Thesis (M.S.)--University of Michigan, 1990.

Thesis (Ph. D.)--Ohio State University, 2006. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2007 Mar 3

Thesis (M.A.)--York University, 2005. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references (leaves 59-67). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url%5Fver=Z39.88-2004&res%5Fdat=xri:pqdiss &rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR11771

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)

>Magister Scientiae - MSc / Prostate cancer is a deadly disease that occurs in the male’s prostate gland. A prostate gland is a walnut structure that forms part of the male’s reproductive system. Prostate cancer is caused by high level than normal of PSA (Gleason score > 4 ng ml-1) in human blood. Some symptoms associated with high levels of PSA include blood in urine, pain when urinating, difficulty in getting and keeping an erection, blood in semen and pain in upper thigh. An immunosensor is a type of biosensor that has an antigen or antibody fragment as its biological recognition component. The specificity of the molecular recognition of antigen by antibodies to form a stable complex is the basis of immunosensor technology. In this work, overoxidized polypyrrole (OvoxPpy) was electrosynthesized as a novel sensor platform on glassy carbon electrode (GCE). The OvoxPpy was then doped with osmium telluride quantum dots(OsTe2QDs) by drop-coating method to form OsTe2QDs|OvoxPpy|GCE system. The morphology and the size of OsTe2QDs|OvoxPpy|GCE nanocomposite were determined using scanning electron microscopy. The size of thioglycolic acid capped osmium telluride quantum dots (TGA-OsTe2QDs) used as support material for the biosensor was about 2.289 nm. These quantum dots showed an excellent photo-absorption properties with an ultraviolet- visible (UV-Vis) photo absortion band occurring at 406nm associated with high band energy of 3.05 eV. The electrochemical immunosensor for PSA was prepared by immobilizing anti- PSA-antibody onto the OsTe2QDs|OvoxPpy|GCE by drop-coating and allowing it to dry for 2h. The nanocomposite sensor platform and the immunosensor were electrochemically characterised by voltammetric and impedimetric techniques. The phase shift in Bode diagram at maximum frequency was indicative of kinetic changes. Charge transfer resistance, Rct, was used as the analytical parameter for measuring the interfacial kinetics which occurred as a result of the bio-recognition event between anti-PSA-antibody and PSA. The impedance of the quantum dot electrode (TGA-OsTe2QDs-Nafion|GCE) was lower (1.490 x 104 kΩ) than the impedance of the immunosensor platform (BSA-Anti-PSA-antibody|TGA-OsTe2 QDs|OvoxPpy|GCE), 2.754 x 104. The Rct of the immunosensor was found to increase with increasing concentration of PSA. The linearity of the immunosensor at the very low concentration range (1.266 - 4.207 fg ml-1) tested, confirms its high sensitivity for PSA.

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 2014-06-11T19:33:24Z (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)

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: 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