Medicine and Health Sciences Commons^™

Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky

Biostatistics Faculty Publications

INTRODUCTION: Less than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions-Availability, Affordability, Accessibility, Accommodation and Acceptability-among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to …

Real-World Evaluation Of Universal Germline Screening For Cancer Treatment-Relevant Pharmacogenes, Megan L. Hutchcraft, Nan Lin, Shulin Zhang, Catherine Sears, Kyle Zacholski, Elizabeth A. Belcher, Eric B. Durbin, John L. Villano, Michael J. Cavnar, Susanne M. Arnold, Frederick R. Ueland, Jill M. Kolesar

Pathology and Laboratory Medicine Faculty Publications

The purpose of this study was to determine the frequency of clinically actionable treatment-relevant germline pharmacogenomic variants in patients with cancer and assess the real-world clinical utility of universal screening using whole-exome sequencing in this population. Cancer patients underwent research-grade germline whole-exome sequencing as a component of sequencing for somatic variants. Analysis in a clinical bioinformatics pipeline identified clinically actionable pharmacogenomic variants. Clinical Pharmacogenetics Implementation Consortium guidelines defined clinical actionability. We assessed clinical utility by reviewing electronic health records to determine the frequency of patients receiving pharmacogenomically actionable anti-cancer agents and associated outcomes. This observational study evaluated 291 patients with …

Elevated Lipid Oxidation Is Associated With Exceeding Gestational Weight Gain Recommendations And Increased Neonatal Anthropometrics: A Cross-Sectional Analysis, Jill M. Maples, Samantha F. Ehrlich, Nikki B. Zite, Kevin J. Pearson, W. Todd Cade, Courtney J. Riedinger, Maire M. Blankenship, Rachel A. Tinius

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Deviations from gestational weight gain (GWG) recommendations are associated with unfavorable maternal and neonatal outcomes. There is a need to understand how maternal substrate metabolism, independent of weight status, may contribute to GWG and neonatal outcomes. The purpose of this study was to explore the potential link between maternal lipid oxidation rate, GWG, and neonatal anthropometric outcomes.

METHODS: Women (N = 32) with a lean pre-pregnancy BMI were recruited during late pregnancy and substrate metabolism was assessed using indirect calorimetry, before and after consumption of a high-fat meal. GWG was categorized as follows: inadequate, adequate, or excess. Shortly …

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski, Zhuwei Zhang, J. Robert Mccorkle, Jodi M. Dejohn, Chi Wang, Rachel W. Miller, Holly H. Gallion, Charles S. Dietrich Iii, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC₅₀ values …

Salvaging Detection Of Early-Stage Ovarian Malignancies When Ca125 Is Not Informative, Charles J. Dunton, Megan L. Hutchcraft, Rowan G. Bullock, Lesley E. Northrop, Frederick R. Ueland

Markey Cancer Center Faculty Publications

Background: Ovarian cancer is the deadliest gynecologic cancer, with no recommended screening test to assist with early detection. Cancer antigen 125 (CA125) is a serum biomarker commonly used by clinicians to assess preoperative cancer risk, but it underperforms in premenopausal women, early-stage malignancies, and several histologic subtypes. OVA1 is a multivariate index assay that combines CA125 and four other serum proteins to assess the malignant risk of an adnexal mass. Objective: To evaluate the performance of OVA1 in a cohort of patients with low-risk serum CA125 values. Study Design: We analyzed patient data from previous collections (N = 2305, prevalence …

Lapatinib And Poziotinib Overcome Abcb1-Mediated Paclitaxel Resistance In Ovarian Cancer, J. Robert Mccorkle, Justin W. Gorski, Jinpeng Liu, Mckayla J. Riggs, Anthony B. Mcdowell Jr., Nan Lin, Chi Wang, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Conventional frontline treatment for ovarian cancer consists of successive chemotherapy cycles of paclitaxel and platinum. Despite the initial favorable responses for most patients, chemotherapy resistance frequently leads to recurrent or refractory disease. New treatment strategies that circumvent or prevent mechanisms of resistance are needed to improve ovarian cancer therapy. We established in vitro paclitaxel-resistant ovarian cancer cell line and organoid models. Gene expression differences in resistant and sensitive lines were analyzed by RNA sequencing. We manipulated candidate genes associated with paclitaxel resistance using siRNA or small molecule inhibitors, and then screened the cells for paclitaxel sensitivity using cell viability assays. …

Primary Bilateral Ovarian Artery Embolization For Uterine Leiomyomatosis In The Setting Of A Rare Anatomic Variant - Hypoplastic Uterine Arteries, Merve Ozen, Shezaan Momin, Charles Ben Myers, Mark Hoffman, Driss Raissi

Radiology Faculty Publications

We present the case of a 50-year-old female who underwent bilateral ovarian artery embolization for uterine fibroids in the setting of hypoplastic uterine arteries. Ovarian artery embolization is usually conducted during uterine artery embolization for fibroids to increase the procedure success when ovarian feeders are seen. The bilateral ovarian artery embolization is rarely performed due to fears of amenorrhea and early menopause from decreased blood supply to both ovaries. According to our knowledge, this the first case report describing primary bilateral ovarian artery embolization in the setting of a rare anatomic variant- hypoplastic uterine arteries. The patient had complete resolution …

Loss Of Obstetric Services In Rural Appalachia: A Qualitative Study Of Community Perceptions, Caroline R. Efird, David Dry, Rachel F. Seidman

Journal of Appalachian Health

Background: As rural hospitals across the United States increasingly downsize or close, the availability of inpatient obstetric services continues to decline in rural areas. In rural Appalachia, the termination of obstetric services threatens to exacerbate the existing risk of adverse birth outcomes for women and infants, yet less is known about how the cessation of these services affects the broader community.

Purpose: The purpose of this paper is to explain how the loss of local obstetric services affects perceptions of healthcare among multi-generational residents of a remote, rural Appalachian community in western North Carolina.

Methods: An interdisciplinary team of researchers …

Preclinical Evaluation Of Artesunate As An Antineoplastic Agent In Ovarian Cancer Treatment, Anthony Mcdowell Jr., Kristen S. Hill, Joseph Robert Mccorkle, Justin W. Gorski, Yilin Zhang, Ameen A. Salahudeen, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

BACKGROUND: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment.

METHODS: Standard cell culture technique with commercially available ovarian cancer cell lines were utilized in cell viability, DNA damage, and cell cycle progression assays to qualify and quantify artesunate treatment effects. Additionally, the sequence of administering artesunate in combination with paclitaxel and carboplatin was determined. The activity of artesunate was also assessed in 3D organoid models of primary ovarian cancer and RNAseq …

Mithramycin And Analogs For Overcoming Cisplatin Resistance In Ovarian Cancer, David Schweer, J. Robert Mccorkle, Jurgen Rohr, Oleg V. Tsodikov, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, …

Mutyh As An Emerging Predictive Biomarker In Ovarian Cancer, Megan L. Hutchcraft, Holly H. Gallion, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Approximately 18% of ovarian cancers have an underlying genetic predisposition and many of the genetic alterations have become intervention and therapy targets. Although mutations in MutY homolog (MUTYH) are best known for MUTYH associated polyposis and colorectal cancer, it plays a role in the development of ovarian cancer. In this review, we discuss the function of the MUTYH gene, mutation epidemiology, and its mechanism for carcinogenesis. We additionally examine its emerging role in the development of ovarian cancer and how it may be used as a predictive and targetable biomarker. MUTYH mutations may confer the risk of ovarian …

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski

Theses and Dissertations--Clinical and Translational Science

The development of patient-derived tumor organoids (TOs) from epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine.

Here, we utilize TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high grade serous epithelial ovarian cancer tumor organoids from tissue obtained during debulking surgery (2 neoadjuvant carboplatin exposed, 4 chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1 and 0.1µM). Cell viability curves and resultant EC50 values were determined …

Impact Of Smoking And Hpv Status On Cervical Cancer Survival In Women Living In Kentucky, 2004-2005 And 2014-2015, Brittany M. Mckinley

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

BACKGROUND/ OBJECTIVE: Cervical cancer is the fourth most commonly occurring malignancy in women worldwide, with an estimated 530,000 new cases and 270,000 new deaths each year (Small et al, 2017). While the incidence of cervical cancer has decreased by approximately 1.9% per year between 2007 and 2011, the death rate has remained stable (Bernard et al, 2014). Studies have shown that nearly all cervical cancer cases are associated with the Human Papilloma Virus (HPV). Many studies support the association of smoking with increased risk of invasive cervical cancer in women with high-risk HPV (Castle et al, 2002; Fang et al, …