Resistance of various cancers to conventional therapies including radio- and chemo- therapy is one of the most investigated phenomena in the molecular and clinical oncology. Recurrent disease is characterized by the presence of metastases, which are responsible for 90% of cancer-related mortality. Fractionated ionizing radiation (fIR) combined with surgery or hormone therapy represent the first-choice treatment for medium to high risk localized prostate carcinoma (PCa). In PCa, the failure of radiotherapy (RT) is often caused by radioresistance and further dissemination of escaping (surviving) cells. To investigate the radioresistance-associated phenotype, we exposed four metastasis- derived human PCa cell lines (DU145, PC-3, LNCaP, and 22RV1) to clinically relevant daily fractions of ionizing radiation (fIR; 35 doses of 2 Gy) resulting in generation of two surviving populations: adherent senescent-like cells expressing common senescence-associated markers and non-adherent anoikis-resistant stem cell-like cells with active Notch signaling and expression of stem cell markers CD133, Oct-4, Sox2, and Nanog. While the radioresistant adherent cells were capable to resume proliferation shortly after the end of irradiation, the non- adherent cells started to proliferate only after their reattachment...

Resumo: O câncer de próstata e a hiperplasia prostática benigna são as duas principais afecções do sistema genital masculino após a quinta década de vida. Além de aspectos étnicos, etários, genéticos, estudos sobre a contaminação ambiental por agentes químicos carcinogênicos, dos hábitos alimentares e do estilo de vida vêm adquirindo importância no entendimento das causas destas afecções. A exposição a contaminantes ambientais, tais como o cádmio e a ingestão de bebidas contendo cafeína têm sido associados com o aparecimento do câncer de próstata e com a hiperplasia prostática benigna, respectivamente. Além disso, existem evidências experimentais de que a exposição da próstata em períodos críticos da sua morfogênese e de rápido crescimento a disruptores endócrinos pode gerar alterações permanentes que levarão ao aparecimento de afecções nos indivíduos adultos e idosos. Neste sentido, por exemplo, a partir da puberdade é comum os homens adquirirem o hábito de fumar e/ou de ingerir bebidas estimulantes, estando, portanto, expostos ao cádmio, presente na fumaça do cigarro, e/ou a cafeína, presente nas bebidas. Desta forma, este trabalho avaliou os efeitos, isolados e combinados, do cádmio e da cafeína, em baixas concentrações, sobre a morfologia e fisiologia da próstata de ratos púberes. Para isto, ratos Wistar com 60 dias de idade foram divididos em quatro grupos (n=15), os quais receberam, via oral, na água de beber, pelo período de 30 dias: Água, Cádmio (10ppm), Cafeína (10mg/l) ou Cafeína+Cádmio, e as próstatas dorsolaterais e ventrais foram processadas histologicamente e foram feitas análises morfológicas, citoquímicas para fibras de colágeno, morfométricas e imunocitoquímicas. Também foram determinadas as concentrações plasmáticas de cádmio e testosterona e intra-prostática de cádmio no... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The prostate cancer and the benign prostate hyperplasia are the main male genitourinary system diseases after the fifty. Besides ethic, age and genetic aspects, studies about environmental contamination, diet and life stile have also emerged as important factors involved in the etiology of these diseases. The exposure to cadmium and the intake of caffeine-containing beverage have been associated with appearing of the prostate cancer and benign prostate hyperplasia, respectively. Furthermore, there are experimental evidences that prostate exposures to endocrine disruptors during a critic period of its morphogenesis and growth may influence the onset of late-life disease. In this sense, for example, from puberty on, many males became smokers and/or start to intake energetic beverage or even yet coffee, thus being exposed to cadmium, from cigarettes and/or to caffeine, from beverage. So, here we investigated the effects of cadmium and caffeine, isolated or combined, in low doses, on rat prostate morphology during puberty. For this, male Wistar rats (n=60), 2 months-old, were divided into four experimental groups (n=15), that received by drinking water and during 30 days: tap water, cadmium (10ppm), caffeine (10ppm), cadmium plus caffeine. The prostatic lobes ventral and dorsolateral were dissected out, weighted and processed for histology. It were made morphological and morphometrical analyses; cytochemistry for collagen and reticular fibers and immunocytochemistry for Ki-67. It were also determined the plasma concentrations of testosterone and cadmium and the ventral lobe intraprostatic concentration of cadmium. The plasma and intraprostatic concentrations of cadmium were increased in the animals treated with cadmium and cadmium plus caffeine. In the conditions of this experiment, the exposure to these two agents did not alter significantly neither the prostatic... (Complete abstract click electronic access below) / Orientador: Sérgio Luis Felisbino / Coorientador: Antônio Francisco Godinho / Banca: Sebastião Roberto Taboga / Banca: Patrícia Aline Boer / Mestre

O acometimento por uma doença crônica como o câncer se constitui em uma ameaça à vida e tem repercussões físicas, psicológicas e sociais no decorrer da existência. No caso do câncer de próstata, sabe-se que seus tratamentos podem interferir na sexualidade masculina, causando perda do desejo sexual e disfunção erétil. Considerando esta realidade, o objetivo deste trabalho foi compreender o modo como homens com câncer de próstata vivenciam e atribuem significados à sua sexualidade. Optou-se pela metodologia da pesquisa qualitativa, na perspectiva da Fenomenologia Ontológico-Hermenêutica de Heidegger. E utilizou-se a história oral de vida como estratégia de acesso aos relatos dos colaboradores. Foram entrevistados 10 homens com câncer de próstata que foram submetidos a tratamentos, com idades entre 51 e 82 anos, pertencentes às classes econômicas D a B2. Os resultados dos relatos possibilitaram a construção de cinco categorias: 1) A temporalidade da infância e da adolescência; 2) A temporalidade da vida adulta: o casamento, a família e os relacionamentos afetivo-sexuais; 3) O adoecimento: as relações afetivo-sexuais após a vivência do câncer; 4) O horizonte do silêncio: o que vela e desvela o ser; e 5) Projeto de vida. A análise interpretativa desvelou a dor e o sofrimento desses homens ao apresentarem disfunção erétil e seqüelas no seu desempenho sexual, atributo do ideal de masculinidade advindo do sistema patriarcal. As vivências de dor remetem-se aos modos de existir autêntico e inautêntico. A inautenticidade foi observada na recusa em aceitar a facticidade da existência, ou seja, a concretude de um corpo que envelhece, adoece e deixa de responder ao desejo sexual. O acometimento pelo câncer de próstata potencializa o contato com a própria finitude, e alguns colaboradores fogem à angústia que surge quando se constata a possibilidade última e mais própria do existir: a morte. Esses homens buscam, então, os tratamentos disponíveis para a disfunção erétil e projetam seu porvir na possibilidade de voltarem a ter ereções satisfatórias, o que expressa o sonho do desempenho sexual vivido na juventude. Todavia, nessa trajetória, alguns colaboradores apresentaram um modo de existir autêntico, evidenciado pela compreensão da temporalidade de sua existência. Seus relatos desvelaram a consciência de que, por não poderem escapar à finitude, lhes resta aceitar as modificações na sexualidade e buscar vivenciá-la de acordo com seus limites e possibilidades. O modo de existir autêntico, que constitui a abertura do homem para o poder-ser-si-mesmo, foi desvelado na afetividade e no diálogo dos colaboradores com suas parceiras. Nesse momento em que os homens perdem a capacidade de ter ereções e sentem-se frágeis em sua masculinidade, se permitem expressar um aspecto fundamental da existência: a afetividade. A abertura para falar sobre si mesmo e ouvir sua parceira evidencia a dimensão do cuidado e da solicitude na relação afetivo-sexual. Os resultados deste estudo apontam para a compreensão ontológica do ser do homem com câncer de próstata na Pós-Modernidade e podem contribuir na construção de práticas de atenção à saúde mais humanizadas. / The effect for a chronic illness as cancer constitutes in a threat the life and has physical, psychological and social repercussions in elapsing of the existence. In the case of cancer of prostate, it is known that its treatment can intervene with the masculinity sexuality, causing loss of the sexual desire and erect dysfunction. Considering this reality, the objective of this work was to understand the way as men with cancer of prostate live deeply and attribute meanings to their sexuality. It was opted to the methodology of the qualitative research, in the perspective of the Martin Heidegger?s Ontological ? Hermeneutical Phenomenology. It was used verbal story of life as strategy of access to the stories of the collaborators. Ten men with cancer of prostate had been interviewed who had been submitted the treatments, with ages between 51 and 82 years, pertaining to economic classes D to B2. The results of the stories make possible the construction of five categories: 1) the temporality of infancy and the adolescence; 2) the temporality of the adult life: the affective marriage, family and sexual relationships; 3) the sickness: sexual affective relations after the experience of cancer; 4) the horizon of silence: what close and disclose the being; 5) life project. The interpretative analyzes exposed the pain and the suffering of these men when presenting erect dysfunction and aftermaths in their sexual performance, attribute of the ideal of masculinity happened of the patriarchal system. The pain experiences send the ways to it to exist authentic and fake. The fake way was observed in the refusal in accepting the fact of the existence, or either the acceptance of a body that ages, sickens and leaves to answer to the sexual desire. The effect for cancer of prostate elevates the contact with the proper end and some collaborators runs away to distresses that it appears when the last possibility is evidenced and more proper to exist: the death. These men search then, the available treatments for the erect dysfunction and project their future in the possibility to come back to have satisfactory erections, what express the dream of the lived sexual performance in youth. However, in this trajectory, some collaborators presents a way to exist authentic, evidenced for the understanding of the temporality of their existence. Their relates disclosed the conscience of that, for not being able to escape to the end, it remains to accept the modifications to them in the sexuality and in accordance with to live deeply their limits and possibilities. The way to exist authentic, that it constitutes the opening of the man to be able to be same itself, was disclosed in the affectivity and the dialogue of the collaborators with their partners. At this moment when the men lose the capacity to have erections and feel themselves fragile in their masculinity, if they allow expressing a basic aspect of the existence: the affectivity. The opening to speak about himself exactly and to hear his partner evidences the dimension of the care and the attention in the affective-sexual relation. The results of this study point with respect to the ontological understanding of the being of the man with cancer of prostate in Post-modernity and can contribute in the construction of practical of attention to health more humanized.

High mobility group A2 (HMGA2) is a non-histone protein highly expressed during the development but is low or absent in most adult tissues. Epithelial-mesenchymal transition (EMT) plays a critical role in prostate cancer progression and metastasis. HMGA2 has been shown to promote EMT in separate studies. Interestingly, wild-type HMGA2 and truncated (lacking the 3’UTR) HMGA2 isoforms are overexpressed in many cancers. However, there are no studies on the role of each isoform in prostate cancer progression. We hypothesized that wild-type and truncated HMGA2 promotes prostate cancer progression by different mechanisms. We analyzed the expression of HMGA2 in the prostate panel by western blot analysis and the localization in prostate tissue microarray by immunohistochemistry. We stably overexpressed wild-type and truncated HMGA2 cDNA in LNCaP cells and measured the expression and the localization of HMGA2 as well as EMT markers. We also performed the migration and cell viability assays. We analyzed phospho-ERK in cells overexpressing HMGA2 as well as inhibition with U0126 (MAPK inhibitor). To explore the role of truncated HMGA2, we measured the reactive oxygen species (ROS) concentration by DCFDA dye, as well as analyzing Jun-D as a putative downstream effector of HMGA2. Additionally, we knocked down Jun-D and performed the migration and cell viability assays. We treated ARCaP-M mesenchymal cells with camalexin, a 3-thizol-2-yl-indole (a natural product, as a candidate to target HMGA2) in vitro and in vivo in nude mice. Our results showed an increase in nuclear HMGA2 expression with prostate cancer progression as compared to normal tissue. LNCaP cells overexpressing wild-type but not truncated HMGA2 displayed nuclear localization and induced EMT via the ERK1/2 pathway, and this effect could be reversed by treating the cells with U0126. Conversely, truncated HMGA2 displayed cytoplasmic expression and increased prostate cancer migration via increasing Jun-D expression and ROS; this could be antagonized by Jun-D knockdown. Finally, treating ARCaP-M aggressive prostate cancer cells with camalexin reduce its expression in vitro and in vivo. In conclusion, both wild-type and truncated HMGA2 induce prostate cancer progression by different mechanisms which may be targeted by camalexin.

Radiotherapy is the most widely used treatment for cancer, with 4 out of 10 cancer patients receiving radiotherapy as part of their treatment. The delineation of gross tumour volume (GTV) is crucial in the treatment of radiotherapy. An automatic contouring system would be beneficial in radiotherapy planning in order to generate objective, accurate and reproducible GTV contours. Image guided radiotherapy (IGRT) acquires patient images just before treatment delivery to allow any necessary positional correction. Consequently, real-time contouring system provides an opportunity to adopt radiotherapy on the treatment day. In this thesis, freely deformable models (FDM) and shape constrained deformable models (SCDMs) were used to automatically delineate the GTV for brain cancer and prostate cancer. Level set method (LSM) is a typical FDM which was used to contour glioma on brain MRI. A series of low level image segmentation methodologies are cascaded to form a case-wise fully automatic initialisation pipeline for the level set function. Dice similarity coefficients (DSCs) were used to evaluate the contours. Results shown a good agreement between clinical contours and LSM contours, in 93% of cases the DSCs was found to be between 60% and 80%. The second significant contribution is a novel development to the active shape model (ASM), a profile feature was selected from pre-computed texture features by minimising the Mahalanobis distance (MD) to obtain the most distinct feature for each landmark, instead of conventional image intensity. A new group-wise registration scheme was applied to solve the correspondence definition within the training data. This ASM model was used to delineated prostate GTV on CT. DSCs for this case was found between 0.75 and 0.91 with the mean DSC 0.81. The last contribution is a fully automatic active appearance model (AAM) which captures image appearance near the GTV boundary. The image appearance of inner GTV was discarded to spare the potential disruption caused by brachytherapy seeds or gold markers. This model outperforms conventional AAM at the prostate base and apex region by involving surround organs. The overall mean DSC for this case is 0.85.

O objetivo deste estudo foi o de medir in vivo as dimensões da próstata, pelo exame ultra-sonográfico, de cães de diferentes tamanhos, com idade entre 1 e 5 anos. Foram realizados exames em 47 cães, sem processos patológicos aparentes. Os pacientes foram divididos em dois grupos de acordo com a idade, Grupo 1: cães entre 12 e 30 meses e Grupo 2: cães entre 31 e 60 meses. Cada grupo foi subdividido em três subgrupos de acordo com o peso. Subgrupos 1 e 4 com animais até 10kg, Subgrupos 2 e 5 com animais entre 11 e 25kg e Subgrupos 3 e 6 com animais acima de 25kg sendo que os Subgrupos 1 a 3 pertencem ao Grupo 1 e os Subgrupos 4 a 6 pertencem ao Grupo 2. As imagens em corte longitudinal e transversal permitiram a observação da próstata, localizada caudalmente à bexiga urinária, de formato arredondado, de contornos regulares e definidos e de ecogenicidade maior que a do baço. Comprimento e altura foram mensurados no plano longitudinal, já a largura foi medida no plano transversal. O Subgrupo 1 apresentou medidas prostáticas de comprimento: 1,19 (±0,16cm); de altura: 1,17 (±0,2cm) e de largura: 1,41 (±0,24cm), valores menores que os obtidos no Subgrupo 4 que apresentou comprimento: 2,14 (±0,13cm); altura: 2,12 (±0,16cm) e largura de 2,59 (±0,21cm). O Subgrupo 2 apresentou valores prostáticos de comprimento: 2,17 (±0,11cm); de altura: 2,04 (±0,15cm) e de largura: 2,64 (±0,13cm), valores menores que os obtidos no Subgrupo 5 que apresentou comprimento: 2,81 (±0,44cm); altura 3,73: (±0,37cm) e largura de 3,29 (±0,38cm). O Subgrupo 3 apresentou valores prostáticos de comprimento 3,09 (±0,21cm); de altura: 2,93 (±0,21cm) e de largura: 3,63 (±0,19cm), valores menores que os obtidos no Subgrupo 6 que apresentou comprimento: 3,47 (±0,31cm); altura: 3,35 (±0,35cm) e largura de 4,03 (±0,28cm). A correlação foi forte entre os valores prostáticos determinados e a massa corpórea dos cães estudados. / The aim of this study was ultrasonographically assess the prostatic dimensions in dogs of different sizes, aging from 1 to 5 years-old. Forty-seven examinations were done, in dogs with no clinical diseases. The patients were divided into two groups according to their ages, such as: Group 1 - from 12 to 30 months-old and Group 2 ? from 31 to 60 months-old. Each group was divided into 3 other groups according to their weight. Subgroup 1 and 4: up to 10 Kg, subgroup 2 and 5: from 11 to 25 Kg and subgroups 3 and 6: over 25 Kg (subgroups 1 to 3 were inserted in Group 1 and subgroups 4 to 6 were inserted in Group 2). The sagittal and transverse planes on ultrasonographic examination provided the entire visualization of the prostate, which was round to normal-shaped, lies caudally to the urinary bladder, with smooth margins and hyperechoic to the spleen. Their length and height were measured on sagittal plane and the width was measured on transverse plane. Regarding the subgroup 1, the mean prostatic length was 1,19 cm (± 0,16 cm), the mean prostatic height was 1,17 cm (± 0,2 cm) and the mean prostatic width was 1,41 cm (± 0,24 cm), and these measurements showed to be shorter than the ones from subgroup 4, such as 2,14 cm (± 0,13) as for the mean length, 2,12 cm (± 0,16 cm) as for the mean height and finally 2,59 cm (± 0,21 cm) as for the mean width. Regarding the subgroup 2, the mean prostatic length was 2,17 cm (± 0,11), the mean height was 2,04 (± 0,15 cm) and the mean width was 2,64 cm (± 0,13), and these measurements showed to be shorter than the ones from subgroup 5, such as 2,81 cm (± 0,44) as for mean length, 3,73 cm (± 0,37 cm) as for the mean height and finally 3,29 cm (± 0,38 cm) as for the mean width. Regarding the subgroup 3, the mean prostatic length was 3,09 cm (± 0,21), the mean height was 2,93 (± 0,21 cm) and the mean width was 3,63 cm (± 0,19), and these measurements showed to be shorter than the ones from subgroup 6, such as 3,47 cm (± 0,31) as for mean length, 3,35 cm (± 0,35 cm) as for the mean height and finally 4,03 cm (± 0,28 cm) as for the mean width. There was a high correlation between the prostatic dimensions and the body mass of theses dogs.

PANDER/FAM3B (PANcreatic-DERived factor) é uma citocina capaz de induzir apoptose em células-β secretoras de insulina e regular a homeostase da glicose nos tecidos periféricos. Considerando que PANDER/FAM3B também é expresso em tumores de próstata, o presente trabalho avaliou o papel desta citocina na inibição da apoptose in vitro, assim como o crescimento e invasividade tumoral de células de carcinoma de próstata da linhagem DU145 in vivo, usando o modelo de superexpressão estável mediada por lentivirus. Os nossos resultados apontam um aumento da viabilidade e uma diminuição da morte celular em células que superexpressam PANDER quando comparadas ao grupo controle. Este efeito protetor é acompanhado por um aumento da expressão de genes anti-apoptoticos e uma diminuição da atividade proteolítica das caspases. Por outro lado, a superexpressão de PANDER/FAM3B por tumores in vivo se correlaciona com aumento da massa tumoral e o aumento de vasos sanguíneos nos tumores. Em síntese, nossos dados demonstram que, em contraste ao papel observado em células β-pancreáticas, o PANDER/FAM3B inibe morte celular e promove a tumorigenicidade e o crescimento tumoral in vivo, sugerindo ao mesmo tempo, algum envolvimento com angiogênese e metástase em células DU145. / PANDER / FAM3B (pancreatic-derived factor) is a cytokine capable of inducing apoptosis in secreting β-cells and insulin to regulate glucose homeostasis in peripheral tissues. Whereas PANDER / FAM3B is also expressed in prostate tumors, this study evaluated the role of this cytokine in the inhibition of apoptosis in vitro as well as tumor growth and invasiveness of prostate carcinoma DU145 cells lineage in vivo, using the model Stable overexpression mediated by lentivirus. Our results suggest that increased viability and decreased cell death in cells that overexpress PANDER when compared to the control group. This protective effect is accompanied by an increased expression of anti-apoptotic genes and a decrease in proteolytic activity of caspases. Moreover, overexpression of PANDER / FAM3B by tumors in vivo correlates with increased tumor mass and the increase of blood vessels in tumors. In summary, our data demonstrate that in contrast to the role observed in pancreatic cells, PANDER / FAM3B inhibits cell death and promotes tumorigenicity and tumor growth in vivo, suggesting at the same time, some involvement in angiogenesis and metastasis in cell DU145.

No mundo inteiro, o carcinoma de próstata ocupa o quinto lugar entre as neoplasias malignas de maior mortalidade. No Brasil, estima-se para o ano de 2001 que, entre os tumores malignos no sexo masculino, o carcinoma de próstata terá a segunda maior taxa de mortalidade e a primeira taxa de incidência (Estimativa da incidência e mortalidade por câncer no Brasil – 2001 – INCA). Uma vez que a taxa de mortalidade por carcinoma de próstata na população brasileira tem aumentado significativamente nos últimos anos, a presente tese se propôs a investigar regiões polimórficas em genes conhecidos que poderiam estar associadas a um aumento na predisposição a esta forma de câncer. Assim sendo, estudamos as regiões polimórficas CAG e GGC do gene do receptor de andrógeno; o polimorfismo C1171T do gene do receptor de vitamina D; o polimorfismo D104N do gene da endostatina; o polimorfismo Pro72Arg do gene p53 e a região polimórfica AAAAC localizada na região 3’ não traduzida do gene MXI1. / In the world’s population prostate carcinoma is the fifth most commom male cancer-related death malignancy. In Brazil, among all male invasive cancers it is expected that prostate carcinoma will have the second highest death rate and the highest incidence rate (Estimativa da incidência e mortalidade por câncer no Brasil, 2001). As the prostate carcinoma death rate in brazilian population has been increasing over the last several years we proposed to investigate polymorphic regions of known genes that might be associated with prostate carcinoma predisposition. We studied the androgen receptor CAG and GGC polymorphic regions, the vitamin D receptor C1171T polymorphism, the endostatin D104N polymorphism, the p53 Pro72Arg polymorphism and the MXI1 AAAAC polymorphic region.

O câncer de próstata é o tumor maligno mais freqüente nos homens com idade superior a 50 anos, excetuando-se os tumores cutâneos. No Brasil estima-se para o ano de 2012 cerca de 60.180 casos novos deste tipo de neoplasia. Os marcadores tumorais permitem fazer o rastreamento do câncer, o diagnóstico diferencial entre uma neoplasia benigna e maligna, a avaliação de prognóstico e o acompanhamento terapêutico, assim como a detecção da recidiva tumoral. Dentre estes marcadores tumorais, tem-se dado muito atenção para as proteínas que mediam e participam da progressão do ciclo celular. A ciclina D1 é uma proteína nuclear de vida curta que é destruída pela via da ubiquitina ATP dependente, e está envolvida na transição celular da fase do ciclo G1 (repouso) para a fase S (síntese) tanto em células normais como em células neoplásicas. A super expressão de ciclina D1 remove a regulação normal do ciclo celular causando proliferação celular descontrolada, um crescimento anormal dos tecidos e a transformação para um fenótipo neoplásico, atuando como oncogene. No presente trabalho foi estudado a expressão de ciclina D1 em adenocarcinomas de próstata, tendo como objetivo avaliar a relação desta proteína com parâmetros epidemiológicos, clínicos e histopatológicos. Adicionalmente também foi feita comparação de escore de Gleason e lateralidade tumoral entre biópsias prostáticas com agulha e de prostatectomias radicais. No ensaio para ciclina D1 foram analisados 85 casos através de imunoistoquímica (IHQ) de material proveniente de prostatectomias radicais diagnosticados com adenocarcinoma de próstata entre os anos de 2005 e 2010 em nosso serviço. O método de avaliação se utilizou de microscopia ótica comum e contagem semi-quantitativa, comparado-se a expressão com achados clínicos, epidemiológicos e histopatológicos utilizando-se Teste T de Fisher, Qui Quadrado, Mann-Whitney, Curva ROC e correlação de Spearman. Os resultados demonstraram correlação positiva de ciclina D1 com escore de Gleason (p<0,05), com volume prostático (p=0,01) e uma tendência a correlação positiva com invasão perineural (p=0,07). Não houve correlação estatística entre ciclina D1 e o aumento de PSA, assim como outros achados histopatológicos. As biópsias prostáticas com agulha apresentaram subestimação em 40% dos casos para escore de Gleason e de 62,3% dos casos para lateralidade tumoral quando comparadas a prostatectomia radical. Já que as taxas de subestimação de escore de Gleason e lateralidade tumoral são relativamente altas e visto a urgência em se padronizar novos biomarcadores para o câncer prostático, sugerimos que ciclina D1 pode ser utilizada como biomarcador em patologia cirúrgica da próstata auxiliando numa gradação histológica mais precisa em biópsias com agulha colaborando para melhor vigilância e escolha terapêutica. / Prostate cancer is the most common malignant tumor in men older than 50 years, except for skin tumors. In Brazil it is estimated for the year 2012 about 60,180 new cases of this type of neoplasm. Tumor markers allow to cancer screening, differential diagnosis between a benign and malignant, assessment of prognosis and therapeutic monitoring, and detection of tumor recurrence. Among these tumor markers, has been given much attention for proteins that mediate and participate in cell cycle progression. Cyclin D1 is a short-lived nuclear protein that is destroyed by the ATP ubiquitin dependent pathway, and is involved in the transition of cell cycle G1 phase (resting) to the S phase (synthesis) cells both in normal and neoplastic cells. The overexpression of cyclin D1 removes the normal regulation of cell cycle causing uncontrolled cell proliferation, abnormal growth of tissues and transformation to a neoplastic phenotype, acting as an oncogene. In the present work we studied the expression of cyclin D1 in prostate adenocarcinomas, and to evaluate the relationship of this protein with epidemiologic factors, clinical and histopathological features. Additionally comparison was also made of Gleason score and laterality between tumor biopsies and prostate needle radical prostatectomies. In the assay for cyclin D1 were 85 cases analyzed by immunohistochemistry (IHC) of material from radical prostatectomies diagnosed with prostate adenocarcinoma between the years 2005 and 2010 at our institution. The evaluation method utilized were light microscopy and semi-quantitative score, comparing the cyclin D1 expression with clinical, epidemiological and histopathological features using Fisher\'s exact test, chi square test, Mann-Whitney test, ROC curve and Spearman correlation. The results showed a positive correlation of cyclin D1 with Gleason score (p <0.05), prostate volume (p = 0.01) and a trend toward positive correlation with perineural invasion (p = 0.07). There was no statistical correlation between cyclin D1 and increased PSA, as well as other histopathologic features. Prostate needle biopsies showed underestimation in 40% of cases for Gleason score and 62.3% of cases for tumor laterality when compared to radical prostatectomy. Since the rates of underestimation of Gleason score and tumor laterality are relatively high and the urgency to standardize new biomarkers for prostate cancer, we suggest that cyclin D1 may be used as biomarkers in surgical pathology of the prostate assisting more accurate histological grading in needle biopsies and collaborating for better surveillance and therapeutic choice.

Diversas são as formas de tratamento do câncer de próstata, com resultados oncológicos e complicações variadas . A crioablação foi proposta nos anos 60 e com a evolução dos métodos de imagem a técnica ressurgiu; 44 pacientes, divididos em 3 grupos (portadores de tumor de alto risco, tumores de baixo risco e falha de tratamento após radioterapia) foram submetidos a crioterapia por via percutânea transperineal. Sobrevida livre de doença foi de 87% no grupo baixo risco, 34% no grupo alto risco e 58% no grupo de resgate após falha de radioterapia. A complicação mais freqüente foi disfunção erétil (94,5%); obstrução infravesical ocorreu em 9 pacientes (20,4%); 6 pacientes (13,6%) apresentaram algum grau de incontinência urinária. Não houve nenhum caso de fístula uretroretal ou mortalidade relacionada ao procedimento / There are several treatments for prostate cancer with an assorted oncologic results and complications. Cryoablation was proposed in the 60 and the improvement of radiological techniques allowed the perineal percutaneous treatment; 44 patients divided into three groups (high risk tumors, low risk tumors and patients with recurrent prostate cancer following radiotherapy) were submitted to perineal percutaneous prostate cryoablation. Biochemical-free survival was 87% in low risk group, 34% in the high-risk group and 58% in salvage cryoablation. Erectile dysfunction was the most frequent complication (94,5%); Infravesical obstruction occurred in 20,4% of the patients and six (13,6%) developed urinary incontinence. There were no urethrorectal fistulae or mortality related to the procedure