Medical Specialties Commons^™

Developing A Multidisciplinary Pediatric Cancer Predisposition Service At A Mid-Sized Children’S Hospital, Amanda M. Harrington, John August D'Orazio

Markey Cancer Center Faculty Publications

Roughly one in ten children and young adults diagnosed with cancer has an underlying genetic variant that may explain his/her malignancy. It is critical to identify patients with cancer predisposition syndromes (CPSs) to provide personalized cancer treatment, surveillance, counseling, psychosocial support, and in some cases, risk-reducing interventions to maximize long-term outcomes. Over the past five years, we developed a comprehensive pediatric CPS program at our institution. We engaged our institutional adult cancer center for clinical cancer genetic counseling services and needed research shared resource facilities. We also initiated a clinical study called “Project Inherited Cancer Risk” (PICR) to identify pediatric …

Dual Orexin Receptor Antagonism With Lemborexant Enhances Microglial Clearance Of Β-Amyloid In Mice, Ashish Sharma, Emiko Segawa, Xiaoying Chen, Sohui Park, Shoutang Wang, Riley E. Irmen, Nicholas J. Constantino, Chanung Wang, Michael F. Kanan, Marco Colonna, Shannon L. Macauley, Jocelyn Y. Cheng, Ken Hatanaka, Margaret Moline, Erik S. Musiek

Sanders-Brown Center on Aging Faculty Publications

Background: Sleep disturbances elevate brain amyloid-beta (Aβ) levels and represent a modifiable risk factor for Alzheimer’s disease (AD). The orexin/hypocretin system regulates sleep–wake behavior and has emerged as a therapeutic target in AD; however, the effects of FDA-approved dual orexin receptor antagonists (DORAs) on amyloid pathology remain unclear. We compared lemborexant, an FDA-approved DORA, to doxepin, an antihistaminergic sleep medication, on amyloid pathology and microglial responses in PSAPP mice.

Methods: PSAPP mice received lemborexant (10 or 30 mg/kg/day), doxepin (35 mg/kg/day), or vehicle for 6 weeks beginning prior to plaque onset or 4 weeks after established pathology. Sleep was assessed …

Effect Of Canagliflozin Pretreatment On The Efficacy Of Insulin Therapy To Rescue Type 1 Diabetes-Related Bone Fragility In Male Mice, Jeffry S. Nyman, R. Clay Bunn, Sasidhar Uppuganti, Elizabeth M. Hennen, Plaban Mishra, Philip D. Ray, Anthony Garcia Mendez, Evangelia Kalaitzoglou, John L. Fowlkes

Barnstable Brown Diabetes Center Faculty Publications

Humans with type 1 diabetes (T1D) have a higher-than-expected fracture risk, and bone is weak in mouse models of T1D. Since hyperglycemia is thought to deleteriously affect tissue-level sensitivity of insulin action, we hypothesized that glucose-lowering by canagliflozin (Cana) improves the ability of insulin treatment to rescue the T1D-related decrease in bone strength. To test this hypothesis, male DBA/2 mice with and without streptozotocin (STZ)-induced hyperglycemia at 8 weeks of age were fed a diet with and without Cana (50 ppm) at 10 weeks of age and then the T1D mice, regardless of placebo diet or Cana diet, were treated …

Evolution Of A Client‐Level Dataset: 20 Years Of National Child Traumatic Stress Network Data Collection, C. A. Purbeck, A. N. Cooke, L. J. Liang, C. Smith, J. Staten, J. Epstein, H. B. Hodgdon, Jessica Eslinger, A. Wells, J. Goodrich, T. H. Bethel, K. Willett, Y. C. Fu, J. A. Fairbank, E. C. Briggs

Center on Trauma and Children Faculty Publications

Objectives: For 20 years, the National Child Traumatic Stress Network's (NCTSN) data collection efforts have been a central mechanism for Clinical Quality Improvement (ClQI). The NCTSN is a federally funded initiative in the United States composed of programs dedicated to raising the standard of care and increasing access to services for children and families who have experienced traumatic events.

Methods: These efforts span three initiatives: the Core Data Set (CDS), the Clinical Improvement through Measurement Initiative (CIMI) Measurement Based Care (MBC), and CIMI Data Sharing (CIMI-DS) that collected and analyzed client-level data to improve care for children and families served …

Durable Left-Ventricular Assist Device Inflow Thrombosis Following External Outflow Graft Obstruction, Mohammad J. Malik, Jin Woo Chung, Matthias Loebe, John C. Gurley, Emma J. Birks, Dhruv Kothari, Masashi Kawabori

Surgery Faculty Publications

Background: External outflow graft obstruction (EOGO) is an emerging complication due to improved pump durability. We experienced a rare sequence of complications, inflow thrombus formation following EOGO with reduced left-ventricular assist device flow.

Case Summary: A 41-year-old man, 2 years post HeartMate 3 (HM3) implantation, presented with low-flow from EOGO. Outflow graft stenting resulted in improvement but returned 1 month later with persistent low flow. Pump thrombosis was excluded. Flow had minimal response to RPM increase. Outflow graft was widely patent. Inflow obstruction was suspected, and HM3-to-HM3 exchange revealed extensive thrombus formation within the inflow cannula. Left-ventricular assist device flow …

Liposome-Encapsulated Clodronate And Cox-2 Inhibitor Treatment Impair Ventilatory Recovery But Improve Compensatory Locomotor Function Following Cervical Spinal Cord Injury In Rats, Aaron L. Silverstein, Chris M. Calulot, Christopher J. Mclouth, John C. Gensel, Warren J. Alilain

Spinal Cord and Brain Injury Research Center Faculty Publications

Over half of all spinal cord injuries (SCIs) in the United States occur at the cervical level and can cause locomotor deficits and life-threatening breathing dysfunction. Interestingly, the bisphosphonate drug clodronate has shown efficacy in ameliorating tissue damage and improving locomotor recovery acutely after experimentally induced thoracic SCI. Thus, we hypothesized that clodronate treatment would improve recovery of breathing and locomotor function following a C2 hemisection (C2Hx) model of cervical SCI in rats. Serendipitously, changes to animal use guidelines led to the inclusion of carprofen, a non-steroidal anti-inflammatory drug (NSAID), as another independent variable in our study. We treated adult …

Traumatic Brain Injury Exacerbates Mitochondrial Dysfunction In App/Ps1 Knock-In Mice Through Time-Dependent Pathways, Elika Z. Moallem, Hemendra J. Vekaria, Teresa Macheda, Margaret R. Hawkins, Kelly N. Roberts, Samir P. Patel, Patrick G. Sullivan, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Cerebral hypometabolism occurs in both traumatic brain injury (TBI) and Alzheimer's disease (AD), but whether these conditions act through distinct or overlapping mechanisms is unclear. TBI disrupts cerebral metabolism via blood–brain barrier damage, altered glucose transporter expression, calcium buffering abnormalities, and oxidative damage to metabolic enzymes. AD-related hypometabolism is linked to amyloid-β (Aβ) effects on mitochondria, including impaired respiration, oxidative stress, and altered mitophagy, fusion, and fission. We tested whether TBI-induced mitochondrial dysfunction exacerbates Aβ-mediated impairment using a closed-head injury (CHI) model in APP/PS1 knock-in (KI) mice. Injuries were delivered at 4–5 months of age, before plaque formation and mitochondrial …

Current Concepts In Hip And Core Assessment To Reduce The Risk Of Acl Injury, Jeremy M. Burnham, Anthony T. Drazick, Ghislain Aminake, Darren L. Johnson, Mary Lloyd Ireland, Brian W. Noehren

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background: Hip and trunk (“core”) muscle dysfunction has emerged as a modifiable contributor to lower-limb biomechanics linked with non-contact anterior cruciate ligament (ACL) injuries. Clinicians increasingly target core stability and control during injury-prevention screening and post-operative rehabilitation programs; however, the literature lacks a focused synthesis of core-directed strategies for ACL injury mitigation. The purpose of this current concepts review is to synthesize current evidence on hip- and core-focused assessment and rehabilitation strategies that may mitigate ACL injury risk.

Design: Current Concepts Review.

Methods: A narrative search of PubMed and Google Scholar (January 2000 – April 2025) identified biomechanical, prospective, interventional, …

Candidate Interaction Partners Of Calpain-5 Suggest Clues To Its Involvement In Neovascular Inflammatory Vitreoretinopathy, Jozsef Gal, Vimala Bondada, Rachel Crasta, Dorothy E. Croall, Calvin P. Vary, James W. Geddes

Spinal Cord and Brain Injury Research Center Faculty Publications

Although calpain-5/CAPN5 is widely expressed in mammals, little is known regarding its functions. Pathogenic mutations of CAPN5 are causal for a devastating autoimmune eye disease, neovascular inflammatory vitreoretinopathy (NIV). To provide insight into both the physiological and pathological roles of CAPN5, it is essential to identify candidate interaction partners and possible substrates. Human SH-SY5Y neuroblastoma cells, transfected with full-length catalytically dead (Cys81Ala) CAPN5-3×FLAG, were used for anti-FLAG co-immunoprecipitation (co-IP) and quantitative proteomics using Sequential Window Acquisition of all THeoretical mass spectra (SWATH-MS). Fifty-one proteins were enriched at least four-fold, p < 0.01, relative to cells transfected with an empty FLAG vector. A high proportion (24/51) of candidate CAPN5 interaction partners are associated with protein quality control, including components of the chaperonin, chaperone, and ubiquitin–proteasome systems. Additional candidate interactors include tubulins, kinases, phosphatases, G proteins, and mitochondrial proteins. CAPN5 interactions for 14 of the candidate proteins were confirmed by co-IP and immunoblotting. Of these 14 proteins, 11 exhibited in vitro calcium-induced proteolysis following co-IP with WT CAPN5-3×FLAG. Impaired calcium-induced proteolysis of co-IP proteins was observed for the pathogenic CAPN5 variants R243L and R289W. Further studies are needed to validate the association of candidate CAPN5 interactors with proteins and complexes suggested by the SWATH-MS and co-IP results, and the possible role of CAPN5 within such complexes. The possible involvement of CAPN5 in protein quality control is relevant to NIV, as defects in protein quality control have been implicated in inherited retinal disorders. Proteomic data are available via ProteomeXchange with identifier PXD068008.

Difficult-To-Treat Rheumatoid Arthritis With Concomitant Yao Syndrome With Response To Dual-Inhibitor Therapy, Nawar Aljundi, Paramarajan Piranavan

Internal Medicine Faculty Publications

No abstract provided.

An Unbiased Molecular Characterization Of Peripartum Cardiomyopathy Hearts Identifies Mast Cell Chymase As A New Diagnostic Candidate, J. F. Mulvey, C. Sailer, J. S. Achter, Gregory Nathaniel Milburn, R. C. Bretherton, K. Kahnert, S. Erbil Bilir, H. Hvid, C. Pyke, F. Gustafsson, L. Adamo, Kenneth S. Campbell, K. M. Herum, A. Lundby

Internal Medicine Faculty Publications

Peripartum cardiomyopathy (PPCM) is a rare form of acute heart failure that develops in women toward the end of pregnancy or early postpartum. No effective, specific treatment for PPCM is available and heart transplantation or mechanical circulatory support may be required in severe cases where drug treatment for heart failure is insufficient. The mechanisms through which the disease progresses are not well understood, and despite similar clinical characteristics to dilated cardiomyopathy of other etiologies (nonperipartum cardiomyopathy; NPCM) it is not known how the molecular remodeling differs between these groups. We aimed to provide insight into the human PPCM heart using …

The Receipt Of Psychological Services And Acceptability Of Local Follow- Up Care For Childhood Cancer Survivors: Are There Rural Vs. Urban Differences?, Tyrone F. Borders, Abigayle Feather, Jerod L. Stapleton, John A. D’Orazio, Eric B. Durbin

Psychology Faculty Publications

Purpose This study examined rural and urban parents’ reports of their children’s receipt of general follow-up care and psychological services, ratings of the acceptability of common sources of follow-up care, and ratings of local/nearby follow-up care access and effectiveness.

Methods A cross-sectional, quantitative survey was conducted among 238 (139 urban, 46 rural adjacent, and 53 rural non-adjacent) parents of childhood cancer survivors (ages 2–17 and at least 2 years since cancer diagnosis) recruited through the Kentucky Cancer Registry. Bivariate analyses and multivariable logistic regressions adjusting for predisposing, enabling, and need factors tested for differences across residence in urban counties, rural …

Comparative Evaluation Of R134a And Hfo‐1234ze Cryogen Spray Cooling Using A Mouse Model With Controllable Epidermal Pigmentation, Wangcun Jia, Yurie Jeong, Crystal Huynh, Oswald Lai, Emily Nguyen, Grant Swajian, Jade Niu, Ayana Kashikar, Joshua Khaw, Hong Pu, Bernard Choi, John August D'Orazio, J. Stuart Nelson, Bahman Anvari

Pediatrics Faculty Publications

Objectives: Cryogen spray cooling (CSC) is critical for protecting the epidermis during laser dermatologic procedures. The widely used cryogen, R134a, has a high global warming potential (GWP), motivating interest in environmentally favorable alternatives such as HFO-1234ze. This study evaluated whether HFO-1234ze provides epidermal protection comparable to R134a during laser exposure and investigated the mechanistic basis underlying any differences in cooling performance.

Methods: Laser-induced epidermal injury in conjunction with two cryogens was assessed in K14-SCF Mc1r^e/e mice with pharmacologically controllable interfollicular epidermal pigmentation. Laser treatment sites were assigned fluences relative to baseline skin lightness (L*) to span subthreshold …

Colon Cancer In Appalachian Kentucky: Unique Genetic, Microbiome And Obesity Findings In A Cohort Comparison, Zeta Chow, Jinpeng Liu, Daheng He, Chi Wang, Tong Gan, Akila Mansour, Nuha Shaker, Caroline Dravillas, Rebecca Hoyd, Eric B. Durbin, Dana L. Napier, Tianyan Gao, Kurt Schaberg, Lyen Huang, Neli Ulrich, Erin Siegel, Stephen Edge, Linda Cook, Bodour Salhia, Michelle L. Churchman, Jill Kolesar, Daniel Spakowicz, B. Mark Evers, Therese J. Bocklage

Markey Cancer Center Faculty Publications

We investigated colon cancer genomics and microenvironmental features in the Appalachian Kentucky population, a group with the highest incidence of colon cancer in the United States. We assessed two inter-related risk factors for colon cancer (obesity and abnormal gut bacterial microbiome) and their genetic associations within this population. To evaluate potential unique characteristics of the high-incidence cohort, we compared 99 propensity-matched colon cancer tumors from Appalachian Kentucky patients to 95 non-Appalachian patient tumors to evaluate driver mutations, differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, immune cell …

Hexavalent Chromium Promotes Malignant Transformation Via Enhanced Translation Of Suv39h1, Yiwei Gu, Yanan Cao, Qing Ye, Yujing Zhang, Zhishan Wang, Chengfeng Yang, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Hexavalent chromium [Cr(VI)] is a widespread environmental carcinogen linked to lung cancer and other malignancies. Although genetic and epigenetic mechanisms of Cr(VI)-induced carcinogenesis have been extensively investigated, the role of translational control has remained largely unexplored. Here, we show that chronic low-dose Cr(VI) exposure in BEAS-2BR human bronchial epithelial cells activates eIF4E-driven cap-dependent translation through mTORC1-mediated phosphorylation and inactivation of the translational repressor 4E-BP1. Pharmacological inhibition of this pathway markedly suppresses Cr(VI)-induced cell transformation, cancer stem cell (CSC)-like properties, and DNA damage. Comparable inhibitory effects are observed following raptor knockdown, which disrupts mTORC1, or expression of a constitutively active non-phosphorylatable …

Rna-Micelles As Self-Assembling Structures For Efficient Co-Delivery Of Synergistic Sirna And Nucleoside Analogues To Treat Crc Lung Metastasis, Kai Jin, Piotr G. Rychahou, Daniel W. Binzel, B. Mark Evers, Peixuan Guo

Markey Cancer Center Faculty Publications

SiRNA has been widely studied in cancer gene silencing over the last 25 years. However, few siRNA-based therapeutics have been approved by the FDA. An RNA-micelle platform provides a powerful therapeutic tool through simple one-step, high-yield production that is capable of efficient colorectal cancer lung metastasis treatment, a current lethal condition with a short survival rate post-diagnosis. Here, it is reported that the use of RNA-micelles co-carrying siRNA and nucleoside analogues to completely inhibit lung metastasis of colorectal cancer (CRC). The major advantage of the RNA-micelle is the successful co-delivery of siRNA and chemotherapeutic agent in a single delivery vehicle …

Geographic Clusters Of Human Papillomavirus-Associated Cancer Incidence In The Us, 2008–2022, Todd Burus, Krystle A. Lang Kuhs, Ashish A. Deshmukh, Haluk Damgacioglu

Markey Cancer Center Faculty Publications

Objective: Despite known state and regional differences, United States (US) county-level patterns of human papillomavirus (HPV)-associated cancer incidence remain unexplored. Methods: In this cross-sectional study, we analyzed US county-level HPV-associated cancer incidence rates from 2008 to 2022 using the US Cancer Statistics Incidence Analytic Database to identify geographic clusters of high and low incidence. Clusters were identified using the Getis-Ord Gi* statistic and assessed for differences in cluster-level sociodemographic characteristics and sex-and-site-specific incidence. Results: We found 373 hot spot and 409 cold spot counties, with median incidence rates of 16.14 and 10.62 per 100,000, respectively. Hot spot counties were particularly …

Case Report: Prolonged Response To Cabozantinib And Pembrolizumab In Treatment-Refractory Metastatic Pancreatic Ductal Adenocarcinoma, Anna M. Reagan, Hannah G. Mcdonald, Jaewon Kang, Hoda Saghaeiannejad Esfahani, Caroline G. Wright, Charles J. Bailey, Carleton S. Ellis, Kaylyn R. Collette, Reema A. Patel, Mayte Murillo, Samantha F. Stokley, Michael J. Cavnar, Prakash Pandalai, Mautin T. Barry-Hundeyin, Jessica Moss, Joseph Kim

Markey Cancer Center Faculty Publications

Immunotherapy has yet to demonstrate durable efficacy in pancreatic ductal adenocarcinoma (PDAC) despite the fact that pancreatic cancer cells have higher levels of immune checkpoint expression than other cancer cell types in which immunotherapy efficacy has been well established. We observed effective cytotoxicity with the combination therapy of pembrolizumab (an anti-PD-1 monoclonal antibody, mAb) and cabozantinib (an anti-MET small molecule) in vivo. This served as the basis for an investigator-initiated phase II clinical trial (NCT05052723). The trial was open to patients with treatment-refractory metastatic PDAC with a single-arm treatment protocol of pembrolizumab and cabozantinib. Here, we report the case of …

Survival Of Patients Diagnosed With Cancer During The Covid-19 Pandemic, Todd Burus, Haluk Damgacioglu, Bin Huang, Thomas C. Tucker, Ashish A. Deshmukh, Krystle A. Lang Kuhs

Markey Cancer Center Faculty Publications

Importance  The effects of COVID-19 pandemic–related disruptions on cancer diagnosis in the US have been widely observed, but their impact on short-term survival has not been assessed.

Objective  To examine 1-year cause-specific survival (CSS) rates among patients diagnosed with cancer during 2020 and 2021 using high-quality cancer registry data.

Design, Setting, and Participants  This population-based cohort study of cancer survival between 2015 and 2021 used the Surveillance, Epidemiology, and End Results 21 Registries (SEER-21) database. The population included individuals with an invasive cancer diagnosis and complete follow-up reported to registries included in SEER-21 between January 1, 2015, and December 31, …

A Phase 1 Dose Escalation Of Lapatinib And Paclitaxel In Recurrent Ovarian Cancer, Connie D. Cao, Joseph Robert Mccorkle, Donglin Yan, Hoda Saghaeiannejad Esfahani, Rani Jayswal, Dava W. Piecoro, Ning Li, Lauren Baldwin, Rachel W. Miller, Christopher P. Desimone, Charles S. Dietrich, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Objective: The development of ABCB1-mediated resistance limits the clinical efficacy of paclitaxel. Lapatinib is a small-molecule reversible tyrosine kinase and ABCB1 inhibitor that could prevent resistance. Our objective was to determine a recommended phase 2 dose (RP2D) of the combination of paclitaxel and lapatinib.

Methods: A phase 1 dose-escalation study utilizing a Bayesian optimal interval (BOIN) design in recurrent ovarian cancer patients was conducted. Patients were pretreated with pulsed lapatinib in the 48 h preceding weekly paclitaxel (80 mg/m²) in 28-day cycles for up to three cycles. We evaluated three lapatinib doses, escalating from 750 to 2000 mg …

Dna-Pkcs Promotes Therapy Resistance And Metastatic Recurrence In Neuroblastoma, Mahnaz Norouzi, Subin Kim, Beibei Zhu, Chi Wang, Natalie Wu, Katherine Somers, Eddy Shih-Hsin Yang, B. Mark Evers, Eric J. Rellinger, Piotr G. Rychahou

Markey Cancer Center Faculty Publications

Purpose: High-risk neuroblastoma presents a serious clinical challenge with survival rates below 50%. Disease relapse most commonly occurs at distant metastatic sites and remains the primary driver of poor outcomes, emphasizing the need for therapies to target drivers of relapse.

Experimental design: This study identified DNA-PKcs as a critical determinant of poor survival and metastatic relapse in neuroblastoma patients. We evaluated which therapeutic modality—chemotherapy or radiotherapy—when combined with DNA-PKcs inhibition, more effectively reduces metastatic burden and prevents recurrence.

Results: Colony-forming assays revealed that established neuroblastoma colonies resist doxorubicin alone and require high-dose doxorubicin paired with DNA-PKcs inhibition to suppress progression. …

A Unique Protein Adjuvant For Precision Immunotherapy To Prevent Recurrence Of Surgically Resected Colorectal Cancer, Yasuhiro Suzuki, Rajesh Mani, B. Mark Evers

Markey Cancer Center Faculty Publications

Effectively activating protective CD8⁺ T cell immunity specifically against cancer antigens is an important pathway to prevent the growth of various types of cancers. A major obstacle in this approach is variations in cancer antigens among patients. A valuable material to overcome the antigen variation among cancer patients is the use of each individual’s own cancer cells for immunization. In colorectal cancer (CRC), approximately one-third of the patients who receive curative surgical resection have a recurrence of cancer. Therefore, the use of surgically resected CRC for immunotherapy to specifically activate the protective CD8⁺ T cells against their own …

Mental Health Needs Of Families Of Patients In Intensive Care Units And The Role Of Mobile Health: Survey Study, Anthony Faiola, Saira Soroya, Zhonglin Hao, Reinhold Munker

Markey Cancer Center Faculty Publications

Background: The experiences of patients with COVID-19 and their families manifested the most devastating effects of family separation since the 1918 Spanish influenza pandemic and, with it, a call for solutions to patient isolation and its effect on family mental health.

Objective: This study examined the recent experiences of families of critical care (intensive care unit; ICU) patients related to anxiety and depression (AD), satisfaction with clinician-family communication, and counseling from mental health and social services. This study explored correlations between these factors and family interest in mobile health (mHealth) designed to improve information flow and communication from patient bedside …

Survival Outcomes Of First-Line Therapy In De Novo Metastatic Urothelial Carcinoma With Histologic Subtypes: A National Cancer Database Analysis, Zin W. Myint, Feitong Lei, Bin Huang

Markey Cancer Center Faculty Publications

Background: Urothelial carcinoma with histologic subtypes represent an aggressive and understudied population frequently excluded from prospective clinical trials. Evidence guiding optimal first-line systemic therapy in de novo metastatic disease with histologic subtypes remains limited.

Method: Patients with de novo stage IV urothelial carcinoma with histologic subtypes diagnosed between 2016 and 2021 were identified from the National Cancer Database (NCDB). Eligible patients received first-line chemotherapy, immunotherapy, or concurrent chemoimmunotherapy (both modalities initiated within 30 days). Overall survival (OS) was compared across groups using Kaplan–Meier methods and compared using log-rank tests and multivariable Cox regression. Result: Among 800 patients, 596 (74.5%) received …

Person‑Level Health Factors Partially Mediate The Association Between Lesbian, Gay, Or Bisexual (Lgb) Identity, Allostatic Load, And Cancer Mortality In Nhanes, Justin Xavier Moore, Alisha Patel, Missy Spears, Tracy Casanova, Heidi L. Weiss, Marvin E. Langston, Keith J. Watts, Donte Boyd, Prajakta Adsul, Meredith S. Duncan, Sydney Howard

Markey Cancer Center Faculty Publications

Purpose: Individuals identifying as Lesbian, Gay, or Bisexual (LGB) with high allostatic load have more than double the cancer mortality risk of heterosexual individuals with high allostatic load. This study explored how person-level health factors mediate the relationship between individuals identifying as LGB with high allostatic load and subsequent risk of cancer mortality.

Methods: We conducted a retrospective analysis of 12,470 participants in the National Health and Nutrition Examination Survey (2001–2010) linked to the National Death Index through 31 December 2019. Survey-weighted Cox regression assessed associations of individuals identifying as LGB and allostatic load with cancer mortality. Person-level health factors …

Oncology Clinicians’ Attitudes On Hormonal Therapy After Chemoradiotherapy For Cervical Cancer, Morgan S. Levy, Marilyn Huang, Charles S. Dietrich, Denise Fabian

Markey Cancer Center Faculty Publications

No abstract provided.

Assessing The Value Of Sequential Next-Generation Sequencing And Multiple Molecular Tumor Board Reviews For Patients With Solid-Tumor Malignancies, Allison L. Swiecki-Sikora, Lydia Williams, Ning Li, Donglin Yan, Evan Bryon, Derek B. Allison, Rachel W. Miller, Charles S. Dietrich, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Purpose: Multidisciplinary molecular tumor boards (MTBs) have demonstrated improved clinical outcomes in various malignancies. Sequential next-generation sequencing (NGS) is widely performed at the time of recurrence, which may lead to multiple MTB reviews. This study assessed the clinical benefit of multiple MTB reviews for sequential NGS.   Methods: A retrospective cohort review was performed to compare patients reviewed once at a single-institution MTB and those reviewed multiple times for the same diagnosis with sequential NGS between January 2016 and December 2023. Demographics were compared, and regression and survival analysis was performed.   Results: In all, 3,702 patients were included, 3,446 (91.6%) were …

Case Report: Prostate Adenocarcinoma With Peritoneal Carcinomatosis And Elevated Cea Mimicking Colorectal Cancer: A Diagnostic Dilemma, Hala Majeed, Nathan R. Shelman, Jitesh A. Patel, Janeesh S. Veedu, Insija I. Selene, Ashlyn Whitesell, Zin W. Myint

Markey Cancer Center Faculty Publications

This case report describes an exceptionally rare manifestation of prostate adenocarcinoma presenting with peritoneal carcinomatosis, rectal obstruction, and markedly elevated carcinoembryonic antigen (CEA), closely mimicking colorectal cancer. A 65-year-old man with localized high-grade prostate adenocarcinoma (Gleason 4 + 4) underwent robotic prostatectomy in November 2020, followed by salvage radiation and stereotactic body radiation therapy for early biochemical recurrence. He achieved an excellent response to androgen deprivation therapy (ADT) combined with abiraterone and prednisone, maintaining an undetectable prostate-specific antigen (PSA) level for over 2 years. In late 2024, the patient developed hematochezia, narrow stools, and abdominal pain. Imaging revealed a rectal …

Eef2k Promotes Immune Evasion In Melanoma Via Cyclin D1–Mediated Stabilization Of Pd-L1, Yijie Ren, Darby J. Ballard, Anil Kumar, Andy F. Song, Mitiksha Gupta, Xiaofang Xiong, Xingcong Ren, Jugal Kishore Das, Jin-Ming Yang, Jianxun Song

Markey Cancer Center Faculty Publications

Eukaryotic elongation factor 2 kinase (eEF2K) is a stress-responsive regulator of protein synthesis implicated in melanoma progression, but its role in tumor immune evasion remains poorly defined. We investigated how eEF2K influences programmed death ligand 1 (PD-L1) expression through modulation of Cyclin D1. We analyzed gene expression and dependency datasets from The Cancer Genome Atlas and the Cancer Dependency Map. Protein–protein interactions were assessed by co-immunoprecipitation. Cyclin D1 was inhibited pharmacologically with palbociclib. Immune responses were evaluated in murine B16-OVA and human A2058 melanoma models using flow cytometry and immunohistochemistry after genetic or pharmacologic modulation of eEF2K and Cyclin D1. …

Implementing A Standardized App-Led Multidisciplinary Medication Review And Reconciliation To Improve Medication Safety Before Systemic Cancer Therapy: An Ambulatory Oncology Quality Improvement Initiative, Sarah R. Hines

DNP Projects

Background

Adult patients initiating systemic cancer therapy frequently present with pre-existing polypharmacy related to chronic comorbidities and cancer-related symptom management. The addition of anticancer therapies and supportive care medications further increases medication burden and the risk of medication-related harm. Although national organizations and institutional policies recommend comprehensive medication review before treatment initiation, implementation remains inconsistent in ambulatory oncology practice.

Purpose

To implement and evaluate a standardized Advanced Practice Provider (APP)-led multidisciplinary medication review and reconciliation process designed to identify medication medication-related safety risks before initiation of systemic cancer therapy in adult oncology patients receiving care in an ambulatory infusion center. …