Translational Medical Research Commons^™

Impact Of Hyperthermia And Mitomycin C On Heat Shock Proteins, Mismatch Repair Proteins, And Cytotoxicity In Colon Cancer, Anna M. Reagan

Theses and Dissertations--Clinical and Translational Science

Cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) is a treatment used for primary peritoneal malignancy or metastases, including colon cancer. We aimed to explore the effects of hyperthermia and/or mitomycin C (MMC) on mismatch repair (MMR) proteins and heat shock proteins (hsps) and the potential for post-HIPEC treatment with pembrolizumab treatment. Colon cancer cells were treated with hyperthermia and/or MMC for 90 minutes. Subcellular fractionation and immunofluorescent imaging were performed to identify protein abundance and localization of MSH2, MLH1, hsp70, and hsp27. Proteomics analysis was performed for HT29 cells. HT29 cells and patient-derived organoids (PDOs) underwent simulated HIPEC and treatment …

Enhancing Public Health Surveillance: Development And Validation Of Machine Learning Models For Suspected Opioid Overdose Detection In Emergency Medical Services Data, Peter J. Rock

Theses and Dissertations--Clinical and Translational Science

The ongoing opioid overdose crisis in the United States requires timely and accurate surveillance systems to inform public health responses. Traditional public health surveillance methods rely on hospital discharge data and death certificates, which suffer from significant reporting delays and miss cases where patients refuse hospital transportation. Emergency Medical Services (EMS) data presents a promising alternative with advantages in timeliness and case ascertainment but lacks validated definitions for suspected opioid overdose (SOO).

This dissertation addresses this critical gap through the development, validation, and fairness assessment of machine learning models with natural language processing (ML-NLP) for identifying SOOs in EMS data. …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …

Assessment Of The Interplay Between Regional Β-Amyloid Burden And White Matter Hyperintensities On Cognition And Default Mode Network In Clinically Normal Older Participants, Doaa G. Ali

Theses and Dissertations--Clinical and Translational Science

Objective: Alzheimer’s disease (AD) and subcortical vascular dementia are considered the most common pathologic contributors to dementia in the aging population. Both frequently coexist in over 80% of community dwelling adults with dementia. The neuropathological development of AD arguably begins with β-amyloid (Aβ) deposition in the brain. This series of studies aims to test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in preclinical AD (pAD) (study1). Since mixed dementia is widely recognized as the norm rather than the exception, the second study aimed to explore the …

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 …

A Pilot Study Of A Multiple Health Behavior Change Intervention For Smokers, Srihari Seshadri

Theses and Dissertations--Clinical and Translational Science

Background: Being both obese and a smoker increases the probability of developing type 2 diabetes, cardiovascular disease, and cancer, diseases that impact Kentucky residents disproportionately. Kentucky (KY) has a high incidence of obesity (34.2%) and smoking (24.5 %). Weight gain associated with smoking cessation also can undermine health benefits of quitting, and may lead to smoking relapse.

Aim: The aim of the pilot study was to implement and evaluate a Multiple Health Behavioral Change (MHBC) program that combines Cooper Clayton Method to Stop Smoking (CCMSS) and the Diabetes Prevention Program (DPP) for weight control.

Method: A 15-week intervention was administered …

The Role Of Fat Grafting And Adipose-Derived Stem Cells In Breast Reconstruction, Krishna S. Vyas

Theses and Dissertations--Clinical and Translational Science

Fat grafting is a common surgical procedure that involves the transfer of fat from one area of the body to another in order to improve contour deformities, such as in breast reconstruction. Advantages of the technique include using autologous tissue rather than a foreign body and the added benefit of having liposuction to remove fat from an undesirable location. Although adipose tissue could be the ideal soft tissue filler, fat grafting is plagued by tremendous variability in long-term retention, with volume survival rates of 20-80%, resulting in suboptimal outcomes and repetitive procedures.

The mechanisms contributing to long-term fat graft survival …

The Metabolomic Effects Of Metformin On Colon Cancer, Jennifer W. Harris

Theses and Dissertations--Clinical and Translational Science

Metformin is an oral biguanide that is prescribed to over 120 million people worldwide for the treatment of conditions including type II diabetes mellitus, polycystic ovarian syndrome, and gestational diabetes. This hypoglycemic agent is rapidly emerging as a potential cost-effective anti-oncogenic agent. Over the past decade multiple epidemiologic studies have consistently associated metformin with decreased cancer incidence and cancer-related mortality. More recently numerous preclinical and clinical studies have demonstrated anti-cancer effects of metformin, leading to the proposal of numerous clinical trials to better understand this drug and its mechanism of action.

Previously experts believed metformin primarily targeted AMP-activated protein kinase …

Primary And Secondary Prevention Of Hepatitis C Virus Among Rural Appalachian People Who Use Drugs, Dustin B. Stephens

Theses and Dissertations--Clinical and Translational Science

Hepatitis C virus (HCV) remains a major cause of morbidity and mortality worldwide, with 3% of the global population chronically infected. Clinical impacts in the United States are projected to increase for two decades, and mortality attributed to HCV now exceeds HIV. Injection drug use (IDU) is the most common route of transmission in the developed world. Advances in treatment offer hope of mitigating HCV impacts, but substantial barriers obstruct people who inject drugs (PWID) from receiving care, particularly in medically underserved regions including Central Appalachia. This study assessed IDU paraphernalia sharing longitudinally over 24 months in a sample of …