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Noronha, Marcelo Ramos. "Adenocarcinoma da próstata = estudo de fatores clinicopatológicos preditivos de progressão bioquímica (PSA) pós-prostatectomia radical." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310489.
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Orientadores: Luciana Rodrigues de Meirelles, Athanase BillisDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: O adenocarcinoma de próstata é a segunda neoplasia maligna que afeta homens, sendo precedida somente pelo cancer de pele. A prostatectomia radical continua sendo a mais aceita estratégia terapêutica para os casos confinado a próstata. Alguns achados clinicopatológicos em pacientes submetidos a prostatectomia radical são controvertidos como tendo valor preditivo de progressão bioquímica pós-cirurgia. O monitoramento da progressão da moléstia pós-prostatectomia radical é feito através de dosagem do PSA sérico cujo aumento pode significar recidiva local e/ou metástases. O valor de corte do PSA sérico indicando progressão é variável entre os autores. Há uma recomendação recente da Associação Americana de Urologia para que este valor seja ?0,2ng/mL com um segundo valor >0,2ng/mL. Não está estabelecido se pacientes mais jovens ou de raça negra mostram taxa de recidiva bioquímica maior. O PSA pré-operatório é um dado de grande importância preditiva, mas não está estabelecido a validade da estratificação dos valores em 3 categorias: 4-10ng/mL, 10-20ng/mL e >20ng/mL. Margens cirúrgicas comprometidas no espécime cirúrgico estão na categoria I (valor preditivo comprovado). É controvertido se a contagem final de Gleason 3+4=7 é semelhante ou não a 4+3=7 como fator preditivo de progressão bioquímica pós-prostatectomia radical. O estudo foi retrospectivo e os dados foram coletados dos prontuários médicos de 300 pacientes submetidos consecutivamente à prostatectomia radical no Hospital de Clínicas da Universidade Estadual de Campinas, no período de janeiro de 1997 a maio de 2007. O objetivo principal do trabalho foi avaliar a progressão bioquímica (PSA) pós prostatectomia radical de acordo com: raça, idade, margens cirúrgicas comprometidas, invasão microscópica do colo vesical, contagem final de Gleason, extensão do tumor, estádio patológico e PSA pré-operatório. Os dados obtidos foram analisados estatisticamente utilizando-se o teste de Mann-Whitney, o produto limite de Kaplan-Meier utilizando-se o teste do log-rank para comparação entre os grupos e o método de Cox para avaliar risco do tempo de progressão bioquímica (PSA) pós-prostatectomia radical. O nível de significância considerado para rejeição da hipótese nula foi p<0,05 bicaudal. Os resultados mais importantes neste trabalho foram: diferença estatisticamente significante quanto ao tempo de progressão bioquímica de pacientes com PSA pré-operatório ?10ng/mL, margens cirúrgicas comprometidas, invasão microscópica do colo vesical, Gleason 4+3=7, tumores mais extensos e tumores não confinados à próstata. Não houve associação da idade e raça com progressão bioquímica. Em análise univariada, os fatores preditivos significantes do tempo e risco de progressão pós-prostatectomia radical foram o PSA pré-operatório, as margens cirúrgicas positivas, a invasão das vesículas seminais, a invasão microscópica do colo vesical e o Gleason 4+3=7. Em análise multivariada, somente PSA pré-operatório, margens positivas e invasão das vesículas seminais mostraram-se fatores preditivos independentes do tempo e risco de progressão bioquímica pós-prostatectomia radical
Abstract: Adenocarcinoma of the prostate is the second malignancy that affects men, being preceded only by skin cancer. Radical prostatectomy remains the most widely accepted treatment strategy for cases confined to the prostate. Some clinical and pathological findings in patients undergoing radical prostatectomy are at issue as having predictive value of biochemical progression after surgery. The monitoring of disease progression after radical prostatectomy is done by measuring concentrations of PSA which can mean increased local recurrence and/or metastases. The cutoff of PSA indicating progression varies among authors. There is a recent recommendation of the American Urological Association that this value is ?0.2ng/mL with a second value >0.2ng/mL. It has not been established whether younger or black patients show higher rate of biochemical recurrence. The preoperative PSA is an important predictive factor for biochemical recurrence, but it has not been established the validity of the stratification of values in three categories: 4-10ng/mL, 10-20ng/mL, and >20ng/mL. Positive surgical margins in the surgical specimen are in category I (proven predictive value). It is controversial whether the final Gleason score 3+4=7 is similar or not to 4+3=7 as a predictor of biochemical progression after radical prostatectomy. The study was based on 300 whole-mount consecutive radical prostatectomies. The aim of this study was to analyse the risk and time for biochemical progression after surgery, according to race, age, positive surgical margins, bladder neck invasion, Gleason score, tumor extension, pathological stage and serum PSA preoperative levels. Time to biochemical progression-free outcome was compared using the Kaplan-Meier product-limit analysis using the log-rank to compare the groups. To assess individual variables for risk and time to biochemical progression, we created a univariate Cox proportional hazards model, and to assess the influence of several variables simultaneously, we developed a final multivariate Cox proportional hazards model of the statistically significant covariates. The most important results were: There was a significant association to time of progression of patients with preoperative PSA ?10ng/mL, positive surgical margins, microscopic invasion of the bladder neck, Gleason 4+3=7, more extensive tumors and non confined tumors. No association of race and age to biochemical progression following radical prostatectomy. On univariate analysis, the significant predictive variables for risk and time to biochemical progression were: preoperative PSA, positive surgical margins, seminal vesicle invasion, microscopic invasion of the bladder neck, and Gleason 4+3=7. On multivariate analysis, only positive surgical margins and seminal vesicle invasion were independent predictive variables
Mestrado
Anatomia Patologica
Mestre em Ciências Médicas
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Silva, Elcio Dias 1951. "Margens cirurgicas na prostatectomia radical : comparação entre cirurgia retropubica e laparoscopica." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312194.
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Orientador: Ubirajara FerreiraDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: margem cirúrgica comprometida ou positiva é definida como tumor estendendo-se na superfície de corte do cirurgião. A porcentagem deste evento, resultante de incisão capsular, varia de 1,3 a 71 % (EPSTEIN, 2001). O objetivo deste estudo é comparar o comprometimento das margens cirúrgicas nas prostatectomias radicais realizadas por via retropúbica e laparoscópica, em dois serviços de referência no Brasil. Pacientes e Métodos: foram analisados os exames anátomo-patológjcos de 179 pacientes submetidos a prostatecomia radical por adenocarcinoma de próstata, 89 por via retropúbica e 90 por via laparoscópica. Critérios de inclusão: pacientes com PSA (antígeno específico da próstata) igual ou menor que 15 ng/ml (nanogramas por mililitro) e Gleason igual ou menor que 7 na biópsia prostática, estádio clínico máximo T2. Resultados: houve comprometimento de margem cirúrgica em 41,57 % dos pacientes submetidos à PRR (prostatectomia radical retropúbica), distribuídos da seguinte maneira: 34,21 % nos estádios pT2 (7,69 % no pT2a, zero no pT2b e 40,98 % no pT2c) e 84,61% nos estádios pT3 (77,77 % no pT3a e 100 % no pT3b). Nos pacientes submetidos a PRL (prostatectomia radical laparoscópica) houve margens cirúrgicas positivas em 24,44 % dos pacientes, distribuídos da seguinte maneira: 20,98 % nos estádios pT2 (11,11 % no pT2a, 27,27 % no pT2b e 21,31 % no pT2c) e 55,55 % nos estádios pT3 (zero % no pT3a e 62,50 % no pT3b). Conclusão: nas amostras analisadas, a proporção de margem cirúrgica positiva foi maior nas prostatectomias radicais realizadas pela via retropúbica do que pela laparoscópica (p= 0,023), em dois serviços de referência nas respectivas técnicas, no Brasil. No entanto, o fato das cirurgias retropúbicas serem realizadas por médicos residentes, em instituição de ensino, e as laparoscópicas realizadas por um único cirurgião experiente, e os exames anátomo-patológicos realizados por técnicas e patologistas distintos, não permite a generalização dos resultados. Maior número de pacientes em estudo prospectivo e randomizado seria necessário para uma melhor comparação entre os grupos
Abstract: Introduction: Compromised or positive surgical margin is defined as a tumor extending at the surgeon cutting surface. A percentage from this event, resulted from capsular incision, varies from 1.3 to 71% (EPSTEIN, 2001). The goal of this study is to compare the compromising of surgical margins at the radical prostatectomies performed through both retropubic and laparoscopic way, in two reference medical services in Brazil. Patients and Methods: pathological examinations were analyzed from 179 patients who underwent to radical prostatectomy by prostate adenocarcinoma, 89 patients by retropubic and 90 patients by laparoscopic way. Inclusion criteria: patients with PSA (prostate specific antigen) equal or less than 15 ng/ml (nanograms by miiiliter) and Gleason score equal or less than 7 at the prostate biopsy, maximum clinical T2 stage. Results: There has been compromising of the surgical margin in 41,57% of the patients who underwent to RRP (radical retropubic prostatectomy), distributed in the following way: 34,21% at pT2 stage (7,69% at pT2a, 0% at pT2b and 40,98% at pT2c) and 84,61% at pT3 (77,77% at pT3a and 100% at pT3b) stage. In the patients who had undergone to LRP (Laparoscopic Radical Prostatectomy), there have been positive surgical margins in 24,44% of the patients as following: 20,98% at pT2 stage (11,11% at pT2a. 27,27% at pT2b and 21,31% at pT2c stage) and 55,55% at pT3 stage (0% at pT3a and 62,50% at pT3b) Conclusion: At the analyzed samples, the proportion of positive surgical margin was greater at the radical prostatectomy performed by retropubic route than by laparocospic one (p=0,023), in two reference medical services using the respective techniques in Brazil. However, the fact that the retropubic surgeries were performed by resident doctors, in teaching school-hospital institution, while the laparoscopic ones were performed by a single expert surgeon and that the pathological examinations were performed by both distinct techniques and pathologists, the result generalization is not allowed. A greater number of patients in a randomized and prospective study would be necessary for a better comparison between the groups
Mestrado
Cirurgia
Mestre em Cirurgia
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Singh, Paras B. "Risk factor analyses for adenocarcinoma of the human prostate." Thesis, Lancaster University, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538609.
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Baca, Sylvan Charles. "The landscape of somatic mutations in primary prostate adenocarcinoma." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:10824.
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Prostate cancer is the second leading cause of cancer deaths among men. Targeted analyses of DNA from prostate cancers have identified recurrent somatic alterations that promote tumor growth and survival. Only recently, however, has the comprehensive analysis of cancer genomes become possible due to rapid advances in DNA sequencing technology.
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Pisani, Carla. "Study of the effects induced by high doses per fraction in radiotherapy: correlations between biological and clinical parameters – the case of intraoperative irradiation of prostate adenocarcinoma." Doctoral thesis, Università del Piemonte Orientale, 2021. http://hdl.handle.net/11579/128008.
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Brasil, Antonio Augusto Azevedo Vital. "Atrofia prostática em espécimes de prostatectomia radical = há relação topográfica com neoplasia intraepitelial prostática alto grau e adenocarcinoma?" [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308454.
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Orientadores: Athanase Billis, Luciana Rodrigues de MeirellesDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A relação entre a atrofia inflamatória com a neoplasia intraepitelial alto grau e o carcinoma, é controversa. Tem sido sugerida uma relação topográfica e que o epitélio proliferativo da atrofia inflamatória possa progredir para neoplasia intraepitelial prostática alto grau (NIPAG) e/ou carcinoma (CA). O propósito do nosso estudo foi analisar em espécimes de prostatectomia radical uma possível relação topográfica entre estas lesões. Um total de 3186 quadrantes pertencentes a 100 prostatectomias radicais completamente representadas, foi analisado. Determinou-se a frequência de quadrantes mostrando: somente atrofia inflamatória (AI), AI+CA, AI+NIPAG, ou AI+NIPAG+CA. A extensão e a distância entre as lesões foram avaliadas através de um método semiquantitativo de contagem de pontos previamente descrito. Também foram analisados focos de atrofia completa ou parcial sem inflamação. Os métodos estatísticos empregados foram os testes de Kruskal-Wallis e Mann-Whitney, e o coeficiente de correlação de Spearman. A média dos quadrantes exibindo somente AI, AI+CA, AI+NIPAG, e AI+NIPAG+CA foi 3.29, 2.51, 0.77, e 0.44; e a amplitude (0-21), (0-11), (0-6), (0-4), respectivamente (p<0.01). A maioria dos focos de AI estavam a uma distância >5mm dos focos de NIPAG e CA. Não houve correlação significativa entre a extensão da AI (p= 0.64, r= 0.05) com a extensão da NIPAG. Houve uma significativa correlação negativa entre a extensão da AI (p=0.01, r=-0.27) com a extensão do CA. Resultados similares foram encontrados considerando focos de atrofia com ou sem inflamação. Focos de atrofia parcial não evidenciaram inflamação crônica inespecífica. Nosso estudo não evidenciou associação topográfica significativa entre AI, NIPAG e/ou CA
Abstract: It is controversial whether there is any relationship of proliferative inflammatory atrophy (PIA) to high-grade prostatic intraepithelial neoplasia (HGPIN) and cancer (CA). It has been suggested a topographic relation and a potential of the proliferative epithelium in PIA to progress to HGPIN and/or CA. The aim of this study was to analyze in radical prostatectomies a possible topographic relation of the lesions. A total of 3186 quadrants from 100 whole-mount consecutive surgical specimens was examined. The frequency of quadrants showing: only PIA, PIA+CA, PIA+HGPIN, or PIA+HGPIN+CA was determined. Extent and distance between the lesions were evaluated by a semiquantitative point-count method previously described. We also studied foci with partial or complete atrophy without inflammation. The statistical methods included the Kruskal-Wallis and the Mann-Whitney tests and the Spearman correlation coefficient. The mean (range) of quadrants showing only PIA, PIA+CA, PIA+HGPIN, and PIA+HGPIN+CA was 3.29 (0-21), 2.51 (0-11), 0.77 (0-6), and 0.44 (0-4), respectively (p<0.01). Most of the foci of PIA were significantly located in a distance >5mm than <5mm from HGPIN or CA. There was no significant correlation between extent of PIA (p=0.64, r=0.05) with extent of HGPIN. There was a significant negative correlation of extent of PIA (p=0.01, r=-0.27) with extent of CA. Similar results were found considering foci either with or without inflammation. Chronic inespecific inflammation was not seen in foci of partial atrophy. A topographic relation of PIA to HGPIN and/or CA was not supported by our study
Mestrado
Anatomia Patologica
Mestre em Ciências Médicas
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Pearcy, Richard Malcolm. "Measurement of individualised quality of life in patients with prostatic adenocarcinoma." Thesis, University of Bristol, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288289.
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Harper, Curt E. "Prostate cancer chemoprevention with genistein and resveratrol in models of spontaneously developing prostate cancer." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2007p/harper.pdf.
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Reggio, Ernesto. ""Tratamento percutâneo do adenocarcinoma de próstata por crioablação"." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5153/tde-12042006-135835/.
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Diversas são as formas de tratamento do câncer de próstata, com resultados oncológicos e complicações variadas . A crioablação foi proposta nos anos 60 e com a evolução dos métodos de imagem a técnica ressurgiu; 44 pacientes, divididos em 3 grupos (portadores de tumor de alto risco, tumores de baixo risco e falha de tratamento após radioterapia) foram submetidos a crioterapia por via percutânea transperineal. Sobrevida livre de doença foi de 87% no grupo baixo risco, 34% no grupo alto risco e 58% no grupo de resgate após falha de radioterapia. A complicação mais freqüente foi disfunção erétil (94,5%); obstrução infravesical ocorreu em 9 pacientes (20,4%); 6 pacientes (13,6%) apresentaram algum grau de incontinência urinária. Não houve nenhum caso de fístula uretroretal ou mortalidade relacionada ao procedimentoThere are several treatments for prostate cancer with an assorted oncologic results and complications. Cryoablation was proposed in the 60 and the improvement of radiological techniques allowed the perineal percutaneous treatment; 44 patients divided into three groups (high risk tumors, low risk tumors and patients with recurrent prostate cancer following radiotherapy) were submitted to perineal percutaneous prostate cryoablation. Biochemical-free survival was 87% in low risk group, 34% in the high-risk group and 58% in salvage cryoablation. Erectile dysfunction was the most frequent complication (94,5%); Infravesical obstruction occurred in 20,4% of the patients and six (13,6%) developed urinary incontinence. There were no urethrorectal fistulae or mortality related to the procedure
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Pereira, Renan Augusto. "Expressão de ciclina D1 em adenocarcinoma de próstata utilizando a técnica de imunohistoquímica." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/17/17143/tde-11062013-075728/.
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O câncer de próstata é o tumor maligno mais freqüente nos homens com idade superior a 50 anos, excetuando-se os tumores cutâneos. No Brasil estima-se para o ano de 2012 cerca de 60.180 casos novos deste tipo de neoplasia. Os marcadores tumorais permitem fazer o rastreamento do câncer, o diagnóstico diferencial entre uma neoplasia benigna e maligna, a avaliação de prognóstico e o acompanhamento terapêutico, assim como a detecção da recidiva tumoral. Dentre estes marcadores tumorais, tem-se dado muito atenção para as proteínas que mediam e participam da progressão do ciclo celular. A ciclina D1 é uma proteína nuclear de vida curta que é destruída pela via da ubiquitina ATP dependente, e está envolvida na transição celular da fase do ciclo G1 (repouso) para a fase S (síntese) tanto em células normais como em células neoplásicas. A super expressão de ciclina D1 remove a regulação normal do ciclo celular causando proliferação celular descontrolada, um crescimento anormal dos tecidos e a transformação para um fenótipo neoplásico, atuando como oncogene. No presente trabalho foi estudado a expressão de ciclina D1 em adenocarcinomas de próstata, tendo como objetivo avaliar a relação desta proteína com parâmetros epidemiológicos, clínicos e histopatológicos. Adicionalmente também foi feita comparação de escore de Gleason e lateralidade tumoral entre biópsias prostáticas com agulha e de prostatectomias radicais. No ensaio para ciclina D1 foram analisados 85 casos através de imunoistoquímica (IHQ) de material proveniente de prostatectomias radicais diagnosticados com adenocarcinoma de próstata entre os anos de 2005 e 2010 em nosso serviço. O método de avaliação se utilizou de microscopia ótica comum e contagem semi-quantitativa, comparado-se a expressão com achados clínicos, epidemiológicos e histopatológicos utilizando-se Teste T de Fisher, Qui Quadrado, Mann-Whitney, Curva ROC e correlação de Spearman. Os resultados demonstraram correlação positiva de ciclina D1 com escore de Gleason (p<0,05), com volume prostático (p=0,01) e uma tendência a correlação positiva com invasão perineural (p=0,07). Não houve correlação estatística entre ciclina D1 e o aumento de PSA, assim como outros achados histopatológicos. As biópsias prostáticas com agulha apresentaram subestimação em 40% dos casos para escore de Gleason e de 62,3% dos casos para lateralidade tumoral quando comparadas a prostatectomia radical. Já que as taxas de subestimação de escore de Gleason e lateralidade tumoral são relativamente altas e visto a urgência em se padronizar novos biomarcadores para o câncer prostático, sugerimos que ciclina D1 pode ser utilizada como biomarcador em patologia cirúrgica da próstata auxiliando numa gradação histológica mais precisa em biópsias com agulha colaborando para melhor vigilância e escolha terapêutica.Prostate cancer is the most common malignant tumor in men older than 50 years, except for skin tumors. In Brazil it is estimated for the year 2012 about 60,180 new cases of this type of neoplasm. Tumor markers allow to cancer screening, differential diagnosis between a benign and malignant, assessment of prognosis and therapeutic monitoring, and detection of tumor recurrence. Among these tumor markers, has been given much attention for proteins that mediate and participate in cell cycle progression. Cyclin D1 is a short-lived nuclear protein that is destroyed by the ATP ubiquitin dependent pathway, and is involved in the transition of cell cycle G1 phase (resting) to the S phase (synthesis) cells both in normal and neoplastic cells. The overexpression of cyclin D1 removes the normal regulation of cell cycle causing uncontrolled cell proliferation, abnormal growth of tissues and transformation to a neoplastic phenotype, acting as an oncogene. In the present work we studied the expression of cyclin D1 in prostate adenocarcinomas, and to evaluate the relationship of this protein with epidemiologic factors, clinical and histopathological features. Additionally comparison was also made of Gleason score and laterality between tumor biopsies and prostate needle radical prostatectomies. In the assay for cyclin D1 were 85 cases analyzed by immunohistochemistry (IHC) of material from radical prostatectomies diagnosed with prostate adenocarcinoma between the years 2005 and 2010 at our institution. The evaluation method utilized were light microscopy and semi-quantitative score, comparing the cyclin D1 expression with clinical, epidemiological and histopathological features using Fisher\'s exact test, chi square test, Mann-Whitney test, ROC curve and Spearman correlation. The results showed a positive correlation of cyclin D1 with Gleason score (p <0.05), prostate volume (p = 0.01) and a trend toward positive correlation with perineural invasion (p = 0.07). There was no statistical correlation between cyclin D1 and increased PSA, as well as other histopathologic features. Prostate needle biopsies showed underestimation in 40% of cases for Gleason score and 62.3% of cases for tumor laterality when compared to radical prostatectomy. Since the rates of underestimation of Gleason score and tumor laterality are relatively high and the urgency to standardize new biomarkers for prostate cancer, we suggest that cyclin D1 may be used as biomarkers in surgical pathology of the prostate assisting more accurate histological grading in needle biopsies and collaborating for better surveillance and therapeutic choice.
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Alhabhbeh, Ammar, Purva Sharma, Mohammad Ali Khan, Koyamangalath Krishnan, and Devapiran Jaishanker. "Adenocarcinoma of Prostate with Small Cell Differentiation Presenting As Refractory Hypokalemia." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/asrf/2020/presentations/29.
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Prostate cancer is among the most common malignancies in males in the United States and adenocarcinoma accounts for 95% of all malignancies of prostate. Rarely prostate cancer can also present as small cell carcinoma. Pure small cell carcinoma is rare at time of initial diagnosis (<2%) however neuroendocrine differentiation into small cell carcinoma may emerge in men who have had previous treatment with ADT for prostate adenocarcinoma. These tumors, sometimes called treatment-related neuroendocrine prostate cancers or aggressive-variant prostate cancers, are increasingly recognized in the castration-resistant phases of disease progression. They account for less than 1% of all prostate cancers. A 73-year-old otherwise male had routine health screening in May 2018. Prostate specific antigen (PSA) level was elevated at 9.53 ng/mL. He had not had a screening PSA for at least two prior years but this was a significant change from prior levels. Patient was asymptomatic however the abnormal laboratory evaluation prompted consultation with Urology. Biopsy of prostate gland confirmed prostatic adenocarcinoma with Gleason's score of 5+ 4 = 9 with bilateral gland involvement. Imaging studies including CT scan of abdomen and pelvis, a bone scan and a PET scan showed no clear evidence of metastatic disease. Patient's clinical stage was determined to be IIIC with T2c N0 M0 disease. Patient began treatment with androgen deprivation therapy and received definitive radiation treatment with external bean radiation therapy from July to September 2018. PSA was 0.08 ng/ml at the end of radiation treatment. Patient did well for about 15 months, after which he had multiple hospital admissions for dyspnea, fluid retention and lower extremity edema. He was also found to have refractory hypokalemia. Patient underwent MRI brain which revealed numerous small enhancing calvarial and skull base lesions consistent with bony metastasis in the skull. Patient also underwent PET/CT scan which showed numerous thoracic spine bony lesions, numerous to count bony metastasis throughout the lumbar spine and pelvis, as well as multiple hepatic lesions. Patient underwent biopsy of right hepatic lobe lesion and pathology was consistent with small cell carcinoma with positive neuroendocrine markers including CD56, synaptophysin and TTF-1. Interestingly patient’s PSA was only 0.09ng/dL. Given refractory hypokalemia, paraneoplastic syndrome was suspected and further work-up was initiated. Serum cortisol levels were elevated at 119.6 mcg/dL (3.7-19.4) and ACTH level was 333 pg/mL (7.2 - 63.3). Aldosterone level was <1 ng/dL (0 - 30.0). Patient was diagnosed with paraneoplastic Cushing syndrome. Given aggressive nature of this small cell transformation, patient was started on treatment with systemic chemotherapy with Carboplatin/Etoposide during the hospital stay, with stabilization of potassium levels. Prostate small cell carcinoma poses a challenge for diagnosis and treatment. In contrast to adenocarcinoma of the prostate, serum prostate-specific antigen (PSA) is not predictive of disease severity, nor is it a useful tumor marker for monitoring progression or surveillance. Patients with prostate small cell cancer presents with more diverse symptoms than any other prostate cancer since it tends to metastasize early. Also paraneoplastic syndromes are more common in prostate small cell cancers as well.
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Paul, Alan Burnett. "β-NGF and its low-affinity receptor (p75LNGFR) in benign prostatic hyperplasia and adenocarcinoma of the prostate." Thesis, University of Edinburgh, 1999. http://hdl.handle.net/1842/29936.
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β-NGF was measured in human benign prostatic hyperplastic (BPH), adenocarcinomatous and normal tissues using an enzyme-linked immunosorbent assay. Concentrations were 1992pg/g wet weight in BPH tissue (SD = 684pg/g), 3100pg/g in adenocarcinomatous tissue (SD = 1503pg/g), and 2690pg/g in normal tissue. mRNA transcripts for β-NGF were demonstrated in prostate tissues by reverse transcription-polymerase chain reaction showing that the β-NGF measured in prostate tissue was endogenously produced. Western blotting allowed the demonstration that immunoreactive β-NGF in the prostate represented dimeric β-NGF and not behaviour β-NGF-like proteins which have been described elsewhere. Immunohistochemistry for β-NGF localised the hormone to the prostate epithelium in BPH, cancer and normal tissue. This epithelial localisation was confirmed by video-assisted tissue morphometric studies. Thereby it was shown that specimen β-NGF concentrations correlated well and statistically significantly with specimen prostatic glandular content. Morphometric studies also allowed the expression of β-NGF concentrations in terms of each specimen's contained, β-NGF secreting, glandular tissue. Thereby it was demonstrated that BPH glandular tissue produced greater concentrations of β-NGF (1597pg/100mg glandular tissue, SD = 788pg/100mg) than did malignant glandular tissue (1058pg/100mg glandular tissue, SD = 559pg/100mg), in spite of the higher concentrations of β-NGF found grossly in adenocarcinomatous tissue. β-NGF concentrations did not correlate with differential of adenocarcinomas or with the degree of neurodocrine differentiation therein. The thesis suggests that human prostatic β-NGF has a role similar to that described in other tissues. That is the maintenance and stimulation of adrenergic nerves. This may be relevant to the widespread use of sympatholytic drugs in the treatment of BPH.
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Donald, Carlton Dewitt. "Cytoskeletal Dynamics and cellular differentiation influence tumor progression and metastatic potential in Prostate Adenocarcinoma." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 1997. http://digitalcommons.auctr.edu/dissertations/3298.
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Cancer cell attachment to and invasion of an extracellular matrix has been associated with metastatic potential. Recently it has become apparent that the extracellular matrix may influence several phenotype properties of metastatic cancer cells. The mechanisms which regulate prostate cancer growth and metastasis may be particularly relevant to the development of clinical strategies for better understanding and ultimate treatment and control of the disease.
Cell-matrix interactions of prostate tumor cells were investigated by comparing the invasive ability through and attachment to reconstructed extracellular matrix components. A correlation was found between metastatic potential and adhesive ability. Non-metastatic AT-1 cells possessed a higher adhesive potential to extracellular matrix components than the highly metastatic cells (Mat-Lu, Mat-LyLu and AT-3) which had higher invasive potentials.
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Toniazzo, Gustavo Piazza. "Correlação entre níveis séricos de PSA e estimativa de volume tumoral em fragmentos de biópsia de próstata em pacientes portadores de adenocarcinoma da próstata." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2005. http://hdl.handle.net/10183/10733.
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Objetivo: Determinar a correlação entre os níveis de PSA, escore Gleason e a estimativa de volume tumoral em fragmentos de biópsia de próstata em pacientes portadores de CaP. Material e Métodos: No período de 26 de abril a 15 de setembro de 2000 foram avaliados 64 pacientes submetidos à dosagem do PSA sérico e com biópsia transretal da próstata compatível com carcinoma. Os fragmentos biopsiados foram analisados quanto ao diagnóstico anatomo-patológico, graduação histológica pelo sistema Gleason e estimativa de volume tumoral através da determinação da proporção de carcinoma nos fragmentos obtidos na biópsia e medida do maior eixo tumoral. Resultados: Este estudo demonstrou a associação positiva entre estimativa de volume tumoral e níveis séricos de PSA. Entre as medidas de volume tumoral a correlação foi de maior magnitude quando se considera a proporção objetiva de carcinoma na amostra. Em relação ao escore Gleason, foi demonstrada associação significativa com níveis séricos de PSA (p<0,01) e com as medidas de volume tumoral (p<0,05). Conclusão:Existe correlação entre níveis séricos de PSA, escore Gleason e estimativa de volume tumoral em fragmentos de biópsia da próstata de pacientes com adenocarcinoma da próstata, porém o impacto dessa associação na determinação prognóstica desses pacientes permanece indeterminada.Purpose: To determine the correlation between serum prostate specific antigen (PSA) levels, Gleason score and tumor volume in prostate needle biopsy cores in patients with prostate cancer. Materials and Methods: A total of 64 patients who underwent prostate biopsy between april 26th and September 15th 2000 had the histologic diagnosis of prostate cancer. Prostate needle biopsy specimens where examined for histologic diagnosis, Gleason score and tumor volume measure through the determination of the cancer ratio in the biopsy cores and by the linear measurement of the biggest tumor axle . Serum PSA levels obtained previously to the biopsy were also determined. Results: We found a positive correlation between tumor volume estimative and PSA serum levels. Considering the tumor volume measures, the cancer ratio in the biopsy cores was the independt measure wich had the strongest correlation. Considering Gleason score, a significant association with PSA serum levels was demonstrated (p<0,01) as well when associated to tumor volume measures, Gleason (p<0,05). Conclusions: There is correlation between PSA serum levels, Gleason score and tumor volume measures in prostate needle biopsy cores in men with prostate cancer, however the impact of this association in the prognostic determination of these patients remains unclear.
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Montico, Fabio 1987. "Estroma reativo e próstata = senescência e inibição da angiogênese x lesões glandulares no modelo TRAMP = Reactive stroma and prostate: senescence and angiogenesis inhibition x glandular lesions in the TRAMP model." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/318023.
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Orientador: Valéria Helena Alves Cagnon QuiteteTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A senescência está associada a modificações hormonais na próstata, resultando em microambiente favorável ao desenvolvimento de lesões neoplásicas. A angiogênese é fundamental para o crescimento tumoral e, na próstata, está sujeita à regulação por andrógenos, sendo sua estimulação um importante evento no estroma reativo associado ao câncer. Assim, a inibição da angiogênese representa terapia promissora no tratamento de neoplasias da próstata. O objetivo deste estudo foi caracterizar aspectos do estroma prostático na senescência e frente a terapias antiangiogênicas e de ablação hormonal, comparando-os com a reação estromal associada a lesões glandulares no modelo TRAMP. Camundongos FVB machos senis (52 semanas) foram submetidos a tratamentos antiangiogênicos com SU5416 (6 mg/kg; i.p.) e/ou TNP-470 (15 mg/kg; s.c.). O bloqueio hormonal foi obtido com finasterida (20 mg/kg; s.c.), isoladamente ou associada a ambos os inibidores. Após 21 dias de tratamento, amostras da próstata dorsolateral foram coletadas para análises morfológicas, imunohistoquímicas e de Western Blotting. A senescência levou à ocorrência de inflamação e de lesões proliferativas na próstata, bem como à maior frequência de células positivas para CD34/VIM e CD34/?SMA e ao aumento de MMP-9, IGFR-1, VEGF, HIF-1?, FGF-2, CD31, VIM e ?SMA, caracterizando semelhança com o microambiente prostático de camundongos TRAMP. Por outro lado, a endostatina e o TGF-? apresentaram-se elevados somente na senescência, mas não ao longo da progressão tumoral no modelo TRAMP. O tratamento com inibidores angiogênicos levou à recuperação e/ou interrupção das alterações glandulares associadas à senescência, mas efeitos diferenciais foram registrados para as drogas. Enquanto o SU5416 atuou principalmente sobre a remodelação tecidual prostática, reduzindo os níveis de MMP-9, VIM e ?SMA bem como a frequência de células positivas para CD34/VIM e CD34/?SMA, o TNP-470 influenciou sobretudo o IGFR-1, o VEGF e o HIF-1?, promovendo inibição de maior amplitude sobre esses fatores. A associação destes inibidores levou à combinação de tais efeitos diferenciais. A finasterida, isoladamente ou associada aos agentes antiangiogênicos, resultou em diminuição dos níveis de MMP-9, IGFR-1, VEGF, HIF-1? e FGF-2 em relação aos controles, embora tenha demonstrado tendência em regular positivamente a expressão de fatores pró-angiogênicos. Todavia, ao contrário da inibição da angiogênese, a ablação hormonal não resultou em diminuição do TGF-?. Assim, concluiu-se que a senescência gerou um microambiente de estroma reativo similar ao do modelo TRAMP, com estímulo aos à proliferação celular, remodelação tecidual, angiogênese e transição endotélio-mesenquimal, certamente propiciando condições favoráveis para o desenvolvimento de lesões prostáticas pré-malignas e malignas. Entretanto, a ausência de adenocarcinoma pouco diferenciado e a menor distribuição das lesões neoplásicas em relação a camundongos TRAMP sugeriram um possível papel protetor da endostatina sobre a próstata na senescência. A terapia antiangiogênica foi eficaz em promover efeitos antitumorais e a inibição da neovascularização, sobretudo frente à combinação dos inibidores, sugerindo que a ação diferencial desses agentes nos processos tumorigênicos resulta em espectro de ação mais amplo para o tratamento. Por fim, ressalta-se que os efeitos benéficos do tratamento com finasterida merecem especial atenção, considerando o potencial desta droga em promover o estroma reativo facilitador do desenvolvimento de desordens glandulares
Abstract: Senescence is associated with hormonal changes in the prostate, leading to a permissive microenvironment for the development of neoplastic lesions. Prostatic angiogenesis is an androgen-regulated process which is fundamental for tumor growth and represents an important event in cancer-associated reactive stroma. Thus, angiogenesis inhibition emerges as a promising therapy in the treatment of prostate neoplasms. The aim herewith was to characterize prostatic stroma during senescence and following antiangiogenic and hormonal ablation therapies, comparing the findings with the reactive stroma phenotype associated to TRAMP model glandular lesions. Elderly male FVB mice (52 week-old) were submitted to antiangiogenic treatments with SU5416 (6 mg/kg; i.p.) and/or TNP-470 (15 mg/kg; s.c.). Hormonal blockage was achieved with finasteride administration (20mg/kg; s.c.), either alone or combined to both inhibitors. After 21 days of treatment, dorsolateral prostate samples were collected for morphological, immunohistochemical and Western Blotting analysis. Senescence led to the occurrence of inflammatory foci and proliferative lesions in the prostate, apart from increased frequency of CD34/VIM and CD34/?SMA positive cells and raised levels of MMP-9, IGFR-1, VEGF, HIF-1?, FGF-2, CD31, VIM and ?SMA, resembling TRAMP mice prostatic microenvironment. On the other hand, endostatin and TGF-? showed higher expression in senescence but not during tumor progression in the TRAMP model. Antiangiogenic treatment resulted in recovery and/or interruption of the senescence-associated glandular changes, showing differential effects for each drug. SU5416 acted mainly on prostatic tissue remodeling, reducing MMP-9, VIM and ?SMA levels as well as the frequency of CD34/VIM and CD34/?SMA positive cells, whereas TNP-470 influenced specially IGFR-1, VEGF and HIF-1?, promoting greater inhibition over these factors. The association between the inhibitors led to synergistic differential effects. Despite presenting a trend to regulate positively pro-angiogenic factor expression, finasteride resulted in decreased MMP-9, IGFR-1, VEGF, HIF-1? and FGF-2 levels relatively to controls, either in isolation or combined to antiangiogenic agents. However, unlike angiogenesis inhibition, hormonal ablation did not lead to decreased TGF-? expression. Thus, it was concluded that senescence created a reactive stroma microenvironment which resembles that verified in the TRAMP model and is characterized by stimulated cell proliferation, tissue remodeling, angiogenesis and endothelial-to-mesenchymal transition. This scenario certainly provided favorable conditions for the development of pre-malignant and malignant prostatic lesions. However, the absence of poor-differentiated adenocarcinoma and the lesser distribution of neoplastic lesions in relation to TRAMP mice suggested a possible protective role of endostatin on the prostate during aging. Antiangiogenic therapy was efficient in promoting antitumor effects and neovascularization inhibition, especially following the combination of inhibitors, suggesting that the differential action of these agents on tumorigenic processes results in a broader spectrum of effects for the treatment. Finally, it is noteworthy that beneficial effects from finasteride treatment must be looked carefully, considering the capacity of this drug to promote a reactive stroma microenvironment favorable to the development of glandular disorders
Doutorado
Anatomia
Doutor em Biologia Celular e Estrutural
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Pham, Hung. "Dietary [gamma]-linolenic acid suppression of prostate cancer growth in the Lobund-Wistar rat model of prostatic adenocarcinoma /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2004. http://uclibs.org/PID/11984.
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Tam, Ngai-chung Neville. "The influence of embryonic urogenital sinus mesenchyme on the cytodifferentiation of the dunning prostatic adenocarcinoma /." Hong Kong : University of Hong Kong, 1995. http://sunzi.lib.hku.hk/hkuto/record.jsp?B16504793.
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Fernandez, Daniel Celestino. "Fourier-transform infrared spectroscopic imaging of prostate histopathology." [Tampa, Fla.] : University of South Florida, 2003. http://purl.fcla.edu/fcla/etd/SFE0000617.
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Lu, Xiaofeng. "Changes in cytodifferentiation of the dunning prostatic adenocarcinoma induced by neonatal rat seminal vesicle mesenchyme /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19852216.
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Shaw, Gregory. "An investigation into the prevention and treatment of androgen independence in adenocarcinoma of the prostate." Thesis, Queen Mary, University of London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.479482.
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Richmond, Oliver H. III. "Extraction, Purification and Evaluation of PRMT5-Inhibitory Phytochemical Compounds for the Treatment of Prostate Adenocarcinoma." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2019. http://digitalcommons.auctr.edu/cauetds/185.
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The development and advancement of prostate cancer is supported by a plethora of genetic and proteomic abnormalities, including events of post-translational modifications. The protein arginine methyltransferase 5 (PRMT5) enzyme regulates epigenetic events of histone modifications and protein post-translational modifications within protein signaling pathways. PRMT5 functions by catalyzing the symmetric dimethylation of terminal arginine residues on target protein substrates. Under abnormal conditions of overexpression and upregulation, PRMT5 methyltransferase activity constitutively drives the growth and proliferation of dysregulated cells. Overexpression or upregulation of PRMT5 correlates with disease progression as observed among numerous cancer types, including breast, colorectal, leukemia, lung, melanoma and prostate cancers. We demonstrated previously that PRMT5 knockdowns attenuated both growth and proliferation of lung and prostatic tumors, in vitro and in vivo. Plants naturally produce chemical toxins as mechanisms of defense against microbial and other biological threats. Human exploitation, consumption and application of agents isolated from plants for therapeutic intervention dates back throughout the millennia. In this study, we extracted, purified and evaluated natural, small, chemical compounds from plant products that antagonize PRMT5 activity in prostate cancer cells. We found that crude and purified extracts of Dendrobium aurantiacum var. denneanum (D. denneanum) plants attenuated prostate tumor growth and proliferation by selective inhibition of PRMT5 methyltransferase activity. These findings establish the first set of natural PRMT5-specific inhibitors reported.
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Nightingale, Joanna. "Investigation of androgen receptor gene transfection into human prostate cancer cells : effects on cellular growth, apoptosis and adhesion." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325852.
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Goodin, Jeremy Lee. "Characterization of Gene Expression During Adenosine 3':5'-Cyclic Monophosphate Induced Neuroendocrine Differentiation in Human Prostatic Adenocarcinoma." Diss., Virginia Tech, 2002. http://hdl.handle.net/10919/26791.
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The LNCaP cell line is a versatile and useful model that is suitable for the study of human prostate cancer in vitro. The elevation of LNCaP intracellular cAMP levels through the addition of membrane permeable cAMP analogues, phosphodiesterase inhibitors, adenylate cyclase activators, or components of the cAMP signal transduction pathway can induce reversible neuroendocrine differentiation. Elucidation of those genes that are differentially expressed between undifferentiated prostate cancer cells and prostate cancer cells that have been induced to differentiate may present new insights for the molecular mechanisms governing neuroendocrine differentiation, early detection of prostate cancer, and/or potential targets for gene therapy. In this study, differential display PCR was used to identify 226 differentially expressed PCR products. Twelve of the differential display PCR products were confirmed by Northern blot analysis and cloned. DNA sequencing and database comparisons were performed. Among the differentially expressed genes, the human ribosomal S3a gene was identified as down regulated in response to LNCaP differentiation. In order to better ascertain the mechanism by which HRS3a gene expression is decreased during differentiation, the promoter region for this gene was analyzed. Electrophoretic mobility shift assay, antibody supershift assays, site-directed mutagenesis, and luciferase reporter gene analysis were employed to authenticate the roles of several transcription factors in the regulation of the HRS3a gene. Two cyclic AMP response elements, a Sp1 element and a GA-binding protein element, were involved in the regulation of HRS3a gene expression. In order to ascertain the effect of HRS3a down regulation in LNCaP cells, antisense phosphorothioate oligonucleotides were designed to inhibit HRS3a gene expression. Treatment of LNCaP cells with antisense HRS3a oligonucleotides did not influence cAMP induced neuroendocrine differentiation but antisense treatment did result in a decrease in LNCaP cell growth. In addition, it was determined that morphological changes associated with cAMP induced differentiation of LNCaP cells from the epithelial to the neuroendocrine state may not require alterations in gene expression nor the expression of novel proteins.Ph. D.
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RAMIREZ, MORALES RAFAEL IGNACIO. "Molecular and cellular effects of mycophenolic acid: study on prostate cancer derived cell lines." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/1064.
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L'acido micofenolico (MPA) è una micotossina nota per la sue proprietà antibiotiche, anti-neoplastiche, immunosoppressorie, antivirali, antimicotiche, e anti-psoriasi. L'MPA è un inibitore reversibile non competitivo dell'IMPDH, l'enzima chiave nella biosintesi delle purine.
Con la riduzione della riserva di nucleosidi, l'MPA inibisce efficacemente la sintesi di RNA e di DNA. L'assenza di divisione del DNA è il meccanismo principale attraverso cui l'acido micofenolico provoca l'arresto del ciclo cellulare. E' stato recentemente dimostrato che l'MPA induce la ridifferenziazione di vari tipi di cellule neoplastiche, tra cui alcune linee cellulari derivate da adenocarcinoma prostatico.
L'obiettivo della nostra ricerca è quello di determinare gli effetti dell'MPA su delle linee cellulari derivate da adenocarcinoma prostatico. L'obiettivo a lungo termine è quello di creare un modello in vitro per lo studio delle escrezioni prostatiche, in particolare dei prostasomi.
Per raggiungere questo obiettivo abbiamo cercato delle prove a lungo e breve termine dell'azione dell'MPA sia a livello citologico che genetico. Abbiamo anche valutato se tali modifiche
venisero mantenute anche dopo la sospensione del trattamento farmacologico.
Abbiamo osservato diversi gradi di ridifferenziazione sulla base di criteri morfologici, fisiologici e molecolari. In particolare, l'MPA ha indotto l'espressione di diversi marcatori molecolari per la differenziazione e la funzione epiteliale, cioè di MME, DPP IV e PSA.
Inoltre, abbiamo rilevato la trascrizione del Recettore Androgeno (AR) in un tipo cellulare in cui l'espressione era precedentemente assente, evento che indica la rimozione della repressione trascrizionale del gene.
Livelli iniziali di HPRT sembrano essere un indicatore della sensibilità delle cellule agli effetti inibitori IMPDH. E' noto che l'esaurimento dei livelli intracellulari di GTP, causato dall'inibizione dell'attività IMPDH da parte dell'MPA, regola l'espressione di IMPDH. Noi mostriamo che nelle cellule prostatiche le isoforme sono regolate autonomamente.
Il nostro lavoro dimostra che l'MPA induce una ridifferenziazione parziale sia fenotipica che funzionale delle linee cellulari derivate dal cancro alla prostata da noi studiate. Inoltre abbiamo ottenuto prove che evidenziano che le modifiche citologiche e molecolari, dovute al ridifferenziazione indotta da MPA, vengono mantenute anche in assenza del farmaco.Mycophenolic Acid (MPA) is a mycotoxin well studied for its antibiotic, anti-neoplastic, immunosuppressant, antiinflammatory, antiviral, antipsoriasis and antifungal properties. MPA is a uncompetitive reversible inhibitor of IMPDH, the pivotal enzyme in purine biosynthesis. By reducing the nucleoside pool, MPA effectively inhibits Ribonucleic Acid (RNA) and Deoxyribonucleic Acid (DNA) synthesis, the main mechanism by which it achieves cell cycle arrest. MPA has been recently shown to induce redifferentiation of various neoplastic cell types, including Prostate Cancer derived cell lines. The goal of our research is to determine the effects of MPA on Prostate Cancer derived cell lines. The long term objective is to establish an in vitro model for the study of prostate derived exosomes, the prostasome. To meet this objective we sought evidence of long and short term effects of MPA both on cytological and genetic levels. We also assesed if these modifications were maintained beyond the pharmacological challenge. We observed varying degrees of redifferentiation, based on the morphological, physiological and molecular criteria. In particular, MPA induced expression of various molecular markers for epithelial differentiation and function, namely MME, DPP IV and PSA. Additionally, we detected transcription of the AR in a cell type where expression was previously absent, indicating the lift of the transcriptional repression of the gene. Initial levels of HPRT seem to be an indicator of cell sensibility to IMPDH inhibitors. The depletion of the GTP pool—caused by the inhibition of IMPDH activity by MPA—is known to regulate the expression of IMPDH. We show that the isoforms are regulated independently. Our work shows that MPA induces partial phenotypical and functional redifferentiation of the Prostate Cancer derived cell lines studied. We show cytological and molecular evidence that MPA induced redifferentiation can be in part sustained after the pharmacological challenge in the absence of the drug.
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Paiva, Greicy Helen Gambarini [UNESP]. "Genes candidatos a marcadores tumorais na progressão do adenocarcinoma de próstata indentificados por análise de HR-CGH e CGH-ARRAY." Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/102718.
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O câncer de próstata (CaP) é a neoplasia mais comumente diagnosticada entre homens no ocidente. Embora tratamentos efetivos para a doença localizada estejam disponíveis atualmente, não há terapia curativa para tumores metastáticos. Além disso, os marcadores diagnósticos utilizados na clínica não conseguem discriminar totalmente a evolução diferencial da doença. Desta forma, o conhecimento das diferenças biológicas entre tumores primários confinados ao órgão e metástases é essencial para o desenvolvimento de novos marcadores e identificação de alvos terapêuticos. Neste estudo a análise baseada na metodologia de HR-CGH cromossômico foi realizada para identificar alterações de ganhos e perdas genômicas em três grupos de amostras: o grupo I, que compreende amostras pareadas de tumor primário e respectivas metástases (11 casos); o grupo II, constituído de pacientes que apresentaram seguimento clínico favorável por mais de 10 anos (5 casos); e o grupo III, constituído por diferentes biópsias do mesmo paciente (5 pacientes com 2 biópsias cada). As amostras foram microdissecadas (amostras a fresco: a partir de lâminas de referência; em blocos de parafina: a laser) e após a obtenção de DNA foram amplificadas (amostras de arquivo: PCR-SCOMP) ou marcadas por nick-translation para a realização de HR-CGH. Os resultados de HR-CGH foram comparados com os dados obtidos da análise de CGH-array num subgrupo de amostras e revelaram concordâncias significativas. Os resultados obtidos na presente investigação revelaram perdas dos cromossomos 1p, 2, 3q, 4p, 5q, 7, 8, 9q, 10q, 11q, 12q, 14q, 15q, 16q, 17q, 18q, 19, 20q e 22q em 80% dos casos avaliados. Além disso, perdas em 17q11.2-25, por exemplo, foram detectadas exclusivamente nos tumores do grupo I e nas suas metástases, e não nos tumores do grupo II, sugerindo que esta alteração deve ser importante...
Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous malignancy and the second leading cause of cancer mortality in men from Occident. Although effective treatments for the localized disease are available, there is no efficient therapy for metastatic tumors. Additionally, clinical diagnostic markers are not able to completely discriminate the differential evolution of the disease. The knowledge of biological differences between localized primary tumors and metastasis can establish new molecular markers and therapeutic targets. In this study, an analysis based on HR-CGH methodology was performed to identify imbalances genomic in three groups of samples: group I, paired samples of primary tumors and its metastasis (11 cases); group II, patients that exhibited favorable follow-up over 10 years (5 cases); and group III, different biopsies from the same patient (5 patients with 2 biopsies each). The tumor samples were submitted to microdissection procedures (fresh samples: from reference slides; paraffin embedded samples: laser), DNA extracted and amplified (archive sample: PCR-SCOMP) or labeled by nick-translation to HR-CGH. The HRCGH results were compared with data obtained from CGH-array analysis of a subgroup of samples and revealed significant concordances. In the present investigation, there were observed losses on chromosomes 1p, 2, 3q, 4p, 5q, 7, 8, 9q, 10q, 11q, 12q, 14q, 15q, 16q, 17q, 18q, 19, 20q and 22q in 80% of the cases. Losses in 17q11.2-25, for instance, were detected exclusively in tumor from group I and its metastasis, but were not found in tumors from group II, suggesting that this alteration must be important in the progression of the disease. Five genes were selected after the comparison between the HR-CGH and CGH-array data. The tumor suppressor genes ARID1A, MTSS1, NME1 and S100A4 and TOP2A (oncogenes) were evaluated by quantitative real time... (Complete abstract click electronic access below)
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Rosa, Thalita Marra. "ALTERAÇÕES GENÔMICAS NO GENE PTEN EM PACIENTES COM ADENOCARCINOMA DE PRÓSTATA EM GOIÂNIA." Pontifícia Universidade Católica de Goiás, 2014. http://localhost:8080/tede/handle/tede/2374.
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Previous issue date: 2014-02-19The use of molecular markers has contributed to the identification of genes and chromosomal alterations in different stages of a given disease can result in a huge breakthrough in determining its pathophysiology. The proposed study focuses his attention on becoming more accessible and understandable for doctors and patients to laboratory diagnostic tools for prostate cancer and socialize them in health promotion. The aim of this study was to understand how loss / gain genomic PTEN is associated with prostate cancer. Changes of the PTEN gene were evaluated in 38 cases of patients with prostate cancer and the fluorescent signals for each probe were counted in 100 interphase nuclei per slide, no overlapping and intact. The occurrence of genomic alterations in PTEN were examined and classified as homozygous , hemizigose , monosomy, gain and loss regions of chromosome 10. The study demonstrated a high rate of monosomic alterations, 76.3% of cases, and hemizigose deletions represented 21.1%, while the gain of chromosome 10 was 2.6%. In the group of patients, 5.2% were hereditary, 36.8% were sporadic and 57.9% family and for all these groups we found alterations in the PTEN gene. The results of this study indicate that homozygous, hemizigose, monosomy and gain of PTEN gene can be observed in patients with sporadic, familial or hereditary prostate carcinoma. To evaluate and compare the variable smoking and changes in the PTEN gene, we observed a high rate of change in smokers , and who smoke have up to 5.7 times to acquire monosomic alterations ( p = 0.0495 ) , showing a significant association between smoking and monosomic alterations. There was no statistically significant association when comparing drinkers patients with alterations in PTEN (p = 0.52 ) , PSA levels x PTEN ( p = 0.58 ) and PSA x age ( p = 0.68 ). The FISH tool allowed the analysis clearly and effectively of the alterations, demonstrating the reliability of this technique for reading the fluorescent signs in each cell.
O uso de marcadores moleculares tem contribuído para a identificação de genes e alterações cromossômicas em diferentes estágios de uma dada doença podendo resultar em um enorme avanço na determinação de sua fisiopatologia. A presente proposta de estudo centra sua atenção em tornar mais acessíveis e compreensíveis para os médicos e para os pacientes as ferramentas laboratoriais de diagnóstico do câncer de próstata e socializá-las na promoção da saúde. O objetivo do presente estudo foi compreender como perda/ganho genômico de PTEN se associa com o câncer de próstata. As alterações do gene PTEN foram avaliadas em 38 casos de pacientes com câncer de próstata e os sinais fluorescentes para cada sonda foram contados em 100 núcleos interfásicos por lâmina, não sobrepostos e intactos A ocorrência das alterações genômicas de PTEN foram examinadas e classificadas em homozigose, hemizigose, monossomia, ganho e perda de regiões do cromossomo 10. O estudo demonstrou um alto índice de alterações do tipo monossômica, 76,3% dos casos, e deleções do tipo hemizigose para 21,1% sendo que a porcentagem de ganho do cromossomo 10 foi de 2,6%. No grupo de pacientes avaliados, 5,2% eram do tipo hereditário, 36,8% familiares e 57,9% esporádicos e para todas essas classificações foi possível encontrar alterações no gene PTEN. Os resultados do presente estudo indicam que alterações do gene PTEN do tipo homozigose, hemizigose, monossomia e ganho podem ser observadas em pacientes com carcinoma prostático esporádico, familial ou hereditário. Ao avaliar e comparar a variável tabagismo e as alterações no gene PTEN pode-se obsevar um alto índice de alterações nos pacientes fumantes, sendo que quem fuma tem 5,7 vezes mais chances de sofres alterações do tipo monossômicas (p= 0,0495), evidenciando uma associação significativamente entre fumantes e alterações monossômicas. Não houve associação estatisticamente significativa quando se comparou os pacientes etilistas com alterações no PTEN (p= 0,52), níveis de PSA x PTEN (p= 0,58) e PSA x idade (p= 0,68). A técnica de FISH possibilitou a análise das alterações de forma clara e eficaz, evidenciando a confiabilidade desta técnica quanto à leitura dos sinais de fluorescência em cada célula.
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Bylund, Annika. "Phytoestrogens and prostate cancer : experimental, clinical, and epidemiological studies." Doctoral thesis, Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1402.
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Paiva, Greicy Helen Gambarini. "Genes candidatos a marcadores tumorais na progressão do adenocarcinoma de próstata indentificados por análise de HR-CGH e CGH-ARRAY." Botucatu : [s.n.], 2009. http://hdl.handle.net/11449/102718.
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Orientador: Silvia Regina RogattoBanca: Spencer L. M. Payão
Banca: Carla Rosemberg
Banca: José Carlos de S. Trindade
Banca: Maria Aparecida M. Rodrigues
Resumo: O câncer de próstata (CaP) é a neoplasia mais comumente diagnosticada entre homens no ocidente. Embora tratamentos efetivos para a doença localizada estejam disponíveis atualmente, não há terapia curativa para tumores metastáticos. Além disso, os marcadores diagnósticos utilizados na clínica não conseguem discriminar totalmente a evolução diferencial da doença. Desta forma, o conhecimento das diferenças biológicas entre tumores primários confinados ao órgão e metástases é essencial para o desenvolvimento de novos marcadores e identificação de alvos terapêuticos. Neste estudo a análise baseada na metodologia de HR-CGH cromossômico foi realizada para identificar alterações de ganhos e perdas genômicas em três grupos de amostras: o grupo I, que compreende amostras pareadas de tumor primário e respectivas metástases (11 casos); o grupo II, constituído de pacientes que apresentaram seguimento clínico favorável por mais de 10 anos (5 casos); e o grupo III, constituído por diferentes biópsias do mesmo paciente (5 pacientes com 2 biópsias cada). As amostras foram microdissecadas (amostras a fresco: a partir de lâminas de referência; em blocos de parafina: a laser) e após a obtenção de DNA foram amplificadas (amostras de arquivo: PCR-SCOMP) ou marcadas por nick-translation para a realização de HR-CGH. Os resultados de HR-CGH foram comparados com os dados obtidos da análise de CGH-array num subgrupo de amostras e revelaram concordâncias significativas. Os resultados obtidos na presente investigação revelaram perdas dos cromossomos 1p, 2, 3q, 4p, 5q, 7, 8, 9q, 10q, 11q, 12q, 14q, 15q, 16q, 17q, 18q, 19, 20q e 22q em 80% dos casos avaliados. Além disso, perdas em 17q11.2-25, por exemplo, foram detectadas exclusivamente nos tumores do grupo I e nas suas metástases, e não nos tumores do grupo II, sugerindo que esta alteração deve ser importante... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous malignancy and the second leading cause of cancer mortality in men from Occident. Although effective treatments for the localized disease are available, there is no efficient therapy for metastatic tumors. Additionally, clinical diagnostic markers are not able to completely discriminate the differential evolution of the disease. The knowledge of biological differences between localized primary tumors and metastasis can establish new molecular markers and therapeutic targets. In this study, an analysis based on HR-CGH methodology was performed to identify imbalances genomic in three groups of samples: group I, paired samples of primary tumors and its metastasis (11 cases); group II, patients that exhibited favorable follow-up over 10 years (5 cases); and group III, different biopsies from the same patient (5 patients with 2 biopsies each). The tumor samples were submitted to microdissection procedures (fresh samples: from reference slides; paraffin embedded samples: laser), DNA extracted and amplified (archive sample: PCR-SCOMP) or labeled by nick-translation to HR-CGH. The HRCGH results were compared with data obtained from CGH-array analysis of a subgroup of samples and revealed significant concordances. In the present investigation, there were observed losses on chromosomes 1p, 2, 3q, 4p, 5q, 7, 8, 9q, 10q, 11q, 12q, 14q, 15q, 16q, 17q, 18q, 19, 20q and 22q in 80% of the cases. Losses in 17q11.2-25, for instance, were detected exclusively in tumor from group I and its metastasis, but were not found in tumors from group II, suggesting that this alteration must be important in the progression of the disease. Five genes were selected after the comparison between the HR-CGH and CGH-array data. The tumor suppressor genes ARID1A, MTSS1, NME1 and S100A4 and TOP2A (oncogenes) were evaluated by quantitative real time... (Complete abstract click electronic access below)
Doutor
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Aleksandra, Fejsa Levakov. "Ekspresija estrogenog receptora β u prekanceroznim lezijama i adenokarcinomu prostate." Phd thesis, Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, 2016. http://www.cris.uns.ac.rs/record.jsf?recordId=99993&source=NDLTD&language=en.
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Adenokarcinom prostate (PCa) je najčešći karcinom u muškaraca. Intraepitelne prostatične neoplazme visokog gradusa (HGPIN) su lezije koje prethode nastanku invazivnog karcinoma i podrazumevaju kompletno odsustvo bazalnih ćelija i invaziju strome malignim acinusima. Estrogeni receptor β (ERβ) se nalazi u jedrima bazalnih i sekretornih ćelija acinusa i delimično u stromalnim ćelijama. Cilj istraživanja je da prikaže i lokalizuje ERβ u različitim morfološkim lezijama prostate: hiperplaziji (BHP), PINu i u PCa sa različitim Gleason scorom. Pretpostavlja se da prekancerozne lezije u svojim različitim fazama evolucije ne koreliraju u potpunosti sa ekspresijom ERβ. LGPIN pokazuje ekspresiju, dok u HGPINu nema ekspresije. Takođe je pretpostavka da ekspresija ERβ postoji u većine srednje diferentovanih PCa, te da se ekspresija posmatranog receptora gubi sa porastom Gleason scora. Ispitivano je pet grupa bolesnika: kontrolna grupa sa BHP i četiri eksperimentalne grupe (PIN i 3 različite grupe PCa). Studija je sprovedena na muškarcima različite starosti u periodu 2010–2012. Nijedan pacijent nije prethodno primio hormonsku terapiju. Sekstant biopsije prostate su bojene na ERβ (Novocastra). Lokalizacija i intenzitet ERβ ekspresije prikazani su kroz skor: 0 = nula; 1 = <1%; 2 = 1–10%; 3 = 11–33%; 4 = 34–66%; 5 = > 66%. Pozitivni fibroblasti i endotelne ćelije su korišćene za poređenje. Smanjena ekspresija ERβ primećena je kod malignih i premalignih lezija prostate naspram BHP. Ekspresija ERβ u epitelnim ćelijama acinusa bila je najslabija u dobro diferentovanim PCa. Kod BHP i dobro diferentovanih PCa bila je veća ekspresija ERβ u bazalnim ćelijama nego u sekretornim. Loše diferentovani PCa prikazali su smanjenje ekspresije ERβ u bazalnim ćelijama. Ukupna ćelijska ekspresija ERβ predstavlja složen i ponekad moguće paradoksalan nalaz, na osnovu čega primarni PCa zadržava ekspresiju ovog receptora, ali ipak značajno nižu u poređenju sa benignim epitelom i premalignim lezijama. Ovaj nalaz podupire stanovište o antiproliferativnoj ulozi ERβ u tkivu prostate.Adenocarcinoma of the prostate (PCa) is the most common cancer in men. High-grade prostatic intraepithelial neoplasia (HGPIN) are lesions that precede to invasive carcinomas and include complete absence of basal cells and stromal invasion by malignant acini. Estrogen receptor ß(ERß) is located in the nuclei of basal and secretory cells and partly in stromal ones.The aim of the research is to describe and localize ERß in different morphological lesions: prostate hyperplasia (BPH), PIN and PCa with different Gleason score. It is assumed that pre-cancerous lesions in different stages of their evolution not correlate completely with the expression ERß. LGPIN shows expression, while there is no expression in HGPIN. It is also an assumption that the expression ERß exists in most medium differentiated PCa, and that the expression of this receptor loses with increasing of Gleason score. Five groups of patient were investigated: control group with BPH and four experimental groups (PIN and 3 different groups of PCa). The study was conducted on men of different ages in the period 2010-2012. None of the patients received prior hormonal therapy. Sextant prostate biopsy were stained on ERß (Novocastra). ERß expression is shown through the score: 0 = zero; 1 = <1%; 2 = 1-10%; 3 = 11-33%; 4 = 34-66%; 5 => 66%. Positive fibroblasts and endothelial cells were used for comparison. Reduced expression was observed in malignant and premalignant lesions of the prostate versus BPH. ERß expression in the epithelial cells of acini was the weakest in well-differentiated PCa. In BPH and well differentiated PCa was greater expression in the basal cells than in secretory ones. Poorly differentiated PCa showed a decreased ERß expression in basal cells. Total cellular expression of ERß is a complex and sometimes paradoxical finding on the basis of which the primary PCa retains expression of this receptor, but significantly lower compared to benign epithelium and premalignant lesions. This finding supports the antiproliferative role of ERß in prostate tissue.
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PETRE, CHRISTIN ELIZABETH. "CYCLIN D1: MECHANISM AND CONSEQUENCE OF ANDROGEN RECEPTOR CO-REPRESSOR ACTIVITY IN PROSTATIC ADENOCARCINOMA." University of Cincinnati / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1085487395.
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Sahlén, Göran. "Formation, storage and secretion of prostasomes in benign and malignant cells and their immunogenicity in prostate cancer patients /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7511.
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Groß, Stephanie [Verfasser]. "Evaluation of Antimicrobial Peptides as Anti-Cancer Agents against Equine Sarcoid and Human Prostate Adenocarcinoma Cells / Stephanie Groß." Berlin : Freie Universität Berlin, 2015. http://d-nb.info/1074870921/34.
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Tomiyama, Alberto Hiroyuki. "Micro RNA em adenocarcinoma de próstata: caracterização da expressão em tumores de baixo grau, órgão-confinados." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5153/tde-07022012-112055/.
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Introdução: Os micro RNA (miRNA) são formados a partir de RNA precursores de fita dupla que contém entre 60 a 110 nucleotídeos e formam estruturas do tipo hairpin. Imediatamente após sua transcrição pela RNA polimerase II a enzima Dicer promove a clivagem do RNA precursor em seqüências menores contendo 19 a 22 nucleotídeos. Após a clivagem, o miRNA integra-se ao complexo silenciador induzido pelo RNA (RISC) que o conduz ao seu RNA mensageiro (mRNA) homólogo recém transcrito. Esta associação promove a degradação do mRNA, ou interfere na tradução da proteína caracterizando um grande mecanismo de controle da expressão dos genes. Este mecanismo está relacionado ao desenvolvimento de órgãos e tecidos, e está envolvido no processo de carcinogênese. Nosso objetivo é identificar um perfil de expressão de miRNA que defina o adenocarcinoma de próstata de prognóstico favorável e desfavorável considerando os níveis de PSA e dados anatomopatológicos. Materiais e métodos: Foram selecionados 53 pacientes com tumores desfavoráveis (mediana do escore de Gleason igual a 8, 79,2% estadiados pT3, mediana de PSA 10,1 ng/mL e mediana do volume tumoral de 23%) e 45 considerados favoráveis (mediana do escore de Gleason igual a 5, 80% estadiados pT2, mediana de PSA de 7,8 ng/mL e mediana do volume tumoral de 11,5%). O controle foi representado por 7 pacientes com hiperplasia prostática benigna (HPB). Todos os pacientes foram submetidos a prostatectomia radical pelo mesmo cirurgião. Os espécimes cirúrgicos foram examinados na sua totalidade pelo mesmo patologista. A análise dos miRNA foi feita a partir de tecido congelado e tecido incluído em parafina usando a técnica da reação em cadeia da polimerase em tempo real quantitativa (qRT-PCR) utilizando primers e sondas Taqman® específicas. O RNU43 foi usado como controle interno. Resultados: Com exceção dos miRNA 199a, 21, 15a, 16 e 25 que se mostraram subexpressos tanto nos casos desfavoráveis como nos favoráveis, houve uma diminuição global na expressão dos miRNA com redução estatisticamente significativa na expressão dos miRNA 143, 145 e 146a, 191, 218 e Let7c em tumores desfavoráveis em relação aos tumores favoráveis. Conclusão: Demonstramos que no processo de transição entre os carcinomas favoráveis e desfavoráveis de próstata existe uma perda global na expressão de miRNA que podem ser importantes controladores de expressão de uma série de genes relacionados a progressão desta neoplasia. Dados experimentais avaliando o papel desses miRNA devem ser conduzidos para que possamos definir seu papel na evolução do câncer de próstataIntroduction: micro RNA (miRNA) are formed from double-stranded RNA precursors that contain between 60-110 nucleotides and form structures such as hairpin. Immediately after their transcription by RNA polymerase II, the enzyme Dicer promotes the cleavage of precursor RNA sequences containing minor 19-22 nucleotides. After cleavage, the miRNA is part of the RNA-induced silencing complex (RISC) that leads to its messenger RNA (mRNA) newly transcribed counterpart. This association promotes the degradation of mRNA, or interferes with the protein translation characterizing a great mechanism for controlling gene expression. This mechanism is related to the development of organs and tissues, and may be involved in the process of carcinogenesis. Our goal is to identify a miRNA expression profile that distinguishes prostate adenocarcinoma of favorable and unfavorable prognosis considering the PSA and pathological findings. Material and Methods: We studied 53 patients with tumors considered unfavorable (Median of Gleason score 8, 79.2% staged pT3, median of PSA 10.1 ng/mL and median of tumor volume of 23%) and 45 considered favorable (Median of Gleason score 5, 80% staged pT2, median of PSA 7.8 ng/mL and median of tumor volume of 11.5%). The control group was represented by seven patients with benign prostatic hyperplasia (BPH). All patients underwent radical prostatectomy by the same surgeon. The surgical specimen was examined entirely by the same pathologist. The analysis of miRNA was made from frozen and paraffin embedded tissue by quantitative real-time polymerase chain reaction (qRT-PCR) using the Taqman® specific primers and probes. The RNU43 was used as a internal control. Results: Except for miRNAs 199a, 21, 15a, 16 e 25 that were underexpressed by both favorable and unfavorable prostate cancer, there was a global decrease of all miRNAs studied, and some differences were statistically significant as miRNAs 143, 145 e 146a, 191, 218 e Let7c that were underexpressed in unfavorable carcinomas compared favorable tumor. Conclusion: We have demonstrated that in the process of transition between favorable and unfavorable prostate cancer there is a global loss of expression of miRNAs. These molecules can be important controllers of a series of genes related to cancer progression. Experimental studies are needed in order to comprehend the role of these genes in prostate carcinogenesis
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Folkvaljon, Yasin. "Prognostic value of the ISUP 2015 Gleason grade groupings." Thesis, Uppsala universitet, Statistiska institutionen, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-256158.
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Background: New prognostic grade groupings were recently proposed for prostate cancer. They are based on Gleason grading of either biopsy or prostatectomy specimen. Former Gleason 6 corresponds to group 1, Gleason 7=3+4 corresponds to group 2, Gleason 7=4+3 corresponds to group 3, Gleason 8 corresponds to group 4, and Gleason 9-10 correspond to group 5. Objective: To assess the prognostic value of Gleason grade groups in men with prostate cancer from a nationwide population‑based cohort. Design, Setting and Participants: From the National Prostate Cancer Register of Sweden, we identified 5,880 men diagnosed with prostate cancer from 2005 to 2007, including 4,325 who had radical prostatectomy and 1,555 treated by radiotherapy. Outcome Measurements and Statistical Analysis: Kaplan-Meier survival analysis was used to calculate the cumulative 4-year biochemical recurrence-free survival. Cox proportional hazards regression models were used to examine the relationship between prognostic Gleason grade groups and biochemical recurrence after radical prostatectomy and radiotherapy. The 4-year biochemical progression-free survival was compared for groups based on biopsy and prostatectomy Gleason grade groups. Results and Limitations: Among men undergoing surgery, the 4‑year biochemical progression-free survival was 89%, 82%, 74%, 77%, and 49% for prognostic Gleason grade groups 1-5 on biopsy. The corresponding 4-year biochemical progression-free survival based on prostatectomy prognostic Gleason grade groups was 92%, 85%, 73%, 63%, and 51% for prognostic Gleason grade groups 1-5. For men undergoing radiotherapy, biopsy prognostic Gleason grade groups 1-5 had 4-year biochemical progression-free survival of 95%, 91%, 85%, 78%, and 70%. After adjusting for preoperative serum prostate specific antigen and clinical stage, biopsy prognostic Gleason grade groups were significant independent predictors of biochemical progression after radical prostatectomy and radiotherapy. There was no central review of pathology. Conclusions: These results confirm the prognostic value of the newly proposed prognostic Gleason grade groups in men undergoing radical prostatectomy and radiotherapy in a population-based setting.
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Miller, Michael Raymond. "Effects and regulation of dystroglycan glycosylation in cancer." Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/3146.
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The interplay between cancer cells and the extracellular matrix (ECM) remains a critical regulator of both normal tissue organization and cancer cell invasion. Proteins that function as ECM receptors function to link the cell with the ECM. Abberations in either the structure of the ECM or the expression of ECM receptors leads to disrupted interaction and downstream signaling effects. Dystroglyan (DG) is an ECM receptor that is expressed in a variety of tissue types and functions to mediate sarcolemma stability, epithelial polarity, and is critical in the early formation of basement membranes. However, DG has primarily been studied in muscle where loss of its function is linked to a host of muscular dystrophies. In the epithelium, the role of DG remains enigmatic. While DG has repeatedly been shown to lose function during cancer development and progression, the mechanism and functional consequence of its loss are currently unknown.
In order to increase our understanding of DG in cancer development, we analyzed its expression and glycosylation, a functional requirement for DG, in a range of prostate cancer cell lines. Previous work has shown DG to be downregulated in prostate cancer, but the mechanism by which this occurs has remained largely unclear. We found that DG expression is maintained while its glycosylation was heterogeneous in the cell lines. Further investigation revealed that lines with hypoglycosylated DG strongly associated with the loss of expression of the glycosyltransferase LARGE2. Further this enzyme is frequently downregulated in human cancers and appears to serve as a required enzyme in DG glycosylation within prostate epithelium. This is the first work to demonstrate the functional requirement of LARGE2 for DG, and the only work to implicate loss-of-function of LARGE2 in cancer progression.
To determine whether loss of LARGE2 is found in other tumor types, we analyzed human clear cell renal cell carcinoma (ccRCC) samples by immunohistochemistry and via in silico analysis with the Cancer Genome Atlas (TCGA). Our work demonstrated a frequent and significant downregulation of LARGE2 expression and its association with DG hypoglycosylation. Additionally, we found the loss of LARGE2 strongly associated with increased mortality. Thus, we again demonstrated a functional requirement of LARGE2 but also found a clinical correlate with increased mortality.
Finally, we examined the functional outcome of DG hypoglycosylation or loss of expression in both a mouse model of prostate cancer and a variety of cell lines models. We found that while loss of DG expression does not increase prostate cancer growth or metastasis in one model of cancer, loss of its glycosylation does seem to mediate downstream metabolic changes within cells. The mechanism for this change remains unclear.
In summary, these studies have contributed to our understanding of DG glycosylation and function in both prostate and renal carcinoma. Additionally, we have shown a novel mechanism by which DG glycosylation is lost with downregulation of LARGE2 expression. Finally, while we were unable to demonstrate a clear mechanism by which signaling changes arose, we were able to demonstrate a strong correlation between DG hypoglycosylation and increased mortality in ccRCC. These insights could be used to improve treatment of multiple cancer types as our understanding of DG function continues to improve.
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Sá, Vanessa Karen de. "Identificação do perfil de expressão dos splicings alternativos dos genes das hialuronidases em adenocarcinoma de próstata." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5153/tde-15122008-151230/.
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Ácido Hialurônico (HA) é um componente da matriz extracelular, responsável pela hidratação e manutenção do equilíbrio osmótico tecidual. Concentrações de HA estão elevadas em vários tipos de cânceres, incluindo próstata. Hialuronidases (HAases), são uma família de enzimas relacionadas com a propagação de infecções bacterianas, toxinas de venenos e progressão tumoral. A quebra do HA em pequenos fragmentos (3-25 dissacarídeos) promovidos pela ação das HAases tipo Hyal1, Hyal2 e Hyal3, está relacionada à promoção do câncer através da indução da angiogênese e estímulo a proliferação através de ativação da via tirosina quinase. Algumas isoformas de HAases, descritas como produto de splicing alternativo, possuem atividade enzimática diversificada. A heterogeneidade de expressão das HAases foi identificada em alguns tipos de câncer e pode ser correlacionada com o comportamento diferenciado dos tumores. Para este trabalho estudamos amostras de 55 pacientes submetidos a prostatectomia radical por carcinoma de próstata (CP) . A média de idade foi 66 anos e o tempo médio de seguimento 73,7 meses. Os pacientes foram divididos em dois grupos para análise dos resultados: 1- Escore de Gleason (EG) >=7 (30) e EG <=6 (25). 2- Comportamento tumoral (recidiva-19, e não recidiva-36), considerando o nível sérico de Antígeno Específico da Próstata (PSA) 0,2 ng/mL. O grupo controle foi representado por 11 pacientes com hiperplasia prostática benigna, submetidos à ressecção retropúbica. As HYAL foram identificadas por PCR, com uso de primers específicos para as variantes 1, 2, 3, 4 e 5 e wt da HYAL1, wt da HYAL2, e wt e variantes 1, 2 e 3 da HYAL3. As HYAL mais freqüentemente expressas pelo CP foram HYAL2-wt (65,4%), HYAL1-v1 (63,3%) e HYAL3-wt (47,2%). Em tecidos prostáticos benignos, a HYAL3-v1 foi expressa em 90,9% dos casos, estando presente em 36% dos tumores com EG baixo, e não expressa em tumores com EG alto (p=<0,001). Nos tumores sem recidiva HYAL1-v3 foi expressa em 30,5% dos casos versus 5,2% em casos que recorreram (p=0,041). HYAL3 v2, foi expressa por 33,3% dos tumores que não recorreram e não expressa em tumores que recorreram (p=0,002). Concluímos que a expressão de HYAL1-v3, HYAL3-v1 e HYAL3-v2 está relacionada a tumores mais diferenciados e com menores taxas de recidiva, podendo ser utilizadas como marcadores na prática clínica identificando candidatos a terapias mais conservadoras.Hyaluronic acid (HA) is a component of the extracellular matrix that hydrates and maintains the osmotic balance of tissues. HA concentration is elevated in several cancers including prostate. Hyaluronidases (HAases) are a family of enzymes related to the spread of bacterial infections, toxins of venoms and probably cancer progression. Small fragments of HA are generated by HAase Hyal1, Hyal2 and Hyal3, stimulating endothelial proliferation and activating mitogen-activated protein kinase pathway. Several isoforms of HAases have been described as a product of alternative splicing, and are responsible for differences in the enzyme activity. The heterogeneity of HAses expression has been identified in tumors and could be related to the differences in their biological behavior. Fifty-five patients submitted to radical prostatectomy for prostate cancer (PC) were the subject of this study. The mean age was 66 years old and the mean follow-up was 73,7 months. Patients were divided into two groups for the analyses: 1- High Gleason score (GE) >=7 (30) and low Gleason score <=6 (25). 2- Tumor behavior; recurrence - 19 and nonrecurrence - 36. Biochemical recurrence was considered when PSA was higher than 0.2 ng/mL. The control was represented by 11 patients submitted to retropubic prostate resection for benign prostatic hyperplasia. The alternative splicing forms of HYAL were identified by PCR, and the primer sequences identified variants 1, 2, 3, 4, 5 e wt of HYAL1, wt of HYAL2, wt and variants 1, 2 and 3 of HYAL3. The HYAL more frequently expressed by PC was HYAL2-wt (65.4%), HYAL1-v1 (63.3%) and HYAL3-wt (47.2%). In benign prostate tissue the main expressed HAase was HYAL3-v1 in 90.9%, being present in 36% of low Gleason score tumors and not expressed by tumors with high Gleason score (p=<0.001). For tumors that not recurred there was expression of HYAL1-v3 in 30.5% of the cases vs. 5.2% in cases that recurred (p=0.041). The same difference was noted regarding the expression of HYAL3-v2, that was expressed by 33.3% of tumors that not recurred and not expressed by tumors that recurred (p=0.002). We conclude that there is a profile of HAase related to low Gleason score and non-recurrent PC that is characterized by expression of HYAL1-v3, HYAL3-v1 and HYAL3-v2 that could be used in clinical practice to choose a better treatment.
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Verona, Erik. "Blocking transforming growth factor beta signaling in stromal cells to inhibit tumor progression in a mouse model of prostate cancer : a dissertation /." San Antonio : UTHSC, 2007. http://proquest.umi.com/pqdweb?did=1414115771&sid=1&Fmt=2&clientId=70986&RQT=309&VName=PQD.
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Bui, Loan Thuy. "Localisation of kallikreins in the prostate and association with prostate cancer progression." Thesis, Queensland University of Technology, 2006. https://eprints.qut.edu.au/16276/1/Loan_Bui_Thesis.pdf.
Full textAbstract:
At present, prostate cancer is a significant public health issue throughout the world and is the second leading cause of cancer deaths in older men. The prostate specific antigen or PSA (which is encoded by the kallikrein 3/KLK3 gene) test is the current most valuable tool for the diagnosis and management of prostate cancer. However, it is insufficiently sensitive and specific for early diagnosis, for staging of prostate cancer or for discriminating between benign prostatic hyperplasia (BPH) and prostate cancer. Recent research has revealed another potential tumour marker, glandular kallikrein 2 (KLK2 gene/hK2 protein), which may be used alone or in conjunction with PSA to overcome some of the limitations of the PSA test. Twelve new kallikrein gene family members have been recently identified and, like hK2 and PSA, many of these genes have been suggested to be involved in carcinogenesis. In this study, the cellular localisation and level of expression of several of these newer kallikreins (KLK4, KLK5, KLK7, KLK8 and KLK11) was examined in prostate tissue, to provide an understanding of the association of their expression with prostatic diseases and their potential as additional biomarkers. Like PSA and hK2, the present observation indicated that each of these proteins, hK4, hK5, hK7, hK8 and hK11, was detected within the cytoplasm of the secretory cells of the prostate glands. For the first time, all of these newly-identified proteins were shown to be expressed in prostatic intraepithelial neoplasia (PIN) lesions, in comparison to normal glands and cancer lesions. In addition to cytoplasmic secretory cell expression, the localisation of hK4 to the basal cells and nuclei in prostatic lesions was intriguing. The intensity of hK4 staining in prostate tissue was strongest in comparison to the other newly-identified kallikrein proteins (hK5, hK7, hK8 and hK11). Therefore, KLK4/hK4 expression was characterised further to define this cellular localisation and examined in non-prostatic tissue and also in a larger number of prostate tissues in an attempt to determine its potential value as a biomarker for prostate disease. Three hK4 antipeptide polyclonal antibodies, derived against N-terminal, mid-region and C-terminal hK4 amino acid sequences, were used. The hK4 N-terminal antipeptide antibody was used to demonstrate the cellular localisation of hK4 in kidney, salivary glands, liver, testis, colon carcinoma, heart, endometrium and ovarian cancer, for the first time. The presence of hK4 in these non-prostate tissues was consistent with the previous reports using RT-PCR. The dual cytoplasmic and nuclear localisation of hK4 observed in the prostate above was also seen in these tissues. Although hK4 was found widely expressed in many human tissue types, indicating that it is not prostate specific in its expression, the highest expression level of hK4 was seen in the prostate. Therefore, detailed expression patterns and levels of KLK4 mRNA and hK4 protein in the normal prostate and prostatic diseases and histopathological lesions were investigated and reported for the first time in this study. Twelve benign prostatic hyperplasia (BPH), 19 adenocarcinoma (Gleason grade 2-5) and 34 bone metastases from prostate cancer were analysed. Using in situ hybridisation, the expression of KLK4 mRNA was detected in the cytoplasm of the secretory cells of both normal and diseased prostate tissue. KLK4 mRNA was also noted in both secretory and basal cells of PIN lesions, but the basal cells of normal glands were negative. Using the hK4 N-terminal and mid-region antipeptide antibodies, hK4 was predominantly localised in the cytoplasm of the secretory cells. The intensity of hK4 staining appeared lowest in normal and BPH, and increased in PIN lesions, high Gleason grade prostate cancer and bone metastases indicating the potential of hK4 as a histopathological marker for prostatic neoplasias. Further studies are required with a larger cohort to determine its utility as a clinical biomarker. Small foci of atypical cells, which were found within normal glands, were also intensely stained. Surprisingly, hK4 protein was found in the nucleus of the secretory cells (but not the basal cells) of high grade PIN and Gleason grade 3 prostate cancer. The detection of KLK4 mRNA and hK4 protein in PIN lesions and small foci of atypical cells suggests that up-regulation of KLK4 expression occurs early in the pathology of prostate carcinogenesis. The finding of basal cell expression is not typical for the kallikreins and it is not clear what role hK4 would play in this cell type. With the use of the hK4 C-terminal antipeptide antibody, the staining was mainly localised in the nuclei of the secretory cells of the prostate glands. Although the nuclear localisation was readily noted in more than 90% of epithelial cells of the prostate gland with the C-terminal antibody, no difference in staining intensity was observed among the histopathological lesions of the prostate. The prominent nuclear localisation with the C-terminal antipeptide antibody was also shown to be distributed throughout the nucleus by using confocal microscopy. Further, by using gold-labelled particles for electron microscopy, the intracellular localisation of these hK4 antipeptide antibodies was reported here for the first time. Similar to the immunohistochemical results, the cytoplasm was the major site of localisation with the N-terminal and mid-region antipeptide antibodies. To further characterise the involvement of KLK4/hK4 in human prostate cancer progression, the transgenic adenocarcinoma mouse prostate (TRAMP) model was used in this study. In this study, mouse KLK4 (also known as enamel matrix serine protease -1, EMSP-1) was shown to be expressed in the TRAMP prostate for the first time. Previous studies had only shown the developing tooth as a site of expression for EMSP-1. The level of EMSP-1 mRNA expression was increased in PIN and prostate cancer lesions of the TRAMP model, while negative or low levels of EMSP-1 mRNA were seen in normal glands or in control mouse prostate tissue. The normal mouse prostate did not stain with any the three hK4 antipeptide antibodies. hK4 N-terminal and mid-region antipeptide antibodies showed positive staining in the cytoplasm of the epithelial cells of PIN and cancer lesions of the mouse prostate. The C-terminal antipeptide antibody showed distinctively nuclear staining and was predominantly localised in the nuclei of the glandular cells of PIN and cancer lesions of the mouse prostate. The expression patterns of both the mRNA and protein level for mouse KLK4 strongly supported the observations of KLK4/hK4 expression in the human prostate and further support the utility of the TRAMP model. Overall, the findings in this thesis indicate a clear association of KLK4/hK4 expression with prostate cancer progression. In addition, several intriguing findings were made in terms of cellular localisation (basal as well as secretory cells; nuclear and cytoplasmic) and high expression in atypical glandular cells and PIN, perhaps indicating an early involvement in prostate disease progression and, additionally, utility as basal cell and PIN histological markers. These findings provide the basis for future studies to confirm the utility of hK4 as a biomarker for prostate cancer progression and identify functional roles in the different cellular compartments.
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Bui, Loan Thuy. "Localisation of kallikreins in the prostate and association with prostate cancer progression." Queensland University of Technology, 2006. http://eprints.qut.edu.au/16276/.
Full textAbstract:
At present, prostate cancer is a significant public health issue throughout the world and is the second leading cause of cancer deaths in older men. The prostate specific antigen or PSA (which is encoded by the kallikrein 3/KLK3 gene) test is the current most valuable tool for the diagnosis and management of prostate cancer. However, it is insufficiently sensitive and specific for early diagnosis, for staging of prostate cancer or for discriminating between benign prostatic hyperplasia (BPH) and prostate cancer. Recent research has revealed another potential tumour marker, glandular kallikrein 2 (KLK2 gene/hK2 protein), which may be used alone or in conjunction with PSA to overcome some of the limitations of the PSA test. Twelve new kallikrein gene family members have been recently identified and, like hK2 and PSA, many of these genes have been suggested to be involved in carcinogenesis. In this study, the cellular localisation and level of expression of several of these newer kallikreins (KLK4, KLK5, KLK7, KLK8 and KLK11) was examined in prostate tissue, to provide an understanding of the association of their expression with prostatic diseases and their potential as additional biomarkers. Like PSA and hK2, the present observation indicated that each of these proteins, hK4, hK5, hK7, hK8 and hK11, was detected within the cytoplasm of the secretory cells of the prostate glands. For the first time, all of these newly-identified proteins were shown to be expressed in prostatic intraepithelial neoplasia (PIN) lesions, in comparison to normal glands and cancer lesions. In addition to cytoplasmic secretory cell expression, the localisation of hK4 to the basal cells and nuclei in prostatic lesions was intriguing. The intensity of hK4 staining in prostate tissue was strongest in comparison to the other newly-identified kallikrein proteins (hK5, hK7, hK8 and hK11). Therefore, KLK4/hK4 expression was characterised further to define this cellular localisation and examined in non-prostatic tissue and also in a larger number of prostate tissues in an attempt to determine its potential value as a biomarker for prostate disease. Three hK4 antipeptide polyclonal antibodies, derived against N-terminal, mid-region and C-terminal hK4 amino acid sequences, were used. The hK4 N-terminal antipeptide antibody was used to demonstrate the cellular localisation of hK4 in kidney, salivary glands, liver, testis, colon carcinoma, heart, endometrium and ovarian cancer, for the first time. The presence of hK4 in these non-prostate tissues was consistent with the previous reports using RT-PCR. The dual cytoplasmic and nuclear localisation of hK4 observed in the prostate above was also seen in these tissues. Although hK4 was found widely expressed in many human tissue types, indicating that it is not prostate specific in its expression, the highest expression level of hK4 was seen in the prostate. Therefore, detailed expression patterns and levels of KLK4 mRNA and hK4 protein in the normal prostate and prostatic diseases and histopathological lesions were investigated and reported for the first time in this study. Twelve benign prostatic hyperplasia (BPH), 19 adenocarcinoma (Gleason grade 2-5) and 34 bone metastases from prostate cancer were analysed. Using in situ hybridisation, the expression of KLK4 mRNA was detected in the cytoplasm of the secretory cells of both normal and diseased prostate tissue. KLK4 mRNA was also noted in both secretory and basal cells of PIN lesions, but the basal cells of normal glands were negative. Using the hK4 N-terminal and mid-region antipeptide antibodies, hK4 was predominantly localised in the cytoplasm of the secretory cells. The intensity of hK4 staining appeared lowest in normal and BPH, and increased in PIN lesions, high Gleason grade prostate cancer and bone metastases indicating the potential of hK4 as a histopathological marker for prostatic neoplasias. Further studies are required with a larger cohort to determine its utility as a clinical biomarker. Small foci of atypical cells, which were found within normal glands, were also intensely stained. Surprisingly, hK4 protein was found in the nucleus of the secretory cells (but not the basal cells) of high grade PIN and Gleason grade 3 prostate cancer. The detection of KLK4 mRNA and hK4 protein in PIN lesions and small foci of atypical cells suggests that up-regulation of KLK4 expression occurs early in the pathology of prostate carcinogenesis. The finding of basal cell expression is not typical for the kallikreins and it is not clear what role hK4 would play in this cell type. With the use of the hK4 C-terminal antipeptide antibody, the staining was mainly localised in the nuclei of the secretory cells of the prostate glands. Although the nuclear localisation was readily noted in more than 90% of epithelial cells of the prostate gland with the C-terminal antibody, no difference in staining intensity was observed among the histopathological lesions of the prostate. The prominent nuclear localisation with the C-terminal antipeptide antibody was also shown to be distributed throughout the nucleus by using confocal microscopy. Further, by using gold-labelled particles for electron microscopy, the intracellular localisation of these hK4 antipeptide antibodies was reported here for the first time. Similar to the immunohistochemical results, the cytoplasm was the major site of localisation with the N-terminal and mid-region antipeptide antibodies. To further characterise the involvement of KLK4/hK4 in human prostate cancer progression, the transgenic adenocarcinoma mouse prostate (TRAMP) model was used in this study. In this study, mouse KLK4 (also known as enamel matrix serine protease -1, EMSP-1) was shown to be expressed in the TRAMP prostate for the first time. Previous studies had only shown the developing tooth as a site of expression for EMSP-1. The level of EMSP-1 mRNA expression was increased in PIN and prostate cancer lesions of the TRAMP model, while negative or low levels of EMSP-1 mRNA were seen in normal glands or in control mouse prostate tissue. The normal mouse prostate did not stain with any the three hK4 antipeptide antibodies. hK4 N-terminal and mid-region antipeptide antibodies showed positive staining in the cytoplasm of the epithelial cells of PIN and cancer lesions of the mouse prostate. The C-terminal antipeptide antibody showed distinctively nuclear staining and was predominantly localised in the nuclei of the glandular cells of PIN and cancer lesions of the mouse prostate. The expression patterns of both the mRNA and protein level for mouse KLK4 strongly supported the observations of KLK4/hK4 expression in the human prostate and further support the utility of the TRAMP model. Overall, the findings in this thesis indicate a clear association of KLK4/hK4 expression with prostate cancer progression. In addition, several intriguing findings were made in terms of cellular localisation (basal as well as secretory cells; nuclear and cytoplasmic) and high expression in atypical glandular cells and PIN, perhaps indicating an early involvement in prostate disease progression and, additionally, utility as basal cell and PIN histological markers. These findings provide the basis for future studies to confirm the utility of hK4 as a biomarker for prostate cancer progression and identify functional roles in the different cellular compartments.
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Williams, Vonetta L. "Race/Ethnic Disparities in Treatment Patterns among Newly Diagnosed Primary Prostate Cancer Patients in Florida." Scholar Commons, 2015. https://scholarcommons.usf.edu/etd/5604.
Full textAbstract:
Study Purpose: The purpose of this study was to examine whether there were differences in patterns of care between African American (AA) and Non-Hispanic White (NHW) men newly diagnosed with prostate cancer in Florida, and how the treatment patterns compare with the National Comprehensive Cancer Network (NCCN) initial treatment recommendations.
Materials and Methods: This retrospective cohort study utilized data from the Florida Cancer Data System (FCDS), to identify incident cases of prostate cancer diagnosed between 1982 and 2012. The variables of interest included: race/ethnicity, marital status, age at diagnosis, stage at diagnosis, tumor grade, year of diagnosis, and treatment modality (singular or multimodality). Adjusted odds ratios (AORs) and 95% confidence intervals were calculated to determine disparities in the receipt of treatment by age at diagnosis, stage at diagnosis and tumor grade between AA and NHW men.
Results: A total of 244,449 AA (30,556 cases or 12.5%) and NHW (213,893 cases or 87.5%) men met the study inclusion/exclusion criteria. AA men were significantly less likely to receive surgery only or surgery in combination with other treatment modalities compared to NHW men, localized disease (AOR=0.66, 95% CI (0.63-0.68), regional disease (AOR=0.63, 95% CI (0.57- 0.71), distant disease (AOR=0.50, 95% CI (0.34-0.75). Comparisons of adherence to the NCCN initial treatment recommendations indicate that AA men with(5% versus 13%). Moreover, AA men in the very high risk group had a higher NCCN initial treatment adherence percentage compared to NHW men (76% versus 70%).
Conclusion: After adjusting for potential demographic and clinical confounders, significant differences exist in the receipt of first course of treatment where AA men were more likely to receive radiation and/or hormone therapy and less likely to receive surgery compared to NHW men. Further research is needed to address this disparity.
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Katz, Betina Stifelman. "Estudo dos genes e microRNAs relacionados à transição epitélio-mesenquimal no adenocarcinoma de próstata." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5153/tde-04082014-102817/.
Full textAbstract:
Introdução: O câncer de próstata (CaP) é o tumor mais comum em homens e a segunda causa de óbito por câncer no Brasil. Com a adoção do rastreamento, a maioria dos pacientes apresenta doença localizada ao diagnóstico, enquanto apenas 4% têm doença metastática. Um dos principais mecanismos responsáveis pela progressão tumoral é a transição epitélio-mesenquimal (TEM). Esse é um programa celular reversível no qual a célula epitelial perde a capacidade de aderência intercelular e assume um fenótipo mesenquimal com potencial invasivo e metastático. A principal característica da TEM é a repressão da E-caderina através de fatores de transcrição que incluem ZEB1, ZEB2, Snail, Slug e Twist1. Os microRNAs também estão envolvidos na regulação do processo, sendo a família do miR-200 uma das mais importantes e uma potente indutora da diferenciação epitelial. Assim sendo, o conhecimento dos fatores envolvidos na TEM no CaP é fundamental para a compreensão do comportamento biológico dessa neoplasia. Objetivos: Analisar a expressão dos genes e microRNAs envolvidos na transição epitélio-mesenquimal em espécimes de câncer de próstata localizado e em linhagens celulares de câncer de próstata metastático. Além disso, correlacionar o perfil de expressão dos genes e microRNAs com parâmetros clínico-patológicos. Material e métodos: O estudo consistiu na análise de espécimes de 51 pacientes com CaP localizado tratados por prostatectomia radical e de linhagens celulares de CaP metastático (LNCaP, DU145 e PC3). O grupo controle foi composto por 10 casos de hiperplasia prostática benigna. A expressão dos genes E-caderina, N-caderina, Vimentina, TGF-beta1, ZEB1, ZEB2, Snail, Slug, Twist1 e PDGF-D e dos microRNAs 200a, 200b, 200c, 429, 141, 203, 205, 183, 373, 21, 9, 1, 495, 29b, 30a, 34a, 155 e 10b foi avaliada através da técnica de PCR em tempo real (qRT-PCR) nos espécimes e nas linhagens. Para correlação com parâmetros clínico-patológicos, os pacientes foram divididos em grupos em relação ao escore de Gleason, estadiamento patológico, PSA pré-operatório, recorrência bioquímica e doença de baixo e alto risco. Para avaliação do tumor metastático, agrupamos as linhagens celulares e comparamo-las com tumores pT3. Resultados: A grande maioria dos casos apresentou superexpressão de E-caderina e Twist1 e subexpressão de N-caderina, Vimentina, TGF-beta1, ZEB1 e Slug. ZEB2, Snail e PDGF-D apresentaram expressão variável. A família do miR-200 e os miRNAs 203, 205, 183, 373 e 21 apresentaram superexpressão, enquanto que os miRNAs 9, 495, 29b e 1 apresentaram subexpressão. Os demais miRNAs apresentaram perfil de expressão variável. Níveis menores de expressão dos miRNAs 200b, 30a e 1 associaram-se significativamente com estadiamento patológico. Os pacientes com expressão reduzida do miR-200b também apresentaram associação com escore de Gleason >= 8 e com menor tempo de sobrevida livre de recorrência bioquímica. Ainda, níveis baixos do miR-30a e níveis elevados de Vimentina e Twist1 associaram-se com grupo de alto risco. As linhagens metastáticas apresentaram níveis de expressão do miR-183 e do Twist1 significativamente maiores quando comparadas ao tumor localizado. Conclusão: O CaP localizado mantém um fenótipo molecular epitelial. Menor expressão dos miRNAs 200b, 30a e 1 está associada com estadiamento mais avançado, sendo que o miR-200b também associou-se com maior escore de Gleason e menor tempo de sobrevida livre de recorrência bioquímica, e o miR-30a, com grupo de alto risco. A maior expressão de Vimentina e Twist1 apresentou associação com o grupo de alto risco. miR-183 e Twist1 apresentam maiores níveis de expressão em linhagens celulares metastáticas em relação ao tumor primário. De acordo com nossos resultados, os miRNAs 200b, 30a, 1 e 183 e os genes Twist1 e Vimentina podem ter um papel importante na progressão do CaP, além de serem potenciais marcadores prognósticosIntroduction: Prostate cancer (PCa) is the most common cancer in men and the second leading cause of cancer-related mortality in Brazil. After the adoption of screening, most patients present with localized disease at the time of diagnosis, while only 4% have metastatic disease. One of the main mechanisms of tumor progression is the epithelial-mesenchymal transition (EMT). This is a reversible cell-biological program in which an epithelial cell loses intercellular adhesion and acquires a mesenchymal phenotype with invasiveness and metastatic potential. The main event in EMT is the repression of E-cadherin by transcriptional factors, including ZEB1, ZEB2, Snail, Slug, and Twist1. microRNAs are also involved in the regulation of this process, and one of the most important ones is the miR-200 family, which is a powerful inducer of epithelial differentiation. Therefore, the knowledge of the factors involved in EMT in PCa is essential to understand the biological behavior of this neoplasia. Objectives: Analysis of gene and miRNA expression involved in epithelial-mesenchymal transition in specimens of localized prostate cancer and metastatic prostate cancer cell lines. Correlation between the gene and miRNA expression profiles and clinicopathological features. Material and Methods: This study consisted in the analysis of specimens from 51 patients with localized PCa treated by radical prostatectomy and of metastatic PCa cell lines (LNCaP, DU145, PC3). The control group was composed by 10 cases of benign prostatic hyperplasia. Gene expression of E-cadherin, N-cadherin, Vimentin, TGF-beta1, ZEB1, ZEB2, Snail, Slug, Twist1, and PDGF-D as well as miRNA expression of 200a, 200b, 200c, 429, 141, 203, 205, 183, 373, 21, 9, 1, 495, 29b, 30a, 34a, 155, and 10b were assessed by Real-Time PCR (qRT-PCR). The patients were divided into groups according to Gleason score, pathological stage, preoperative PSA, biochemical recurrence, and low and high-risk disease. For evaluation of metastatic tumor, the cell lines were grouped and compared to pT3 tumors. Results: The vast majority of the cases showed overexpression of E-cadherin and Twist1 and underexpression of N-cadherin, Vimentin, TGF-beta1, ZEB1, and Slug. ZEB2, Snail, and PDGF-D showed a variable expression pattern. miRNA-200 family and miRNAs 203, 205, 183, 373, and 21 were overexpressed, while miRNAs 9, 495, 29b, and 1 were underexpressed. The remaining miRNAs showed a variable expression pattern. Lower expression levels of miRNAs 200b, 30a, and 1 were significantly associated with pathological stage. Patients with lower expression of miR-200b also showed association with Gleason score >= 8 and biochemical recurrence-free survival (BRFS). Furthermore, low expression levels of miR-30a and high expression levels of Vimentin and Twist1 were associated with high-risk group. The metastatic PCa cell lines showed significantly higher expression levels of miR-183 and Twist1 in comparison to the primary tumor. Conclusion: Localized prostate cancer maintains a molecular epithelial phenotype. Lower expression of miRNAs 200b, 30a, and 1 was associated with higher stage. Low levels of miR-200b were also associated with high Gleason score and shorter BRFS, and miR-30a, with high-risk group. High expression levels of Vimentin and Twist1 were associated with high-risk group. miR-183 and Twist1 levels were higher in metastatic cell lines than in the primary tumor. According to our results, miRNAs 200b, 30a, 1, and 183 and the genes Twist1 and Vimentin might play an important role in the progression of PCa and may turn to be important prognostic markers
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Schmid, Hans-Peter. "The clinically organ-confined adenocarcinoma of the prostate : natural history, selection criteria for radical prostatectomy and prognostic factors based on long-term follow-up /." Darmstadt : Steinkopff, 1994. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Ragavan, Narasimhan. "An analysis of hormone or carcinogen metabolising enzyme expression in human prostate in relation to susceptibility to adenocarcinoma and an epidemiological investigation of lifestyle risk factors." Thesis, Lancaster University, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504184.
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Binneman, Brigitte. "Selective induction of apoptosis by 7- methyljuglone, its derivatives and isolated compounds from foeniculum vulgare Mill. on human cancer cells." Diss., Pretoria : [s.n.], 2009. http://upetd.up.ac.za/thesis/available/etd-06112009-173251/.
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Souza, Paulo José Gonçalves de. "Frequência de Adenocarcinoma Prostático em biópsias de 12 ou 18 fragmentos de pacientes com valores de PSA total entre 2,5 e 10 ng/ml, relação PSAlivre / PSAtotal ≤ 19% e densidade do PSA ≥ 15ng/ml/cc." Universidade Federal de Juiz de Fora (UFJF), 2016. https://repositorio.ufjf.br/jspui/handle/ufjf/4068.
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Introdução: O PSA ( antígeno prostático específico ) é a principal ferramenta no rastreamento do Câncer de Próstata. Estudos buscam melhoria no diagnóstico criando combinações do PSA com suas variáveis: PSAlivre/PSAtotal; Densidade do PSA; Velocidade do PSA; associação com a idade do paciente; etnia e hereditariedade para Câncer de Próstata. O diagnóstico do Câncer de Próstata é realizado através da análise do tecido prostático, obtido através da biópsia prostática, guiada por ultrassonografia, sendo considerado o procedimento padrão. O objetivo deste trabalho é avaliar a frequência de Câncer de Próstata em homens: submetidos 18 fragmentos de biópsia prostática e comparar com a positividade se analisados apenas os 12 fragmentos iniciais. Material e método: Entre maio de 2008 a outubro de 2013, foram analisados 216 prontuários de pacientes, submetidos à biópsia prostática com 18 fragmentos, que apresentavam PSAtotal ≥ 2,5ng/ml, PSAlivre/PSAtotal ≤ 19%, densidade PSA ≥ 0,15 ng/ml/cc, com toque retal normal, e ausência de nódulos prostáticos à ultrassonografia transretal. As biópsias prostáticas por agulha foram guiadas por Ultrassonografia transretal e distribuídas da seguinte maneira: 3 fragmentos base direita; 3 fragmentos base esquerda; 3 fragmentos 1/3 médio direito; 3 fragmentos 1/3 médio esquerdo; 3 fragmentos ápice direito e 3 fragmentos ápice esquerdo. Estes foram numerados de 1 a 18 e separados em 2 grupos: grupo 1 com os fragmentos 1 a 12, sendo 2 fragmentos de cada região prostática e o grupo 2 com os fragmentos 13 a 18, sendo 1 fragmento de cada região prostática, cada fragmento foi analisado separadamente. Foi realizada comparação da positividade entre os 18 fragmentos e apenas os 12 iniciais. Os pacientes com diagnóstico de câncer nos 12 fragmentos iniciais foram comparados com aqueles apenas na avaliação de todos os 18 fragmentos com relação aos valores do PSA e volume prostático. Resultados: Foram avaliados 216 homens com idade média de 64 +- 8,0 anos, com extremos de 34 a 90 anos. A incidência de pacientes com Câncer de Próstata em 12 fragmentos foi de 42/216 (19,44%) e em 18 fragmentos a incidência foi de 58/216 (26,85%); com aumento de 38% na capacidade de detecção, o que nos revela 7,45% a mais de tumores. Ao compararmos os pacientes que apresentaram positividade da biópsia já nos 12 primeiros fragmentos (42 pacientes), com aqueles com positividade apenas na avaliação de todos os 18 fragmentos (16 pacientes), verificamos que: os pacientes com positividade apenas com 18 fragmentos apresentaram maior valor de PSA e próstata maiores. O que leva a consideração que pacientes com próstata maiores e maiores valores de PSA se beneficiariam de um maior número de fragmentos. Conclusões: A análise de 18 fragmentos de biópsia de próstata em relação a 12 fragmentos, mostrou aumento de positividade na detecção de câncer de próstata e estes pacientes tiveram benefício com o aumento do número de fragmentos e apresentaram maior PSA e maior volume de próstata.
Introduction: PSA (Prostate-Specific Antigen) is the main tool for screening for prostate cancer, and studies now seek to improve the diagnosis by creating combinations of PSA with its variables, free/total PSA, PSA density, PSA velocity, and an association with the patient's age, ethnicity and heredity for prostate cancer.The diagnosis of prostate cancer is achieved by the analysis of prostatic tissue obtained by prostate biopsy guided by ultrasound, and it is considered the standard procedure. The objective of this study was to evaluate prostate cancer frequency in men undergoing prostate biopsy of 18 fragments and to compare that with positivity, when only the first 12 fragments were analyzed. Materials and methods: from May 2008 to October 2013, 216 medical records of patients undergoing prostate biopsy that had total PSA between 2.5 and 10 ng/ml, free/total PSA ≤ 19%, PSA density ≥ 0.15 ng/ml/cc3 with normal digital rectal exam and absence of prostate nodules of trans rectal ultrasonography were analyzed. The trans rectal ultrasound guided biopsies involving using needles were distributed as follows:3 right base fragments, 3 left base fragments, 3 1/3 right mid fragments, 3 1/3 left mid fragments, 3 right apex and 3 left apex fragments. These fragments were numbered from 1 to 18 and separated into 2 groups: Group 1 - 1 to 12, with two fragments of each prostatic region - and Group 2 - 13 to 18, with one fragment from each prostatic region (each fragment being analyzed separately).Positive comparison was made between the 18 fragments and only the first 12.Patients diagnosed with cancer in the first 12 fragments were compared with those for which all 18 fragments were analyzed regarding the values of PSA and prostate volume. Results: 216 men with mean age of 64 + - 8.0 years, with extremes 34-90 years were evaluated. The prevalence of patients with prostate cancer in 12 fragments was 42/216 (19.44%), and in 18 fragments it was 58/216 (26.85%); with an increase of 38% in the detection capacity, which shows 7.45% more tumors. When comparing the patients who had positive biopsy in the first 12 fragments (42 patients) with those with positivity only in the evaluation of all 18 fragments (16 patients), it was found that patients with positivity only in the 18 fragments showed higher PSA value and larger prostates. This leads to consider that patients with larger prostates and higher PSA values would benefit from a greater number of fragments. Conclusions: the analysis of 18 prostate biopsy samples compared to 12 fragments showed a positive increase in prostate cancer detection. Also, the patients who were benefited from the increase in the number of fragments had higher PSA and larger prostate volume.
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Luz, Willame de Araújo. "AVALIAÇÃO CIENCIOMÉTRICA DO ADENOCARCINOMA DE PRÓSTATA, UTILIZANDO O FISH COMO FERRAMENTA CITOMOLECULAR PARA ANÁLISE DO GENE PTEN, NA BASE DE DADOS SCOPUS NO PERÍODO DE 2005 A 2015." Pontifícia Universidade Católica de Goiás, 2016. http://localhost:8080/tede/handle/tede/2402.
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Previous issue date: 2016-03-10Cancer is defined as a chronic multifactorial disease, characterized by the uncontrolled growth of cells that invade tissues and organs and can spread to other body regions. It s a major public health problem worldwide, especially in developing countries due to the accelerated growth of the population of higher age group. This scientometric study emphasized in the evaluation of prostate adenocarcinoma using FISH as citomolecular tool for analysis of the PTEN gene in Scopus database in the period 2005-2015. The study survey was conducted using the keywords: "prostatic neoplasms and PTEN and FISH". Different approaches have been made to go throught the analysis of the scientific production of the articles included in this study as the type of publication (experimental or review ), the number of articles - year , authors, scientific areas, journals, impact factor of the journals that published, among others. As a result, it was observed that the number of publications throughout the study period undergoes variation over ten years. Magazines belonging to developed countries show that they invest in cutting-edge research and are dominant as to its scientific prestige. The Brazilian scientific production has grown significantly in recent years. The intellectual, social and economic impact of publications produced in Brazil is still low significance and has much to grow, a fact that should be changed with greater financial investment by government as private institutions in scientific production area, thus improving the credibility of research institutions and our researchers. Therefore, it is concluded that this scientometrical analysis have shown the quantitative studies on prostate carcinoma, highlighting the importance of each of the proposed objectives, seeking alternatives to improve the growth of science and the visibility of productions on this topic in the global scientific activity.
O câncer é definido como uma enfermidade multicausal crônica, caracterizada pelo crescimento descontrolado das células, que invadem os tecidos e órgãos, podendo espalhar-se para outras regiões do corpo. É um importante problema de saúde pública em todo o mundo, especialmente nos países em desenvolvimento, devido ao acelerado crescimento da população de faixa etária mais elevada. Esse estudo cienciométrico se deteve na avaliação do adenocarcinoma de próstata utilizando a FISH como ferramenta citomolecular para análise do gene PTEN, na base de dados SCOPUS no período de 2005 a 2015. Para isso, o levantamento do estudo foi realizado utilizando as palavras-chave: prostatic neoplasms and PTEN and FISH . Diferentes abordagens foram realizadas para se fazer a análise da produção científica dos artigos incluídos nesse estudo como: tipo de publicação (experimental ou revisão), número de artigos-ano, autores, áreas científicas, revistas, fator de impacto das revistas que mais publicaram, dentre outros. Como resultado, observou-se que a quantidade de publicações ao longo do período estudado sofre uma variação no decorrer dos dez anos. Revistas pertencentes a países desenvolvidos, mostram que estes investem em pesquisa de ponta e são dominantes quanto ao seu prestígio científico. A produção científica brasileira tem crescido significativamente nos últimos anos, o impacto intelectual, social e econômico das publicações produzidas no Brasil continua com baixa significância e tem muito a crescer, fato esse que deve ser alterado com maiores investimentos financeiros por parte governamental quanto das instituições privadas, na área de produção científica, melhorando assim, a credibilidade das instituições de pesquisa e dos nossos pesquisadores. Portanto, conclui-se que nesta análise cienciométrica, foram apresentados os dados de estudos quantitativos sobre o adenocarcinoma de próstata, evidenciando a importância de cada um dos objetivos propostos, buscando alternativas para melhorar o crescimento da ciência e a visibilidade das produções sobre este tema no contexto da atividade científica mundial.
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Amadei, Larissa Pereira da Ponte. "Evolução bioquímica através de medidas seriadas de antígeno prostático específico (PSA) de pacientes submetidos a braquiterapia com implante de sementes de 125I no tratamento do adenocarcinoma de próstata." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5151/tde-29012009-091700/.
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INTRODUÇÃO: Nos pacientes com câncer de próstata considerados de baixo risco, a braquiterapia de baixa taxa de dose (BBTD) utilizando sementes de 125I é uma excelente opção, com seguimento após o tratamento, devendo ser feito por meio de medidas seriadas de PSA. A avaliação de falha bioquímica após radioterapia, definida por elevação do PSA, tem sido feita pelo critério da ASTRO (American Society for Therapeutic Radiology and Oncology) e, mais recentemente, pelo critério do consenso de Phoenix. OBJETIVOS: Avaliar a sobrevida livre de falha bioquímica (SLFB) de pacientes submetidos à BBTD pelos critérios ASTRO e Phoenix e as relações entre eles com as falhas clínicas. Correlacionar essas sobrevidas com idade, grau histológico de Gleason, estadiamento clínico, PSA inicial, porcentagem de fragmentos positivos na biópsia, invasão perineural, volume prostático na ultra-sonografia diagnóstica, hormonioterapia neoadjuvante, bounce e D90 (dose recebida por 90% do volume de próstata). MÉTODO: Estudo retrospectivo de 329 pacientes tratados, entre julho de 1998 e dezembro de 2002, no serviço de Radioterapia do Hospital Sírio-Libanês, São Paulo. Foram excluídos 18 pacientes que tinham recebido braquiterapia associada à RT externa, 18 pacientes classificados como de alto risco, 61 casos com menos de dois anos de seguimento mínimo e 12, com dados incompletos nos prontuários. Portanto, 220 pacientes formaram a base desta análise. RESULTADOS: Cento e vinte e um (55%) pacientes foram classificados como de baixo risco e 99 (45%) de risco intermediário. O seguimento mediano foi de 53,5 meses (24 a 116); 74 pacientes (33,6%) fizeram algum tipo de bloqueio hormonal por um tempo mediano de 90 dias e 66 pacientes (30%) apresentaram bounce. O tempo médio para o aparecimento do bounce foi de 15 meses, com um nadir médio de 0,30ng/mL. A SLFB em cinco anos pelo critério ASTRO foi de 83% e de 88,3% pelo Phoenix (p < 0,05). Para os pacientes de risco baixo e intermediário, respectivamente, 86,7% e 78,4% pela definição ASTRO (p = 0,069) e 88,5% e 77,9% de acordo com Phoenix (p = 0,016). Na análise multivariada, PSA inicial < 10 ng/mL e porcentagem de fragmentos positivos < 50% foram fatores prognósticos favoráveis em relação à falha (p < 0,05) pelo critério ASTRO. De acordo com o critério Phoenix, PSA inicial < 10 ng/mL, grau histológico de Gleason < 7, porcentagem de fragmentos positivos < 50% e grupo de baixo risco foram os fatores independentes favoráveis, preditivos de falha bioquímica (p < 0,05). CONCLUSÕES: Os dados de sobrevida livre de falha bioquímica em cinco anos para pacientes de risco baixo e intermediário desta análise foram comparáveis aos da literatura. Nesta análise, não houve diferença entre as definições ASTRO e Phoenix de falha. PSA, escore de Gleason, porcentagem de fragmentos positivos na biópsia e grupo de risco foram os fatores prognósticos independentes para falha bioquímica.INTRODUCTION: Patients with low-risk prostate adenocarcinoma may be very well treated by low dose-rate brachytherapy (LDR) using 125I seeds. Follow-up with periodical serum prostate specific antigen (PSA) dosages is used to determine the effectiveness of treatment. Biochemical relapse may be defined either by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, or, more recently, by the Phoenix Consensus criteria. PURPOSE: To evaluate and compare biochemical failure-free survival (BFFS) of patients treated with LDR brachytherapy using ASTRO and Phoenix criteria. Also, to correlate BFFS with age, Gleason score, clinical stage, initial PSA, percentage of positive prostate biopsies, perineural invasion, prostate volume at diagnostic ultrasound, neoadjuvant hormone therapy, bounce, and D90 (dose received by 90% of the prostate). METHODS: A cohort of 329 patients who received LDR brachytherapy for prostate cancer, between 1998 and 2002 at Hospital Sírio-Libanês, São Paulo, was retrospectively studied. Eighteen patients who received external beam irradiation were excluded, together with another 18 high-risk patients, 61 with less than 2 years minimal followup, and 12 with incomplete record data. So, 220 patients were the basis of this study. RESULTS: One hundred and twenty one (55%) were low-risk patients and 99 (45%) were intermediate-risk. Median follow-up was 53.5 months (24-116); 74 (33.6%) patients received neoadjuvant hormone therapy during a median period of 90 days, and 66 (30%) presented bounce. Mean time till bounce was 15 months, with mean nadir of 0,30ng/mL. The 5-year BFFS was 83% using ASTRO criteria, and 88.3% using Phoenix (p > 0,05). Low and intermediate-risk patients presented, respectively, 86.7% and 78.4% 5-year BFFS using ASTRO definition (p = 0,069), and 88.5% and 77.9%, considering Phoenix criteria (p = 0,016). In multivariate analysis, initial PSA < 10 ng/mL, and percentage of positive prostate biopsies < 50% were favorable prognostic factors, regarding biochemical relapse using ASTRO criteria (p < 0,05), while initial PSA < 10 ng/mL, Gleason score < 7, percentage of positive prostate biopsies < 50%, and low-risk group were detected as independent favorable prognostic factors using Phoenix definition (p < 0,05). CONCLUSIONS: The 5-year estimates of BFFS using both criteria, for low and intermediate-risk patients, were similar to previous published data, with no significant difference between them. Initial PSA, Gleason score, percentage of positive prostate biopsies, and risk group were independent prognostic factors for biochemical relapse.
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Cintra, Maria Letícia 1951. "Graduação histologica do adenocarcinoma da prostata : reprodutibilidade intra-observador dos sistemas Mostofi, Gleason e Bocking." [s.n.], 1989. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308444.
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Orientador : Athanase BillisTese (doutorado) - Universidade Estadualde Campinas, Faculdade de Ciencias Medicas
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Resumo: A graduação histológica do adenocarcinoma da próstata, de indiscutível relevãncia no prognóstico deste tumor, apresenta um carãter subjetivo que nos propusemos a estudar, testando a reprodutibilidade intra-observadorde três dos sistemas de diferenciação tumoral mais empregados no mo mento: MOSTOFI, GLEASON e BOCKING. Foram selecionadas 139 neoplasias e subdivididas em grupos de acordo com o tipo de procedimento cirúrgico adotado na sua exérese (ressecção trans-u retraI ou prostatectomia aberta) e segundo o número de fragmentos acometidos pelo tumor...Observação: O resumo, na integra, podera ser visualizado no texto completo da tese digital
Abstract: In carcinoma of the prostate, histological grade is a significant prognostic marker and may inf1uence treatment p1anning. The main prob1em appears tobethat grading is subjective. In the current investigation, intraobserver variation of the three most emp10yed grading systems -MOSTOFI, GLEASON and BOCKING is examined....Note: The complete abstract is available with the full electronic digital thesis or dissertations
Doutorado
Doutor em Medicina
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Alves, Flávia Cilene Maciel da Cruz [UNESP]. "Alterações epigenéticas em adenocarcinomas de próstata." Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/104551.
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As alterações epigenéticas desempenham funções críticas na regulação de vários genes, funções celulares e conseqüentes mudanças no controle do ciclo celular. Estas modificações têm sido associadas ao desenvolvimento tumoral. Em câncer de próstata, muitos genes hipermetilados foram descritos e indicados como potenciais marcadores diagnósticos, incluindo RARB, RASSF1A, SFN e CDH1. O presente estudo tem como objetivo avaliar a freqüência da hipermetilação dos genes SFN, RARB, RASSF1A e CDH1 nos adenocarcinomas de próstata (CaP) e correlacionar essas alterações com a expressão gênica e proteica e com parâmetros clínicos e histopatológicos. O padrão de metilação dos genes SFN, RARB, RASSF1A e CDH1 foi determinado por PCR-metilação específica em 68 amostras de CaP e em 27 amostras de próstata não neoplásicas (PNN). Expressão dos transcritos RARB e RASSF1A foram avaliados por RT-PCR quantitativo em 73 amostras de CaP, 15 amostras de tecidos prostáticos adjacentes não neoplásicos (PAdj) e dois tecidos prostáticos normais (N). A expressão das proteínas foi avaliada por imunohistoquímica em 141 amostras de CaP, 40 PAdj e dois N. Os resultados foram correlacionados com parâmetros clinico-histopatológicos. A expressão proteica de E-caderina também foi investigada em uma série de 39 CaP e 27 PNN. Os genes RARB e RASSF1A apresentaram-se hipermetilados em CaP (P<0,0001 e P = 0,0017, respectivamente), mas nenhuma diferença foi detectada para SFN. Os níveis dos transcritos e proteínas RASSF1A foram semelhantes entre amostras de CaP e PAdj. Entre os tumores foi detectada a diminuição dos níveis de transcritos de RAR (P=0,001) e da proteína (P=0,0007). Níveis diminídos do mRNA foram associados com a hipermetilação de RARB. A expressão proteica de RAR era nuclear e citoplasmática nos tecidos tumorais. A análise multivaria...
Epigenetic alterations play critical roles in regulation of several genes and cellular functions and their deregulation may disrupt the cellular control leading to tumor development. In prostate cancer (PCa), many hypermethylated genes have been described and indicated as potential prostate cancer diagnostic markers, including RARB, RASSF1A, SFN and CDH1. The current study aimed to evaluate SFN, RARB, RASSF1A, and CDH1hypermethylation frequencies in prostate carcinoma (PCa) and to correlate these alterations with down-regulations at transcriptional and protein levels and with clinical outcome. Methylation pattern of SFN, RARB, RASSF1A and CDH1 were determined by methylationspecific PCR (MSP) in 68 PCa samples and 27 non-neoplastic prostate tissues (NNP). RARB and RASSF1A transcripts expression were evaluated by quantitative RT-PCR in 73 PCa, 15 adjacent nonneoplastic prostate tissues (AdjP) and two normal prostate (N). Methylation and mRNA analysis for RARB and RASSF1A were done in matched samples from 30 PCa and 10 AdjP. Protein expression assessed by immunohistochemistry was evaluated in an independent cohort of 141 PCa, 40 AdjP and two normal prostate tissues. Paired E-cadherin protein and methylation analysis was also investigated in 33 PCa and 20 NNP. The findings were correlated with clinicopathological parameters. RARB and RASSF1A genes were hypermethylated in PCa (P <0.0001 and P = 0.0017, respectively), but no difference was detected for SFN. RASSF1A mRNA and protein levels were similar in PCa and AdjP samples. Down-expression of RAR in transcript (P=0.001) and protein (P=0.0007) levels were detected in tumors. Lower mRNA levels were associated with RARB hypermethylation. Nuclear and cytoplasmic RAR protein expression was detected in tumor tissues. Multivariate analysis demonstrated that cytoplasmic RAR immunostaining was independently associated with decreased... (Complete abstract click electronic access below)
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Alves, Flávia Cilene Maciel da Cruz. "Alterações epigenéticas em adenocarcinomas de próstata /." Botucatu : [s.n.], 2009. http://hdl.handle.net/11449/104551.
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Orientador: Sílvia Regina RogattoBanca: José Carlos Souza Trindade
Banca: Aparecido Donizete Agostinho
Banca: Cristina Victorino Krepischi Santos
Banca: Renata Coudry
Resumo: As alterações epigenéticas desempenham funções críticas na regulação de vários genes, funções celulares e conseqüentes mudanças no controle do ciclo celular. Estas modificações têm sido associadas ao desenvolvimento tumoral. Em câncer de próstata, muitos genes hipermetilados foram descritos e indicados como potenciais marcadores diagnósticos, incluindo RARB, RASSF1A, SFN e CDH1. O presente estudo tem como objetivo avaliar a freqüência da hipermetilação dos genes SFN, RARB, RASSF1A e CDH1 nos adenocarcinomas de próstata (CaP) e correlacionar essas alterações com a expressão gênica e proteica e com parâmetros clínicos e histopatológicos. O padrão de metilação dos genes SFN, RARB, RASSF1A e CDH1 foi determinado por PCR-metilação específica em 68 amostras de CaP e em 27 amostras de próstata não neoplásicas (PNN). Expressão dos transcritos RARB e RASSF1A foram avaliados por RT-PCR quantitativo em 73 amostras de CaP, 15 amostras de tecidos prostáticos adjacentes não neoplásicos (PAdj) e dois tecidos prostáticos normais (N). A expressão das proteínas foi avaliada por imunohistoquímica em 141 amostras de CaP, 40 PAdj e dois N. Os resultados foram correlacionados com parâmetros clinico-histopatológicos. A expressão proteica de E-caderina também foi investigada em uma série de 39 CaP e 27 PNN. Os genes RARB e RASSF1A apresentaram-se hipermetilados em CaP (P<0,0001 e P = 0,0017, respectivamente), mas nenhuma diferença foi detectada para SFN. Os níveis dos transcritos e proteínas RASSF1A foram semelhantes entre amostras de CaP e PAdj. Entre os tumores foi detectada a diminuição dos níveis de transcritos de RAR (P=0,001) e da proteína (P=0,0007). Níveis diminídos do mRNA foram associados com a hipermetilação de RARB. A expressão proteica de RAR era nuclear e citoplasmática nos tecidos tumorais. A análise multivaria... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Epigenetic alterations play critical roles in regulation of several genes and cellular functions and their deregulation may disrupt the cellular control leading to tumor development. In prostate cancer (PCa), many hypermethylated genes have been described and indicated as potential prostate cancer diagnostic markers, including RARB, RASSF1A, SFN and CDH1. The current study aimed to evaluate SFN, RARB, RASSF1A, and CDH1hypermethylation frequencies in prostate carcinoma (PCa) and to correlate these alterations with down-regulations at transcriptional and protein levels and with clinical outcome. Methylation pattern of SFN, RARB, RASSF1A and CDH1 were determined by methylationspecific PCR (MSP) in 68 PCa samples and 27 non-neoplastic prostate tissues (NNP). RARB and RASSF1A transcripts expression were evaluated by quantitative RT-PCR in 73 PCa, 15 adjacent nonneoplastic prostate tissues (AdjP) and two normal prostate (N). Methylation and mRNA analysis for RARB and RASSF1A were done in matched samples from 30 PCa and 10 AdjP. Protein expression assessed by immunohistochemistry was evaluated in an independent cohort of 141 PCa, 40 AdjP and two normal prostate tissues. Paired E-cadherin protein and methylation analysis was also investigated in 33 PCa and 20 NNP. The findings were correlated with clinicopathological parameters. RARB and RASSF1A genes were hypermethylated in PCa (P <0.0001 and P = 0.0017, respectively), but no difference was detected for SFN. RASSF1A mRNA and protein levels were similar in PCa and AdjP samples. Down-expression of RAR in transcript (P=0.001) and protein (P=0.0007) levels were detected in tumors. Lower mRNA levels were associated with RARB hypermethylation. Nuclear and cytoplasmic RAR protein expression was detected in tumor tissues. Multivariate analysis demonstrated that cytoplasmic RAR immunostaining was independently associated with decreased... (Complete abstract click electronic access below)
Doutor