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- ItemAcesso aberto (Open Access)Adenomas hipofisários: relação entre invasividade e índice proliferativo tumoral(Academia Brasileira de Neurologia - ABNEURO, 2000-12-01) Tella Jr, Oswaldo Inácio de [UNIFESP]; Herculano, Marco Antonio [UNIFESP]; Delcelo, Rosana [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)We evaluated clinically, radiologically and surgically a series of 76 pituitary adenomas. All cases were assessed immunohistochemically and in 49 patients the PCNA monoclonal antibody was measured. The most frequent types found were the bihormonal adenomas, followed by prolactinomas and non secreting adenomas. The bihormonal adenomas, non secreting adenonas and the sub unit alfa producing adenomas were proportionally more invase as determined by radiological criteria (CTscan or MRI). In 59 patients a transphenoidal approach was used, six cases were operated on transcranially and in 11 patients we used a combination of both approach. Total resection were achieved in 32 cases, most of which were microadenomas, in 15 cases the resection was subtotal and partial in 29 cases. Diabetes insipidus was the most frequent endocrine complication. It was observed that secreting adenomas tend to be associated with an increased PCNA and invasive adenomas correlated with PCNA 3 and 4. An improvement in vision was observed in 85% of macroadenomas seen after a total, subtotal or partial resection.
- ItemSomente MetadadadosAdrenocorticotropin-producing pituitary carcinoma with expression of c-erbB-2 and high PCNA index: A comparative study with pituitary adenomas and normal pituitary tissues(Humana Press Inc, 1998-03-01) Nose-Alberti, V; Mesquita, MIS; Martin, L. C.; Kayath, M. J.; Universidade Federal de São Paulo (UNIFESP)Pituitary carcinomas are very rare neoplasms with a poor prognosis. We report a case of Cushing's disease resulting from a pituitary carcinoma in a ZZ-yr-old female, who died of massive hepatic failure. At autopsy, there was invasion of the parasellar structures and vasculature by the tumor, which stained positively only for ACTH. There were two metastatic nodules in the liver, which also stained positively for ACTH. When compared to other cases of Cushing's disease (n = 52), other pituitary adenomas (n = 292), and normal pituitary tissues (n = 21), the pituitary carcinoma was the only one with c-erbB-2 membrane staining in both the sellar-located tissue and liver metastasis. C-erbB-2 staining was present in the cytoplasm of a variable number of cells in 40% of the invasive adenomas (n = 103), while only 1.2% of the noninvasive tumors (n = 241) expressed this protein (p < 0.001). No particular immunohistological type preferentially expressed this protein. in normal pituitary tissues, 10% of the cells expressed cytoplasmic c-erbB-2. A higher index of proliferating cell nuclear antigen (PCNA) in the primary tumor and liver metastasis (10%) was also found compared to other ACTH-secreting adenomas (invasive, 3.4 +/- 1.9% vs 1.7 +/- 1.5% in noninvasive) and other pituitary tumors (invasive, 2.9 +/- 1.5% vs 1.5 +/- 1.3% in noninvasive). the PCNA index was significantly higher in invasive tumors than in noninvasive adenomas (p = 0.004). PCNA staining was negative in normal pituitary tissues. Staining for p53, pRB and p(21ras) was negative in the carcinoma and liver metastasis. We suggest that the c-erbB-2 membrane pattern and a higher PCNA index may indicate a worse prognosis in adenohypophyseal neoplasia.
- ItemAcesso aberto (Open Access)Análise histopatológica e imuno-histoquímica (antígeno nuclear de proliferação celular) de pacientes com carcinoma cervical invasor antes e após radioterapia e cirurgia(Associação Médica Brasileira, 2002-03-01) Rosal, Marta Alves [UNIFESP]; Goncalves, Wagner Jose [UNIFESP]; Alves, Maria Teresa de Seixas [UNIFESP]; Baracat, Edmund Chada [UNIFESP]; Lima, Geraldo Rodrigues de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)OBJECTIVE: To search for residual disease and to analyse the Proliferating Cellular Nuclear Antigen (PCNA) status, in patients with cervical squamous cell carcinoma, treated with both radiotherapy and surgery. METHODS: Histological slides from 16 patients with uterine cervix cancer, treated between April 1986 and August 1998, with preoperative radiotherapy and surgery, were reviewed. PCNA imunohistochemical reactivity of these samples was evalued, using the IMAGELAB 2.3 computer image analysis system. RESULTS: Residual carcinoma were found in eight cases (50%) and no malignant features was found in eight cases (50%). The mean value of PCNA before radiotherapy in patients with residual cancer was 61.56% and in cases without residual cancer was 60%. Its expression before radiotherapy was between 27.91% and 89.93% (60% average), while after radiotherapy it varied between 55.80% and 86.73% (74% average). CONCLUSIONS: The association between preoperative radiotherapy followed by surgery is adequated to treat patients with cervical cancer, when radical treatment is not possible. Meanwhile, exclusive radiotherapy shows a significant failure rate, detected after surgery and PCNA analysis.
- ItemAcesso aberto (Open Access)Analysis of p53 expression and proliferative assessment using PCNA in localized prostate carcinoma(Associação Brasileira de Divulgação Científica, 1999-03-01) Leite, Kátia Ramos Moreira [UNIFESP]; Srougi, Miguel [UNIFESP]; Nesrallah, Luciano João [UNIFESP]; Camara-Lopes, Luiz H [UNIFESP]; Hospital Sírio Libanês; Universidade Federal de São Paulo (UNIFESP)The surgical specimens from 51 men submitted to radical prostatectomy for localized prostate cancer were examined by immunohistochemistry using proliferation cell nuclear antigen (PCNA) monoclonal antibody to evaluate the proliferative index (PI). The relationship between PI, biological variables and p53 protein expression was evaluated by immunohistochemistry. PI was low in invasive localized prostate carcinoma (mean, 12.4%) and the incidence of PCNA-positive cells was significantly higher in tumors with p53 expression (P = 0.0226). There was no statistical difference in PCNA values when biological parameters such as Gleason score, tumor volume, extraprostatic involvement, seminal vesicle infiltration or lymph node metastasis were considered. We conclude that proliferative activity is usually low in prostate carcinoma but is correlated with p53 immune staining, indicating that p53 is important in cell cycle control in this neoplasm.
- ItemSomente MetadadadosApoptosis, PCNA and p53 in hepatocellular carcinoma(H G E Update Medical Publishing S A, 2002-07-01) Paiva, C.; Oshima, Celina Tizuko Fujiyama [UNIFESP]; Lanzoni, Valeria Pereira [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Background/Aims: The regulation of cell number is present in normal tissues but is lost in malignant neoplasms. The real :meaning of these alterations is not well known. Apoptosis is the programmed cell death. p53, a tumor supressor gene, has an important function in DNA repair and in regulation of apoptosis. Mutations of p53 were described in malignant tumors and can be the cause of the alterations of this balance. Proliferating cell nuclear antigen is an auxiliary protein present during G1-late phase and S phase.The aim of this study was to compare cell proliferation, apoptosis and expression of p53 in hepatocellular carcinoma.Methodology: Fifteen patients with hepatocellular carcinoma were included. Ten patients were men. The mean age of the patients was 55.53 years old. Cirrhosis was positive in nine patients, 5 were HBsAg positive and none were anti-HCV positive. The mean level of AST and ALT were respectively, 62.79 and 50.64. Formalin-fixed and paraffin-embedded tissues from these patients were examined retrospectively. Apoptosis were measured by counting the number of apoptotic bodies in 500 tumoral cells. The expression of p53 oncogene and the PCNA were determined by immunohistochemical method, using avidin-biotin method (DAKO). The p53 were considered positive when the number of positive nuclei was more than 5% of the tumoral cells. The proliferative activity was determined by proliferating cell nuclear antigen labeling index.Results: The proliferating cell nuclear antigen-labeling index ranged from 0.48 and 0.95 (mean: 0.82). The p53 was positive in five patients. The number of apoptotic bodies counted ranged from 0 to 15 (mean: 4.20). There were no differences among p53 and the mean levels of proliferating cell nuclear antigen labeling index or p53 and the number of apoptotic bodies.Conclusions: A high index of proliferation has been shown in the patients studied. Positivity of p53 was seen in less than a half of the patients (35.71%). The index of apoptotic bodies observed was very low. Our results suggest that high-grade proliferation is not associated with increase of apoptosis in hepatocellular carcinoma.
- ItemAcesso aberto (Open Access)Desdiferenciação do câncer da próstata após terapia antiandrogênica(Associação Médica Brasileira, 2005-04-01) Moritz, Rogério [UNIFESP]; Srougi, Miguel [UNIFESP]; Ortiz, Valdemar [UNIFESP]; Leite, Kátia Ramos Moreira [UNIFESP]; Nesrallah, Luciano [UNIFESP]; Dall'oglio, Marcos [UNIFESP]; Sant'anna, Alexandre Crippa [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)BACKGROUND: Neoadjuvant androgen deprivation in prostate cancer induces tumor volume regression but does not improve outcome of the patient. A possible explanation for this phenomenon could be an increase of the residual tumor aggressiveness brought about by antiandrogen therapy. The purpose of the present study was to evaluate the frequency of tumor dedifferentiation following androgen blockade in prostate cancer and to determine if the remaining tumor shows signs of increased aggressiveness. METHODS: Thirty patients bearing locally advanced prostate cancer (stages T2c - T3) were submitted to neoadjuvant anti-androgenic therapy during four months followed by radical prostatectomy. Gleason scores from biopsy and surgical specimens were compared. Furthermore, the cell proliferation index was evaluated by immunohistochemistry assay for PCNA, tests with strong nuclear staining were considered positive. The percentage of positive nuclei, counted in 500 cells, was determined in several categories of the Gleason score from surgical specimens. RESULTS: In 11(37%) surgical specimens the Gleason score was equal or lower than that found in the biopsy and in 19 (63%) the total score was higher in the surgical specimens (p<0.05). The median of PCNA expression was 4.5%, 10%, 12% and 14% in Gleason scores 2-4, 5-6,7 and 8-10, respectively (p>0.05). The median of cell proliferation indexes was 9% for glandular or specimen confined tumors and was 17% for extraprostatic tumors (p<0.05). CONCLUSION: The lower Gleason score was found in almost 2/3 of patients submitted to antiandrogen therapy. However, the cell proliferation index measured by PCNA was the same for tumors with lower or higher Gleason scores. It seems that cell dedifferentiation seen after neoadjuvant androgen deprivation represents a mere morphologic phenomenon and not a real increase in tumor aggressiveness.
- ItemAcesso aberto (Open Access)Efeitos da melatonina na histomorfologia, na expressão dos receptores esteroídicos, do VEGF e do PCNA em ovários de ratas pinealectomizada(Universidade Federal de São Paulo (UNIFESP), 2009) Romeu, Lucrecia Regina Gomes [UNIFESP]; Motta, Eduardo Leme Alves da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
- ItemSomente MetadadadosEffect of a half dose of tamoxifen on proliferative activity in normal breast tissue(Elsevier B.V., 1999-10-01) Bernardes, JRM; Nonogaki, S.; Seixas, M. T.; Lima, G. R. de; Baracat, E. C.; Gebrim, L. H.; Universidade Federal de São Paulo (UNIFESP)Objectives: To investigate the proliferative activity of the mammary gland epithelium and plasma levels of progesterone, estradiol, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) in premenopausal women treated with 10 and 20 mg of tamoxifen (TAM) for 22 days. Patients and methods: A randomized double-blind study was performed with 43 premenopausal women with a diagnosis of fibroadenoma of the breast. the patients were divided into three groups: A (n = 15, placebo); B (n = 15, TAM 10 mg/day) and C (n = 13, TAM 20 mg/day). They started taking an oral dose of TAM or placebo on the very first day of the menstrual cycle. Lumpectomy was performed on the 22nd day of therapy. Normal breast tissue samples were collected during surgery, immediately immersed in 10% buffered formalin, processed for routine histology and immunohistochemistry for proliferating cell nuclear antigen (PCNA) detection. Two peripheral blood samples were collected, both on the 22nd day of the menstrual cycle, in order to evaluate the hormone levels. PCNA expressing epithelial cells were quantified by using a digital program Kontron Image System KS-300 in 1000 cells (400 x). Results: the percentage of cells expressing PCNA was significantly higher in the group receiving placebo (group A, 50.3%) when compared to groups receiving TAM 10 or 20 mg/day (group B, 24.1%; and group C, 23.2%, respectively) (P < 0.001). Differences between groups B and C were not significant. Levels of progesterone, estradiol and SHBG were significantly higher in B and C groups compared to group A. Increasing concentrations of FSH (P < 0.0045) and lower levels of prolactin (P < 0.0055) were only found in the group receiving 20 mg/day of TAM (group C). Conclusions: A 22-day TAM therapy, either with 10 or 20 mg/day, significantly reduced the PCNA expression and therefore the proliferative activity of the normal human breast tissue. Increasing levels of estradiol, progesterone and SHBG were associated with TAM therapy at 10 or 20 mg/day. However, a significant change of the level of FSH and prolactin was reached only with a 20-mg/day dose. (C) 1999 International Federation of Gynecology and Obstetrics.
- ItemSomente MetadadadosThe effect of tamoxifen on the proliferative activity of fibroadenomas(Elsevier B.V., 2002-05-01) Bernardes, JRM; Seixas, M. T.; Gebrim, L. H.; Universidade Federal de São Paulo (UNIFESP)
- ItemSomente MetadadadosEffects of melatonin on histomorphology and on the expression of steroid receptors, VEGF, and PCNA in ovaries of pinealectomized female rats(Elsevier B.V., 2011-03-01) Romeu, Lucrecia Regina Gomes [UNIFESP]; Motta, Eduardo Leme Alves da [UNIFESP]; Maganhin, Carla Cristina [UNIFESP]; Oshima, Celina Tizuko Fujiyama [UNIFESP]; Fonseca, Marcelle Cavalcante [UNIFESP]; Barrueco, Karina Fonseca [UNIFESP]; Simões, Ricardo Santos [UNIFESP]; Pellegrino, Renata [UNIFESP]; Baracat, Edmund Chada [UNIFESP]; Soares Júnior, José Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objective: To evaluate the effect of melatonin both on the ovaries of pinealectomized female rats through histomorphometric analysis and on steroid receptors, proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF) expression.Design: Experimental study.Setting: Federal University of São Paulo, Brazil.Animal(s): Forty female rats.Intervention(s): Forty rats were divided equally into four groups: GI-vehicle without surgery; GII-surgery without removal of the pineal gland (sham); GIII-pinealectomized with vehicle; and GIV-pinealectomized with melatonin treatment. After treatment for 3 consecutive months, the animals were killed and their ovaries removed for analysis.Main Outcome Measure(s): Estrogen and progesterone receptors, histologic and immunohistochemical analysis.Result(s): the GIII samples presented signals of proliferation on ovarian surface epithelium and interstitial cells as well as high expressions of PCNA and VEGF in those structures compared with GI, GII, and GIV. Also, the levels of progesterone receptor (fmol/g) in ovaries of GIII (250.6 +/- 32.4) were significantly lower than in those of GI (429.0 +/- 23,8), GII (442.3 +/- 30.2), and GIV (564.1 +/- 78.7). the levels of progesterone in GIII were superior to those in GI, GII, and GIV.Conclusion(s): Our findings suggest that melatonin may attenuate proliferation in ovarian structures and increase the number of luteal bodies as well as the levels of progesterone receptor. (Fertil Steril (R) 2011;95:1379-84. (C)2011 by American Society for Reproductive Medicine.)
- ItemSomente MetadadadosFTY720 and lung tumor development(Elsevier B.V., 2009-06-01) Antunes Salinas, Natalia Regina [UNIFESP]; Oshima, Celina Tizuko Fujiyama [UNIFESP]; Cury, Patricia Maluf; Cordeiro, Jose Antonio; Bueno, Valquiria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)FTY720 has been shown to prevent cancer development in experimental models but there is no report whether this beneficial effect is associated with the time point of the drug administration. Lung adenoma was induced in mice by urethane injection followed by different periods of FTY720 administration in order to evaluate lung tumor development. BALB/c mice received urethane intraperitoneally in two doses of 1.5 g/kg and were submitted to five daily doses of FTY720 (1 mg/kg/day) starting just after urethane injection (G2 n = 5), 4 weeks after urethane injection (G3 n = 10), 8 weeks after urethane injection (G4 n = 10) and no FTY720 administration (G1 n = 5). Twenty-four weeks after urethane administration mice were evaluated for the number of leukocyte in blood, lymphocytes in spleen, and lungs were evaluated for changes in histology, PCNA and VEGF expression. Lung nodules were present in higher numbers both in non treated (G1; 0.0-7.0) and FTY720 treated 8 weeks after urethane injection (G4: 0.0-6.0). G4 Group also presented the highest number of papillary nodules. G1 and G4 groups presented the lower number of splenocytes and neutrophils. in early time FTY720 treated mice (G2) we observed a slight decrease in PCNA staining and also the lower percentage of VEGF intense staining. Therefore, our data suggest that the benefits of FTY720 treatment are time-dependent and when administered in early periods after lung tumor induction this drug could impair cancer development. (C) 2008 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosStudy of immunohistochemical expression of insulin-like growth factor I and proliferating cell nuclear antigen in thyroid gland papillary carcinoma and its metastasis(Wiley-Blackwell, 1999-12-01) Silva, G. B.; Maciel, Rui Monteiro de Barros [UNIFESP]; Takahashi, Mirian Hideco [UNIFESP]; Alberti, Vania Nose [UNIFESP]; Castro, IV; Saldiva, Paulo Hilário Nascimento [UNIFESP]; Durazzo, M. D.; Ferraz, A. R.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Background. Several tumor factors are associated with papillary thyroid cancer. Most studies do not compare the expressions of these factors in the primary tumors and in their associated cervical metastasis.Methods. Paraffin sections of 20 patients with papillary carcinoma of the thyroid gland with lymph node metastasis were studied. The presence and distribution of insulin-like growth factor I (IGF-I) and proliferating cell nuclear antigen (PCNA) was analyzed, through immunohistochemical technique, in both primaries and lymph node metastasis. The results were correlated with clinical-pathologic data (sex, age, size of primary, multicentricity, thyroid capsule invasion, lymphatic and blood vessels invasion, development of distant metastasis, and associated thyroid diseases).Results. The qualitative analysis showed the reaction for IGF-I was present in more than 90% of the neoplastic cells in both primaries and lymph node metastasis. No correlation with the clinical-pathlogical features was observed. Regarding the PCNA, the mean percentage of nuclei stained showed no statistical difference between primaries and metastasis (p = 0.598). Except for age, clinicopathologic data had no influence on the mean percentage of nuclei stained. A correlation was verified between the percentage of cells stained by PCNA in primary tumors and the patients' age (p < 0.01).Conclusions. The expressions of these tumor factors are equally intense for both primary and metastatic tissue in papillary thyroid cancer. Despite the small size of the sample, the expressions of ICE-I and PCNA could not be associated to clinical-pathologic features, except for the age. As patients over 40 years old had higher expression of PCNA, this marker may have prognostic significance for patients with papillary thyroid cancer. (C) 1999 John Wiley & Sons, Inc. Head Neck 21: 723-727, 1999.
- ItemAcesso aberto (Open Access)Trypanosoma cruzi DNA replication includes the sequential recruitment of pre-replication and replication machineries close to nuclear periphery(Taylor & Francis Inc, 2011-03-01) Calderano, Simone Guedes [UNIFESP]; Godoy, Patricia Diogo de Melo [UNIFESP]; Motta, Maria Cristina M.; Mortara, Renato Arruda [UNIFESP]; Schenkman, Sergio [UNIFESP]; Elias, Maria Carolina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Rio de Janeiro (UFRJ)In eukaryotes, many nuclear processes are spatially compartmentalized. Previously, we have shown that in Trypanosoma cruzi, an early-divergent eukaryote, DNA replication occurs at the nuclear periphery where chromosomes remain constrained during the S phase of the cell cycle. We followed Orc1/Cdc6, a pre-replication machinery component and the proliferating cell nuclear antigen (PCNA), a component of replication machinery, during the cell cycle of this protozoon. We found that, at the G(1) stage, TcOrc1/Cdc6 and TcPCNA are dispersed throughout the nuclear space. During the G(1)/S transition, TcOrc1/Cdc6 migrates to a region close to nuclear periphery. At the onset of S phase, TcPCNA is loaded onto the DNA and remains constrained close to nuclear periphery. Finally, in G(2), mitosis and cytokinesis, TcOrc1/Cdc6 and TcPCNA are dispersed throughout the nuclear space. Based on these findings, we propose that DNA replication in T. cruzi is accomplished by the organization of functional machineries in a spatial-temporal manner.