Introdução: A prostatectomia perineal tem sido proposta como um procedimento seguro e pouco invasivo, sem comprometer os princípios oncológicos. No entanto, este acesso tem sido questionado sobre o risco de promover a incontinência anal. Objetivo: avaliar os efeitos do acesso para a prostatectomia perineal no mecanismo de continência anal. Métodos: Trinta e um pacientes com indicação cirúrgica de prostatectomia perineal foram avaliados entre agosto de 2008 e maio de 2009. Dados do pré e pós operatório (8 meses): estadiamento do câncer de próstata, a avaliação clínica (Índice de incontinência anal da Cleveland Clinic - CCISS), índice de qualidade de vida na incontinência anal (FIQL) e manometria anorretal. Os parâmetros médios manométricos foram: pressão de repouso (RP / mmHg), pressão de contração voluntária máxima (MSP / mmHg), zona de alta pressão (ZAP / cm), índice de fadiga do esfíncter (SFI / min.), índice de assimetria esfincteriana (SAI /%), limiar de sensibilidade retal (RST / ml) e volume retal máximo tolerado (MTRV / ml). Resultados: Foi concluída a avaliação em vinte e três pacientes, com média de idade de 65 (54-72) anos. Pré-operatório: o peso médio da próstata foi de 34,5 (24-54) gramas, Gleason intervalo de valor da pontuação 06/07. Os valores médios pré e pós-operatório da CCISS foram 0,9 ± 1,9 e 0,7 ± 1,2 (p> 0,05) e não houve uma mudança significativa no valor FIQL. Os valores médios pré e pós operatório de parâmetros manométricos foram, respectivamente: RP: 64 ± 23 e 65 ± 17, SP: 130 ± 41 e 117 ± 40, ZAP: 3,0 ± 0,9 e 2,7 ± 0,8, SFI: 3,0 ± 2,1 ± 11 e 5.4, RST: 76 ± 25 e 71 ± 35, MTRV 157 ± 48 e 156 ± 56, e SAI: 22,4 ± 9 e 14,4 ± 5, sendo o SAI o único parâmetro com mudança estatisticamente significativa (p: 0, 003). Conclusão: O acesso perineal para prostatectomia não afetou os parâmetros de continência anal. Houve, no entanto melhora na simetria esfincteriana / Introduction: Perineal prostatectomy has been proposed as a less invasive and a safer procedure, without compromise of oncological principles. However, this access has been questioned about the risk of promoting anal incontinence. Purpose: this study aimed to evaluate the effects of perineal access for prostatectomy in continence mechanism. Methods: Thirty one patients with surgical indication for perineal prostatectomy were evaluated between August 2008 and May 2009. Preoperative and postoperative (8 months) data included: prostate cancer staging, clinical evaluation (Cleveland Clinic anal incontinence score system - CCISS), Fecal incontinence quality of life score (FIQL) and anal manometry. Mean manometric parameter were: resting pressure (RP/mmHg), maximal squeeze pressure (MSP/mmHg), high pressure zone (HPZ/cm), sphincter fatigue index (SFI/min), sphincter asymmetry index (SAI/%), rectal sensory threshold (RST/ml) and maximum tolerated rectal volume (MTRV/ml). Results: Twenty three patients, mean age 65 (54-72) years, completed evaluation. Preoperative: prostate weight was 34.5 (24-54) grams, Gleason score value range 6 /7. Mean pre and postoperative values of CCISS were 0.9±1.9 and 0.7±1.2 (p>0.05) and there was not a significant change in FIQLS value. The mean preoperative and postoperative values of manometric parameters were, respectively: RP: 64±23 and 65±17, SP: 130±41 and 117±40, HPZ: 3.0±0.9 and 2.7±0.8, SFI: 3.0±11and 2.1 ±5.4, RST: 76±25 and 71±35, MTRV 157±48 and 156±56, and SAI: 22.4±9 and 14.4±5. Significant statistics change only in the SAI (p=0,003). Conclusion: The perineal prostatectomy did not affect anal continence parameters

INTRODUÇÃO: Braquiterapia de alta taxa de dose (BATD) para o câncer de próstata pode ser uma boa opção para escalonamento de dose, como um reforço de dose, associada à radioterapia externa, principalmente se não há disponibilidade de radioterapia tridimensional conformada ou tecnologia mais avançada. OBJETIVOS: Neste trabalho, analisaram-se os resultados e as toxicidades de um reforço de dose com BATD prévio à radioterapia externa convencional ou tridimensional conformada em pacientes portadores de câncer localizado da próstata. Fatores prognósticos relacionados à sobrevida livre de doença, além de toxicidade do tratamento também foram estudados. MÉTODOS: Estudo retrospectivo de 403 pacientes com adenocarcinoma localizado da próstata tratados entre dezembro de 2000 e março de 2004, que receberam 3 esquemas de fracionamento distintos de BATD de acordo com o seu grupo de risco: três frações de 5,5 a 6 Gy, 6 a 6,5 Gy ou 6,5 a 7 Gy, para baixo, médio ou alto risco, respectivamente, em um único implante, no decorrer de 24h de internação. A radioterapia externa convencional ou conformada compreendeu dose de 45 Gy na próstata e vesículas seminais. Foram realizadas análises uni e multivariada para avaliação dos fatores prognósticos relacionados à sobrevida livre de falha bioquímica e toxicidades. RESULTADOS: A idade mediana dos pacientes foi de 68 anos, com PSA médio de 9g/ml, peso prostático médio de 35 cc. Grau histológico de Gleason igual a 6 ocorreu em 43% dos casos, estádio menor do que T2c em 97%, presença de nódulo prostático em 49%; 11% dos pacientes apresentaram história de ressecção transuretral e 16% obstrução urinária prévias. No grupo de baixo risco foram classificados 36.1% dos pacientes, 42.8% no grupo de risco intermediário e 21.1% foram considerados de alto risco. Hormonioterapia neoadjuvante por até 6 meses foi utilizada em 64% dos casos e teleterapia conformada em 19%. O seguimento médio foi de 50 meses (mediano de 48,4 meses), variando de 24 a 113 meses. Nove (2,2%) pacientes não responderam ao tratamento e 4,5% evoluíram a óbito por neoplasia prostática em um tempo médio de 22 meses. Falha bioquímica, tanto pelo critério ASTRO, quanto PHOENIX ocorreu em 9,6% dos pacientes. Entretanto, o tempo médio para falha foi de 13 meses pelo critério ASTRO e 26 meses pelo PHOENIX. O único fator preditivo de falha bioquímica pela análise multivariada por ambos os critérios ASTRO e PHOENIX foi a presença de nódulos prostáticos, mas pacientes com menos de 60 anos apresentaram maior chance de falha apenas pela definição de PHOENIX. Toxicidades urinárias agudas como retenção e hematúria ocorreram em 2,8% e 1,3% dos casos, respectivamente; sendo 23,7% grau 1, 15,1% grau 2 e 2% grau 3. Estenose uretral tardia foi observada em 8,5% dos pacientes e as toxicidades urinárias tardias foram grau 1 em 8,8%, grau 2 em 3,9%, grau 3, em 7,7% e grau 4, em 0,3% dos casos. Toxicidade urinária aguda foi relacionada a obstrução urinária prévia e maior dose de braquiterapia na uretra. Estenose uretral tardia também foi relacionada à maior dose uretral pela braquiterapia e com maior idade. Toxicidade retal precoce ocorreu como grau 1 em 14,8% dos pacientes; como grau 2, em 10,5%; e como grau 3, em 1,3%. Toxicidade retal tardia ocorreu como grau 1 em 3,4% dos pacientes; como grau 2, em 1,5%; como grau 3, em 0,3%; e como grau 4, em 0,3%. O risco para toxicidades retais agudas e tardias foi maior quando teleterapia conformada foi utilizada. Foi observada dor na glande em 4,9% dos pacientes e 71% apresentaram disfunção erétil tardiamente. O uso de Sildenafil foi eficiente em 59%. Pacientes mais velhos, ou com uma ou mais comorbidades, comprometimento prévio da ereção, ou que receberam radioterapia externa conformada apresentaram maior incidência de disfunção erétil. CONCLUSÕES: a associação de BATD como um reforço de dose para teleterapia mostrou ser um método viável e seguro apresentando boa eficácia e toxicidade aceitável. Os fatores relacionados à sobrevida e toxicidade podem colaborar na melhor seleção e tratamento de pacientes com câncer de próstata localizado. / INTRODUCTION: high dose-rate brachytherapy (HDR) for prostate cancer may be a nice treatment option for dose escalation as a boost, when associated to external beam irradiation, mainly if 3D conformal or more advanced technology is not available. PURPOSE: this study analyzes the results and toxicities of HDR brachytherapy boost prior to external beam radiotherapy with 2D or 3D conformal irradiation in patients with localized prostate cancer. Prognostic factors associated to overall and disease-free survival, as well as to treatment related toxicity were also studied. METHODS: A retrospective study of 403 patients with localized prostate adenocarcinoma treated between December 2000 and March 2004 was performed. According to the risk group, three fractions of HDR brachytherapy were delivered in the course of 24 hours, with a single implant: 5.5 to 6 Gy per fraction for low risk, 6 to 6.5 Gy per fraction for intermediate risk, and 6.5 to 7 Gy per fraction for high risk patients. The interval between fractions was of at least 6 hours. Conventional 2D or 3D conformal external beam irradiation was delivered to the prostate and seminal vesicles with 25 fractions of 1.8Gy (45Gy), about 2 weeks after brachytherapy. Multivariate analysis was done to evaluate unfavorable prognostic factors for biochemical failure free survival (BFFS). RESULTS: Patients presented a median age of 68 years, mean PSA of 9g/ml, and average prostate weight of 35 cc. Gleason score was equal to 6 in 43% of the cases, and 97% of the cases were at a stage lower than T2c. Prostate nodules were present in 49% of the patients; prior history of transurethral resection or urinary obstruction was present in 11% and 16% of the patients, respectively. There were 36.1% patients in the low risk group, 42.8% in the intermediate, and 21.1% in the high risk groups, respectively. Up to six months of neoadjuvant hormone therapy was used in 64% of the cases. External beam radiation was delivered with 3D conformal radiation in 19% of patients. The mean follow-up was 50 months ranging from 24 to 113 months (median 48,4 months). Nine patients (2.2%) did not respond to treatment. Death from prostate cancer occurred in 4.5% of the cases in a mean period of 22 months. Biochemical failure occurred in 9.6% according to both ASTRO and Phoenix consensus criteria. However, the mean time to relapse was 13 months using the ASTRO criteria and 26 months with the Phoenix definition. The five-year BFFS using the ASTRO criteria was 94.3%, 86.9% and 86.6% for the low, intermediate and high risk groups, respectively. Using the Phoenix criteria, 92.4%, 88.0% and 85.3% for the low, intermediate and high risk groups, respectively (p = 0.109). The only feature predicting biochemical failure (BF) in the multivariate analysis by both ASTRO and Phoenix criteria was the presence of prostate nodules, but patients younger than 60 years presented higher chance of BF using Phoenix criteria only. Acute urinary toxicities as urinary retention and hematúria occurred respectively in 2.8% and 1.3% of the patients. They presented as grade 1 in 23.7%, grade 2 in 15.1% and grade 3 in 2%. Late urethral stenosis was observed in 8.5% and late urinary toxicity was grade 1 in 8.8% of the patients, grade 2 in 3.9%, grade 3 in 7.7% and grade 4 in 0.3%. Acute urinary toxicity was related to previous urinary obstruction and higher brachytherapy dose to the urethra. Late urethral stenosis was related to older age and higher brachytherapy dose. Grade 1 early rectal toxicity occurred in 14.8% of the patients, grade 2 in 10.5% and grade 3 in 1.3%. Late rectal toxicity occurred as grade 1 in 3.4% of patients, as grade 2 in 1.5%, grade 3 in 0.3% and grade 4 in 0.3%. The risk of acute and late rectal toxicity was higher when 3D conformal irradiation was used. Glans pain was observed in 4.9% of the patients. Late sexual impotence occurred in 71% of cases. Sildenafil was effective in 59%. Sexual impotence presented a higher incidence in older patients with one or two co-morbidities, previous sexual impairment, or 3D conformal irradiation. CONCLUSIONS: the association of HDR brachytherapy as a boost for external beam irradiation seems to be a feasible and safe procedure, with good efficacy and acceptable toxicity. Factors related to survival and toxicity can help to better select and manage patients with localized prostate carcinoma.

Introdução: Um dos principais obstáculos para compreensão dos eventos biológicos envolvidos no câncer é a falta de modelos adequados para o estudo in vitro em especial em relação ao câncer de próstata (CaP) e ao câncer de bexiga (CaB). Há um número limitado de linhagens celulares de CaP e de CaB sendo a maioria proveniente de tumores invasivos e metastáticos. Sabe-se ainda, que existem diferenças étnicas entre as populações quanto ao comportamento de neoplasias. Desta forma, a pesquisa baseada em linhagens de uma população homogênea seria fonte de resultados limitados, não contemplando a diversidade que sabidamente ocorre entre os diferentes grupos. Além desse aspecto, as linhagens celulares comerciais são na sua maioria adquiridas na Coleção Americana de Culturas de Tecido (ATCC, do inglês American Tissue Cell Culture) que apesar de serem bem padronizadas, requerem processos de importação com aumento do custo e demandas burocráticas que dificultam a pesquisa. Portanto, consideramos vital para a compreensão dos fenômenos relacionados à carcinogênese, assim como estudos de resistência a drogas, quimioprevenção e novas estratégias terapêuticas, o desenvolvimento de linhagens tumorais derivadas de tumores primários que acometem a nossa população, peculiarmente miscigenada. No presente trabalho, fragmentos de carcinoma urotelial da bexiga e de adenocarcinoma da próstata foram obtidos durante cirurgia para remoção de tumores primários de pacientes tratados e acompanhados na Divisão de Urologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP) e no Hospital Sírio Libanês. As linhagens estabelecidas a partir destes fragmentos foram caracterizadas através da análise da cinética de crescimento, análises imunocitoquímicas e anormalidades cromossômicas incluindo cariótipo e hibridização in situ por fluorescência (FISH). Além disso, as linhagens obtidas foram submetidas a estudos de quimiossensibilidade com o uso dos compostos curcumin e Prima-1. Avaliamos ainda, a tumorigenicidade de nossas linhagens em camundongos atímicos. Os resultados deste trabalho demonstram o desenvolvimento de três linhagens de CaB e três linhagens de CaP sendo as mesmas não tumorigênicas em camundongos atímicos. Além disso, demonstramos que o curcumin na concentração de 50 M induziu morte celular em todas as linhagens estudadas, sendo seu efeito mais evidente nas linhagens de CaP. Por fim, Prima-1 reduziu a viabilidade celular independente do status de p53 nas linhagens de CaB / Introduction: One of the main obstacles for understanding biological events involved in cancer is the lack of appropriated models for in vitro studies especially for prostate cancer (PC) and bladder cancer (BC). There are a limited number of PC and BC cell lines being the majority originated from metastatic and invasive tumors. Also it is well known that there are ethnic differences between populations concerning the behavior of tumors. In such a way, the research based on cell lines derived from a homogenous population should be source of limited results, not contemplating the diversity known to occur among different groups. In addition the commercial cell lines are generally acquired at American Tissue Cell Culture (ATCC) that although wellestablished requires importation processes with cost increase and bureaucratic demands that difficult the research. Therefore we consider vital to the comprehension of the carcinogenesis phenomena, as well as drug resistance studies, chemoprevention and new therapeutic strategies, the development of tumor lineages derived from primary tumors that assail our miscigenated population. At the present work, fragments of bladder urothelial carcinoma and prostate adenocarcinoma were obtained by surgical resection of primary tumors from patients treated and followed in the Division of Urology of the Clinical Hospital of the São Paulo University (FMUSP) and Syrian Lebanese Hospital. The cell lines established from these fragments were characterized through growth kinetic, immunocytochemistry and chromosome abnormalities including karyotyping and Fluorescence in situ hybridization (FISH). Moreover, the cell lines were submitted to chemosensitivity studies using curcumin and Prima-1 and analyzed regarding their tumorigenicity in athymic mice. The results of this work show the development of three BC and three PC cell lines that were not tumorigenic in athymic mice. Curcumin at 50 M concentration induced cell death in all studied lineages, being more effective in PC cell lines. Finally, PRIMA-1 reduced the cellular viability independent of the p53 status in BC cell lines

INTRODUÇÃO: Incontinência urinária (IU) é uma complicação comum após prostatectomia radical. Apesar da recuperação da continência ser adquirida pela maioria dos pacientes, esta pode demorar de um a dois anos. Neste trabalho, estudou-se o efeito da reabilitação do assoalho pélvico com biofeedback (RAPB) precoce sobre a gravidade e duração da IU até 12 meses após a prostatectomia radical retropúbica (PRR). MÉTODOS: Realizou-se um estudo prospectivo, controlado e randomizado comparando a RAPB precoce, aos cuidados usuais. A amostra incluiu 73 homens entre 47 e 76 anos, que elegeram a PRR para o tratamento de câncer de próstata localizado e que poderiam cumprir a agenda do programa ambulatorial. Os pacientes foram randomizados em grupo de tratamento (n=36) e grupo controle (n=37). Após a retirada do catéter, os pacientes do grupo de tratamento receberam RAPB uma vez por semana enquanto estavam incontinentes por no máximo 12 semanas e praticaram exercícios domiciliares. Pacientes do grupo controle receberam instruções usuais para contraírem os músculos do assoalho pélvico. Ambos os grupos foram avaliados antes da cirurgia e um, três, seis e 12 meses após a PRR. A força muscular do assoalho pélvico (FMAP) foi avaliada pela escala de Oxford. Os sintomas de incontinência foram medidos pelo domínio de incontinência do Questionário da Sociedade Internacional de Continência para homens (ICSmaleSF). O impacto da IU sobre a qualidade de vida foi medido pelo Questionário de Impacto da Incontinência (IIQ-7). Continência urinária foi definida como o uso de uma proteção ou menos por dia. A incontinência foi graduada pelo teste de fraldas de 24h em leve (perdas menores que 20g), moderada (perdas entre 21 e 74g) e grave (perdas maiores que 75g). RESULTADOS: A avaliação pré-operatória não mostrou diferenças de idade, diabetes, índice de massa corpórea, peso da próstata, FMAP ou sintomas miccionais entre os grupos. Após 12 meses de cirurgia, 25 (96.2%) dos pacientes do grupo de tratamento e 20 (75.0%) pacientes do grupo controle estavam continentes (p=0.028). A redução do risco absoluto foi 21.2% (95% CI: 3.4538.81%) e o risco relativo de recuperação da continência foi 1.28 (95% CI: 1.021.69). O número necessário para tratar foi 5 (95% CI: 2.628.6). O percentual de incontinência grave foi maior no grupo controle em um mês (p=0.015), três meses (p=0.038), seis meses (p=0.012) e 12 meses (p=0.021). Os sintomas de incontinência diminuíram significativamente no grupo de tratamento em um mês (p=0.011), três meses (p=0.002) e 12 meses (p=0.04), mas não em seis meses (p=0.063). A FMAP foi maior após o tratamento em um mês (p=0.043), três meses (p<0.001), seis meses (p=0.021) e 12 meses (p=0.035). O impacto da IU sobre a qualidade de vida foi significativamente melhor no grupo de tratamento no primeiro mês (p=0.025). CONCLUSÕES: A reabilitação do assoalho pélvico com biofeedback precoce diminuiu a gravidade e duração da incontinência urinária após prostatectomia radical retropúbica / INTRODUCTION: Urinary incontinence (UI) is a common complication after radical prostatectomy. Although recovery of continence is achieved by most patients, it can take one to two years. This study tested the effectiveness of pelvic floor biofeedback training (PFBT) on the severity and duration of UI up to 12 months following radical retropubic prostatectomy (RRP). METHODS: This study was a prospective, controlled, randomized trial comparing early postoperative PFBT to usual care. The sample included 73 men between 47 and 76 years old who elected RRP for treatment of clinically localized prostate cancer and could comply with the ambulatory treatment schedule. Patients were randomized into a treatment group (n=36) and a control group (n=37). After catheter removal, patients in the treatment group received PFBT once a week for as long as they were incontinent for a maximum of 12 weeks and practiced exercises at home. Patients in the control group received the usual instructions to contract the pelvic floor muscles. Both groups were evaluated before surgery and one, three, six and 12 months after RRP. Pelvic floor muscle strength (PFMS) was evaluated by the Oxford Scale. Incontinence symptoms were measured by the incontinence part of the International Continence Society Male Short Form Questionnaire (ICSmaleSF). The impact of incontinence on quality of life was measured by the Incontinence Impact Questionnaire (IIQ-7). Urinary continence was defined as the use of one or less pad per day. Incontinence was graduated by the 24h pad test in mild (less than 20g), moderate (between 21 and 74g) and severe (more than 75g). RESULTS: The preoperative assessment did not show differences in age, diabetes, body mass index, prostate weight, PFMS or voiding symptoms between the groups. At 12 months postoperatively, 25 (96.2%) patients in the treatment group and 20 (75.0%) in the control group were continent (p=0.028). The absolute risk reduction was 21.2% (95% CI: 3.4538.81%) and the relative risk of recovering continence was 1.28 (95% CI: 1.021.69). The number needed to treat was 5 (95% CI: 2.628.6). The percentage of severe incontinence was stronger for the control group at one month (p=0.015), three months (p=0.038), six months (p=0.012) and 12 months (p=0.021). Incontinence symptoms significantly decreased in the treatment group at one month (p=0.011), three months (p=0.002) and 12 months (p=0.04), but not at six months (p=0.063). PFMS was stronger after PFBT at one month (p=0.043), three months (p<0.001), six months (p=0.021) and 12 months (p=0.035). The impact of UI on quality of life was significantly improved for the treated group in the first month (p=0.025). CONCLUSIONS: Early pelvic floor biofeedback training decreased the severity and duration of urinary incontinence after radical retropubic prostatectomy

Xiao, Lijia. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 139-158). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

INTRODUÇÃO: Este estudo analisou o impacto da experiência em prostatectomia radical robótica na curva inicial da prostatectomia laparoscópica através dos resultados perioperatórios e funcionais e oncológicos precoces de 110 pacientes com câncer de próstata. PACIENTES E MÉTODOS: 110 pacientes, selecionados aleatoriamente, foram submetidos a PRL por dois cirurgiões com experiência prévia em cirurgia minimamente invasiva e PRR, no Instituto do Câncer do Estado de São Paulo. Os dados foram coletados prospectivamente. Foi utilizada abordagem transperitoneal simulando a técnica robótica. RESULTADOS: Houve uma redução significativa no tempo operatório que diminuiu até o caso 40, quando atingiu um platô. O volume de sangramento mediano foi 250ml (variação 50-1000ml). Nenhum paciente foi transfundido. As complicações foram distribuídas uniformemente ao longo da casuística. A taxa de margens positivas foi de 28,2% (pT2: 20%, pT3: 43,6%), e não apresentou tendência a redução. 61,3% das margens foram apicais. A taxa de continência foi de 88% e atingiu um platô próximo a 95% após 75 casos. CONCLUSÃO: Esse estudo mostra que existem múltiplas curvas no processo de aprendizado da PRL. A curva mais curta foi para tempo operatório. A curva para margens cirúrgicas não foi completada e necessita de intervenção para melhora dos resultados principalmente relacionados a margem apical. A transição entre as técnicas de prostatectomia pode ser considerada segura baseada nas baixas taxas de complicações, ausência de complicações graves ou transfusões sanguíneas / INTRODUCTION: This study analyzed the impact of the experience with Robotic-Assisted Laparoscopic Prostatectomy (RALP) on the initial experience with Laparoscopic Radical Prostatectomy (LRP) by examining perioperative results and early outcomes of 110 patients. LRPs were performed by two robotic fellowship trained surgeons with daily practice in RALP. PATIENTS and METHODS: 110 LRP was used to treat aleatory selected patients. The patients were divided into 4 groups for prospective analyses. A transperitoneal approach that simulates the RALP technique was used. RESULTS: The median operative time was 163 minutes (110 - 240), and this time significantly decreased through case 40, when the time plateaued (p = 0.0007). The median blood loss was 250 ml. No patients required blood transfusion. There were no life-threatening complications or deaths. Minor complications were uniformly distributed along the serie (P= 0,6401). The overall positive surgical margins (PSM) rate was 28.2% (20% in pT2 and 43.6% in pT3). PSM was in the prostate apex in 61.3% of cases. At the 12-month follow-up, 88% of men were continent (0-1 pad). CONCLUSION: The present study shows that there are multiple learning curves for LRP. The shallowest learning curve was seen for the operative time. Surgeons transitioning between the RALP and LRP techniques were considered competent based on the low perioperative complication rate, absence of major complications, and lack of blood transfusions. This study shows that a learning curve still exists and that there are factors that must be considered by surgeons transitioning between the two techniques

Yuen Mong Ting. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 155-169). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract (English) --- p.ii / Abstract (Chinese) --- p.v / Contents --- p.vi / Chapter Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- Developmental biology of the prostate --- p.1 / Chapter 1.1.1 --- Development of the prostate gland in humans and rodents --- p.1 / Chapter 1.1.2 --- Mesenchymal-epithelial interaction --- p.2 / Chapter 1.2 --- Overview of the endocrinology of prostate --- p.3 / Chapter 1.3 --- Estrogen in male and prostate gland --- p.4 / Chapter 1.3.1 --- Stimulating effect of estrogen on prostate gland --- p.4 / Chapter 1.3.2 --- Inhibitory effect of estrogen on prostate gland --- p.5 / Chapter 1.4 --- Study of the role of estrogen receptors in prostate gland with the use of estrogen receptor knockout mice --- p.6 / Chapter 1.4.1 --- The two isoforms of estrogen receptors (ER): ERα and ERβ --- p.6 / Chapter 1.4.2 --- The use of estrogen receptor knockout mice for the study of ER --- p.7 / Chapter 1.5 --- Estrogen as a carcinogen --- p.8 / Chapter 1.5.1 --- Formation of DNA adducts --- p.8 / Chapter 1.5.2 --- Formation of oxidants --- p.9 / Chapter 1.5.3 --- Estrogen as a microtubule-disrupting agent --- p.10 / Chapter 1.6 --- Estrogen carcinogenicity in animal models --- p.11 / Chapter 1.6.1 --- Syrian golden hamster model --- p.11 / Chapter 1.6.2 --- Rat model --- p.12 / Chapter 1.7 --- Animal models of prostate cancer by hormonal induction --- p.12 / Chapter 1.7.1 --- Canine model --- p.13 / Chapter 1.7.2 --- Noble rat model --- p.13 / Chapter 1.7.3 --- Sprague-Dawley rat model --- p.15 / Chapter 1.7.4 --- Wistar and F344 rat model --- p.15 / Chapter 1.8 --- Perinatal estrogen exposure and prostate development --- p.16 / Chapter 1.8.1 --- Prenatal estrogen exposure --- p.15 / Chapter 1.8.2 --- Neonatal estrogen exposure --- p.17 / Chapter 1.9 --- Therapeutic use of synthetic estrogen --- p.18 / Chapter 1.9.1 --- Use of diethylstilbestrol in treating prostate cancer --- p.18 / Chapter 1.9.2 --- Use of diethylstilbestrol during pregnancy --- p.19 / Chapter 1.10 --- Estrogen contamination in food --- p.20 / Chapter 1.10.1 --- Estrogen in milk and dairy products --- p.20 / Chapter 1.10.2 --- Estrogen in meat --- p.21 / Figure 1.1 --- p.23 / Chapter Chapter 2. --- Materials and methods --- p.25 / Chapter 2.1 --- In vitro study of estrogen carcninogenicity in normal prostatic cell line --- p.25 / Chapter 2.1.1 --- NRP-152 cell line --- p.25 / Chapter 2.1.2 --- In vitro estrogen treatment on NRP-152 cells --- p.25 / Chapter 2.1.3 --- Colony formation by soft agar assay --- p.27 / Chapter 2.1.4 --- Determination of growth parameters of estrogen-treated and untreated NRP-152 cells --- p.29 / Chapter 2.1.5 --- Gene expression profiling in estrogen-transformed and untreated parental NRP-152 cells by cDNA microarray --- p.30 / Chapter 2.1.6 --- Immunohistochemistry of cultured cells --- p.34 / Chapter 2.1.7 --- Immunofluorescence on cultured cells --- p.36 / Chapter 2.1.8 --- Electron microscopy of the estrogen-transformed and untreated parental NRP-152 cells --- p.37 / Chapter 2.1.9 --- Tumorigenicity in nude mice --- p.38 / Chapter 2.1.10 --- Protein expressions and Western blottings in estrogen-transformed and untreated parental NRP-152 cells --- p.39 / Chapter 2.2 --- In vivo study of estrorgen carcinogenicity in rat protstate gland --- p.41 / Chapter 2.2.1 --- Origin and supply of Noble rats --- p.41 / Chapter 2.2.2 --- Perinatal estrogen imprinting on male Noble rats with diethylstilbestrol --- p.42 / Chapter 2.2.3 --- Long-term hormonal treatment with sex steroids on male Noble rats at adulthood --- p.43 / Chapter 2.2.4 --- Morphological study of Noble rat prostates --- p.44 / Chapter 2.2.5 --- Protein expressions by immunohistochemistry in estrogen-primed and hormone-treated Noble rat prostates --- p.45 / Tables 2.1 -2.2 --- p.48 / Chapter Chapter 3. --- Results --- p.50 / Chapter 3.1 --- In vitro study --- p.50 / Chapter 3.1.1 --- Dose selection for estrogen treatment of NRP-152 cells from cell proliferation assay --- p.50 / Chapter 3.1.2 --- Colony formation in soft agar --- p.50 / Chapter 3.1.3 --- Morphology of NRP-152 cells and the estrogen-transformed clones --- p.51 / Chapter 3.1.4 --- Study of growth parameters --- p.52 / Chapter 3.1.5 --- CDNA array analysis of differentia] gene pattern --- p.53 / Chapter 3.1.6 --- Immunohistochemistry of untreated parental and estrogen- transformed NRP-152 cells --- p.55 / Chapter 3.1.7 --- Electron microscopy --- p.58 / Chapter 3.1.8 --- Tumorigenicity of NRP-152 cells and the estrogen-transformed clones --- p.59 / Chapter 3.1.9 --- Western blottings --- p.59 / Chapter 3.2 --- In vivo study --- p.52 / Chapter 3.2.1 --- Survival of male Nobel rats during perinatal and long-term hormone treatment --- p.62 / Chapter 3.2.2 --- Histological studies of Noble rat prostates --- p.63 / Chapter 3.2.3 --- Immunohistochemistry of the hormone-treated and control Noble rat prostates --- p.65 / Figure 3.1.1 -3.1.44 --- p.73 / Figure 3.2.1 - 3.2.50 --- p.97 / Table 3.1 -3.4 --- p.117 / Chapter Chapter 4. --- Discussions --- p.121 / Chapter 4.1 --- The study on the transformation of cells and soft agar assay --- p.121 / Chapter 4.2 --- Growth patterns of the estrogen-transformed clones --- p.123 / Chapter 4.3 --- Altered differential gene expression --- p.124 / Chapter 4.3.1 --- TUBA --- p.124 / Chapter 4.3.2 --- PTEN --- p.125 / Chapter 4.3.3 --- RAP 1A --- p.126 / Chapter 4.3.4 --- BRCA2 --- p.126 / Chapter 4.4 --- Ultrastructural study in the estrogen-transformed and untreated parental NRP-152 cells --- p.127 / Chapter 4.5 --- Neoplastic lesions induced in prostates of estrogen-imprinted and long-term combined hormone treated Noble rats --- p.129 / Chapter 4.6 --- Altered protein expressions in estrogen-transformed NRP-152 cells and estrogen-imprinted and hormone-treated Noble rat prostates --- p.132 / Chapter 4.6.1 --- Alteration in steroid hormone receptors --- p.132 / Chapter 4.6.2 --- Alternation in cytoskeleton (tubulin-α) --- p.138 / Chapter 4.6.3 --- Alternation in PTEN --- p.141 / Chapter 4.6.4 --- Alternation in Rap1 --- p.143 / Chapter 4.6.5 --- Alternation in BRCA2 --- p.145 / Chapter 4.6.6 --- "Altered in scavenger enzyme (Superoxide dismutase, SOD-1)" --- p.147 / Chapter Chapter 5. --- Summary --- p.150 / Reference --- p.155

In summary, the present findings have demonstrated the important roles of CFTR in prostatitis and cancer development, which may provide new insight into the understanding of the prostate in health and disease. The present findings may also have potential application in diagnosis and prognosis of cancer. / In the first part of the study, the possible role and a bacterial killing mechanism involving CFTR-mediated bicarbonate secretion in prostatitis were investigated in a rat prostate model. CFTR was found to be expressed in the epithelium of rat ventral prostate. Experiments using cultured rat primary prostate epithelial cells demonstrated that CFTR was involved in mediating bicarbonate extrusion across the prostate epithelium. The expression of CFTR and carbonic anhydrase II (CAII), a key enzyme involved in cellular HCO 3- production, along with several pro-inflammatory cytokines including IL-6, IL-1beta, TNF-alpha, was significantly up-regulated in the primary culture of rat prostate epithelial cells upon E.coli-LPS challenge. Inhibition of CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO3- content (>50mM), rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO 3- on bacterial killing was confirmed by its ability to suppress bacterial initiation factors in E coli. The relevance of the CFTR-mediated HCO3- secretion in human was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. The present results have demonstrated that CFTR plays a previously undefined role in prostatitis and could be up-regulated during the inflammation in prostate as a host defense mechanism to increase bicarbonate secretion for bacterial killing. / In the second part of the study, the possible role of CFTR in prostate cancer development and the underlying mechanisms were investigated. Our results showed that the expression of CFTR and CAII in prostate was remarkably decreased in aged rat prostate. We observed that testosterone could up-regulate the expression of CFTR and CAII in vitro and in vivo , indicating that the declined male hormones during aging may be responsible for the observed age-dependent expression of CFTR. In the present study, we found that inhibition of CFTR enhanced cell proliferation/anti-apoptosis in the prostate primary epithelial cells. CFTR was detected in all examined prostate cell lines, but with relatively higher expression levels in immortalized cell lines (PZ-HPV-7, PNT1A, PNT2C2) than in cancer cell lines (PC-3, DU-145, LNCaP). Immunohistological studies showed that the expression of CFTR was dramatically reduced in prostate cancer specimens as compared to that in normal prostate tissues. Furthermore, our gain and loss of function studies showed that knockdown of CFTR profoundly enhanced cell proliferation, cell adhesion, invasion and migration, while inhibited apoptosis in prostate cancer cell lines, overexpression of CFTR dramatically suppressed tumorigenic phenotype of cancer cells. Soft agar anchorage-independent growth assay showed that knockdown of CFTR in prostate cancer cells increased the number of colonies formed in soft agar. More importantly, we demonstrated that CFTR knockdown promoted the tumor growth in vivo and forced overexpression of CFTR in prostate cancer cells and ultrasound-mediated gene transfer of CFTR inhibited xenograft tumor growth in vivo. Mechanistically, multiple mechanisms were identified to contribute to the CFTR- mediated tumor suppressive effects. Firstly, CFTR chloride channel function was implicated in the regulation of apoptosis in prostate cancer cells. Secondly, CFTR up-regulated the transcription level of miR-34a and miR-193b, both of which have been indicated as tumor suppressors in multiple cancers. Thirdly, 11 cancer-related genes were found to be up- or down-regulated by CFTR using PCR-array. These data demonstrated that CFTR may play an important role in prostate cancer development by acting as a tumor suppressor. / The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel conducting both Cl- and HCO3 -. It is expressed in epithelial cells of a wide variety of tissues. CFTR is also known to be expressed in human prostate; however, the physiological role of CFTR in the prostate and related diseases remains largely unknown. This thesis explored the biological roles of CFTR in prostatitis and cancer development. / Xie, Chen. / Adviser: Chan LiShaw Chang. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 175-192). / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

In order to further investigate the functions of ERRbeta/gamma in prostate cancer, the following aspects were explored in my study. My results show that: (1) Expressions of ERRbeta/gamma was down-regulated in prostate cancer cell lines and prostate cancer tissues. And only the short-form but not other ERRbeta isoforms was expressed in prostatic cells. (2) Overexpression of ERRbeta/gamma significantly inhibited the cell proliferation in vivo and in vitro. (3) Cell cycle analysis showed that S-phase fraction of ERRbeta/gamma stable clones was significantly decreased, while there was no significantly induced apoptosis by ERRbeta/gamma overexpression. This was confirmed by BrdU incorporation assay. (4) Expressions of two cyclin-CDK inhibitors p21Cip1/Waf1 and p27Kip1 were increased significantly in ERRgamma clones, but only p21 in ERRbeta clones. (5) P21 and p27 gene promoters could be transactived by ERRgamma, but only p21 by ERRbeta. The transactivity of p21 by ERRbeta can be potently enhanced by PGC-1alpha (6) Deletion mutants of ERRgamma showed the transaction of p21 required an intact DNA-binding domain. (7) DY131, the ERRbeta/gamma agonist, further potentiated the growth inhibition in ERRbeta/gamma-stable clones in a dose-dependent manner. (8) There were increase in number of giant potential-active mitochondria and accumulation of lipid droplets in ERRbeta-clones. / Prostate cancer is the most common diagnosed cancers in men in western countries. Despite the substantial clinical significance, the mechanisms underlying the development and progression of prostate cancer are poorly understood. ERRs(alpha, beta, gamma) belong to orphan nuclear. All ERR subtypes share significant homology with estrogen receptors (ERs) in their protein structures. Functionally ERRalpha shares, regulates same target genes with ERalpha and is involved in carcinogenesis, while the ERRbeta and ERRgamma are still unknown. / The results obtained indicate that ERRbeta/gamma inhibit proliferation of prostate cancer cells by arresting of cell cycle progression, suggesting a tumor suppressor function for ERRbeta/gamma in prostate cancer. p21 may be the key mediator of this suppressor function, and the p21 is the target gene of ERRbeta/gamma. The selective ERRbeta/gamma agonist, DY131, potently inhibited the proliferation of ERRbeta/gamma-positive prostate cancer cells, suggesting ERRbeta and gamma could be a potential therapeutic target for prostate cancer therapy. / Yu, Shan. / "July 2007." / Adviser: Franky L. Chan. / Source: Dissertation Abstracts International, Volume: 69-01, Section: B, page: 0238. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 140-165). / 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.

Tse, Ho Man. / Thesis (M.Phil)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 166-173). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / 撮要 --- p.v / Table of Content --- p.vi / Chapter Chapter 1: --- Introduction --- p.1 / Chapter 1.1 --- Basis of Prostate Cancer --- p.1 / Chapter 1.1.1 --- Epidemiology and Risk Factors of Prostate Cancer --- p.1 / Chapter 1.1.2 --- Pathology of Prostate Cancer --- p.2 / Chapter 1.1.3 --- Treatment Approaches for Prostate Cancer --- p.4 / Chapter 1.2 --- Sex Hormones and Prostate Cancer --- p.7 / Chapter 1.2.1 --- Prostate Development --- p.7 / Chapter 1.2.2 --- Involvement of Sex Hormones in Prostate Cancer --- p.8 / Chapter 1.2.3 --- Molecular Mechanisms of Sex Hormones --- p.13 / Chapter 1.2.4 --- Hormone Receptor Antagonists --- p.15 / Chapter 1.3 --- Involvement of microRNAs in Cancer --- p.19 / Chapter 1.3.1 --- Basis of microRNAs --- p.19 / Chapter 1.3.2 --- Aberrant microRNA Expressions in Cancers --- p.23 / Chapter 1.3.3 --- Current Understandings on Regulations of micro RN A Expressions --- p.26 / Chapter 1.3.4 --- Regulation of miRNA Expressions by Hormones --- p.29 / Chapter 1.4 --- "Effects of the Anti-estrogen ICI 182,780 on Prostate Cancer Cells" --- p.30 / Chapter 1.4.1 --- "ICI 182,780 Inhibits Cell Growth ofDU145" --- p.30 / Chapter 1.5 --- Objectives of Project --- p.32 / Chapter Chapter 2: --- Materials --- p.34 / Chapter 2.1 --- Bacteria Strain --- p.34 / Chapter 2.2 --- Tissue Culture Media --- p.34 / Chapter 2.3 --- Plasmids --- p.34 / Chapter 2.4 --- Kits and Accessories --- p.35 / Chapter 2.5 --- Reagents and Solutions --- p.36 / Chapter 2.6 --- DNA Oligos --- p.38 / Chapter 2.7 --- Equipments --- p.40 / Chapter Chapter 3: --- Methods --- p.41 / Chapter 3.1 --- Cell Culture Conditions --- p.41 / Chapter 3.2 --- miRNA Expression Profiling of DU145 --- p.41 / Chapter 3.2.1 --- RNA Isolation --- p.41 / Chapter 3.2.2 --- miRNA Microarray Profiling ofDU145 : --- p.42 / Chapter 3.2.2.1 --- Fluorescent Labeling of RNA and Microarray Hybridization --- p.42 / Chapter 3.2.2.2 --- Scanning and Analysis of Signals --- p.46 / Chapter 3.2.3 --- Confirming miR-765 Up-regulation by ICI with qRT-PCR --- p.46 / Chapter 3.2.3.1 --- Assessing ERp Dependency in miR-765 Induction --- p.48 / Chapter 3.2.4 --- Effects of ICI on ARHGEF11 Expression --- p.49 / Chapter 3.2.4.1 --- Reverse Transcription of mRNA --- p.50 / Chapter 3.2.4.2 --- Quantitative Real-Time PCR for Gene mRNA expression --- p.50 / Chapter 3.3 --- Characterizing the Promoter Region of miR-765 --- p.52 / Chapter 3.3.1 --- Cloning of miR-765 Promoter into pGL3-Basic Vector --- p.52 / Chapter 3.3.1.1 --- PCR Amplification of miR-765 Putative Promoter Region --- p.52 / Chapter 3.3.1.2 --- Ligation of the Amplified Regions in pGL3-Basic Vector --- p.55 / Chapter 3.3.1.3 --- Transformation and Screening of pGL3-765 Plasmid --- p.57 / Chapter 3.3.1.4 --- Preparation of pGL3-765 Plasmid DNA --- p.59 / Chapter 3.3.2 --- Preparation of Truncated miR- 765 Promoter Clones --- p.60 / Chapter 3.3.2.1 --- pGL3-765-Trunc#l --- p.61 / Chapter 3.3.2.2 --- pGL3-765-Trunc#2 --- p.62 / Chapter 3.3.2.3 --- pGL3-765-Trunc#3 --- p.62 / Chapter 3.3.3 --- Assessing the miR- 765 Promoter Activities --- p.63 / Chapter 3.3.3.1 --- Optimizing Transfection Conditions --- p.64 / Chapter 3.3.3.2 --- Co-transfection of pGL3-765 and pRL-CMV into DU145 Cells.. --- p.64 / Chapter 3.3.3.3 --- Measuring Luciferase Activities --- p.65 / Chapter 3.3.4 --- Computational Prediction of Transcription Factor Binding Sites on miR-765 Promoter --- p.66 / Chapter 3.4 --- Characterizing the Promoter Region of ARHGEF11.. --- p.67 / Chapter 3.4.1 --- Cloning of ARHGEF11 Promoter into pGL3-Basic Vector (pGL3-ARH) --- p.67 / Chapter 3.4.1.1 --- PCR Amplification of ARHGEF11 Putative Promoter Region --- p.67 / Chapter 3.4.1.2 --- Ligation of the Amplified Regions in pGL3-Basic Vector --- p.68 / Chapter 3.4.1.3 --- Preparation of Plasmid DNA --- p.69 / Chapter 3.4.2 --- Preparation of Truncated ARHGEF11 Promoter Clones --- p.69 / Chapter 3.4.2.1 --- pGL3-ARH-Trunc#l --- p.69 / Chapter 3.4.2.2 --- pGL3-ARH-Trunc#2 --- p.70 / Chapter 3.4.2.3 --- pGL3-ARH-Trunc#3 --- p.71 / Chapter 3.4.3 --- Assessing ARHGEF11 Promoter Activities --- p.72 / Chapter 3.5 --- Identifying Transcription Factor Binding Sites on ARHGEF11 Promoter with EMS A --- p.73 / Chapter 3.5.1 --- Computational Prediction --- p.73 / Chapter 3.5.2 --- Preparation of Biotinylated Probe for use in EMSA --- p.73 / Chapter 3.5.3 --- Preparation of Specific Competitors --- p.74 / Chapter 3.5.4 --- Preparation of DU145 Nuclear and Cytoplasmic Extracts --- p.75 / Chapter 3.5.4.1 --- Preparation of Extracts --- p.75 / Chapter 3.5.4.2 --- Measuring Protein Concentrations --- p.76 / Chapter 3.5.5 --- EMSA Detection of Interaction between Protein and Probe --- p.76 / Chapter 3.6 --- Assessing Biological Significances of miR-765 --- p.78 / Chapter 3.6.1 --- Effects of ICI on DU145 Cells Growth --- p.79 / Chapter 3.6.2 --- Effects of ICI on DU145 Migration Ability --- p.79 / Chapter 3.6.2.1 --- Monolayer Wound Healing Assay --- p.79 / Chapter 3.6.2.2 --- Transwell Migration Assay --- p.80 / Chapter 3.6.3 --- Validating Functionality of Ectopic miR- 765 --- p.81 / Chapter 3.6.3.1 --- miR-765 Recognition Sequence --- p.81 / Chapter 3.6.3.2 --- Preparation of pMIR-765 vector --- p.82 / Chapter 3.6.3.3 --- Ectopic Introduction of miR-765 into DU145 Cells --- p.84 / Chapter 3.6.3.4 --- "Verifying Functionality, of Ectopic miR-765" --- p.84 / Chapter 3.6.4 --- Effects of miR-765 on DU145 Growth --- p.86 / Chapter 3.6.5 --- Effects of miR-765 on DU145 Migration Ability --- p.86 / Chapter 3.7 --- Statistical Analysis --- p.87 / Chapter Chapter 4: --- Results --- p.88 / Chapter 4.1 --- "Identifying ICI 182,780-Regulated miRNA in DU145 Cells" --- p.88 / Chapter 4.1.1 --- miRNA Expression Profiling of DU145 with Microarray --- p.88 / Chapter 4.1.2 --- "Confirming Induction of miR-765 by ICI 182,780 with qRT-PCR" --- p.91 / Chapter 4.1.3 --- "ARHGEF11, Host Gene of miR-765" --- p.95 / Chapter 4.1.4 --- "Induction of ARHGEF 11 by ICI 182,780" --- p.96 / Chapter 4.2 --- Characterization miR-765 Promoter Region --- p.98 / Chapter 4.2.1 --- Cloning of miR- 765 Promoter Region into pGLS-Basic Vector --- p.98 / Chapter 4.2.2 --- Promoter Activity of miR-765 Promoter --- p.100 / Chapter 4.2.3 --- Deletion Mapping of miR- 765 Promoter Region --- p.102 / Chapter 4.2.4 --- Promoter Activities and Inducibitiy of Truncated miR-765 Promoters --- p.103 / Chapter 4.2.5 --- Computational Prediction of Transcription Factor Binding Sites on miR-765 Promoter --- p.105 / Chapter 4.3 --- Characterization of ARHGEF 11 Promoter Region --- p.107 / Chapter 4.3.1 --- Cloning of ARHGEF 11 Promoter --- p.107 / Chapter 4.3.2 --- Promoter Activitiy of ARHGEFll Promoter --- p.109 / Chapter 4.3.3 --- Deletion Mapping of ARHGEFll Promoter --- p.111 / Chapter 4.3.4 --- Promoter Activities and Inducibitiy of Truncated ARHGEF 11 Promoters --- p.113 / Chapter 4.4 --- Identifying Transcription Factor Binding Sites on ARHGEF 11 Promoter --- p.115 / Chapter 4.4.1 --- Computational Prediction of Transcription Factor Binding Sites onARHGEFll Promoter --- p.115 / Chapter 4.4.2 --- Preparation of Probe and Specific Competitors for EMSA --- p.117 / Chapter 4.4.3 --- Interaction between DU145 Nuclear Extract and ARHGEF 11 Promoter Region --- p.119 / Chapter 4.5 --- Biological Significances of miR-765 --- p.122 / Chapter 4.2.1 --- "Effects of ICI 182,780 on DU145 Cell growth" --- p.122 / Chapter 4.2.2 --- "Effects of ICI 182,780 on DU145 Cell Migration" --- p.124 / Chapter 4.2.3 --- Verifying Functionality of Ectopic miR-765 --- p.131 / Chapter 4.2.4 --- Effects of miR-765 on DU145 Cell Growth --- p.133 / Chapter 4.2.5 --- Effects of miR-765 on DU145 Cell Migration --- p.135 / Chapter Chapter 5: --- Discussion --- p.138 / Chapter 5.1 --- "Identifying miR-765 as an Up-regulated miRNA by ICI 182,780" --- p.139 / Chapter 5.1.1 --- "Information about ICI 182,780" --- p.139 / Chapter 5.1.2 --- miRNA Profiling of DU145 --- p.139 / Chapter 5.1.3 --- "Confirming Induction of miR-765 by ICI 182,780 and ERβ dependency with qRT-PCR" --- p.140 / Chapter 5.1.4 --- "Up-regulation of miR-765 Host Gene, ARHGEF11, by ICI" --- p.141 / Chapter 5.2 --- Regulatory Elements of miR-765 Expression --- p.143 / Chapter 5.2.1 --- Own Upstream promoter of miR- 765 --- p.144 / Chapter 5.2.2 --- Promoter of Host Gene ARHGEF11 --- p.146 / Chapter 5.2.3 --- Interaction between ARHGEF11 Promoter Critical Region and Transcription Factors --- p.147 / Chapter 5.2.4 --- Involvement of independent Promoter and Host Gene Promoter in miR-765 Regulation --- p.757 / Chapter 5.3 --- Biological Significances of miR-765 on DU145 --- p.153 / Chapter 5.4 --- Significance of Findings and Future Studies --- p.158 / Chapter 5.4.1 --- Clinical Significance --- p.158 / Chapter 5.4.2 --- Future Studies --- p.161 / Chapter Chapter 6: --- Conclusion --- p.163 / Chapter Chapter 7: --- References --- p.166