CARACTERIZAÇÃO DE METABÓLITOS E ATIVIDADE CITOTÓXICA DO EXTRATO DE Penicillium purpurogenum DE AMBIENTE MARINHO EM MODELO DE CÂNCER DE MAMA IN VITRO E IN VIVO.
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFMA |
Texto Completo: | https://tedebc.ufma.br/jspui/handle/tede/tede/3503 |
Resumo: | Microfungi are a promising yet unexplored source of new chemical substances with antitumor activity, which in this scenario represent an area with potential for development. To further elucidate the role of Penicillium purpurogenum extract, this study investigated the in vitro antitumor effect on breast tumor cells (MDA-MB-231 and MCF-7) and an in vivo murine Ehrlich tumor model. P. purpurogenum was fermented for 21 days, filtered, concentrated and lyophilized, giving rise to two extracts: ethyl acetate extract of the broth (FR1) and of the mycelial biomass (FR2). For the determination of the chemical composition of the extracts a chemical analysis was performed by direct infusion (ESI/MS). For the evaluation of the cytotoxicity, a MTT [(3-fluorouracil-2-yl) -2,5-diphenyl-tetrazolium bromide] assay was performed with cancer cell lines in the times of 24, 48 and 72 hours. In the in vivo experiment with Ehrlich's tumor, Swiss females were separated into seven groups (n = 10 / group). The intraperitoneal treatment was done daily with phosphate buffer solution in the negative control group (CTL-), with cyclophosphamide (25 mg/kg) in the positive control group (CTL+) and the fungus extract (FR1) at doses 4, 20 and 100 mg/kg in the experimental group. Half of the animals in each group were euthanized 15 days after tumor inoculation, and the other half was kept alive for survival follow-up. Tumor development was evaluated by the weight of the animals, volume and area of the inoculated paw and, after euthanasia, the tumor was weighted. Total blood was collected for the determination of haematological parameters. Spleen, medulla and draining lymph node were obtained for lymphoid cell count. Fragments of the paw with tumor, kidney and liver were histopathologically evaluated. The results of the chemical analysis demonstrated that extracts FR1 and FR2 are rich in meroterpenoids. In the in vitro evaluation, the FR1 extract presented cytotoxicity for MCF-7 with IC50 values of 43.97μg / mL, 23.01μg / mL and 13.85μg / mL. For MDA-MB-23, IC50 values found were of 170 μg / mL, 44.60 μg / mL and 25.46 μg / mL in 24, 48 and 72 h, respectively. All these values were lower when compared to FR2. In the verification of the sensitivity index (SI) it was observed that both extracts showed a better selectivity than the standard drugs. In the in vivo assay, tumor development after treatment demonstrated that the FR1, at all doses, and CTL + treated groups showed a significant reduction of tumor area when compared to CTL-. Treatment with FR1 also promoted an increase in the life expectancy of the tumor bearing animals. The cellularity of the lymphoid organs of FR1 treated animals presented a dose dependent reduction when compared to CTL-. When evaluating the cytokines in the serum of the animals, TNF-α production was higher in the non-induction group treated with the extract when compared to CTL-. There was no change in the haematological parameters analyzed in any of the groups. Regarding the histopathological analysis, the groups treated with the extract at doses of 20 and 100 mg/kg presented less intense inflammatory infiltrates. The groups treated with higher concentrations of the extract showed smaller areas of necrosis. These results indicate that the extract of P. purpurogenum exhibits antitumor property, suggesting that its immunomodulatory role would be involved in this response. |
id |
UFMA_e0db495c19476aa4e6fbe055585a61ed |
---|---|
oai_identifier_str |
oai:tede2:tede/3503 |
network_acronym_str |
UFMA |
network_name_str |
Biblioteca Digital de Teses e Dissertações da UFMA |
repository_id_str |
2131 |
spelling |
NASCIMENTO, Maria do Desterro Soares Brandãohttp://lattes.cnpq.br/3958174822396319SANTOS, Ana Paula Silva de Azevedo doshttp://lattes.cnpq.br/8224124082144965SOUZA, Fernando Almeidahttp://lattes.cnpq.br/4432122198480808NASCIMENTO, Maria do Desterro Soares Brandãohttp://lattes.cnpq.br/3958174822396319SANTOS, Ana Paula Silva de Azevedo doshttp://lattes.cnpq.br/8224124082144965SOUZA, Fernando Almeida dehttp://lattes.cnpq.br/4432122198480808SILVA, Ana Lúcia Abreuhttp://lattes.cnpq.br/8288733951324759BORGES, Antônio Carlos Romãohttp://lattes.cnpq.br/4315209704773266http://lattes.cnpq.br/3933255152524601TELES, Amanda Mara2022-03-23T14:47:59Z2020-07-14TELES, Amanda Mara. Caracterização de metabólitos e atividade citotóxica do extrato de Penicillium purpurogenum de ambiente marinho em modelo de câncer de mama in vitro e in vivo.. 2020. 149 f. Tese( Programa de Pós-Graduação em Biotecnologia - RENORBIO/CCBS) - Universidade Federal do Maranhão, São Luís, 2020.https://tedebc.ufma.br/jspui/handle/tede/tede/3503Microfungi are a promising yet unexplored source of new chemical substances with antitumor activity, which in this scenario represent an area with potential for development. To further elucidate the role of Penicillium purpurogenum extract, this study investigated the in vitro antitumor effect on breast tumor cells (MDA-MB-231 and MCF-7) and an in vivo murine Ehrlich tumor model. P. purpurogenum was fermented for 21 days, filtered, concentrated and lyophilized, giving rise to two extracts: ethyl acetate extract of the broth (FR1) and of the mycelial biomass (FR2). For the determination of the chemical composition of the extracts a chemical analysis was performed by direct infusion (ESI/MS). For the evaluation of the cytotoxicity, a MTT [(3-fluorouracil-2-yl) -2,5-diphenyl-tetrazolium bromide] assay was performed with cancer cell lines in the times of 24, 48 and 72 hours. In the in vivo experiment with Ehrlich's tumor, Swiss females were separated into seven groups (n = 10 / group). The intraperitoneal treatment was done daily with phosphate buffer solution in the negative control group (CTL-), with cyclophosphamide (25 mg/kg) in the positive control group (CTL+) and the fungus extract (FR1) at doses 4, 20 and 100 mg/kg in the experimental group. Half of the animals in each group were euthanized 15 days after tumor inoculation, and the other half was kept alive for survival follow-up. Tumor development was evaluated by the weight of the animals, volume and area of the inoculated paw and, after euthanasia, the tumor was weighted. Total blood was collected for the determination of haematological parameters. Spleen, medulla and draining lymph node were obtained for lymphoid cell count. Fragments of the paw with tumor, kidney and liver were histopathologically evaluated. The results of the chemical analysis demonstrated that extracts FR1 and FR2 are rich in meroterpenoids. In the in vitro evaluation, the FR1 extract presented cytotoxicity for MCF-7 with IC50 values of 43.97μg / mL, 23.01μg / mL and 13.85μg / mL. For MDA-MB-23, IC50 values found were of 170 μg / mL, 44.60 μg / mL and 25.46 μg / mL in 24, 48 and 72 h, respectively. All these values were lower when compared to FR2. In the verification of the sensitivity index (SI) it was observed that both extracts showed a better selectivity than the standard drugs. In the in vivo assay, tumor development after treatment demonstrated that the FR1, at all doses, and CTL + treated groups showed a significant reduction of tumor area when compared to CTL-. Treatment with FR1 also promoted an increase in the life expectancy of the tumor bearing animals. The cellularity of the lymphoid organs of FR1 treated animals presented a dose dependent reduction when compared to CTL-. When evaluating the cytokines in the serum of the animals, TNF-α production was higher in the non-induction group treated with the extract when compared to CTL-. There was no change in the haematological parameters analyzed in any of the groups. Regarding the histopathological analysis, the groups treated with the extract at doses of 20 and 100 mg/kg presented less intense inflammatory infiltrates. The groups treated with higher concentrations of the extract showed smaller areas of necrosis. These results indicate that the extract of P. purpurogenum exhibits antitumor property, suggesting that its immunomodulatory role would be involved in this response.O microfungo é uma fonte promissora e ainda pouco explorada de novas substâncias químicas direcionadas a atividade antitumoral, que neste cenário representam uma área com potencial de desenvolvimento. Para melhor elucidar o papel do extrato de Penicillium purpurogenum, este estudo investigou o efeito antitumoral in vitro em células tumorais de mama (MDA-MB-231 e MCF-7) e em modelo in vivo de tumor murino de Ehrlich. O extrato de P. purpurogenum foi fermentado por 21 dias, filtrado, concentrado e liofilizado, dando origem a dois extratos: de acetato de etila do caldo (FR1) e da biomassa micelial (FR2). Para a determinação da composição química dos extratos foi realizado análise química por infusão direta (ESI/MS). Para avaliação da citotoxicidade foi utilizado o ensaio de MTT (brometo de [3-(4,5-dimetiltiazol-2yl)-2,5-difenil tetrazolium]),com as linhagens de câncer de mama nos tempos de 24, 48 e 72 horas. No ensaio in vivo com tumor de Ehrlich foram utilizados camundongos da linhagem Swiss fêmeas separadas em sete grupos (n=10/grupo). O tratamento intraperitoneal foi feito diariamente, com solução tampão fosfato no grupo controle negativo (CTL-), com ciclofosfamida (25 mg/kg) no grupo controle positivo (CTL+) e com o extrato de fungo (FR1) nas doses 4, 20 e 100 mg/kg no grupo experimental. Metade dos animais de cada grupo foram eutanasiados 15 dias após o inóculo do tumor, e a outra metade foi mantida viva para acompanhamento da sobrevida. O desenvolvimento tumoral foi avaliado pelo peso dos animais, volume e área da pata inoculada e, após a eutanásia, o peso tumor. O sangue total foi coletado para determinação de parâmetros hematológicos. Baço, médula e linfonodo drenante foram obtidos para realização da contagem das células linfóides. Fragmentos da pata com tumor, rim e fígado foram avaliados histopatologicamente. Os resultados da análise química demonstraram que os extratos FR1 e FR2 são ricos em meroterpenoides. Na avaliação in vitro o extrato FR1 apresentou citotoxicidade com IC50, mas baixos quando comparados a FR2, para MCF-7 com IC50 de 43,97µg/mL, 23,01µg/mL e 13,85µg/mL, enquanto que, para a MDA-MB-231, IC50 de 170µg/mL, 44,60µg/mL e 25,46µg/mL em 24, 48 e 72h, respectivamente. Na verificação do índice de sensibilidade (IS) foi observado que ambos os extratos mostraram uma melhor seletividade do que as drogas padrões. No ensaio in vivo, o desenvolvimento do tumor após tratamento demonstrou que os grupos tratados com FR1, em todas as doses, e CTL+ apresentaram uma redução significativa da área do tumor quando comparados ao CTL-. O tratamento com FR1 promoveu ainda um aumento da expectativa de vida dos animais portadores de tumor. A celularidade dos órgãos linfoides dos animais tratados com FR1 apresentou uma redução dose dependente quando comparadas ao CTL-. Ao avaliar as citocinas no soro dos animais, a produção de TNF-α foi maior no grupo sem indução tratado com o extrato quando comparado ao CTL-. Não houve alteração dos parâmetros hematológicos analisados em nenhum dos grupos. Em relação à análise histopatológica, os grupos tratados com o extrato nas doses de 20 e 100mg/kg apresentaram infiltrados inflamatórios menos intensos. Os grupos tratados com maior concentração do extrato exibiram menores áreas de necrose. Estes resultados indicam que o extrato de P. purpurogenum exibe propriedade antitumoral, sugerindo ainda que seu papel imunomodulador estaria envolvido nessa resposta.Submitted by Maria Aparecida (cidazen@gmail.com) on 2022-03-23T14:47:59Z No. of bitstreams: 1 AMANDA MARA TELES.pdf: 47242972 bytes, checksum: 1b912d9cbb210a83ce0b85caf76eadd4 (MD5)Made available in DSpace on 2022-03-23T14:47:59Z (GMT). No. of bitstreams: 1 AMANDA MARA TELES.pdf: 47242972 bytes, checksum: 1b912d9cbb210a83ce0b85caf76eadd4 (MD5) Previous issue date: 2020-07-14FAPEMAapplication/pdfporUniversidade Federal do MaranhãoPROGRAMA DE PÓS-GRADUAÇÃO EM BIOTECNOLOGIA - RENORBIO/CCBSUFMABrasilDEPARTAMENTO DE MEDICINA I/CCBSCâncer;tumor de Ehlich;Penicillium purpurogenum;meroterpenoides;antitumoral;MCF-7;MDA-MB-231;MCF-10ACancer;Ehlich tumor;Penicillium purpurogenum;antitumoral;meroterpenoids;MCF-7;MDA-MB-231;MCF-10ACancerologiaCARACTERIZAÇÃO DE METABÓLITOS E ATIVIDADE CITOTÓXICA DO EXTRATO DE Penicillium purpurogenum DE AMBIENTE MARINHO EM MODELO DE CÂNCER DE MAMA IN VITRO E IN VIVO.CHARACTERIZATION OF METABOLITES AND CYTOTOXIC ACTIVITY OF Penicillium purpurogenum EXTRACT DERIVED FROM A MARINE ENVIRONMENT IN AN IN VITRO AND IN VIVO BREAST CANCER MODEL.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFMAinstname:Universidade Federal do Maranhão (UFMA)instacron:UFMAORIGINALAMANDA MARA TELES.pdfAMANDA MARA TELES.pdfapplication/pdf47242972http://tedebc.ufma.br:8080/bitstream/tede/3503/2/AMANDA+MARA+TELES.pdf1b912d9cbb210a83ce0b85caf76eadd4MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82255http://tedebc.ufma.br:8080/bitstream/tede/3503/1/license.txt97eeade1fce43278e63fe063657f8083MD51tede/35032022-03-23 11:47:59.509oai:tede2: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Biblioteca Digital de Teses e Dissertaçõeshttps://tedebc.ufma.br/jspui/PUBhttp://tedebc.ufma.br:8080/oai/requestrepositorio@ufma.br||repositorio@ufma.bropendoar:21312022-03-23T14:47:59Biblioteca Digital de Teses e Dissertações da UFMA - Universidade Federal do Maranhão (UFMA)false |
dc.title.por.fl_str_mv |
CARACTERIZAÇÃO DE METABÓLITOS E ATIVIDADE CITOTÓXICA DO EXTRATO DE Penicillium purpurogenum DE AMBIENTE MARINHO EM MODELO DE CÂNCER DE MAMA IN VITRO E IN VIVO. |
dc.title.alternative.eng.fl_str_mv |
CHARACTERIZATION OF METABOLITES AND CYTOTOXIC ACTIVITY OF Penicillium purpurogenum EXTRACT DERIVED FROM A MARINE ENVIRONMENT IN AN IN VITRO AND IN VIVO BREAST CANCER MODEL. |
title |
CARACTERIZAÇÃO DE METABÓLITOS E ATIVIDADE CITOTÓXICA DO EXTRATO DE Penicillium purpurogenum DE AMBIENTE MARINHO EM MODELO DE CÂNCER DE MAMA IN VITRO E IN VIVO. |
spellingShingle |
CARACTERIZAÇÃO DE METABÓLITOS E ATIVIDADE CITOTÓXICA DO EXTRATO DE Penicillium purpurogenum DE AMBIENTE MARINHO EM MODELO DE CÂNCER DE MAMA IN VITRO E IN VIVO. TELES, Amanda Mara Câncer; tumor de Ehlich; Penicillium purpurogenum; meroterpenoides; antitumoral; MCF-7; MDA-MB-231; MCF-10A Cancer; Ehlich tumor; Penicillium purpurogenum; antitumoral; meroterpenoids; MCF-7; MDA-MB-231; MCF-10A Cancerologia |
title_short |
CARACTERIZAÇÃO DE METABÓLITOS E ATIVIDADE CITOTÓXICA DO EXTRATO DE Penicillium purpurogenum DE AMBIENTE MARINHO EM MODELO DE CÂNCER DE MAMA IN VITRO E IN VIVO. |
title_full |
CARACTERIZAÇÃO DE METABÓLITOS E ATIVIDADE CITOTÓXICA DO EXTRATO DE Penicillium purpurogenum DE AMBIENTE MARINHO EM MODELO DE CÂNCER DE MAMA IN VITRO E IN VIVO. |
title_fullStr |
CARACTERIZAÇÃO DE METABÓLITOS E ATIVIDADE CITOTÓXICA DO EXTRATO DE Penicillium purpurogenum DE AMBIENTE MARINHO EM MODELO DE CÂNCER DE MAMA IN VITRO E IN VIVO. |
title_full_unstemmed |
CARACTERIZAÇÃO DE METABÓLITOS E ATIVIDADE CITOTÓXICA DO EXTRATO DE Penicillium purpurogenum DE AMBIENTE MARINHO EM MODELO DE CÂNCER DE MAMA IN VITRO E IN VIVO. |
title_sort |
CARACTERIZAÇÃO DE METABÓLITOS E ATIVIDADE CITOTÓXICA DO EXTRATO DE Penicillium purpurogenum DE AMBIENTE MARINHO EM MODELO DE CÂNCER DE MAMA IN VITRO E IN VIVO. |
author |
TELES, Amanda Mara |
author_facet |
TELES, Amanda Mara |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
NASCIMENTO, Maria do Desterro Soares Brandão |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3958174822396319 |
dc.contributor.advisor-co1.fl_str_mv |
SANTOS, Ana Paula Silva de Azevedo dos |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/8224124082144965 |
dc.contributor.advisor-co2.fl_str_mv |
SOUZA, Fernando Almeida |
dc.contributor.advisor-co2Lattes.fl_str_mv |
http://lattes.cnpq.br/4432122198480808 |
dc.contributor.referee1.fl_str_mv |
NASCIMENTO, Maria do Desterro Soares Brandão |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/3958174822396319 |
dc.contributor.referee2.fl_str_mv |
SANTOS, Ana Paula Silva de Azevedo dos |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/8224124082144965 |
dc.contributor.referee3.fl_str_mv |
SOUZA, Fernando Almeida de |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/4432122198480808 |
dc.contributor.referee4.fl_str_mv |
SILVA, Ana Lúcia Abreu |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/8288733951324759 |
dc.contributor.referee5.fl_str_mv |
BORGES, Antônio Carlos Romão |
dc.contributor.referee5Lattes.fl_str_mv |
http://lattes.cnpq.br/4315209704773266 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3933255152524601 |
dc.contributor.author.fl_str_mv |
TELES, Amanda Mara |
contributor_str_mv |
NASCIMENTO, Maria do Desterro Soares Brandão SANTOS, Ana Paula Silva de Azevedo dos SOUZA, Fernando Almeida NASCIMENTO, Maria do Desterro Soares Brandão SANTOS, Ana Paula Silva de Azevedo dos SOUZA, Fernando Almeida de SILVA, Ana Lúcia Abreu BORGES, Antônio Carlos Romão |
dc.subject.por.fl_str_mv |
Câncer; tumor de Ehlich; Penicillium purpurogenum; meroterpenoides; antitumoral; MCF-7; MDA-MB-231; MCF-10A |
topic |
Câncer; tumor de Ehlich; Penicillium purpurogenum; meroterpenoides; antitumoral; MCF-7; MDA-MB-231; MCF-10A Cancer; Ehlich tumor; Penicillium purpurogenum; antitumoral; meroterpenoids; MCF-7; MDA-MB-231; MCF-10A Cancerologia |
dc.subject.eng.fl_str_mv |
Cancer; Ehlich tumor; Penicillium purpurogenum; antitumoral; meroterpenoids; MCF-7; MDA-MB-231; MCF-10A |
dc.subject.cnpq.fl_str_mv |
Cancerologia |
description |
Microfungi are a promising yet unexplored source of new chemical substances with antitumor activity, which in this scenario represent an area with potential for development. To further elucidate the role of Penicillium purpurogenum extract, this study investigated the in vitro antitumor effect on breast tumor cells (MDA-MB-231 and MCF-7) and an in vivo murine Ehrlich tumor model. P. purpurogenum was fermented for 21 days, filtered, concentrated and lyophilized, giving rise to two extracts: ethyl acetate extract of the broth (FR1) and of the mycelial biomass (FR2). For the determination of the chemical composition of the extracts a chemical analysis was performed by direct infusion (ESI/MS). For the evaluation of the cytotoxicity, a MTT [(3-fluorouracil-2-yl) -2,5-diphenyl-tetrazolium bromide] assay was performed with cancer cell lines in the times of 24, 48 and 72 hours. In the in vivo experiment with Ehrlich's tumor, Swiss females were separated into seven groups (n = 10 / group). The intraperitoneal treatment was done daily with phosphate buffer solution in the negative control group (CTL-), with cyclophosphamide (25 mg/kg) in the positive control group (CTL+) and the fungus extract (FR1) at doses 4, 20 and 100 mg/kg in the experimental group. Half of the animals in each group were euthanized 15 days after tumor inoculation, and the other half was kept alive for survival follow-up. Tumor development was evaluated by the weight of the animals, volume and area of the inoculated paw and, after euthanasia, the tumor was weighted. Total blood was collected for the determination of haematological parameters. Spleen, medulla and draining lymph node were obtained for lymphoid cell count. Fragments of the paw with tumor, kidney and liver were histopathologically evaluated. The results of the chemical analysis demonstrated that extracts FR1 and FR2 are rich in meroterpenoids. In the in vitro evaluation, the FR1 extract presented cytotoxicity for MCF-7 with IC50 values of 43.97μg / mL, 23.01μg / mL and 13.85μg / mL. For MDA-MB-23, IC50 values found were of 170 μg / mL, 44.60 μg / mL and 25.46 μg / mL in 24, 48 and 72 h, respectively. All these values were lower when compared to FR2. In the verification of the sensitivity index (SI) it was observed that both extracts showed a better selectivity than the standard drugs. In the in vivo assay, tumor development after treatment demonstrated that the FR1, at all doses, and CTL + treated groups showed a significant reduction of tumor area when compared to CTL-. Treatment with FR1 also promoted an increase in the life expectancy of the tumor bearing animals. The cellularity of the lymphoid organs of FR1 treated animals presented a dose dependent reduction when compared to CTL-. When evaluating the cytokines in the serum of the animals, TNF-α production was higher in the non-induction group treated with the extract when compared to CTL-. There was no change in the haematological parameters analyzed in any of the groups. Regarding the histopathological analysis, the groups treated with the extract at doses of 20 and 100 mg/kg presented less intense inflammatory infiltrates. The groups treated with higher concentrations of the extract showed smaller areas of necrosis. These results indicate that the extract of P. purpurogenum exhibits antitumor property, suggesting that its immunomodulatory role would be involved in this response. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-07-14 |
dc.date.accessioned.fl_str_mv |
2022-03-23T14:47:59Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
TELES, Amanda Mara. Caracterização de metabólitos e atividade citotóxica do extrato de Penicillium purpurogenum de ambiente marinho em modelo de câncer de mama in vitro e in vivo.. 2020. 149 f. Tese( Programa de Pós-Graduação em Biotecnologia - RENORBIO/CCBS) - Universidade Federal do Maranhão, São Luís, 2020. |
dc.identifier.uri.fl_str_mv |
https://tedebc.ufma.br/jspui/handle/tede/tede/3503 |
identifier_str_mv |
TELES, Amanda Mara. Caracterização de metabólitos e atividade citotóxica do extrato de Penicillium purpurogenum de ambiente marinho em modelo de câncer de mama in vitro e in vivo.. 2020. 149 f. Tese( Programa de Pós-Graduação em Biotecnologia - RENORBIO/CCBS) - Universidade Federal do Maranhão, São Luís, 2020. |
url |
https://tedebc.ufma.br/jspui/handle/tede/tede/3503 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal do Maranhão |
dc.publisher.program.fl_str_mv |
PROGRAMA DE PÓS-GRADUAÇÃO EM BIOTECNOLOGIA - RENORBIO/CCBS |
dc.publisher.initials.fl_str_mv |
UFMA |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
DEPARTAMENTO DE MEDICINA I/CCBS |
publisher.none.fl_str_mv |
Universidade Federal do Maranhão |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFMA instname:Universidade Federal do Maranhão (UFMA) instacron:UFMA |
instname_str |
Universidade Federal do Maranhão (UFMA) |
instacron_str |
UFMA |
institution |
UFMA |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFMA |
collection |
Biblioteca Digital de Teses e Dissertações da UFMA |
bitstream.url.fl_str_mv |
http://tedebc.ufma.br:8080/bitstream/tede/3503/2/AMANDA+MARA+TELES.pdf http://tedebc.ufma.br:8080/bitstream/tede/3503/1/license.txt |
bitstream.checksum.fl_str_mv |
1b912d9cbb210a83ce0b85caf76eadd4 97eeade1fce43278e63fe063657f8083 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFMA - Universidade Federal do Maranhão (UFMA) |
repository.mail.fl_str_mv |
repositorio@ufma.br||repositorio@ufma.br |
_version_ |
1800303804695969792 |