Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UERJ |
Texto Completo: | http://www.bdtd.uerj.br/handle/1/16153 |
Resumo: | The World Health Organization (WHO) estimates for 2030, 27 million incident cases of cancer. In Brazil, according to the National Cancer Institute, there were estimated 518,510 new cases of cancer for the years 2012 and 2013. From this estimation, 52,680 will correspond to breast cancer (BC), with an estimated risk of 52 new cases per 100,000 women. BC is one of the most common cancers worldwide. Today it is known that the treatment of the BC may lead to the emergence of different late adverse effects, including osteoporosis. One of the main causes of osteoporosis is the early menopause, which occurs with decreasing the serum estrogen concentration. This study aimed to evaluate the effects on bone matrix induced by chemotherapy , simulating a treatment for BC in Wistar rats .Wistar rats, approximately 3 months old, were divided into a control group and the group receiving polichemotherapy with docetaxel + cyclophosphamide (TC). Chemotherapy was administered in 4 cycles, with an interval of 1 week between them. The rats were euthanized 5 months after the end of treatment, so that the late effects could be evaluated. Several studies were performed: dosage of serum estradiol levels, histological tests by immunohistochemistry, micro X-ray fluorescence, micro-computed tomography and also transmission and scanning electron microscopy.Analyzing the results together, it is suggested that the initial step in the development of osteoporosis caused by multidrug TC is the reduction in the ovarian function. This event leads to decreased serum concentration of estrogen, which causes uterine atrophy. Concomitant to these facts, the TC causes a reduction in the concentration of zinc in the bone tissue. These results associated cause an imbalance in the osteoblast/osteoclast ratio in the bone tissue. The reduction in estrogen leads to decreased apoptosis of osteoclasts, while the reduction of zinc inhibits osteoblast function. This imbalance affects the bone turnover in order to increase bone resorption. Thus, the percentage of bone is reduced, and the trabeculae become thinner and spaced. The endpoint of this process is osteoporosis.The administration of docetaxel and cyclophosphamide together leads to decreased bone mass in the trabecular, thinning and increasing the space between them. These observations suggest that the rats treated with TC developed osteoporosis. We conclude that both the estrogen and the zinc play a fundamental role in the development of this disease after chemotherapy with TC. |
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Almeida, Carlos Eduardo Veloso dehttp://lattes.cnpq.br/6836623990976293Mencalha, André Luizhttp://lattes.cnpq.br/2640957642674082Machado, Samara Cristina Ferreirahttp://lattes.cnpq.br/5969643866391869Pinheiro, Nadja Limahttp://lattes.cnpq.br/2704840396057478http://lattes.cnpq.br/4879823436707004Andrade, Cherley Borba Vieira de2021-04-26T01:11:07Z2014-06-022013-12-16ANDRADE, Cherley Borba Vieira de. Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea. 2013. 69 f. Tese (Doutorado em Biociências) - Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013.http://www.bdtd.uerj.br/handle/1/16153The World Health Organization (WHO) estimates for 2030, 27 million incident cases of cancer. In Brazil, according to the National Cancer Institute, there were estimated 518,510 new cases of cancer for the years 2012 and 2013. From this estimation, 52,680 will correspond to breast cancer (BC), with an estimated risk of 52 new cases per 100,000 women. BC is one of the most common cancers worldwide. Today it is known that the treatment of the BC may lead to the emergence of different late adverse effects, including osteoporosis. One of the main causes of osteoporosis is the early menopause, which occurs with decreasing the serum estrogen concentration. This study aimed to evaluate the effects on bone matrix induced by chemotherapy , simulating a treatment for BC in Wistar rats .Wistar rats, approximately 3 months old, were divided into a control group and the group receiving polichemotherapy with docetaxel + cyclophosphamide (TC). Chemotherapy was administered in 4 cycles, with an interval of 1 week between them. The rats were euthanized 5 months after the end of treatment, so that the late effects could be evaluated. Several studies were performed: dosage of serum estradiol levels, histological tests by immunohistochemistry, micro X-ray fluorescence, micro-computed tomography and also transmission and scanning electron microscopy.Analyzing the results together, it is suggested that the initial step in the development of osteoporosis caused by multidrug TC is the reduction in the ovarian function. This event leads to decreased serum concentration of estrogen, which causes uterine atrophy. Concomitant to these facts, the TC causes a reduction in the concentration of zinc in the bone tissue. These results associated cause an imbalance in the osteoblast/osteoclast ratio in the bone tissue. The reduction in estrogen leads to decreased apoptosis of osteoclasts, while the reduction of zinc inhibits osteoblast function. This imbalance affects the bone turnover in order to increase bone resorption. Thus, the percentage of bone is reduced, and the trabeculae become thinner and spaced. The endpoint of this process is osteoporosis.The administration of docetaxel and cyclophosphamide together leads to decreased bone mass in the trabecular, thinning and increasing the space between them. These observations suggest that the rats treated with TC developed osteoporosis. We conclude that both the estrogen and the zinc play a fundamental role in the development of this disease after chemotherapy with TC.A Organização Mundial de Saúde (OMS) estima para 2030, 27 milhões de casos incidentes de câncer. No Brasil, segundo o Instituto Nacional do Câncer, foram estimados 518.510 casos novos de câncer para os anos de 2012 e 2013. Dessa estimativa, 52.680 correspondem ao câncer de mama (CM), com um risco estimado de 52 novos casos a cada 100.000 mulheres. O câncer de mama é um dos tipos de câncer mais comuns no mundo todo. Hoje se sabe que o tratamento para o CM pode levar ao surgimento de diferentes efeitos adversos tardios, entre eles a osteoporose. Uma das principais causas de surgimento da osteoporose é a menopausa precoce, que ocorre através da diminuição da concentração de estrogênio sérico. Este trabalho teve como objetivo avaliar os efeitos na matriz óssea induzidos pela quimioterapia, simulando um tratamento para o CM, em ratas Wistar.Ratas Wistar, com aproximadamente 3 meses de idade, foram divididas em: grupo controle e grupo que recebeu quimioterapia com poliquimioterápico docetaxel + ciclofosfamida (TC). A quimioterapia foi administrada em 4 ciclos, com intervalo de 1 semana entre eles. Os ratos foram submetidos à eutanásia 5 meses após o término do tratamento, para que os efeitos tardios pudessem ser avaliados. Vários estudos foram conduzidos: dosagem sorológica de estradiol, ensaios histológicos através de imunohistoquímica, micro-fluorescência de Raios-X, micro-tomografia computadorizada. Além de microscopia eletrônica de transmissão e varredura.Analisando os resultados obtidos em conjunto, sugere-se que a etapa inicial para o desenvolvimento da osteoporose, causada pelo poliquimioterápico TC, seja a diminuição da função ovariana. Este evento leva à diminuição da concentração de estrogênio sérico, o que causa a atrofia uterina. Concomitante a estes fatos, o TC causa redução na concentração de zinco no tecido ósseo. Estes resultados associados causam um desequilíbrio na relação osteoblastos/osteoclastos no osso. A redução do estrogênio leva à diminuição da apoptose de osteoclastos, enquanto que a redução do zinco inibe a função dos osteoblastos. Este desequilíbrio interfere no turnover do osso, de forma a aumentar a reabsorção óssea. Deste modo, o percentual de osso fica reduzido, as trabéculas tornam-se mais finas e espaçadas. O endpoint deste processo é a osteoporose.A administração dos poliquimioterápicos docetaxel e ciclofosfamida em conjunto leva a diminuição da massa óssea, a adelgaçamento das trabéculas e o aumento do espaço entre elas. Estas observações sugerem que realmente as ratas tratadas com TC apresentam osteoporose. Concluímos que tanto o estrogênio quanto o zinco têm papel fundamental no desenvolvimento desta patologia após quimioterapia com TC.Submitted by Boris INFORMAT (boris@uerj.br) on 2021-04-26T01:11:07Z No. of bitstreams: 1 Efeito do docetaxel e da ciclofosfamida nas alteracoes da ma.pdf: 2000640 bytes, checksum: 8826b9a8b90797d22df7ec24b9d1271d (MD5)Made available in DSpace on 2021-04-26T01:11:07Z (GMT). No. of bitstreams: 1 Efeito do docetaxel e da ciclofosfamida nas alteracoes da ma.pdf: 2000640 bytes, checksum: 8826b9a8b90797d22df7ec24b9d1271d (MD5) Previous issue date: 2013-12-16Comissão Nacional de Energia Nuclearapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em BiociênciasUERJBRCentro Biomédico::Instituto de Biologia Roberto Alcantara GomesBreast câncerEarly menopauseOsteoporosisDocetaxelCâncer de mamaMenopausa precoceOsteoporoseDocetaxelMamas - CâncerNeoplasias da mama - QuimioterapiaOsteoporoseAntineoplásicos - Uso terapêuticoCNPQ::CIENCIAS BIOLOGICAS::BIOFISICAEfeito do docetaxel e da ciclofosfamida nas alterações da matriz ósseaThe docetaxel and the cyclophosphamida effect at bone matrix alterationsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALTese - Cherley Borba Vieira de Andrade - 2013 - Completaapplication/pdf2000640http://www.bdtd.uerj.br/bitstream/1/16153/1/Tese+-+Cherley+Borba+Vieira+de+Andrade+-+2013+-+Completa8826b9a8b90797d22df7ec24b9d1271dMD511/161532024-02-26 11:24:58.914oai:www.bdtd.uerj.br:1/16153Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T14:24:58Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false |
dc.title.por.fl_str_mv |
Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea |
dc.title.alternative.eng.fl_str_mv |
The docetaxel and the cyclophosphamida effect at bone matrix alterations |
title |
Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea |
spellingShingle |
Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea Andrade, Cherley Borba Vieira de Breast câncer Early menopause Osteoporosis Docetaxel Câncer de mama Menopausa precoce Osteoporose Docetaxel Mamas - Câncer Neoplasias da mama - Quimioterapia Osteoporose Antineoplásicos - Uso terapêutico CNPQ::CIENCIAS BIOLOGICAS::BIOFISICA |
title_short |
Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea |
title_full |
Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea |
title_fullStr |
Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea |
title_full_unstemmed |
Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea |
title_sort |
Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea |
author |
Andrade, Cherley Borba Vieira de |
author_facet |
Andrade, Cherley Borba Vieira de |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Almeida, Carlos Eduardo Veloso de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6836623990976293 |
dc.contributor.referee1.fl_str_mv |
Mencalha, André Luiz |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/2640957642674082 |
dc.contributor.referee2.fl_str_mv |
Machado, Samara Cristina Ferreira |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/5969643866391869 |
dc.contributor.referee3.fl_str_mv |
Pinheiro, Nadja Lima |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/2704840396057478 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4879823436707004 |
dc.contributor.author.fl_str_mv |
Andrade, Cherley Borba Vieira de |
contributor_str_mv |
Almeida, Carlos Eduardo Veloso de Mencalha, André Luiz Machado, Samara Cristina Ferreira Pinheiro, Nadja Lima |
dc.subject.eng.fl_str_mv |
Breast câncer Early menopause Osteoporosis Docetaxel |
topic |
Breast câncer Early menopause Osteoporosis Docetaxel Câncer de mama Menopausa precoce Osteoporose Docetaxel Mamas - Câncer Neoplasias da mama - Quimioterapia Osteoporose Antineoplásicos - Uso terapêutico CNPQ::CIENCIAS BIOLOGICAS::BIOFISICA |
dc.subject.por.fl_str_mv |
Câncer de mama Menopausa precoce Osteoporose Docetaxel Mamas - Câncer Neoplasias da mama - Quimioterapia Osteoporose Antineoplásicos - Uso terapêutico |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOFISICA |
description |
The World Health Organization (WHO) estimates for 2030, 27 million incident cases of cancer. In Brazil, according to the National Cancer Institute, there were estimated 518,510 new cases of cancer for the years 2012 and 2013. From this estimation, 52,680 will correspond to breast cancer (BC), with an estimated risk of 52 new cases per 100,000 women. BC is one of the most common cancers worldwide. Today it is known that the treatment of the BC may lead to the emergence of different late adverse effects, including osteoporosis. One of the main causes of osteoporosis is the early menopause, which occurs with decreasing the serum estrogen concentration. This study aimed to evaluate the effects on bone matrix induced by chemotherapy , simulating a treatment for BC in Wistar rats .Wistar rats, approximately 3 months old, were divided into a control group and the group receiving polichemotherapy with docetaxel + cyclophosphamide (TC). Chemotherapy was administered in 4 cycles, with an interval of 1 week between them. The rats were euthanized 5 months after the end of treatment, so that the late effects could be evaluated. Several studies were performed: dosage of serum estradiol levels, histological tests by immunohistochemistry, micro X-ray fluorescence, micro-computed tomography and also transmission and scanning electron microscopy.Analyzing the results together, it is suggested that the initial step in the development of osteoporosis caused by multidrug TC is the reduction in the ovarian function. This event leads to decreased serum concentration of estrogen, which causes uterine atrophy. Concomitant to these facts, the TC causes a reduction in the concentration of zinc in the bone tissue. These results associated cause an imbalance in the osteoblast/osteoclast ratio in the bone tissue. The reduction in estrogen leads to decreased apoptosis of osteoclasts, while the reduction of zinc inhibits osteoblast function. This imbalance affects the bone turnover in order to increase bone resorption. Thus, the percentage of bone is reduced, and the trabeculae become thinner and spaced. The endpoint of this process is osteoporosis.The administration of docetaxel and cyclophosphamide together leads to decreased bone mass in the trabecular, thinning and increasing the space between them. These observations suggest that the rats treated with TC developed osteoporosis. We conclude that both the estrogen and the zinc play a fundamental role in the development of this disease after chemotherapy with TC. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-12-16 |
dc.date.available.fl_str_mv |
2014-06-02 |
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2021-04-26T01:11:07Z |
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ANDRADE, Cherley Borba Vieira de. Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea. 2013. 69 f. Tese (Doutorado em Biociências) - Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013. |
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http://www.bdtd.uerj.br/handle/1/16153 |
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ANDRADE, Cherley Borba Vieira de. Efeito do docetaxel e da ciclofosfamida nas alterações da matriz óssea. 2013. 69 f. Tese (Doutorado em Biociências) - Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013. |
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Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes |
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Universidade do Estado do Rio de Janeiro |
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