Digital Commons Network^™

Clinical Outcomes With Perioperative Nivolumab By Nodal Status In Patients With Stage Iii Resectable Nsclc: Phase 3 Checkmate 77t Exploratory Analysis, Mariano Provencio, Mark M Awad, Jonathan D Spicer, Annelies Janssens, Fedor Moiseyenko, Yang Gao, Yasutaka Watanabe, Aurelia Alexandru, Florian Guisier, Nikolaj Frost, Fabio Franke, T Jeroen Nicolaas Hiltermann, Jie He, Fumihiro Tanaka, Shun Lu, Cinthya Coronado Erdmann, Padma Sathyanarayana, Phuong Tran, Vipul Devas, Tina Cascone

Faculty, Staff and Student Publications

Individuals with non-small-cell lung cancer (NSCLC) with metastases to the ipsilateral mediastinum or subcarinal lymph nodes (N2 disease) have poor long-term survival. This exploratory analysis from the randomized phase 3 CheckMate 77T study assessed clinical outcomes by nodal status in individuals with stage III NSCLC who received neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab (nivolumab) versus neoadjuvant chemotherapy followed by surgery and adjuvant placebo (placebo). Here we show that among patients with N2 disease, nivolumab versus placebo improved event-free survival (1-year rate, 70% versus 45%; hazard ratio, 0.46 (95% confidence interval, 0.30–0.70)) and pathological complete response rate …

Bovine Colostrum And Late-Onset Sepsis In Premature Infants: A Multicenter Randomized Controlled Trial (Bcsp Study), Hany Wifky Gendy Michael, Hassan Mohamed Hassan Mohamed, Dalia Abu Elmaaref Mohamed Ibrahim

Journal of Medicine in Scientific Research

Aim: Neonatal sepsis and necrotizing enterocolitis (NEC) have a great impact on morbidity and mortality in immature newborns. We performed our trial to examine the impact of enteral bovine colostrum administration upon late neonatal sepsis in premature newborns. Patients &Procedures: The study included neonates who had a birth weight (BW) of 1-1.8 kg, a gestational age (GA) of full 28-34 weeks, and a postnatal age of ≤ 96 hours. A blinded, randomized, placebo-controlled study was done using two groups; one of them received bovine colostrum daily within the first 96 hours starting from the 2nd day of feeding and for …

Auditory Memory In Children Who Stutter, Sanaa Mahran Mohamed Qandel, Nihal Hisham Abdelhamid Mostafa, Nihal Hisham Abdelhamid

Journal of Medicine in Scientific Research

Background Stuttering has been described as a disorder in motor speech in which disruption in the timing between laryngeal, respiratory, and vocal tract rhythm of speech. It is characterized by prolongations and involuntary repetitions of sounds. Children who stutter (CWS) characterized by inability to produce sounds, with intra-phonemic disruption and involuntary silent pauses. Many studies have examined central auditory processing skills and reported impairments, yet auditory memory skills have not been adequately evaluated, leaving a gap in the available information. Aim of the study Assessing auditory memory performance and auditory memory abilities in CWS. Methods: Measuring recognition memory, memory for …

Early Clinical Outcomes Of The Use Of Del Nido Versus Intermittent Warm Blood Cardioplegia After Isolated Coronary Artery Bypass Surgery, Ahmed Abdalla Mohamed, Ahmed M Elshemy, Sherif M Elboghdady, Wael S Nekhila, Ismail R Barrada

Journal of Medicine in Scientific Research

Background While the best approach to protecting the heart during surgery varies based on the specific operation and the surgeon's preferences, del Nido cardioplegia, initially successful in children, is gaining traction as an alternative to the traditional blood cardioplegia in adult cardiac procedures. Aim This investigation comparatively analysed the early postoperative consequences in adult patients undergoing isolated coronary artery bypass grafting, contrasting the application of del Nido cardioplegia with conventional warm blood cardioplegia techniques. Methods Randomised controlled clinical research was conducted to compare the efficacy of antegrade del Nido (DNC) and intermittent warm blood cardioplegia (IWBC) in safeguarding myocardial function …

Prevalence Of Diabetic-Nephropathy In Children And Adolescents With Type-One- Diabetes Mellitus: A Recent Perspective, Randa Mohamed Darwish, Ayat Ibrahim Ghanem, Jehan Ibrahim Altohamy, Dina Mahmoud Khalifa

Journal of Medicine in Scientific Research

Background Among the most important microvascular complications in Type-one-Diabetes Mellitus (T-1-DM) in adolescents and children, Diabetic-nephropathy (DN) stands high. Early detection is crucial to prevent its progress to chronic kidney disease. Objective This study was designed aiming at the elaboration of an updated prevalence for Diabetic-nephropathy and to identify the risk factors among pediatric patients age group with T-1-DM . Methods The present cross-sectional-study was conducted starting from September 2023 to September 2025 including a group of 100 cases of adolescents and children with T-1- DM (aged 5–16 years) and 100-matched age and sex healthy control group. Clinical evaluation included …

Usage Of Valved Conduit In Replacing The Mitral Valve In Heavily Calcific Or Destroyed Annulus: A Prospective Cohort Study, Yosry M Thakeb, Ahmed Kamel Abdel Ghany Hassan, Wael Abdelatief Mohamed Elhakeem

Journal of Medicine in Scientific Research

Background: Heavily calcified or destroyed mitral annulus present significant technical challenges for conventional valve replacement, often requiring alternative surgical strategies. Aim: To evaluate the safety, efficacy, operative outcomes, and the competency of valved conduit in patients with heavily calcified or destroyed mitral valve annulus. Methods: Fifteen patients (mean age 58.8±8.21 years, 53.3% female) underwent valved conduit mitral valve replacement at the Cardiothoracic Surgery Department, National Heart Institute, General Organization for Teaching Hospitals and Institutes (GOTHI), Egypt. Preoperatively, 80% presented in NYHA class III-IV with mean ejection fraction of 37.6±7.65% and pulmonary artery pressure of 50.6±11.39 mmHg. Bioprosthetic valves were used …

A Randomized Controlled Trial In A Teaching Hospital Comparing The Outcomes Of ‎Single-Layer Versus Double-Layer Uterine Suturing With Polyglactin In The Development ‎Of Uterine Niche Following Caesarean Section, Ahmed A. Kassab, Ali E. Khayal

Journal of Medicine in Scientific Research

Background Caesarean section (CS) rates are rising globally, with Egypt reporting one of the highest rates. A potential complication of CS is the development of a uterine scar defect, or niche, which may be associated with abnormal bleeding, dysmenorrhea, and infertility. The technique of uterine closure may play a significant role in the prevention of niche formation. Aim To evaluate the effectiveness of double-layer uterine closure versus single-layer closure in preventing niche formation after a first CS, as assessed by transvaginal ultrasound (TVUS) at six weeks postpartum. Methods This randomized controlled trial was conducted at Mataryia Teaching Hospital, Cairo, including …

Socioeconomic Factors Affecting Pulmonary Functiontest Follow-Up Rates, Celine Agidigbo

Williams Honors College, Honors Research Projects

Background

Chronic obstructive pulmonary disease (COPD) and asthma are associated with significant physical, mental, and social burdens that impact patients’ quality of life (Franssen et al., 2018). Pulmonary function testing (PFT) is an essential diagnostic test for identifying and managing pulmonary conditions. Missed or delayed follow-up after abnormal PFT results may derail disease management and lead to frequent hospital readmissions, thereby disease management and patient outcomes.

According to Braveman et al. (2010), socioeconomic status (SES), defined by factors such as income, education, and employment, has been widely associated with disparities in healthcare access and outcomes. This paper examines the impact …

Age-Related Ultrastructural Differences In The Dorsal Cortex Of The Inferior Colliculus In The Fischer Brown Norway Rat, Kylee M. Tenney, Dakota Smallridge, Gillian Barach, Gurveer Singh, Erin Beskitt, Justine Busby, Syllissa Duncan, Alexa Wawrzyniak, Brenda Vega, Nick Tokar, Andrew Ohl, Jesse Young, Jeffrey Mellott

Williams Honors College, Honors Research Projects

The inferior colliculus is a nucleus in the auditory midbrain that plays an important role in sound and speech processing through how it encodes temporal precision. Temporal precision depends on the balance of inhibition and excitation within the IC. This balance degrades during aging. Age-related changes in synapses have been described in the lemniscal IC as a contributing factor for this imbalance. However, it is unknown if aging affects synapses throughout the non-lemniscal IC in a similar manner. We sought to determine this by examining the dorsal cortex of the IC. The ICd is a non-lemniscal nucleus that is well …

Associations Between Oral Hormonal Contraceptive Use, Digestive And Other Health Symptoms In Young Women, Silviana E. Buzatu

Honors Undergraduate Theses

Oral hormonal contraceptives (OHCs) are widely used among reproductive-age women; however, their gastrointestinal (GI) side effects remain understudied. The present study examined associations between OHC use, GI, physical, and psychological symptom burden in a large sample of undergraduate women. Participants (N = 669) aged 18 to 25 years were recruited from UCF’s SONA system and classified into three groups based on self-reported contraceptive status: no birth control, combined estrogen–progestin OHC, and progestin-only OHC. Participants completed GI questionnaires, as well as physical and mental health symptoms ones.

Multivariate analyses indicated that overall GI symptom profiles did not differ significantly by birth …

Impact Of Senescence On Breast Cancer Outcomes, Gracie Sous

Honors Undergraduate Theses

Cellular senescence is a biological process in which damaged cells exit the cell cycle while remaining metabolically active and accumulating within tissues. Senescence plays a complex role in breast cancer progression, largely through the secretion of senescence-associated secretory phenotype (SASP) factors. These factors include a broad range of inflammatory cytokines, chemokines, and signaling molecules that can influence the tumor microenvironment.

Studies suggest that senescence may significantly promote cancer metastasis. Therefore, this study aims to investigate the genes involved in cancer progression and to improve understanding of how SASP is regulated, which is critical for improving breast cancer outcomes. The central …

Decoding A Decade: Evolution In Distal Radius Fracture Techniques From Past To Present, Embracing The Efcr Method, Natasha G. Dark, Ahmed S. Raihane, Laurie G. Wells, Deana Mercer

Western Journal of Orthopaedics

No abstract provided.

Conventional Versus Advanced Imaging Selection For Endovascular Treatment Of Basilar Artery Occlusion Strokes., Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Sami Al Kasab, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M. Starke, Marios-Nikos Psychogios, Edgar A. Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Jonathan A. Grossberg, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G. Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S. Park, Michael R. Levitt, Waleed Brinjikji, Mark Moss, Travis Dumont, Ergun Daglioglu, Richard Williamson, Pedro Navia, Reade De Leacy, Shakeel Chowdhry, David J. Altschul, Alejandro M. Spiotta, Peter Kan

Department of Medicine Faculty Papers

INTRODUCTION: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear.

PATIENTS AND METHODS: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in …

From Screens To Stress: Public Health Implications Of Cancer Worry In A Digitally Connected World, Shreya Mathur, Ethan Burns, Michael Pokojovy, Tzu-Liang Bill Tseng, Sunil Mathur

Mathematics & Statistics Faculty Publications

Aims:

This study examines how digital information environments, genetic testing experiences, health behaviors, and psychological distress influence cancer-related worry among adults in the United States. It further considers the public health implications of elevated or reduced cancer worry for prevention and risk communication.

Methods:

Data were drawn from a nationally representative survey of 6,252 U.S. adults. Measures included reliance on social media for health decision-making, smoking status, history of genetic testing, and psychological distress. Multivariable analyses assessed associations between these factors and levels of cancer worry.

Results/Findings:

Reliance on social media for health decisions was associated with greater cancer worry, …

Blood Flow Regulates Metabolism In Hematopoietic Development, Pamela L Wenzel

Faculty, Staff and Student Publications

Blood flow modifies oxygen availability and biomechanical forces within the vasculature of the embryo as the hematopoietic system develops. The aorta-gonad-mesonephros (AGM) envelops the largest artery in the body and is a critical site for the emergence of hematopoietic stem cells (HSCs). Herein, I discuss the role of hypoxia-inducible factors (HIFs) and force as determinants of metabolism and fate determination. To address the effects of blood flow on hematopoietic development, I employ mouse embryo models and biomimetic culture. Real-time cell metabolic analyses show that oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) are altered by flow in cultures of …

A Framework For Digital Energy Modulation And Translation In Projectional X-Ray Imaging, Richard R. Wargo

Theses and Dissertations

In projectional X-ray imaging, acquisition energy fundamentally influences subject contrast, image noise, and radiation dose. While dual-energy techniques exploit spectral differences to optimize contrast and enable material separation, acquiring multiple images of the same anatomy often requires additional exposures and increased system complexity.

This dissertation presents a framework for digital energy modulation (DEM), in which computational models are trained to translate projection images between energy domains without requiring additional X-ray acquisitions. DEM is conceived as a generalizable strategy for controlled contrast modulation in projection imaging, with potential applications in image optimization, radiation therapy alignment, and dual-energy applications.

The framework was …

Commissioning & Daily Qa Of Converted Linac For Electron Flash, Tomaj Javidtash

Theses and Dissertations

Ultra-high dose rate (FLASH) radiotherapy has demonstrated promising normal tissue sparing in preclinical studies; however, the lack of standardized dosimetry, commissioning, and quality assurance (QA) methodologies remains a major barrier to its reproducible and safe implementation. In particular, conventional clinical commissioning and QA protocols are not directly applicable at FLASH dose rates due to challenges associated with detector response, dose-per-pulse effects, and beam control limitations.

This thesis presents the commissioning of a converted Varian 21EX linear accelerator for electron FLASH operation within the Division of Medical Physics at the Virginia Commonwealth University (VCU) Department of Radiation Oncology. Comprehensive beam characterization …

Revisiting Nasal Polyp Scoring In Clinical Trials: Interpretive Variability And The Need For Standardization, Leigh J. Sowerby, Babak Pourmomenarabi, Antonino Maniaci, Olivia Ginty, Joseph Khristian Han

Department of Otolaryngology (ENT) Faculty Publications

[Introduction] Borish et al. provided an excellent review highlighting methodological variability among the six pivotal Phase III trials [1]. One critical yet overlooked issue is the inconsistent application of the endoscopic nasal polyp score (NPS), a primary outcome measure in all trials.

Dupilumab In Chronic Rhinosinusitis Without Nasal Polyps: Randomized Phase 2 Trial (Orion), Stella E. Lee, Anju T. Peters, Philippe Gevaert, Joseph K. Han, Claus Bachert, Francisco Moreira Da Silva, Andrés Rosenblüt, Chih-Chi Hu, Jennifer Maloney, Paolo Caferra, Adrianna Michalak, Andrew P. Fontenot, Lacey B. Robinson, Neelam A. Phadke

Department of Otolaryngology (ENT) Faculty Publications

BACKGROUND: Chronic rhinosinusitis (CRS) is often driven by type 2 inflammation and is characterized by nasal obstruction/ discharge, facial pain/pressure, and/or reduced smell, either with or without nasal polyps (CRSwNP or CRSsNP).

OBJECTIVE: To test whether dupilumab improves radiographic features in CRSsNP. Methods: ORION (NCT04678856), a phase 2, randomized, multicenter, double blind, placebo-controlled study, assessed dupilumab efficacy and safety in adults with uncontrolled CRSsNP. Patients were randomized 1:1 to dupilumab or placebo for 24 to 52 weeks. Endpoints included changes from baseline at week 24 in Lund–Mackay computed tomography (LMK-CT) score (dupilumab only [primary] and vs placebo [secondary]), sinus Total …

Indirect Treatment Comparison Of Tezepelumab Versus Other Biologics In Severe Chronic Rhinosinusitis With Nasal Polyps: A Systematic Literature Review And Network Meta-Analysis, Joseph K. Han, Joaquim Mullol, Claire Hopkins, Oliver Pfaar, Martin Desrosiers, Jason Steenkamp, Danny Gibson, Santiago Zuluaga Sanchez, Andrew Foster, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

Introduction

This study compared the efficacy of tezepelumab with other approved biologics and endoscopic sinus surgery (ESS) using indirect treatment comparisons (ITCs) in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP).

Methods

Randomized controlled trials (RCTs) identified via a systematic literature review (SLR) were synthesized in a network meta-analysis (NMA). Outcomes included change from baseline in nasal polyp score (NPS), nasal congestion/obstruction score (NCS/NOS), difficulty with sense of smell (DSS), Sino-Nasal Outcome Test-22 (SNOT-22) score, Lund Mackay score (LMS), time to nasal polyposis (NP) surgery decision, proportions requiring NP surgery or systemic corticosteroids (SCS), time to SCS use, …

Socialization Interventions For Older Adults In Assisted Living Facilities: A Systematic Review, Anoop S. Muvva

Honors Undergraduate Theses

Older adults, defined as individuals over the age of 65, are a growing population in the United States, with projections estimating this group will reach approximately 80 million persons by 2050. Over 90% of older adults are diagnosed with a chronic condition, which can make it difficult to carry out the activities of daily living. As a result, some older adults reside in assisted living facilities, where dedicated staff provide daily support. However, issues in the delivery of care within these settings, including unmet socialization needs and complications among care staff, may contribute to social isolation. Programs designed to address …

Analyzing Early Medieval Perspectives Of Fetal Development, Nivedha Srinivasan

Honors Undergraduate Theses

This thesis examines early medieval perspectives of fetal development by analyzing two manuscripts: British Library, Cotton Tiberius A III and Leiden University, Vossianus lat. Q69. This study will investigate how knowledge of pregnancy was shared throughout England before the establishment of universities. Interest in medieval reproductive language has piqued in importance in recent years, especially due to modern legal debates surrounding reproductive rights. By examining descriptions of the nine months of fetal development in these two manuscripts, as well as in widely known earlier medical texts like Pliny’s Natural History and Vindicianus’ Gynaecia, this research explores how monastic writers in …

The Knowledge, Experiences, And Attitudes Of Nurses Regarding Trauma-Informed Care For Sexually Abused Intrapartum Patients, Kayleigh Mcgraw

Honors Undergraduate Theses

Labor and delivery nurses care for women from diverse backgrounds who are preparing for a life-changing event, often marked by fear, excitement, sadness, and joy. However, 1 in 5 women in the United States have experienced rape or attempted rape, and for these survivors, labor can become re-traumatizing. Many report flashbacks, dissociation, and a sense of “being back in the rape” during childbirth. Research further links prior sexual assault to unplanned cesareans, traumatic births, and childbirth-related PTSD. Trauma-informed care (TIC) provides a framework to reduce these risks by encouraging providers to understand trauma, recognize signs of distress, and act to …

Timelines Of Care: Analyzing Treatment Access For Women With Ongoing Reproductive Health Needs, Nyla M. Keith

Honors Undergraduate Theses

Mandates in the United States created pressure on an already strained healthcare system post-COVID-19 pandemic. With new regulations placed upon abortion care forcing the closing of low-cost health clinics such as Planned Parenthood, legislation that has made health insurance more expensive, and rising pharmaceutical prices, women’s OB/GYN care in America has struggled to meet patient needs. A cross-sectional survey was developed and distributed to four clinics in the Orlando area to assess patients' perceived access to care and identify barriers to receiving OB/GYN care. The survey took approximately 10 – 15 minutes to complete, was available in print and online …

Synthesis And Characterization Of Glass-Ceramic Nanoparticles And Nanobubbles For Integration Into Bone Regenerative Biomaterials, Sun Latt

Honors Undergraduate Theses

Osteoporosis affects over 200 million individuals worldwide and is characterized by an imbalance between osteoclastic bone resorption and osteoblastic bone formation, leading to fragility fractures that significantly diminish quality of life. Current clinical bone cements, such as poly(methyl methacrylate), are limited by poor osseointegration, toxic monomers, and an inability to address the underlying pathophysiology of osteoporosis. This work presents the synthesis, characterization, and systematic in vitro evaluation of a sol-gel-derived, magnesium-incorporated glass-ceramic (GC) nanoparticle within the CaO-MgO-SiO₂ system for incorporation into a novel hydrogel bone cement and bioresorbable magnesium implants. XRD confirmed a biphasic amorphous-crystalline diopside composition, and TEM …

Effect Of Plant-Based Vs. Standard American Diet On Cardiovascular Parameters In College Students, Timothy J. Horanic

Honors Undergraduate Theses

This study examines how adherence to different dietary patterns—specifically a plant-based diet compared to the standard American diet—can influence physiological indicators tied to cardiovascular health, including heart rate variability (HRV), blood pressure (BP), and heart rate (HR). Among these markers, HRV is considered especially sensitive to autonomic nervous system (ANS) regulation and may offer earlier insight into physiological stress or dysfunction than HR or BP alone. Although nutritional habits are widely believed to impact heart health, few investigations have focused on how specific long-term diets affect autonomic and cardiovascular metrics in healthy, college-aged adults. This study aims to investigate if …

Relationships Between Quadriceps Neuromuscular Function And Time From Surgery Following Acl Reconstruction Are Sex-Specific, Tatiana Restrepo

Honors Undergraduate Theses

Anterior cruciate ligament reconstruction (ACLR) is associated with persistent quadriceps dysfunction, including muscular weakness and altered spinal and cortical excitability. While recovery has been widely studied, most investigations focus on isolated domains and fixed postoperative time points. Emerging evidence suggests females often experience slower or less complete quadriceps recovery compared to males, yet the time-dependent nature of these sex-specific outcomes remains unclear. The purpose of this study is to examine whether relationships between time since ACLR and quadriceps neuromuscular outcomes differ by sex across muscular, spinal, and cortical domains. Adults aged 18–35 with a history of primary, unilateral ACLR were …

A Systematic Literature Review Of The Menstrual Cycle And Its Impact On Aerobic Performance In Female Athletes, Jaymie G. Loidolt

Honors Undergraduate Theses

The purpose of this systematic review is to examine existing literature regarding the menstrual cycle and its impact on aerobic performance in female athletes. This comprehensive review was conducted using the PRISMA 2020 method of analysis. All studies included involved normally menstruating females conditioned in endurance sport. Studies analyzing anaerobic sports, abnormally menstruating females, or physically inactive females were excluded. The databases used included: PubMed, Sport Discus, and Web of Science. The results of these were imported into JBIsumari for deduplication, title and abstract, and full text screening. The results conclude objective performance variables are unchanged regarding the phase of …

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 …