Navegando por Palavras-chave "hTERT"

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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 expression and prognosis in B-chronic lymphocytic leukemia
    (Oxford Univ Press, 2004-10-01) Tchirkov, A.; Chaleteix, C.; Magnac, C.; Vasconcelos, Yuri [UNIFESP]; Davi, F.; Michel, A.; Kwiatkowski, F.; Tournilhac, O.; Dighiero, G.; Travade, P.; Ctr Jean Perrin; CHU; Inst Pasteur; Hop La Pitie Salpetriere; Universidade Federal de São Paulo (UNIFESP)
    Background: in B-chronic lymphocytic leukemia (B-CLL), there is a need for molecular markers to predict the evolution of this heterogeneous disease in individual patients. the level of expression of the human telomerase reverse transcriptase (hTERT) gene has been associated with disease aggressiveness in human cancers. the purpose of the present study was to examine the prognostic significance of hTERT expression in B-CLL.Patients and methods: We used real-time reverse transcription-PCR to quantitate the amount of hTERT transcripts in mononuclear blood cells from 90 B-CLL patients. in addition, samples were analyzed for somatic mutations in the immunoglobulin V (IgV) genes.Results: the expression of hTERT gene was detected in 59% of patients. the level of expression increased with advancing B-CLL stage (P = 0.0064). Patients expressing hTERT showed significantly shorter survival than hTERT-negative patients (P=0.000034), irrespective of the disease stage. On average, the level hTERT mRNA expression was seven-fold higher in the poor-prognosis B-CLL group with unmutated IgV than in the Ig-mutated group (p< 10(-7)). the level of hTERT expression discriminated the Ig-unmutated from Ig-mutated B-CLL in 89% of cases.Conclusion: Our data indicate that hTERT expression in B-CLL may serve as a molecular prognostic marker.
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    hTERT methylation and expression in gastric cancer
    (Taylor & Francis Ltd, 2009-01-01) Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Oliveira Silva, Patricia Natalia; Frias Lisboa, Luara Carolina; Lima, Eleonidas Moura; Calcagno, Danielle Queiroz; Assumpcao, Paulo Pimentel; Burbano, Rommel Rodriguez; Cardoso Smith, Marilia de Arruda [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fed Univ Para
    Gastric cancer is the second most prevalent cause of cancer death worldwide. DNA methylation is a common event in gastric carcinogenesis. hTERT seems to be the rate-limiting determinant of telomerase activation, which is responsible for stability and life span. hTERT hypermethylation has been associated with telomerase expression. in the present study, we investigated the promoter methylation status and hTERT protein expression in gastric cancer and normal mucosa samples. One hundred and nine gastric cancer and 53 normal mucosa samples were investigated through methylation-specific PCR. Immunohistochemistry was analysed using peroxidase in 55 gastric cancer and 18 normal gastric mucosa samples. This is the first study evaluating hTERT methylation status in gastric carcinogenesis. We did not observe hTERT protein expression in normal gastric mucosa. Moreover, hTERT expression was observed in 80% of tumours and was associated with gastric cancer (p < 0.0001). Partial methylation was the most frequent pattern in gastric samples, even in normal mucosa. the frequency of specimens presenting hypermethylation was significantly higher in tumours than in normal mucosa samples (p = 0.0002), although the presence of hypermethylated promoter was not associated with a higher frequency of hTERT expression. A low correlation between hTERT protein expression and methylation was verified in gastric cancer samples. There was a clear difference in the frequency of hTERT expression and methylation within tumoral and non-tumoral tissues. Methylation status and telomerase expression may be useful for the diagnosis of gastric cancer and may have an impact on the anti-telomerase strategy for cancer therapy.
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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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    Study of hTERT and Histone 3 Mutations in Medulloblastoma
    (Karger, 2017) Viana-Pereira, Marta; Almeida, Gisele Caravina; Stávale, João Norberto [UNIFESP]; Malheiro, Susana [UNIFESP]; Clara, Carlos; Lobo, Patricia; Pimentel, Jose; Reis, Rui Manuel
    Hotspot activating mutations of the telomerase reverse transcriptase (hTERT) promoter region were recently described in several tumor types. These mutations lead to enhanced expression of telomerase, being responsible for telomere maintenance and allowing continuous cell division. Additionally, there are alternative telomere maintenance mechanisms, associated with histone H3 mutations, responsible for disrupting the histone code and affecting the regulation of transcription. Here, we investigated the clinical relevance of these mechanistically related molecules in nnedulloblastoma. Sixty-nine medulloblastomas, formalin fixed and paraffin embedded, from a cohort of patients aged 1.5-70 years, were used to investigate the hotspot mutations of the hTERT promoter region, i.e. H3F3A and HIST1H3B, using Sanger sequencing. We successfully sequenced hTERT in all 69 medulloblastoma samples and identified a total of 19 mutated cases (27.5%). c.-124:G>A and c.-146:G>A mutations were detected, respectively, in 16 and 3 samples. Similar to previous reports, hTERT mutations were more frequent in older patients (p < 0.0001), being found only in 5 patients <20 years of age. In addition, hTERT-mutated tumors were more frequently recurrent (p = 0.026) and hTERT mutations were significantly enriched in tumors located in the right cerebellar hemisphere (p = 0.039). No mutations were found on the H3F3A or HIST1H3B genes. hTERT promoter mutations are frequent in medulloblastoma and are associated with older patients, prone to recurrence and located in the right cerebellar hemisphere. On the other hand, histone 3 mutations do not seem to be present in nnedulloblastoma. (C) 2016 S. Karger AG, Basel