Most of the bio-applications of semiconductor quantum dots (QDs) show and utilize their superior optical properties over organic fluorophores. An estimated 3-35% of all cancer deaths could be avoided through early detection, therefore, there is a critical need to develop sensitive probes. The objectives of this work are: Research the phenomena of "blue" photoluminescence (PL) spectral shift on the dried bioconjugated QDs and develop the relevant mechanism; Develop a methodology that will allow successful confirmation of the bioconjugation reaction between biomolecules and QDs; Propose a modification of an existent method or approach to employ the "blue" spectral shift of bioconjugated QDs for early cancer detection. Results indicated that the "blue" spectral shift, observed for dried on the silicon substrates bioconjugated QDs, is increased with the time of storage and reaches 30-40nm in 14 days. It is accelerated at elevated temperatures and slowed down at lower temperatures. Larger size QDs generate spectral shifts of larger magnitudes, and the spectral shift is positively correlated with the biomolecule's size/weight. This phenomenon is explained by elastic and compression stress due to nonhomogenious drying of the QD droplet and the reaction with the solid surface. Agarose gel electrophoresis technique, optimized with organic dye fluorescamine, is suitable for bioconjugation verification. The optimal running parameters were found to be 2% agarose gel, 1.5V working voltage, 0.5X TBE as a running buffer, and about 120 mins running time. The spectral shift was implemented for improving the sensitivity of Prostate Specific Antigen (PSA) Enzyme-Linked ImmunoSorbent Assay (ELISA). It was found that QD ELISA could be as much, as 100 times more sensitive than the regular commercial ELISA, based on the enzymatic detection. The results of this work show that QDs may be very useful for early detection of several types of cancers, including prostate cancer in men and breast/ovarian/uterine cancers in women.

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Abstract Title: The Relationship between Perceived Personal Risk of getting Prostate cancer and Prostate-Specific Antigen (PSA) Screening Yeatoe G. McIntosh, MPH Candidate Advisor: Emmanuel Anum, MBChB, MPH, PHD Preceptor: Emmanuel Anum, MBChB, MPH, PHD Background: Prostate cancer is one of the most common cancer diagnoses in the United States. The American Cancer Society estimates that in 2008 28,660 deaths would be attributed to prostate cancer, projecting it to be the leading cause of cancer deaths in U.S. men. Despite the potential threat this cancer presents to men and the potential for improved disease outcomes from early detection, guidelines for screening for prostate cancer are varied, and disparities in screening prevalence exist. In addition, disparities in knowledge about prostate cancer screening and misconceptions about the disease seem widespread. The main purpose of this study was to determine the relationship between perceived personal risk of getting prostate cancer and prostate cancer screening with the Prostate-specific antigen (PSA) test. Methods: Data were collected from the 2003 Health Information National Trends Survey (HINTS). Overall, 1,815 men ages 35 and above were included in the sample after exclusion of men ages 18-34. Logistic regression analyses were conducted to assess the association between perceived personal risk and prostate cancer screening with PSA test, while testing for interaction and further adjusting for possible confounders. A reduced model, in which variables with non-significant Wald chi-squared statistic had been excluded, was compared to the full model to access the change in parameter estimates. Using the model-based approach, we compared models with interaction terms to the one without interaction terms using the likelihood ratio test. Parameter estimates from the best fitting model were reported using the design-based method. SAS version 9.1 statistical software was used for analyses. Results: Among men ages 35-49, those who perceived their risk as high, were significantly less likely to screen than those who perceived their risk as low (OR: 0.20 95% CI: 0.05-0.78). Within ages 50-64 and 65 and above, there were no significant differences between perceived risk levels and PSA testing. Men, who did receive healthcare provider recommendation for screening, were more likely to obtain prostate cancer (PSA) screening than men who did not receive such recommendation (OR: 92.56 95% CI 36.56, 234.36). Conclusions: The relationship between perceived personal risk of getting prostate cancer and PSA screening is modified by age. As men aged, their odds of screening increased. The most significant predictor of PSA screening was health provider recommendation. PSA screening showed no association with either race or household income.

Introdução: A hiperplasia prostática benigna (HPB), uma das doenças mais comuns do homem idoso, pode estar associada com sintomas do trato urinário inferior que afetam sua qualidade de vida. A prostatectomia aberta é uma das opções de tratamento. O antígeno prostático específico (PSA) pode estar aumentado em pacientes com HPB, reduzindo sua especificidade diagnóstica para câncer de próstata. O objetivo do estudo é avaliar o comportamento do PSA após a prostatectomia aberta, particularmente, em pacientes com o exame aumentado no pré-operatório. Método: Foi realizado um estudo prospectivo com 130 pacientes submetidos à prostatectomia aberta no HCFMUSP de julho de 2000 a setembro de 2003. Os pacientes foram divididos em dois grupos de estudo. O grupo caso foi composto por pacientes com PSA > = 4,0ng/ml e o grupo controle formado por pacientes com PSA < 4,0ng/ml. Após seis a doze meses das operações foram realizados exame digital retal e PSA. Os pacientes com exame digital retal anormal ou PSA após a prostatectomia > = 4,0ng/ml ou queda percentual do PSA < 70% do valor inicial foram biopsiados. Resultados: Em média, os pacientes apresentaram 71,18 anos e 10,81ng/ml de nível sérico de PSA total. O tamanho da próstata e o peso do adenoma foram, em média, de 122,91cm³ e 76,54g, respectivamente. A necessidade da sonda vesical foi vista em 42,31% (55/130) dos pacientes. O exame digital retal foi anormal em 11,54% (15/130) dos pacientes. A presença de prostatite crônica ocorreu em 49,23% (64/130) das análises histológicas dos espécimes cirúrgicos. Apresentaram PSA aumentado 76,15% (99/130) dos pacientes, formando o grupo caso. Não se encontrou variável que apresentasse diferença estatisticamente significativa entre os grupos para justificar o aumento do PSA. Câncer de próstata incidental foi verificado em 6,51% (8/130) dos pacientes. Em média, a queda percentual do PSA foi de 81,13% do valor inicial após 10,1 meses da operação. Pacientes do grupo caso apresentaram queda de 85,16% e pacientes do grupo controle queda de 67,01% (p = 0,004). Em média, o PSA após a prostatectomia aberta foi de 1,38ng/ml. Pacientes do grupo caso apresentaram média de 1,56ng/ml enquanto que os pacientes do grupo controle tiveram média de 0,73ng/ml (p = 0,001). Observou-se PSA > = 4,0ng/ml após a prostatectomia aberta em 6,56% (8/122) dos pacientes. Houve correlação positiva entre a variação do PSA e o peso do adenoma (r = 0,262, p = 0,004). Foi diagnosticado câncer de próstata em 4,1% (5/122) dos pacientes. Todos pacientes pertenciam ao grupo caso e tiveram PSA > = 4,0ng/ml após a operação. Conclusão: A maioria dos pacientes apresentou PSA pré-operatório aumentado. O comportamento do PSA se caracterizou por queda percentual acentuada após 10,1 meses da prostatectomia aberta. Os pacientes com PSA préoperatório aumentado apresentaram queda mais expressiva, porém com valores mais elevados de PSA após a prostatectomia aberta em relação aos pacientes com PSA pré-operatório normal. / INTRODUCTION: Benign prostatic hyperplasia (BPH), a common aging male disease, is associated with lower urinary tract symptoms that may affect overall quality of life. Open prostatectomy is one of the treatment options. Prostate-specific antigen (PSA) specificity for prostate cancer is impaired because patients with BPH may have elevated PSA. The PSA evolution after open prostatectomy is the objective of this study, particularly, in patients with elevated PSA before operation. Methods: A prospective study was made with 130 patients undergoing open prostatectomy for BPH from July 2000 to September 2003 at HCFMUSP. Patients were divided into two study groups by PSA cut-off value. Patients with PSA > = 4,0 ng/ml integrated case group. Patients with PSA < 4,0ng/ml integrated control group. Digital rectal examination and PSA were repeated after six to 12 months after operation. Biopsy was performed in patients with altered digital rectal examination, PSA > = 4,0ng/ml or PSA reduction less than 70%. Results: Mean patient age was 71,18 years. Total PSA average value was 10,81ng/ml. The mean prostatic volume and adenoma weight was 122,91cm³ and 76,54g, respectively. 42,31% (55/130) of patients had an indwelling catheter. Digital rectal examination was altered in 11,54% (15/130) of patients. Pathologic examinations of the prostatic specimens showed chronic prostatitis in 49,23% (64/130) of them. PSA was elevated in 76,15% (99/130) of patients. They composed the case group. It was not found any factor between study groups that showed significant difference to justify the elevated PSA. Incidental prostate cancer was detected in 6,15% (8/130) of patients. The mean PSA reduction was 81,13% 10,1 months after open prostatectomy. The mean PSA reduction was 85,16% and 67,01% for case group and control group patients, respectively (p = 0,004). PSA average value was 1,38ng/ml 10,1 months after open prostatectomy. PSA average value was 1,56ng/ml and 0,73ng/ml for case group and control group patients, respectively (p = 0,001). Only 6,56% (8/122) of patients had PSA > = 4,0ng/ml after open prostatectomy. It was observed statistical correlation between adenoma weight and PSA change (r = 0,262, p = 0,004). Prostate cancer was detected in 4,1% (5/122) of patients. All of them had elevated PSA after operation and belonged to case group. Conclusions: Most of patients had preoperative elevated PSA. It was observed an important PSA reduction 10,1 months after open prostatectomy. Patients with preoperative elevated PSA had more important reduction but higher postoperative PSA values than patients with preoperative normal PSA.

Introdução: A hiperplasia prostática benigna (HPB), uma das doenças mais comuns do homem idoso, pode estar associada com sintomas do trato urinário inferior que afetam sua qualidade de vida. A prostatectomia aberta é uma das opções de tratamento. O antígeno prostático específico (PSA) pode estar aumentado em pacientes com HPB, reduzindo sua especificidade diagnóstica para câncer de próstata. O objetivo do estudo é avaliar o comportamento do PSA após a prostatectomia aberta, particularmente, em pacientes com o exame aumentado no pré-operatório. Método: Foi realizado um estudo prospectivo com 130 pacientes submetidos à prostatectomia aberta no HCFMUSP de julho de 2000 a setembro de 2003. Os pacientes foram divididos em dois grupos de estudo. O grupo caso foi composto por pacientes com PSA > = 4,0ng/ml e o grupo controle formado por pacientes com PSA < 4,0ng/ml. Após seis a doze meses das operações foram realizados exame digital retal e PSA. Os pacientes com exame digital retal anormal ou PSA após a prostatectomia > = 4,0ng/ml ou queda percentual do PSA < 70% do valor inicial foram biopsiados. Resultados: Em média, os pacientes apresentaram 71,18 anos e 10,81ng/ml de nível sérico de PSA total. O tamanho da próstata e o peso do adenoma foram, em média, de 122,91cm³ e 76,54g, respectivamente. A necessidade da sonda vesical foi vista em 42,31% (55/130) dos pacientes. O exame digital retal foi anormal em 11,54% (15/130) dos pacientes. A presença de prostatite crônica ocorreu em 49,23% (64/130) das análises histológicas dos espécimes cirúrgicos. Apresentaram PSA aumentado 76,15% (99/130) dos pacientes, formando o grupo caso. Não se encontrou variável que apresentasse diferença estatisticamente significativa entre os grupos para justificar o aumento do PSA. Câncer de próstata incidental foi verificado em 6,51% (8/130) dos pacientes. Em média, a queda percentual do PSA foi de 81,13% do valor inicial após 10,1 meses da operação. Pacientes do grupo caso apresentaram queda de 85,16% e pacientes do grupo controle queda de 67,01% (p = 0,004). Em média, o PSA após a prostatectomia aberta foi de 1,38ng/ml. Pacientes do grupo caso apresentaram média de 1,56ng/ml enquanto que os pacientes do grupo controle tiveram média de 0,73ng/ml (p = 0,001). Observou-se PSA > = 4,0ng/ml após a prostatectomia aberta em 6,56% (8/122) dos pacientes. Houve correlação positiva entre a variação do PSA e o peso do adenoma (r = 0,262, p = 0,004). Foi diagnosticado câncer de próstata em 4,1% (5/122) dos pacientes. Todos pacientes pertenciam ao grupo caso e tiveram PSA > = 4,0ng/ml após a operação. Conclusão: A maioria dos pacientes apresentou PSA pré-operatório aumentado. O comportamento do PSA se caracterizou por queda percentual acentuada após 10,1 meses da prostatectomia aberta. Os pacientes com PSA préoperatório aumentado apresentaram queda mais expressiva, porém com valores mais elevados de PSA após a prostatectomia aberta em relação aos pacientes com PSA pré-operatório normal. / INTRODUCTION: Benign prostatic hyperplasia (BPH), a common aging male disease, is associated with lower urinary tract symptoms that may affect overall quality of life. Open prostatectomy is one of the treatment options. Prostate-specific antigen (PSA) specificity for prostate cancer is impaired because patients with BPH may have elevated PSA. The PSA evolution after open prostatectomy is the objective of this study, particularly, in patients with elevated PSA before operation. Methods: A prospective study was made with 130 patients undergoing open prostatectomy for BPH from July 2000 to September 2003 at HCFMUSP. Patients were divided into two study groups by PSA cut-off value. Patients with PSA > = 4,0 ng/ml integrated case group. Patients with PSA < 4,0ng/ml integrated control group. Digital rectal examination and PSA were repeated after six to 12 months after operation. Biopsy was performed in patients with altered digital rectal examination, PSA > = 4,0ng/ml or PSA reduction less than 70%. Results: Mean patient age was 71,18 years. Total PSA average value was 10,81ng/ml. The mean prostatic volume and adenoma weight was 122,91cm³ and 76,54g, respectively. 42,31% (55/130) of patients had an indwelling catheter. Digital rectal examination was altered in 11,54% (15/130) of patients. Pathologic examinations of the prostatic specimens showed chronic prostatitis in 49,23% (64/130) of them. PSA was elevated in 76,15% (99/130) of patients. They composed the case group. It was not found any factor between study groups that showed significant difference to justify the elevated PSA. Incidental prostate cancer was detected in 6,15% (8/130) of patients. The mean PSA reduction was 81,13% 10,1 months after open prostatectomy. The mean PSA reduction was 85,16% and 67,01% for case group and control group patients, respectively (p = 0,004). PSA average value was 1,38ng/ml 10,1 months after open prostatectomy. PSA average value was 1,56ng/ml and 0,73ng/ml for case group and control group patients, respectively (p = 0,001). Only 6,56% (8/122) of patients had PSA > = 4,0ng/ml after open prostatectomy. It was observed statistical correlation between adenoma weight and PSA change (r = 0,262, p = 0,004). Prostate cancer was detected in 4,1% (5/122) of patients. All of them had elevated PSA after operation and belonged to case group. Conclusions: Most of patients had preoperative elevated PSA. It was observed an important PSA reduction 10,1 months after open prostatectomy. Patients with preoperative elevated PSA had more important reduction but higher postoperative PSA values than patients with preoperative normal PSA.

The national recommendations for use of the prostate specific antigen (PSA) test for prostate cancer screening have been modified over the years as scientific evidence emerged. Current screening recommendations discourage widespread PSA screening for men at low to average risk, but provide specific guidelines for shared-decision making between men and their health providers about the benefits and risks of PSA testing. This study was an examination of relationships between men’s assessment of the quality of their care and communication with their health providers, the extent to which providers engage men in recommended discussions about PSA testing, and factors associated with shared-decision making and PSA testing. Secondary data from the U.S. Health Information National Trends Survey 4, Cycle 2 that included men with no history of prostate cancer and in the recommended age ranges for prostate cancer screening were analyzed (N=777). Non-Hispanic white men rated their quality of care higher than men of other races (c2 (49, n=635) = 7.23, p = 0.0098), whereas Hispanic men gave the lowest ratings compared to other men (c2 (49, n=635) = 5.42, p = 0.024). Previous PSA testing was reported by 64% of the men, 56% of whom stated that they discussed screening with their provider and 80% reported that they were asked if they wanted to have the test done. However, only 21% - 39% reported having ever discussed the pros and cons of PSA testing. Discussing PSA testing with a provider was the strongest predictor of obtaining the test (OR=69.5, CI = 23.6 – 204.6) but the effect was significantly modified when providers and patients engaged in the shared-decision making process (OR = 47.42, CI = 14.91 – 150.74). Age, education level and perceived quality of care were consistent, positive predictors of PSA testing. These results indicate there is a gap in provider-patient discussions about PSA screening and suggest that health providers may not be following the recommended guidelines for the content of the discussions needed to facilitate shared-decision making. Effective provider-based interventions to increase shared-decision-making about PSA testing are needed if the national objectives for prostate cancer screening are to be met.

The influences of posttranslational modifications on the functions of the versatile serpin protein C inhibitor (PCI) were studied. PCI is a serine protease inhibitor that is expressed in many tissues and secreted to various fluids in human, including blood plasma, seminal plasma, and urine. PCI in blood can act both as an anticoagulant and a procoagulant and is believed to play a role in pathogen defence. PCI in reproductive tissues is believed to regulate human reproduction at several steps, including the fertilization process. Due to the broad protease specificity and the contradictory activities, the physiological role of PCI is elusive. In this work the inhibitor was purified from blood and seminal plasma by immunoaffinity chromatography. Blood-derived PCI was found to be highly heterogeneous, due to variations in posttranslational modifications. The occupancy and structures of N- and O-glycans attached to blood plasma PCI and N-glycans of seminal plasma PCI were determined by mass spectrometry. An O-glycosylation site at Thr 20 was identified in PCI derived from blood. N-glycan structures of PCI isolated from blood and seminal plasma differed markedly, demonstrating that they are expressed in a tissue-specific manner. Proteolytic processing also appeared to be tissue-specific, since N-terminally cleaved PCI was found in PCI isolated both from blood and seminal plasma, but the length of the lacking segment differed. The effects of the N-linked glycans and the N-terminus of PCI on protease inhibition were determined using enzymatic measurements with chromogenic substrates. The N-glycans and the N-terminus had different effects on the inhibition of thrombin, factor Xa and prostate specific antigen, demonstrating that posttranslational modifications of PCI affect its functional specificity. These findings enhance the understanding of the regulation of the various functions of PCI and may potentially be used for the production of specialized PCI variants for medical purposes.

Serum PSA (Prostate Specific Antigen) level is used for prediction of prostatic carcinoma, but it suffers from weak sensitivity and specificity. We applied logistic regression, artificial neural networks, decision tree, and genetic algorithm to prostate cancer prediction problem to design a model for Turkish population. A hybrid model of logistic regression and decision tree has been designed. The model could prevent 33 biopsies (4.4% of our patients who have PSA level between 0 and 10) from our data set without a loss from sensitivity. The prepared online decision support tool and a questionnaire were published on a website. Fifty urologists have completed the questionnaire. Cronbach&rsquo / s alpha was 0.770. On a five graded Likert scale, the mean score of &ldquo / attitude to computer use in healthcare&rdquo / (ACH) was 4.2. The mean of eight responses related to the online tool (Attitude to Decision Support Tool / ADST), was 3.7. ADST was correlated with ACH (r=0.351, p=0.013). Physicians who have positive attitude to computer use in healthcare tend to use the tool (r=0.459, p=0.001). The first factor influencing the opinions of the urologists was the attitude of the user to computer use in healthcare, the other factor was the attitude of the user to the decision support tool itself. To increase the acceptance, education and training of physicians in the use of information technologies in healthcare, informing users about the logic of the decision support tool, and redesigning the system according to user feedback may be helpful.

The objectives were to 1) conduct a meta-analysis to assess the association between alpha-linolenic acid (ALA) and prostate cancer; 2) analyze a trial of ALA on coronary heart disease with PSA as a post hoc outcome; 3) assess the effect of trial serum and also ALA directly on LNCaP cell growth. 1) The ALA meta-analysis of prospective and case-control studies showed no overall effect on prostate cancer. However, removal of one study from the analysis of prospective studies changed the result to a significant protective effect (RR=0.91; 95%CI:0.83,0.99). 2) No significant treatment difference was seen in the change in PSA in the randomized controlled trial. 3) The ALA treatment serum from the clinical trial did not affect LNCaP cell growth. However, ALA decreased LNCaP cell growth in a dose dependent manner when added to cell culture. The results provide no positive evidence for an effect of ALA on prostate cancer.

The objectives were to 1) conduct a meta-analysis to assess the association between alpha-linolenic acid (ALA) and prostate cancer; 2) analyze a trial of ALA on coronary heart disease with PSA as a post hoc outcome; 3) assess the effect of trial serum and also ALA directly on LNCaP cell growth. 1) The ALA meta-analysis of prospective and case-control studies showed no overall effect on prostate cancer. However, removal of one study from the analysis of prospective studies changed the result to a significant protective effect (RR=0.91; 95%CI:0.83,0.99). 2) No significant treatment difference was seen in the change in PSA in the randomized controlled trial. 3) The ALA treatment serum from the clinical trial did not affect LNCaP cell growth. However, ALA decreased LNCaP cell growth in a dose dependent manner when added to cell culture. The results provide no positive evidence for an effect of ALA on prostate cancer.