Introdução: O câncer de próstata é a neoplasia maligna não-cutânea mais frequente nos homens brasileiros. Seu rastreamento é tema controverso na literatura, e a maioria das entidades médicas não recomenda sua realização a partir dos 70 anos. Não existem estudos sobre suas características nessa faixa etária da população brasileira, que não é submetida a rastreamento ativo sistemático. Objetivos: Avaliar a prevalência e critérios de agressividade do câncer de próstata diagnosticado por rastreamento ativo em homens com idade inferior e superior a 70 anos no Brasil. Pacientes e métodos: Estudo transversal retrospectivo incluindo 17.571 voluntários no Brasil, submetidos a rastreamento ativo através de toque retal e dosagem sérica do antígeno prostático específico (PSA), entre janeiro de 2004 e dezembro de 2007. Os critérios de indicação para a biópsia foram: PSA>4,0ng/ml, ou PSA entre 2,5 e 4,0ng/ml com relação PSA livre/total <=15%, ou toque retal suspeito. Todos os homens rastreados foram divididos em dois grupos etários: grupo A, entre 45 e 69 anos; grupo B, acima de 70 anos. Os grupos foram comparados com relação a prevalência e critérios de agressividade da doença (valor do PSA sérico, escore de Gleason da biópsia e estadiamento clínico TNM). Resultados e discussão: A prevalência do câncer de próstata na nossa amostra foi de 3,71%. O grupo dos homens com mais de 70 anos apresentou prevalência da doença 2,9 vezes maior (RP 2,90; p <0,001), o valor médio de PSA foi mais elevado nos acometidos (17,28ng/ml no grupo B versus 9,54ng/ml no grupo A), assim como ocorreu maior chance de haver portadores de câncer com PSA acima de 10,0ng/ml (OR 2,63; p=0,003). No grupo de homens com mais de 70 anos também houve uma prevalência 3,59 vezes maior do padrão histológico mais agressivo (Gleason 8-10: RP 3,59; p<0,001) e maior prevalência de doença metastática (RP 4,95; p<0,05). Conclusão: O rastreamento do câncer de próstata nos homens com idade acima de 70 anos e expectativa de vida superior a 10 anos pode ser relevante no Brasil. Neste grupo etário detectamos uma maior prevalência desta doença, quando comparado ao grupo de idade entre 45 e 69 anos. Nosso estudo também demonstrou que o grupo de homens com mais de 70 anos possui maior probabilidade de apresentar doença de alto risco ao diagnóstico (PSA sérico mais elevado e em faixas de maior risco; escore de Gleason 8 a 10 e disseminação metastática à distância mais frequentes) / Background: Prostate cancer (PC) is the leading non-cutaneous malignancy among Brazilian men. PC may present as an indolent or aggressive life-threatening disease. There is no consensus in the literature regarding PC screening, and most medical organizations do not recommend it over the age of 70 years old. There are no studies in the literature addressing this topic in the Brazilian population. Objectives: To compare the prevalence and the aggressiveness of prostate cancer diagnosed, by active screening, in men under and over 70 years. Patients and methods: We performed a retrospective cross-sectional study including 17,571 volunteers. Screening was performed by digital rectal examination and prostatespecific antigen (PSA) measurement. Individuals who met the criteria for PC suspicion (PSA>4.0ng/ml, or PSA 2.5-4.0ng/ml with free/total PSA ratio <=15%, or suspicious digital rectal examination) underwent prostate biopsy. Those diagnosed with cancer were staged. The screened men were stratified by age in two groups: group A, between 45 and 69 years old, and group B, over 70 years old. The groups were compared regarding PC prevalence and its aggressiveness criteria (seric PSA value, Gleason score from biopsy and TNM staging). Results and discussion: The prevalence of prostate cancer was 3.71% in all population. The group of men over 70 years old had disease prevalence 2.9 times higher (RP 2.90; p<0.001); higher mean PSA value in men diagnosed with prostate cancer (17.28ng/ml vs. 9.54ng/ml); and greater likelihood to present PC when PSA level was above 10.0ng/ml (OR 2.63; p=0.003), when compared with men between 45 and 69 years old. The group of men aged over 70 years also presented a prevalence of histologic aggressive disease 3.59 times higher (Gleason 8-10: RP 3.59, p<0.001) and greater prevalence of metastatic disease (RP 4,95; p<0,05). Conclusion: Our study reveals that men over 70 years old presented a higher prevalence of prostate cancer and a higher probability to present high-risk disease at diagnosis (higher PSA; Gleason score 8-10 and metastatic disease more frequent), when compared to men aged 45-69 years. Screening for prostate cancer in men aged over 70 years and life expectancy over 10 years may be relevant in Brazil

INTRODUÇÃO: O câncer de próstata ocupa o segundo lugar entre as neoplasias de maior incidência na população masculina mundial. Uma vez estabelecido o diagnóstico, o estadiamento passa a ter papel fundamental na escolha da opção e tática terapêuticas. OBJETIVO: Avaliar as diferenças clínicas, laboratoriais e anatomopatológicas dos pacientes e determinar a acurácia, a sensibilidade, a especificidade e os valores preditivos positivo e negativo de vários exames pré-operatórios, avaliando isoladamente e em conjunto aqueles capazes de melhor prever o estadiamento local do câncer prostático. MÉTODOS: Foram analisados o antígeno prostático específico (PSA), as densidades de PSA calculadas pelos exames de ressonância magnética e ultra-som (DPSA), a graduação de Gleason, o número de sextantes positivos e a porcentagem de fragmentos positivos nas biópsias, as probabilidades de doença intraprostática, doença extracapsular e comprometimento das vesículas seminais segundo os nomogramas de Kattan e Partin, e os resultados dos exames de toque retal, da ressonância magnética com bobina endorretal e do ultra-som com Doppler de amplitude em relação ao estadiamento do câncer de próstata em 49 pacientes submetidos à prostatectomia radical. Os resultados foram comparados com os resultados anatomopatológicos. RESULTADOS: Dos 49 pacientes com tumores classificados clinicamente como intraprostáticos, respectivamente 59,2 %, 51,0 % e 32,7 % dos pacientes foram subestadiados clinicamente em relação à doença extraprostática, doença extracapsular e comprometimento das vesículas seminais. Estadiamentos clínicos iniciais tiveram taxas de subestadiamento menores e estadiamentos clínicos mais avançados tiveram taxas de subestadiamento maiores. As médias da maioria dos parâmetros clínicos e laboratoriais dos pacientes com doença avançada apresentaram valores maiores do que as médias dos pacientes com doença localizada. A biópsia prostática superestimou a graduação histopatológica final de Gleason em 10,2 % dos casos, subestimou a graduação em 49,0 % dos casos e a correlação foi idêntica em 40,8 %. A ressonância magnética, quando comparada aos outros parâmetros analisados de forma isolada, apresentou os maiores valores de acurácia na discriminação doença intraprostática x doença extraprostática (73,5 %), doença intracapsular x doença extracapsular (81,6 %) e comprometimento ou não das vesículas seminais (77,6 %). A acurácia geral dos modelos de regressão logística baseada nas variáveis contempladas foi de 71,4 % na previsão de doença extraprostática, 87,2 % na previsão de doença extracapsular e 81,0 % na previsão de comprometimento das vesículas seminais. CONCLUSÃO: A ressonância magnética com bobina endorretal se mostrou ser um dos melhores métodos para o estadiamento local do câncer de próstata e pode ser considerada no estudo de pacientes selecionados / INTRODUCTION: The prostate cancer is the second more frequent neoplasia in the worldwide male population. Since the diagnosis is established, the staging has a fundamental role on the choice of therapeutic option and tactics. OBJECTIVE: To evaluate the clinical, laboratory and anatomopathological differences of patients and determine the accuracy, sensitiveness, specificity and positive and negative predictive values of several preoperative examinations, by evaluating individually and conjointly those which are able to better predict the local staging of prostate cancer. METHODS: The prostate-specific antigen (PSA) was analyzed as well as the PSA densities (PSAD) were calculated through the magnetic resonance and ultrasound, the Gleason\'s grading, the number of positive sextants and the percentage of positive fragments in biopsies, the probabilities of intraprostatic disease, extracapsular disease and involvement of seminal vesicles according to Kattan and Partin\'s nomograms, and the results of rectal palpations, the use of endorectal coil magnetic resonance imaging and the use of amplitude Doppler ultrasound in relation to the staging of prostate cancer in 49 patients who were submitted to radical prostatectomy. The results were compared with the anatomopathological results. RESULTS: Among 49 patients with tumors clinically classified as intraprostatic, 59.2%, 51.0% and 32.7% patients respectively were clinically understaged in relation to extraprostatic disease, extracapsular disease and involvement of seminal vesicles. The initial clinical staging had lower substaging rates and the more advanced clinical staging had higher substaging rates. The averages of most clinical and laboratory parameters of patients with advanced disease presented values higher than the averages of patients with localized disease. The prostatic biopsy overestimated the Gleason\'s final histopathologic grade in 10.2% of cases, underestimated the grade in 49.0 % of cases and had identical correlation in 40.8%. The magnetic resonance imaging, when compared with all of other parameters analyzed isolately, presented the highest accuracy values in the discrimination intraprostatic disease x extraprostatic disease (73.5%), intracapsular disease x extracapsular disease (81.6 %) and the presence of seminal vesicles involvement (77.6%). The general accuracy of logistic regression models based on contemplated variables was of 71.4% in the extraprostatic disease prediction, 87.2% in the extracapsular disease prediction and 81.0% in the prediction of involvement of seminal vesicles. CONCLUSION: The use of endorectal coil magnetic resonance imaging was one of the best predictors of local staging of prostate cancer and could be considered in the study of selected patients

Introdução: O emprego da técnica de RT-PCR na detecção da expressão de genes epiteliais como a CK-19 no sangue periférico de pacientes com câncer de próstata é uma oportunidade para avaliar a progressão tumoral ao nível molecular na ausência de doença clinicamente mensurável. Material e métodos: Inicialmente 10 pacientes com nível sérico de PSA< 2ng/ml e toque retal sugestivo de hiperplasia prostática benigna foram incluídos como grupo controle através de coleta de sangue única para dosagem do transcrito da CK-19. Subsequentemente,foram seguidos de maneira prospectiva 44 pacientes com câncer de próstata (21 com doença localizada e 23 com doença metastática), com coleta de sangue seriada a cada 3 meses por 18 meses. Foi medida a expressão sérica do transcrito da CK-19 por RT-PCR na fração leucocitária do sangue periférico e correlacionada aos níveis séricos de PSA e outras variáveis clinicas e patológicas. Resultados: Nenhum de 10 pacientes controles apresentou expressão do transcrito da CK-19 no sangue periférico. Nos pacientes com câncer de próstata a expressão do transcrito da CK-19 na entrada do estudo não se correlacionou com o escore de Gleason, estádio clínico e os níveis séricos de DHL, Hemoglobina, PSA, Fosfatase alcalina ou Testosterona. A presença de pelo menos uma dosagem positiva de CK-19 durante o seguimento se correlacionou com o tempo para a progressão bioquímica do PSA na amostra como um todo(p=0,049) e no subgrupo com doença metastática(p=0,032). Conclusão: Não houve expressão do transcrito da CK-19 na fração mononuclear do sangue periférico em homens do grupo controle. Nos pacientes com câncer de próstata não houve correlação entre a expressão do transcrito da CK-19 na entrada do estudo e as principais variáveis clínicas e patológicas de prognóstico. Nos pacientes com câncer de próstata, a presença de pelo menos uma dosagem positiva para o transcrito da CK-19 no seguimento se correlacionou com um menor tempo para recidiva bioquímica , especialmente no subgrupo de pacientes com doença metastática tratados com hormonioterapia / Background: The recent introduction of sensitive RT-PCR-based techniques for the detection of epithelial antigen expression, such as CK-19,in the peripheral blood of prostate cancer patients may provide an opportunity to evaluate early tumor progression at the molecular level, even in the absence of measurable disease. Methods: Ten men with PSA <2ng/ml and digital rectal examination suggestive for benign prostatic hyperplasia were included as controls by only one colleted blood sample to measure of CK-19 transcript. We also studied serially collected blood samples of 44 patients with prostate cancer (21 with localized and 23 with metastatic disease) every three months for 18 months. We measured CK-19 transcript expression in the peripheral blood mononuclear fraction (PBMN) of these samples by RT-PCR and correlated it with PSA values and other clinical and pathologic variables. Results: None of the 10 normal control men showed CK-19 transcript expression in their PBMN. In the patients with prostate cancer, CK-19 transcript positivity at entry did not correlate with Gleason score, clinical stage, DHL, hemoglobin level, PSA, alkaline phosphatase or testosterone levels. Having at least one positive CK- 19 result during follow up correlated significantly with time to PSA progression in all coorte (p = 0.049) and in the subgroup of metastatic disease (p = 0.032). Conclusion: There are no expression of CK-19 transcript in the PBMN of control men. In prostate cancer patients there are no correlation between CK-19 at entry and the most important clinical and pathological prognostic variables. Prostate cancer patients that had at least one CK-19 transcript expression in the peripheral blood present lower time to PSA progression, specially metastatic patients receiving hormonal therapy

Cai, Ganhui. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 160-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

In recent years, three dimensional (3D)-culture technique has emerged as a very popular approach to reconstruct tissue architectures and develop experimental models for studying epithelial cancers. However, 3D culture models of prostate epithelial cells to mimic prostate cancer development are relatively rare, making it highly desirable to develop and characterize novel 3D culture models suitable for studying prostate cancer. Recently, epithelial-mesenchymal transition (EMT) has emerged as an important mechanism for cancer cell invasion. The zinc finger transcriptional factor Snail as a key regulator of EMT has been found to contribute to aggressive progression in many types of neoplasms. Even though several studies corroborated that EMT is implicated in prostate cancer, the expression patterns of Snail in normal prostate and prostate cancer, and the functional role of Snail in prostate cancer as well as its relation with EMT are still unknown. Based on this background, my major efforts were to establish a 3D culture model of human prostatic epithelial cells with structural and functional relevance to prostate gland and to employ this model to study the functional role of Snail in the prostate cancer. / When embedded in Matrigel for 3D culture, BPH-1 cells developed into growth-arrested acinar structures with a hollow lumen. Ultrastructural examination of BPH-1 spheroids by electricon microscopy indicated that BPH-1 spheroids displayed a polarized differentiation phenotype. Immunoflurescence analysis of polarized epithelial markers further confirmed that BPH-1 spheroids were polarized. In contrast, tumorigenic BPH-1CAFTD cells exhibited disorganized and continuously proliferating structures in Matrigel, with polarized epithelial markers randomly diffused or completely lost. In addition, BPH-1 CAFTD cells displayed significantly higher invasive capacity in comparison to BPH-1 cells by transwell invasion assay. Moreover, LY294002 treatment of BPH-1CAFTD1 and BPH-1CAFTD3 cells in 3D cultures resulted in impaired cell proliferation as evidenced by reduced colony size and decreased Ki-67 index, and western blot analysis showed that cyclin D1 protein levels were significantly decreased, while p21 protein levels were slightly up-regulated in LY294002-treated 3D cultures. Additionally, LY94002 significantly decreased the invasive capacity of BPH-1CAFTD1 and BPH-1CAFTD3 cells. Interestingly, LY294002 treatment completely reverted the disorganized non-polar 3D structures of BPH-1CAFTD1 cells to well-organized polarized spheroid structures in Matrigel, but failed to restore the polarized differentiation in 3D cultures of BPH-1CAFTD3 cells, which still formed compact aggregates as shown by confocal immunofluorescence analysis. Snail protein was barely detected in the epithelial cells of human benign prostatic tissue but significantly elevated as nuclear protein in primary prostate cancer and bone metastatic specimens by immunohistochemical analysis. Snail transcript levels were weakly expressed in a majority of nonmalignant prostatic epithelial cell lines, while markedly increased in almost all tested cancer cell lines. Snail expression induced a morphological switch to more scattered and spindle-shaped appearance in BPH-1 and BPH-1CAFTD1 cells in 2D culture, and immunofluorescence analysis of several EMT specific markers indicated that Snail-expressing cells underwent EMT. In 3D contexts, Snail-expressing cells developed into more disorganized structures with many cords or protrusions, with a concurrent EMT change as evidenced by reduced E-cadherin and increased vimentin expression. In addition, Snail expression augmented the invasive capacities in both BPH-1 cells and BPH-lCAFTD1 cells, but did not significantly affect the migratory capacities. Snail expression enhanced the MMP2 activity in BPH-1 cells and promoted both MMP-2 and MMP-9 activities in BPH-1CAFTD1 cells. Moreover, Snail expression enhanced anchorage-independent growth capability in BPH-1 cells, but failed to initiate tumor formation in nude-mice. Lastly, Snail expression induced a dramatic increase in FoxC2 and SPARC transcripts but a marked decrease in claudin-1 and p63 transcripts. / Chu, Jianhong. / Adviser: Franky Chan Leung. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3448. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 143-166). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Prostate cancer remains one of the most commonly diagnosed cancers in men and is a leading cause of cancer death. While great success has been achieved at curing early stage prostate cancer, limited success has been obtained when treating late-stage hormone independent prostate cancer. This is due to the increased propensity for skeletal and non-skeletal metastases. Thus development of novel effective therapeutic modalities against late stage prostate cancer is of critical importance. / Towards these objectives, I have focused my attention on the role of prostate secretory protein (PSP-94) which is expressed in normal individuals and in patients with early stage prostate cancer. Using our well established in vivo models of prostate cancer, I have evaluated the ability of PSP-94 and its amino acids 31-45 required (PCK3145) to decrease tumor growth and skeletal metastases in vivo and evaluated the potential mechanism(s) associated with PCK3145 anti-cancer actions. / Prostatic cancer can also develop as a result of epigenetic activation of tumor promoting genes. To evaluate the role of methylation in prostate cancer, late stage prostate cancer cells were treated with the universal methylating agent S-adenosylmethionine (SAM) and an anti-sense oligonucleotide directed against MBD2 (AS). Scrambled oligonucleotide was included as a control (S). Both SAM and MBD2-AS resulted in inhibition in uPA, MMP-2 and VEGF production leading to decreased tumor cell invasive capacity. However, SAM and MBD2-AS were not able to either further repress partially methylated genes (GSTP1) or reactivate already methylated genes (AR). Furthermore, SAM and MBD2-AS treatment resulted in significant reduction in tumor growth in vivo . Immunohistochemical and RT-PCR analyses carried out on SAM and MBD2-AS tumors revealed decreased protein and mRNA expression of uPA and MMP-2 which was partially due to increased methylation of the respective promoters even after 10 weeks post in vitro treatment as analyzed by bisulfate sequencing. In addition decreased levels of angiogenesis and tumor survival markers were observed. / Collectively, these studies are aimed at the development of novel reliable approached to diagnose and treat advanced, hormone refractory prostate cancer to reduce tumor associated morbidity and mortality.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 4 uppsatser.

Thesis (Ph.D. in Toxicology) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 144-170). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

Diss. (sammanfattning) Umeå : Umeå universitet, 2008. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed on June 26, 2009). Includes bibliographical references.