Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/33890 http://dx.doi.org/10.1371/journal.pone.0021988 |
Resumo: | The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. in the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. in the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9(th) day though on the 14(th) day presented total tumor remission. in the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. the last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940(th) day. the level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. the hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. in cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. in MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and duration of anticancer treatments. |
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Ferreira Borges da Costa, Joana de FatimaLeal, Mariana Ferreira [UNIFESP]Raiol Silva, Tanielly CristinaAndrade Junior, Edilson FerreiraRezende, Alexandre PingarilhoPereira Carneiro Muniz, Jose AugustoLacreta Junior, Antonio Carlos CunhaAssumpcao, Paulo PimentelCalcagno, Danielle Queiroz [UNIFESP]Demachki, SamiaRabenhorst, Silvia Helena BaremSmith, Marilia de Arruda Cardoso [UNIFESP]Burbano, Rommel RodriguezFed Univ ParaUniversidade Federal de São Paulo (UNIFESP)Minist SaudeUniversidade Federal de Lavras (UFLA)Univ Fed Ceara2016-01-24T14:17:00Z2016-01-24T14:17:00Z2011-07-21Plos One. San Francisco: Public Library Science, v. 6, n. 7, 13 p., 2011.1932-6203http://repositorio.unifesp.br/handle/11600/33890http://dx.doi.org/10.1371/journal.pone.0021988WOS000292956800017.pdf10.1371/journal.pone.0021988WOS:000292956800017The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. in the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. in the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9(th) day though on the 14(th) day presented total tumor remission. in the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. the last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940(th) day. the level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. the hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. in cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. in MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and duration of anticancer treatments.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fed Univ Para, Inst Ciencias Biol, Lab Citogenet Humana, BR-66059 Belem, Para, BrazilUniversidade Federal de São Paulo, Dept Morfol & Genet, Disciplina Genet, São Paulo, BrazilMinist Saude, Ctr Nacl Primatas, Ananindeua, BrazilUniv Fed Lavras, Dept Vet Med, Lavras, BrazilFed Univ Para, Hosp Univ Joao de Barros Barreto, BR-66059 Belem, Para, BrazilUniv Fed Ceara, Escola Med, Dept Patol & Med Forense, Genet Mol Lab, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, Dept Morfol & Genet, Disciplina Genet, São Paulo, BrazilCNPq: 550885/2007-2CNPq: 302774/2009-2CNPq: 301609/2007-1FAPESP: 2007/02470-3FAPESP: 2010/11174-1Web of Science13engPublic Library SciencePlos OneExperimental Gastric Carcinogenesis in Cebus apella Nonhuman Primatesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000292956800017.pdfapplication/pdf730138${dspace.ui.url}/bitstream/11600/33890/1/WOS000292956800017.pdf4c9843002935c5659359387eed133d22MD51open accessTEXTWOS000292956800017.pdf.txtWOS000292956800017.pdf.txtExtracted texttext/plain66326${dspace.ui.url}/bitstream/11600/33890/2/WOS000292956800017.pdf.txt0c388cfab3043a4523e9661a05fcdf0fMD52open access11600/338902023-01-30 22:20:24.913open accessoai:repositorio.unifesp.br:11600/33890Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-01-31T01:20:24Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates |
title |
Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates |
spellingShingle |
Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates Ferreira Borges da Costa, Joana de Fatima |
title_short |
Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates |
title_full |
Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates |
title_fullStr |
Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates |
title_full_unstemmed |
Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates |
title_sort |
Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates |
author |
Ferreira Borges da Costa, Joana de Fatima |
author_facet |
Ferreira Borges da Costa, Joana de Fatima Leal, Mariana Ferreira [UNIFESP] Raiol Silva, Tanielly Cristina Andrade Junior, Edilson Ferreira Rezende, Alexandre Pingarilho Pereira Carneiro Muniz, Jose Augusto Lacreta Junior, Antonio Carlos Cunha Assumpcao, Paulo Pimentel Calcagno, Danielle Queiroz [UNIFESP] Demachki, Samia Rabenhorst, Silvia Helena Barem Smith, Marilia de Arruda Cardoso [UNIFESP] Burbano, Rommel Rodriguez |
author_role |
author |
author2 |
Leal, Mariana Ferreira [UNIFESP] Raiol Silva, Tanielly Cristina Andrade Junior, Edilson Ferreira Rezende, Alexandre Pingarilho Pereira Carneiro Muniz, Jose Augusto Lacreta Junior, Antonio Carlos Cunha Assumpcao, Paulo Pimentel Calcagno, Danielle Queiroz [UNIFESP] Demachki, Samia Rabenhorst, Silvia Helena Barem Smith, Marilia de Arruda Cardoso [UNIFESP] Burbano, Rommel Rodriguez |
author2_role |
author author author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Fed Univ Para Universidade Federal de São Paulo (UNIFESP) Minist Saude Universidade Federal de Lavras (UFLA) Univ Fed Ceara |
dc.contributor.author.fl_str_mv |
Ferreira Borges da Costa, Joana de Fatima Leal, Mariana Ferreira [UNIFESP] Raiol Silva, Tanielly Cristina Andrade Junior, Edilson Ferreira Rezende, Alexandre Pingarilho Pereira Carneiro Muniz, Jose Augusto Lacreta Junior, Antonio Carlos Cunha Assumpcao, Paulo Pimentel Calcagno, Danielle Queiroz [UNIFESP] Demachki, Samia Rabenhorst, Silvia Helena Barem Smith, Marilia de Arruda Cardoso [UNIFESP] Burbano, Rommel Rodriguez |
description |
The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. in the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. in the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9(th) day though on the 14(th) day presented total tumor remission. in the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. the last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940(th) day. the level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. the hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. in cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. in MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and duration of anticancer treatments. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-07-21 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:17:00Z |
dc.date.available.fl_str_mv |
2016-01-24T14:17:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
Plos One. San Francisco: Public Library Science, v. 6, n. 7, 13 p., 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/33890 http://dx.doi.org/10.1371/journal.pone.0021988 |
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1932-6203 |
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WOS000292956800017.pdf |
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10.1371/journal.pone.0021988 |
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WOS:000292956800017 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 6, n. 7, 13 p., 2011. 1932-6203 WOS000292956800017.pdf 10.1371/journal.pone.0021988 WOS:000292956800017 |
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http://repositorio.unifesp.br/handle/11600/33890 http://dx.doi.org/10.1371/journal.pone.0021988 |
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Public Library Science |
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