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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.
61

Role of PAX2 in Maintaining the Differentiation of Oviductal Epithelium and Inhibiting the Transition to a Stem Cell State

Alwosaibai, Kholoud January 2016 (has links)
Several studies have proposed the fallopian tube epithelium as a site of origin of ovarian cancer. The discovery of precursor lesions in the fallopian tube in patients at risk for ovarian cancer supports a probable origin for high-grade serous ovarian carcinoma in this tissue. While the fallopian tube epithelium consists of three distinct cell types, the paired box protein 2 (PAX2) positive cells and potentially the CD44 positive stem-like cells are most relevant to ovarian cancer. Loss of PAX2 expression in the fallopian tube cells is considered to be an early event in epithelial transformation, but the specific role of PAX2 in this transition is unknown. The aim of this study was to define the role of PAX2 in oviductal epithelial cells (OVE) cells and in mouse ovarian surface epithelial cells (MOSE), and to understand its contribution to the formation of serous precursor lesions in the fallopian tubes. Herein, we studied the OVE response to transforming growth factor β (TGFβ, a cytokine found in follicular fluid) and provide evidence of its potential involvement in the regulation of stem cell-like behaviors that may contribute to formation of cancer-initiating cells. Treatment of primary cultures of OVE cells with TGFβ at concentrations found in ovulatory follicular fluid induced an epithelial-mesenchymal transition (EMT) with expected changes in proliferation, cell morphology and expression of SNAIL, Vimentin and E-cadherin. EMT was also associated with decreased expression of PAX2 and an increase in the fraction of cells expressing CD44. Pax2 knockdown in OVE cells and overexpression in ovarian epithelial cells confirmed that PAX2 inhibits CD44 expression and regulates the degree of epithelial differentiation of OVE cells. These results suggest that the loss of PAX2 seen in serous tubal intraepithelial carcinomas (STIC) leads to a shift to a more mesenchymal phenotype associated with stem-like features. Pax2 overexpression in MOSE cells also induced the formation of vascular channels both in vitro and in vivo, which indicate a possible contribution of PAX2 to ovarian cancer progression by increasing the vascular channels to supply nutrients to the tumor cells. Furthermore, since loss of PAX2 in STIC was found associated with P53 and BRCA1 mutations, OVE cells with mutations of the tumor suppressor genes Trp53 and Brca1 were studied. We found that loss of Trp53 with or without loss of Brca1 increased cell proliferation and colony formation in vitro. In addition, loss of Trp53 induced OVE cells to undergo EMT and induced the expression of stem cell–associated genes. We therefore suggest a potential contribution of stem cells in initiating the precursor lesions in the fallopian tubes in combination with tumor suppressor gene mutation.
62

The Impact of Adipose-Associated Stromal Cells on the Metastatic Potential of Ovarian Cancer

Shea, Amanda A. 22 January 2014 (has links)
Obesity is a major global health concern due to its steadily increasing rates and significant contribution to numerous diseases, including cancer. Ovarian cancer specifically, is associated with a 30% increased risk with obesity, although the mechanisms for this are unknown. Waist-to-hip ratio has been especially associated with ovarian cancer, suggesting that visceral fat may be the greatest contributor. Here, we investigated individual visceral fat depots as independent contributors to cancer progression, specifically focusing on adipose tissue-derived stem and progenitor cells, which have previously been shown to be recruited by cancer cells and participate in cancer progression. We confirmed that ovarian cancer tumor burden was indeed significantly increased in mice on a high fat as compared to low fat diet. To further investigate mechanisms, we examined changes in progenitor populations that occurred in intra-abdominal parametrial (pmWAT), retroperitoneal (rpWAT), and omental (omWAT) white adipose tissue (WAT) depots with cancer presence. The greatest tumor burden was evident in omWAT, which also displayed an increase in CD45- cells but a decrease in adipose progenitor cells (APC) and endothelial progenitor cells, suggesting that there was an increase in stromal cells, but that the stem cells were pushed towards differentiation. PmWAT and rpWAT showed remarkably stable progenitor populations. However, a tumor from pmWAT had a significant presence of CD45- cells, actually matching that of its surrounding tissue and differing from the omWAT tumors, indicating that microenvironment has a major influence on tumor stromal cells. We also found that with high fat diet, many cancer-associated changes were exacerbated, such as an increased inflammatory response in all tissues and further decreases in APCs in omWAT. In vitro studies further confirmed that ovarian cancer cells and SVF cells were able to directly interact. Additionally, SVF cells were able to increase the proliferation, mobility, and invasiveness of cancer cells. Conversely, co-culturing also enhanced the proliferation and mobility of SVF cells, providing further evidence that SVF cells may be recruited by cancer cells and that their relationship may be bilateral. Thus, this study provides a good foundation for examining the cellular contributions of adipose tissue to cancer. By further characterizing the mechanism for the association between obesity and cancer development, we could find novel targets to decrease the progress of cancer development in at-risk obese individuals. / Ph. D.
63

Impact of obesity on stromal vascular fraction in adipose tissue as it relates to ovarian cancer

Davis, Grace Nicole 18 May 2020 (has links)
Ovarian cancer is considered to be one of the deadliest gynecological diseases. Over 21,000 women are expected to be diagnosed with this fatal disease in 2020 alone. Obesity, but more specifically a high waist-to-hip ratio, is indicative of abdominal obesity and has been correlated with increased risk of ovarian cancer. How abdominal obesity contributes to this increased risk has not been clearly delineated but much of the current research has been focused on the role of adipocytes. However, in addition to the adipocytes, abdominal white adipose tissue contains the stromal vascular fraction (SVF) which includes stem and progenitor cell populations, immune cells, and fibroblasts. Since the SVF can also be recruited by the cancer cells, we investigated how obesity affects the survival and metastatic potential of cancer cells by investigating changes in the expression of genes that contribute to survival, proliferation, migration, adherence, and invasion. We used culture conditions that mimic the non-permissive peritoneal environment. Cancer related genes, such as Dkc1, Ccnd2, Lig4, and Snai2, were upregulated when adipose derived stem cells (ADSC) were added into MOSE-LTICv spheroids. It was found that peritoneal serous fluid (PSF) from obese mice significantly increased migration of MOSE-LTICv (Serum vs PSF, 517.8 vs 1158.6). These studies brought new knowledge into the field of obesity and ovarian cancer risk and provided direction for future studies involving potential cellular and molecular targets for ovarian cancer diagnosis and treatment. / Master of Science / Ovarian cancer affects many women in the United States. Obesity or more specifically, carrying more weight around the waist, can affect a woman's risk of developing ovarian cancer. Abdominal fat needs to be researched to see if abdominal obesity can affect ovarian cancer on the cellular level. Researchers have looked into how fat cells, known as adipocytes, can affect the progression of ovarian cancer, but more research needs to be done on the contributions of other cells found within adipose tissue. Other cells in abdominal fat include cells such as immune cells, stem and progenitor cells and fibroblasts. We have explored how adipose stem cells from obese mice affect the DNA or "the blueprints" of the cells, survival, and progression of mouse ovarian cancer cells. We found that when adipose stem cells are combined with ovarian cancer cells the expression of certain genes or particular "blueprints" increased. The genes whose expression increased included Dkc1, Ccnd2, Lig4, and Snai2 and when deregulated can cause ovarian cancer cells to become more aggressive. The abdominal fluid from obese mice was found to increase migration of ovarian cancer cells which simulates an increase in metastatic potential. This information has given new insight into the obesity and ovarian cancer relationship.
64

Identification of novel microRNAs as potential biomarkers for the early diagnosis of ovarian cancer using an in-silico approach

Zahra, Latib January 2019 (has links)
Philosophiae Doctor - PhD / Ovarian cancer (OC) is the most fatal gynaecologic malignancy that is generally diagnosed in the advanced stages, resulting in a low survival rate of about 40%. This emphasizes the need to identify a biomarker that can allow for accurate diagnosis at stage I. MicroRNAs (miRNAs) are appealing as biomarkers due to their stability, non-invasiveness, and differential expression in tumour tissue compared to healthy tissue. Since they are non-coding, their biological functions can be uncovered by examining their target genes and thus identifying their regulatory pathways and processes. This study aimed to identify miRNAs and genes as candidate biomarkers for early stage OC diagnosis, through two distinct in silico approaches. The first pipeline was based on sequence similarity between miRNAs with a proven mechanism in OC and miRNAs with no known role. This resulted in 9 candidate miRNAs, that have not been previously implicated in OC, that showed 90-99% similarity to a miRNA involved in OC. Following a series of in silico experimentations, it was uncovered that these miRNAs share 12 gene targets that are expressed in the ovary and also have proven implications in the disease. Since the miRNAs target genes contribute to OC onset and progression, it strengthens the notion that the miRNAs may be dysregulated as well. Using TCGA, the second pipeline involved analysing patient clinical data along with implementing statistical measures to isolate miRNAs and genes with high expression in OC. This resulted in 26 miRNAs and 25 genes being shortlisted as the potential candidates for OC management. It was also noted that targeting interactions occur between 15 miRNAs and 16 genes identified through this pipeline. In total, 35 miRNAs and 37 genes were identified from both pipelines.
65

Finding Combination of Features from Promoter Regions for Ovarian Cancer-related Gene Group Classification

Olayan, Rawan S. 12 1900 (has links)
In classification problems, it is always important to use the suitable combination of features that will be employed by classifiers. Generating the right combination of features usually results in good classifiers. In the situation when the problem is not well understood, data items are usually described by many features in the hope that some of these may be the relevant or most relevant ones. In this study, we focus on one such problem related to genes implicated in ovarian cancer (OC). We try to recognize two important OC-related gene groups: oncogenes, which support the development and progression of OC, and oncosuppressors, which oppose such tendencies. For this, we use the properties of promoters of these genes. We identified potential “regulatory features” that characterize OC-related oncogenes and oncosuppressors promoters. In our study, we used 211 oncogenes and 39 oncosuppressors. For these, we identified 538 characteristic sequence motifs from their promoters. Promoters are annotated by these motifs and derived feature vectors used to develop classification models. We made a comparison of a number of classification models in their ability to distinguish oncogenes from oncosuppressors. Based on 10-fold cross-validation, the resultant model was able to separate the two classes with sensitivity of 96% and specificity of 100% with the complete set of features. Moreover, we developed another recognition model where we attempted to distinguish oncogenes and oncosuppressors as one group from other OC-related genes. That model achieved accuracy of 82%. We believe that the results of this study will help in discovering other OC-related oncogenes and oncosuppressors not identified as yet.
66

The evolution of hyperthermic intraperitoneal chemotherapy in the setting of advanced ovarian cancer

Quindlen, Kevin John 14 June 2019 (has links)
Ovarian cancer is the second most common, and first most lethal gynecological cancer. It will affect one in seventy-eight women, and is commonly diagnosed in the later stages of the disease. The majority of the cancer’s lifespan is spent within the peritoneal cavity. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an innovative new treatment that has been proven as an effective treatment in other peritoneal cancers. There is strong scientific evidence to support HIPEC as an ideal treatment for advanced ovarian cancer. Over the past two decades, there has been an increase in the number of studies focused on the efficacy of HIPEC with regards to advanced ovarian cancer. These studies have shown great promise, with two very recent phase III studies showing resounding results. It is also clear that there is a need for standardization throughout these scientific studies in order to reasonably introduce HIPEC as a standard of treatment.
67

Contactless Dielectrophoresis towards Drug Screening and Microdevice Development for Cell Sorting

Elvington, Elizabeth Ashcraft Savage 08 July 2013 (has links)
Firstly, this work demonstrates that contactless dielectrophoresis (cDEP) was useful to detect a reversal in the electrical phenotype of late-stage ovarian cancer cells to a profile similar to that of slow-growing early-stage ovarian epithelial cells after treatment with a non-toxic bioactive metabolite, sphingosine. Current chemotherapeutics are highly toxic to patients and can cause severe adverse side effects, so non-toxic treatments that could slow or reverse cancer growth would be advantageous. This is the first instance of cDEP for detecting induced changes in cell structure, showing its potential as a rapid, non-biomarker-based drug screening platform. Specifically, low frequency contactless dielectrophoresis devices previously designed by Sano et al were used to extract the crossover frequency and specific membrane capacitance of early and late stage mouse ovarian surface epithelial (MOSE-E and MOSE-L) cells when untreated, treated with the anti-cancer sphingosine (So) metabolite and with a generally cancer-supporting sphingosine-1-phosphate (S1P) metabolite. The specific membrane capacitance of MOSE-L cells treated with So decreased and the normalized crossover frequency increased to levels matching MOSE-E cells. Secondly, a new multilayer cDEP device featuring curved interdigitated electrode channels overlaying a straight sample channel for the purpose of cell sorting was designed, computationally modeled, fabricated, and tested. The goal of this design was to achieve continuous multi-stream sorting of cells, and preliminary testing demonstrated that prostate cancer PC3 cells were continuously deflected toward the top of the channel under an electric field, as predicted by the numerical model. / Master of Science
68

Hospital Based Traceback of Ovarian Cancer Patients: a Feasibility Study

Weinmann, Simone Marin January 2021 (has links)
No description available.
69

The Monkey in the Wrench: MiR-181a's Role in Promoting Adipogenesis and Ovarian Cancer Transformation

Knarr, Matthew J. 23 May 2019 (has links)
No description available.
70

Modulating Lipid Flux Sensitizes Tumours in a Fatty Tumour Microenvironment to Oncolytic Virus Therapy

Abera, Surendran 14 July 2022 (has links)
No description available.

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