Real-World Use Of Bevacizumab For Treatment Of Advanced Ovarian Cancer Among Elderly Women In The U.S., Janet Hildebrand

MUSC Theses and Dissertations

Bevacizumab, a targeted VEGF inhibitor, is recommended for treatment of advanced ovarian cancer based on clinical trials demonstrating improved progression-free survival when added to standard chemotherapy. This study describes demographic, clinical and social factors, and outcomes associated with bevacizumab use among ovarian cancer patients in the US Medicare 5% sample. Kaplan-Meier curves and propensity score-weighted Cox proportional hazards models were used to estimate overall survival (OS) comparing bevacizumab to non-bevacizumab regimens. Of 3,760 patients with a principal diagnosis of ovarian cancer from 2016 to 2019, 1,508 had at least one observed line of chemotherapy; 457 had a second line following …

Ovarian Cancer Survivorship Checklist, Emily Lott

Seton Hall University Dissertations and Theses (ETDs)

Background: The cancer survivorship population has been growing significantly in the last few years due to advancements in treatments such as immunotherapy, targeted medications and other types of chemotherapy. However, these survivors can have lifelong symptom burdens due to their diagnoses and adverse effects of their curative therapies. Symptoms are not always physical and can include emotional distress. Ovarian cancer patients in particular tend to have symptom complications because of their disease process. Symptoms include pain, constipation, neuropathy and fatigue. Ovarian cancer patients also experience a high level of cancer relapses. Early detection is key in cancer recurrences for patients …

Data-Driven Biomarker Panel Discovery In Ovarian Cancer Using Heterogenous Data Fusion On Exosomal And Non-Exosomal Microrna Expression Data, Paritra Mandal

All Dissertations

Ovarian cancer (OC) is an aggressive gynecological cancer and is currently the 5th leading cause of deaths due to cancer in women. High mortality rates are attributable to the vague pathogenesis and asymptomatic nature of the early stages. The development of a liquid biopsy for routine OC screening could help identify the disease at an earlier stage, making treatments more likely to be effective thereby increasing survival rates. Exosomes, small (~100nm) extracellular vesicles present in body fluids, have been shown to contain cancer-progression, onset, and related factors, making them good candidates for use in liquid biopsies. However, to date, only …

Enhancing Quality Of Life For Ovarian Cancer Patients, Kelly Marie Liguori

Doctor of Nursing Practice Scholarly Projects

Problem Statement: Ovarian cancer is associated with a delayed onset of symptoms and late diagnosis and therefore has increased morbidity and mortality (Momenimovahed et al., 2019). These patients face multiple health complications, frequent hospital admissions, and may suffer from an overall poor quality of life (Marks, 2020). Purpose: This project aimed to determine if implementing FACT-O, a patient-reported quality-of-life screening tool, led to increased pastoral care consults and patient-reported quality-of-life for ovarian cancer patients. Methods: Iowa Model of Evidence-Based Practice was used for this project. Upon admission to 3Tower at CMC Main during a 3-month period, all patients with ovarian …

Inducing Alternative Forms Of Cell Death In Multidrug Resistant Ovarian Cancer, Chloe Reese Kotrba

Undergraduate Honors Thesis Collection

Ovarian cancer remains the deadliest gynecological cancer for women today. In 2021, an estimated 21,410 new cases of ovarian cancer were diagnosed in the US, and approximately 13,770 of these women will not survive the disease[2]. This malignancy’s low survival rate is attributed to late diagnoses, as well as the cancer’s tendency to recur after chemotherapy treatment due to acquired drug resistance. The standard of care for this disease includes surgery and chemotherapy. One of the commonly used chemotherapeutic drugs is cisplatin, which works by inducing a programmed form of cell death known as apoptosis. However, many ovarian cancer tumors …

Targeting Metabolic Adaptations To Anti-Angiogenic Therapy In Ovarian Cancer, Deanna M. Glassman, Deanna Glassman

Dissertations & Theses (Open Access)

ABSTRACT

Background: Ovarian cancer is the most lethal gynecologic malignancy. Despite modest clinical improvements with anti-VEGF antibody (AVA) therapy, adaptive resistance is nearly ubiquitous and additional therapeutic options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance.

Purpose: To assess the efficacy of a glutaminase inhibitor as a means of exploiting the metabolic vulnerability of glutamine dependence that develops as a result of adaptive resistance to AVA therapy.

Experimental Design: We used a glutaminase inhibitor (GLSi) synthesized at MD Anderson Cancer Center for all in vitro and in vivo experiments. …

Increasing Genetic Testing Rates To Improve Early Detection And Prevention Of Breast And Ovarian Cancer In Women, Makensey Beth Durrant

UNLV Theses, Dissertations, Professional Papers, and Capstones

Screening rates for cancer related genetic mutations are low in the primary care setting, despite evidence-based guidelines recommending screening in all patients who meet criteria. Genetic mutations, such as the breast cancer susceptibility 1 and 2 (BRCA1/2) gene mutations, drastically increase breast and ovarian cancer risk in patients. The United States Preventive Services Task Force (USPSTF) and the National Comprehensive Cancer Network (NCCN) provide evidence-based guidelines on criteria for genetic testing in women at risk for breast and ovarian cancer related gene mutations. Primary care providers (PCPs), including advanced practice registered nurses (APRNs), are at the front lines of preventative …

Crosstalk Between Hippo And Rb Tumour Suppressor Pathways In Ovarian Cancer, Fatmata Sesay

Theses and Dissertations

The cell cycle is a highly regulated process that ensures the timely and accurate division of cells. Events of the normal cell cycle fall under two categories - positive and negative regulatory mechanisms. The first category, positive regulatory machinery, includes active protein complexes of cyclins in association with their partnering cyclin-dependent kinases (cyclin/CDK), which mediate series of phosphorylation events that relay a cell cycle progression from one stage to the next. The second category, the negative regulatory mechanisms, include the checkpoint controls consisting of the retinoblastoma (RB) family of proteins, some of which can form a transcriptional repressor complex DREAM. …

Molecular Mechanism And Impact Of Sox2 Regulation By The Transforming Growth Factor-Ss Members In Ovarian Cancer Survival And Metastasis, Zainab Shonibare

All ETDs from UAB

Ovarian cancer is the second most common and deadliest cancer of the female reproductive system affecting women in the United States and worldwide. The poor survival outcome seen in ovarian cancer is attributed to the subtleness of its early-stage symptoms, resulting in a majority of patients at initial diagnosis presenting with an advanced-stage disease with metastasis to other parts of the body. Hence, there is an urgent need to better understand the molecular etiology of metastasis to help develop effective therapeutic options and improve clinical outcomes in ovarian cancer patients. Ovarian cancer, an intra-abdominal cancer, most preferably undergoes metastasis via …

Novel Peptide Biomaterials For Enhanced Delivery Of Sirna Cargo For Treatment Of Ovarian Cancer, Timothy Samec

All Dissertations

Ovarian cancer is the 7^th leading cause of cancer related death and the 5^th most commonly diagnosed cancer among women. Primarily diagnosed in stage III or stage IV, aggressive treatment is necessary and involves surgical debulking and administration of systemic chemotherapeutics. Unfortunately, these strategies fall short in effectively treating ovarian cancer and many patients experience local disease recurrence, development of multidrug resistant tumors, regional or distant metastatic events, or a combination of the three. As such, there is a significant need for additional treatment options and methods of delivery to improve therapeutic efficacy and disease survivability.

RNA interference …

Development Of Quantitative Molecular Photoacoustic Imaging For Noninvasive Cancer Diagnostics, Cayla Zandbergen

Dissertations & Theses (Open Access)

Traditional diagnostic imaging provides clinicians with anatomical information that guides both diagnosis and treatment planning; however, once a tumor has progressed enough to be visible, it has often reached an advanced stage. Molecular imaging techniques allow for real-time visualization of chemical and biological processes via imaging of specific biomarkers, which can facilitate detection of malignancies before they become visible. One biomarker of interest is blood oxygen saturation (SO₂) due to its correlation with hypoxia, which is associated with increased tumor malignancy; some studies have also established SO₂ as an independent biomarker of disease progression. Additionally, because cancerous …

Diabetes, Anti-Diabetic Medication Use, And The Risk Of Ovarian Cancer, Chantaezia Joseph

Theses and Dissertations

Background- Although ovarian cancer is a rare disease, it is the 5th leading cause of cancer-related deaths among women in the United States. Diabetes is a serious chronic disease that plagues over 436 million adults worldwide and was ranked 7th in causes of death in the US in 2017. Epidemiologic evidence suggests that diabetes may lead to an increased risk of ovarian cancer due to shared risk factors such as sedentary behaviors, smoking and poor diet or through biological mechanisms related to hyperglycemia and obesity, but the epidemiologic evidence yields mixed results. Certain anti-diabetic medications may increase the risk …

Breastfeeding Information And Breastfeeding Duration Among African American Women With A Family History Of Breast Or Ovarian Cancer, Aleatha Johnson

Walden Dissertations and Doctoral Studies

Decades of research supports the notion that breastfeeding may help prevent breast and ovarian cancer in women. Women with a family history of these cancers are at greater risk. African American women have the lowest breastfeeding rates, yet the highest breast and ovarian cancer mortality rates. No studies have been conducted exploring the impact of being informed about breastfeeding from health care providers, breastfeeding support services, or family and friends and the relationship between their knowledge of family history of breast or ovarian cancer and breastfeeding duration for African American women. The purpose of this quantitative study was to determine …

Eukaryotic Initiation Factor 5a2 (Eif5a2) Contributes To Ovarian Tumor Growth And Metastasis, Guannan Zhao

Theses and Dissertations (ETD)

Ovarian cancer has the highest mortality rate among all gynecological malignancies due to lack of effective biomarkers for early diagnosis. The majority of ovarian cancer patients are already at an advanced stage when diagnosed. In addition, ovarian cancers often become chemoresistant and metastatic, and recur following initial chemotherapy.

Directed Evolution Of Macrocyclic Peptides For Inhibition Of Autophagy, Joshua Gray

Dissertations & Theses (Open Access)

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of …

Formulation And Validation Of Nanoparticle Controlled Delivery For Chemotherapeutic Drug Products, Shani L. Levit

Theses and Dissertations

Taxol, a formulation of paclitaxel (PTX), is one of the most widely used anticancer drugs, particularly for treating recurring ovarian carcinomas following surgery. Clinically, PTX is used in combination with other drugs such as lapatinib (LAP) to increase treatment efficacy. Delivering drug combinations with nanoparticles has the potential to improve chemotherapy outcomes. In this study, we use Flash NanoPrecipitation, a rapid, scalable process to encapsulate weakly hydrophobic drugs (logP in vitro. Encapsulating either PTX or LAP into nanoparticles increases drug potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than …

Identifying And Targeting Adaptive Changes To Bet Inhibition In Ovarian Cancer, Christopher Lafargue

Dissertations & Theses (Open Access)

Purpose: To identify combination strategies using Bromodomain and Extra-Terminal Domain (BET) inhibitors in a mechanism driven fashion to maximize anti-tumor activity, and to determine the efficacy of BET inhibitor combinations in pre-clinical ovarian cancer mouse models.

Experimental Design: We used a novel, previously uncharacterized pan-BET inhibitor, CN210, for all in vitro (MTT, apoptosis, protein expression, reverse phase protein array (RPPA) analysis and in vivo (orthotopic mouse model)) experiments. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib, as well as the mechanistic target of rapamycin (mTOR) inhibitors rapamycin and INK-128 were also used. Statistical analyses of in vitro and in vivo experiments …

In Vitro Evaluation Of Ovarian Cancer Tumorigenesis As A Function Of Quinone Oxidoreducatse-1 And Cell Phenotype, Milcah S. Jackson

LSU Doctoral Dissertations

In vitro multicellular spheroids are attractive model systems for assessing genetic and epigenetic changes that occur in diseased tissues. Understanding how such alterations in gene and subsequent protein expression affect disease progression and metastasis, drug resistance, and recurrence is of great interest in cancer research. In this regard, examining expression and activity of proteins, such as those with cytoprotective ability that are overexpressed in cancer cells, in addition to cell phenotype (i.e., stem-like, epithelial, mesenchymal, or mixed), are two ways to evaluate genetic and epigenetic changes. Moreover, determining the impact that cytoprotective proteins and cell phenotype have on tumor formation …

Cellular Localization Of Rad51d Mutant Proteins And The Application Of Art To Increase Scientific Literacy In America, Claire L. Chabot

Senior Theses

Ovarian cancers are the leading cause of death from cancer of the female reproductive system. Approximately 50% of ovarian cancers have defects in the homologous recombination (HR) DNA repair pathway that is required for the repair of DNA double-stranded breaks. The status of HR genes, such as BRCA1, BRCA2, and the RAD51 family, contributes to ovarian cancer development as well as treatment decisions regarding chemotherapy, radiation, and immunotherapy. The overarching goal of this project is to identify new insights into HR that can integrate with Precision Medicine Initiatives and align with the goals of the Cancer Moonshot 2020 Program. I …

Pathophysiology Of Ovarian Cancer, Christina Eagle

Nursing Student Class Projects (Formerly MSN)

This poster project is a culmination of evidence-based practice research conducted to educate on the lethality of ovarian cancer and the importance of early detection of the vague signs and symptoms associated with this disease. Worldwide, approximately 240,000 women are diagnosed with ovarian cancer each year, and 140,200 were projected to succumb to this disease in 2016 (Kroeger, Jr. & Drapkin, 2017). This case-to-fatality ratio is nearly three times that of breast cancer, making ovarian cancer the most lethal gynecological malignancy in developed countries (Kroeger, Jr. & Drapkin, 2017). Educating women about the risk factors and the elusive signs and …

Effects Of A Ketogenic Diet On Body Composition, Metabolic Health, And Quality Of Life In Ovarian And Endometrial Cancer Patients, Caroline Whitney Cohen

All ETDs from UAB

Ketogenic diets (KDs) have garnered considerable research attention in recent years, having been investigated as a therapy for neurologic, metabolic, and even dermatologic diseases. Recent research has also focused on KDs as a potential intervention for cancer, with preclinical studies demonstrating profound effects such as inhibiting tumor growth, enhancing the effects of radiation and chemotherapy, and prolonging survival. However, to date few studies have been conducted in cancer patients. In order to determine if KDs might augment existing cancer treatment protocols, additional research is needed. Accordingly, the objective of this project was to conduct the first randomized, controlled trial examining …

Controlling The Uncontrollable: Understanding The Relationships Between Psychological Distress, Physical Impairment, And Acceptance Among Women With Gynecological Cancer, Kirby L. Williams

MSU Graduate Theses

As women age, the risk for being diagnosed with any gynecological cancer increases. Despite outnumbering the number of breast cancer diagnoses in a given year, there are significantly fewer studies addressing gynecological cancers. Treatment for gynecological cancers can be incredibly debilitating, both physically and psychologically. Although previous studies have evaluated and shown a relationship between physical impairment and perceived control on psychological distress in cancer patients during treatment, none have evaluated the influence of willingness and acceptance. The present study sought to expand this theory by assessing 25 gynecological cancer participants via self-report measures. Utilizing structural equation modelling, a moderated …

Identifying Molecular Targets And Validating Novel Therapies For Ovarian Cancer, Alejandro Villar-Prados

Dissertations & Theses (Open Access)

Re-purposing of targeted therapies for additional tumor types is a promising avenue for expanding treatment options for cancer patients, however accurately predicting what re-purposed targeted therapy will be effective remains challenging. To address this need, we developed a Therapy Predicting Tool (TPT) that accurately predicts the beneficial therapeutic effect of clinically relevant targeted therapies and the downstream pathways they may impact in the cancer of interest. Using ovarian cancer as a model to biologically validate our tool, we determined that Bromodomain and Extra-Terminal motif inhibitors (BETis), which target proteins such as BRD4, held the greatest promise to produce therapeutic effects …

Evaluating Fty720 As An Anticancer Agent In Models Of Ovarian Cancer, Kelly Marie Kreitzburg

All ETDs from UAB

Despite satisfactory initial responses to frontline therapies that combine tumor debulking with platinum and taxane-based chemotherapies, ovarian cancer remains the principle cause of gynecological malignancies. Drug resistance at relapse contributes to poor outcomes for women diagnosed with advanced disease and underscores the need for novel therapeutic strategies. Compelling data have implicated bioactive sphingolipids and their metabolism in the development and progression of ovarian cancer. Aberrations in sphingolipid metabolism that limit levels of the tumor suppressor lipid ceramide contribute to chemotherapy resistance. This dissertation presents work investigating the anticancer efficacy of the immunomodulatory drug FTY720. The sphingosine analog FTY720 has shown …

The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv

Theses & Dissertations

Ovarian granulosa cells are the major somatic components of the ovarian follicle. Proper proliferation and differentiation of ovarian granulosa cells are essential for successful follicle development. Accumulating evidence indicates that the Hippo-YAP signaling pathway plays critical roles in both development and tumorigenesis of several organs. The present study aims to investigate the role of Yes-associated protein 1 (YAP) in ovarian granulosa cell proliferation, differentiation, and malignant transformation. At first, we found that nuclear YAP (active) was highly expressed in proliferative granulosa cells, whereas cytoplasmic YAP (inactive) was detected mainly in terminally-differentiated luteal cells. Further studies suggested that endogenous YAP activity …

The Role Of Elevated Hyaluronan-Mediated Motility Receptor (Rhamm/Hmmr) In Ovarian Cancer, Stephanie T. Buttermore

USF Tampa Graduate Theses and Dissertations

Ovarian cancer (OC) has the highest mortality among gynecological cancers. The high mortality is associated with the lack of an accurate screening tool to detect disease in early stage. As a result the majority of OCs are diagnosed in late stage. Further, the molecular events responsible for malignant transformation in the ovary remain poorly understood. Consequently, delineating key molecular players driving OC could help elucidate potential diagnostic, prognostic and therapeutic targets.

Receptor for hyaluronan-mediated motility (RHAMM) belongs to a group of hyaladherins, which share a common ability to bind to hyaluronan (HA). Intracellularly, RHAMM is involved in microtubule spindle assembly …

Role Of Amylase In Ovarian Cancer, Mai Mohamed

USF Tampa Graduate Theses and Dissertations

Ovarian cancer (OC) accounts for 4% of all cancer cases and 4.2% of all cancer deaths worldwide. OC is the most lethal gynecological cancer because it lacks early disease symptoms and does not have a specific diagnostic marker. As a result, more than 70% of OC patients are diagnosed in later stages when the disease has already metastasized and the 5-year survival rate has decreased to less than 20% compared with approximately 90% survival for women diagnosed with early stage disease. Therefore, I initiated my studies with a computational analysis of the 27 most commonly reported literature-derived ovarian cancer (LDOC) …

Molecular Determinants Of Residual Disease In Ovarian Cancer, Kshipra M. Gharpure

Dissertations & Theses (Open Access)

The standard treatment for high grade serous ovarian cancer is primary cytoreductive surgery followed by adjuvant chemotherapy. Residual disease followed by surgery is associated with adverse overall and progression-free survival as well as poor response to adjuvant chemotherapy. Accurate identification of patients at high risk of residual disease will help avoid unnecessary surgeries and help in triaging these patients to neoadjuvant chemotherapy prior to interval surgical debulking. In this study, we address this clinical issue by identifying and validating molecular biomarkers that can predict the likelihood of residual disease in ovarian cancer patients. Using publically available databases and microarray datasets, …

Prevention Of Ovarian And Endometrial Cancer By Combined Oral Contraceptives: A Demographics Study, Joanna S. Heywood

CMC Senior Theses

Endometrial cancer is the most common gynecologic cancer with 54,870 cases occurring in the United States in 2015 and causing 10,170 deaths, an 18.5% mortality rate (Elit and Reade, 2015). Ovarian cancer, while less common, is much more fatal. In 2015 in the United States, 21,290 cases occurred and resulted in 14,180 deaths, a 66.6% mortality rate. This mortality rate makes ovarian cancer the fifth most deadly cancer for women in the United States, which is largely explained by ineffective screening strategies and limited treatment possibilities (Cramer, 2012). Thus, developing effective prevention strategies is especially important to saving the lives …

Activity Behavior And Physiological Profile Of Advanced-Stage Ovarian Cancer Survivors, Christelle Schofield

Theses: Doctorates and Masters

Background: Advanced-stage ovarian cancer survivors (OCS) often experience a multitude of disease symptoms and treatment-related side-effects. Additionally, most OCS are older, have comorbidities, are overweight or obese, and report being insufficiently physically active. Ovarian cancer survivors may benefit from exercise oncology interventions to reduce symptom-burden, manage comorbidities, minimize functional decline and maximize health-related quality of life (HRQoL). However, current knowledge gaps regarding the physiological characteristics of OCS throughout the entire survivorship spectrum challenge the development of tailored exercise interventions.

Purpose: The overall purpose of this thesis was to provide a more comprehensive physiological and activity behavior profile of post-treatment advanced-stage …