The research goal was to document differences in the epidemiology of prostate cancer among multicultural men [non-Hispanic White (NHW), Hispanic (H), non-Hispanic Black (NHB)], and Black subgroups, particularly among NHB subgroups [US-born (USB) and Caribbean-born (CBB)]. Study findings will be useful in supporting further research into Black subgroups. Aim 1 explored changes over time in reported prostate cancer prevalence, by race/ethnicity and by birthplace (within the Black subgroups). Aim 2 investigated relationships between observed and latent variables. The analytical approaches included confirmatory factor analysis (CFA for measurement models) and structural equation modeling (SEM for regression models). National Center for Health Statistics, National Health Interview Survey (NHIS) data from 1999 – 2008 were used. The study sample included men aged 18 and older, grouped by race/ethnicity. Among the CBB group, survey respondents were limited to the English-speaking Caribbean. Prostate cancer prevalence, by race showed a higher trend among NHB men than NHW men overall, however differences over time were not significant. CBB men reported a higher proportion of prostate cancer among cancers diagnosed than USB men overall. Due to small sample sizes, stable prostate cancer prevalence trends could not be assessed over time nor could trends in the receipt of a PSA exam among NHB men when stratified by birthplace. USB and CBB men differ significantly in their screening behavior. The effect of SES on PSA screening adjusted for risk factors was statistically significant while latent variable lifestyle was not. Among risk factors, family history of cancer exhibited a consistent positive effect on PSA screening for both USB and CBB men. Among the CBB men, the number of years lived in the US did not significantly affect PSA screening behavior. When NHB men are stratified by birthplace, CBB men had a higher overall prevalence of prostate cancer diagnoses than USB men although not statistically significant. USB men were 2 to 3 times more likely to have had a PSA exam compared to CBB men, but among CBB men birthplace did not make a significant difference in screening behavior. Latent variable SES, but not lifestyle, significantly affected the likelihood of a PSA exam.

No description available.

Estrogens maintain the appropriate androgen-estrogen balance for normal regulation of the structure and function of the male reproductive tract, including the prostate gland. This research investigated viability of cells and expression of selected genes in prostate carcinoma cells (PC-3) exposed to bisphenol A (BPA), an estrogen-like substance present in a number of plastic materials. PC-3 cells are able to metabolize BPA at concentrations below 100 µM. BPA exposure at concentrations between 1nM and 100 µM does not increase or significantly reduce cell viability of these cells. Although the genes investigated in this study (GSTP1 and MGMT) did not show a significant change in expression following in vitro exposure to BPA, the positive control ethinyl estradiol (EE2) caused an increase in GSTP1 expression at mRNA level. These results indicate that BPA does not affect the viability of prostate cells, and motivate a need for further research to identify other genes that could be affected by BPA.

Abstract 1.1 Introduction The over-diagnosis and over-treatment of prostate cancer is a major public health concern, and in 2012 the United States Preventive Services Taskforce (USPSTF) recommended against prostate cancer screening. Prostate cancer is usually detected by performing a prostate biopsy. Previously, many men received a biopsy at the first sign of an elevated cancer risk identified by screening. Currently, physicians have more tools are their disposal to select men for biopsy who are likely to have clinically significant cancers, including repeat prostate specific antigen (PSA) testing, PSA density, PSA velocity, PSA free/total ratio, and age-specific cutoffs. These tests allow physicians to reduce the number of unnecessary biopsies performed on lower risk patients. One would expect that the use of these tests, in addition to more selective screening, would decrease the incidence of prostate biopsies in the population. I hypothesized that in the last 10 years in Ontario: 1) the incidence of prostate biopsy has decreased, 2) the proportion of biopsies that are malignant has increased, and 3) patients receiving biopsies are healthier. 1.2 Methods I performed a secondary analysis of population-based administrative databases. I validated the prostate biopsy procedure code in the Ontario Health Insurance Plan (OHIP) then used this code to create a cohort of Ontario men who received their first prostate biopsy between 1992 and 2012. Crude and age standardized incidence rates of prostate biopsy were determined for each study year. Era-specific inter-censal population estimates from Statistics Canada were used to establish the number of men at risk of biopsy each year. Changes over time in prostate biopsy incidence were examined using negative binomial regression by comparing the biopsy incidence of each year to a referent year expressed as incident density ratios. Similar analyses were performed to examine changes over time in the proportion of biopsies that are malignant and the health status of patients receiving biopsy. Health status was determined by calculating the Aggregated Diagnosis Group (ADG) score for each patient. 1.3 Results The sensitivity of the OHIP prostate biopsy code improved during the study period and was approximately 90% in recent years. The specificity for identifying the first prostate biopsy a patient received was estimated to exceed 95%. The crude and age standardized incidence of prostate biopsy in Ontario gradually increased between 1992 and 2007 and then dropped sharply in 2008 and 2012. Overall, 39% of biopsies were malignant but this proportion increased during the study period. The health status of patients receiving biopsy, as measured by the ADG score, improved over the study period. 1.4 Conclusions This is the first study to report crude and age standardized prostate biopsy incidence in a population. We found that previously rising biopsy rates decreased significantly in 2008 and 2012 in conjunction with changes to the perceived utility of prostate cancer screening. More years of follow up are required to determine if these changes were transient or the start of broad practice changes.

The potential of using FTIR imaging as analytical technique combined with pre-processing and multivariate analysis methods was investigated. FTIR spectroscopy has been used in the past to investigate aspects of prostate cancer cells and tissues, successfully showing the separation of spectral data taken from benign prostate samples and cancerous prostate samples of varying Gleason grade. This work was ground-breaking, diagnosing different grades of cancer in the same way to the original histopathologist-assigned grades of the tissue. The advent of FTIR imaging and its recent commercial availability has allowed the much more specific collection of FTIR spectra in the form of infrared images corresponding to hyperspectral cubes of data. Optimised protocols for FTIR imaging were developed for the collection of such images from prostate cancer tissue samples, so that the highest quality data could be obtained as time efficiently as possible. With the recent development of a resonant Mie scattering correction algorithm, the pre-processing of data could be done rigorously, eliminating all physical effects from spectral data for the first time. Hierarchical cluster analysis and K-means cluster analysis were employed as image clustering methods to classify the tissue based on morphology. Imaging data that had RMieS-EMSC, vector normalisation and a second derivative applied showed the best cluster assignment as advised by an experienced histopathologist.A large scale study was devised based on the author’s previous work to try and classify metastatic from non-metastatic prostate cancer epithelium using FTIR images. A method for the isolation of epithelial spectra was devised by the immunohistochemical staining of the tissue sample after data collection to highlight the epithelium, and overlaying the optical image of the stained tissue with the FTIR image. Resulting epithelial spectra were extracted from the FTIR images of the two tissue classes. Principal component analysis was applied to the data, and artificial neural network were constructed using training and test sets of patient-associated spectra. Experiments were done investigating whether non-metastatic cancer epithelium classified differently to non-cancerous epithelium, and whether epithelial spectra from patients with metastatic cancer would classify differently to patients with non-metastatic cancer. The non-metastatic data did not separate well from the non-cancer data. PCA results showed the metastatic data separated from the non-metastatic data very well, and seemingly robust ANNs were also developed to classify the data.

Thesis (MSc)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: Prostate cancer (CaP) has the highest incidence of any malignancy affecting South African males. The aetiology of prostate carcinoma indicate that ethnicity is one of the most important risk factors. The causes of these ethnic differences are unknown but presumably involve both environmental and genetic factors. Carcinoma of the prostate is androgen dependent, and it has been suggested that variations in androgen metabolism and synthesis may affect an individuals' risk. Therefore, genes involved in these pathways are candidates for determining CaP susceptibility. In this study two candidate genes in the androgen biosynthetic and metabolic pathway were analysed, viz., the androgen receptor gene (AR), involved in androgen transport and transcriptional activation, and the cytochrome p450c17a gene (CYP17), important for testosterone biosynthesis. Comprehensive mutation detection assays were designed (appropriate for analysis of archival paraffin-embedded material) for almost the entire coding region (excluding polymorphic repeat sequences), and including all splice site junctions of the AR gene, as well as the entire coding region of CYP17. The aim of this study was thus to determine the type and frequencies of genetic variants of these androgen metabolism genes within the diverse South African population, and to determine if the observed ethnic variation in the incidence and progression of CaP can be explained by ethnic-based genetic differences. For high sensitivity mutation detection, the most powerful of the pre-screening methods was used, namely denaturing gradient gel electrophoresis (DGGE). 20 CaP and 25 control benign prostatic hyperplasia (BPH) tissue samples were screened in order to identify possible mutations. Blood samples from the same patients were analysed in order to determine whether mutations are germline and therefore present in all cells of the body. Additional blood samples from the Western Province Blood Transfusion Service (WPBTS) (Refer to section 2.1.2, Table) were also analysed in order to determine the frequency of identified polymorphisms within the general population. Certain polymorphisms were further analysed in paraffin-embedded wax material (exclusively from Blacks) to determine the distribution of these polymorphisms in the Black population. Direct sequencing of mutant-containing DNA fragments was performed to determine the exact location and nature of mutation. Using the AR- DGGE assay 4 novel mutations were identified as well as a previously reported codon 211 (E211) polymorphism. With the CYP17- DGGE assay, 3 novel single nucleotide polymorphisms (SNPs) were detected. Three base variants occured, in codons 36 (L36), 46 (H46) and 65 (S65), as well as intronic substitutions in intron 4 (IVS+58G4C) and intron 6 (IVS-25C7A). Frequencies of SNPs were measured in the CaP and BPH samples. In conclusion, the identified polymorphisms could be used as markers in determining CaP susceptibility and may thus facilitate the identification of individuals with a high- or low-risk of developing carcinoma of the prostate. / AFRIKAANSE OPSOMMING: Prostaatkanker vertoon die hoogste voorkoms van enige kwaardaardigheid wat Suid-Afrikaanse mans aantas. Die etiologie van prostaatkarsinoom dui aan dat etnisiteit een van die mees belangrike risikofaktore is. Oorsake van hierdie etniese verskille is onbekend, maar vermoedelik is omgewing en genetiese faktore albei betrokke. Karsinoom van die prostaat is androgeenafhanklik en daar is voorgestel dat variasies in androgeenmetabolisme en androgeensintese 'n persoon se risiko mag affekteer. Gevolglik, is gene betrokke in hierdie paaie kandidate vir die bepaling van prostaatkanker vatbaarheid. In hierdie studie het ons twee kandidaat gene in die androgeen biosintetiese en metaboliese pad geanaliseer, naamlik, die androgeen reseptor geen (AR), betrokke in androgeen vervoer en aktivering van transkripsie, en die sitokroom p450c17a geen (CYP17), belangrik vir testosteroon biosintese. Ons het omvattende mutasie-bespeurings-essai-sisteme ontwikkel (ook uitvoerbaar op argivale paraffien-bewaarde materiaal), wat amper vir die hele koderende streek van die AR geen gebruik kan word (uitsluitend herhalende polimorfiese reekse) en wat alle splytpunt-aansluitings van die AR geen insluit, asook vir die hele koderende streek van CYP17. Die doel van hierdie studie was dus om die tipe en frekwensies van genetiese variante van androgeen metabolisme gene in ons diverse Suid-Afrikaanse bevolking te bepaal, en om vas te stel of die waarneembare etniese wisseling in die insidensie en vordering van prostaatkanker verstaan kan word deur etnies gebaseerde genetiese verskille. Die mees sensitiewe tegniek wat tans beskikbaar is vir vooraf-sifting vir onbekende mutasies is gekies, naamlik denaturerende gradiënt gel elektroforese (DGGE). Om moontlike mutasies op te spoor, het ons 20 prostaatkanker en 25 benijne prostaathiperplasie (BPH) monsters geanaliseer. Analise was gedoen op bloedmonsters van dieselfde pasiënte om vas te stel of kiemlyn mutasies (in alle liggaamselle) teenwoordig is. Bykomstige bloedmonsters (van die Westelike Provinsie Bloedoortappingsdiens) is ook geanaliseer om die frekwensie van bespeurde polimorfismes in die algemene bevolking te bepaal. Argivale paraffien-bewaarde materiaal (eksklusief van Swartes) is ook geanaliseer om die verspreiding van sekere polimorfismes in die Swart bevolking te bepaal. Direkte DNA volgorde bepaling van mutante DNA fragmente is uitgevoer om die ligging en tipe van mutasies te bepaal. Met die toepassing van ons AR-DGGE mutasiesisteem het ons 4 nuwe mutasies ontdek asook 'n kodon 211 (E211) polimorfisme wat voorheen gevind is. Vyf enkel nukleotied polimorfismes is met die CYP17-DGGE mutasiesisteem opgespoor. Die polimorfismes sluit in: drie basis veranderinge wat voorkom in kodons 36 (L36), 46 (H46) en 65 (S65), asook introniese substitutisies in intron 4 (IVS+58G4C) en intron 6 (IVS-25C7 A). Frekwensies van die polimorfismes was bereken in die prostaatkanker en BPH monsters. Die resultate aangebied in hierdie tesis dui aan dat die gevonde polimorfismes as merkers gebruik kan word om prostaatkanker vatbaarheid te bepaal en daardeur individue te identifiseer met 'n hoë of lae risiko vir prostaatkarsinoom ontwikkeling.

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among men in the United States. In African American men, the disease is typically detected at a more advanced stage and mortality is twice the rate of Caucasian men. However, African American men are less likely to participate in prostate cancer screening. The purpose of this descriptive study was to assess the relationship between health beliefs, knowledge, and selected demographic variables (age, income and education) and a man’s decision to participate in prostate cancer screening among African American men dwelling in rural communities. The conceptual framework for the study was the Health Belief Model. Participants for the study were recruited through contacts within rural communities within west central Alabama. A convenience sample of 90 African American men between the ages of 40-82 years of age was recruited. Analysis of the research data indicated that there was a statistically significant difference in motivation (health belief), knowledge, and age of men who participated in prostate cancer screening compared to those who did not participate in prostate cancer screening. Forward logistic regression was used to determine which independent variables [health beliefs (benefits, barriers, motivation); knowledge; age; income; and education] were predictors of prostate cancer screening. Results indicated the overall model of one predictor, motivation, was statistically reliable in predicting prostate cancer screening participation among the rural dwelling men surveyed. The model accounted for 15 to 20% of the variance. The sensitivity of the model in predicting those who would participate in prostate cancer screening was 85%. The odds of those who would participate in prostate cancer screening were 1.3 times greater for each one unit increase in motivation. Results indicate a need for more educational and motivational interventions to promote informed decision making by African American men in regards to prostate screening activities. These interventions need to be culturally sensitive and geared toward African American men, specifically those living in rural areas.

published_or_final_version / abstract / toc / Physiology / Master / Master of Philosophy

Submitted in fulfillment of the requirements of the Degree in Chemistry, Durban University of Technology, 2017. / High prevalence and mortality cases of prostate cancer (PCa) have increased around the world, particularly in developing countries. Several forthcoming factors have been revealed nowadays, one of them is due to the incapability of the diagnostic methods to produce reliable results, which impacts negatively on cancer-treatment. However, a sensitive diagnosis of PCa cells remains a challenge in the field of biosensors. Emerging whole-cell detection as biosensing targets has opened up avenues for successful cancer diagnostics, due to high selectivity among other cells. A switchable and flexible surface-based graphene material is one of the techniques that revolutionized smart biodevice platforms in biosensor technology. In this present study, a covalently linked poly-(N-isopropylacrylamide) (PNIPAM) to graphene oxide surface has been employed as “on/off”-switchable aptamer-based sensor for the detection of PC3 whole-cancer cell. The constructed surface has benefitted from PNIPAM, as the thermal-stimulus agent, which allows the coil-to-globule transitions by triggering temperature changes. When the system is above its lower critical solution temperature (LCST) of 32oC, PNIPAM will exist as hydrophobic -globular state providing an “on” binding region for the whole-cell, reaching the interactions on the biosurface. The “off” binding systems is only possibly when the PNIPAM turns into extended-state by lowering its temperature below LCST. The first principle studies have successfully characterized the electronic behavior with particular emphasis of PNIPAM monomer functions along with the description of the structural energetics of complex through density functional theory (DFT). Docking studies have further been performed to predict a plausible binding aptamer toward the protein-representative PCa cell. To better understand the prospect of an aptamer-based tunable biosensor, molecular dynamics (MD) highlighted the behavior of PNIPAM-grafted GO in exhibiting a globular and extended conformations at above and below LCST, permitting the biomolecules to interact with each other as well as to avoid interactions, respectively. Experimental studies have been included to validate the theoretical predictions by fabricating real-biosensor systems using electrochemical impedance technique, resulting a low-detection limit down to 14 cells/mL. Engagement between theoretical and experimental studies delivered an enhanced tunable-biosensor performance for the detection of whole cell prostate cancer. / M

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy