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Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates

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      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.

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      Most cited references 56

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      The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
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            Author and article information

            Affiliations
            [1 ]Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil
            [2 ]Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, Brazil
            [3 ]Centro Nacional de Primatas, Ministério da Saúde, Ananindeua, Brazil
            [4 ]Departamento de Medicina Veterinária, Universidade Federal de Lavras, Lavras, Brazil
            [5 ]Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, Brazil
            [6 ]Laboratório de Genética Molecular, Departamento de Patologia e Medicina Forense, Escola de Medicina, Universidade Federal do Ceará, Fortaleza, Brazil
            University of Georgia, United States of America
            Author notes

            Conceived and designed the experiments: MFL MdACS RRB. Performed the experiments: JdFFBdC MFL TCRS EFAJ APR DQC. Analyzed the data: JdFFBdC MFL PPA SD SHBR JAPCM ACCLJ DQC MdACS RRB. Contributed reagents/materials/analysis tools: JAPCM ACCLJ SHBR. Wrote the paper: MFL JdFFBdC DQC MdACS RRB.

            Contributors
            Role: Editor
            Journal
            PLoS One
            plos
            plosone
            PLoS ONE
            Public Library of Science (San Francisco, USA )
            1932-6203
            2011
            21 July 2011
            : 6
            : 7
            3140998
            21811552
            PONE-D-11-03343
            10.1371/journal.pone.0021988
            (Editor)
            Borges da Costa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
            Counts
            Pages: 13
            Categories
            Research Article
            Biology
            Computational Biology
            Molecular Genetics
            Gene Expression
            Genetics
            Cancer Genetics
            Cytogenetics
            Gene Expression
            Molecular Cell Biology
            Gene Expression
            Toxicology
            Genetic Toxicology
            Medicine
            Oncology
            Cancers and Neoplasms
            Gastrointestinal Tumors
            Gastric Cancer
            Cancer Treatment

            Uncategorized

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