AvaliaÃÃo experimental da atividade antitumoral da vacina peptÃdica anticÃncer (vacina HasumiÂ)

Detalhes bibliográficos
Autor(a) principal: MÃrcio Roberto Pinho Pereira
Data de Publicação: 2003
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=294
Resumo: The Hasumi vaccine is based on peptides of plasmatic membrane of tumor cells and a extract of bovine spleen associated with immunostimulants substances. The aim of the present work was to evaluate the possible anticancer effect of the Hasumi vaccine and its mechanism of action in animals inoculated with experimental tumors. For the evaluation of the in vivo antitumoral activity, two groups of female Wistar rats were subcutaneously inoculated with 1.0 X 106 cells of the Walker 256 carcinossarcoma in the armpit area. The groups were subcutaneously vaccinated immediately with 500 ÂL of Hasumi vaccine (250 ÂL of peptides) or 500 ÂL of saline, and then, they received boosters of these doses every other day until their death. It was analyzed their survival function and the volume of tumor growth during the treatment period. The blood of these animals was taken for cell count. Other two groups of rats were also inoculated with 1.0 X 106 cells of the Walker 256 carcinossarcoma but they suffered surgical excision of the tumor 5 days after inoculation. After surgery, they received the same treatment of the above mentioned groups. In another set of experiments, four groups of mice C57BL/6 were inoculated with 1.0 X 106 melanoma B/16 cells maintained in culture. Three groups were subcutaneously vaccinated with 1 ÂL, 10 ÂL, 100 ÂL of Hasumi vaccine (0.006 g, 0.06 g, and 0.6 g of peptides) diluted in 200 ÂL of saline solution, and the fourth group received only 200 ÂL of saline. The animals received reinforcements of those doses every 7 days until their death. During the treatment, it was measured the volume of the tumor and the survival time of the animals. Other four groups of mice C57BL/6 were also treated in the same way that the previous groups, however the vaccination were performed by intraperitoneal injection. For the evaluation of the immunogenicity of the Hasumi vaccine, five groups of Swiss mice were immunized with 200 ÂL (100 Âg of peptides) of Hasumi vaccine. Egg-albumine (100 Âg) was used as positive control. The results showed that inoculated animals treated with Hasumi vaccine had their tumor partially inhibited. The total blood count revealed the Hasumi vaccine reverted the leukocytes rising observed in control group, suggesting an anti-inflammatory activity of the vaccine. The animals that suffered surgical retreat of the tumor plus vaccination also presented an inhibition of the tumor growth, and an animal was completely cured. The Hasumi vaccine was also active in mice inoculated with melanoma, and the vaccine seemed to be more efficient when injected intraperitoneally. The presence of antibodies IgG1 was verified by the method of PCA, indicating an immune answer of the Th2 type that is favorable to the anti-inflammatory activity, but it was not possible to detect antipeptides antibodies using ELISA assay. Our results suggest that Hasumi vaccine, as the most alike against cancer vaccines, shows an antitumor in vivo activity with some efficiency, suiting an induction of an immune response of Th2 type.
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spelling info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisAvaliaÃÃo experimental da atividade antitumoral da vacina peptÃdica anticÃncer (vacina HasumiÂ)Experimental approach of the antitumoral activity of a peptide anticancer vaccine (Hasumi VaccineÂ) 2003-04-20Manoel Odorico de Moraes Filho04854543353http://lattes.cnpq.br/0701679734111287ClÃudia do à Pessoa52089118415http://lattes.cnpq.br/1305553577433058Maria da Guia Silva Lima00201413353http://lattes.cnpq.br/090218447270636962961993334http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4769112A4MÃrcio Roberto Pinho PereiraUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em FarmacologiaUFCBRDrug Screening Assays, AntitumorEnsaios de SeleÃÃo de Medicamentos AntitumoraisFARMACOLOGIAThe Hasumi vaccine is based on peptides of plasmatic membrane of tumor cells and a extract of bovine spleen associated with immunostimulants substances. The aim of the present work was to evaluate the possible anticancer effect of the Hasumi vaccine and its mechanism of action in animals inoculated with experimental tumors. For the evaluation of the in vivo antitumoral activity, two groups of female Wistar rats were subcutaneously inoculated with 1.0 X 106 cells of the Walker 256 carcinossarcoma in the armpit area. The groups were subcutaneously vaccinated immediately with 500 ÂL of Hasumi vaccine (250 ÂL of peptides) or 500 ÂL of saline, and then, they received boosters of these doses every other day until their death. It was analyzed their survival function and the volume of tumor growth during the treatment period. The blood of these animals was taken for cell count. Other two groups of rats were also inoculated with 1.0 X 106 cells of the Walker 256 carcinossarcoma but they suffered surgical excision of the tumor 5 days after inoculation. After surgery, they received the same treatment of the above mentioned groups. In another set of experiments, four groups of mice C57BL/6 were inoculated with 1.0 X 106 melanoma B/16 cells maintained in culture. Three groups were subcutaneously vaccinated with 1 ÂL, 10 ÂL, 100 ÂL of Hasumi vaccine (0.006 g, 0.06 g, and 0.6 g of peptides) diluted in 200 ÂL of saline solution, and the fourth group received only 200 ÂL of saline. The animals received reinforcements of those doses every 7 days until their death. During the treatment, it was measured the volume of the tumor and the survival time of the animals. Other four groups of mice C57BL/6 were also treated in the same way that the previous groups, however the vaccination were performed by intraperitoneal injection. For the evaluation of the immunogenicity of the Hasumi vaccine, five groups of Swiss mice were immunized with 200 ÂL (100 Âg of peptides) of Hasumi vaccine. Egg-albumine (100 Âg) was used as positive control. The results showed that inoculated animals treated with Hasumi vaccine had their tumor partially inhibited. The total blood count revealed the Hasumi vaccine reverted the leukocytes rising observed in control group, suggesting an anti-inflammatory activity of the vaccine. The animals that suffered surgical retreat of the tumor plus vaccination also presented an inhibition of the tumor growth, and an animal was completely cured. The Hasumi vaccine was also active in mice inoculated with melanoma, and the vaccine seemed to be more efficient when injected intraperitoneally. The presence of antibodies IgG1 was verified by the method of PCA, indicating an immune answer of the Th2 type that is favorable to the anti-inflammatory activity, but it was not possible to detect antipeptides antibodies using ELISA assay. Our results suggest that Hasumi vaccine, as the most alike against cancer vaccines, shows an antitumor in vivo activity with some efficiency, suiting an induction of an immune response of Th2 type.A vacina Hasumi à formada de peptÃdeos localizados na membrana plasmÃtica de cÃlulas tumorais e um extrato de baÃo bovino associado a substÃncias imunoestimulantes. O objetivo do presente trabalho foi avaliar o possÃvel efeito anticÃncer da vacina Hasumi, e seu possÃvel mecanismo de aÃÃo, em animais inoculados com tumores experimentais. Para a avaliaÃÃo da atividade antitumoral in vivo foram utilizados dois grupos de ratos Wistar fÃmeas inoculados com 1,0 X 106 cÃlulas do carcinossarcoma de Walker 256 via subcutÃnea na regiÃo da axila. Os animais dos grupos controle e tratado foram imediatamente vacinados com 500 ÂL de vacina Hasumi (3 Âg de peptÃdeos) e 500 ÂL de salina, respectivamente, pela via subcutÃnea e receberam reforÃos dessas doses em dias alternados atà sua morte. Os parÃmetros avaliados foram a sobrevida e o crescimento tumoral durante o perÃodo de tratamento. Amostras de sangue foram coletadas dos animais controles e tratados para a obtenÃÃo do hemograma. Outros dois grupos de ratos tambÃm foram inoculados com 1,0 X 106 cÃlulas do carcinossarcoma de Walker 256 mas sofreram excisÃo cirÃrgica do tumor 5 dias apÃs a sua inoculaÃÃo. ApÃs a cirurgia, receberam o mesmo tratamento dos outros dois grupos acima citados. Em um outro experimento, quatro grupos de camundongos C57BL/6 foram inoculados com 1,0 X 106 cÃlulas de melanoma B/16 mantido em cultura. TrÃs grupos foram imediatamente vacinados com 1 ÂL, 10 ÂL, 100 ÂL de vacina Hasumi (0,006 Âg, 0,06 Âg, e 0,6 Âg de peptÃdeos) diluÃdos em 200 ÂL de soluÃÃo salina, e o quarto grupo recebeu 200 ÂL de salina pela via subcutÃnea. Todos os camundongos receberam reforÃos dessas doses a cada 7 dias atà a sua morte. Foram avaliados o crescimento tumoral e a sobrevida do animal. Outros quatro grupos de camundongos C57BL/6 tambÃm foram tratados da mesma forma que os grupos anteriores, a nÃo ser pela vacinaÃÃo intraperitoneal. Para a avaliaÃÃo da imunogenicidade da vacina Hasumi, cinco grupos de camundongos Swiss foram imunizados pela via subcutÃnea com 200 ÂL (2,4 Âg de peptÃdeos) de vacina Hasumi para identificaÃÃo de anticorpos anti-peptÃdeos. Como controle positivo, outro grupo de camundongos foi imunizado com 100 Âg de Ovalbumina. Os ratos inoculados com carcinosarcoma de Walker 256 vacinados tiveram seu tumor parcialmente inibido. O hemograma revelou a ausÃncia de aumento da quantidade de leucÃcitos 10 dias apÃs a inoculaÃÃo do tumor nos animais imunizados, sugerindo uma atividade antiinflamatÃria da vacina. Os ratos que sofreram retirada cirÃrgica do tumor de Walker 256 e foram vacinados tambÃm sofreram inibiÃÃo do crescimento do tumor, sendo que um animal ficou completamente curado. Os camundongos inoculados com o melanoma e vacinados pela via intraperitoneal tiveram seu cresimento tumoral inibido de forma significativamente superior quando comparados aos animais vacinados pela via subcutÃnea em todas as doses testadas. Foi constatado a presenÃa de anticorpos IgG1 anti-peptÃdeos pelo mÃtodo do PCA, indicando uma resposta imune do tipo Th2 que à favorÃvel à atividade antiinflamatÃria, mas nÃo foi possÃvel detectar anticorpos anti-peptÃdeos pelo mÃtodo de ELISA. Nossos resultados sugerem que a vacina Hasumi, assim como a maioria das vacinas anticÃncer em estudo, apresenta uma atividade antitumoral in vivo com eficiÃncia diferente para cada animal, favorecendo a induÃÃo de uma resposta imune do tipo Th2.nÃo hÃhttp://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=294application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:13:21Zmail@mail.com -
dc.title.pt.fl_str_mv AvaliaÃÃo experimental da atividade antitumoral da vacina peptÃdica anticÃncer (vacina HasumiÂ)
dc.title.alternative..fl_str_mv Experimental approach of the antitumoral activity of a peptide anticancer vaccine (Hasumi VaccineÂ)
title AvaliaÃÃo experimental da atividade antitumoral da vacina peptÃdica anticÃncer (vacina HasumiÂ)
spellingShingle AvaliaÃÃo experimental da atividade antitumoral da vacina peptÃdica anticÃncer (vacina HasumiÂ)
MÃrcio Roberto Pinho Pereira
Ensaios de SeleÃÃo de Medicamentos Antitumorais
FARMACOLOGIA
title_short AvaliaÃÃo experimental da atividade antitumoral da vacina peptÃdica anticÃncer (vacina HasumiÂ)
title_full AvaliaÃÃo experimental da atividade antitumoral da vacina peptÃdica anticÃncer (vacina HasumiÂ)
title_fullStr AvaliaÃÃo experimental da atividade antitumoral da vacina peptÃdica anticÃncer (vacina HasumiÂ)
title_full_unstemmed AvaliaÃÃo experimental da atividade antitumoral da vacina peptÃdica anticÃncer (vacina HasumiÂ)
title_sort AvaliaÃÃo experimental da atividade antitumoral da vacina peptÃdica anticÃncer (vacina HasumiÂ)
author MÃrcio Roberto Pinho Pereira
author_facet MÃrcio Roberto Pinho Pereira
author_role author
dc.contributor.advisor1.fl_str_mv Manoel Odorico de Moraes Filho
dc.contributor.advisor1ID.fl_str_mv 04854543353
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0701679734111287
dc.contributor.referee1.fl_str_mv ClÃudia do à Pessoa
dc.contributor.referee1ID.fl_str_mv 52089118415
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/1305553577433058
dc.contributor.referee2.fl_str_mv Maria da Guia Silva Lima
dc.contributor.referee2ID.fl_str_mv 00201413353
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/0902184472706369
dc.contributor.authorID.fl_str_mv 62961993334
dc.contributor.authorLattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4769112A4
dc.contributor.author.fl_str_mv MÃrcio Roberto Pinho Pereira
contributor_str_mv Manoel Odorico de Moraes Filho
ClÃudia do à Pessoa
Maria da Guia Silva Lima
dc.subject.por.fl_str_mv Ensaios de SeleÃÃo de Medicamentos Antitumorais
topic Ensaios de SeleÃÃo de Medicamentos Antitumorais
FARMACOLOGIA
dc.subject.cnpq.fl_str_mv FARMACOLOGIA
dc.description.sponsorship.fl_txt_mv nÃo hÃ
dc.description.abstract..fl_txt_mv The Hasumi vaccine is based on peptides of plasmatic membrane of tumor cells and a extract of bovine spleen associated with immunostimulants substances. The aim of the present work was to evaluate the possible anticancer effect of the Hasumi vaccine and its mechanism of action in animals inoculated with experimental tumors. For the evaluation of the in vivo antitumoral activity, two groups of female Wistar rats were subcutaneously inoculated with 1.0 X 106 cells of the Walker 256 carcinossarcoma in the armpit area. The groups were subcutaneously vaccinated immediately with 500 ÂL of Hasumi vaccine (250 ÂL of peptides) or 500 ÂL of saline, and then, they received boosters of these doses every other day until their death. It was analyzed their survival function and the volume of tumor growth during the treatment period. The blood of these animals was taken for cell count. Other two groups of rats were also inoculated with 1.0 X 106 cells of the Walker 256 carcinossarcoma but they suffered surgical excision of the tumor 5 days after inoculation. After surgery, they received the same treatment of the above mentioned groups. In another set of experiments, four groups of mice C57BL/6 were inoculated with 1.0 X 106 melanoma B/16 cells maintained in culture. Three groups were subcutaneously vaccinated with 1 ÂL, 10 ÂL, 100 ÂL of Hasumi vaccine (0.006 g, 0.06 g, and 0.6 g of peptides) diluted in 200 ÂL of saline solution, and the fourth group received only 200 ÂL of saline. The animals received reinforcements of those doses every 7 days until their death. During the treatment, it was measured the volume of the tumor and the survival time of the animals. Other four groups of mice C57BL/6 were also treated in the same way that the previous groups, however the vaccination were performed by intraperitoneal injection. For the evaluation of the immunogenicity of the Hasumi vaccine, five groups of Swiss mice were immunized with 200 ÂL (100 Âg of peptides) of Hasumi vaccine. Egg-albumine (100 Âg) was used as positive control. The results showed that inoculated animals treated with Hasumi vaccine had their tumor partially inhibited. The total blood count revealed the Hasumi vaccine reverted the leukocytes rising observed in control group, suggesting an anti-inflammatory activity of the vaccine. The animals that suffered surgical retreat of the tumor plus vaccination also presented an inhibition of the tumor growth, and an animal was completely cured. The Hasumi vaccine was also active in mice inoculated with melanoma, and the vaccine seemed to be more efficient when injected intraperitoneally. The presence of antibodies IgG1 was verified by the method of PCA, indicating an immune answer of the Th2 type that is favorable to the anti-inflammatory activity, but it was not possible to detect antipeptides antibodies using ELISA assay. Our results suggest that Hasumi vaccine, as the most alike against cancer vaccines, shows an antitumor in vivo activity with some efficiency, suiting an induction of an immune response of Th2 type.
dc.description.abstract.por.fl_txt_mv A vacina Hasumi à formada de peptÃdeos localizados na membrana plasmÃtica de cÃlulas tumorais e um extrato de baÃo bovino associado a substÃncias imunoestimulantes. O objetivo do presente trabalho foi avaliar o possÃvel efeito anticÃncer da vacina Hasumi, e seu possÃvel mecanismo de aÃÃo, em animais inoculados com tumores experimentais. Para a avaliaÃÃo da atividade antitumoral in vivo foram utilizados dois grupos de ratos Wistar fÃmeas inoculados com 1,0 X 106 cÃlulas do carcinossarcoma de Walker 256 via subcutÃnea na regiÃo da axila. Os animais dos grupos controle e tratado foram imediatamente vacinados com 500 ÂL de vacina Hasumi (3 Âg de peptÃdeos) e 500 ÂL de salina, respectivamente, pela via subcutÃnea e receberam reforÃos dessas doses em dias alternados atà sua morte. Os parÃmetros avaliados foram a sobrevida e o crescimento tumoral durante o perÃodo de tratamento. Amostras de sangue foram coletadas dos animais controles e tratados para a obtenÃÃo do hemograma. Outros dois grupos de ratos tambÃm foram inoculados com 1,0 X 106 cÃlulas do carcinossarcoma de Walker 256 mas sofreram excisÃo cirÃrgica do tumor 5 dias apÃs a sua inoculaÃÃo. ApÃs a cirurgia, receberam o mesmo tratamento dos outros dois grupos acima citados. Em um outro experimento, quatro grupos de camundongos C57BL/6 foram inoculados com 1,0 X 106 cÃlulas de melanoma B/16 mantido em cultura. TrÃs grupos foram imediatamente vacinados com 1 ÂL, 10 ÂL, 100 ÂL de vacina Hasumi (0,006 Âg, 0,06 Âg, e 0,6 Âg de peptÃdeos) diluÃdos em 200 ÂL de soluÃÃo salina, e o quarto grupo recebeu 200 ÂL de salina pela via subcutÃnea. Todos os camundongos receberam reforÃos dessas doses a cada 7 dias atà a sua morte. Foram avaliados o crescimento tumoral e a sobrevida do animal. Outros quatro grupos de camundongos C57BL/6 tambÃm foram tratados da mesma forma que os grupos anteriores, a nÃo ser pela vacinaÃÃo intraperitoneal. Para a avaliaÃÃo da imunogenicidade da vacina Hasumi, cinco grupos de camundongos Swiss foram imunizados pela via subcutÃnea com 200 ÂL (2,4 Âg de peptÃdeos) de vacina Hasumi para identificaÃÃo de anticorpos anti-peptÃdeos. Como controle positivo, outro grupo de camundongos foi imunizado com 100 Âg de Ovalbumina. Os ratos inoculados com carcinosarcoma de Walker 256 vacinados tiveram seu tumor parcialmente inibido. O hemograma revelou a ausÃncia de aumento da quantidade de leucÃcitos 10 dias apÃs a inoculaÃÃo do tumor nos animais imunizados, sugerindo uma atividade antiinflamatÃria da vacina. Os ratos que sofreram retirada cirÃrgica do tumor de Walker 256 e foram vacinados tambÃm sofreram inibiÃÃo do crescimento do tumor, sendo que um animal ficou completamente curado. Os camundongos inoculados com o melanoma e vacinados pela via intraperitoneal tiveram seu cresimento tumoral inibido de forma significativamente superior quando comparados aos animais vacinados pela via subcutÃnea em todas as doses testadas. Foi constatado a presenÃa de anticorpos IgG1 anti-peptÃdeos pelo mÃtodo do PCA, indicando uma resposta imune do tipo Th2 que à favorÃvel à atividade antiinflamatÃria, mas nÃo foi possÃvel detectar anticorpos anti-peptÃdeos pelo mÃtodo de ELISA. Nossos resultados sugerem que a vacina Hasumi, assim como a maioria das vacinas anticÃncer em estudo, apresenta uma atividade antitumoral in vivo com eficiÃncia diferente para cada animal, favorecendo a induÃÃo de uma resposta imune do tipo Th2.
description The Hasumi vaccine is based on peptides of plasmatic membrane of tumor cells and a extract of bovine spleen associated with immunostimulants substances. The aim of the present work was to evaluate the possible anticancer effect of the Hasumi vaccine and its mechanism of action in animals inoculated with experimental tumors. For the evaluation of the in vivo antitumoral activity, two groups of female Wistar rats were subcutaneously inoculated with 1.0 X 106 cells of the Walker 256 carcinossarcoma in the armpit area. The groups were subcutaneously vaccinated immediately with 500 ÂL of Hasumi vaccine (250 ÂL of peptides) or 500 ÂL of saline, and then, they received boosters of these doses every other day until their death. It was analyzed their survival function and the volume of tumor growth during the treatment period. The blood of these animals was taken for cell count. Other two groups of rats were also inoculated with 1.0 X 106 cells of the Walker 256 carcinossarcoma but they suffered surgical excision of the tumor 5 days after inoculation. After surgery, they received the same treatment of the above mentioned groups. In another set of experiments, four groups of mice C57BL/6 were inoculated with 1.0 X 106 melanoma B/16 cells maintained in culture. Three groups were subcutaneously vaccinated with 1 ÂL, 10 ÂL, 100 ÂL of Hasumi vaccine (0.006 g, 0.06 g, and 0.6 g of peptides) diluted in 200 ÂL of saline solution, and the fourth group received only 200 ÂL of saline. The animals received reinforcements of those doses every 7 days until their death. During the treatment, it was measured the volume of the tumor and the survival time of the animals. Other four groups of mice C57BL/6 were also treated in the same way that the previous groups, however the vaccination were performed by intraperitoneal injection. For the evaluation of the immunogenicity of the Hasumi vaccine, five groups of Swiss mice were immunized with 200 ÂL (100 Âg of peptides) of Hasumi vaccine. Egg-albumine (100 Âg) was used as positive control. The results showed that inoculated animals treated with Hasumi vaccine had their tumor partially inhibited. The total blood count revealed the Hasumi vaccine reverted the leukocytes rising observed in control group, suggesting an anti-inflammatory activity of the vaccine. The animals that suffered surgical retreat of the tumor plus vaccination also presented an inhibition of the tumor growth, and an animal was completely cured. The Hasumi vaccine was also active in mice inoculated with melanoma, and the vaccine seemed to be more efficient when injected intraperitoneally. The presence of antibodies IgG1 was verified by the method of PCA, indicating an immune answer of the Th2 type that is favorable to the anti-inflammatory activity, but it was not possible to detect antipeptides antibodies using ELISA assay. Our results suggest that Hasumi vaccine, as the most alike against cancer vaccines, shows an antitumor in vivo activity with some efficiency, suiting an induction of an immune response of Th2 type.
publishDate 2003
dc.date.issued.fl_str_mv 2003-04-20
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.publisher.none.fl_str_mv Universidade Federal do CearÃ
dc.publisher.program.fl_str_mv Programa de PÃs-GraduaÃÃo em Farmacologia
dc.publisher.initials.fl_str_mv UFC
dc.publisher.country.fl_str_mv BR
publisher.none.fl_str_mv Universidade Federal do CearÃ
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFC
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