Medical Specialties Commons^™

Cognitive Rehabilitation Of Brain Tumor Survivors: A Systematic Review, Rabeet Tariq, Hafiza Fatima Aziz, Shahier Paracha, Nida Zahid, Timothy J. Ainger, Farhan A. Mirza, Syed Ather Enam

Neurology Faculty Publications

Background Cognitive decline is commonly seen in brain tumor (BT) patients and is associated with a worsened prognosis. Cognitive rehabilitation (CR) for cancer-related cognitive dysfunction has been widely studied for non-central nervous system cancers; however, recent emerging research has commenced documenting CR strategies for BT patients and survivors. Our objective was to review the current literature on various CR modalities in patients and BT survivors.

Methods The review was conducted in accordance with the PRISMA guidelines. The studies on CR were searched across 3 databases using a predefined search strategy. After removing duplicates, performing initial and full-text screenings, and applying …

Tam Receptors Mediate The Fpr2-Driven Pain Resolution And Fibrinolysis After Nerve Injury, Beate Hartmannsberger, Adel Ben‑Kraiem, Sofia Kramer, Carolina Guidolin, Ida Kazerani, Kathrin Doppler, Dominique Thomas, Robert Gurke, Marco Sisignano, Pranav P. Kalelkar, Andrés J. García, Paula V. Monje, Michael Sammeth, Asma Nusrat, Alexander Brack, Susanne M. Krug, Claudia Sommer, Heike L. Rittner

Markey Cancer Center Faculty Publications

Nerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothe- lial and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery. To this end, we analysed the nerve barrier property portfolio, pain behaviour battery and lipidomics for precursors of specialized pro-resolving meditators (SPMs) and their receptors in chronic constriction injury of the rat sciatic nerve to identify tar- gets for pain resolution by resealing the selected nerve barriers. Of the three nerve barriers—perineurium, capillaries and myelin—only capillary tightness specifically against larger molecules, such as fibrinogen, recuperated with …

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage, Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John A. D'Orazio, D. Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K. St. Clair, Luksana Chaiswing

Markey Cancer Center Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off- target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage …

Engaging Nurses In Effective Cost Of Care Conversations To Address Cancer-Related Financial Toxicity: Results From An Exploratory Survey, Jean Edward, Amanda T. Wiggins, Louis G. Baser, Haafsah Fariduddin, Joanna F. Doran, Monica F. Bryant, John August D'Orazio, Kimberly D. Northrip

Markey Cancer Center Faculty Publications

Few evidence-based trainings exist on how to equip healthcare providers, particularly nurses, with the skills to engage in cost of care conversations with patients/caregivers to mitigate the impact of cancer-related financial toxicity. This study evaluated a pilot training developed in collaboration with Triage Cancer® to prepare oncology nurses to identify and assist patients/caregivers facing financial and/or legal barriers to care. Ten pediatric oncology nurses completed the training and pre/post-surveys on behaviors related to financial and legal need screening, frequency and comfort level of answering questions, knowledge, and behavior changes, along with training evaluation questions. At baseline, six nurses reported never …

Pharmacological Or Genetic Inhibition Of Ltcc Promotes Cardiomyocyte Proliferation Through Inhibition Of Calcineurin Activity, Lynn A. C. Devilée, Abou Bakr M. Salama, Jessica M. Miller, Janice D. Reid, Qinghui Ou, Nourhan M. Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K. Rosengart, Douglas A. Andres, Jonathan Satin, Tamer M. A. Mohamed, James E. Hudson, Riham R. E. Abouleisa

Markey Cancer Center Faculty Publications

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M. Kusminski, Terry D. Hinds Jr., Philipp E. Scherer

Markey Cancer Center Faculty Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

Urobilin Derived From Bilirubin Bioconversion Binds Albumin And May Interfere With Bilirubin Interacting With Albumin: Implications For Disease Pathology, Kevin I. Williams, Priyanka Suryadevara, Chang-Guo Zhan, Terry D. Hinds Jr., Zachary A. Kipp

Markey Cancer Center Faculty Publications

Background/Objectives: Bilirubin is a hydrophobic molecule that binds the carrier protein albumin for transport through systemic circulation. Bilirubin is cleared from the body through the liver and excreted into the intestines, where the microbiota modifies the chemical structure, forming urobilin, which can be reabsorbed into circulation by the hepatic portal vein. Urobilin has no known function. It is also unknown whether urobilin binds albumin for transport in circulation. We hypothesized that because of the likeness of their chemical structures, urobilin would also bind albumin like bilirubin does. Methods: First, we used in silico docking to predict if urobilin would bind …

Heme Oxygenase, Biliverdin Reductase, And Bilirubin Pathways Regulate Oxidative Stress And Insulin Resistance: A Focus On Diabetes And Therapeutics, Wang-Hsin Lee, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Evelyn A. Bates, Olufunto O. Badmus, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.6%. Shockingly, the global T2DM population is anticipated to double by 2050 compared with 2021. Prior studies indicate that oxidative stress and inflammation are instrumental in causing insulin resistance and instigating metabolic diseases. Numerous methods and drugs have been designed to combat insulin resistance, including metformin, thiazolidinediones (TZDs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1RA), and dipeptidyl peptidase 4 inhibitors (DPP4i). Bilirubin is an antioxidant with …

Dissecting The Biophysical Mechanisms Of Oleate Hydratase Association With Membranes, William A. Lathram, Robert J. Neff, Ashley N. Zalla, James D. Brien, Vivekanandan Subramanian, Christopher D. Radka

Markey Cancer Center Faculty Publications

This study investigates the dynamics of oleate hydratase (OhyA), a bacterial flavoenzyme from Staphylococcus aureus, and its interactions with lipid membranes, focusing on the factors influencing membrane binding and oligomerization. OhyA catalyzes the hydration of unsaturated fatty acids, playing a key role in bacterial pathogenesis by neutralizing host antimicrobial fatty acids. OhyA binds the membrane bilayer to access membrane-embedded substrates for catalysis, and structural studies have revealed that OhyA forms oligomers on membrane surfaces, stabilized by both protein-protein and protein-lipid interactions. Using fluorescence correlation spectroscopy (FCS), we examined the effects of membrane curvature and lipid availability on OhyA binding to …

Advances In Magnetic Nanoparticles For Molecular Medicine, Xiaoyue Yang, Sarah E. Kubican, Zhongchao Yi, Sheng Tong

Markey Cancer Center Faculty Publications

Magnetic nanoparticles (MNPs) are highly versatile nanomaterials in nanomedicine, owing to their diverse magnetic properties, which can be tailored through variations in size, shape, composition, and exposure to inductive magnetic fields. Over four decades of research have led to the clinical approval or ongoing trials of several MNP formulations, fueling continued innovation. Beyond traditional applications in drug delivery, imaging, and cancer hyperthermia, MNPs have increasingly advanced into molecular medicine. Under external magnetic fields, MNPs can generate mechano- or thermal stimuli to modulate individual molecules or cells deep within tissue, offering precise, remote control of biological processes at cellular and molecular …

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 integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at …

Engaging Nurses In Effective Cost Of Care Conversations To Address Cancer-Related Financial Toxicity: Results From An Exploratory Survey, Jean Edward, Abigail Wiggins, Louis G. Baser, Haafsah Fariduddin, Joanna F. Doran, Monica F. Bryant, John A. D'Orazio, Kimberly D. Northrip

Markey Cancer Center Faculty Publications

Few evidence-based trainings exist on how to equip healthcare providers, particularly nurses, with the skills to engage in cost of care conversations with patients/caregivers to mitigate the impact of cancer-related financial toxicity. This study evaluated a pilot training developed in collaboration with Triage Cancer® to prepare oncology nurses to identify and assist patients/caregivers facing financial and/or legal barriers to care. Ten pediatric oncology nurses completed the training and pre/post-surveys on behaviors related to financial and legal need screening, frequency and comfort level of answering questions, knowledge, and behavior changes, along with training evaluation questions. At baseline, six nurses reported never …

Association Between Education And Allostatic Load With Risk Of Cancer Mortality Among Hispanic Women, Melissa Lopez-Pentecost, Cynthia Li, Marlo Vernon, Sydney P. Howard, Jessica Amezcua, Justin Xavier Moore

Markey Cancer Center Faculty Publications

Purpose: Cancer remains the leading cause of death among Hispanics in the US. While social determinants of health, such as educational attainment, have been linked to negative health outcomes, their biological mechanisms remain poorly understood. We evaluated the association between educational attainment and allostatic load (AL), a measure of chronic physiologic stress, with risk of cancer mortality in Hispanic women from the National Health and Nutrition Examination Survey (NHANES).

Methods: We performed a retrospective analysis among 5637 Hispanic women in NHANES from 1988 to 2010 with follow-up data through 2019. Educational attainment was categorized into a two-level variable: less than …

Functional Assessment Of Migration And Adhesion To Quantify Cancer Cell Aggression, Lauren E. Mehanna, James D. Boyd, Chloe G. Walker, Adrianna R. Osborne, Martha E. Grady, Brad J. Berron

Markey Cancer Center Faculty Publications

During epithelial-to-mesenchymal transition (EMT), cancer cells lose their cell–cell adhesion junctions as they become more metastatic, altering cell motility and focal adhesion disassembly associated with increased detachment from the primary tumor and a migratory response into nearby tissue and vasculature. Current in vitro strategies characterizing a cell’s metastatic potential heavily favor quantifying the presence of cell adhesion biomarkers through biochemical analysis; however, mechanical cues such as adhesion and motility directly relate to cell metastatic potential without needing to first identify a cell specific biomarker for a particular type of cancer. This paper presents a comprehensive comparison of two functional metrics …

Inclusion Of Surgery In Multimodality Treatment Is Predictive Of Better Survival In Stage Iiia Non-Small Cell Lung Cancer: An Inverse Probability Treatment-Weighting Analysis, Feitong Lei, Janeesh Sekkath-Veedu, Bin Huang, Quan Chen, Mansi Shah-Jadeja, Thomas E. Stinchcombe, Zhonglin Hao

Markey Cancer Center Faculty Publications

Introduction: Stage IIIA non-small cell lung cancers (NSCLC) are treated with surgery-based multimodality approach or definitive chemoradiation therapy plus durvalumab consolidation. It is not clear whether surgery-based multimodality therapy has any survival advantage over definitive chemoradiation plus immunotherapy consolidation.

Method: National Cancer Database (NCDB) was used to identify NSCLC patients at stage IIIA (AJCC8, T3N1/T4N0-1 or T1N2/T2N2) who are treated with surgery-based multimodality approach or definitive chemoradiation plus durvalumab. Survival between groups were compared using inverse probability treatment weighting (IPTW)-adjusted Kaplan Meier curves and Cox proportional hazards regression analysis. Results were independently confirmed by Landmark Inverse and Clone Censor Weight …

M1 Macrophage‑Engineered Vesicles Have Anti‑Cancer Activity In Ovarian Cancer, Connie D. Cao, J. Robert Mccorkle, Derek B. Allison, Donglin Yan, Kristen S. Hill, Lan Li, Rani Jayswal, David Schweer, Charles S. Dietrich Iii, Frederick R. Ueland, Christopher I. Richards, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Background: Ovarian cancer typically presents at an advanced stage, has a poor prognosis, and is a leading cause of cancer-related deaths in women. Extracellular vesicles (EVs) are cell membrane-derived nanoparticles that function in specific cell- to-cell communication and are under development as novel drug delivery vehicles and modulators of the tumor microenvironment. Artificial cell-derived vesicles (ACDVs) from M1 macrophages are able to repolarize macrophages from a M2 to a M1 phenotype and target tumor cells in in vitro studies.

Results: In this study, we generated engineered EVs (EEVs) by membrane disruption of M1 macrophages (MEVs) with and without cisplatin to …

Measuring The Impact Of A Catchment Area Surveillance Tool On Cancer Center Adopters, Todd Burus, Caree R. Mcafee, Natalie P. Wilhite, Pamela C. Hull

Markey Cancer Center Faculty Publications

Background: The University of Kentucky Markey Cancer Center developed the data gathering and visualization platform Cancer InFocus (CIF) as a solution for cancer center catchment area surveillance. CIF was released in June 2022 and made available for use to other institutions through a no‐cost licensing agreement. The purpose of this study was to evaluate the impact CIF has had on cancer centers since its release.

Methods: The authors adapted an existing management evaluation framework to assess the impact of CIF across three spheres—idea dissemination, product engagement, and adopter satisfaction. This assessment included an online survey administered between the dates of …

Tracking Community Outreach And Engagement Activities Among National Cancer Institute-Designated Cancer Centers, Todd Burus, Caree R. Mcafee, Pamela C. Hull, Amy E. Leader, Christopher Mcnair

Markey Cancer Center Faculty Publications

The National Cancer Institute’s (NCI) Cancer Center Support Grant mandates that NCI-designated cancer centers establish a Community Outreach and Engagement (COE) component to help direct efforts at reducing cancer burden within their catchment areas. Despite the critical role of COE offices, little is known about how they track and evaluate outreach activities and outcomes. We gathered information on current practices from representatives of 40 out of 65 COE offices using an online survey. Although nearly all responding centers (97.5%) tracked COE activities, no consensus existed on resources used, and satisfaction with current solutions was mixed (51.0% not satisfied). Respondents expressed …

Biparental Inheritance Of Germline-Specific Chromosomes In The Sea Lamprey And Their Roles In Oocytes, Vladimir A. Timoshevskiy, Nataliya Timoshevskaya, Kaan İ. Eşkut, Kasturi Rajandran, Jeramiah J. Smith

Markey Cancer Center Faculty Publications

Many eukaryotic species undergo programmed elimination of specific chromosomes during embryogenesis, typically retaining these chromosomes only in their germ cells. In some species, programmatic elimination of GRCs, or sex chromosomes, also occurs in a sex-specific manner, with specific chromosomes being transmitted or eliminated by only one sex. As such, these chromosomes provide a unique perspective on the evolution of gene functions that are advantageous to the germline and genetic tradeoffs between somatic vs germline or oocyte vs sperm biology. While GRCs have been extensively characterized in male sea lampreys (Petromyzon marinus), the status of GRCs in females has not yet …

Cryptic To Conventional Cytogenetics: Philadelphia- Like All Presenting With Hypereosinophilia, Zena Chahine, Leonard Yenwong Fai, Sainan Wei, Ayman Qasrawi

Markey Cancer Center Faculty Publications

BCR::ABL1-like B-lymphoblastic leukaemia (B-ALL) neoplasms lack the BCR::ABL1 translocation but have a gene expression profile like BCR::ABL1 positive B-ALL. This includes alterations in cytokine receptors and signalling genes, such as CRLF2, ABL1, ABL2, JAK2, PDGFRB and EPOR. Cases with CRLF2 rearrangements account for approximately 50% of cases of Philadelphia-like acute lymphoblastic leukaemia (Ph-like ALL), and the frequency of specific genomic lesions varies with ethnicity such that IGH::CRLF2 translocations are more common in Hispanics and Native Americans. We report two cases of BCR::ABL1-like ALL, with significant eosinophilia. A Hispanic man in his early 20s and a Hispanic woman in her 50s …

Cabozantinib Selectively Induces Proteasomal Degradation Of P53 Somatic Mutant Y220c And Impedes Tumor Growth, Fang Lin Lv, Lu Zhang, Cheng Ji, Lei Peng, Mingxian Zhu, Shumin Yang, Shunli Dong, Mingxuan Zhou, Fanfan Guo, Zhenyun Li, Fang Wang, Youguo Chen, Jinhua Zhou, Xingcong Ren, Genhai Shen, Jin-Ming Yang, Bin Li, Yi Zhang

Markey Cancer Center Faculty Publications

Inactivation of p53 by mutations commonly occurs in human cancer. The mutated p53 proteins may escape proteolytic degradation and exhibit high expression in tumors and acquire gain-of-function activity that promotes tumor progression and chemo-resistance. Therefore, selectively targeting of the gain-of-function p53 mutants may serve as a promising therapeutic strategy for cancer prevention and treatment. In this study, we identified cabozantinib, a multikinase inhibitor currently used in the clinical treatment of several types of cancer, as a selective inducer of proteasomal degradation of the p53-Y220C mutant. We demonstrate that cabozantinib disrupts the interaction between p53Y220C and USP7, a deubiquitylating enzyme, resulting …

A Comparison Of Adjuvant Therapy Modality And Treatment Outcomes Between Appalachian And Non-Appalachian Patients With High-Risk Endometrial Carcinoma, Josie D. Llanora, Gregory S. Hawk, Laura M. Harbin, Sara Lee, Madison Lane, Madison T. Hickey, Elizabeth Pendygraft, Lauren Baldwin, Megan L. Hutchcraft

Markey Cancer Center Faculty Publications

Objective: The incidence and mortality of endometrial cancer is increasing. After surgical staging, patients with high-risk disease often undergo adjuvant treatment, which may include systemic therapy, radiation therapy, or combined modalities. Patients in rural Appalachia have limited access to subspecialty care needed for optimal disease management. This study aims to compare adjuvant treatment regimens and outcomes among patients with high-risk endometrial cancer living in Appalachian and non-Appalachian regions.

Methods: We retrospectively identified 179 patients with high-risk endometrial carcinoma who underwent surgical staging at a single academic medical center and received adjuvant therapy between 2012 and 2019. Patients were identified as …

African American And African-Born Black Women’S Perspectives And Experiences With A Cervical Health Education And Hpv-Self Sampling Intervention, Shania Jones, Abubakari Wuni, Adaeze Aroh, Adebola Olamide Adegboyega

Markey Cancer Center Faculty Publications

Background/Objectives: A combination of cervical cancer prevention education and the provision of HPV self-collection kits has been found to increase the uptake of HPV testing among women. However, there is limited research evaluating the perspectives and experiences of women who have participated in a cancer prevention education and received a complimentary HPV self-collection kit. We report the experiences of women who took part in Health is Wealth: a cervical health intervention and received a complimentary HPV self-sampling kit for cervical cancer screening.

Methods: This pilot qualitative study enrolled twenty-four women who participated in one-on-one semi-structured interviews to provide feedback and …

A High-Throughput Workflow For Assessing Self-Renewal Using Colony Formation Assays, Majd Al-Hamaly, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

The colony formation assay (CFA) is a widely used method to assess the self-renewal capacity of cancer cells and evaluate how this property is affected by drug treatment. This protocol presents a streamlined, high-throughput CFA workflow optimized for T-cell acute lymphoblastic leukemia (T-ALL), making it suitable for large-scale drug screening projects. Colonies are grown in a methylcellulose-based 3D matrix and quantified using an automated analysis pipeline, allowing robust estimation of colony number and size. This cost-effective approach provides a scalable platform for identifying compounds that impair self-renewal, facilitating prioritization of hits for validation in more complex in vivo models.

Analysis Of Facilitators Of And Barriers To Enactment Of State Regulation Of Indoor Tanning By Minors, Carolyn J. Heckman, Anna Mitarotondo, David B. Buller, Julia Berteletti, Kevin Schroth, Jerod L. Stapleton, Robert P. Dellavalle

Markey Cancer Center Faculty Publications

Background: Indoor tanning (IT) causes skin cancers, including potentially deadly melanoma. IT often starts during youth, a critical time for deleterious skin damage. About half of the US states have enacted laws banning IT for minors under age 18.

Purpose: This study reports qualitative findings from interviews with key informants (KIs) involved in IT legislative efforts to identify/describe factors influencing law enactment, based on the multiple streams framework.

Methods: Guided by expert advisors and using snowball-sampling, KIs from 16 states with most recently enacted IT laws regulating minor access and states without restrictions were contacted. In virtual interviews, KIs shared …

Capturing Community Perspectives In A Statewide Cancer Needs Assessment: Online Focus Group Study, Jessica R. Thompson, Keeghan Francis, Caree R. Mcafee, Madeline Brown, Todd Burus, Melinda Rogers, Connie L. Sorrell, Elizabeth A. Westbrook, Lovoria B. Williams, Jennifer Redmond Knight, Elaine Russell, Natalie P. Wilhite, Pamela C. Hull

Markey Cancer Center Faculty Publications

Background: Kentucky has the highest all-site cancer incidence and mortality rates in the United States. Conducting needs assessments in a large geographic area, such as an entire state, poses challenges in collecting qualitative data from diverse rural and urban contexts. In 2021, a steering committee was formed to drive a multimethod, statewide cancer needs assessment (CNA) to identify the future priorities for all cancer-related care in Kentucky.

Objective: We aimed to report on the online focus group component of the CNA by documenting existing community resources and perceived needs across the cancer care continuum. In addition, we aimed to explore …

Characterization Of P53 P.T253i As A Pathogenic Mutation Underlying Li-Fraumeni Syndrome, Nathaniel C. Holcomb, Amanda M. Harrington, Hong Pu, Berina Halilovic, Nathan R. Shelman, Shulin Zhang, Catherine Sears, Terra Armstrong, Brent J. Shelton, Lauren Corum, John A. D'Orazio

Markey Cancer Center Faculty Publications

We identified a germline TP53 c.758C > T (p.T253I) mutation in the TP53 tumor suppressor gene in a pediatric adrenocortical carcinoma (ACC) patient. Characteristic of pathogenic p53 mutations, we observed upregulation of total p53 protein levels in the patient’s ACC and concurrent suppression of the wild-type (WT) TP53 allele. As ACC can be associated with Li-Fraumeni Syndrome (LFS) and the mutation has not yet been linked to LFS, we sought to characterize the functionality of the T253I mutation. We acquired p53^-/-HEK293 cells and stably transduced them with GFP-tagged wild type (T253) or T253I p53 as well as two established …

Cisplatin-Loaded M1 Macrophage-Derived Vesicles Have Anti-Cancer Activity In Osteosarcoma, Namrata Anand, Joseph Robert Mccorkle, David Schweer, Lan Li, Kristen S. Hill, Melissa A. Fath, Derek B. Allison, Christopher L. Richards, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Osteosarcoma (OS) is a relatively rare bone malignancy that primarily affects children and young adults and is associated with significant morbidity and mortality. Cisplatin is a mainstay of treatment, but its efficacy is limited by off-target toxicities. Immunotherapy is not effective due to a poor antigenic tumor microenvironment. Here, we address these challenges by using manufactured M1 macrophage-derived vesicles (MVs) loaded with cisplatin. Human blood and mouse RAW 264.7 M1 macrophages were used to prepare empty (E-MVs) and cisplatin-loaded MVs (C-MVs). Human OS cell lines were used in vitro and in a tibia xenograft mouse model to evaluate the anti-cancer …

Differences In The Cancer Burden And Current Funding Of Nci-Designated Cancer Centers, Todd Burus, Caree R. Mcafee, Pamela C. Hull

Markey Cancer Center Faculty Publications

Importance  National Cancer Institute (NCI)-designated clinical and comprehensive cancer centers are required to define a geographic catchment area (CA) in which they focus research, outreach, and engagement efforts for the purposes of reducing cancer burden, particularly among certain vulnerable populations. A comprehensive analysis of the cancer burden of these catchment areas and their association with cancer center funding through the Cancer Center Support Grant (CCSG) has not been performed.

Objective  To examine CA cancer burden indicators and cancer center CCSG funding during the 2023 federal fiscal year (FY23).

Design, Setting, and Participants  This population-based cross-sectional study assessed cancer center cancer …

Disparities In Human Papillomavirus–Associated Cancer Incidence By Appalachian Residence, Todd Burus, Melina Windon, Yasminka A. Jakubek, Krystle A. Lang Kuhs

Markey Cancer Center Faculty Publications

Importance  Poor socioeconomic conditions and corresponding health disparities have historically characterized the Appalachian region of the US. Low uptake of the human papillomavirus (HPV) vaccine and high rates of cervical cancer have been observed in the region; however, a comprehensive assessment of HPV-associated cancer in Appalachia has not been performed.

Objective  To compare the burden of HPV-associated cancer incidence between the Appalachian and non-Appalachian regions of the US.

Design, Setting, and Participants  This cross-sectional study of HPV-associated cancer incidence rates and trends used the US Cancer Statistics Incidence Analytic Database, covering 99% of the US population and 100% of the …