Abstract Prostate cancer is the most frequently diagnosed cancer in men in industrialized countries. Despite the substantial clinical importance of the disease, the mechanisms underlying the development and progression of prostate cancer are poorly understood. In the present study, fragment analysis of chromosome arm 16q was carried out with the aim of searching for sites of consistent chromosomal deletion, possibly uncovering the location of target genes that become inactivated in prostate carcinogenesis. The highest percentage of loss of heterozygosity (LOH) was found at chromosomal region 16q24.1-q24.2, including the gene for 17β-hydroxysteroid dehydrogenase/17-ketosteroid reductase (17HSD/KSR) type 2, HSD17B2. The data further indicated an association between loss of the most commonly deleted region and clinically aggressive features of the disease. A fragment analysis performed using sequential primary and locally recurrent prostate cancer specimens suggested the location of the genes related to prostate cancer progression to be at 16q24.3 and, further, gave rise to a hypothesis of the potential role of locus HSD17B2 as a prognostic marker for prostate cancer progression. Quantitative real-time polymerase chain reaction (PCR) revealed a decreased HSD17B2 gene copy number in prostate cancer specimens compared to their normal counterparts. A diminished HSD17B2 gene copy number was significantly associated with poor differentiation of the tumor. The progression of prostate cancer during androgen deprivation is a serious clinical problem, the molecular mechanisms of which largely remain to be clarified. The present data of enzyme activity measurements performed using high-performance liquid chromatography (HPLC) provided evidence of a substantial decrease in oxidative and an increase in reductive 17HSD/KSR activity during the transition of prostate cancer LNCaP cells into an androgen-independent state. Further, the changes detected in the activities largely coincided with the changes in the relative expression levels of genes for the potential 17HSD/KSR isoenzymes; 17HSD/KSR types 2, 5, and 7, as evidenced by relative quantitative reverse transcription PCR (RT-PCR). The data on the expression analysis of mRNA for 17HSD/KSR types 5 and 7 in prostate tissue specimens performed using in situ hybridization showed a moderately low but constitutive level for 17HSD/KSR7 mRNA in tissues of cancerous as well as hyperplastic origin. The expression of mRNA for 17HSD/KSR type 5, instead, varied considerably between different specimens, the highest expressions being strongly associated with aggressive and metastatic prostate cancer. Interestingly, furthermore, the intense expression of 17HSD/KSR5 was significantly associated with the androgen deprivation achieved either surgically or medically. Since 17HSD/KSRs critically contribute to the control of the bioavailability of active sex steroid hormones locally in the prostate, the variation in intraprostatic 17HSD/KSR activity might be crucially involved in the regulation of the growth and function of the organ.

Objetivos: La calidad de vida de pacientes en estadios III y IV de cáncer de próstata disminuye significativamente debido a varios factores como: efectos secundarios al tratamiento, pronóstico de la enfermedad, entre otros. Este estudio busca describir qué áreas de la calidad de vida son más afectadas y en qué medida, en pacientes con tratamiento antineoplásico. Material y métodos: El estudio es descriptivo transversal. Se calculó un tamaño muestral de 81 pacientes. Se incluyeron a aquellos entre 50 y 80 años, con diagnóstico histopatológico de cáncer de próstata en estadios clínicos III y IV y que recibieron tratamiento entre 3 meses y 2 años en el INEN. Para evaluar calidad de vida se empleó el UCLA-PCI-SF y el SF-12 v2. Para evaluar riesgo de episodio depresivo mayor se empleó el test de Zung abreviado. Resultados: Se incluyeron 82 pacientes. La edad media fue 68,2, el 51.2% tenía estadio III y el 48.8% estadio IV. El 7,3% recibió radioterapia, 56% terapia hormonal y 36.7% tratamiento combinado. Las áreas más afectadas fueron la función sexual y urinaria con una mediana de puntaje de 2.5 y 43.75, respectivamente. El 57.3% de los pacientes presentó riesgo de desarrollar un episodio depresivo mayor. Conclusión: La calidad de vida está afectada significativamente en pacientes con cáncer de próstata avanzado, siendo la función sexual la más comprometida. Un alto porcentaje tuvo riesgo de depresión mayor. Se recomienda introducir intervenciones de salud mental e intervenciones para abordar la disfunción sexual en este grupo de pacientes.

Prostate cancer is the third most common cancer in men globally, and the most common cancer among men in the United States. Dietary choices may play an important role in developing prostate cancer; in particular, a higher dairy product intake has been associated with an increased risk of developing prostate cancer. The overall positive association between milk consumption and the risk of prostate cancer development and prostate cancer mortality has been well documented in multiple epidemiological studies. However, there is limited literature on the association between types of milk, as classified by fat content (skim, low fat, and whole), and the risk of developing prostate cancer. When further examining current state of the literature on this topic, there is a number of epidemiologic studies assessing the relationship between prostate cancer and milk consumption. On the contrary, very few experimental studies explore this topic. Further experimental research may be necessary to examine the relationship between dairy and dairy products consumption and the increased risk of development of prostate cancer. At this time, there are no formal clinical recommendations regarding dairy products consumption for patients who are at risk of prostate cancer development or who have a history of prostate cancer. In this manuscript, we sought to systematically review the existing literature on the association between milk consumption classified by fat content, and the risk of developing prostate cancer. These findings may be useful for the clinicians who provide recommendations for the patients at risk of developing prostate cancer.

Prostate cancer is the most common newly diagnosed non-skin cancer and the second leading cause of cancer death in men. It is a unique neoplasm because of the large discrepancy between its clinical incidence and the much higher incidence of latent cancer. Predicting the prognosis of prostate cancer, especially the cancers detected incidentally or by screening, remains a clinically important problem. Immunoreactivity for Onco-antigen 519 (OA- 519), a recently described fatty acid synthase (FAS), has been associated with poor prognosis in breast cancers. The authors have previously shown that its detection in prostate cancer correlated with high-grade, large volume, and advanced stage tumors. This study examines the association between OA- 519 immunoreactivity in primary prostate cancer and disease progression. The authors used immunohistochemistry with an affinity-purified anti-OA-519 antibody and examined primary prostate cancers (stages A1 to D1) from 99 men with a mean follow-up of 4 years (range= 2 to 9.3). Survival analysis was used to evaluate differences in progression-free survival. OA-519 immunoreactivity was seen in 56 (57%) of the 99 primary prostate cancers examined. OA-519-positive cancers were more likely to progress than the OA- 519-negative cancers (P < .04). Univariate survival analysis showed that OA- 519 (FAS), histological grade (Gleason score), and clinical stage were significant predictors of disease progression. Multivariate analyses of all cases showed that only histological grade was significant. However, multivariate analysis of the 85 cancers with Gleason scores 2-7 (ie, low to intermediate grade) showed OA-519 (FAS) immunoreactivity to be the only statistically significant predictor of cancer progression (P<.02). Expression of the fatty acid synthase OA-519 by prostate cancers is potentially a clinically useful predictor of disease progression. It appears to be independent of histological grade (Gleason score), at least in cancers with low to intermediate grades. Further studies are needed to evaluate the role of fatty acid synthase in malignancy and the potential therapeutic implications of enzyme blockers.

Purpose: Ultrasonically measured intravesical prostatic protrusion may be a promising noninvasive method of assessing bladder outlet obstruction. Previous investigations of this technique focused on patients with acute urinary retention and symptomatic men identified in urology clinics, which may not reflect the distribution of intravesical prostatic protrusion in community dwelling men. Materials and Methods: In 2006 a total of 322 white men residing in Olmsted County, Minnesota underwent transrectal ultrasound examination which permitted direct measurement of intravesical prostatic protrusion. Cross-sectional associations between lower urinary tract symptoms/benign prostatic enlargement and intravesical prostatic protrusion were measured. Rapid increases in lower urinary tract symptoms/benign prostatic enlargement measures as predictors of severe intravesical prostatic protrusion were also assessed. Results: Overall 10% of these men had an intravesical prostatic protrusion of 10 mm or greater. Greater intravesical prostatic protrusion was weakly correlated with greater prostate volume (rs = 0.28), higher obstructive symptoms (rs = 0.18) and lower peak urinary flow rate (rs = -0.18). Men with the most rapidly growing prostate before intravesical prostatic protrusion measurement were 3 times more likely to have an intravesical prostatic protrusion of 10 mm or greater. Men with an intravesical prostatic protrusion of 10 mm or greater were more likely to use medications for lower urinary tract symptoms/benign prostatic enlargement compared to those with an intravesical prostatic protrusion less than 10 mm (adjusted OR 2.95, 95% CI 1.23-7.06). Conclusions: These population based data provide reference ranges for future studies of intravesical prostatic protrusion as a predictor of adverse urological outcomes. Intravesical prostatic protrusion is significantly correlated with greater prostate volume, higher obstructive symptoms and lower peak urinary flow rate, suggesting that it may have clinical usefulness in predicting the need for treatment.

Apesar de existir novas técnicas e múltiplas alternativas terapêuticas para o câncer de próstata localmente avançado, esta enfermidade se constitui em um grande problema de saúde pública mundial, resultando em índices significativos de morbidade e mortalidade, gerando desta forma um desafio para urologistas e oncologistas. Existem múltiplas e bem sucedidas estratégias de tratamento da doença localizada, tais como: a prostatectomia radical, a radioterapia externa conformacional, a braquiterapia e a crioablação. Em contraste, o tratamento da doença metastática e localmente avançada, freqüentemente necessita da alguma forma de bloqueio hormonal. Não existe consenso em vários aspectos da terapia hormonal para tumores localmente avançados tais como: o tipo de bloqueio androgênico a ser usado, terapia hormonal precoce ou tardia, associação com outras modalidades terapêuticas e o uso de bloqueio intermitente. Foi realizada uma revisão crítica deste tipo de tratamento, bem como as indicações atuais de bloqueio hormonal nos tumores de próstata localmente avançado. Não existem estudos prospectivos e randomizados que comparem as diversas formas de tratamento cirúrgico versus radioterápico do câncer de próstata localmente avançado. A hormonioterapia adjuvante à prostatectomia radical, na doença localmente avançada, parece reduzir a progressão tumoral bioquímica, porém, não há estudo que evidencie melhora na sobrevida livre de metástase ou na sobrevida global. O bloqueio androgênico neoadjuvante à prostatectomia radical aumenta a proporção dos pacientes com doença órgão-confinada e margens cirúrgicas negativas, porém sem efeito nas taxas de falha bioquímica do tratamento. A terapia hormonal adjuvante à radioterapia em pacientes portadores de câncer de próstata localmente avançado oferece vantagens na sobrevida global. A terapia hormonal neoadjuvante à radioterapia, em estudos multicêntricos e randomizados, resulta em melhor controle local do tumor bem como prolonga a sobrevida doença-específica. Não há, porém evidência de melhora na sobrevida global. O tratamento por tempo prolongado com bloqueadores hormonais adjuvante à radioterapia mostrou-se superior em relação à sobrevida global e sobrevida livre de doença quando comparado a um período curto de bloqueio, principalmente em pacientes com tumores indiferenciados (Gleason 8-10). Os análogos LHRH, orquiectomia ou o dietilestilbestrol se mostraram como opções de monoterapia, igualmente eficazes, para os pacientes que iniciam terapia hormonal de primeira linha, no tratamento da doença localmente avançada. Não existe evidência que justifique o bloqueio androgênico máximo como terapia hormonal de primeira linha ao invés de monoterapia. Existem vantagens potenciais na qualidade de vida e nos custos do tratamento quando realizada a ablação intermitente, mas a sua eficácia a longo prazo necessita ser confirmada / Despite new techniques and multiple therapeutic alternatives, locally advanced prostate cancer is a serious public health problem, resulting in significant morbidity and mortality rates, that remains a great challenge for urologists and oncologists. Several therapeutic strategies to treat localized prostate cancer have been successful such as conformational external beam radiation therapy, brachytherapy and cryoablation. In contrast, treatment of metastatic and locally advanced tumors may often involve androgenic suppression. However, there are no consensus on several aspects of hormonal therapy for locally advanced tumors such as the type of antiandrogenic drug to be used, early versus delayed hormonal therapy, association with other therapeutic modalities and the use of intermittent blockade. We set out to critically review important aspects and current indications of hormonal blockade in the locally advanced prostate tumors. There are no prospective and randomized study that compares current forms of surgical treatment versus radiation therapy of locally advanced prostate cancer. After radical prostatectomy, adjuvant hormonal therapy in the locally advanced disease reduces biochemical failure rates, although no benefit has been shown regarding metastatic free survival or overall suvival. Neoadjuvant androgen blockade enhances the proportion of patients with organ-confined disease and negative surgical margins but no benefit is seen regarding biochemical free recurrence. Neoadjuvant hormonal therapy to the radiotherapy improves local tumor control as well as it prolongs the diseasespecific survival, although there are no survival advantage. Adjuvant hormonal therapy offers overall survival advantage in patients with locally advanced prostate cancer treated with radiotherapy Long term adjuvant hormonal blockade offers survival benefit for patients with high Gleason score (8-10). LHRH analogues, bilateral orquiectomy and dietilestilbestrol were shown are equally effective as adjuvant therapy for patients with locally disease advanced. There are evidences that maximum androgenic blockade are not more efficient than monotherapy. Potential quality of life and costs advantages of intermittent ablation could be considered an alternative treatment for this group of patient

Submitted by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-20T15:54:57Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) JORGE HENRIQUETESE COM CORREÇÕES DA BANCA JAN 2017.pdf: 4201838 bytes, checksum: f47ae0fb55a2d648c74ac2facf85217d (MD5) / Approved for entry into archive by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-20T15:55:06Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) JORGE HENRIQUETESE COM CORREÇÕES DA BANCA JAN 2017.pdf: 4201838 bytes, checksum: f47ae0fb55a2d648c74ac2facf85217d (MD5) / Made available in DSpace on 2017-09-20T15:55:06Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) JORGE HENRIQUETESE COM CORREÇÕES DA BANCA JAN 2017.pdf: 4201838 bytes, checksum: f47ae0fb55a2d648c74ac2facf85217d (MD5) Previous issue date: 2016 / Universidade Federal Fluminense. Centro de Ciências Médicas. Instituto Biomédico. Departamento de Morfologia. Anatomia Humana / A uretra masculina humana possui uma macro estrutura uniforme. Apesar disso apresenta evidências clínicas, morfológicas e moleculares ao longo de seus segmentos, que indicam haver diferenças estruturais e patológicas entre os mesmos. A maioria das alterações da uretra prostática (UP), em homens acima dos 50 anos, são consideradas como sendo secundárias à compressão devido ao crescimento de nódulos fibromatosos hiperplásicos do tecido prostático. Os sinais obstrutivos consequentes a Hiperplasia Prostática Benigna (HPB) incluem hesitação para iniciar a micção, redução da força e calibre do jato urinário, bem como, tardiamente, retenção urinária. Para tentar explicar as alterações que ocorreram na estrutura histológica da UP, no processo da HPB, estudamos as variações qualitativas e quantitativas que ocorreram na densidade volumétrica (Vv) do componente fibroso da matriz extracelular (MEC) e do músculo liso da UP de pacientes com HPB submetidos a tratamento cirúrgico. Foram estudadas amostras obtidas da UP de 10 pacientes com HPB sintomática, submetidos à prostatectomia aberta. Os pacientes não tinham história de tratamento prévio, para HPB. A idade dos pacientes selecionados para o presente estudo variou entre 63 a 79 anos. Para fins de comparação, foram usadas amostras controle obtidas durante a necropsia de 10 indivíduos adultos jovens com idades variando de 18 a 25 anos, vítimas de morte violenta sem comprometimento do sistema urogenital e/ou manipulação uretral. Todas as Próstatas do grupo controle apresentavam peso entre 20-25g, sendo consideradas adultas e dentro dos limites da normalidade. As amostras foram fixadas em solução de formol 10% e processadas para inclusão em parafina. Para análise da Vv, foram usadas as técnicas de coloração de tricrômico de Masson e, de Weigert. Também foram submetidas a análise imunohistoquímica. A Vv do componente fibroso da MEC e do músculo liso foi determinada pela análise de 25 campos aleatórios de cada fragmento de UP usando um sistema teste M-42. Os dados quantitativos foram analisados por meio do teste de Kolmogorov-Smirnov e Mann-Whitney. A Vv (%médio±SD) nos grupos controle e HPB foram respectivamente: 20,3±0,3 e 17,12±1,1 para as fibras do sistema elástico (p <0,007); 29,7 ± 1,9 e 25,1 ± 2,4 para colágeno (p <0,03). A Vv do músculo liso apresentou aumento, não significativo, no grupo HPB, 49,9 ± 0,4 e 52,3 ± 2,3. Por outro lado, 21,9±1,5 e 29,1±1,2 para a fibronectina (P < 0. 0001). / The human male urethra has a uniform structure. Despite this, presents morphological, molecular and clinical evidence throughout their segments that indicates pathological and structural differences between them. Most of changes in prostatic urethra (PU) in men over 50 years, are considered to be secondary to compression due to the growth of fibrous hyperplastic prostate tissue nodules. The signs of obstructive Benign Prostatic Hyperplasia (BPH) reflect the decreased distendibility of the prostatic urethra; that includes hesitation to begin urination, reduced force and caliber of the urinary stream, as well as (late) retention. To explain the histological, structural changes that occurred in the prostatic urethra, studies were made to analyse the changes in quality and quantity that occurred in the volumetric density of the fibrous component of the extracellular matrix (ECM) and smooth muscle of the urethra of patients with BPH submitted to surgical treatment. Samples were obtained from the urethra of 10 patients with symptomatic BPH who had undergone open prostatectomy. No patient had a history of previous treatment for BPH. The age ranged from 63-79 years. To compare we used control samples obtained during autopsy of 10 young adults subjects aged 18-25 that died from violent death without involvement of the urogenital system or uretral manipulation. The samples were fixed in formalin 10% and processed for paraffin embedding. For analysis of Vv, were used staining techniques tricomic Masson and Weigert. Were also submitted to immunohistochemical analysis. The Vv fibrous component of MEC and smooth muscle was determined by the analysis of 25 random fields of each fragment of a test system using M-42. Quantitative data were analyzed using the olmogorov-Smirnov and Mann-Whitney test. The Vv (mean ± SD) in the control and BPH groups respectively were: 20.3±0.3 and 17.12±1.1 in the elastic fiber system (p<0.007); and 29.7±1.9 and 25.1±2.4 in the collagen compartment (p<0.03). Smooth muscle cell volume was increased in BPH cases, 49.9±0.4 and 52.3±2.3 (not statistically significant). On other hand was 21.9±1.5 and 29.1±1.2 in the fibronectin (P < 0. 0001).

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 164-179).

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 137-144).

Apesar de existir novas técnicas e múltiplas alternativas terapêuticas para o câncer de próstata localmente avançado, esta enfermidade se constitui em um grande problema de saúde pública mundial, resultando em índices significativos de morbidade e mortalidade, gerando desta forma um desafio para urologistas e oncologistas. Existem múltiplas e bem sucedidas estratégias de tratamento da doença localizada, tais como: a prostatectomia radical, a radioterapia externa conformacional, a braquiterapia e a crioablação. Em contraste, o tratamento da doença metastática e localmente avançada, freqüentemente necessita da alguma forma de bloqueio hormonal. Não existe consenso em vários aspectos da terapia hormonal para tumores localmente avançados tais como: o tipo de bloqueio androgênico a ser usado, terapia hormonal precoce ou tardia, associação com outras modalidades terapêuticas e o uso de bloqueio intermitente. Foi realizada uma revisão crítica deste tipo de tratamento, bem como as indicações atuais de bloqueio hormonal nos tumores de próstata localmente avançado. Não existem estudos prospectivos e randomizados que comparem as diversas formas de tratamento cirúrgico versus radioterápico do câncer de próstata localmente avançado. A hormonioterapia adjuvante à prostatectomia radical, na doença localmente avançada, parece reduzir a progressão tumoral bioquímica, porém, não há estudo que evidencie melhora na sobrevida livre de metástase ou na sobrevida global. O bloqueio androgênico neoadjuvante à prostatectomia radical aumenta a proporção dos pacientes com doença órgão-confinada e margens cirúrgicas negativas, porém sem efeito nas taxas de falha bioquímica do tratamento. A terapia hormonal adjuvante à radioterapia em pacientes portadores de câncer de próstata localmente avançado oferece vantagens na sobrevida global. A terapia hormonal neoadjuvante à radioterapia, em estudos multicêntricos e randomizados, resulta em melhor controle local do tumor bem como prolonga a sobrevida doença-específica. Não há, porém evidência de melhora na sobrevida global. O tratamento por tempo prolongado com bloqueadores hormonais adjuvante à radioterapia mostrou-se superior em relação à sobrevida global e sobrevida livre de doença quando comparado a um período curto de bloqueio, principalmente em pacientes com tumores indiferenciados (Gleason 8-10). Os análogos LHRH, orquiectomia ou o dietilestilbestrol se mostraram como opções de monoterapia, igualmente eficazes, para os pacientes que iniciam terapia hormonal de primeira linha, no tratamento da doença localmente avançada. Não existe evidência que justifique o bloqueio androgênico máximo como terapia hormonal de primeira linha ao invés de monoterapia. Existem vantagens potenciais na qualidade de vida e nos custos do tratamento quando realizada a ablação intermitente, mas a sua eficácia a longo prazo necessita ser confirmada / Despite new techniques and multiple therapeutic alternatives, locally advanced prostate cancer is a serious public health problem, resulting in significant morbidity and mortality rates, that remains a great challenge for urologists and oncologists. Several therapeutic strategies to treat localized prostate cancer have been successful such as conformational external beam radiation therapy, brachytherapy and cryoablation. In contrast, treatment of metastatic and locally advanced tumors may often involve androgenic suppression. However, there are no consensus on several aspects of hormonal therapy for locally advanced tumors such as the type of antiandrogenic drug to be used, early versus delayed hormonal therapy, association with other therapeutic modalities and the use of intermittent blockade. We set out to critically review important aspects and current indications of hormonal blockade in the locally advanced prostate tumors. There are no prospective and randomized study that compares current forms of surgical treatment versus radiation therapy of locally advanced prostate cancer. After radical prostatectomy, adjuvant hormonal therapy in the locally advanced disease reduces biochemical failure rates, although no benefit has been shown regarding metastatic free survival or overall suvival. Neoadjuvant androgen blockade enhances the proportion of patients with organ-confined disease and negative surgical margins but no benefit is seen regarding biochemical free recurrence. Neoadjuvant hormonal therapy to the radiotherapy improves local tumor control as well as it prolongs the diseasespecific survival, although there are no survival advantage. Adjuvant hormonal therapy offers overall survival advantage in patients with locally advanced prostate cancer treated with radiotherapy Long term adjuvant hormonal blockade offers survival benefit for patients with high Gleason score (8-10). LHRH analogues, bilateral orquiectomy and dietilestilbestrol were shown are equally effective as adjuvant therapy for patients with locally disease advanced. There are evidences that maximum androgenic blockade are not more efficient than monotherapy. Potential quality of life and costs advantages of intermittent ablation could be considered an alternative treatment for this group of patient