Navegando por Palavras-chave "TP53"

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    Análise de polimorfismos nos códons 11, 72 e 248 do gene TP53 em mulheres com câncer de mama
    (Universidade Federal de São Paulo (UNIFESP), 2015-02-29) Almeida, Bruna Cristine de [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; Kosugi, Cíntia Meirelles de Camargo [UNIFESP]; http://lattes.cnpq.br/9096212469685166; http://lattes.cnpq.br/7917312029683516; http://lattes.cnpq.br/6489308507235006; Universidade Federal de São Paulo (UNIFESP)
    Introdução: Câncer de mama é a neoplasia maligna mais frequente entre as mulheres no Brasil. O gene TP53, codifica a proteína de nome p53 que está relacionada com a regulação do ciclo celular e apoptose, apresenta polimorfismos que podem ter influência funcional. Os polimorfismos investigados foram: TP53*11 onde ocorre a troca de base nitrogenada G para C (Glu->Gln) no éxons 2; TP53*72 no qual a troca de base consiste em C para G (Pro->Arg) no éxons 4 e TP53*248 onde a troca de base é G para A (Arg->Gln) localizada no éxon 7. Objetivo: Avaliar se há associação entre a presença dos polimorfismos no gene TP53 (códons 11, 72 e 248) em pacientes com e sem câncer de mama e a relação das variáveis clínicas e anatomopatológicas. Métodos: Estudo transversal onde foram analisadas 393 mulheres (N = 188 mulheres com câncer de mama; N = 205 mulheres sem câncer de mama) por meio de PCR-RFLP em DNA extraídos de sangue periférico. As mulheres apresentaram idades entre 26 e 80 anos. Resultados: Os códons 11 e 248 do gene TP53 não apresentaram variações genéticas. O TP53*11 apresentou a seguinte distribuição genotípica: 100% Glu/Glu tanto para o Grupo Caso como para o Controle. Do mesmo modo, foi obtido para TP53*248: Arg/Arg 100% para ambos os grupos. As análises do códon 72 apresentaram as seguintes distribuições genotípicas: Pro/Pro 16,10%; Pro/Arg 42,44% e Arg/Arg 41,46% para o Grupo Controle e Pro/Pro 15,43%; Pro/Arg 42,55% e Arg/Arg 42,02% para o Grupo Caso (OR = 1,052; 95% CI = 0,6108-1,812; p = 0,9823). As amostras encontram-se em equilíbrio de Hardy-Weinberg. Os dados clínicos patológicos, grau nuclear (p = 0,0084) e grau histológico adaptado (p = 0,0265), bem como a frequência alélica do grau histológico adaptado (p = 0,0057) mostraram significância estatística. Levando-se a crer que os polimorfismos nestes códons apresentam relevância clínica para o câncer de mama. No entanto, comparando-se os grupos não foram observadas diferenças estatisticamente significantes. Conclusões: Apenas o polimorfismo do códon 72 está condicionado com associação às variáveis clínicas estudadas. Sendo que os SNPs, TP53*11 e TP53*248, parecem não estar associados ao câncer de mama.
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    hTERT and TP53 deregulation in intestinal-type gastric carcinogenesis in non-human primates
    (Springer, 2013-08-01) Leal, Mariana Ferreira [UNIFESP]; Calcagno, Danielle Queiroz [UNIFESP]; Khayat, Andre Salim; Raiol Silva, Tanielly Cristina; Pereira Carneiro Muniz, Jose Augusto; Assumpcao, Paulo Pimentel; Cardoso Smith, Marilia de Arruda [UNIFESP]; Burbano, Rommel Rodriguez; Universidade Federal de São Paulo (UNIFESP); Fed Univ Para; Minist Saude
    Despite the high incidence, the molecular events involved in intestinal-type gastric carcinogenesis remains unclear. We previously established an intestinal-type gastric carcinogenesis model in Cebus apella, a New World monkey. in the present study, we evaluated hTERT and TP53 mRNA expression, as well as their protein immunoreactivity, in normal mucosa, non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and intestinal-type gastric cancer samples of non-human primates treated with N-methyl-nitrosourea. in addition, we evaluated the number of TP53 copies in these samples. Although hTERT immunoreactivity was only detected in gastric cancer, a continuous increase of hTERT mRNA expression was observed from non-atrophic gastritis to gastric tumors. No sample presented p53 immunoreactivity. However, we also observed a continuous decrease of TP53 mRNA expression during the sequential steps of gastric carcinogenesis. Moreover, loss of TP53 copies was observed in intestinal metaplasia and gastric cancer samples. Our study highlights that hTERT and TP53 have a key role in intestinal-type gastric cancer initiation.
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    hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions
    (Biomed Central Ltd, 2012-07-06) Silva, Tanielly Cristina Raiol; Leal, Mariana Ferreira [UNIFESP]; Calcagno, Danielle Queiroz [UNIFESP]; Souza, Carolina Rosal Teixeira de; Khayat, Andre Salim; Santos, Ney Pereira Carneiro dos; Montenegro, Raquel Carvalho; Rabenhorst, Silvia Helena Barem; Nascimento, Mayara Quaresma; Assumpcao, Paulo Pimentel; Smith, Marilia de Arruda Cardoso [UNIFESP]; Burbano, Rommel Rodriguez; Universidade Federal de São Paulo (UNIFESP); Fed Univ Para; Univ Fed Ceara
    Background: Gastric cancer is a serious public health problem in Northern Brazil and in the world due to its high incidence and mortality. Despite the severity of the disease, more research is needed to better understand the molecular events involved in this intestinal-type gastric carcinogenesis process. Since precancerous lesions precede intestinal-type gastric cancer, here, we evaluated the hTERT, MYC, and TP53 mRNA and protein expression, as well as TP33 copy number, in gastric preneoplastic lesions.Methods: We evaluated 19 superficial gastritis, 18 atrophic gastritis, and 18 intestinal metaplasia from cancer-free individuals of Northern Brazil. Quantitative reverse transcription PCR was used to analyze the mRNA expression and immunohistochemical methods were used to assess protein immunoreactivity in tissue samples. the number of TP53 gene copies was investigated in gastric diseases by quantitative PCR.Results: We observed hTERT, MYC, and p53 immunoreactivity only in intestinal metaplasia samples. the immunoreactivity of these proteins was strongly associated with each other. A significantly higher MYC mRNA expression was observed in intestinal metaplasia compared to gastritis samples. Loss of TP53 was also only detected in intestinal metaplasia specimens.Conclusions: We demonstrated that hTERT, MYC, and TP53 are deregulated in intestinal metaplasia of individuals from Northern Brazil and these alterations may facilitate tumor initiation.
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    Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with gastric cancer
    (Associação Brasileira de Divulgação Científica, 2008-06-01) Lima, Eleonidas Moura; Leal, Mariana Ferreira [UNIFESP]; Burbano, Rommel Rodríguez [UNIFESP]; Khayat, Andre Salim; Assumpção, Paulo Pimentes de [UNIFESP]; Bello, Maria Jose; Rey, J.a.; Smith, Marilia de Arruda Cardoso [UNIFESP]; Casartelli, Carla; Universidade Federal do Piauí Colegiado de Biomedicina; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Pará Instituto de Ciências Biológicas Laboratório de Citogenética Humana; Hospital João de Barros Barreto Serviço de Cirurgia; Instituto de Investigaciones Biomedicas; Universidade de São Paulo (USP)
    Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide. DNA methylation is the most studied epigenetic alteration, occurring through a methyl radical addition to the cytosine base adjacent to guanine. Many tumor genes are inactivated by DNA methylation in gastric cancer. We evaluated the DNA methylation status of ANAPC1, CDKN2A and TP53 by methylation-specific PCR in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosa in individuals from Northern Brazil. All gastric cancer samples were advanced stage adenocarcinomas. Gastric samples were surgically obtained at the João de Barros Barreto University Hospital, State of Pará, and were stored at -80°C before DNA extraction. Patients had never been submitted to chemotherapy or radiotherapy, nor did they have any other diagnosed cancer. None of the gastric cancer samples presented methylated DNA sequences for ANAPC1 and TP53. CDKN2A methylation was not detected in any normal gastric mucosa; however, the CDKN2A promoter was methylated in 30.4% of gastric cancer samples, with 35% methylation in diffuse-type and 26.9% in intestinal-type cancers. CDKN2A methylation was associated with the carcinogenesis process for ~30% diffuse-type and intestinal-type compared to non-neoplastic samples. Thus, ANAPC1 and TP53 methylation was probably not implicated in gastric carcinogenesis in our samples. CDKN2A can be implicated in the carcinogenesis process of only a subset of gastric neoplasias.
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    MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
    (Biomed Central Ltd, 2013-09-23) Calcagno, Danielle Queiroz [UNIFESP]; Freitas, Vanessa Morais; Leal, Mariana Ferreira [UNIFESP]; Souza, Carolina Rosal Teixeira de; Demachki, Samia; Montenegro, Raquel; Assumpcao, Paulo Pimentel; Khayat, Andre Salim; Smith, Marilia de Arruda Cardoso [UNIFESP]; Santos, Andrea Kely Campos Ribeiro dos; Burbano, Rommel Rodriguez; Fed Univ Para; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Background: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation.Methods: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines.Results: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. in vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells.Conclusion: in conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.
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    TP53 gene polymorphisms at codons 11, 72, and 248 and association with endometriosis in a Brazilian population
    (Funpec-editora, 2014-01-01) Camargo-Kosugi, Cintia Meirelles de [UNIFESP]; D'Amora, Paulo [UNIFESP]; Kleine, Joao Paulo Ferreira de Oliveira [UNIFESP]; Carvalho, Cristina Valletta de [UNIFESP]; Sato, Hélio [UNIFESP]; Schor, Eduardo [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    We evaluated the association between TP53 gene polymorphisms and endometriosis in Brazilian women. Genomic DNA was extracted from swabs of buccal cells collected from hospital patients. TP53 gene polymorphisms were investigated at three codons: TP53*11 Glu/Gln or Lys (GAG->CAG or AAG), TP53*72 Arg/Pro (CCG->CCC), and TP53*248 Arg/Thr (CGG->TCG) using the polymerase chain reaction-restriction fragment length polymorphism method. TP53*11 presented the following genotypic distribution: the control group was 98.28% homozygous wild-type (Glu) and 1.72% homozygous variant (Gln/Lys), and the heterozygous genotype was not identified. the genotypic distribution in the endometriosis group was 96% homozygous wild-type (Glu) and 4% heterozygous (Glu-Gln/Lys); the homozygous variant genotype was not identified (P = 0.02). TP53*72 showed the following genotypic distribution: the control group was 29.75% homozygous wild-type (Arg), 47.11% heterozygous (Arg-Pro), and 23.14% homozygous variant (Pro). the genotypic distribution in the endometriosis group was 16.15% homozygous wildtype (Arg), 51.54% heterozygous (Arg-Pro), and 32.31% homozygous variant (Pro) (odds ratio = 2.26; 95% confidence interval = 1.19-4.03; P = 0.02). Only one patient had the homozygous TP53*248 genotype (Arg-Trp/Gln); all other patients were homozygous wild-type in both the control and endometriosis groups (P = 0.51; NS). We found that TP53*72 polymorphism may be associated with susceptibility to endometriosis; the presence of at least 1 polymorphic allele increased the chance of disease development by 2.26-fold. Hence, this genetic variant is a potential candidate marker for endometriosis.