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‣ Pretreatment tumor volume estimation based on total serum psa in patients with localized prostate cancer

KATO, Raphael Barroso; SROUGI, Victor; SALVADORI, Fernanda Aburesi; AYRES, Pedro Paulo Marino Rodrigues; LEITE, Katia Moreira; Srougi, Miguel
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica
Português
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OBJECTIVES: To establish a formula that estimates tumor volume in localized prostate cancer based on serum prostate specific antigen levels. One of the main prognostic variables in localized prostate cancer is tumor volume, which can be precisely defined only after prostate extirpation. The present study defines a simple method that allows for estimation of tumor volume before treatment, which can help to establish a better therapeutic strategy for each patient. METHODS: From 1997 to 2002, 735 patients with prostate cancer of stagesT1c-T2c without any previous treatment were submitted to radical prostatectomy. Surgical specimens were evaluated by the same pathologist and the total tumor volume (in cc) and the relative tumor volume (as the percent of the total prostate volume) were determined using the grid morphometric method. Pretreatment serum prostate specific antigen was correlated with tumor volume in each patient using a linear regression model. RESULTS: There were positive correlations between the serum levels of prostate specific antigen and the total tumor volume in cc (p<0.001) and the relative tumor volume as a percentage (p<0.001). For each ng/ml unit increment of serum prostate specific antigen, there was a 0.302 cc increase in total tumor volume and a 0.7% increase in relative tumor volume. Total and percent tumor volume could be calculated...

‣ Chronic Ethanol Consumption Alters All-Trans-Retinoic Acid Concentration and Expression of Their Receptors on the Prostate: A Possible Link Between Alcoholism and Prostate Damage

Fontanelli, Beatriz A.F.; Chuffa, Luiz G.A.; Teixeira, Giovana R.; Amorim, João P.A.; Mendes, Leonardo O.; Pinheiro, Patricia F.F.; Kurokawa, Cilmery S.; Pereira, Sérgio; Fávaro, Wagner J.; Martins, Otávio A.; Mello Júnior, Wílson de; Martinez, Marc
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 49-56
Português
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Background: Ethanol (EtOH) alters the all-trans-retinoic acid (ATRA) levels in some tissues. Retinol and ATRA are essential for cell proliferation, differentiation, and maintenance of prostate homeostasis. It has been suggested that disturbances in retinol/ATRA concentration as well as in the expression of retinoic acid receptors (RARs) contribute to benign prostate hyperplasia and prostate cancer. This study aimed to evaluate whether EtOH consumption is able to alter retinol and ATRA levels in the plasma and prostate tissue as well as the expression of RARs, cell proliferation, and apoptosis index. Methods: All animals were divided into 4 groups (n = 10/group). UChA: rats fed 10% (v/v) EtOH ad libitum; UChACo: EtOH-naïve rats without access to EtOH; UChB: rats fed 10% (v/v) EtOH ad libitum; UChBCo: EtOH-naïve rats without access to EtOH. Animals were euthanized by decapitation after 60 days of EtOH consumption for high-performance liquid chromatography and light microscopy analysis. Results: EtOH reduced plasma retinol concentration in both UChA and UChB groups, while the retinol concentration was not significantly different in prostate tissue. Conversely, plasma and prostate ATRA levels increased in UChB group compared with controls...

‣ Retinol, ácido retinóico e seus receptores e o índice de proliferação celular e de apoptose no lobo dorsolateral da próstata de ratos adultos UCh (bebedores voluntários de etanol a 10%); Retinol, retinoic acid and its receptors and the rate of cell proliferation/apoptosis in the dorsolateral prostate lobe of adult UCh rats (10% (v/v) ethanol voluntary drinkers)

Beatriz Aparecida Fioruci
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 25/03/2011 Português
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A exposição ao etanol altera a concentração do retinol e do all-trans-ácido retinóico (atAR) em vários tecidos. Os retinóides, retinol e atAR, são importantes para a diferenciação e manutenção das células epiteliais da próstata. O atAR se liga aos receptores de ácido retinóico (RARα, β e γ) e a interação receptor/ligante com a sequência responsiva ao retinóide no DNA, levam à transcrição de genes alvos. Assim, o atAR exerce efeitos no crescimento celular, diferenciação e apoptose, sendo essencial no desenvolvimento e diferenciação de órgãos e tecidos. Nosso objetivo foi analisar o retinol, o ácido retinóico e seus receptores, bem como, o índice de proliferação celular e de apoptose no lobo dorsolateral da próstata de ratos adultos UCh. Os animais foram divididos em quatro grupos experimentais (n=10/grupo): UChA (ingestão voluntária de etanol a 10% (v/v); UChACo (controle - ausência de etanol); UChB (ingestão voluntária de etanol a 10% (v/v) e UChBCo (controle - ausência de etanol). Após 150 dias de experimentação, os animais foram eutanasiados por decapitação e o sangue do tronco e os lobos dorsolaterais das próstatas foram coletados e processados: (1) para análises da concentração do retinol e do atAR no plasma e na próstata por meio de HPLC; (2) e análises de microscopia de luz para a proliferação celular (Ki-67)...

‣ Efeitos da exposição à baixa dose de etinilestradiol durante as fases pré-natal e puberal sobre a próstata masculina e feminina de gerbilos senis = : Effects of exposure to low dose of ethinylestradiol during the prenatal and puberal phases on male and female prostate of senile gerbils; Effects of exposure to low dose of ethinylestradiol during the prenatal and puberal phases on male and female prostate of senile gerbils

Ana Paula da Silva Perez
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 24/02/2014 Português
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Os disruptores endócrinos (DE) são agentes exógenos que interferem no funcionamento do sistema endócrino. O 17α-etinilestradiol (EE), um importante componente dos contraceptivos orais é um exemplo de DE. Alguns estudos com roedores machos e fêmeas relataram que a exposição aos DE durante o período pré-natal foi capaz de eliciar proliferações patológicas no sistema reprodutor, incluindo a próstata do animal adulto. Entretanto, pouco se sabe sobre a real ação do estrógeno nas próstatas de machos e fêmeas, principalmente quando se leva em consideração o comportamento de ambas às próstatas durante o desequilíbrio dos níveis de hormônios esteroides que ocorre na puberdade e durante o envelhecimento dessas glândulas. Assim o presente estudo, teve como objetivos avaliar por análises morfológicas, sorológicas e imunohistoquímica quais foram os efeitos da exposição à baixa dose de EE durante os períodos pré-natal e puberal sobre a próstata ventral masculina e na próstata feminina de gerbilo senil. Deste modo, nós dividimos os grupos experimentais de acordo com o período de exposição ao EE (15µg/kg/dia). EE/PRÉ durante o período pré-natal, EE/PUB durante a puberdade e o EE/PRÉ-PUB durante o período pré-natal e puberdade. A exposição à estrógenos sintéticos durante o desenvolvimento afeta o eixo hipotálamo-pituitária gonadal...

‣ Efeitos do consumo crônico de etanol sobre a atividade de MMP-2/MMP-9 e sobre o metabolismo do ácido retinóico nos lobos dorsais e laterais da próstata de ratos adultos= : Effects of chronic ethanol consumption on the activity of MMP-2/MMP-9 and on retinoic acid metabolism in the dorsal and lateral prostate lobes of adult rats; Effects of chronic ethanol consumption on the activity of MMP-2/MMP-9 and on retinoic acid metabolism in the dorsal and lateral prostate lobes of adult rats

Beatriz Aparecida Fioruci Fontanelli
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 30/10/2014 Português
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Pesquisadores têm mostrado que o consumo crônico de etanol altera a concentração do ácido retinóico, metabólito ativo da vitamina A, em muitos órgãos, incluindo a próstata. O ácido retinóico é essencial para o desenvolvimento normal da próstata e para a manutenção de sua homeostase. Alterações na concentração e no metabolismo do ácido retinóico estão relacionadas com o desenvolvimento de lesão na próstata. Adicionalmente, a atividade de metaloproteinases da matriz extracelular (MMPs), também está relacionada com o desenvolvimento de alterações na próstata. Assim, o presente trabalho teve por objetivo descrever os efeitos dos consumos, baixo e alto, de etanol sobre as proteínas envolvidas na síntese e no catabolismo do ácido retinóico (artigo I), bem como, sobre a atividade enzimática das MMPs (artigo II) nos lobos dorsais e laterais da próstata.Vinte ratos adultos (~ 90 dias de idade) de cada variedade, UChA e UChB, foram divididos nos grupos (n=10/grupo): UChA (consumo baixo de etanol, 0,2-2 g/kg/dia), UChAC (ratos que não consumiram etanol); UChB (consumo alto de etanol, > 2g/kg/dia), UChBC (ratos que não consumiram etanol).Após o período experimental (~ 150 dias de idade), os ratos foram eutanasiados por decapitação e os lobos dorsais e laterais das próstatas foram coletados e dissecados: (1) para avaliar os níveis e a localização das proteínas ALDH1A1...

‣ Monocarboxylate transporter 2 (MCT2) as putative biomarker in prostate cancer

Pértega-Gomes, Nelma; Vízcaíno, Ramón; Gouveia, Carlos; Jerónimo, Carmen; Henrique, Rui M.; Lopes, Carlos; Baltazar, Fátima
Fonte: Wiley-Blackwell Publicador: Wiley-Blackwell
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
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INTRODUCTION: Monocarboxylate transporter 2 (MCT2) is a transmembrane protein involved in the transport of monocarboxylates such as pyruvate and lactate. In a previous study we described overexpression of MCT2 in prostate carcinoma raising the hypothesis of using MCT2 as a possible biomarker in prostate cancer. With the present study we aimed to compare the pattern of expression of MCT2 and alpha-methylacyl-CoA racemase (AMACR), in prostate carcinoma, PIN lesions, non-neoplastic prostate tissue, and normal prostate and compare their sensitivity and specificity. Also, we wanted to evaluate the value of using MCT2 in combination with AMACR and the negative markers 34βE12 or p63 to detect prostate cancer. METHODS: A total of 349 cases, including prostate carcinoma, non-neoplastic prostate tissue and PIN lesions, from radical prostatectomies were examined by immunohistochemistry for AMACR, MCT2, p63, and 34βE12, using tissue microarrays (TMAs). Normal prostate from radical cystoprostatectomy was also studied. RESULTS: Our study revealed that MCT2, similarly to AMACR, was consistently expressed in prostate cancer regardless of the Gleason score. In combination with AMACR and p63 or 34βE12, MCT2 helped to improve the diagnosis of prostate carcinoma. Also...

‣ Correlation of hepatitis C and prostate cancer, inverse correlation of basal cell hyperplasia or prostatitis and epidemic syphilis of unknown duration

Krystyna,Annika; Safi,Tarang; Briggs,William M.; Schwalb,Murray D.
Fonte: Sociedade Brasileira de Urologia Publicador: Sociedade Brasileira de Urologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2011 Português
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PURPOSE: The accuracy of prostate specific antigen (PSA) to detect prostate cancer has not yet been determined. Autopsy evidence suggests one-third of men have evidence of prostate cancer. Correlation between prostate cancer and sexually transmitted infection is indeterminate. MATERIALS AND METHODS: A retrospective database was created of all men who underwent transrectal ultrasound guided prostate biopsy over 3 years. Men were 49% African or African Caribbean, and 51% Central or South American. Information about prostate specific antigen, cholesterol, hepatitis A, B and C, human immunodeficiency virus, syphilis, tuberculin skin testing and histology were collected. RESULTS: Hepatitis C antibody detection correlated with prostate cancer OR 11.2 (95% CI 3.0 to 72.4). The odds of prostate cancer increased annually (p = 0.0003). However, no correlation was found between prostate cancer and the following: PSA, biopsy date, repeat biopsy, more than 12 cores at biopsy, total cholesterol, high density lipoprotein, triglycerides, low density lipoprotein, risk measure reported with free and total PSA, hepatitis B surface antibody, high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. Histologic prostatitis and basal cell hyperplasia were inversely correlated with prostate cancer. Syphilis of unknown duration occurred in 17% of men with indeterminate correlation to prostate cancer. CONCLUSION: In inner city men of African and African-Caribbean...

‣ Genetic Polymorphisms of the Glycine N-Methyltransferase and Prostate Cancer Risk in the Health Professionals Follow-Up Study

Chen, Marcelo; Huang, Yi-Ling; Huang, Yu-Chuen; Shui, Irene M.; Giovannucci, Edward; Chen, Yen-Ching; Chen, Yi-Ming Arthur
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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Purpose Glycine N-methyltransferase (GNMT) affects genetic stability by regulating the ratio of S-adenosylmethionine to S-adenosylhomocysteine, by binding to folate, and by interacting with environmental carcinogens. In Taiwanese men, GNMT was found to be a tumor susceptibility gene for prostate cancer. However, the association of GNMT with prostate cancer risk in other ethnicities has not been studied. It was recently reported that sarcosine, which is regulated by GNMT, increased markedly in metastatic prostate cancer. We hereby explored the association of GNMT polymorphisms with prostate cancer risk in individuals of European descent from the Health Professionals Follow-up Study (HPFS). Methods: A total of 661 incident prostate cancer cases and 656 controls were identified from HPFS. The GNMT short tandem repeat polymorphism 1 (STRP1), 4-bp insertion/deletion polymorphisms (INS/DEL) and the single nucleotide polymorphism rs10948059 were genotyped to test for their association with prostate cancer risk. Results: The rs10948059 T/T genotype was associated with a 1.62-fold increase in prostate cancer risk (95% confidence interval (CI): 1.18, 2.22) when compared with the C/C genotype. The STRP1 ≥16GAs/≥16GAs genotype was associated with decreased risk of prostate cancer when compared with the <16GAs/<16GAs genotype (odds ratio (OR) = 0.68; 95% CI: 0.46...

‣ Immuno-oncology of human prostate cancer : phenotypical characterization and study of the tumor-derived, androgen-regulated immunosuppressive microenvironment

Gannon, Philippe
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
Português
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Le cancer de la prostate est le cancer le plus fréquemment diagnostiqué chez les hommes canadiens et la troisième cause de décès relié au cancer. Lorsque diagnostiqué à un stade précoce de la maladie, le cancer de la prostate est traité de manière curative par chirurgie et radiothérapie. Par contre, les thérapies actuelles ne peuvent éradiquer la maladie lorsqu’elle progresse à des stades avancés. Ces thérapies, comme la chimiothérapie et l’hormonothérapie, demeurent donc palliatives. Il est primordial d’optimiser de nouvelles thérapies visant l’élimination des cellules cancéreuses chez les patients atteints des stades avancés de la maladie. Une de ces nouvelles options thérapeutiques est l’immunothérapie. L’immunothérapie du cancer a fait des progrès considérables durant les dernières années. Cependant, les avancements encourageants obtenus lors d’essais précliniques ne se sont pas encore traduits en des résultats cliniques significatifs. En ce qui concerne le cancer de la prostate, les résultats négligeables suivants des interventions immunothérapeutiques peuvent être causés par le fait que la plupart des études sur le microenvironnement immunologique furent effectuées chez des modèles animaux. De plus la majorité des études sur l’immunologie tumorale humaine furent effectuées chez des patients atteints d’autres cancers...

‣ Transforming growth factor-β-mediated signaling in T lymphocytes impacts on prostate-specific immunity and early prostate tumor progression; Transforming growth factor-beta-mediated signaling in T lymphocytes impacts on prostate-specific immunity and early prostate tumor progression

Diener, K.; Woods, A.; Manavis, J.; Brown, M.; Hayball, J.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2009 Português
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T cells are in general tolerant of prostate-specific tumor antigens. That prostate tumor tissue makes transforming growth factor-beta (TGFbeta) is thought to play a role in the induction of T-cell tolerance within the host and to contribute to tumor progression itself. Here we sought to investigate the influence of TGFbeta signaling on prostate antigen-specific T-cell responses as well as prostate tumorogenesis in an autochthonous murine model of the disease. The response of naive and activated ovalbumin (OVA) antigen-specific T cells, which had been rendered incapable of responding to TGFbeta through T-cell-specific transgenic expression of a dominant-negative variant of the TGFbeta receptor II (dnTGFRII), was analyzed after adoptive transfer into prostate OVA-expressing transgenic (POET) mice. The role of TGFbeta signaling in endogenous T cells in mice, which spontaneously form tumors, was also assessed by monitoring prostate tumor formation and progression in F1 progeny of productive matings between transgenic adenocarcinoma of the mouse prostate (TRAMP) and dnTGFRII mice. TGFbeta-resistant CD8(+) T cells proliferated more and produced IFNgamma more readily after OVA stimulation in vitro. OVA-specific T cells did not damage the prostate gland of POET mice irrespective of TGFbeta responsiveness. However...

‣ The role of epigenetic modifications in prostate tumourigenesis.

Chiam, Karen HuiQin
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2010 Português
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Prostate cancer is the second-leading cause of cancer death in Australian men. Current therapies for advanced prostate cancer are not curative and most patients eventually develop castrate resistant prostate cancer. Epigenetic modifications are heritable and reversible biochemical changes of the chromatin that regulate gene expression and are important in prostate tumourigenesis. There is also evidence that excess foetal nutrition is associated with increased risk of developing prostate cancer. Hence, the aims of this thesis were to determine the involvement of epigenetic modifications in: the early origin of prostate cancer, prostate cancer progression, as prognostic and therapeutic targets in prostate cancer. The first aim of this thesis was to use a rodent model to determine if a maternal high fat diet (MHFD) is associated with increased risk of prostate cancer in offspring. Offspring exposed to a MHFD had increased incidence of prostate abnormalities compared to offspring exposed to a maternal control diet. GSTP1 is hypermethylated and silenced in human prostate cancer and was decreased in these offspring prostates. The MHFD altered the male offspring prostates microRNA expression and provided insights of possible underlying mechanisms that support a link between MHFD and risk of prostate cancer in adult offspring. The second aim was to investigate if specific histone modifications H3K18Ac and H3K4diMe were prognostic markers for prostate cancer. High levels of H3K18Ac and H3K4diMe were associated with increased risk of prostate cancer relapse respectively. To further investigate the underlying mechanisms...

‣ Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study

Mitra, A.; Suthers, G.
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
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Study Type – Diagnostic (validating cohort) Level of Evidence 1b What’s known on the subject? and What does the study add? Scientists have found a number of genetic factors that increase prostate cancer risk, including heritable mutations in the genes BRCA1 and BRCA2. These mutations are not common but can have major impact, as a BRCA2 mutation increases risk by up to seven-fold while a BRCA1 mutation is thought to double risk in men under 65. The IMPACT study aims to determine whether targeted screening in men with a known BRCA1 or BRCA2 mutation would lead to earlier diagnosis of prostate cancers. This data from the IMPACT study adds to the increasing evidence that BRCA mutation carriers develop more aggressive disease. Although these are early results, it appears that PSA screening is more accurate at predicting potentially aggressive prostate cancer among men at higher risk of the disease due to a genetic predisposition than general population screening. This study provides support for continued screening in men with genetic mutations. OBJECTIVE: To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls)...

‣ Characterisation of the co-chaperone small glutamine-rich tetratricopeptide repeat containing protein alpha as a regulator of androgen receptor activity in prostate cancer cells.

Trotta, Andrew Paul
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2011 Português
Relevância na Pesquisa
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Prostate cancer remains one of the leading causes of cancer related morbidity and mortality in Australian men. The androgen receptor (AR) is an intracellular transcription factor that mediates the biological actions of circulating androgens to drive the growth and survival of prostate cancer cells. However, current treatment options for non-localised, advanced stage prostate cancer invariably fail, which is a consequence of continued AR signalling during all stages of disease progression. Therefore, understanding the regulatory mechanisms of AR action is essential for the development of more effective therapies. Molecular regulation of the AR can occur during the process of protein maturation. This includes the incorporation of tetratricopeptide repeat (TPR) containing co-chaperones into the heat shock protein 90 (Hsp90) molecular chaperone complex, which collectively acts to generate AR proteins capable of high affinity ligand binding, nuclear translocation and gene regulation. The co-chaperone small glutamine-rich TPR containing protein alpha (SGTA) acts to restrict AR nuclear translocation and thereby regulate AR transcriptional activity. The clinical implications of SGTA are evident by a decline in protein levels with prostate cancer progression. The loss of SGTA may therefore disrupt the regulatory process of AR cytoplasmic retention...

‣ Androgen signalling in the prostate cancer microenvironment.

Leach, Damien Alexander
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2014 Português
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Prostate cancer remains the second leading cause of cancer related death in Australian males, with approximately 28000 Australian men being diagnosed in 2007 and more than 3000 deaths as a result of this disease. The probability of patient survival from prostate cancer is greatly diminished when the disease has spread outside of the confines of the prostate. Disease spread, or the potential for spread, also determines the therapy received by the patient, be it surgical removal, chemotherapy, radiotherapy, or hormonal therapy, or any of these in combination. The advent of serum PSA testing has allowed for both earlier and increased detection of prostate cancer over the past 20 years. Despite this, the mortality rate for prostate cancer has remained relatively constant. Moreover, it is thought that increased detection may lead to over diagnosis and over treatment of indolent disease in up to 50% of cases, burdening patients who would not actually die from prostate cancer. Central to this issue is that there is no accurate means of predicting, at the time of diagnosis, the likelihood of prostate cancer becoming aggressive and metastasising, and thus identifying the patient population that would benefit most from more aggressive treatment. The prostate is a glandular structure composed of secretory epithelial cells embedded in a stroma containing smooth muscle cells...

‣ Curcumin action in prostate cancer cells and fibroblasts.

Giorgio, Lauren
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2014 Português
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Curcumin is a component of the Indian spice turmeric that has shown anti-cancer activity across a range of models. This includes prostate cancer, the most commonly diagnosed cancer in Australia. While much of the current literature relates to epithelial cells, there is no information regarding curcumin activity or resistance in prostate fibroblasts. With curcumin recently entering clinical trials for prostate cancer and being increasingly used as a dietary supplement, it is critical to gain an understanding of curcumin action and potential resistance in these cells, given their reported contribution to cancer progression. Furthermore, with drug resistance being a major setback to cancer therapy, it is also important to investigate curcumin-based combination strategies to enhance efficacy and avoid the development of resistance. The aims of this thesis were therefore to comparatively investigate mechanisms of curcumin action in prostate cancer cells and fibroblasts, to explore the potential for curcumin resistance to occur in prostate fibroblasts and to examine the ability of curcumin to re-sensitise prostate cancers resistant to drozitumab, a monoclonal antibody against death receptor 5 (DR5). Curcumin inhibited prostate cancer cell and fibroblast viability...

‣ The female prostate and prostate-specific antigen. lmmunohistochemical localization, implications of this prostate marker in women and reasons for using the term "prostate" in the human female

Zaviacic, M.; Ablin, R.J.
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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Prostate-specific antigen (PSA) is currently the most frequently used marker for the identification of normal and pathologically altered prostatic tissue in the male and female. Immunohistochemically PSA is expressed in the highly specialized apically-superficial layer of female and male secretory cells of the prostate gland, as well as in uroepithelial cells at other sites of the urogenital tract of both sexes. Unique active moieties of cells of the female and the male prostate gland and in other parts of the urogenital tract are indicative of secretory and protective function of specialized prostatic and uroepithelial cells with strong immunological properties given by the presence of PSA. In clinical practice, PSA is a valuable marker for the diagnosis and monitoring of diseases of the male and the female prostate, especially carcinoma. In the female, similarly as in the male, the prostate (Skene's gland) is the principal source of PSA. The value of PSA in women increases in the pathological female prostate, e.g., carcinoma. Nevertheless, the total amount of PSA in the female is the sum of normal or pathological female prostate and non-prostatic female tissues production, e.g., of diseased female breast tissue. The expression of an antigen specific for the male prostate...

‣ Evaluating DNA damage response (DDR) activation in human prostate cancer

Delouya, Guila
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
Português
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Introduction: Au Canada, le cancer de la prostate est le cancer le plus fréquemment diagnostiqué chez les hommes et le plus mortel après les cancers du poumon et du côlon. Il y a place à optimiser le traitement du cancer de la prostate de manière à mettre en œuvre une médecine personnalisée qui s’adapte aux caractéristiques de la maladie de chaque patient de façon individuelle. Dans ce mémoire, nous avons évalué la réponse aux dommages de l’ADN (RDA) comme biomarqueur potentiel du cancer de la prostate. Les lésions potentiellement oncogènes de l'ADN déclenche une cascade de signalisation favorisant la réparation de l'ADN et l’activation des points de contrôle du cycle cellulaire pour préserver l’intégrité du génome. La RDA est un mécanisme central de suppression tumorale chez l’homme. La RDA joue un rôle important dans l’arrêt de la prolifération des cellules dont les génomes sont compromis, et donc, prévient la progression du cancer en agissant comme une barrière. Cette réponse cellulaire détermine également comment les cellules normales et cancéreuses réagissent aux agents utilisés pour endommager l'ADN lors du traitement du cancer comme la radiothérapie ou la chimiothérapie, en plus la présence d...

‣ Comparison of quality of life after stereotactic body radiotherapy and surgery for early-stage prostate cancer

Katz, Alan; Ferrer Forés, Maria Montserrat; Suárez Novo, José Francisco
Fonte: Universidade Autônoma de Barcelona Publicador: Universidade Autônoma de Barcelona
Tipo: Artigo de Revista Científica Formato: application/pdf
Publicado em //2012 Português
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Background: As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Methods: Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24, and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. Results: The largest differences in QOL occurred in the first 1–6 months after treatment...

‣ HES5 silencing is an early and recurrent change in prostate tumourigenesis

Massie, Charles E.; Spiteri, Inmaculada; Ross-Adams, Helen; Luxton, Hayley; Kay, Jonathan; Whitaker, Hayley C.; Dunning, Mark J.; Lamb, Alastair D.; Ramos-Montoya, Antonio; Brewer, Daniel S.; Cooper, Colin S.; Eeles, Rosalind; UK Prostate ICGC Group; Warr
Fonte: BioScientifica Publicador: BioScientifica
Tipo: Article; published version
Português
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This is the final version of the article. It was originally published in the Endocrine-Related Cancer, April 1, 2015 22 131-144 doi: 10.1530/ERC-14-0454.; Prostate cancer is the most common cancer in men, resulting in over 10?000?deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation profiling in a series of multi-focal prostate tumours, we identify promoter methylation of the transcription factor HES5 as an early event in prostate tumourigenesis. We confirm that this epigenetic alteration occurs in 86?97% of cases in two independent prostate cancer cohorts (n=49 and n=39 tumour?normal pairs). Treatment of prostate cancer cells with the demethylating agent 5-aza-2?-deoxycytidine increased HES5 expression and downregulated its transcriptional target HES6, consistent with functional silencing of the HES5 gene in prostate cancer. Finally, we identify and test a transcriptional module involving the AR, ERG, HES1 and HES6 and propose a model for the impact of HES5 silencing on tumourigenesis as a starting point for future functional studies.; The authors are grateful to study volunteers for their participation and staff at the Welcome Trust Clinical Research Facility...

‣ Targeting Histone Deacetylases in Advanced Prostate Cancer

Brunner, Abigail Maria
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2015 Português
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The androgen receptor (AR) signaling axis is a well-established therapeutic target in prostate cancer, due to its central role in tumor maintenance and progression. Although patients respond initially to androgen deprivation therapies and AR antagonists, they invariably progress to a castration-resistant state. Consequently, there is an unmet need for agents that target the AR signaling axis in a unique manner.

Histone deacetylase (HDAC) inhibitors repress AR signaling and prostate cancer growth in cellular and xenograft models. However, HDAC inhibitors also induce epithelial to mesenchymal (EMT) and neuroendocrine differentiation, both of which are associated with prostate cancer progression and aggressiveness. Given that 18 different HDAC isoforms have been identified in humans, and non-selective or Class I (HDAC1, 2, 3, and 8) HDAC inhibitors have been used in most of these studies, the relative contribution of individual HDAC isoforms to AR transcriptional activity and prostate cancer pathophysiology remains to be elucidated. The overarching goals of this study were to (1) determine the role of individual Class I HDACs in AR transcriptional activity and prostate cancer growth, (2) identify selective HDAC inhibitors that have reduced adverse profiles to the treatment of prostate cancer...