Medical Specialties Commons^™

Saphenous Vein Harvesting With Endoscopy Versus No-Touch Technique: Short-Term Results, Tamer El Bannaa, Mohamed M. Mohamed, Ahmed Zayed, Yasser A. Sadek

Journal of Medicine in Scientific Research

Objective ‘No-touch’ (NT) saphenous vein harvesting maintains vasa vasorum, resulting in less medial ischemic affection, which leads to improved short-term and long-term patency. However, it may also be associated with a higher rate of wound complications. Endovascular vein harvesting (EVH) has a low rate of wound complications but also a tendency toward a lower patency rate. The aim was to compare wound complications and short-term symptomatic relief, which could be an indication of functioning grafts. Patients and methods During a 2-year period (2018–2019), in a nonrandomized prospective study, we monitored patients after coronary artery bypass graft for recurrence of ischemic …

Voice Quality Assessment In Cases Of Vocal Fold Gaps After Single Growth Factor Injection, Amr Roushdyel Badrawy, Asmaa Abdel Hamid, Israa Eltaweel, Azza Abdel Aziz Azzam

Journal of Medicine in Scientific Research

In severe vocal fold (VF) lesions, deposits of disorganized, thick collagen bundles and little hyaluronic acid (HA) are deposited in the superficial layer of lamina propria (SLP). These changes lead to severe dysphonia and aspiration, which could be complicated by fatal pneumonia. Unfortunately, no specific treatment has been recognized due to unpredictable VF regeneration. Current progress in regenerative medicine has allowed the development of tissue engineering techniques using cells, scaffolds, and growth factors (GFs). Extrinsic GFs application could help in the induction of the regenerative process. The work aims to assess the voice quality after a single GF injection of …

The Heads-Ed: A Psychosocial Screening For Pediatric Patients In Emergency Departments: A Systematic Review, Jessica Burns

Theses and Dissertations

The rates of mental health (MH) conditions among the pediatric population are rising steadily (Abramson, 2022; Clark et al., 2019). Given that MH symptoms and concerns frequently present in the emergency department (ED)-particularly since the onset of the COVID-19 pandemic-the ED setting may be a practical and effective setting to implement screening measures to identify youth at risk for mental illness and suicide (Leeb et al., 2020; Leff et al., 2021). This integrative systematic review examined the extent to which the HEADS-ED, one specific psychosocial screening measure, has been administered in the ED setting with youth and which healthcare professionals …

The Mechanisms Of Trail Resistance In Triple-Negative Breast Cancer, Julio Macias Pimentel

Wayne State University Dissertations

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks targeted therapies. Previous studies have shown that TNBC cells are highly sensitive to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), making it a promising agent for treating TNBC. However, the development of TRAIL resistance limits its further clinical development, and the underlying mechanisms are not fully understood. In this study, we report the role of PD-L1 and inflammation in TRAIL resistance. Specifically, we found that TRAIL treatment increases PD-L1 expression in TRAIL-sensitive cells and that basal PD-L1 expression is increased in acquired TRAIL-resistant cells. Mechanistically, we found …

Mechanistic Insights Into The Therapeutic Potential Of Adjunctive Thymosin Beta-4 Treatment In Pseudomonas Aeruginosa-Induced Keratitis, Yuxin Wang

Wayne State University Dissertations

Tβ4, a naturally occurring 43-amino acid protein, has been found to promote wound healing and reduce corneal inflammation. Topical Tβ4 as a therapeutic agent in conjunction with ciprofloxacin improves the outcome of Pseudomonas aeruginosa-induced keratitis by regulating the cellular functions of PMNs and MΦs and enhancing the production of SPMs. Understanding the mechanisms of Tβ4 provides valuable insights and novel therapeutic potential for resolving disease pathogenesis not only in the cornea but also in other infectious and immune-regulated inflammatory conditions.

Perioperative Outcomes Of Patients With Bleeding Disorders Undergoing Major Surgery At An Academic Hemophilia Treatment Center, Ruben Rhoades, Zachary French, Amy Yang, Karen Walsh, Douglass A. Drelich, Steven E. Mckenzie

Department of Medicine Faculty Papers

Persons with bleeding disorders (PwBD) are at high risk for bleeding with invasive procedures. However, the risk of bleeding in PwBD undergoing major surgery and outcomes of patients managed perioperatively at a hemophilia treatment center (HTC) are not well described. We performed a retrospective review of surgical outcomes among PwBD undergoing major surgery between January 1st, 2017 and December 31st, 2019 at the Cardeza Foundation Hemophilia and Thrombosis Center in Philadelphia, PA. The primary outcome was postoperative bleeding, assessed according to the ISTH-SSC's 2010 definition. Secondary outcomes included use of unplanned postoperative hemostatic therapy, LOS, and 30-day readmission rate. Results …

Verification Of Proton Range Predictions In Proton Treatment Planning Using X-Ray Ct Or Proton Ct Imaging, Nicholas S. Yee

Graduate Research Theses & Dissertations

The objective of this paper is to compare the range errors for two treatment plans; one using x-ray CT and the other using proton CT for calculating dose distributions in an animal tissue phantom. We shot 150 MeV proton beam through a meat phantom to a film stack to measure the exponential drop of dose at the Bragg peak until zero dose remained. Plotting the depth dose curves and performing gamma analyses are two ways to quantify the proton range errors when comparing them to depth dose curves from film measurements in the phantom. The depth dose curves give us …

Energy Cost Of Walking In Diabetic Partial-Foot Amputees As Related To Amputation Level, Nicholas Obias, Javier La Fontaine, Javier Cavazos, Luis Venegas, Hafizur Rahman

School of Podiatric Medicine - Student Research

This review will explore how the energy cost of walking changes with different levels of partial-foot amputation in diabetic patients. Patient populations with advanced stages of diabetes and associated complications have a high incidence of distal lower extremity amputation. Diabetes associated conditions and altered foot function in post-amputation patients affect gait biomechanics and energy expenditure in gait. We will review studies utilizing advanced biomechanical tools to quantify and compare energy expenditure (defined as cardiac function and oxygen consumption) in established post-operative partial-foot amputees at various levels (post-operative day >90*) to controls. Dr. Rahman and his team aim to provide further …

Coronary Heart Disease And Ischemic Stroke Polygenic Risk Scores And Atherosclerotic Cardiovascular Disease In A Diverse, Population-Based Cohort Study, Allison Bebo, Jamie A Jarmul, Mark J Pletcher, Natalie R Hasbani, David Couper, Vijay Nambi, Christie M Ballantyne, Myriam Fornage, Alanna C Morrison, Christy L Avery, Paul S De Vries

Faculty, Staff and Student Publications

The predictive ability of coronary heart disease (CHD) and ischemic stroke (IS) polygenic risk scores (PRS) have been evaluated individually, but whether they predict the combined outcome of atherosclerotic cardiovascular disease (ASCVD) remains insufficiently researched. It is also unclear whether associations of the CHD and IS PRS with ASCVD are independent of subclinical atherosclerosis measures. 7,286 White and 2,016 Black participants from the population-based Atherosclerosis Risk in Communities study who were free of cardiovascular disease and type 2 diabetes at baseline were included. We computed previously validated CHD and IS PRS consisting of 1,745,179 and 3,225,583 genetic variants, respectively. Cox …

Premature Senescence And Cardiovascular Disease Following Cancer Treatments: Mechanistic Insights, Ashita Jain, Diego Casanova, Alejandra Valdivia Padilla, Angelica Paniagua Bojorges, Sivareddy Kotla, Kyung Ae Ko, Venkata S K Samanthapudi, Khanh Chau, Minh T H Nguyen, Jake Wen, Selina L Hernandez Gonzalez, Shaefali P Rodgers, Elizabeth A Olmsted-Davis, Dale J Hamilton, Cielito Reyes-Gibby, Sai-Ching J Yeung, John P Cooke, Joerg Herrmann, Eduardo N Chini, Xiaolei Xu, Syed Wamique Yusuf, Momoko Yoshimoto, Philip L Lorenzi, Brain Hobbs, Sunil Krishnan, Efstratios Koutroumpakis, Nicolas L Palaskas, Guangyu Wang, Anita Deswal, Steven H Lin, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, especially among the aging population. The "response-to-injury" model proposed by Dr. Russell Ross in 1999 emphasizes inflammation as a critical factor in atherosclerosis development, with atherosclerotic plaques forming due to endothelial cell (EC) injury, followed by myeloid cell adhesion and invasion into the blood vessel walls. Recent evidence indicates that cancer and its treatments can lead to long-term complications, including CVD. Cellular senescence, a hallmark of aging, is implicated in CVD pathogenesis, particularly in cancer survivors. However, the precise mechanisms linking premature senescence to CVD in cancer survivors remain …

Uncovering The Role Of Fat-Infiltrated Axillary Lymph Nodes In Obesity-Related Diseases With Statistical And Machine Learning Analyses, Qingyuan Song

Dartmouth College Ph.D Dissertations

The link between obesity and pathogenesis is a complex and multifaceted area of research that is yet to be fully understood. Ample evidence exists to demonstrate the direct relationship between excessive internal fat and various health conditions such as cancer, and metabolic and cardiovascular diseases. The infiltration of ectopic fat into axillary lymph nodes, observable on breast cancer screening images, has been shown to be correlated with body mass index (BMI) in women undergoing screening. This study aimed to explore the relationship between fat-infiltrated axillary lymph nodes (FIN) and obesity-related diseases, with the goal of evaluating the clinical value of …

Diagnostic Accuracy Of Different Cut-Off Values Of Adenosine Deaminase Levels In Tuberculous Pleural Effusion, Kiran Iqbal Masood, Shayan Shahid, Kauser Jabeen, Joveria Farooqi, Sabeika Raza Kerawala, Muhammad Irfan

Department of Pathology and Laboratory Medicine

Objective: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion.
Method: The prospective study was conducted from 2014 to 2016 at the Aga Khan University Hospital, Karachi, and comprised pleural fluid samples of adult patients with and without tuberculosis which were tested for adenosine deaminase levels, and divided into tuberculosis group A and non-tuberculosis group B. Sensitivity, specificity, negative predictive value and positive predictive value were calculated using different cut-offs. Data was analysed using IBM SPSS (Statistical Package for Social Sciences) version 21.0 (IBM Corp., Armonk, …

Work Difficulties, Work Restrictions, And Disability Benefits In People With Functional Seizures: A Survey Study, Jared Woodward, A A Asadi-Pooya, Bridget Mildon, Benjamin Tolchin

Department of Neurology Faculty Papers

Purpose: Functional seizures (FS) cause significant long-term disability and clinicians offer differing views on proper work restrictions and qualifications for disability benefits in this population. We assess the views and perspectives of experienced disability and work limitations in people living with functional seizures. Methods: Between (4/29/2020–1/13/2021) an open-access 21-item internet survey was conducted via FNDHope.org; allowing for people living with self-reported functional seizures to remark on topics of work difficulties, work restrictions, qualifications for disability benefits, and driving. Demographic information was collected, and univariate and multivariate logistic regressions were used to evaluate potential predictors of current employment status. Results: One …

Pediatric In-Hospital Cardiac Arrests: We Have More To Learn About Patient Demographics And Outcomes, Nathan Lavoy, John Cowden, Jenna Miller, Asdis Finnsdottir Wagner, Shekinah Hensley, Stephen Pfeiffer

Presentations

Introduction: Prior pediatric studies show an association between patient demographics and mortality after in-hospital cardiac arrests (IHCA). To our knowledge, this has not been assessed in pediatric intensive care units (PICU). This study aims to evaluate the impact of demographics and code characteristics on outcomes after IHCA in a quaternary referral PICU. Methods: A single center retrospective review of PICU IHCA events from 2010-2021 was performed. Patient demographics included age, gender, race/ethnicity, and language. Primary diagnosis was defined as cardiac or non-cardiac. The use of ECMO, CRRT, or defibrillation were included as code characteristics. The primary outcome was survival to …

Protein S In Coagulation And Inflammation, Martha Mega Silvia Sim

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein S (PS) is a key regulator, which links inflammation and coagulation and performs multiple proposed functions in both processes. PS exists in the blood as a free soluble form (~40%), bound to complement component 4b-binding protein/ C4BP (~60%), and packaged in platelet α-granules (~2.5%). Subendothelial tissue factor (TF), upon exposure to blood, initiates coagulation, a proteolytic cascade which results in the activation of thrombin, the enzyme responsible for formation of a fibrin clot. PS is a critical anticoagulant that inhibits multiple steps of this process. Only the free fraction of PS has full anticoagulant properties, as C4BP blocks this …

Metabolic Reprogramming Driven By Ezh2 Inhibition Depends On Cell–Matrix Interactions, Teresa W-M Fan, Jahid M. M. Islam, Richard M. Higashi, Penghui Lin, Christine F. Brainson, Andrew N. Lane

Markey Cancer Center Faculty Publications

EZH2 (Enhancer of Zeste Homolog 2), a subunit of Poly- comb Repressive Complex 2 (PRC2), catalyzes the trimethyla- tion of histone H3 at lysine 27 (H3K27me3), which represses expression of genes. It also has PRC2-independent functions, including transcriptional coactivation of oncogenes, and is frequently overexpressed in lung cancers. Clinically, EZH2 in- hibition can be achieved with the FDA-approved drug EPZ- 6438 (tazemetostat). To realize the full potential of EZH2 blockade, it is critical to understand how cell-cell/cell-matrix interactions present in 3D tissue and cell culture systems in- fluences this blockade in terms of growth-related metabolic functions. Here, we show that …

A Monoadduct Generating Ru(Ii) Complex Induces Ribosome Biogenesis Stress And Is A Molecular Mimic Of Phenanthriplatin, Richard Joseph Mitchell, Sarah M. Kriger, Alexander D. Fenton, Dmytro Havrylyuk, Ankit Pandeya, Yang Sun, Tami Smith, Jason E. Derouchey, David K. Heidary, Edith C. Glazer

Markey Cancer Center Faculty Publications

Ruthenium complexes are often investigated as potential replacements for platinum-based chemotherapeutics in hopes of identifying systems with improved tolerability in vivo and reduced susceptibility to cellular resistance mechanisms. Inspired by phenanthriplatin, a non-traditional platinum agent that contains only one labile ligand, monofunctional ruthenium polypyridyl agents have been developed, but until now, few demonstrated promising anticancer activity. Here we introduce a potent new scaffold, based on [Ru(tpy)(dip)Cl]Cl (tpy = 2,20:60,200-terpyridine and dip = 4,7-diphenyl-1,10-phenanthroline) in pursuit of effective Ru(II )-based monofunctional agents. Notably, the extension of the terpyridine at the 40 position with an aromatic ring resulted in a molecule that …

Assessment Of Opioid-Induced Immunomodulation In Experimental And Clinical Sepsis, Brittany Dawn Bissell, Jamie L. Sturgill, Maria E. C. Bruno, Erick D. Lewis, Marlene E. Starr

Markey Cancer Center Faculty Publications

CONTEXT: Opioids remain a standard supportive therapy in patients admitted to the ICU with sepsis. However, as preclinical models indicate an association between opioid exposure and immunosuppression, the use of this class of drugs warrants investigation. The objective of this study was to investigate whether opioid exposure causes immunosuppression in patients with sepsis, and to use a murine sepsis model to determine the effects of opioid exposure on secondary infection.

HYPOTHESIS: We hypothesized opioid exposure would be associated with immunosuppression in patients with sepsis and secondary infection in a murine sepsis model.

METHODS AND MODELS: This was a two-phase preclinical …

Bilirubin Levels Are Negatively Correlated With Adiposity In Obese Men And Women, And Its Catabolized Product, Urobilin, Is Positively Associated With Insulin Resistance, Zachary A. Kipp, Mei Xu, Evelyn A. Bates, Wang-Hsin Lee, Philip A. Kern, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Bilirubin levels in obese humans and rodents have been shown to be lower than in their lean counterparts. Some studies have proposed that the glucuronyl UGT1A1 enzyme that clears bilirubin from the blood increases in the liver with obesity. UGT1A1 clearance of bilirubin allows more conjugated bilirubin to enter the intestine, where it is catabolized into urobilin, which can be then absorbed via the hepatic portal vein. We hypothesized that when bilirubin levels are decreased, the urobilin increases in the plasma of obese humans, as compared to lean humans. To test this, we measured plasma levels of bilirubin and urobilin, …

Computational Investigation Of A Series Of Small Molecules As Potential Compounds For Lysyl Hydroxylase-2 (Lh2) Inhibition, Yazdan Maghsoud, Erik Antonio Vázquez-Montelongo, Xudong Yang, Chengwen Liu, Zhifeng Jing, Juhoon Lee, Matthew Harger, Ally K. Smith, Miguel Espinoza, Hou-Fu Guo, Jonathan M. Kurie, Kevin N. Dalby, Pengyu Ren, G. Andrés Cisneros

Markey Cancer Center Faculty Publications

The catalytic function of lysyl hydroxylase-2 (LH2), a member of the Fe(II)/αKG-dependent oxygenase superfamily, is to catalyze the hydroxylation of lysine to hydroxylysine in collagen, resulting in stable hydroxylysine aldehyde-derived collagen cross- links (HLCCs). Reports show that high amounts of LH2 lead to the accumulation of HLCCs, causing fibrosis and specific types of cancer metastasis. Some members of the Fe(II)/αKG-dependent family have also been reported to have intramolecular O2 tunnels, which aid in transporting one of the required cosubstrates into the active site. While LH2 can be a promising target to combat these diseases, efficacious inhibitors are still lacking. We …

Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self- renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 …

Extracellular Vesicle Distribution And Localization In Skeletal Muscle At Rest And Following Disuse Atrophy, Ahmed Ismaeel, Douglas W. Van Pelt, Zachary Hettinger, Xu Fu, Christopher I. Richards, Timothy A. Butterfield, Jonathan J. Petrocelli, Ivan J. Vechetti Jr., Amy L. Confides, Micah J. Drummond, Esther E. Dupont-Versteegden

Markey Cancer Center Faculty Publications

Background Skeletal muscle (SkM) is a large, secretory organ that produces and releases myokines that can have autocrine, paracrine, and endocrine effects. Whether extracellular vesicles (EVs) also play a role in the SkM adaptive response and ability to communicate with other tissues is not well understood. The purpose of this study was to investigate EV biogenesis factors, marker expression, and localization across cell types in the skeletal muscle. We also aimed to investigate whether EV concentrations are altered by disuse atrophy.

Methods To identify the potential markers of SkM‑derived EVs, EVs were isolated from rat serum using density gradient ultracentrifugation, …

Glycolytic Regulation Of Intestinal Stem Cell Self-Renewal And Differentiation, Chang Li, Yuning Zhou, Ruozheng Wei, Dana L. Napier, Tomoko Sengoku, Michael Alstott, Jinpeng Liu, Chi Wang, Yekaterina Y. Zaytseva, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

BACKGROUND AND AIMS: The intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis. An imbalance in this highly regimented process within the intestinal crypts is associated with several intestinal pathologies. Although metabolic changes are known to play a pivotal role in cell proliferation and differentiation, how glycolysis contributes to intestinal epithelial homeostasis remains to be defined.

METHODS: Small intestines were harvested from mice with specific hexokinase 2 (HK2) deletion in the intestinal epithelium or LGR5þ stem cells. Glycolysis was measured using the Seahorse XFe96 analyzer. Expression of phospho-p38 mitogen- activated protein kinase, the transcription factor atonal homolog 1, …

Impact Of The Affordable Care Act On Providing Equitable Healthcare Access For Ibd In The Kentucky Appalachian Region, Jennifer T. Castle, Brittany Levy, Anthony A. Mangino, Hannah G. Mcdonald, Erin E. Mcatee, Jitesh A. Patel, B. Mark Evers, Avinash S. Bhakta

Markey Cancer Center Faculty Publications

BACKGROUND: Medicaid expansion improved insurance coverage for patients with chronic conditions and low income. The effect of Medicaid expansion on patients with IBD from high-poverty communities is unknown.

OBJECTIVE: This study aimed to evaluate the impact of Medicaid expansion in Kentucky on care for patients with IBD from the Eastern Kentucky Appalachian community, a historically impoverished area.

DESIGN: This study was a retrospective, descriptive, and ecological study.

SETTINGS: This study was conducted in Kentucky using the Hospital Inpatient Discharge and Outpatient Services Database.

PATIENTS: All encounters for IBD care for 2009–2020 for patients from the Eastern Kentucky Appalachian region were …

Long-Term Kidney Function Recovery And Mortality After Covid-19-Associated Acute Kidney Injury: An International Multi-Centre Observational Cohort Study, Byom W. L. Tan, Bryce W. Q. Tan, Kee Yuan Ngiam, The Consortium For Clinical Characterization Of Covid-19 By Ehr (4ce)

Markey Cancer Center Faculty Publications

Background While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking.

Methods A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021.

Findings Advanced age (HR 2.77, 95%CI 2.53–3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03–4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55–5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14–1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37–0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17–1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20–1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45–1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80–13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10–1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32–1.67) and 365 days (RR 1.54, 95%CI 1.21–1.96) compared to COVID-19 patients with no AKI.

Interpretation COVID-19-associated …

Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 …

Suppressing Hepatic Ugt1a1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways And Lipid Species And Improves Fatty Liver Disease, Evelyn A. Bates, Zachary A. Kipp, Genesee J. Martinez, Olufunto O. Badmus, Mangala M. Soundarapandian, Donald Foster, Mei Xu, Justin F. Creeden, Jennifer R. Greer, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR). In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks to induce NAFLD and were treated subcutaneously with GNUR or sham (CTRL) once weekly for six weeks while continuing the HFD. The results show that GNUR treatments significantly raised plasma bilirubin levels and …

Impact Of The Appalachian Career Training In Oncology (Action) Program On Undergraduate Participants, Carol Hanley, Lauren Hudson, Chris Prichard, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Kentucky ranks first in the nation in cancer incidence and mortality. The Appalachian region of the state experiences the highest cancer disparities due to inequities in many social determinants of health. As a strategy for addressing cancer and education disparities in the region, the Appalachian Career Training in Oncology (ACTION) Program at the University of Kentucky Markey Cancer Center engaged 16 Appalachian-native undergraduate student participants annually in cancer-related activities. Students were recruited on an annual basis for the 2-year ACTION program. Entry, mid-point, and exit surveys were administered to participants. Classical test theory and exploratory factor analysis were used to …

A Qualitative Study Of Participant Perceptions Of A Cancer Research Education Program, Olivia Allran, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Kentucky ranks first in the nation in cancer incidence and mortality rates, with the greatest burden of disease being in the Appalachian region. The cancer disparities in the Appalachian region of the state are tied to high poverty rates, low education attainment, low health care access, and high rates of poor health behaviors, such as tobacco use. The University of Kentucky (UK) Markey Cancer Center (MCC) developed the Appalachian Career Training in Oncology (ACTION) program to address the cancer and education disparities in the region. ACTION is a two-year program that focuses on cancer education and training for high school …

The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li

Markey Cancer Center Faculty Publications

Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exo- somes to reprogram the factors associated with the tumor microenvironment (TME) causing tu- mor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with re- ceptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some pa- tients show …