title: Experimental gastric carcinogenesis in Cebus apella nonhuman primates.
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.
authors.affiliation: Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil.
authors.forename: Joana de Fátima Ferreira Borges
authors.initials: Jde F
authors.lastname: da Costa
authors.forename: Mariana Ferreira
authors.initials: MF
authors.lastname: Leal
authors.forename: Tanielly Cristina Raiol
authors.initials: TC
authors.lastname: Silva
authors.forename: Edilson Ferreira
authors.initials: EF
authors.lastname: Andrade Junior
authors.forename: Alexandre Pingarilho
authors.initials: AP
authors.lastname: Rezende
authors.forename: José Augusto Pereira Carneiro
authors.initials: JA
authors.lastname: Muniz
authors.forename: Antonio Carlos Cunha
authors.initials: AC
authors.lastname: Lacreta Junior
authors.forename: Paulo Pimentel
authors.initials: PP
authors.lastname: Assumpção
authors.forename: Danielle Queiroz
authors.initials: DQ
authors.lastname: Calcagno
authors.forename: Samia
authors.initials: S
authors.lastname: Demachki
authors.forename: Silvia Helena Barem
authors.initials: SH
authors.lastname: Rabenhorst
authors.forename: Marília de Arruda Cardoso
authors.initials: Mde A
authors.lastname: Smith
authors.forename: Rommel Rodriguez
authors.initials: RR
authors.lastname: Burbano
mesh_terms: D000818:Animals; D002428:Cebus; D002460:Cell Line; D003435:Crotalid Venoms / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D018628:Gene Dosage / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008770:Methylnitrosourea; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D014463:Ultrasonography
chemical_list: C513575:Canova medication; D003435:Crotalid Venoms; D010936:Plant Extracts; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D008770:Methylnitrosourea