Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/10354 |
Resumo: | Despite recent advances in cancer prevention and treatment, bladder urothelial carcinoma continues to be one of the most common types of malignant neoplasms in the world, with a 20% mortality rate. The cells and molecules of the immune system are fundamental components of the tumor microenvironment. Probably the fact that the neoplastic cell shares antigens with normal cells, have high growth rate and suffer edition, contributes to its resistance to the antitumor immune response. Even with these obstacles, the immune response remains one of the best bets in the malignant neoplasms treatment. In the past, homeostatic cell death, which often occurs through apoptosis, was irrelevant to the antitumor immune response since it was unable to stimulate the immune system. However, in recent years, it has been observed that certain types of apoptosis were able to induce immune response against dead cell antigens, particularly when they were derived from malignant neoplasms. This type of phenomenon was called immunogenic cell death (ICD). Despite advances in the discovery of the mechanisms involved in cell death associated with various tumor lines, no work to date has evaluated its efficacy in the model of bladder cancer induced by chemotherapeutics commonly used in the treatment of this disease.Therefore, the aim of the present study was to evaluate the action of cisplatin, mitoxantrone, daunorubicin, doxorubicin and epirubicin on the viability of MB49 lineage cellsand to identify the best dose with apoptotic activity of cisplatin, mitoxantrone, daunorubicin and doxorubicin. The results showed that chemotherapeutics agents, in their pharmaceutical formulation, performed well against MB49 cells in vitro. Cisplatin and mitoxantrone proved to be efficient in producing apoptosis, but only in vivo tests could confirm their immunogenic effect on these cells. In addition, this work showed that the effects of viability may be quite divergent depending on the dose and time evaluated and the need for a follow-up of viability after treatment withdrawal. In addition, this work showed that the effects of viability might be quite divergent depending on the dose and time evaluated and the need to observe viability after treatment withdrawal. It is concluded that the drug formulations of daunorubicin, epirubicin, doxorubicin and mitoxantrone produced varying degrees of apoptotic death in vitro, depending on exposure time and drug concentration. |
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Trevisoli, Pablo Gil MortolBorra, Ricardo Carneirohttp://lattes.cnpq.br/5655362515357840http://lattes.cnpq.br/254501332395432702107563-cf29-477a-99e2-d952063e48292018-08-13T18:31:32Z2018-08-13T18:31:32Z2018-03-29TREVISOLI, Pablo Gil Mortol. Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino. 2018. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10354.https://repositorio.ufscar.br/handle/ufscar/10354Despite recent advances in cancer prevention and treatment, bladder urothelial carcinoma continues to be one of the most common types of malignant neoplasms in the world, with a 20% mortality rate. The cells and molecules of the immune system are fundamental components of the tumor microenvironment. Probably the fact that the neoplastic cell shares antigens with normal cells, have high growth rate and suffer edition, contributes to its resistance to the antitumor immune response. Even with these obstacles, the immune response remains one of the best bets in the malignant neoplasms treatment. In the past, homeostatic cell death, which often occurs through apoptosis, was irrelevant to the antitumor immune response since it was unable to stimulate the immune system. However, in recent years, it has been observed that certain types of apoptosis were able to induce immune response against dead cell antigens, particularly when they were derived from malignant neoplasms. This type of phenomenon was called immunogenic cell death (ICD). Despite advances in the discovery of the mechanisms involved in cell death associated with various tumor lines, no work to date has evaluated its efficacy in the model of bladder cancer induced by chemotherapeutics commonly used in the treatment of this disease.Therefore, the aim of the present study was to evaluate the action of cisplatin, mitoxantrone, daunorubicin, doxorubicin and epirubicin on the viability of MB49 lineage cellsand to identify the best dose with apoptotic activity of cisplatin, mitoxantrone, daunorubicin and doxorubicin. The results showed that chemotherapeutics agents, in their pharmaceutical formulation, performed well against MB49 cells in vitro. Cisplatin and mitoxantrone proved to be efficient in producing apoptosis, but only in vivo tests could confirm their immunogenic effect on these cells. In addition, this work showed that the effects of viability may be quite divergent depending on the dose and time evaluated and the need for a follow-up of viability after treatment withdrawal. In addition, this work showed that the effects of viability might be quite divergent depending on the dose and time evaluated and the need to observe viability after treatment withdrawal. It is concluded that the drug formulations of daunorubicin, epirubicin, doxorubicin and mitoxantrone produced varying degrees of apoptotic death in vitro, depending on exposure time and drug concentration.Apesar dos recentes avanços nas áreas de prevenção e tratamento do câncer, o carcinoma urotelial de bexiga continua sendo um dos tipos mais comuns de neoplasias malignas no mundo, com índices de mortalidade de 20% dos casos. As células e moléculas do sistema imunológico são componentes fundamentais do microambiente tumoral. Provavelmente o fato de a célula neoplásica compartilhar antígenos com as células normais, de possuir alta taxa de crescimento e sofrer edição contribuem para a sua resistência em relação à resposta imunológica antitumoral. Mesmo com estes contratempos, a resposta imunológica continua sendo uma das melhores apostas no tratamento das neoplasias malignas. No passado, a morte celular homeostática, que muitas vezes ocorre por meio de apoptose, foi irrelevante para a resposta imune antitumoral uma vez que era incapaz de estimular o sistema imunológico. Porém, nos últimos anos, foi observado que certos tipos de apoptoses eram capazes de induzir resposta imune contra antígenos de células mortas, em particular quando elas eram derivadas de neoplasias malignas. Este tipo de fenômeno foi denominado de morte celular imunogênica (ICD). Apesar dos avanços na descoberta dos mecanismos envolvidos na morte celular associado às várias linhagens tumorais, nenhum trabalho até o presente momento avaliou sua eficácia em modelo de câncer de bexiga induzida pelos quimioterápicos comumente utilizados no tratamento dessa doença. Sendo assim, o presente trabalho procurou avaliar a ação dos quimioterápicos cisplatina, mitoxantrona, daunorrubicina, doxorrubicina e epirrubicina na viabilidade das células de linhagem MB49 e identificando a melhor dose com atividade apoptóticada cisplatina, mitoxantrona, daunorrubicina e doxorrubicina. Os resultados mostraram que os quimioterápicos em sua formulação farmacêutica apresentaram um bom desempenho contra as células MB49 in vitro e a cisplatina e a mitoxantrona mostraram-se eficientes em produzir apoptose, porém somente os testes in vivo poderão confirmar seu efeito imunogênico sobre essas células. Além disso, este trabalho mostrou que os efeitos da viabilidade podem ser bastante divergentes dependendo da dose e do tempo avaliados e a necessidade de um acompanhamento da viabilidade após a remoção dos tratamentos. Deste modo, conclui-se que as formulações medicamentosas da daunorrubicina, epirrubicina, doxorrubicina e da mitoxantrona produziram graus variados de morte apoptótica in vitro, dependente do tempo de exposição e da concentração dos medicamentos.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)porUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEvUFSCarCâncer de BexigaApoptoseCisplatinaMitoxantronaDaunorrubicinaDoxorrubicinaEpirrubicinaCIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULARCIENCIAS BIOLOGICAS::IMUNOLOGIACIENCIAS DA SAUDEComparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murinoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisOnline600600fc96fc18-cc22-487c-927f-5b0b6f04b3deinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALTrevisoli PGM 2018 v final .pdfTrevisoli PGM 2018 v final .pdfapplication/pdf1282184https://repositorio.ufscar.br/bitstream/ufscar/10354/1/Trevisoli%20PGM%202018%20v%20final%20.pdf8b7ef6c772f9646bb72b0bf5a82060f9MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81957https://repositorio.ufscar.br/bitstream/ufscar/10354/4/license.txtae0398b6f8b235e40ad82cba6c50031dMD54TEXTTrevisoli PGM 2018 v final .pdf.txtTrevisoli PGM 2018 v final .pdf.txtExtracted texttext/plain110819https://repositorio.ufscar.br/bitstream/ufscar/10354/5/Trevisoli%20PGM%202018%20v%20final%20.pdf.txt31000d6072c9ee267d2f87404dafffe0MD55THUMBNAILTrevisoli PGM 2018 v final .pdf.jpgTrevisoli PGM 2018 v final .pdf.jpgIM Thumbnailimage/jpeg6497https://repositorio.ufscar.br/bitstream/ufscar/10354/6/Trevisoli%20PGM%202018%20v%20final%20.pdf.jpge354d09e30586216bb18bf4ac4732552MD56ufscar/103542023-09-18 18:31:16.324oai:repositorio.ufscar.br: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Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:31:16Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino |
title |
Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino |
spellingShingle |
Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino Trevisoli, Pablo Gil Mortol Câncer de Bexiga Apoptose Cisplatina Mitoxantrona Daunorrubicina Doxorrubicina Epirrubicina CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR CIENCIAS BIOLOGICAS::IMUNOLOGIA CIENCIAS DA SAUDE |
title_short |
Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino |
title_full |
Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino |
title_fullStr |
Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino |
title_full_unstemmed |
Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino |
title_sort |
Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino |
author |
Trevisoli, Pablo Gil Mortol |
author_facet |
Trevisoli, Pablo Gil Mortol |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/2545013323954327 |
dc.contributor.author.fl_str_mv |
Trevisoli, Pablo Gil Mortol |
dc.contributor.advisor1.fl_str_mv |
Borra, Ricardo Carneiro |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5655362515357840 |
dc.contributor.authorID.fl_str_mv |
02107563-cf29-477a-99e2-d952063e4829 |
contributor_str_mv |
Borra, Ricardo Carneiro |
dc.subject.por.fl_str_mv |
Câncer de Bexiga Apoptose Cisplatina Mitoxantrona Daunorrubicina Doxorrubicina Epirrubicina |
topic |
Câncer de Bexiga Apoptose Cisplatina Mitoxantrona Daunorrubicina Doxorrubicina Epirrubicina CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR CIENCIAS BIOLOGICAS::IMUNOLOGIA CIENCIAS DA SAUDE |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR CIENCIAS BIOLOGICAS::IMUNOLOGIA CIENCIAS DA SAUDE |
description |
Despite recent advances in cancer prevention and treatment, bladder urothelial carcinoma continues to be one of the most common types of malignant neoplasms in the world, with a 20% mortality rate. The cells and molecules of the immune system are fundamental components of the tumor microenvironment. Probably the fact that the neoplastic cell shares antigens with normal cells, have high growth rate and suffer edition, contributes to its resistance to the antitumor immune response. Even with these obstacles, the immune response remains one of the best bets in the malignant neoplasms treatment. In the past, homeostatic cell death, which often occurs through apoptosis, was irrelevant to the antitumor immune response since it was unable to stimulate the immune system. However, in recent years, it has been observed that certain types of apoptosis were able to induce immune response against dead cell antigens, particularly when they were derived from malignant neoplasms. This type of phenomenon was called immunogenic cell death (ICD). Despite advances in the discovery of the mechanisms involved in cell death associated with various tumor lines, no work to date has evaluated its efficacy in the model of bladder cancer induced by chemotherapeutics commonly used in the treatment of this disease.Therefore, the aim of the present study was to evaluate the action of cisplatin, mitoxantrone, daunorubicin, doxorubicin and epirubicin on the viability of MB49 lineage cellsand to identify the best dose with apoptotic activity of cisplatin, mitoxantrone, daunorubicin and doxorubicin. The results showed that chemotherapeutics agents, in their pharmaceutical formulation, performed well against MB49 cells in vitro. Cisplatin and mitoxantrone proved to be efficient in producing apoptosis, but only in vivo tests could confirm their immunogenic effect on these cells. In addition, this work showed that the effects of viability may be quite divergent depending on the dose and time evaluated and the need for a follow-up of viability after treatment withdrawal. In addition, this work showed that the effects of viability might be quite divergent depending on the dose and time evaluated and the need to observe viability after treatment withdrawal. It is concluded that the drug formulations of daunorubicin, epirubicin, doxorubicin and mitoxantrone produced varying degrees of apoptotic death in vitro, depending on exposure time and drug concentration. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-08-13T18:31:32Z |
dc.date.available.fl_str_mv |
2018-08-13T18:31:32Z |
dc.date.issued.fl_str_mv |
2018-03-29 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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dc.identifier.citation.fl_str_mv |
TREVISOLI, Pablo Gil Mortol. Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino. 2018. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10354. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/10354 |
identifier_str_mv |
TREVISOLI, Pablo Gil Mortol. Comparação da capacidade de formulações medicamentosas de diferentes quimioterápicos em induzir morte celular em células da linhagem MB49 de tumor de bexiga murino. 2018. Dissertação (Mestrado em Genética Evolutiva e Biologia Molecular) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/10354. |
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https://repositorio.ufscar.br/handle/ufscar/10354 |
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openAccess |
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Universidade Federal de São Carlos Câmpus São Carlos |
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Programa de Pós-Graduação em Genética Evolutiva e Biologia Molecular - PPGGEv |
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UFSCar |
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Universidade Federal de São Carlos Câmpus São Carlos |
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