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.

Percutaneous needle placement, a minimally invasive procedure performed dozens of millions in the U.S. each year, relies on dedicated skill and long-term training due to difficult control of needle trajectory inside tissue and mental registration of images to locations inside the patient. Inaccurate needle placement may miss cancer tumors during diagnosis or eradicate healthy tissue during therapy. MRI provides ideal procedure guidance with the merit of excellent soft tissue contrast and volumetric imaging for high spatial resolution visualization of targets and surgical tool. However, manual insertion in the bore of an MRI scanner has awkward ergonomics due to difficult access to the patient, making both training and intervention even harder. To overcome the challenges related to MRI electromagnetic compatibility and mechanical constraints of the confined close-bore, a modular networked robotic system utilizing piezoelectric actuation for fully actuated prostate biopsy and brachytherapy is developed and evaluated with accuracy study. To enhance manipulation dexterity, two kinds of steerable continuum needle robots are developed. The asymmetric tip needle robot performs needle rotation and translation control to minimize tissue deformation, and increase steering dexterity to compensate placement error under continuous MRI guidance. The MRI-guided concentric tube robot is deployed to access delicate surgical sites that are traditionally inaccessible by straight and rigid surgical tools without relying on tissue reaction force. The master-slave teleoperation system with hybrid actuation is the first of its kind for prostate intervention with force feedback. The teleoperation controller provides the feel and functionality of manual needle insertion. Fabry- Perot interferometer based fiber optic force sensor is developed for the slave manipulator to measure needle insertion force and render proprioception feedback during teleoperation.

Made available in DSpace on 2016-04-28T20:40:17Z (GMT). No. of bitstreams: 1 Licia Ferreira Caire.pdf: 1034574 bytes, checksum: 09b9f70995105a8373219082f77e4b8c (MD5) Previous issue date: 2010-05-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The fact that almost all the studies returned through the systematic review concerned the keywords cancer and hypnosis‟ aimed just relate statistical data, as so the rare number of researches associating psychologic aspects and the hypnotic self-experience reported instigate a qualitative method for the atual study. The goal of this research was interpreting and understanding the impact of self-experienced during the hypnotic state by each prostate cancer patient about his self realize of health, thrust in treatment and improvement of strategies to make a future better. Without to forget the anguish which starts with the diagnosis and interventions possible. 12 prostate cancer patients were companied along 5 sessions of hypnotherapy weakly each one during around one hour. The instruments consisted individuals interview before the start of the five hypnotherapy sessions, another one before each weakly session so as after each one; Hypnotic Interventions and registration of the interview. It was choose the Thematic Technique to select the subjects to be analyzed under the theoretical considerations of Psychosomatic, Psychobiology and Erickson Hypnotherapy. Subjects which demonstrated be relevant to analyze and discussion because the recurrence and anguish that brings were: Feelings and Impulses about the Impact with the Diagnosis, Meanings of Cancer and Thrust in Cure; Self-realize about Cancer Health, Improvement about Capacity of believe that makes a Future is possible. Conclusion indicated that 100% of the followers patients mentioned fell themselves better about the health, thrust in cure, improvement in the humor and increases on the strategies with the stress situations / Considerando o reduzido número de pesquisas realizadas sobre o tema câncer e hipnose que associassem aspectos psicológicos vivenciais e existenciais advindos da experiência do sujeito frente a técnica de hipnose e, tendo em vista que a quase totalidade de pesquisas retornadas a partir da revisão bibliográfica objetivava conjugar dados estatísticos, justificou-se uma pesquisa qualitativa com objetivo de interpretar e compreender o impacto das re-significações vivenciais experienciadas em estado hipnótico por cada paciente com câncer de próstata frente sua auto-percepção de saúde, crença no tratamento e capacidade de prospectar o futuro; sem negligenciar as angústias existenciais deflagradas desde o diagnóstico e intervenções. Foram acompanhados 12 sujeitos com câncer de próstata durante 5 sessões de hipnoterapia escalonadas semanalmente com duração de 1 hora. Os instrumentos consistiram em entrevistas individuais semi-dirigidas realizadas antes do início do tratamento hipnoterápico, antes de cada sessão semanal e após cada sessão; Intervenções hipnóticas e Registros das entrevistas. Foi eleita a Técnica de Análise Temática para a seleção de temas a serem analisados à luz dos preceitos teóricos psicossomáticos, da Psicobiologia e da Hipnoterapia Ericksoniana. Os Temas que mereceram destaque para análise e discussão de conteúdo devido à recorrência e angústia que despertaram foram: Sentimentos e Impulsos ao Impacto do Diagnóstico; Significado do Câncer e Crença na Cura; Auto-percepção da Melhora do Câncer; Retomada da Capacidade de Prospectar o Futuro. A conclusão indicou que 100% dos pacientes acompanhados referiram melhora na saúde, certeza da cura, retomada do humor e incremento nas estratégias de enfrentamento às situações estressógenas

Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-04-24T12:41:11Z No. of bitstreams: 1 ShirleyPontesDissertacao2018.pdf: 1632850 bytes, checksum: 1119ac63b939927d264497f421422810 (MD5) / Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-04-24T12:41:31Z (GMT) No. of bitstreams: 1 ShirleyPontesDissertacao2018.pdf: 1632850 bytes, checksum: 1119ac63b939927d264497f421422810 (MD5) / Made available in DSpace on 2018-04-24T12:41:31Z (GMT). No. of bitstreams: 1 ShirleyPontesDissertacao2018.pdf: 1632850 bytes, checksum: 1119ac63b939927d264497f421422810 (MD5) Previous issue date: 2018-02-23 / The diagnosis and treatment of prostate cancer can cause significant changes in the life of men influencing their quality of life. The objective of this study was to evaluate the health-related quality of life of patients with prostate cancer submitted to radiotherapy. It is a descriptive cross-sectional study with non-probabilistic sampling. Subjects eligible for the study were 120 men with prostate cancer who underwent on treatments at HUB - CACON. The instruments used were EORTC QLQ-C30 and the International Index Of Erectil Function- IIEF-5. The research project was approved by the Ethics and Research Committee of the Faculty of Medicine of the Catholic University of Brasilia under the number CAAE: 58197916.8.0000.0029.: The profile os subjects is aged between 70 and 79 years (42.3%), with elementary school (72.3%), brown (44.6%), married or had a partner (75.6%). Among the comorbidities, the highest incidence was arterial hypertension (70%) followed by Diabetes MellitusII (33.8%). The most frequent toxicities resulting from RT treatment, was dysuria (43%), followed by diarrhea (22.3%). The analysis of IIEF-5 allows to observe that 79.2% suffer from severe erectile dysfunction.. The prostate cancer treatments tend to cause negative impacts on sexual function and self-perceived quality of life. The age does not influence role performance, and isolated or simultaneous treatments proved to be important factor to erectile function score. Conclusion: The group who have undergone to RT + RP suffer more from pain and fatigue, and the group who have undergone to RT + CQ suffer more insomnia. All participants who have undergone RT + PR + CQ suffer severe erectile dysfunction. Considering the findings of this study, it confirm that the patients with prostate cancer who manage maintain erectile function moderate, mild and normal, they as well maintain their social roles as work, family relationships and marriage. They also keep their emotions balanced and control their irritability, tension, depression, and they feel less fatigue. This study allows to understand the local reality and corroborates with the findings of other studies carried out in different regions and social contexts. / O diagn??stico e o tratamento do c??ncer de pr??stata podem provocar mudan??as significativas na vida dos homens e influenciar a sua qualidade de vida. O objetivo deste estudo foi avaliar a qualidade de vida relacionada ?? sa??de e a fun????o er??til dos pacientes com c??ncer de pr??stata. Trata-se de um estudo descritivo de corte transversal com amostragem n??o probabil??stica. Os indiv??duos eleg??veis para o estudo foram 120 homens portadores de c??ncer de pr??stata, que se submeteram ?? radioterapia no HUB ??? CACON. Os instrumentos utilizados foram o EORTC QLQ-C30, e o ??ndice Internacional de Fun????o Er??til IIEF-5. O projeto de pesquisa foi aprovado pelo Comit?? de ??tica e Pesquisa da Faculdade de Medicina da Universidade Cat??lica de Bras??lia sob o n??mero CAAE: 58197916.8.0000.0029. O perfil do participante ?? idade entre 70 a 79 anos (42,3%), com ensino fundamental (72,3%), da cor parda (44,6%), casado ou tinha uma companheira (75,6%). Dentre as comorbidades a de maior incid??ncia foi hipertens??o arterial (70%) seguida de Diabetes Mellitus tipo 2 (33,8%). As toxicidades decorrentes do tratamento com RT, a mais frequente foi dis??ria (43%), seguida por diarreia (22,3%). A an??lise do IIEF- 5 permite observar o ??ndice de disfun????o er??til dos participantes, em que 79,2% dos participantes sofrem de disfun????o er??til severa. Discuss??o: Os tratamentos de c??ncer de pr??stata tendem a causar impactos negativos na fun????o sexual. E na autopercep????o da qualidade de vida. A idade n??o influencia no desempenho de papeis sociais. Os tratamentos se realizados isolados ou simultaneamente provaram ser um importante fator no escore da fun????o er??til. Conclus??o: O grupo que se submeteu a RT + RP sofre mais de dor e fadiga, o grupo que se submeteu a RT + CQ sofre mais de ins??nia e todos os participantes que se submeteram a RT + PR + CQ sofrem de disfun????o er??til severa. Considerando os achados desse estudo, se confirma que pacientes com c??ncer de pr??stata que conseguem manter a fun????o er??til entre moderada, leve e normal, tamb??m mant??m os desempenho de papeis sociais como trabalho, fam??lia, relacionamentos e o casamento. Eles tamb??m conseguem manter as emo????es mais equilibradas como controle da irritabilidade, tens??o e depress??o, e sentem menos fadiga.. Este estudo permite entender a realidade local bem como corrobora os achados de outros estudos em diferentes regi??es e contextos sociais.

O câncer de próstata é a segunda causa de morte entre homens no Brasil. É tipo um câncer de crescimento lento, podendo levar anos para o tumor atingir 1 cm3, porém, em alguns casos ele pode se espalhar pelo corpo, sendo o osso o principal sítio de metástase. No estágio de desenvolvimento do câncer conhecido como metástase, o principal tratamento consiste em terapia de restrição andrógena, levando as células prostáticas a pararem de proliferar, uma vez que elas crescem em resposta a presença de hormônios andrógenos, como a diidrotestosterona e testosterona. Porém, em alguns casos, as células proliferam mesmo na ausência de andrógenos e isto se deve a diversos fatores que, em geral, estão associados a mutações no receptor andrógeno e/ou alterações no metabolismo andrógeno. Quando isto acontece, os tratamentos disponíveis são menos efetivos e costumam falhar. Porém, estudos sugerem que o γ-orizanol, um fitoesterol extraído do óleo do farelo do arroz; e extratos amplamente utilizados na medicina popular, como o extrato hidroalcólico de Thuya occidentalis, poderiam atuar inibindo o desenvolvimento e progressão do câncer de próstata. Neste estudo, com o uso de abordagens bioquímicas e de biologia molecular, foi demonstrado que o tratamento com γ-orizanol diminui a viabilidade e biomassa celular em cultura, associado ao aumento da morte celular por apoptose e/ou necrose, em linhagens celulares responsivas (LNCaP) e não-responsivas a andrógenos (PC3 e DU145), além de aumentar a pERK1/2 em células LNCaP e DU145. O γ-orizanol também foi capaz de bloquear o ciclo celular em G2/M nas células PC3 e LNCaP e em G0/G1 nas células DU145. Estes efeitos foram ainda acompanhados por uma redução da expressão do gene e proteína caveolina-1- uma importante molécula envolvida no aumento da agressividade do câncer de próstata, e também, na progressão da doença para o fenótipo andrógeno resistente - nas células não-responsivas a andrógenos, e do gene PCGEM1 - gene específico da próstata regulado por andrógeno - nas células LNCaP e DU145. Ainda, γ-orizanol também mostrou capacidade de regular vários miRNAs - pequenas moléculas de RNA não codificantes de proteínas - envolvidos no controle de funções associadas ao desenvolvimento, progressão e invasão no câncer de próstata, como o miR16-1, miR19b-2, miR24b-1, miR24b-2, miR99a, miR133a-5p, miR182-5p, miR198 e miR222. O extrato hidroalcólico de Thuya occidentalis reduziu a viabilidade e biomassa celular nas linhagens responsiva (LNCaP) e não-responsivas (DU145 e PC3) a andrógenos, além de induzir parada do ciclo celular na fase G0/G1 nas células DU145 e aumentar a morte celular por apoptose e/ou necrose em todas as linhagens. Da mesma forma que o γ-orizanol, este extrato reduziu a expressão da caveolina-1 nas linhagens não-responsivas a andrógenos. Trabalhos anteriores mostram que o monoterpeno α-tujona é o principal composto ativo do extrato de Thuya occidentalis. Por cromatografia gasosa acoplada a detector de massas foi mostrada a existência de 0,0016 μg de α-tujona na dose de extrato usada neste estudo. No entanto, o tratamento com 0,0016μg de α-tujona foi efetivo somente sobre linhagem LNCaP, não tendo efeito sobre as outras linhagens estudadas, reforçando a hipótese da diferença de sensibilidade entre as linhagens responsivas e não responsivas a andrógeno e mostrando a contribuição de outros componentes do extrato nos efeitos observados neste estudo. Concluindo, estes resultados demonstram que tanto γ-orizanol como o extrato de Thuya occidentalis podem vir a ser agentes terapêuticos promissores no tratamento de câncer de próstata, não só por inibirem o crescimento celular, mas também e principalmente pela possibilidade de induzirem a recuperação da sensibilidade a andrógenos, aumentando as possibilidades de tratamento da doença. / Prostate cancer is the second cause of death among men in Brazil. It is a slowgrowing cancer and it may take years for tumor to reach 1 cm3, but in some cases it can spread throughout the body and the bone is the main site of metastasis. At this cancer stage known as metastasis, the principal treatment involves antiandrogen therapy, leading to prostate cells stop proliferating, because they grow in response to presence of androgens such as testosterone and dihydrotestosterone. However, in some cases, the cells can proliferate even in the absence of androgens and this fact occurs due to many factors and they are generally associated with mutations in the androgen receptor and/or alterations in androgen metabolism. In this stage, the treatments available are less effective and usually fail. However, studies suggest that γ-oryzanol, a phytosterol extracted of rice bran oil; and extracts widely used in folk medicine, as Thuya occidentalis hidroalcolic extract, could act inhibiting the development and progression of prostate cancer. In this study, using molecular biology and biochemical approaches we showed that γ- oryzanol treatment was able to decrease cell viability and biomass in culture, and this fact was linked to increased cell death by apoptosis and/or necrosis in androgen responsive (LNCaP) and unresponsive (DU145 and PC3) prostate cancer cell lines, besides increasing pERK1/2 in LNCaP and DU145 cells. γ- oryzanol was also able to cause cell cycle arrest at G2/M phase in LNCaP and PC3 cells and at G0/G1 phase in DU145 cells. These effects were also accompanied by a reduction in caveolin-1 gene and protein expression - an important molecule related to high aggressiveness in prostate cancer and also in the progression of the disease to androgen resistant phenotype - in androgen unresponsive cells, and also PCGEM1 gene - a prostate specific gene regulated by androgens - in LNCaP and DU145 cells. γ-oryzanol also showed ability to regulate several miRNAs - small non-coding RNA molecules - involved in the control of many functions associated with the development, progression and invasion of prostate cancer, such as miR16-1, miR19b-2, miR24b-1, miR24b-2, miR99a, miR133a-5p, miR182-5p, miR198 and miR222. Thuya occidentalis hidroalcolic extract also reduce cell viability and biomass in androgen responsive (LNCaP) and unresponsive (DU145 and PC3) cells, in addition to inducing cell cycle arrest at G0/G1 phase in DU145 cells and to increase apoptosis and/or necrosis cell death in all cell lines. The same way that γ-oryzanol, this extract reduced the caveolin-1 expression in androgen unresponsive prostate cancer cells. Prior studies showed that the monoterpene α-thujone is the main active compound in the T. occidentalis extract. By gas chromatography coupled to mass detector it was showed the existence of 0.0016 μg of α-thujone in extract dose used in this study. However, the treatment with 0.0016 μg of α-thujone was effective only on LNCaP cell line, having no effect on the other studied lines, supporting the hypothesis of difference in sensitivity between responsive and unresponsive cell lines and showing the contribution of other components in the effects caused by the extract, observed it this study. In conclusion, these results demonstrate that both γ-oryzanol as T. occidentalis extract may become promising therapeutic agents in treatment of prostate cancer, not only inhibit cell growth but also and manly by the possibility of inducing the recovery of androgen sensitivity, increasing the treatment chances of treatment this disease.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Objetivo El antígeno prostático específico es utilizado en el diagnóstico de patologías prostáticas. No existe un estudio en Perú que proponga un punto de corte de PSA index para discriminar entre cáncer de próstata e hiperplasia prostática benigna para la indicación de biopsia prostática. Actualmente, se emplean diferentes puntos de corte basados en estudios internacionales. Material y métodos Se realizó un estudio de validación diagnóstica de PSA index para discriminar entre ambas entidades en pacientes con un PSA total entre 4,0 ng/ml y 9,9 ng/ml. Fueron incluidos 356 pacientes con diagnóstico de hiperplasia prostática benigna o cáncer de próstata mediante biopsia prostática. Se evaluó la sensibilidad, especificidad, los valores predictivos y los cocientes de probabilidad de los valores de PSA index de 15 hasta 25%. Se graficó la curva ROC. Resultados Un PSA index de 17% posee mejores valores de sensibilidad (87,8%), especificidad (62,2%) y valores predictivos (valor predictivo positivo de 62,4% y valor predictivo negativo de 87,4%) respecto a otros para disminuir el número de biopsias negativas. El cociente de probabilidad positivo fue 2,3 y el cociente de probabilidad negativo fue 0,1. El área bajo la curva fue 0,75 [IC 95%, 0,71 a 0,79]. Conclusión Se sugiere un PSA index de 17% como punto de corte para discriminar entre hiperplasia prostática benigna y cáncer de próstata en pacientes que acuden a consulta ambulatoria con un PSA total entre 4,0 ng/ml y 9,9 ng/ml. Se recomienda este valor si se desea reducir el número de biopsias prostáticas negativas. / Revisión por pares

Le sélénium est reconnu comme un micronutriment important pour l'homme et les animaux. Plusieurs études ont montré qu'une supplementation en sélénium dans le régime alimentaire pourrait être bénéfique contre les cancers du foie, du colon, du pancréas et de la prostate. Le mécanisme anti-carcinogène du sélénium se produit au niveau systémique, cellulaire et nucléaire. Ces processus peuvent également impliquer le système immunitaire et ne doivent pas être interprétés par un seul mécanisme. Jusqu'à présent son mécanisme d'action est encore inconnu. L'objectif de cette étude était d'étudier l'effet des composés du sélénium, à faibles concentrations, sur la capacité de réparation de l'ADN dans les cellules du cancer de la prostate LNCaP (p53 compétentes). Ce travail est divisé en trois parties. La première partie du travail a été consacrée à étudier l'effet des deux composés du sélénium (SS et SM) sur les propriétés cytotoxiques et génotoxiques de différents stress oxydatifs et non oxydatifs. Les résultats ont montré qu'un prétraitement avec une faible dose en Se stimulait la synthèse des sélénoprotéines, et protègait contre la toxicité et les dommages oxydatifs à l'ADN induites par les UVA ou H2O2, mais pas par MMS ou UVC. La deuxième partie a été consacrée à l'influence de la supplementation en sélénium sur la capacité de réparation de l'ADN. Notre travail a clairement montré l'augmentation de l'efficacité d'excision de certaines glycosylases que n'est pas nécessairement corrélée à une augmentation de l'expression génique et /ou protéiques. Enfin, la troisième partie de notre travail a été dédiée à l'optimisation de la technique Host Cell Reactivation (HCR) qui nous a permis d'étudier la capacité de réparation de l'ADN in cellulo, afin de cibler les partenaires impliqués dans la voie de signalisation affectées par la supplémentation en sélénium. En conclusion, nous pourront penser que le mécanisme d'action du sélénium est représenté par un délicat équilibre entre l'activation et la répression de l'activité de certaines protéines qui induit des changements conformationnels plus ou moins directement impliqués dans la réparation de l'ADN et la progression de la croissance cellulaire. / Selenium was recognized as an important micronutrient for both humans and animals. Several studies showed that increased selenium in the diet might be beneficial against liver, colon, pancreas and prostate cancer. The anticarcinogenic actions of Se occur at the systemic, cellular and nuclear level. These actions may also involve the immune system and thus cannot be interpreted by a single mechanism. Until now its mechanisms of action are not well understood. The objective of this study was to investigate the effect of selenocompounds at low doses on DNA repair capacity in the p53-proficient LNCaP prostate cancer cells. This work is divided into three parts. The first part of the work was devoted to study the effect of two selenocompounds (SS and SM) on the cytotoxic and genotoxic properties of various oxidative and non oxidative stresses. The results showed that low doses of Se pre-treatment stimulates selenoprotein synthesis, protects against toxicity and oxidative DNA damage induced by UVA or H2O2 but not by MMS or UVC. The second part of our investigation was devoted to the influence of selenium supplementation on DNA repair capacity. Our work clearly showed an increase in excision efficiency of the glycosylases activity that was not necessarily correlated with an increase of gene expression and/or protein levels. Finally, the third part of our work was devoted to the optimization of Host Cell Reactivation assay (HCR) to study the DNA repair capacity in cellulo, in order to target the partners involved in the signalling pathway affected by selenium supplementation. In conclusion, we could image that the mechanism of action of selenium is represented by a delicate balance between activation and repression of protein activity that induces conformational changes of several proteins more or less directly involved in DNA repair and progression of cell growth.

Breast and prostate cancers are the most commonly diagnosed forms of cancer in women and men in the United States. The federal government has played an active role in dedicating resources toward breast and prostate cancers since the early 1990s, when policy actors successfully lobbied Congress to adopt policies that increased awareness and spending. Using theories of social construction, I argue that the key to their success was the ability of these policy actors to socially construct the illnesses of breast and prostate cancers into politically attractive public issues that appealed to federal policymakers. Through the use of embedded collective case study and content analysis of newspaper coverage and congressional data, this dissertation demonstrates how the social constructions of these illnesses impacted the way that breast and prostate cancers were treated as they moved through the policy process. The way in which social construction influenced the types of policies that were adopted to deal with these illnesses is also examined. Because social construction is a multidimensional and dynamic process, several different elements of this process were examined in this dissertation: the ways that policy actors attracted attention to these illnesses, how gender influenced advocacy efforts, the symbolic aspects of these illnesses, and the way the illnesses were defined on systemic and institutional agendas. Since this dissertation examines two different policy issues, the similarities and differences in breast and prostate cancer policymaking were analyzed. I found that discussing breast and prostate cancers in relation to their social constructions provides support for the importance of symbolism and non-rational policy-making processes. / by Jocilyn Martinez. / Thesis (Ph.D.)--Florida Atlantic University, 2010. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2010. Mode of access: World Wide Web.

Le cancer de la prostate est la pathologie tumorale la plus fréquente aux Antilles. Notre étude a pour but d’étudier certains facteurs de risque de survenue et de récidive. Pour mener à bien cette étude, nous avons utilisé les patients inclus dans l’étude cas-témoins Karuprostate, et une cohorte de patients après prostatectomie radicale.Les principaux résultats et conclusions de ma thèse portent sur :a) L’étude des facteurs génétiques en lien avec le métabolisme des xénobiotiques dans le risque de survenue du cancer de la prostate en Guadeloupe. Le nombre exact de copies (CNV) des gènes codant pour les Glutathion S transférases GSTM1 et GSTT1 ont été déterminés chez 629 cas incidents de cancer de la prostate et 622 témoins. Les hommes présentant 2, 3 ou plus de copies de GSTT1 présentent un risque significativement augmenté de cancer de la prostate. De même les hommes avec 3, 4, 5 ou plus de copies combinant GSTM1 et GSTT1 présentent un risqué augmenté de survenue de la maladie.b) L’étude des facteurs génétiques en lien avec le métabolisme des œstrogènes dans le risque de survenue du cancer de la prostate en Guadeloupe. Cinq polymorphismes (3 SNP concernant CYP17, CYP1B1 et COMT, ainsi que de polymorphismes de taille concernant CYP19 et UGT1A1) ont été étudiés et comparés chez 498 cas incidents et 565 témoins. Les sujets présentant le génotype AA de COMT présentent un risque significativement diminué de survenue du cancer la prostate. Aucune association significative n’a été retrouvée avec les autres polymorphismes étudiés. Une étude portant sur 150 cas incidents de cancer de la prostate et 150 témoins issus d’une population du Congo-Zaïre a fait l’objet de ces mêmes génotypages avec les mêmes résultats.c) L’influence des expositions environnementales à des polluants persistants présentant des propriétés hormonales sur la récidive biologique de cancer de la prostate après prostatectomie radicale. Les concentrations plasmatiques en chlordécone, DDE (principal métabolite du DDT) et en PCBs ont été mesurés chez 340 sujets porteurs d’un cancer de la prostate ayant subi une prostatectomie radicale. L’exposition (préopératoire) au chlordécone a été retrouvée associé à une augmentation significative du risque de récidive biologique. A l’inverse, les concentrations croissantes en DDE ont été retrouvées associées à une diminution significative du risque de récidive biologique. Aucune association n’a été retrouvée entre l’exposition au PCB153 et la récidive de la maladie.d) Les facteurs de risque de récidive de cancer de la prostate clinique et histologique ont été étudiés sur 964 patients qui ont bénéficié d’une prostatectomie radicale avec un suivi média de 4,8 ans. Le diabète, le PSA, le stade clinique avancé, le score de Gleason élevé, un pourcentage de biopsie de prostate élevé, le stade pathologique avancé, la présence de marge positive sont des facteurs prédictifs de récidive biologique après prostatectomie radicale. Nos résultats montrent que la survenue et la récidive du cancer de la prostate sont sous l’influence des facteurs génétiques et environnementaux. Le contexte génétique et environnemental spécifique à la Guadeloupe expliquerait en partie la forte incidence du cancer de la prostate.Par ailleurs, d’autres travaux intégreront d’autres gènes dans le futur. Le projet ambitieux à venir est la création d’une cohorte prospective de tous les patients atteints d’un cancer de la prostate tout stade confondu. / Prostate cancer is the most common tumor pathology in West Indies. Our study aims to study risk factors of occurrence and recurrence.To carry out this study, we used the patients included in the case-control study called Karuprostate and a cohort of patients after radical prostatectomy.The main results and conclusions of my work are:a) The study of genetic factors related to the metabolism of xenobiotics and the risk of prostate cancer occurrence in Guadeloupe. The exact number (CNV) gene encoding the glutathione S transferases GSTT1 and GSTM1 were determined in 629 incident cases of prostate cancer and 622 controls. Men having 2, 3 or more copies of GSTT1 have a significantly increased risk of prostate cancer. Similarly men with 3, 4, 5 or more copies of GSTM1 and GSTT1 combined have an increased risk of disease occurrence.b) The study of genetic factors related to estrogen metabolism and the risk of prostate cancer occurrence in Guadeloupe. Five polymorphisms (SNP 3 on CYP17, CYP1B1 and COMT as well as size and UGT1A1 polymorphisms on CYP19) were studied and compared in 498 incident cases and 565 controls. Individuals with the AA genotype COMT have a significantly decreased risk of prostate cancer occurrence. No significant association was found with other studied polymorphisms. A study of 150 incident cases of prostate cancer and 150 controls from a population of Congo-Zaire was the subject of these same genotyping, with the same results.c) The influence of environmental exposure to persistent pollutants with hormonal properties of biochemical recurrence of prostate cancer after radical prostatectomy. The plasma concentrations of chlordecone, DDE (the main metabolite of DDT) and PCBs were measured in 340 subjects with prostate cancer who underwent radical prostatectomy. The exhibition (preoperative) to chlordecone was found associated with a significant increased risk of biochemical recurrence. Conversely, the increasing concentrations of DDE were found associated with a significantly decreased risk of biochemical recurrence. No association was found between exposure to PCB153 and recurrence of the disease.d) The clinical and histological risk factors of recurrence of prostate cancer were studied in 964 patients who underwent radical prostatectomy with a médian follow-up of 4.8 years. Diabetes, PSA, advanced clinical stage, high Gleason score, a high percentage of prostate biopsy, advanced pathological stage, the presence of positive margins are predictors of biochemical recurrence after radical prostatectomy.Our results show that the occurrence and recurrence of prostate cancer are Under influence of genetic and environmental factors. The specific genetic and environmental context in Guadeloupe may partly explain the high incidence of prostate cancer.In addition, further work will incorporate other genes in the future. The next ambitious project is the creation of a prospective cohort of all patients with all prostate cancer stages.

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.