Medical Specialties Commons^™

Promoting A More Diverse And Inclusive Research Workforce Through The Research Scholars Program, Nancy Schoenberg, Jimmy Robinson, Margaret J. Mcgladrey, Lisa A. Cassis, Darwin Conwell, Kevin J. Pearson, Lisa R. Tannock, Donna Wilcock, Stephanie White

Markey Cancer Center Faculty Publications

Background

Novel and comprehensive approaches are needed to address shortcomings in the diversity and inclu- siveness of the scientific workforce. In response to this need and informed by multiple programs and data sources, we created the Research Scholars Program (RSP). The RSP is a yearlong program for early-career faculty with an overall objective to overcome barriers to the academic success, retention, progression, and promotion of groups underrepre- sented in biomedical and behavioral research. The goal of the RSP is to increase research confidence and productivity, build a supportive research community, and reduce isolation by providing personal and group research enrichment …

A Novel Protozoa Parasite-Derived Protein Adjuvant Is Effective In Immunization With Cancer Cells To Activate The Cancer-Specific Protective Immunity And Inhibit The Cancer Growth In A Murine Model Of Colorectal Cancer, Rajesh Mani, Chloe G. Martin, Kanal E. Balu, Qingding Wang, Piotr G. Rychahou, Tadahide Izumi, B. Mark Evers, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Cancer-specific CD8+ cytotoxic T cells play important roles in preventing cancer growth, and IFN-γ, in addition to IL-12 and type I interferon, is critical for activating CD8+ cytotoxic T cells. We recently identified the capability of the amino-terminus region of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii, an intracellular protozoan parasite, to activate IFN-γ production of microglia, a tissue-resident macrophage population. Therefore, in the present study, we examined whether recombinant GRA6Nt protein (rGRA6Nt) functions as an effective adjuvant to potently activate cancer-specific protective immunity using a murine model of MC38 colorectal cancer (CRC). When mice were immunized with non-replicable …

Neurotensin Accelerates Atherosclerosis And Increases Circulating Levels Of Short-Chain And Saturated Triglycerides, Jing Li, Liping Yang, Jun Song, Baoxiang Yan, Andrew J. Morris, Hunter Moseley, Robert M. Flight, Chi Wang, Jinpeng Liu, Heidi L. Weiss, Edward F. Morris, Ilyes Abdelhamid, Mathias J. Gerl, Olle Melander, Susan Smyth, B. Mark Evers

Markey Cancer Center Faculty Publications

Background and aims: Obesity and type 2 diabetes are significant risk factors for atherosclerotic cardiovascular disease (CVD) worldwide, but the underlying pathophysiological links are poorly understood. Neurotensin (NT), a 13-amino-acid hormone peptide, facilitates intestinal fat absorption and contributes to obesity in mice fed a high-fat diet. Elevated levels of pro-NT (a stable NT precursor produced in equimolar amounts relative to NT) are associated with obesity, type 2 diabetes, and CVD in humans. Whether NT is a causative factor in CVD is unknown.

Methods: Nt+/+ and Nt–/– mice were either injected with adeno-associated virus encoding PCSK9 mutants or crossed with Ldlr–/– …

Structure, Dynamics, And Redox Reactivity Of An All-Purpose Flavodoxin, Sharique Khan, Ahmadullah Ansari, Monica Brachi, Debarati Das, Wassim El Housseini, Shelley Minteer, Anne-Francis Miller

Markey Cancer Center Faculty Publications

The flavodoxin of Rhodopseudomonas palustris CGA009 (Rp9Fld) supplies highly reducing equivalents to crucial en- zymes such as hydrogenase, especially when the organism is iron-restricted. By acquiring those electrons from photodriven electron flow via the bifurcating electron transfer flavoprotein, Rp9Fld provides solar power to vital metabolic processes. To understand Rp9Fld’s ability to work with diverse partners, we solved its crystal structure. We observed the canonical fla- vodoxin (Fld) fold and features common to other long-chain Flds but not all the surface loops thought to recognize part- ner proteins. Moreover, some of the loops display alternative structures and dynamics. To advance studies …

Impacts Of Xylazine On Fentanyl Demand, Body Weight, And Acute Withdrawal In Rats: A Comparison To Lofexidine, Safiyah M. Sadek, Shailesh N. Khatri, Zachary A. Kipp, Kelly E. Dunn, Joshua S. Beckmann, William W. Stoops, Terry D. Hinds, Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl’s behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is …

Oxycodone Withdrawal Is Associated With Increased Cocaine Self-Administration And Aberrant Accumbens Glutamate Plasticity In Rats, Shailesh N. Khatri, Hanaa Ulangkaya, Erin E. Maher, Safiyah M. Sadek, Mei Hong, Andrea M. Woodcox, William W. Stoops, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Individuals with opioid use disorder (OUD) frequently use other substances, including cocaine. Opioid with- drawal is associated with increased likelihood of cocaine use, which may represent an attempt to ameliorate opioid withdrawal effects. Clinically, 30% of co-using individuals take opioids and cocaine exclusively in a sequential manner. Preclinical studies evaluating mechanisms of drug use typically study drugs in isolation. However, polysubstance use is a highly prevalent clinical issue and thus, we established a novel preclinical model of sequential oxycodone and cocaine self-administration (SA) whereby rats acquired oxycodone and cocaine SA in an A-B-A-B design. Somatic signs of withdrawal were evaluated …

Perfluorooctanesulfonic Acid Exposure Leads To Downregulation Of 3-Hydroxy-3-Methylglutaryl-Coa Synthase 2 Expression And Upregulation Of Markers Associated With Intestinal Carcinogenesis In Mouse Intestinal Tissues, Josiane Weber Tessmann, Pan Deng, Jerika Durham, Chang Li, Moumita Banerjee, Qingding Wang, Ryan A. Goettl, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Bernhard Hennig, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Perfluorooctanesulfonic acid (PFOS) is a widely recognized environment pollutant known for its high bio- accumulation potential and a long elimination half-life. Several studies have shown that PFOS can alter multiple biological pathways and negatively affect human health. Considering the direct exposure to the gastrointestinal (GI) tract to environmental pollutants, PFOS can potentially disrupt intestinal homeostasis. However, there is limited knowledge about the effect of PFOS exposure on normal intestinal tissues, and its contribution to GI- associated diseases remains to be determined. In this study, we examined the effect of PFOS exposure on the gene expression profile of intestinal tissues of …

Retinoic Acid-Mediated Inhibition Of Mouse Coronavirus Replication Is Dependent On Irf3 And Camkk, Justin H. Franco, Ryan A. Harris, William G. Ryan, Roger Travis Taylor, Robert E. Mccullumsmith, Saurabh Chattopadhyay, Zhixing K. Pan

Markey Cancer Center Faculty Publications

The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties. Due to its impact on different signaling pathways, RA’s mechanism of action during coronavirus infection has not been thoroughly described. To determine RA’s mechanism of action, we examined its effect against a mouse coronavirus, mouse hepatitis …

Sedimentation Of Large, Soluble Proteins Up To 140 Kda For 1h-Detected Mas Nmr And 13c Dnp Nmr – Practical Aspects, Dallas Bell, Florian Lindemann, Lisa Gerland, Hanna Aucharova, Alexander Klein, Daniel Friedrich, Matthias Hiller, Kristof Grohe, Tobias Meier, Barth Van Rossum, Anne Diehl, Jon Hughes, Leonard J. Mueller, Rasmus Linser, Anne-Frances Miller, Hartmut Oschkinat

Markey Cancer Center Faculty Publications

Solution NMR is typically applied to biological systems with molecular weights < 40 kDa whereas magic-angle-spinning (MAS) solid-state NMR traditionally targets very large, oligomeric proteins and complexes exceeding 500 kDa in mass, including fibrils and crystalline protein preparations. Here, we propose that the gap between these size regimes can be filled by the approach presented that enables investigation of large, soluble and fully protonated proteins in the range of 40–140 kDa. As a key step, ultracentrifugation produces a highly concentrated, gel-like state, resembling a dense phase in spontaneous liquid-liquid phase separation (LLPS). By means of three examples, a Sulfolobus acidocaldarius bifurcat- ing electron transfer flavoprotein (SaETF), tryptophan synthases from Salmonella typhimurium (StTS) and their dimeric β-subunits from Pyrococcus furiosus (PfTrpB), we show that such samples yield well-resolved proton-detected 2D and 3D NMR spectra at 100 kHz MAS without heterogeneous broadening, similar to diluted liquids. Herein, we provide practical guidance on centrifugation conditions and tools, sample behavior, and line widths expected. We demonstrate that the observed chemical shifts correspond to those obtained from μM/low mM solutions or crystalline samples, indicating structural integrity. Nitrogen line widths as low as 20–30 Hz are observed. The presented approach is advantageous for proteins or nucleic acids that cannot be deuterated due to the expression system used, or where relevant protons cannot be re-incorporated after expression in deuterated medium, and it circumvents crystallization. Importantly, it allows the use of low-glycerol buffers in dynamic nuclear polarization (DNP) NMR of proteins as demonstrated with the cyanobacterial phytochrome Cph1.

Terminally Differentiated Effector Memory T Cells Associate With Cognitive And Ad-Related Biomarkers In An Aging-Based Community Cohort, Edric Winford, Jenny Lutshumba, Barbara J. Martin, Donna M. Wilcock, Gregory A. Jicha, Barbara S. Nikolajczyk, Ann M. Stowe, Adam D. Bachstetter

Markey Cancer Center Faculty Publications

Background and purpose: The immune response changes during aging and the progression of Alzheimer’s disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called TEMRA) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in TEMRAs are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline. This study aimed to examine whether TEMRAs are associated with cognition and plasma biomarkers of AD, neurodegeneration, and neuroinflammation in a community-based cohort of older adults.

Methods: Study participants from …

Cooperative Nucleic Acid Binding By Poly Adp‑Ribose Polymerase 1, Manana Melikishvili, Michael G. Fried, Yvonne N. Fondufe‑Mittendorf

Markey Cancer Center Faculty Publications

Poly (ADP)‑ribose polymerase 1 (PARP1) is an abundant nuclear protein well‑known for its role in DNA repair yet also participates in DNA replication, transcription, and co‑transcriptional splicing, where DNA is undamaged. Thus, binding to undamaged regions in DNA and RNA is likely a part of PARP1’s normal repertoire. Here we describe analyses of PARP1 binding to two short single‑stranded DNAs, a single‑stranded RNA, and a double stranded DNA. The investigations involved comparing the wild‑ type (WT) full‑length enzyme with mutants lacking the catalytic domain (∆CAT) or zinc fingers 1 and 2 (∆Zn1∆Zn2). All three protein types exhibited monomeric characteristics in …

Non-Transcriptional Irf7 Interacts With Nf-Κb To Inhibit Viral Inflammation, Shumin Fan, Sonam Popli, Sukanya Chakravarty, Ritu Chakravarty, Saurabh Chattopadhyay

Markey Cancer Center Faculty Publications

Interferon (IFN) regulatory factors (IRF) are key transcrip- tion factors in cellular antiviral responses. IRF7, a virus- inducible IRF, expressed primarily in myeloid cells, is required for transcriptional induction of interferon α and antiviral genes. IRF7 is activated by virus-induced phosphory- lation in the cytoplasm, leading to its translocation to the nu- cleus for transcriptional activity. Here, we revealed a nontranscriptional activity of IRF7 contributing to its antiviral functions. IRF7 interacted with the pro-inflammatory tran- scription factor NF-κB-p65 and inhibited the induction of in- flammatory target genes. Using knockdown, knockout, and overexpression strategies, we demonstrated that IRF7 inhibited NF-κB–dependent inflammatory …

Foxs1 Is Increased In Liver Fibrosis And Regulates Tgfβ Responsiveness And Proliferation Pathways In Human Hepatic Stellate Cells, Evelyn A. Bates, Zachary A. Kipp, Wang-Hsin Lee, Genesee J. Martinez, Lauren Weaver, Kathryn N. Becker, Sally Pauss, Justin F. Creeden, Garrett B. Anspach, Robert N. Helsley, Mei Xu, Maria E. C. Bruno, Marlene E. Starr, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Liver fibrosis commences with liver injury stimulating transforming growth factor beta (TGFβ) activation of hepatic stellate cells (HSCs), causing scarring and irreversible damage. TGFβ induces expression of the transcription factor Forkhead box S1 (FOXS1) in hepatocytes and may have a role in the pathogenesis of hepatocellular carcinoma (HCC). To date, no studies have determined how it affects HSCs. We analyzed human livers with cirrhosis, HCC, and a murine fibrosis model and found that FOXS1 expression is significantly higher in fibrotic livers but not in HCC. Next, we treated human LX2 HSC cells with TGFβ to activate fibrotic pathways, and FOXS1 …

Nac1 Promotes Stemness And Regulates Myeloid-Derived Cell Status In Triple-Negative Breast Cancer, Chrispus Ngule, Ruyi Shi, Xingcong Ren, Hongyan Jia, Felix Oyelami, Dong Li, Younhee Park, Jinhwan Kim, Hami Hemati, Yi Zhang, Xiaofang Xiong, Andrew Shinkle, Nathan L. Vanderford, Sara Bachert, Binhua P. Zhou, Jianlong Wang, Jianxun Song, Xia Liu, Jin-Ming Yang

Markey Cancer Center Faculty Publications

Triple negative breast cancer (TNBC) is a particularly lethal breast cancer (BC) subtype driven by cancer stem cells (CSCs) and an immunosuppressive microenvironment. Our study reveals that nucleus accumbens associated pro- tein 1 (NAC1), a member of the BTB/POZ gene family, plays a crucial role in TNBC by maintaining tumor stemness and influencing myeloid-derived suppressor cells (MDSCs). High NAC1 expression correlates with worse TNBC prognosis. NAC1 knockdown reduced CSC markers and tumor cell proliferation, migration, and invasion. Addition- ally, NAC1 affects oncogenic pathways such as the CD44-JAK1-STAT3 axis and immunosuppressive signals (TGFβ, IL-6). Intriguingly, the impact of NAC1 on tumor …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integ- rity of the intestinal epithelium plays a key role in inflammatory diseases and gastro- intestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differenti- ation. Repression of endogenous miR-27a-3p leads to increased enterocyte differen- tiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell …

Novel Endoscopic Approach For Treatment Of Malignant Tracheoesophageal Fistula (Tef): A Case Report, Haris Zia, Matthew D. Mccoy, Jamie L. Sturgill, Walid Hadid, Ashish P. Maskey

Markey Cancer Center Faculty Publications

Cardiac septal occluder (CSO) can be used endoscopically in treatment of tracheoesophageal fis- tula (TEF). We present a case of metastatic cervical cancer with direct tracheal invasion resulting in malignant TEF treated previously with radiotherapy and tracheal stenting twice. This TEF was closed by CSO - patent foramen ovale (PFO) occluder as palliative management to prevent recur- rent aspiration pneumonia, decrease morbidity and improve quality of life.

Implementation Of An Evidence-Based Bundle To Educate Nurses In The Care Of Adult Post-Transplant Diabetes Mellitus Patients, Christine Slaughter

DNP Projects

Background: After solid organ transplantation, between 10-40% of patients develop post-transplant diabetes mellitus (PTDM) due to the immunosuppression regimen, infection, stress response and pain. Hyperglycemia events are common and managing glycemic targets is critical to decrease the likelihood of graft failure and mortality.

Purpose: To determine the impact of an evidenced-based bundle education strategy on the perceived confidence/knowledge of nurses and on their documentation compliance in the care of adult solid organ post-transplant diabetes mellitus patients.

Methods: A single group, pretest-posttest design was implemented to evaluate the effectiveness of the electronic educational program on the nurses perceived confidence/knowledge regarding glycemic …

Utilizing The Stop-Bang Questionnaire To Assess Risk Of Obstructive Sleep Apnea In Hospitalized Patients With Heart Failure To Facilitate Sleep Medicine Referrals Upon Discharge, Chelsea Mitchell

DNP Projects

Background: Obstructive sleep apnea (OSA) is the most common sleep-breathing disorder. Undiagnosed OSA is highly prevalent in the population, especially in those with heart failure. OSA and heart failure combined create a negative feedback loop that can lead to poor clinical outcomes. Unfortunately, many cardiac patients are never screened for OSA.

Purpose: The purpose of this project is to improve screening rates for OSA via the STOP-Bang questionnaire and establish an efficient and effective process for referrals to sleep medicine for heart failure patients screening high-risk.

Methods: The design was a quality improvement project with pre- and post-testing and a …

Improving Knowledge, Confidence, And Competency Among Icu Nurses Concerning The Benefits Of Using The Uk Ventilator Separation Protocol, Brittany Monroe

DNP Projects

Background: The trauma intensive care unit (ICU) at University of Kentucky (UK) Healthcare uses a ventilator separation protocol which provides specific guidelines on the successful weaning of patients from mechanical ventilation. However, many of the nurses are not aware of this protocol as formal education is not included in their orientation or training. This lack of knowledge can lead to risks such as increased patient morbidity, mortality, ICU length of stay, and healthcare-related costs. Research shows that using structured mechanical ventilator weaning tools in the ICU can shorten the duration of mechanical ventilation, which in turn, lowers these associated risks. …

The Impact Of Lung Cancer Screening Education On Knowledge And Screening Rates In A Kentucky Cancer Survivorship Clinic, Alexandra Isler

DNP Projects

Background: Lung cancer is a significant problem in Kentucky, which ranks fourth in the nation in adults who currently smoke. Early detection, through lung cancer screening, can prevent untimely deaths. Several barriers to screening exist including lack of knowledge and awareness among patients regarding lung cancer screening. By increasing knowledge, at risk patients can take the necessary steps to decrease incidence of late stage diagnoses.

Purpose: The purpose of this project was to evaluate patients’ knowledge of lung cancer screening and referral and screening rates before and after one-on-one patient education.

Methods: This was a quality improvement project that used …

The Effect Of An Educational Intervention On Early Mobility Compliance In Oncology Nurses, Jonathan A. Hacker

DNP Projects

Background: Geriatric adult patients admitted into acute care hospital settings are at risk of functional decline in their capacity for activities of daily living and independent ambulation. Many of these patients fail to achieve pre-hospitalization levels of function and continue to decline, requiring additional support and care after discharge. Current literature supports early mobilization and ambulation during hospitalization. However, ambulation and patient mobilization has been shown to be the most missed item of nursing care. There is a gap in literature and patient outcome data regarding the impact of early mobilization on medical-surgical patient populations.

Purpose: The purpose of this …

Evaluation Of Nutritional Guidance From Providers For Patients With Type 2 Diabetes In A Primary Care Setting, Whitney Rice

DNP Projects

Background: Adherence to diet is a challenging part of managing type 2 diabetes mellitus (T2DM). Guidelines recommend including a registered dietician and/or a diabetes educator. While this is the gold standard, there are barriers to implementation in primary care. The Starting the Conversation (STC) diet recall tool can aid primary care providers (PCPs) in providing brief nutrition counseling for patients with T2DM. Purpose: To evaluate the perceptions and practices of PCPs regarding dietary education and documentation for patients with T2DM after provider education and initiation of the STC tool. Methods: This was a quality improvement project using a quasi-experimental pretest …

An Educational Intervention To Improve Neonatal Icu Nurses’ Breastfeeding Support Knowledge, Self-Efficacy, And Breastfeeding Rates At Discharge, Sarah Money

DNP Projects

Background: The benefits of breastfeeding for both mother and baby are known. It is recommended that all infants be exclusively breastfed until six months (Meek & Noble, 2022; North et al., 2021). Despite this, breastfeeding rates remain low, especially in medically fragile infants requiring care in the neonatal intensive care unit (NICU) (Rollins et al., 2016). Receipt of evidence-based breastfeeding support by healthcare providers has been shown to improve breastfeeding success; however, many healthcare providers report not being comfortable or knowledgeable enough to offer support consistently (Mulcahy et al., 2022; Rollins et al., 2016).

Purpose: This study aims …

Mediation By Fatalism Of The Association Between Symptom Burden And Self-Care Management In Patients With Heart Failure, Ashmita Thapa, Misook L. Chung, Jia-Rong Wu, Abigail Latimer, Terry A. Lennie, Gia Mudd-Martin, Chin-Yen Lin, Jessica Harman Thompson, Junghee Kang, Debra K. Moser

UK CARES Faculty Publications

Background: Clinicians and researchers often assume that symptom burden is associated with self-care management (SCM) in patients with heart failure (HF). However, that association is often not borne out in simple regression analyses and may be because another variable mediates the association. Fatalism is an appropriate candidate for mediation and is the belief that circumstances are predetermined without opportunity for control by individuals.

Objective: Our objective was to determine whether fatalism mediated the relationship of symptom burden with SCM among adults with HF.

Methods: We conducted a secondary analysis (N = 95) from a clinical trial. We used Self-care of …

Mediators Of The Association Between Cognitive Function And Self-Care Behaviors In Patients Hospitalized With An Exacerbation Of Heart Failure, Jia-Rong Wu, Chin-Yen Lin, Abigail Latimer, Muna Hassan Hammash, Debra K. Moser

UK CARES Faculty Publications

Background: Patients with heart failure (HF) must engage in self-care, yet their self-care is often poor. Cognitive function commonly is impaired in HF and is associated with poor self-care. Heart failure knowledge and self-care confidence also are needed to preform self-care. Few investigators have examined mediators of the association of cognitive function with self-care.

Objectives: The aim of this study was to determine whether HF knowledge and self-care confidence mediated the association of cognitive function with self-care maintenance and management among patients with HF.

Methods: This was a cross-sectional observational study of 164 patients with HF. Cognitive function was assessed …

Champions To Enhance Implementation Of Clinical And Community-Based Interventions In Cancer: A Scoping Review, Joseph Astorino Nicola, M. Muska Nataliansyah, Maria A. Lopez‑Olivo, Adebola Adegboyega, Kelly A. Hirko, Lou‑Anne R. Chichester, Nora L. Nock, Pamela Ginex, Shannon M. Christy, Paul Levett

Nursing Faculty Publications

Background Champions are integral across research in cancer, yet studies exploring their roles are limited and have produced mixed results. The current review examines and synthesizes descriptions of how champions emerged and the types of activities they most often performed. By examining evidence from across the translational research continuum, this scoping review aims to characterize the role of champions and strategies that facilitate their involvement in the implementation of cancer care interventions in both clinical and community‑based settings.

Methods This scoping review was designed and implemented in compliance with PRISMA‑ScR. The review focused on peer‑reviewed articles in English‑language journals. We …

Communication With Physicians And Family About Breast Cancer Recurrence, Kimberly M. Kelly, Pragya Rai, Jamie L. Studts, Stephanie Dickinson, Beate Henschel, Mark Dignan, Mara D. Chambers, Hannah Hazard-Jenkins

UK CARES Faculty Publications

Objective: Adequate physician-patient communication about cancer recurrence is vital to quality of life and to informed decision-making related to survivorship care. The current study was guided by a cognitive-affective framework to examine communication with family and physicians about breast cancer recurrence risk.

Methods: A survey of recently-diagnosed, early-stage breast cancer patients in Appalachia investigated physician- patient and familial communication about breast cancer recurrence risk.

Results: Over 30% of participants reported not talking to family or physicians about breast cancer recurrence risk. Younger patients reported more conversations, and speaking with physicians was associated with greater perception risk factors associated with recurrence …

A Gold-Based Inhibitor Of Oxidative Phosphorylation Is Effective Against Triple Negative Breast Cancer, R. Tyler Mertens, Jong Hyun Kim, Samuel Ofori, Chibuzor Ngozi Olelewe, Paul J. Kamitsuka, Gunnar F. Kwakye, Samuel G. Awuah

Markey Cancer Center Faculty Publications

Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis with limited treatment options. New treatment paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning with high anticancer potency in vitro and in vivo. Here, we show that an efficacious Au(III) dithiocarbamate (AuDTC) compound induce mitochondrial dysfunction and oxidative damage in cancer cells. Efficacy of AuDTC in TNBC mouse models harboring mito- chondrial oxidative phosphorylation (OXPHOS) dependence and metabolic heterogeneity establishes its thera- peutic potential following systemic …

Cell Aggregation Activates Small Gtpase Rac1 And Induces Cd44 Cleavage By Maintaining Lipid Raft Integrity, Dong Li, Younhee Park, Hami Hemati, Xia Liu

Markey Cancer Center Faculty Publications

Lipid rafts are highly ordered membrane domains that are enriched in cholesterol and glycosphingolipids and serve as major platforms for signal transduction. Cell detachment from the extracellular matrix (ECM) triggers lipid raft disruption and anoikis, which is a barrier for cancer cells to metastasize. Compared to single circulating tumor cells (CTCs), our recent studies have demonstrated that CD44-mediatd cell aggregation enhances the stemness, survival and metastatic ability of aggregated cells. Here, we investigated whether and how lipid rafts are involved in CD44-mediated cell aggregation. We found that cell detachment, which mimics the condition when tumor cells detach from the ECM …

Deficiency Of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality And Lung Injury In Mice, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Luke W. Meredith, Brittany Dong, Qian Wang, Ling Guo, Xiangan Li, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock, Marlene E. Starr, Christopher M. Waters, Preetha Shridas

Saha Cardiovascular Research Center Faculty Publications

Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated …