7c7a9fb2MD52tde/13632014-07-30 03:06:22.291open.accessoai:repositorio.bc.ufg.br:tde/1363http://repositorio.bc.ufg.br/tedeRepositório InstitucionalPUBhttps://repositorio.bc.ufg.br/tedeserver/oai/requestgrt.bc@ufg.bropendoar:oai:repositorio.bc.ufg.br:tede/12342014-07-30T06:06:22Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)false
dc.title.por.fl_str_mv Avaliação da expressão da granzima b e sua relação com o prognóstico do carcinoma espinocelular de boca
dc.title.alternative.eng.fl_str_mv Evaluation of the expression of granzyme b and its relationship with the prognosis of carcinoma of the mouth
title Avaliação da expressão da granzima b e sua relação com o prognóstico do carcinoma espinocelular de boca
spellingShingle Avaliação da expressão da granzima b e sua relação com o prognóstico do carcinoma espinocelular de boca
COSTA, Nádia do Lago
Câncer de boca
carcinoma espinocelular de boca
granzima B
apoptose
oral cancer
oral squamous cell carcinoma
granzyme B
apoptosis
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA::CLINICA ODONTOLOGICA
title_short Avaliação da expressão da granzima b e sua relação com o prognóstico do carcinoma espinocelular de boca
title_full Avaliação da expressão da granzima b e sua relação com o prognóstico do carcinoma espinocelular de boca
title_fullStr Avaliação da expressão da granzima b e sua relação com o prognóstico do carcinoma espinocelular de boca
title_full_unstemmed Avaliação da expressão da granzima b e sua relação com o prognóstico do carcinoma espinocelular de boca
title_sort Avaliação da expressão da granzima b e sua relação com o prognóstico do carcinoma espinocelular de boca
author COSTA, Nádia do Lago
author_facet COSTA, Nádia do Lago
author_role author
dc.contributor.advisor1.fl_str_mv BATISTA, Aline Carvalho
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0199082642322002
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/9120865567187887
dc.contributor.author.fl_str_mv COSTA, Nádia do Lago
contributor_str_mv BATISTA, Aline Carvalho
dc.subject.por.fl_str_mv Câncer de boca
carcinoma espinocelular de boca
granzima B
apoptose
topic Câncer de boca
carcinoma espinocelular de boca
granzima B
apoptose
oral cancer
oral squamous cell carcinoma
granzyme B
apoptosis
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA::CLINICA ODONTOLOGICA
dc.subject.eng.fl_str_mv oral cancer
oral squamous cell carcinoma
granzyme B
apoptosis
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA::CLINICA ODONTOLOGICA
description The cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are more effective in fighting cancer because these cells recognize tumor cells and release cytotoxic granules rich in perforin and granzyme B (GB). The perforin form pores in tumor cells allowing the influx of GB. When inside the cell, the GB promotes tumor cell death through apoptosis. In this context, high expression of GB into the microenvironment of different types of cancers has been considered a key event for effective antitumor immunity. Therefore, the objective of this study was to identify and quantify GB+ cells, peri- and intratumoral, and its relationship with clinical prognostic parameters (size of the primary lesion, location, metastasis and survival) and microscopic (microscopic grading and cell proliferation index and apoptosis of neoplastic cells) of squamous cell carcinoma (SCC) of the oral cavity. GB+ cells were identified by the technique of immunohistochemistry, a method of polymer, in 20 samples from patients with SCC of the oral cavity that had metastasized to cervical lymph nodes and in 35 samples from patients with SCC of the oral cavity without metastasis to cervical lymph nodes. Our results showed that the density of peritumoral GB+ cells was significantly higher in the non-metastatic SCC when compared with metastatic group (p=0.03). In addition, patients with high expression of peritumoral GB had a longer survival than those with low expression of this protease (Kaplan Meier, Log Rank p=0.02). We showed also that patients with high density of peritumoral GB+ cells showed a low percentage of neoplastic cells bcl2+ (antiapoptotic protein) (P=0.004) and high density of neoplastic cells Bax+ (apoptotic protein) (p=0.031) when compared to the group of low density of peritumoral GB+ cells. In agreement with these data, patients who had a high density of peritumoral GB+ cells showed high expression of Annexin V by neoplastic cells. Additionally, the density of GB+ cells intratumoral and peritumoral was significantly higher in the T1 and T2 (39.44±7.21 and 14.61±3.60, respectively) when compared to T3 and T4 (31.03±3.76 and 11.90±1.88, respectively), however these results were not statistically significant (p>0.05). The association between the density of cells GB+ and other characteristics of SCC of the oral cavity, such as location, tumor proliferation and tumor grading was not observed. Our findings suggest that the increased of expression of GB in tumor microenvironment of SCC of the oral cavity may have beneficial effect against neoplastics cells, contributing to apoptosis of these cells, lower lymph node involvement and increased survival time of patients.
publishDate 2010
dc.date.issued.fl_str_mv 2010-02-26
dc.date.available.fl_str_mv 2011-01-06
dc.date.accessioned.fl_str_mv 2014-07-29T15:21:56Z
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dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.citation.fl_str_mv COSTA, Nádia do Lago. Evaluation of the expression of granzyme b and its relationship with the prognosis of carcinoma of the mouth. 2010. 45 f. Dissertação (Mestrado em Ciência da Saúde) - Universidade Federal de Goiás, Goiânia, 2010.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tde/1363
identifier_str_mv COSTA, Nádia do Lago. Evaluation of the expression of granzyme b and its relationship with the prognosis of carcinoma of the mouth. 2010. 45 f. Dissertação (Mestrado em Ciência da Saúde) - Universidade Federal de Goiás, Goiânia, 2010.
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dc.publisher.department.fl_str_mv Ciência da Saúde
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