Made available in DSpace on 2014-06-11T19:32:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2003Bitstream added on 2014-06-13T20:04:42Z : No. of bitstreams: 1 jesus_cmn_dr_botfm.pdf: 799844 bytes, checksum: 3ebe5aaa75e6d8139ab67773e5687f59 (MD5) / Avaliar a taxa de detecção de câncer da próstata (CAP) e necessidade de aumentar o número de fragmentos em próstatas maiores de 60 cmd. Determinar a taxa de complicações das biópsias da próstata e os possíveis fatores de risco e suas repercussões em pacientes submetidos à biópsia de próstata. Comparar o tratamento de duração longa com sulfametoxazol-trimetoprim (SMZ-TMP) com o tratamento de duração curta com ciprofloxacina, avaliando a eficácia na prevenção de complicações e os custos do tratamento. PACIENTES E MÉTODOS: foram realizadas biópsias em 174 pacientes que apresentavam anormalidade ao exame digital da próstata (EDP) ou PSA maior que 4ng/ml ou ambos. Em 106 pacientes, foi utilizada a profilaxia das complicações infecciosas com SMZ-TMP (960mg) duas vezes ao dia, via oral, por uma semana. Nos 68 pacientes restantes, foi administrada a ciprofloxacina 500mg, por via oral, somente em duas tomadas. Foram realizadas seis biópsias em próstatas menores que 60cmd e em próstatas maiores foram retirados 12 fragmentos em média. As complicações pós-biópsia foram anotadas após o término do procedimento e em consultas posteriores (uma semana e um mês após o procedimento). Algumas condições foram investigadas, como possíveis fatores de risco para biópsias de próstata: idade, câncer da próstata, diabetes melitus, hipertensão arterial, antecedentes de prostatite, uso de ácido acetilsalicílico (AAS), volume prostático, número de biópsias e uso de sonda vesical de demora. RESULTADOS: Foram diagnosticados 43 casos de câncer da próstata (24,7%). Não houve diferença estatisticamente significante entre o diagnóstico de CAP feito com a retirada de seis fragmentos em relação ao método de retirada de 12 fragmentos em próstatas... / To evaluate the rates for prostate cancer detection (PC), for complications in prostate biopsies and the possible risk factors and their repercussions. To compare the long term treatment with sulfamethoxazole-trimethoprim (SMZ-TMP) and the short term treatment with two ciprofloxacin doses in relation to their effectiveness and costs of the treatment in preventing complications. PATIENTS AND METHODS: Biopsies were accomplished in 174 patients that presented abnormality in digital rectal exam (DRE) or/and PSA larger than 4ng/ml. In 106 patients, prophylaxis of the infectious complications was made with SMZ-TMP (960mg) twice a day, orally, for one week. In the 68 remaining patients, ciprofloxacin 500mg was orally administered only twice a day. Six biopsies were accomplished in prostates smaller than 60cmd, and in larger ones around 12 fragments were sampled. The complications of guided-biopsy were noted in the end of the procedure and in the follow-ups (one week and one month after the procedure). Some possible risk factors were investigated, such as age, prostate cancer, diabetes melitus, arterial hypertension, previous prostatitis, use of acetilsalicilic acid, prostatic volume, number of biopsies and use of urethral catheter. RESULTS: Forty-three cases of prostate cancer were diagnosed (24.7%). There was no statistical difference between PC diagnoses with sampling of six fragments and the method of withdrawal with 12 fragments. However, three PC diagnoses were only accomplished with the 12 fragment biopsies, corresponding to 6.9% in the total of the diagnosed neoplasms. These cases would be lost if the biopsy had been accomplished with the conventional sextant method. There were 272 complications in prostate guided-biopsies: minor (98.2%) and major (1.8%). Common complications were of hemorrhagic nature (75.3%), when the most usual one was... (Complete abstract, click electronic address below)

Orientador: Rejane Maira Góes / Resumo: O consumo excessivo de lipídios na dieta constitui um problema na alimentação da sociedade atual, contribuindo para o desenvolvimento de doenças e de cânceres como o de mama, de próstata e de cólon. Se tratando da próstata, os lipídios podem ter ação direta, ou por mediadores celulares deles derivados e desequilibrar os níveis de esteroides sexuais. Contudo, alguns componentes dietéticos exercem papel benéfico para a saúde prostática ou mesmo propriedades terapêuticas, como a curcumina. Existe, portanto, interesse crescente na ação da curcumina sobre a próstata, e seus análogos sintéticos vem sendo testados para aplicação no tratamento de doenças prostáticas. Sabendo-se que componentes da dieta materna podem afetar a próstata masculina permanentemente, por programação do desenvolvimento, este estudo avaliou as consequências da dieta materna enriquecida com lipídios saturados da banha de porco, durante a gestação e lactação de ratos Wistar, associada ou não à suplementação alimentar com curcumina, além da ingestão do óleo de milho comercial, sobre a histofisiologia da próstata ventral da prole na idade adulta. Ratos Wistar foram divididos em cinco grupos (n=12 por grupo; 12 semanas de idade), segundo o regime alimentar ao qual as mães foram submetidas da 8ª sem. de idade até o desmame dos filhotes: C - dieta padrão; O- dieta padrão e óleo de milho (100µL em dias alternados, via gavagem); Cm - dieta padrão e óleo de milho contendo curcumina (100mg/kg de peso corporal, em dias... / Abstract: Excessive consumption of lipids in the diet is a problem in the feeding of current society, contributing to the development of diseases and cancers such as breast, prostate and colon. Lipids can have direct action on the prostate gland, or by cellular mediators derived from them and unbalance levels of sexual steroids. However, some dietary components play a beneficial role in prostate health or even therapeutic properties, such as curcumin. There is, therefore, growing interest in the action of curcumin on the prostate, and its synthetic analogues have been tested for application in the treatment of prostatic diseases. Knowing that components of the maternal diet can permanently affect the male prostate gland by developmental programming, this study evaluated the consequences of the maternal diet enriched with lard saturated lipids during gestation and lactation of Wistar rats, associated or not with dietary supplementation with curcumin, in addition to the commercial corn oil intake, on the histophysiology of the ventral prostate of the offspring in adulthood. Wistar rats were divided into five groups (n = 12 per group, 12 weeks old), according to the diet to which the mothers were submitted from the 8th week of age until the weaning of the pups: C - standard diet; O- standard diet and corn oil (100 μL on alternate days, via gavage); Cm - standard diet and corn oil containing curcumin (100mg / kg body weight, every other day, via gavage); L - diet enriched with lard (31% of... / Mestre

Mammalian homolog Tribbles (Trbs) is a newly characterized protein family that includes three different isoforms: Trb1, Trb2, and Trb3. Tribbles are serine/threonine kinases lacking catalytic activity, thus their classification as pseudokinases. Despite their catalytic inactivity, Tribbles can interact with different proteins and regulate different biological functions. The most studied tribble family member, Trb3, was reported to play a major role in Drosophila's ventral furrow formation. Further studies revealed that Trb3 is also involved in diabetes, stress-response, and development. Previously, Trb3 upregulation was detected in certain types of cancer but its function remains unknown. The goal of our study is to gain a better understanding of the biological function of Trb3 in cancer, including the molecular mechanism of action. Using the cohort analysis, we identified higher levels of Trb3 in the lung tumor compared to the normal tissue. Furthermore, higher Trb3 expression in the lung tissue was associated with a poor survival in cancer patients. Silencing of Trb3 in A549 promoted cell growth. On the other hand, overexpression of Trb3 in NCI-H358 inhibited cell growth. The analysis of cell cycle gene profiling revealed a decrease in several genes that are essential for cell cycle progression in S phase in Trb3 overexpressed NCI-H358. The cell proliferation protein, Ki67, was also decreased in Trb3 overexpressed NCI-H358 cells. Moreover, Tb3 overexpressed cells formed higher colony number in soft agar assay and depicted higher migration ability in the Boyden chamber assay. Mesenchymal markers SNAIL, TWIST and N-cadherin were upregulated while epithelial E-cadherin was significantly reduced. Interestingly, prosurvival protein Akt was also reduced post Trb3 overexpression. Trb3 expression was associated with a poor survival. However, we discovered that Trb3 overexpression inhibited cell growth. Thus, we hypothesized that Trb3 expression might contribute to tumorigenesis during cellular metabolic stress. In order to understand the potential role of Trb3 in metabolic stress, NCI-H358 cells were treated with five different cellular stressors to mimic the tumor microenvironment. All stressors used were shown to induce endogenous Trb3 expression. Moreover, stress proteins ATF4, CHOP and ASNS were induced by all stressors. One of the stressors used was rotenone, an inhibitor of the complex I of the electron transport chain. Rotenone treatment induced Trb3 expression. This expression inversely correlated with cytochrome C expression. Furthermore, Trb3 expression positively correlated with the expression of mitophagic genes PINK1, Parkin and p62, which suggest that Trb3 is induced during ROS-mediated oxidative stress to participate in the clearing of damaged mitochondria. This targeted clearing of the mitochondria, a process known as mitophagy is essential for the cell survival of the lung cancer cells. Last, Trb3 overexpression rendered cancer cells resistant to docetaxel and cisplatin, two chemotherapeutic drugs used in lung cancer treatment. On the other hand, Trb3 depleted cells were more sensitive to the drugs. Our results suggest that Trb3 is activated in the primary tumor to promote metabolic adaptation through cell cycle arrest and the inhibition of aerobic glucose metabolism through Akt inhibition. Furthermore, Trb3 is essential during cell survival post ROS-mediated stress and participates in the clearing of damaged mitochondria during mitophagy. Last, stress-mediated activation of Trb3 confers lung cancer cells with chemoresistance and suggest that Trb3 could be a potential target in lung cancer therapy.

Made available in DSpace on 2014-06-11T19:32:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-05-03Bitstream added on 2014-06-13T18:44:21Z : No. of bitstreams: 1 disantis_gw_dr_botfmvz_prot.pdf: 4486819 bytes, checksum: 22bfb6868fb6b4112ac603f50cd0b4e4 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A neoplasia intra-epitelial prostática (HGPIN) e a atrofia inflamatória proliferativa (PIA) são lesões potencialmente pré-malignas encontradas na próstata humana (De Marzo et aI., 1999; Bostwick e Qian, 2004). HGPIN tem sido relatada na próstata canina com características semelhantes às observadas em humanos (Waters et aI., 1997), porém a PIA ainda não foi caracterizada nesta espécie. O presente trabalho objetivou a avaliação imunoistoquímica do índice proliferativo (PCNA e Ki67), da expressão de proteínas pró-apoptose (caspase-3), genes supressores de tumores (p-53), genes inibidores de apoptose (bcl-2) e de moléculas de adesão (E-caderina), além da avaliação histoquímica do estado proliferativo (AgNOR) e da determinação de mensurações nucleares por análise quantitativa computadorizada de imagens (AQCI) em focos HGPIN, PIA e em ácinos normais da próstata canina. Considerando os resultados de ácinos normais, constatou-se que as lesões estudadas apresentam alto índice proliferativo; capacidade proliferativa no compartimento epitelial secretor; ausência de expressão de p-53; perda de expressão de E-caderina; padrão de AgNOR semelhante ao de ácinos normais; e núcleos celulares maiores e com fator de circunferência maior. Focos de PIA exibem ainda índice apoptótico semelhante ao de ácinos normais e predomínio do linfócitos T, quando considerado o infiltrado Iinfocítico. Tais achados aproximam estas duas lesões entre si e sugerem que possam estar envolvidas no processo de transformação neoplásica da próstata canina. / Prostatic intraepithelial neoplasia (HGPIN) and proliferative inflammatory atrophy (PIA) are potentially premalignant lesions, found in human prostate (De Marzo et aI., 1999; Bostwick e Qian, 2004). HGPIN have been reported in canine prostate (Waters et aI., 1997), and share the same aspects with the humans, and PIA hadn't been described in the dogs. The aim of this work was to evaluate, by immunohistochemistry proliferative index (PCNA and KI-67), proapoptotic proteins expression (caspase 3), tumour suppressor gene (p-53), adhesion molecules (Ecadherin), histochemical proliferative status (AgNOR) and nuclear measurement by image computer quantitative analysis (AQCI) in HGPIN focus, PIA e normal acinus in canine prostate. Comparing the normal acinus results, the lesions showed higher proliferative index, secretory epithelial cells capable of proliferation, absence of p-53 expression, loss of E-cadherin expression, AgNOR patterns similar to normal acinus, cellular nucleus bigger and with higher nuclear round factor. PIA had the same apoptotic index as the normal acinus and mainly T Iymphocytes in the inflammatory infiltrate. Our findings allow us to consider these two lesions close to each other, and they may be involved in the process of neoplastic transformation of canine prostate.

Made available in DSpace on 2014-06-11T19:33:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-05-26Bitstream added on 2014-06-13T18:45:03Z : No. of bitstreams: 1 alves_fcmc_dr_botfm.pdf: 1089125 bytes, checksum: 9611b9c1532f063a91add4577e898f7f (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / As alterações epigenéticas desempenham funções críticas na regulação de vários genes, funções celulares e conseqüentes mudanças no controle do ciclo celular. Estas modificações têm sido associadas ao desenvolvimento tumoral. Em câncer de próstata, muitos genes hipermetilados foram descritos e indicados como potenciais marcadores diagnósticos, incluindo RARB, RASSF1A, SFN e CDH1. O presente estudo tem como objetivo avaliar a freqüência da hipermetilação dos genes SFN, RARB, RASSF1A e CDH1 nos adenocarcinomas de próstata (CaP) e correlacionar essas alterações com a expressão gênica e proteica e com parâmetros clínicos e histopatológicos. O padrão de metilação dos genes SFN, RARB, RASSF1A e CDH1 foi determinado por PCR-metilação específica em 68 amostras de CaP e em 27 amostras de próstata não neoplásicas (PNN). Expressão dos transcritos RARB e RASSF1A foram avaliados por RT-PCR quantitativo em 73 amostras de CaP, 15 amostras de tecidos prostáticos adjacentes não neoplásicos (PAdj) e dois tecidos prostáticos normais (N). A expressão das proteínas foi avaliada por imunohistoquímica em 141 amostras de CaP, 40 PAdj e dois N. Os resultados foram correlacionados com parâmetros clinico-histopatológicos. A expressão proteica de E-caderina também foi investigada em uma série de 39 CaP e 27 PNN. Os genes RARB e RASSF1A apresentaram-se hipermetilados em CaP (P<0,0001 e P = 0,0017, respectivamente), mas nenhuma diferença foi detectada para SFN. Os níveis dos transcritos e proteínas RASSF1A foram semelhantes entre amostras de CaP e PAdj. Entre os tumores foi detectada a diminuição dos níveis de transcritos de RAR (P=0,001) e da proteína (P=0,0007). Níveis diminídos do mRNA foram associados com a hipermetilação de RARB. A expressão proteica de RAR era nuclear e citoplasmática nos tecidos tumorais. A análise multivaria... / Epigenetic alterations play critical roles in regulation of several genes and cellular functions and their deregulation may disrupt the cellular control leading to tumor development. In prostate cancer (PCa), many hypermethylated genes have been described and indicated as potential prostate cancer diagnostic markers, including RARB, RASSF1A, SFN and CDH1. The current study aimed to evaluate SFN, RARB, RASSF1A, and CDH1hypermethylation frequencies in prostate carcinoma (PCa) and to correlate these alterations with down-regulations at transcriptional and protein levels and with clinical outcome. Methylation pattern of SFN, RARB, RASSF1A and CDH1 were determined by methylationspecific PCR (MSP) in 68 PCa samples and 27 non-neoplastic prostate tissues (NNP). RARB and RASSF1A transcripts expression were evaluated by quantitative RT-PCR in 73 PCa, 15 adjacent nonneoplastic prostate tissues (AdjP) and two normal prostate (N). Methylation and mRNA analysis for RARB and RASSF1A were done in matched samples from 30 PCa and 10 AdjP. Protein expression assessed by immunohistochemistry was evaluated in an independent cohort of 141 PCa, 40 AdjP and two normal prostate tissues. Paired E-cadherin protein and methylation analysis was also investigated in 33 PCa and 20 NNP. The findings were correlated with clinicopathological parameters. RARB and RASSF1A genes were hypermethylated in PCa (P <0.0001 and P = 0.0017, respectively), but no difference was detected for SFN. RASSF1A mRNA and protein levels were similar in PCa and AdjP samples. Down-expression of RAR in transcript (P=0.001) and protein (P=0.0007) levels were detected in tumors. Lower mRNA levels were associated with RARB hypermethylation. Nuclear and cytoplasmic RAR protein expression was detected in tumor tissues. Multivariate analysis demonstrated that cytoplasmic RAR immunostaining was independently associated with decreased... (Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:27:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-27Bitstream added on 2014-06-13T19:57:00Z : No. of bitstreams: 1 ihlaseh_sm_me_botfm.pdf: 228425 bytes, checksum: d8ddb66a9f9af259ca5de94c447588a1 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O câncer de próstata (CaP) é um problema de saúde pública devido suas altas taxas de incidência e de mortalidade. Atualmente, os marcadores disponíveis para o diagnóstico e prognóstico não são capazes de diferenciar os CaPs indolentes dos que progridem mais agressivamente. Estudos moleculares usando análises em larga escala, como hibridação genômica comparativa baseada em arrays (aCGH), permitem a identificação de vários genes candidatos a marcadores. Estudos prévios de nosso grupo usando hibridação aCGH em CaP demonstraram amplificação em 7q21.13, onde estão mapeados os genes STEAP1 e STEAP2 (sixtransmembrane epithelial antigen of prostate 1 e 2). Esses genes apresentam expressão aumentada em diversas linhagens de células neoplásicas, incluindo as de próstata. No entanto, seu papel no desenvolvimento e progressão do CaP permanece desconhecido. Há evidências de que eles codificam antígenos tumorais com potencial para serem utilizados como marcadores prognósticos. O presente trabalho visou determinar o perfil de expressão dos genes STEAP1 e STEAP2 por RT-PCR quantitativa em tempo real (qRT-PCR) em adenocarcinomas primários de próstata, em amostras de tecido não-neoplásico adjacente aos tumores e em hiperplasias nodulares da próstata (HNP). Amostras de próstatas avaliadas histologicamente como normais foram obtidas de necropsias e usadas como controles. Os pacientes foram agrupados em três classes segundo o risco de recorrência do tumor (baixo, moderado e alto) de acordo com o PSA (antígeno prostático sérico), a graduação histológica e o estadiamento dos tumores. Foi observado aumento de expressão dos genes STEAP1 e STEAP2 em 28% e 38% das amostras, respectivamente; em três pacientes com alto risco de recorrência houve aumento simultâneo da expressão dos dois genes. A expressão... / Available prognostic markers as serum PSA levels, Gleason differentiation scores and tumor staging have not been able to discriminate indolent from aggressive tumors. Increased expressions of STEAP1 and STEAP2 genes (six-transmembrane epithelial antigen of prostate 1 e 2) have been shown in neoplastic cell lineages from prostate, urinary bladder, ovary and other tumors. Previously, using comparative genomic hybridization based in arrays in prostate adenocarcinomas and their metastasis, we described genomic gains at the 7q21.13. In this region are mapped the STEAP1 and STEAP2 genes. The involvement of these genes in PCa development and progression remains to be clarified. These genes possibly express tumoral antigens and are putative molecular markers.The objective of the present study was to determine the gene expression profiles of the STEAP1 e STEAP2 genes by real time quantitative PCR in primary prostate adenocarcinomas, surrounding non-neoplastic tissues, and in nodular hyperplasia of the prostate. The results were associate with tumor pathologic characteristics and patients clinical features. Samples from histologically confirmed normal prostates obtained from necropsies were used as normal controls. According to potential risk for tumor recurrence (low, moderate and high risk) patients were classified in three groups depending on the serum PSA levels, Gleason scores, and tumor stages. Increased expression of STEAP1 e STEAP2 genes were registered in 28% and 38% of samples, respectively; both genes presented simultaneously increased expression level in three high-risk cases. Similar pattern of expression were detected in the majority of CaP (Spearman r=0,63; p<0,0001) and non-neoplastic surrounding tissue (Spearman r=0,78; p=0,0002) samples. Compared to the non-neoplastic surrounding tissues there was significant increase of STEAP1 gene expression in PCa samples... (Complete abstract click electronic access below)

Orientador: Sílvia Regina Rogatto / Banca: José Carlos Souza Trindade / Banca: Aparecido Donizete Agostinho / Banca: Cristina Victorino Krepischi Santos / Banca: Renata Coudry / Resumo: As alterações epigenéticas desempenham funções críticas na regulação de vários genes, funções celulares e conseqüentes mudanças no controle do ciclo celular. Estas modificações têm sido associadas ao desenvolvimento tumoral. Em câncer de próstata, muitos genes hipermetilados foram descritos e indicados como potenciais marcadores diagnósticos, incluindo RARB, RASSF1A, SFN e CDH1. O presente estudo tem como objetivo avaliar a freqüência da hipermetilação dos genes SFN, RARB, RASSF1A e CDH1 nos adenocarcinomas de próstata (CaP) e correlacionar essas alterações com a expressão gênica e proteica e com parâmetros clínicos e histopatológicos. O padrão de metilação dos genes SFN, RARB, RASSF1A e CDH1 foi determinado por PCR-metilação específica em 68 amostras de CaP e em 27 amostras de próstata não neoplásicas (PNN). Expressão dos transcritos RARB e RASSF1A foram avaliados por RT-PCR quantitativo em 73 amostras de CaP, 15 amostras de tecidos prostáticos adjacentes não neoplásicos (PAdj) e dois tecidos prostáticos normais (N). A expressão das proteínas foi avaliada por imunohistoquímica em 141 amostras de CaP, 40 PAdj e dois N. Os resultados foram correlacionados com parâmetros clinico-histopatológicos. A expressão proteica de E-caderina também foi investigada em uma série de 39 CaP e 27 PNN. Os genes RARB e RASSF1A apresentaram-se hipermetilados em CaP (P<0,0001 e P = 0,0017, respectivamente), mas nenhuma diferença foi detectada para SFN. Os níveis dos transcritos e proteínas RASSF1A foram semelhantes entre amostras de CaP e PAdj. Entre os tumores foi detectada a diminuição dos níveis de transcritos de RAR (P=0,001) e da proteína (P=0,0007). Níveis diminídos do mRNA foram associados com a hipermetilação de RARB. A expressão proteica de RAR era nuclear e citoplasmática nos tecidos tumorais. A análise multivaria... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Epigenetic alterations play critical roles in regulation of several genes and cellular functions and their deregulation may disrupt the cellular control leading to tumor development. In prostate cancer (PCa), many hypermethylated genes have been described and indicated as potential prostate cancer diagnostic markers, including RARB, RASSF1A, SFN and CDH1. The current study aimed to evaluate SFN, RARB, RASSF1A, and CDH1hypermethylation frequencies in prostate carcinoma (PCa) and to correlate these alterations with down-regulations at transcriptional and protein levels and with clinical outcome. Methylation pattern of SFN, RARB, RASSF1A and CDH1 were determined by methylationspecific PCR (MSP) in 68 PCa samples and 27 non-neoplastic prostate tissues (NNP). RARB and RASSF1A transcripts expression were evaluated by quantitative RT-PCR in 73 PCa, 15 adjacent nonneoplastic prostate tissues (AdjP) and two normal prostate (N). Methylation and mRNA analysis for RARB and RASSF1A were done in matched samples from 30 PCa and 10 AdjP. Protein expression assessed by immunohistochemistry was evaluated in an independent cohort of 141 PCa, 40 AdjP and two normal prostate tissues. Paired E-cadherin protein and methylation analysis was also investigated in 33 PCa and 20 NNP. The findings were correlated with clinicopathological parameters. RARB and RASSF1A genes were hypermethylated in PCa (P <0.0001 and P = 0.0017, respectively), but no difference was detected for SFN. RASSF1A mRNA and protein levels were similar in PCa and AdjP samples. Down-expression of RAR in transcript (P=0.001) and protein (P=0.0007) levels were detected in tumors. Lower mRNA levels were associated with RARB hypermethylation. Nuclear and cytoplasmic RAR protein expression was detected in tumor tissues. Multivariate analysis demonstrated that cytoplasmic RAR immunostaining was independently associated with decreased... (Complete abstract click electronic access below) / Doutor

Thesis (MTech (Biomedical Technology))--Cape Technikon, 2011. / Cancer of the prostate gland is now recognised as one of the principal medical problems in males. In the USA, cancer of the prostate is the second most commonly diagnosed cancer after skin cancer and the second most common cause of death from cancer after lung cancer. In South Africa, prostate cancer is the second most common cancer, with an estimated annual incidence of 19.1 per LOO000 men (Sitas, 1994). However, this incidence is probably under-estimated, due to incomplete records. Comparison of the incidence of prostate cancer in the different racial groups shows that it is the second most common malignancy in the White, Black (African) and Mixed (Coloured) race groups, and the fourth most common malignancy in Asian (Indian) men in South Africa. Metastatic prostate cancer is refractory to hormone therapy and remains incurable. Hence, novel therapeutic approaches are needed. These anticancer drugs can be tested in tumour cell lines, and cell culture methods also permit testing of optimum conditions.

Orientador: Patrícia Simone Leite Vilamaior / Banca: Marilia de Freitas Calmon Saiki / Banca: Silvia Borges Pimentel de Oliveira / Resumo: A morfogênese prostática do gerbilo inicia-se no 20º dia de vida pré-natal, sendo a ramificação no 1º dia do nascimento e a maturação glandular no final na puberdade. Isto contrasta com a glândula prostática de humanos, a qual tem todo o seu desenvolvimento no período pré-natal. A crisina, um flavonoide encontrado em várias espécies vegetais, como Passiflora coerula, Passiflora naringenina e em altas concentrações no mel (cerca de 5,3 mg/kg) e na própolis (28 g/L), apresenta ação inibitória sobre a enzima aromatase, a qual é responsável por catalisar a conversão de andrógenos em estrógenos. Poucos estudos relatam os efeitos da crisina, principalmente sobre a próstata. Portanto, este trabalho analisou, através de métodos morfológicos, morfométricos, sorológicos e imunoistoquímicos os efeitos da exposição à crisina, durante o período de lactação, sobre a próstata ventral de gerbilos machos adultos. Para isso, três grupos experimentais foram formados: Grupo crisina (CR), as mães receberam por gavagem 50 mg/kg/dia de crisina diluída em óleo de milho durante 14 dias do período de lactação; Grupo controle veículo (CV), as mães receberam óleo de milho no mesmo período de CR; Grupo controle (CO), as mães não receberam tratamento. Os filhotes machos foram eutanasiados com 120 dias de vida. A exposição à crisina no período neonatal não promoveu o desenvolvimento de desordens prostáticas nos gerbilos adultos, entretanto, observaram-se alterações no padrão morfológico da glândula. Assim, podemos afirmar que a crisina atuou como um desregulador endócrino sobre a próstata / Abstract: The morphogenesis prostatic of gerbil initiates from 20th day of prenatal period, the branching begins at the 1st day of birth and its final glandular maturation happen at end puberty. This is contrasts with prostate gland humans, which has all its development occurs in prenatal period. The chrysin a flavonoid foun in many vegetables species, like Passiflora coerula, Passiflora naringenin and in high concentrations in honey (about 5.3 mg / kg) and propolis (28 g / L), shows inhibitory action of the aromatase enzyme activity, which catalyzes the conversion of androgens to estrogens. Few studies have reported the effects of chrysin, especially on prostate. Thus, this study analyzed through morphological, morphometric, serologic and immunohistochemical methods the effects of the chrysin during the lactation period in the ventral prostate of adult male gerbils. For this, three experimental groups were formed. Chrysin group (CR): the mothers received by gavage 50 mg/kg/day of chrysin diluted in corn oil during 14 days of lactation period. Control vehicle group (CV): the mothers received corn oil in the same period CR. Control group (CO), the mothers received no treatment. The male offspring were euthanized at 120 days old. Exposure to chrysin in the neonatal period did not promote the development of prostatic disorders in adult gerbils, however, there were changes in the morphology of the gland. So we can say that chrysin presented endocrine disrupter actions on the prostate / Mestre

Orientador: Luiz Antônio Corrêa / Resumo: Avaliar a taxa de detecção de câncer da próstata (CAP) e necessidade de aumentar o número de fragmentos em próstatas maiores de 60 cmd. Determinar a taxa de complicações das biópsias da próstata e os possíveis fatores de risco e suas repercussões em pacientes submetidos à biópsia de próstata. Comparar o tratamento de duração longa com sulfametoxazol-trimetoprim (SMZ-TMP) com o tratamento de duração curta com ciprofloxacina, avaliando a eficácia na prevenção de complicações e os custos do tratamento. PACIENTES E MÉTODOS: foram realizadas biópsias em 174 pacientes que apresentavam anormalidade ao exame digital da próstata (EDP) ou PSA maior que 4ng/ml ou ambos. Em 106 pacientes, foi utilizada a profilaxia das complicações infecciosas com SMZ-TMP (960mg) duas vezes ao dia, via oral, por uma semana. Nos 68 pacientes restantes, foi administrada a ciprofloxacina 500mg, por via oral, somente em duas tomadas. Foram realizadas seis biópsias em próstatas menores que 60cmd e em próstatas maiores foram retirados 12 fragmentos em média. As complicações pós-biópsia foram anotadas após o término do procedimento e em consultas posteriores (uma semana e um mês após o procedimento). Algumas condições foram investigadas, como possíveis fatores de risco para biópsias de próstata: idade, câncer da próstata, diabetes melitus, hipertensão arterial, antecedentes de prostatite, uso de ácido acetilsalicílico (AAS), volume prostático, número de biópsias e uso de sonda vesical de demora. RESULTADOS: Foram diagnosticados 43 casos de câncer da próstata (24,7%). Não houve diferença estatisticamente significante entre o diagnóstico de CAP feito com a retirada de seis fragmentos em relação ao método de retirada de 12 fragmentos em próstatas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: To evaluate the rates for prostate cancer detection (PC), for complications in prostate biopsies and the possible risk factors and their repercussions. To compare the long term treatment with sulfamethoxazole-trimethoprim (SMZ-TMP) and the short term treatment with two ciprofloxacin doses in relation to their effectiveness and costs of the treatment in preventing complications. PATIENTS AND METHODS: Biopsies were accomplished in 174 patients that presented abnormality in digital rectal exam (DRE) or/and PSA larger than 4ng/ml. In 106 patients, prophylaxis of the infectious complications was made with SMZ-TMP (960mg) twice a day, orally, for one week. In the 68 remaining patients, ciprofloxacin 500mg was orally administered only twice a day. Six biopsies were accomplished in prostates smaller than 60cmd, and in larger ones around 12 fragments were sampled. The complications of guided-biopsy were noted in the end of the procedure and in the follow-ups (one week and one month after the procedure). Some possible risk factors were investigated, such as age, prostate cancer, diabetes melitus, arterial hypertension, previous prostatitis, use of acetilsalicilic acid, prostatic volume, number of biopsies and use of urethral catheter. RESULTS: Forty-three cases of prostate cancer were diagnosed (24.7%). There was no statistical difference between PC diagnoses with sampling of six fragments and the method of withdrawal with 12 fragments. However, three PC diagnoses were only accomplished with the 12 fragment biopsies, corresponding to 6.9% in the total of the diagnosed neoplasms. These cases would be lost if the biopsy had been accomplished with the conventional sextant method. There were 272 complications in prostate guided-biopsies: minor (98.2%) and major (1.8%). Common complications were of hemorrhagic nature (75.3%), when the most usual one was... (Complete abstract, click electronic address below) / Doutor