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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.

MicroRNAs as Prognostic Biomarkers in Prostate Cancer

Gordanpour, Aida 12 December 2012 (has links)
Prostate cancer, one of the most common cancers among men, can be relatively harmless or extremely aggressive. The most widely used biomarker for the disease, the PSA test, is not independently diagnostic or prognostic of prostate cancer. One of the main challenges of prostate cancer research is to find reliable and effective prognostic biomarkers that will predict cancer recurrence following surgery, in order to identify clinically significant prostate cancer and improve management of the disease. In recent years, microRNAs (miRNAs) have been identified as master regulators of cellular processes, and dysregulated miRNAs have been associated with cancer development and progression. The intent of my PhD research program was to uncover novel miRNAs that contribute to prostate cancer pathogenesis in order to assess their potential as predictors of clinical progression. By analyzing a large cohort of primary prostate cancer samples, we have discovered that microRNA-221 (miR-221) is associated with metastasis and biochemical recurrence in prostate cancer, and is downregulated in TMPRSS2:ERG fusion gene- positive tumors. In addition, we have determined that microRNA-182 (miR-182) is overexpressed in prostate cancer and is associated with increased metastasis and clinical progression by targeting a tumors suppressor Forkhead box O1 (FOXO1). Overall, this work introduces novel candidate miRNA genes and downstream targets that are aberrantly expressed in more aggressive prostate cancer, and presents a potentially significant role for miRNAs as prognostic biomarkers that are associated with clinical progression, and perhaps aids in defining how miRNAs might one day serve as anti-cancer therapeutic agents.

The role of stroma in prostatic epithelial function : the development of a model system

Hayward, Simon William January 1991 (has links)
No description available.

The development of FTIR-imaging for the study of human prostate cancer biopsies

Dorling, Konrad January 2013 (has links)
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.

Identification of potential biomarkers for the detection of aggressive prostate cancer

Whiteland, Helen Louise January 2012 (has links)
No description available.

LncRNA PVT1 Associates with c-Myc and Stabilizes Oncogenic Signaling in Prostate Cancer

Jones, Rachel, Jones, Rachel January 2017 (has links)
Understanding the factors that affect c-Myc in prostate cancer is critical to developing an effective means of treatment for aggressive, castration-resistant forms of the disease. Myc is an oncogene known to be overexpressed and stabilized in many types of cancer, prostate included. Recent insights into breast cancer have revealed that Myc protein retains a longer half-life in cancer cells, but the cause for this has yet to be deduced. Due to its close proximity and proven interaction with Myc, I propose that the lncRNA PVT1 is stabilizing Myc and facilitating its activation of target genes in castration-resistant prostate cancer. To explore this hypothesis, metastatic prostate cancer DU145 cells were transfected with both siRNAs and ASOs targeting PVT1. Cells were analyzed for changes in different protein levels, as well as binding partners, through the use of immunoprecipitation and western blot. These results were verified with RT-qPCR data to confirm knockdown levels of PVT1. Proliferation assays were also conducted to explore the proliferative abilities of cells when PVT1 levels were decreased. Transfection of PVT1 with siRNA yielded about a 50% knockdown, while ASO targeting brought PVT1 levels down 80%. PVT1 inhibition had different effects on the level of c-Myc in cells depending on the method of transfection used--while transfection with anti-PVT1 siRNAs slightly decrease the amount of c-Myc protein in the cell, transfection using ASOs significantly increases c-Myc. Most importantly, proliferation of DU145 cells decreased with PVT1 knockdown by ASOs. Removal of this lncRNA, therefore, hinders that oncogenic potential for growth of prostate cancer cells. Since Myc poses a difficult target for cancer therapy, any new method to mitigate its oncogenic signaling would be invaluable. Targeting lncRNA PVT1 may be a successful method of doing just that, but more work needs to be done to explore the effects of different knockdown strategies. It is clear, however, that the relationship between Myc and PVT1 is a convoluted interaction that warrants further research. A breakthrough in this area could lead to huge improvements in the way prostate cancer is diagnosed and treated.

The Epidemiology of Prostate Cancer Among Multiethnic Men

Kellier, Nicole 21 October 2011 (has links)
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.

In Vitro Effects of Bisphenol A on Prostate Cells: Searching for Clues of Environmental Carcinogenesis

Sienkiewicz, Marta January 2012 (has links)
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.

Temporal Changes in Prostate Biopsy Use in Ontario

Lavallée, Luke Thomas January 2016 (has links)
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.

Cytoskeletal Dynamics and cellular differentiation influence tumor progression and metastatic potential in Prostate Adenocarcinoma

Donald, Carlton Dewitt 01 July 1997 (has links)
Cancer cell attachment to and invasion of an extracellular matrix has been associated with metastatic potential. Recently it has become apparent that the extracellular matrix may influence several phenotype properties of metastatic cancer cells. The mechanisms which regulate prostate cancer growth and metastasis may be particularly relevant to the development of clinical strategies for better understanding and ultimate treatment and control of the disease. Cell-matrix interactions of prostate tumor cells were investigated by comparing the invasive ability through and attachment to reconstructed extracellular matrix components. A correlation was found between metastatic potential and adhesive ability. Non-metastatic AT-1 cells possessed a higher adhesive potential to extracellular matrix components than the highly metastatic cells (Mat-Lu, Mat-LyLu and AT-3) which had higher invasive potentials.

Characterisation of epidermal growth factor receptor (EGF-R) in the human prostate

Maddy, Samuel Quarcoo January 1988 (has links)
No description available.

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