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Title: Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates
Authors: 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
Fed Univ Para
Universidade Federal de São Paulo (UNIFESP)
Minist Saude
Universidade Federal de Lavras (UFLA)
Univ Fed Ceara
Issue Date: 21-Jul-2011
Publisher: Public Library Science
Citation: Plos One. San Francisco: Public Library Science, v. 6, n. 7, 13 p., 2011.
Abstract: 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.
ISSN: 1932-6203
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