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- ItemSomente MetadadadosExpression Profiling of Cell Cycle Regulatory Proteins in Oropharyngeal Carcinomas Using Tissue Microarrays(Int Inst Anticancer Research, 2010-05-01) Ribeiro, Daniel Araki [UNIFESP]; Nascimento, Fábio Dupart [UNIFESP]; Fracalossi, Ana Carolina Cuzzuol [UNIFESP]; Gomes, Thiago Simao [UNIFESP]; Oshima, Celina Tizuko Fujiyama [UNIFESP]; Franco, Marcello Fabiano de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Aim: The aim of this study was to investigate the expressions of cell cycle regulatory proteins such as p53, p16, p21, and Rb in squamous cell carcinoma of the oropharynx and their relation to histological differentiation, staging of disease, and prognosis. Patients and Methods: Paraffin blocks from 21 primary tumors were obtained from archives of the Department of Pathology, Paulista Medical School, Federal University of Sao Paulo, UNIFESP/EPM. Immunohistochemistry was used to detect the expression of p53, p16, p21, and Rb by means of tissue microarrays. Results: Expression of p53, p21, p16 and Rb was not correlated with the stage of disease, histopathological grading or recurrence in squamous cell carcinoma of the oropharynx. Conclusion: Taken together, our results suggest that p53, p16, p21 and Rb are not reliable biomarkers for prognosis of the tumor severity or recurrence in squamous cell carcinoma of the oropharynx as depicted by tissue microarrays and immunohistochemistry.
- ItemSomente MetadadadosGrape juice concentrate modulates p16 expression in high fat diet-induced liver steatosis in Wistar rats(Informa Healthcare, 2012-04-01) Ferreira, Andressa Orlandeli [UNIFESP]; Boiago Golluecke, Andrea Pittelli; Noguti, Juliana [UNIFESP]; Pereira da Silva, Victor Hugo [UNIFESP]; Hojo Yamamura, Elsa Tiemi; Ribeiro, Daniel Araki [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Catolica SantosPurpose: the goal of this study was to investigate whether subchronic treatment with grape juice concentrate is able to protect the liver from high fat diet injury in rats. the effects of grape juice concentrate treatment on histopathological changes, and immunohistochemistry for p53, p16 and p21 were evaluated.Methods: Male Wistar rats (n = 18) were distributed into three groups: group 1: negative control; group 2: cholesterol at 1% (w/w) in their diet, treated during 5 weeks; and group 3: cholesterol at 1% in their chow during 5 weeks, and grape juice concentrate at 222 mg per day in their drinking-water in the last week only.Results: the results pointed out that treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in the cholesterol-exposed group when compared to group 2. However, grape juice concentrate was able to modulate p16 immunoexpression when compared to high fat diet group. p53 and p21 did not show any significant statistical differences among groups.Conclusion: Taken together, our results suggest that subchronic grape juice concentrate administration was able to modulate cell cycle control by downregulation of p16 immunoexpression in high fat diet-induced liver steatosis in rats.
- ItemSomente MetadadadosImmunocytochemical expression of p16(INK4A) and Ki-67 in cytologically negative and equivocal Pap smears positive for oncogenic human papillomavirus(Lippincott Williams & Wilkins, 2005-04-01) Longatto, A.; Utagawa, M. L.; Shirata, N. K.; Pereira, SMM; Namiyama, G. M.; Kanamura, C. T.; Santos, G. D.; Oliveira, M. A. de; Wakamatsu, A.; Nonogaki, S.; Roteli-Martins, C.; di Loreto, C.; Ferraz, MDMD; Maeda, MYS; Alves, VAF; Syrjanen, K.; Adolfo Lutz Inst; Univ Minho; Universidade Federal de São Paulo (UNIFESP); Leonor Mendes Barros Hosp; Universidade de São Paulo (USP); Turku UnivThis study was designed to analyze the cross-sectional comparison of the p16(INK4A) and Ki-67 immunocytochemical expression in negative and equivocal (atypical squamous cells of undetermined significance (ASC-US)) liquid-based cytology (LBQ samples testing positive for high-risk human papillomavirus (HPV) types with HC2 assay or polymerase-chain reaction (PCR). A series of 199 consecutive LBC specimens derived from the same number of women participating in the ongoing Latin American Screening Study at Leonor Mendes de Barros Hospital, São Paulo, were analyzed using immunocytochemistry for expression of p16(INK4A) and Ki-67 in negative and equivocal LBC samples testing positive for high-risk HPV types with hybrid capture 11 test (HC2) or PCR. All patients with at least one test positive (cytology, PCR, and/or HC2) were followed each 6 months for 3 years. the follow-up procedure consisted of visual examination, colposcopic inspection, cytology, and HC2 assay. Among the negative cytologic samples, 101 were HPV-positive and 55 HPV-negative. of the HPV-positive group, 59 of 101 cases (58.4%) were positive for both p16 and M67 inummostaining, and 17 of 101 (16.8%) were negative for both. the proportion of Ki-67-positivity increased almost in parallel with the increasing grade of p16-positivity (p = 0.0001 for linear trend). in the HPV-negative group, both markers were negative in 41 of 55 cases (74.5%), and no statistical relationship was observed between the two markers (Pearson, p = 0.595). HPV-positive ASC-US samples demonstrated a simultaneous positive immunoreaction for p 16 and Ki67 in 11 of 16 cases (68.7%), whereas 3 (18.7%) were concurrently negative. the relationship between the two markers was of borderline significance (Pearson, p = 0.053), but no linear relationship was found between the graded p16 and Ki-67 expression (p = 0.065 for linear trend). in the HPV-negative ASGUS group, there was no statistical association between the graded p16 and Ki-67 positivity (Pearson, p = 0.28 1). After 36 months of follow-up of the ASC-US patients, 6 women still displayed ASC-US smear, of which 4 of 6 were HPV-positive and expressed both p16 and Ki-67 markers. Two of 43 ASC-US smears had high-grade intraepithelial lesion (2.3%). All of those were positive for HPV, p16 and Ki-67. Patients with ASC-US diagnosis and positive high-risk HPV status and positive for p16(INK4A) Ki67 should be carefully observed to exclude occurrence of a squamous intraepithelial lesion. the combination of these two markers can be a useful implement for management of women with equivocal cytology.
- ItemSomente MetadadadosNo mutations found in exon 2 of gene p16CDKN2A during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide(Springer, 2009-02-01) Minicucci, Eliana Maria; Silva, Glenda Nicioli da; Ribeiro, Daniel Araki [UNIFESP]; Favero Salvadori, Daisy Maria; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)The medium-term tongue carcinogenesis assay is a useful model for studying oral squamous cell carcinomas phase by phase. the present study aimed to investigate mutations in exon 2 of gene p16CDKN2A during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO) using direct DNA-sequencing method. A total of 30 male Wistar rats were treated with 4-nitroquinoline 1-oxide (4NQO) in drinking water for 4, 12, and 20 weeks at 50 ppm dose. Ten animals were used as negative control. No histopathological changes in tongue epithelia were observed among controls or in the group treated for 4 weeks with 4NQO. Following 12-week treatment, hyperplasia and epithelial dysplasia were found in mild and moderate forms. At 20 weeks, the tongue presented moderate and/or severe oral dysplasia and squamous cell carcinoma, with squamous cell carcinoma in the majority of animals. No mutations were found in any experimental period evaluated that corresponded to normal oral mucosa, hyperplasia, dysplasia and squamous cell carcinomas. Taken together, our results suggest that p16CDKN2A mutations in exon 2 are not involved in the multistep tongue carcinogenesis of Wistar rats induced by 4NQO.
- ItemSomente Metadadadosp16 gene methylation lacks correlation with angiogenesis and prognosis in multiple myeloma(Elsevier B.V., 2005-05-26) Ribas, C.; Colleoni, GWB; Felix, R. S.; Silva, MRR; Caballero, O. L.; Brait, M.; Bordin, J. O.; Universidade Federal de São Paulo (UNIFESP); Ludwig Inst Canc ResMethylation of p16 gene is a relatively frequent molecular finding in multiple myeloma (MM), but its clinical implication is disputable. Cell cycle regulators are now recognized as active in the control of angiogenesis, which is an integral component of pathogenesis and a target for new treatment modalities of this disease. On such background, we focused on determining whether loss of p16 function by methylation could be associated with increased angiogenesis and VEGF expression, and the prognostic relevance of p16 methylation in 50 untreated, newly diagnosed MM patients. Thirty-one percent (13/42) of 42 patients assessable for p16 gene methylation showed to be methylation-positive. High-angiogenesis was present in 73% of cases, but methylation of the p16 gene did not associate with angiogenesis or with VEGF expression. Also, p16 methylation did not show prognostic relevance or correlation with the clinical and laboratory parameters of prognostic significance in univariate analysis. PI 6 immunoexpression presented only a faint agreement with the molecular study. Therefore, p 16 methylation seems to have no correlation with angiogenesis and VEGF expression, neither with overall and event-free survival in MM patients. Besides, P16 immunohistochemistry seems inadequate to substitute the molecular study of methylation in this type of tumor cells. Additional studies are needed to clarify the correspondence between the epigenetic alteration of the p16 gene and its protein immunexpression, and the clinical relevance of p16 methylation in MM patients. (c) 2004 Elsevier Ireland Ltd. All rights reserved.