Navegando por Palavras-chave "Prostate cancer"

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    Ação de inibidores recombinantes de Bauhinia sobre a linhagem celular de câncer de próstata
    (Universidade Federal de São Paulo (UNIFESP), 2009-02-27) Diniz, Paula Malloy Mota [UNIFESP]; Oliva, Maria Luiza Vilela [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Prostate cancer occurs in Brazil with high rates of incidence and mortality. Invasion from the primary tumor and metastasis result in poorer prognosis. Diverse classes of protein play a role for the progression of metastasis. Tissue kallikreins, e.g., hK3 (PSA) and integrins are directly related to this neoplasia, as well as, in cell adhesion, differentiation and cellular proliferation processes. Compounds that interfere in these processes are targeted for investigation. In this work, using prostate cancer cellular line PC-3, the effects of two recombinant inhibitors of Bauhinia sp. seeds were studied, the Bauhinia bauhinioides kallikrein inhibitor (rBbKI) and the modified rBbKIm, in which the signal motif RGD, present in the inhibitor BrTI from B. rufa, was inserted. The rBbKI and rBbKIm has shown different effects on cell PC3 viability, being rBbKIm more efficient than rBbKI and inhibiting 70% of PC3 cell viability (50 μM, 72h), in all the conditions analyzed. The rBbKIm has interfered in the cell cycle of PC-3, increasing the number of cells in apoptosis and decreasing the number of cells in G2 face (mitosis). In the cell adhesion, rBbKIm (25 μM), containing the adhesion motif RGD, has inhibited approximately 30% of the PC-3 adhesion on fibronectin, in contrast to rBbKI that has caused 20% of cell adhesion. The confocal microscopy analysis has shown that rBbKI and rBbKIm interact with cell membrane. The results indicate that the inhibitors act by different mechanisms, which still to be established.
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    Acurácia na reprodutibilidade do posicionamento diário de pacientes submetidos a radioterapia conformada (RT3D) para câncer de próstata
    (Colégio Brasileiro de Radiologia e Diagnóstico por Imagem, 2010-08-01) Giordani, Adelmo José [UNIFESP]; Dias, Rodrigo Souza [UNIFESP]; Segreto, Helena Regina Comodo [UNIFESP]; Segreto, Roberto Araujo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    OBJECTIVE: To evaluate the reproducibility of daily patients' setup in 3D conformal radiotherapy for prostate cancer. MATERIALS AND METHODS: The present study evaluated a total of 960 radiological images (anterior and lateral views) of 120 patients submitted to conformal radiotherapy for prostate cancer with the isocentric technique. A 6 MV particle accelerator was utilized in the process. A specific protocol for prostate radiotherapy planning and treatment was applied, with the patients placed in supine position, hands on the chest and legs placed on and appropriate support. Daily, the patients were positioned according to previously made skin markings in alignment with the in-room laser. The portal images were compared with digitally reconstructed radiographies (DRR) in the Eclipse treatment planning system based on the tomographic images. Radiography was performed at the first day, and weekly afterwards until the treatment was completed. RESULTS: The following average position shifts were observed: 1.99 ± 1.25 mm craniocaudally, 1.37 ± 0.84 mm laterally, and 1.94 ± 1.10 mm anteroposteriorly. CONCLUSION: The use of specific protocols for patients' setup is feasible in the clinical practice, allowing appropriate reproducibility and quick correction of possible errors in conformal radiotherapy for prostate cancer.
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    Análise comparativa dos histogramas de dose e volume entre planejamentos tridimensionais conformados e convencionais não conformados na radioterapia do câncer de próstata
    (Colégio Brasileiro de Radiologia e Diagnóstico por Imagem, 2009-04-01) Feitosa, Sílvia Moreira [UNIFESP]; Giordani, Adelmo José [UNIFESP]; Dias, Rodrigo Souza [UNIFESP]; Segreto, Helena Regina Comodo [UNIFESP]; Segreto, Roberto Araujo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    OBJECTIVE: The present study was aimed at comparing conformal and non-conformal radiotherapy plans designed for patients with prostate cancer, by analyzing radiation doses in target volumes and organs at risk. MATERIALS AND METHODS: Radiotherapy plans for 40 patients with prostate cancer were analyzed. Conformal, conformal isocentric and non-conformal plans utilizing the source-surface distance were simulated for each of the patients for comparison of radiation dose in target volumes and organs at risk. For comparison purposes, dose-volume histograms for target volumes and organs at risk were analyzed. RESULTS: Median doses were significantly lower in the conformal planning, with 25%, 40% and 60% volumes in the rectum and 30% and 60% in the bladder. The median doses were significantly lower in the conformal planning analyzing the right and left coxofemoral joints. Maximum, mean and median doses in the clinical target volume and in the planned target volume were significantly higher in the conformal planning. CONCLUSION: The present study has demonstrated that the conformal radiotherapy planning for prostate cancer allows the delivery of higher doses to the target volume and lower doses to adjacent healthy tissues.
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    ANKHD1, a novel component of the Hippo signaling pathway, promotes YAP1 activation and cell cycle progression in prostate cancer cells
    (Elsevier B.V., 2014-06-10) Machado-Neto, Joao Agostinho; Lazarini, Mariana; Favaro, Patricia [UNIFESP]; Franchi, Gilberto Carlos; Nowill, Alexandre Eduardo; Olalla Saad, Sara Teresinha; Traina, Fabiola; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    ANKHD1 is a multiple ankyrin repeat containing protein, recently identified as a novel member of the Hippo signaling pathway. the present study aimed to investigate the role of ANKHDI in DU145 and LNCaP prostate cancer cells. ANKHD1 and YAP1 were found to be highly expressed in prostate cancer cells, and ANKHD1 silencing decreased cell growth, delayed cell cycle progression at the S phase, and reduced tumor xenograft growth. Moreover, ANKHD1 knockdown down-regulated YAP1 expression and activation, and reduced the expression of CCNA2, a YAP1 target gene. These findings indicate that ANKHD1 is a positive regulator of YAP1 and promotes cell growth and cell cycle progression through Cyclin A upregulation. (C) 2014 Elsevier Inc. All rights reserved.
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    Avaliação da resposta bioquímica no câncer inicial de próstata: experiência uninstitucional comparando teleterapia exclusiva ou associada à braquiterapia de alta taxa de dose
    (Colégio Brasileiro de Radiologia e Diagnóstico por Imagem, 2004-08-01) Castro, Douglas Guedes De; Pellizzon, Antônio Cássio Assis; Chen, Michael Jenwei; Nishimoto, Inês Nobuko; Maia, Maria Aparecida Conte; Novaes, Paulo Eduardo Ribeiro Dos Santos; Fogaroli, Ricardo César; Ferrigno, Robson; Salvajoli, João Victor [UNIFESP]; Hospital do Câncer A.C. Camargo Departamento de Radioterapia; Universidade de São Paulo (USP); Hospital do Câncer A.C. Camargo Centro de Estudos; Universidade Metodista de Santos Faculdade de Medicina; Hospital do Câncer A.C. Camargo; Universidade Federal de São Paulo (UNIFESP); Faculdade de Medicina de Marília
    OBJECTIVE: To compare the biochemical response in patients with locally advanced prostate cancer treated with external beam radiation therapy alone or in combination with conformal brachytherapy boost. MATERIALS AND METHODS: From November 1997 to January 2000, 74 patients received 45 Gy of pelvic external irradiation and four were treated with high dose rate iridium-192 conformal boost implants of 4 Gy each (BT). These were compared with 29 other patients treated with 45 Gy of pelvic external irradiation followed by a 24 Gy of bilateral ARC boost (RT) from October 1996 to February 2000. Some patients received neoadjuvant androgen deprivation therapy. Three-year actuarial biochemical control rates (BC3) and pretreatment biochemical response predictors such as prostate-specific antigen pretreatment (PSAi), Gleason score (GS) and clinical stage (CS), were evaluated. RESULTS: Median follow-up was of 25 months for the RT group and 37 months for the BT group. BC3 was 51% versus 73% (p = 0.032) for RT and BT, respectively. Comparisons of biochemical control by treatment group stratified by PSAi showed that BC3 for RT versus BT was 85.7% versus 79.1% (p = 0.76) for PSAi < 10 ng/mL and 38% versus 68% (p = 0.023) for PSAi > 10 ng/mL, respectively. For patients with GS < 6, BC3 was 37% versus 80% (p = 0.001) for RT versus BT and, for patients with GS > 6, BC3 was 78% versus 55% (p = 0.58) for RT versus BT, respectively. For patients with CS < T2a, BC3 was 36% versus 74% (p = 0.018) for RT versus BT and, for patients with CS > T2a, BC3 was 73% versus 69% (p = 0.692) for RT versus BT, respectively. The relative risk of biochemical relapse was 2.3 (95% IC: 1.0-5.1) for patients in RT group compared to the BT group. When adjusted for PSAi and GS, the relative risk of biochemical relapse was 2.4 (95% IC: 1.0-5.7). CONCLUSION: The treatment modality was an independent prognostic factor for biochemical relapse, with a significant improvement in the biochemical control with BT. These early results suggest that this treatment was most beneficial in patients with PSAi > 10 ng/mL, CS < T2a and GS < 6.
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    Avaliação do efeito da eletroestimulação funcional como reabilitação peniana na função erétil de pacientes submetidos à prostatectomia radical
    (Universidade Federal de São Paulo (UNIFESP), 2018-09-24) Bispo, Ana Paula dos Santos [UNIFESP]; Mesquita, Roberto Andre Soler [UNIFESP]; http://lattes.cnpq.br/9038872306641159; http://lattes.cnpq.br/2262290125054480; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Erectile dysfunction (ED) after radical prostatectomy is a peculiar form of ED, which preserved with the direct causal event. Objective: To evaluate the effect of functional electrostimulation as a penile rehabilitation procedure on the erectile function of postprostatectomy patients. Methods: This was a prospective, blind, randomized, shamcontrolled trial with 49 patients at the Division of Urology of UNIFESPEPM, through 2014 to 2017. The study included patients undergoing radical prostatectomy with bilateral preservation of the neurovascular bundle, with previous unassisted normal erectile function (International Index of Erectile Function – Erectile Function domain [IIEFEF] score ≥ 26). Patients were undergo functional electrostimulation (FES) or sham procedure. Penile rehabilitation was performed for 6 months, with frequency: 50 Hz; pulse width: 250 microseconds; contraction: 6 seconds; rest: 12 seconds. Patients were evaluated at 1, 3, 6, 9 and 12 months after the start of the procedures. The primary endpoint was proportion of patients with IIEFEF score ≥ 22 after 12 months of the start of treatment. Secondary endpoints included rate of positive responses to Sexual Encounter Profile (SEP) questions 2 and 3 and to Global Assessment Question (GAQ) questions 1 and 2. Results: After 12 months of the start of the study procedures 52.2% and 19.2% of patients reached IIEFEF score ≥ 22 in FES and sham groups, respectively (p = 0,016). A significantly higher proportion of patients in FES group compared to sham group had positive responses to SEP2 and GAQ1 from the 6th month to the end of the study. There was numerical, but no statistical, difference in the rate of SEP3 and GAQ2 positive responses between the groups. Conclusion: Functional electrostimulation was efficacious and safe as a penile rehabilitation procedure in improving recovery of erectile function in patients undergoing radical prostatectomy.
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    Avaliação prostpectiva de heparam sulfato, condroitim sulfato e ácido hialurônico em pacientes com câncer de próstata
    (Universidade Federal de São Paulo (UNIFESP), 2018-06-28) Silva, Matheus Neves Ribeiro Da [UNIFESP]; Pinhal, Maria Aparecida Da Silva [UNIFESP]; http://lattes.cnpq.br/7511274763693292; http://lattes.cnpq.br/8143551334488274; Universidade Federal de São Paulo (UNIFESP)
    Prostate cancer in Brazil represents the most common type of cancer among men after skin cancer. Although there are effective tests for the diagnosis of prostate cancer, there are still discussions about the most appropriate and non-invasive method for such diagnosis, always looking for less invasive methods to evaluate the possible prognosis of the disease. The present study aimed to evaluate urinary levels of chondroitin sulfate (CS) and heparan sulfate (HS), as well as plasma levels of hyaluronic acid (HA) in patients with prostate cancer, before and after treatment, compared with individuals which was not affected by neoplasia. Plasma samples were used to quantify AH and urine for CS and HS quantification from forty-four patients with prostate cancer and fourteen controls (non-affected individuals). Laboratory and pathological clinical data were correlated with the quantification of glycosaminoglycans by statistical analysis. There was no difference in the urinary levels of CS and HS among patients with prostate cancer and the control group. However, sulfated glycosaminoglycans (HS and CS) were analyzed in urine samples collected before and after treatment, and an increased in urinary excretion of heparan sulfate was observed after surgery, followed by decrease in the excretion of chondroitin sulfate after hormone therapy. The level of serum hyaluronic acid showed a significant increase in patients with prostate cancer (39.68 ± 30.00 ng / ml), compared to the control group (15.04 ± 7.11 ng / ml), p = 0.004. We also observed a significant increase in hyaluronic acid in patients with high-risk of prostate cancer, following the D'Amico classification, compared to low-risk patients (p = 0.0214). Patients submitted to surgery had a significant reduction in the level of AH (p = 0.029). The quantification of serum hyaluronic acid represents a noninvasive test with potential use in the diagnostic and prognostic evaluation of prostate cancer. Future studies are essential to confirm the unprecedented but preliminary results obtained in the present study.
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    Contribuição da densidade do PSA para predizer o câncer da próstata em pacientes com valores de PSA entre 2,6 e 10,0 ng/ml
    (Colégio Brasileiro de Radiologia e Diagnóstico por Imagem, 2011-08-01) Castro, Hugo Alexandre Sócrates de [UNIFESP]; Iared, Wagner [UNIFESP]; Shigueoka, David Carlos [UNIFESP]; Mourão, José Eduardo [UNIFESP]; Ajzen, Sergio Aron [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    OBJECTIVE: To study the profile of patients with PSA level between 2.6 and 10.0 ng/ml and submitted to prostate biopsy, determining possible patterns that might lead to a reduction of unnecessary biopsies. MATERIALS AND METHODS: In the period from 2007 to 2009, a cross-sectional study was developed with 1,282 patients with PSA levels between 2.6 and 10.0 ng/ml, and submitted to prostate biopsy. RESULTS: Cancer prevalence was 28.6%. On average, the patients with positive biopsies were older, with higher PSA levels and density, and smaller prostate volume as compared with the patients with negative biopsies. In the analysis of PSA density, the cancer patients averaged 0.31 ng/ml/cc, while patients with negative results averaged 0.10 ng/ml/cc. Utilizing a cutoff value of 0.15 ng/ml/cc for PSA density as a cancer positiveness criterion, the authors obtained sensitivity of 74% and specificity of 70%. The cutoff value should be reduced to increase the sensitivity. With a cutoff value of 0.09 ng/ml/cc, sensitivity reached 84% (CI 95%: 80-87%), and specificity, 75% (CI 95%: 72-78%). CONCLUSION: The systematic use of PSA density as an indicator to proceed with the investigation of a patient with biopsy could substantially reduce the amount of unnecessary procedures.
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    Correlação entre a graduação histológica de biópsias e do espécimen cirúrgico em câncer da prostata
    (Colégio Brasileiro de Cirurgiões, 1999-02-01) Cury, José [UNIFESP]; Srougi, Miguel [UNIFESP]; Leite, Kátia Ramos Moreira [UNIFESP]; Lopes, Luiz Heraldo Camara; Carneiro, Paulo Campos; Universidade Federal de São Paulo (UNIFESP); Hospital Sírio Libanês; Universidade de São Paulo (USP)
    The treatment of patients with adenocarcinoma of the prostate is based on the tumor stage and grade. For this reason the interpretation of the biopsy especimen is crucial and demands a great expertize from its examiner. ln order to define the accuracy of biopsy interpretation we settled the present study, trying to correlate the relationship between the histological grade of the biopsy especimens and the definitive pathological report read by the same pathologist. One hundred and twenty patients with localized prostate cancer stages TI - T3a submitted to radical prostatectomy were evaluated. The histological grade of the tumor was defined using the Gleason score sistem and a correlation was made between the score of biopsy and the surgical especimens. Complete agreement of the Gleason score was seen in 39 patients (32,5%) and if 1 digit discordance (± 1 Gleason score) was not considered, agreement was seen in 81 patients (67,5%). Seventy five tumors (62,5%) were undergraded and the rate of discordance was more common in patients with grade 2 to 4 tumors. According to our date, we conclude that the histological evaluation of the biopsy especimen in prostate cancer tends to underevaluate the true Gleason score of the tumor.
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    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.
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    Desenvolvimento de adenovírus helper de sistema adenoviral de alta capacidade capaz de expressar biomoléculas com atividade antitumoral
    (Universidade Federal de São Paulo, 2023-08-23) Toneto, Nicholas Pietro Agulha [UNIFESP]; Tamura, Rodrigo Esaki [UNIFESP]; http://lattes.cnpq.br/3338898252490486; http://lattes.cnpq.br/9474021458317872
    Os vetores adenovirais são os mais utilizados para transferência de genes em ensaios clínicos de terapia gênica. Isso se atribuí principalmente por apresentarem alta capacidade de armazenamento e expressão gênica e menos efeitos genotóxicos. Além disso, os vetores adenovirais de alta capacidade apresentam menor imunogenicidade, o que se deve à remoção de todos os genes virais, porém dependem de um vírus helper para sintetizar a partícula viral e assim serem obtidos. No entanto, no processo de produção viral, existe a possibilidade de contaminação pelo vírus helper, que não apresenta o gene terapêutico, o que reduz a eficácia da terapia gênica. Portanto, nosso objetivo é eliminar essa contaminação, e para atingir este objetivo, o vetor adenoviral de alta capacidade e o vírus helper terão limitações de empacotamento, devido à especificidade do sorotipo da sequência de empacotamento e das proteínas envolvidas neste processo. Paralelamente, faremos a triagem de um banco de bactérias de compostagem e de extratos de origem vegetal, afim de encontrar novos compostos com atividade antitumoral contra células de câncer de próstata. Essa coleção de bactérias foi obtida no Zoológico de São Paulo durante um Projeto Temático da FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo) e os extratos vegetais foram fornecidos pelo Prof. Dr. João Lago da UFABC. Os vetores adenovirais foram clonados por arranjo de Gibson e técnicas clássicas de biologia molecular. As biomoléculas de origem bacteriana e vegetal foram avaliadas quanto à redução da viabilidade celular, e com os compostos de plantas já identificados e isolados foram realizados outros ensaios como determinação do IC50, proliferação celular e morte celular. Identificamos moléculas bioativas com atividade antitumoral, com foco principal nas células do câncer de próstata. E quanto ao vetor helper, obtivemos o vetor através de clonagens porém não conseguimos sintetizar o vírus. Dessa forma, uma perspectiva desses trabalhos será o uso do vetor adenoviral de alta capacidade com contaminação menor ou zero do vírus helper para expressar moléculas de origem bacteriana ou vegetal com atividade antitumoral
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    Early Diagnosis of Prostate Cancer by Citrate Determination in Urine with Europium-Oxytetracycline Complex
    (Soc Applied Spectroscopy, 2012-08-01) Silva, Flavia R. O. [UNIFESP]; Nabeshima, Camila Tiemi [UNIFESP]; Bellini, Maria H.; Courrol, Lilia C. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); IPEN CNEN SP
    Normal prostate tissue contains high levels of citrate. in the presence of prostate cancer, the citrate level is diminished. in this paper we show that it is possible to use europium oxytetracycline complex as a citrate fluorescent probe and consequently as a prostate cancer probe. We analyzed normal nude male mice urine and urine from nude male mice in which prostate cancer was induced by intraprostatic inoculation of DU145 cells. the urine samples were collected from the animals at the 7th, 14th, 21st, and 35th days after the surgery procedures. the intensity of europium emission at 615 nm in europium oxytetracycline complex in the presence of citrate increases linearly. the citrate concentrations were determined from a calculated calibration curve. A concentration decrease in malignant prostate urine from the normal (PBS group) urine value from similar to 8.0 mM to similar to 2.4 mM (tumor group at 35th day) was found. the obtained results indicated that europium oxytetracycline provides a significant biomarker for prostate cancer detection with a direct, accurate, noninvasive, and non-enzymatic method for measurement of citrate in biological fluids.
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    Efeitos da ativação dos receptores estrogênicos na expressão e na localização de N-caderina em células de câncer prostático independentes de andrógenos
    (Universidade Federal de São Paulo (UNIFESP), 2017-07-31) Silva, Rafael de Souza [UNIFESP]; Porto, Catarina Segreti [UNIFESP]; Lombardi, Ana Paola Giometti [UNIFESP]; Vicente, Carolina Meloni [UNIFESP]; Ana Paola Giometti Lombardi: http://lattes.cnpq.br/3012202070649059; Carolina Meloni Vicente: http://lattes.cnpq.br/2222473909041643; http://lattes.cnpq.br/6262412968631187; http://lattes.cnpq.br/9064114811735332; Universidade Federal de São Paulo (UNIFESP)
    Andrógenos, estrógenos e as interações estroma-epitélio estão envolvidos no desenvolvimento do câncer prostático. Apesar da maioria dos cânceres prostáticos depender de andrógenos para o crescimento nos estágios iniciais e ser responsiva à terapia de ablação androgênica, em muitos casos o tumor progride para um fenótipo independente de andrógeno ou também denominado resistente à castração (CRPC), que tende a progredir e levar à metástase e contra o qual não há uma terapia efetiva. Os mecanismos envolvidos no desenvolvimento do CRPC não estão esclarecidos. Estudo do nosso laboratório mostrou a expressão dos receptores estrogênicos ESR1 (ERα) e ESR2 (ERβ) nas células PC-3, usada como modelo de CRPC. Além disso, os estrógenos desempenham um papel na proliferação das células PC-3 por meio de uma nova via de sinalização envolvendo a ativação de β-catenina mediada pelo ESR2. N-caderina está conectada via α-catenina e β-catenina ao citoesqueleto e funciona como um componente da adesão celular e como molécula sinalizadora. N-caderina tem surgido como um importante alvo terapêutico e está envolvida na regulação da proliferação, sobrevivência, invasão e metástase de células cancerígenas. Assim, o objetivo deste estudo foi investigar os efeitos da ativação dos receptores estrogênicos na expressão e na localização de N-caderina nas células de câncer prostático independentes de andrógenos. O presente estudo utilizou as linhagens de célula de câncer prostático independente de andrógenos PC-3 (células de metástase óssea de adenocarcinoma prostático grau IV) e DU-145 (células de metástase cerebral de carcinoma prostático) e de células epiteliais de próstata (PNT1A), obtida de um homem pós-puberdade e imortalizadas com SV40. As células foram incubadas na ausência (controle) ou na presença de 17-β-estradiol (E2), agonista seletivo do ESR1 (PPT) ou agonista seletivo do ESR2 (DPN) (10 nM) por 10 e 30 minutos, e 1, 2, 24 and 48 horas. Em outros experimentos, as células foram pré-incubadas ou não com o antagonista seletivo do ESR2 (PHTPP, 10 nM) por 30 minutos e, então, incubadas com o agonista seletivo do ESR2 (DPN 10 nM) por 24 horas. Ensaios de Western blot e imunofluorescência para a detecção de N-caderina foram realizados nas células PC-3, DU-145 e PNT1A A N-caderina foi detectada preferencialmente na membrana plasmática das células PNT1A, sugerindo o envolvimento desta proteína na adesão célula-célula. A expressão de N-caderina foi maior as células PC-3 (células altamente metastáticas) do que nas células DU-145. Imunomarcação para esta proteína foi detectada preferencialmente no citoplasma destas células, sugerindo alterações no processo de exocitose, endocitose e/ou reciclagem desta proteína e o rompimento do complexo de adesão. O tratamento das células PC-3 com o 17β-estradiol (E2) ou com o agonista seletivo do ESR1 (PPT) não afetou a expressão de N-caderina. Por outro lado, o agonista seletivo do ESR2 (DPN) induziu diminuição da expressão de N-caderina nas células PC-3. Este efeito foi bloqueado pelo pré-tratamento com o antagonista seletivo do ESR2 (PHTPP), indicando o envolvimento do ESR2 na regulação da expressão da N-caderina. A ativação do ESR1 ou do ESR2 não alterou a expressão e a localização da N-caderina nas células PNT1A e DU-145. Nossos resultados, em conjunto com os obtidos anteriormente no nosso laboratório, indicam que a ativação do ESR2 diminuiu a expressão de N-caderina liberando a β-catenina para o citoplasma. A β-catenina pode regular a transcrição de genes alvos envolvidos com a proliferação e, provavelmente, com a migração e a invasão celular. Em conclusão, nossos resultados mostraram uma expressão diferencial da N-caderina em células de câncer prostático independentes de andrógenos e uma localização preferencialmente citoplasmática, sugerindo alterações no processo de exocitose, endocitose e/ou reciclagem desta proteína. Além disso, a ativação dos receptores estrogênicos ESR2, mas não do ESR1, levou à diminuição da expressão da N-caderina. Com a redução dos níveis de N-caderina, há a liberação de β-catenina para o citoplasma, sua translocação para o núcleo e ativação gênica. A identificação de novas vias de sinalização intracelulares poderá ter importância no desenvolvimento de alvos terapêuticos para o tratamento do CRPC.
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    Enhancement of blood porphyrin emission intensity with aminolevulinic acid administration: A new concept for photodynamic diagnosis of early prostate cancer
    (Elsevier B.V., 2011-03-01) Silva, Flávia Rodrigues de Oliveira [UNIFESP]; Bellini, Maria Helena [UNIFESP]; Nabeshima, Camila Tiemi [UNIFESP]; Schor, Nestor [UNIFESP]; Vieira, Nilson Dias; Courrol, Lilia Coronato [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Ctr Lasers & Aplicacoes
    Background: the objective of this paper was to verify if the oral administration of delta-aminolevulinic acid (ALA) in animals with prostate tumor can increase the sensitivity of cancer diagnosis by protoporphyrin IX blood autofluorescence. in this study, the autofluorescence of blood porphyrin was analyzed using fluorescence spectroscopy on healthy male NUDE mice and in those with prostate cancer induced by the inoculation of DU145 cells.Methods: A total of 18 male NUDE mice, similar to 8 weeks old on arrival were divided into 3 groups: Control, Tumor and ALA Tumor. the autofluorescence of blood porphyrin of the groups was analyzed using fluorescence spectroscopy at different days after tumor induction, to monitor the tumor progression. Emission spectra were obtained by exciting the samples at 405 nm. the animals inoculated had their blood collected with and without oral ALA solution administration to compare PPIX endogenous (Tumor group) and exogenous (ALA Tumor group) signal intensity and to establish a method to diagnosis early prostate cancer.Results: Significant differences were observed in autofluorescence intensities measured in the 575-725 nm spectral regions for the studied groups.Conclusions: the results showed an enhancement of almost 100% in blood PPIX fluorescence, using the oral administration of delta-aminolevulinic acid on male NUDE mice with prostate cancer, making fluorescence measurements more accurate and sensitive since the first week after tumor induction. (C) 2010 Elsevier B.V. All rights reserved.
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    Identificação de produtos do sobrenadante bacteriano com propriedade antitumoral em células de câncer de próstata
    (Universidade Federal de São Paulo, 2021-02-19) Toneto, Nicholas Pietro Agulha [UNIFESP]; Tamura, Rodrigo Esaki [UNIFESP]; Oliveira, Julio Cezar Franco de [UNIFESP]; http://lattes.cnpq.br/5745233659737350; http://lattes.cnpq.br/3338898252490486; http://lattes.cnpq.br/9474021458317872
    O câncer de próstata é o tipo de tumor mais recorrente e o segundo com maior letalidade, em homens. Apesar da prostatectomia ser muito eficaz para o seu tratamento, em alguns casos o câncer pode voltar ainda mais agressivo, como uma metástase. O qual até o momento ainda não apresenta um tratamento efetivo. Entretanto, terapias bacterianas antitumorais tem sido cada vez mais estudadas e demonstrado sua capacidade de atuar contra tumores. Apresentando alternativas diferentes de tratamento, desde a utilização de bactérias como vetores ou então a extração das toxinas bacterianas com atividade antitumoral. Com isto alguns produtos do metabolismo bacteriano já foram demonstrados na literatura como sendo capazes de induzir a morte de células tumorais e têm sido testados em Ensaios clínicos como agentes antitumorais. Nosso laboratório possui uma coleção de isolados bacterianos provenientes de compostagem de matéria orgânica do Zoológico de São Paulo. Desta forma, em nosso trabalho testamos a atividade antitumoral de sobrenadante de culturas de 36 isolados de bactérias de compostagem sobre células de tumor de próstata PC3 e DU145 em cultura. Inicialmente procedemos a padronização do teste de atividade antitumoral com sobrenadante de culturas bacterianas crescidas em meio LB (Luria Bertani) ou em meio DMEM (Dulbeco Modified Eagle´s Medium). O ensaio utilizando meio DMEM mostrou-se mais adequado por não interferir na viabilidade das células tumorais em cultura. Realizada esta padronização, iniciou-se a análise da atividade antitumoral, e a partir de 36 isolados investigados, o sobrenadante de 3 isolados exibiram comprometimento da viabilidade das células tumorais por meio de ensaios com Prestoblue. Dentre os isolados cujos sobrenadantes reduzem a viabilidade das células tumorais em cultura, temos bactérias dos gêneros Serratia e Bacillus. Sendo estes identificados por MALDI-TOF e sequenciamento do gene do RNA Ribossomal 16S.
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    Intracavernous injection in the treatment of erectile dysfunction after radical prostatectomy: an observational study
    (Associação Paulista de Medicina - APM, 2001-07-01) Claro, Joaquim de Almeida [UNIFESP]; Aboim, José Elêrton de [UNIFESP]; Maríngolo, Marcelo [UNIFESP]; Andrade, Enrico [UNIFESP]; Aguiar, Wilson [UNIFESP]; Nogueira, Marcos [UNIFESP]; Nardozza Júnior, Archimedes [UNIFESP]; Srougi, Miguel [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    CONTEXT: Despite the recent improvements in performing radical retropubic prostatectomy that have led to a considerable decrease in the complication rate, erectile dysfunction still represents a major problem. Moreover, less invasive treatment options that are emerging for erectile dysfunction have not shown satisfactory results in managing these patients. OBJECTIVE: To study the efficacy and side effects of self-injection therapy in the treatment of men who had become impotent after undergoing radical prostatectomy due to prostate cancer, over a study period of 96 months. DESIGN: Observational study. SETTING: University Referral Center. PARTICIPANTS: 168 patients with erectile dysfunction, aged 43 to 78 years old, who underwent radical retropubic prostatectomy due to localized prostate cancer. PROCEDURES: The patients were treated with self-injection therapy using papaverine, phentolamine and prostaglandin E1, at home. RESULTS: This study showed an acceptable 94.6% success rate, with no life-threatening complications. In addition to this, our series presented a 13.1% cure rate with this therapy. CONCLUSION: Self-injection therapy with papaverine, phentolamine and prostaglandin E1 is effective and safe in the treatment of erectile dysfunction after radical prostatectomy.
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    Intrinsic Fluorescence of Protoporphyrin IX from Blood Samples Can Yield Information on the Growth of Prostate Tumours
    (Springer, 2010-11-01) Silva, Flávia Rodrigues de Oliveira [UNIFESP]; Helena Bellini, Maria [UNIFESP]; Regina Tristao, Vivian [UNIFESP]; Schor, Nestor [UNIFESP]; Vieira, Nilson Dias; Courrol, Lilia Coronato [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); IPEN CNEN SP
    Prostate cancer is one of the most common types of cancer in men, and unfortunately many prostate tumours remain asymptomatic until they reach advanced stages. Diagnosis is typically performed through Prostate-Specific Antigen (PSA) quantification, Digital Rectal Examination (DRE) and Transrectal Ultrasonography (TU). the antigen (PSA) is secreted by all prostatic epithelial cells and not exclusively by cancerous ones, so its concentration also increases in the presence of other prostatic diseases. DRE and TU are not reliable for early detection, when histological analysis of prostate tissue obtained from a biopsy is necessary. in this context, fluorescence techniques are very important for the diagnosis of cancer. in this paper we explore the potential of using endogenous phorphyrin blood fluorescence as tumour marker for prostate cancer. Substances such as porphyrin derivatives accumulate substantially more in tumours than in normal tissues; thus, measuring blood porphyrin concentration by autofluorescence intensity may provide a good parameter for determining tumour stage. in this study, the autofluorescence of blood porphyrin was analyzed using fluorescence and excitation spectroscopy on healthy male NUDE mice and in those with prostate cancer induced by inoculation of DU145 cells. A significant contrast between the blood of normal and cancer subjects could be established. Blood porphyrin fluorophore showed an enhancement on the fluorescence band around 632 nm following tumour growth. Fluorescence detection has advantages over other light-based investigation methods: high sensitivity, high speed and safety. However it does carry the drawback of low specificity of detection. the extraction of blood porphyrin using acetone can solve this problem, since optical excitation of further molecular species can be excluded, and light scattering from blood samples is negligible.
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    Low frequency of human papillomavirus detection in prostate tissue from individuals from Northern Brazil
    (Instituto Oswaldo Cruz, Ministério da Saúde, 2009-07-01) Silvestre, Rodrigo Vellasco Duarte; Leal, Mariana Ferreira [UNIFESP]; Demachki, Samia; Nahum, Márcia Cristina de Souza; Bernardes, Julio Guilherme Balieiro; Rabenhorst, Silvia Helena Barem; Smith, Marilia de Arruda Cardoso [UNIFESP]; Mello, Wyller Alencar de; Guimarães, Adriana Costa; Burbano, Rommel Rodríguez [UNIFESP]; Departamento de Anatomia Patológica; Universidade Federal de São Paulo (UNIFESP); Hospital Universitário João de Barros Barreto Departamento de Cirurgia; Universidade Federal do Ceará Escola de Medicina Departamento de Patologia e Medicina Forense; Ministério da Saúde Fundação Nacional de Saúde Fundação Nacional de Saúde; Universidade Federal do Pará Instituto de Ciências Biológicas Laboratório de Citogenética Humana
    The presence of human papillomavirus (HPV) was evaluated in 65 samples of prostate tumours and six samples of prostates with benign prostatic hyperplasia from individuals from Northern Brazil. We used a highly sensitive test, the Linear Array HPV Genotyping Test, to detect 37 high and low-risk HPV types. In this study, only 3% of tumour samples showed HPV infection. Our findings support the conclusion that, despite the high incidence of HPV infection in the geographic regions studied, HPV was not associated with a higher risk of prostate cancer. To our knowledge, this is the first study evaluating the frequency of HPV detection in prostatic tissue of individuals from Brazil.
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    Lumican expression, localization and antitumor activity in prostate cancer
    (Elsevier B.V., 2013-04-15) Coulson-Thomas, Vivien Jane [UNIFESP]; Coulson-Thomas, Yvette May [UNIFESP]; Gesteira, Tarsis Ferreira [UNIFESP]; Paula, Claudia Alessandra Andrade de [UNIFESP]; Carneiro, Celia Regina Whitaker [UNIFESP]; Ortiz, Valdemar [UNIFESP]; Toma, Leny [UNIFESP]; Kao, Winston W. Y.; Nader, Helena Bonciani [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Cincinnati
    The stromal reaction surrounding tumors leads to the formation of a tumor-specific microenvironment, which may play either a restrictive role or a supportive role in the growth and progression of the tumors. Lumican, a small leucine-rich proteoglycan (SLRP) of the extracellular matrix (ECM), regulates collagen fibrillogenesis. Recently, lumican has also been shown to regulate cell behavior during embryonic development, tissue repair and tumor progression. the role of lumican in cancer varies according to the type of tumor. in this study we analyze the role of lumican in the pathogenesis of prostate cancer both in vivo and in vitro. Overall lumican up-regulation was observed in the primary tumors analyzed through both real-time PCR and immunostaining. the increase in lumican expression was observed in the reactive stroma surrounding prostate primary tumors with fibrotic deposition surrounding the acinar glands. in vitro analysis demonstrated that lumican inhibited both the migration and invasion of metastatic prostate cancer cells isolated from lymph node, bone and brain. Moreover, prostate cancer cells seeded on lumican presented a decrease in the formation of cellular projections, lamellipodia detected by a decreased rearrangement in ZO-1, keratin 8/18, integrin beta 1 and MT1-MMP, and invadopodia detected by disruption of alpha-smooth muscle actin, cortactin and N-WASP. Moreover, a significant increase in prostate cancer cell invasion was observed through the peritoneum of lumican knockout mice, further demonstrating the restrictive role lumican present in the ECM has on prostate cancer invasion. in conclusion, lumican present in the reactive stroma surrounding prostate primary tumors plays a restrictive role on cancer progression, and we therefore postulate that lumican could be a valuable marker in prostate cancer staging. (C) 2013 Elsevier Inc. All rights reserved.
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    Receptores estrogênicos regulam a migração e a invasão das células de câncer prostático independentes de andrógenos Pc-3
    (Universidade Federal de São Paulo (UNIFESP), 2018-11-28) Lombardi, Ana Paola Giometti [UNIFESP]; Porto, Catarina Segreti [UNIFESP]; Vicente, Carolina Meloni; http://lattes.cnpq.br/2222473909041643; http://lattes.cnpq.br/6262412968631187; http://lattes.cnpq.br/3012202070649059; Universidade Federal de São Paulo (UNIFESP)
    Recent studies from our laboratory have shown the expression of estrogen receptors ESR1 (ERα) and ESR2 (ERβ) in androgenindependent prostate cancer cells (PC3), used as castrationresistant prostate cancer models. Furthermore, estrogen plays a role in PC3 cell proliferation through a novel pathway, involving ESR2mediated activation of βcatenin. It is important to emphasize that nonphosphorylated βcatenin associate with transcription factor TCF/LEF1 in the nucleus, and, together with coactivators, is implicated in cell proliferation, migration, and invasion in several cancer types. This study was performed to investigate the effects of estrogen receptors activation and the proteins involved with intracellular signaling pathways, such as SRC, PI3K, AKT and βcatenin, on migration, invasion and colony formation of the androgenindependent prostate cancer cells PC3. It showed that: 1. The treatment of PC3 cells with 17βestradiol (E2), ESR1selective agonist PPT and ESR2selective agonist DPN induced a rapid increase in the phosphorylation state of SRC. These effects were blocked by ESR2selective antagonist (PHTPP), ESR1selective antagonist (MPP) and selective inhibitor of the SRC family of protein tyrosine kinases (PP2). 2. A diffuse immunostaining for nonphosphorylated βcatenin was detected in the cytoplasm of PC3 cells. Low levels of nonphosphorylated βcatenin immunostaining were also detected near the plasma membrane. Treatment of PC3 cells with DPN for 2 hour markedly increased nonphosphorylated βcatenin expression in cytoplasm, near the plasma membrane and nuclei. These effects were blocked by pretreatment with PP2, suggesting the involvement of SRC on βcatenin expression induced by DPN. 3. Treatment with E2 and ESR2selective agonists (DPN and ERB041) caused an enhancement on migration and invasion of PC3 cells. The pretreatment with ESR2selective antagonist (PHTPP) decreased the effect of E2 and blunted the effect induced by DPN on migration and invasion of PC3 cells, indicating that ESR2 is involved in these processes. Previous study from our laboratory showed that ESR2selective agonist DPN increased ESR1 levels. In fact, treatment with ESR1selective antagonist (MPP) decreased 30% the migration and 25% the invasion of PC3 cells induced by DPN. These results suggest that ESR1 also plays a role in the regulation of DPNESR2 effects. On the other hand, ESR1selective agonist (PPT) did not have any effect on cell migration, but increased cell invasion (27%). The pretreatment with MPP blunted the effect induced by PPT on cell invasion, indicating that ESR1 is also involved in this process. 4. The upregulation induced by DPN on migration and invasion of PC3 cells was blocked by pretreatment with PKF 118310, a compound that disrupts the complex βcateninTCF/ LEF transcription factor, suggesting the involvement of ESR2βcatenin on migration and invasion of PC3 cells. The pretreatment with PPT did not have any effect on cell migration, but increased cell invasion (27%). This effect was partially reduced (59%) by PKF 118310, suggesting also the involvement of ESR1βcatenin on invasion of PC3 cells. 5. The pretreatment with SRC inhibitor (PP2), PI3K inhibitor (Wortmannin), AKT inhibitor (MK2206) and metalloproteases (MMPs) inhibitor (GM6001) blunted the effect induced by DPN and reduced the effect induced by PPT on invasion of PC3 cells. VEGF inhibitor (Bevacizumab) decreased the effect of both agonists DPN and PPT on invasion of PC3 cells. Taken together, these results suggest the involvement of these estrogen receptors and these intracellular proteins on invasion of PC3 cells. It is important to emphasize the upregulation of VEGF expression by E2, DPN and PPT. This effect was blunted by PKF 118310, indicating the involvement of βcatenin. 6. To further analyze the tumorigenic potential of estrogen receptors in PC3 cells, we performed the colony formation, anchorageindependent growth assay. E2, PPT and DPN increased the number and the size of colony formed by PC3 cells (rounds spheroids strutures) compared with control (absence of agonists). Furthermore, E2, PPT and DPN formed stellate or invasive structures. These effects were blocked by MPP and PHTTP, indicating that ESR1 and ESR2 are upstream receptors regulating these processes. The proteins involved in the intracellular signaling pathways of these receptors, such as βcatenin, SRC, PI3K and AKT also was involved the tumorigenic potential of estrogen receptors in PC3 cells. In summary, the activation of ESR2 (ERβ1 isoform) by the ESR2selective agonist (DPN) increases βcatenin expression and induces migration, cell invasion and colony formation. Activation of ESR1 by ESR1selective agonist (PPT) also enhances βcatenin expression, cell invasion, and colony formation. In addition to βcatenin expression, stimulation of ESR2 and ESR1 active SRC, PI3K, AKT, metalloproteinases and VEGF and these proteins are also involved in cell invasion and colony formation of PC3 cells. It is important to mention that the effects of ESR2 activation are predominant in these cells when compared to the activation of ESR1. Future studies in animal, xenographic, and large tissue models of prostate cancer patients could improve our understanding of the role of ESR2 and ESR1 in this cancer. The identification of new signaling pathways is important in the development of therapeutic targets for the treatment of CRPC. Combining therapies targeting more than one pathway is the logical approach coming from these new molecular evidences in order to obtain longer lasting clinical responses and increase the survival of patients with prostate cancer.