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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.

TINT Tumor Indicating Normal Tissue : new field of diagnostic biomarkers for prostate cancer

Adamo, Hanibal Hani January 2016 (has links)
Background: Prostate cancer is the most common cancer in Sweden. Due its highly variable behavior, multifocal nature, and insufficient diagnostic methods, prostate cancer is difficult to diagnose and prognosticate. Some patients have an aggressive lethal disease, but the majority of prostate cancer patients have slow-growing, non-lethal disease with long expected survival without treatment. Current diagnostic methods―serum levels of prostate-specific antigen (PSA) and histological grading of biopsied prostate tissue―often do not give the information required to be able to safely differentiate indolent tumors from potentially lethal ones. Many prostate cancers are difficult to detect by imaging, so tissue biopsy cannot be safely guided towards the tumor, and particularly not towards the most aggressive forms. To overcome this problem, multiple needle biopsies are taken from the organ, but biopsies are small and they sample less than 1% of the whole prostate. In this thesis, we explore the non-malignant prostate tissue adjacent to tumors, which is always sampled in biopsies, and we study adaptive changes in this tissue, which may provide new diagnostic and prognostic markers for prostate cancer. We have therefore proposed that this type of tissue should be termed TINT (Tumor Instructed/indicating Normal Tissue).  Methods: In our studies, we used orthotopic rat prostate cancer models with tumors of different aggressiveness. We also used clinical materials from patients diagnosed with prostate cancer at transurethral resection (1975‒1990); the majority of these men were followed with watchful waiting. Analyses were performed with whole-genome expression array, quantitative real-time PCR, immunohistochemistry, and western blotting.  Results: Using the animal model, we found that the presence of a tumor induces changes in gene expression in the surrounding tumor-bearing organ (TINT). The gene signature of TINT was linked to processes such as extracellular matrix organization, immune responses, and inflammation. We also showed that some of these adaptive TINT changes appear to be related to the aggressiveness and metastatic potential of the growing tumor, such as increases in macrophages, in mast cells, in vascular densities, and in vascular cell-proliferation. Some of these findings were confirmed by our observations in patient samples. We found that high staining of the extracellular matrix component hyaluronan in the stroma of the non-malignant prostate tissue was prognostic for short cancer-specific survival. We also found that an elevated proportion of C/EBP-beta positive epithelial cells in non-malignant (TINT) prostate tissue was associated with a good prognosis.  Conclusions: Using animal experiments and patient samples, we showed that the presence of prostate cancer induces changes in the tumor-bearing organ, alterations associated with tumor aggressiveness, and that grading of these changes in TINT can be used to predict outcome in prostate cancer patients.

Measurement of individualised quality of life in patients with prostatic adenocarcinoma

Pearcy, Richard Malcolm January 2003 (has links)
No description available.


Jiang, Hongmei 01 August 2014 (has links)
Accounting for 14% of all new cancer diagnosis in the United States, prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer related death in the United States. Prognosis for patients diagnosed with metastatic disease is especially poor, since no effective treatments have been developed (1). In this study, we examined the expression and function of POU5F1B, a protein-encoding pseudogene of the homeodomain transcription factor Oct4, in prostate cancer. POU5F1B is located at 8q24, a "gene desert" containing numerous alleles associated with prostate cancer risk. A recent study has indicated that a number of these risk alleles are correlated with POU5F1B expression and prostate cancer susceptibility. The role of POU5F1B in prostate cancer carcinogenesis and progression, however, is not known. In our study, we found that POU5F1B expression is upregulated in prostate cancers and highly overexpressed by high grade (Gleason ≥8) and metastatic prostate cancers. We cloned POU5F1B from prostate cancer cell lines, which contains prostate cancer risk associated SNPs, including a missense mutation inside the homeobox DNA binding domain, to study the functional effects of POU5F1B overexpression in prostate cancers. Here, we report that POU5F1B from prostate tumor encodes functional proteins that exhibit gene transactivation activity comparable to its parent gene, Oct4. Further, we report that POU5F1B overexpression in prostate cancer cell lines increases prostate cancer cell proliferation, migration, anchorage independent growth, and drug resistance in vitro and tumor xenograft growth in vivo. Conversely, shRNA mediated knockdown of endogenous POU5F1B expression in prostate cancer cells inhibit cell proliferation in vitro and tumor growth in vivo, as well as prolong tumor free survival in animal models. The data provide compelling evidence that POU5F1B is an important mediator of prostate cancer progression. We further examined the molecular mechanism behind POU5F1B driven prostate cancer progression. Our studies found that POU5F1B overexpression suppresses E-Cadherin expression at both mRNA and protein levels. Our studies further found POU5F1B overexpression in prostate cancer cells increases Wnt1, TCF1, and TCF4 expression, as well as increased Wnt/β-Catenin signaling - indicating the induction of epithelial-to-mesenchymal transition (EMT) in POU5F1B overexpressing cells(2). Consistently, qPCR analysis found that POU5F1B overexpression significantly increased the expressions of numerous EMT related genes and prostate cancer stem cell markers. Functional studies further confirmed that the transactivation activity of Nanog, another stem cell related transcription factor, is dramatically increased in POU5F1B overexpressing cells. Taken together, our data strongly suggests that POU5F1B overexpression drives prostate cancer progression through the induction of EMT and conferment of stem-cell properties to tumor cells. In summary, our data demonstrated that POU5F1B is overexpressed in prostate tumors, especially high-grade and metastatic tumors, and is a functional driver of prostate cancer progression by inducing EMT in prostate cancer cells. Our study also showed that POU5F1B can potentially be targeted to treat prostate cancer. Based on our findings, depletion of POU5F1B may reduce the risk of metastatic disease or tumor recurrence when used with concurrent therapies in early state tumors and may attenuate treatment resistance in diseases at advanced stages.

ADAMs as EGFR ligand sheddases in prostate cancer

Willems, Sofie Henriëtte January 2011 (has links)
No description available.

A study of Hes6 as a transcriptional regulator in castrate resistant prostate cancer

Lamb, Alastair David Gordon January 2012 (has links)
No description available.

A study of kinases at the interface between metabolic stress and cell cycle control in prostate cancer

Bon, Hélène January 2013 (has links)
No description available.

Generating small molecules and biological tools towards overcoming prostate cancer

Cheung, Samantha Pui San January 2011 (has links)
No description available.

The natural history of prostate cancer in the preclinical phase

Pashayan, Nora January 2011 (has links)
No description available.

Changing narratives of prostate cancer 1990-2010

Montgomery, Anne January 2015 (has links)
Prostate cancer (PCa) is a unique and controversial disease. This is at least due to the high prevalence of latent disease, increasing amounts of which is being diagnosed, most of which is indolent and not lead to death, and for which treatment carries significant risks. An increasing concern in medical sociology is how various social structures and actors contribute to the diagnosis and experience of conditions. For PCa, these include print media as an information source for men with prostate cancer (MWPCa), and PCa organisations (PCaOrgs) which have recently emerged in the UK. Yet, there is a distinct lack of UK studies of print media representation of PCa, of PCaOrgs, interaction between the two, and how any of this may impact on the experience of MWPCa. This thesis aims to address this deficit by drawing on narrative and framing theory to study 201 illness narratives of PCa across time: 140 illness narratives of MWPCa in UK newspapers 1990-2010; 20 with MWPCa interviewed in each of 2000 and 2010; and 21 with advocates around PCaOrgs in 2010. I ask: how have PCaOrgs and the UK print media been a force for change in the UK regarding how PCa is addressed and experienced by MWPCa? And more broadly what does this say about narrative structure and form. My findings indicate that though PCaOrgs and print media told stories of injustice around PCa, the substantive focus of this injustice changed over time—from PCa as “neglected” and “taboo” in the 1990s to other “pockets of injustice” since 2000. While one might expect that this to lessen any interactional difficulty that MWPCa experience in disclosing their illness, my study suggests this may not be so. My findings show how ideas of resonance and dissonance contribute to understanding the recursive and repetitive language around PCa.

Delineating a functional role for the urinary biomarker Lipocalin 2 in prostate cancer

Hazan, Allon January 2014 (has links)
Prostate cancer (PCa) is the most commonly diagnosed cancer amongst Western males. PCa progression is strongly linked to steroid receptor signalling, however the modulation of steroid receptor expression in PCa is incompletely understood. Lipocalin 2 (LCN2) is a secreted protein which binds to Fe3+-containing siderophores and was originally identified as part of the innate immune response. LCN2 has been proposed as a potential biomarker for a range of cancers. However, LCN2 effects appear to be tissue specific. LCN2 expression is associated with poor prognosis in breast cancer, but with good prognosis in pancreatic cancer where it has been used therapeutically. The role of LCN2 in prostate cancer is poorly understood, in particular its effects on steroid receptor regulation. To elucidate the role of LCN2 in prostate cancer, the LCN2 gene was ectopically expressed in LNCaP cells to generate the LNCaP-LCN2 cell line. LNCaP-LCN2 cells had elevated androgen receptor expression which was linked to increased levels of KLK3 (PSA). LNCaP-LCN2 cells also had reduced levels of Estrogen receptor α (ERα), but increased expression of ERβ. This was combined with higher levels of E-cadherin, but not to changes in other EMT markers. Reciprocally, LCN2 was suppressed using RNAi in the PC3 cell line to generate PC3-shLCN2 cells. PC3-shLCN2 displayed a distinct change in morphology, with increased cell size and a sub-population of multi-nucleated and highly enlarged cells. PC3-shLCN2 cells had reduced proliferation, and lost the ability to form colonies in a 3D substrate. With regards to steroid receptors, PC3-shLCN2 cells had increased ERα expression, but reduced ERβ expression. This was also combined with a loss of E-cadherin and EGFR. Microarray analysis of PC3-shLCN2 cells identified changes to expression of a wide range of genes including VEGF-R, SPARC and KLK6. Functional grouping of differentially expressed genes suggests that LCN2 in involved in a range of cellular processes including hormone receptor response, Wnt signalling and cell cytoskeletal integrity. Many, but not all genes identified by microarray were responsive to recombinant LCN2 protein indicating a paracrine function for the protein. Treatment of PC3 cells with the iron chelator Deferoxamine resulted in phenotypic changes similar to those found in PC3-shLCN2 cells which suggest that LCN2 functions in part due to intracellular iron regulation. In summary, the data presented in this thesis suggests that LCN2 has both pro- and anti- tumourigenic properties in prostate cancer and that the protein is involved in a much wider range of functions than previously described.

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