Medicine and Health Sciences Commons^™

Spontaneous Pneumothorax In A Male High School Wrestler, Laura Breese, Sara Stiltner

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

OBJECTIVE/BACKGROUND
A pneumothorax is the presence of air in the pleural space, it is a life threatening condition and can be classified as spontaneous, acquired, or by pathophysiology. (1)(2) This specific case presents the incident of a spontaneous pneumothorax in an adolescent population.

Engineering A Novel Treg Population To Control Autoimmune Diabetes, Sofia Colon Guzman, Elly Puckett, Mary A. Markiewicz, Ryan T. Fischer

Research Days

We created a model to test the immunosuppressive capacity of Helios+FOXP3+ eTregs compared to nTregs against islet-specific autoreactive T cells. We also showed that nTregs decrease the response of these cytotoxic T cells when co-cultured with BetaLox5 cells.

Targeting The Beiging Of Muscle-Associated Adipose Tissue To Promote Muscle Regeneration, Jacob C. Parson

WUSM Theses and Dissertations – All Programs

The expansion of intra-muscular adipose tissue (IMAT) between myofibers and epi-muscular adipose tissue (EMAT) outside of the muscle boundary accompanies numerous pathologies including diabetes, muscular dystrophy, and aging. IMAT and EMAT are anatomically juxtaposed to myofibers. Some evidence supports that IMAT and EMAT impede muscle function. This is potentially due to paracrine factors that are secreted by IMAT/EMAT. Different adipose depots can be classified in numerous ways including where they are located anatomically as well as the factors in which they secrete. Unlike classical white fat, adipose depots classified as brown or beige, noted by the marker uncoupling protein-1 (UCP-1) …

Sickle Cell Mice Exhibit Elevated Plasma Bilirubin And Altered Intracranial Cerebral Blood Velocities That Are Exacerbated By Hypoxia-Reoxygenation, Francisco J. Nunez, Ashraf M. Mohieldin, Amy Y. Pan, Sean P. Palecek, Rahima Zennadi, Ramani Ramchandran, Kevin R. Rarick, Surya M. Nauli

Pharmacy Faculty Articles and Research

Sickle cell disease (SCD) is a genetic disorder characterized by sickle red blood cells (RBCs). Sickle RBCs cause cerebral vasculopathies including vaso-occlusive events, leading to ischemia-reperfusion injury and hypoxic tissue environment. To date, the physiological blood flow velocities in cerebral vessels of preclinical SCD models has not been evaluated under hypoxic-reoxygenation. In our study, we used transcranial ultrasound techniques to measure abnormal blood flow velocities in the internal carotid (ICA) and middle cerebral arteries (MCA) of transgenic sickle cell mice (SS) challenged with hypoxia-reoxygenation. Our study showed that SS mice that underwent hypoxic stress exhibited lower relative mean velocities in …

Core Temperature While Swimming In Warm Open Water With And Without A Wetsuit, Katsiaryna Afanasyeva

UNLV Theses, Dissertations, Professional Papers, and Capstones

Triathlon is a popular sport which attract participants from all over the world. In general, triathlon is a safe sport with risk of death being about 1.74 deaths per 100,000 participants (Harris et al., 2017). The swimming portion of the race can be dangerous, posing particular risks due to open water conditions and the physical demands of the event. This study investigated the effects of wetsuit use on core temperature in warm open-water swimming (27.9–28.3°C). Four experienced triathletes (2 males, 2 females; age 49.50 ± 7.83 years) completed two 700-meter open-water swims at a submaximal pace—once wearing their personal full-sleeve …

Expanding Anatomy Academy In The Las Vegas Metropolitan Area: A Service Learning Project To Improve Childhood Health Through Supplemental Educational Sessions, Alekzander Hall, Brandon Paige, Marlee Parkin, David Sanchez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Childhood obesity is a growing epidemic in the United States, with approximately 18.5% of US children presenting with obesity. High levels of obesity are less common in higher income communities, but increasingly more prevalent in lower income communities. Currently in Clark County, Nevada, more specifically in lower socioeconomic communities and Title I schools within the Las Vegas area, there is an opportunity to educate students about the components of a healthier lifestyle to provide children with the tools to improve their health. Anatomy Academy (AA) is an eight-week health education program that was created to teach fourth and fifth grade …

Oral Prevalence Of Selenomonas Noxia Differs Among Orthodontic Patients Compared To Non-Orthodontic Controls: A Retrospective Biorepository Analysis, Kyle Hodges

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: The introduction of fixed orthodontic brackets in orthodontic therapy has the potential to significantly alter the oral microbial flora. Most orthodontic research has focused on cariogenic pathogens, while some evidence has demonstrated an increase in many known periodontal pathogens. However, little is known about the prevalence of the gram-negative periodontal pathogen, Selenomonas noxia (SN) among these patients.Methods: Using an existing saliva biorepository, n=208 samples from adult and pediatric orthodontic and non-orthodontic patients were identified and screened for the presence of SN using qPCR and validated primers. Results: In the pediatric study sample (n=89) 36% tested positive for the presence …

Assessing The Effects Of Streptozotocin-Induced Hyperglycemia On Amyloid Beta Accumulation And Cognitive Behavior In A Mouse Model Of Alzheimer’S Disease-Related Pathology, Andrew Adonay Ortiz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is an irreversible and devastating neurodegenerative disease characterized by progressive synaptic, dendritic, glial, and neuronal loss, collectively leading to impairments in learning, memory, and deterioration of cognitive and behavioral functions. AD is the most common form of dementia accounting for 60-80% of all cases. AD affects approximately 7 million Americans and is the 6th leading cause of death in the US. Furthermore, by 2050, the US is projected to spend over $1.1 trillion on AD-related treatments. Pathological hallmarks of AD include beta-amyloid (Aβ) plaques, intracellular neurofibrillary tangles (NFTs), and chronic neuroinflammation, which can promote and exacerbate both …

Detection And Quantification Of Total Airborne Fungi And Coccidioides Species In Environmental Samples, Theresa T. Roehr

UNLV Theses, Dissertations, Professional Papers, and Capstones

Fungal exposure can cause acute and chronic illnesses or exacerbate existing illnesses. Some fungi are opportunistic pathogens and can lead to serious systemic fungal infections. In 2020, more than 150 million cases of severe fungal infections were reported globally resulting in an estimated 1.7 million deaths. Coccidioidomycosis, or Valley fever, is classified as a serious fungal infection caused by the fungi Coccidioides immitis and C. posadasii. These particular fungi are prevalent in the soil of the Southwestern United States, including Las Vegas, Nevada. In 2024, there were a total of 269 cases of Valley fever reported in Nevada, and …

Torque Efficacy Of Cadmus Bracket Design Using Clear Aligners, Joseph Soderberg

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: Clear aligner therapy (CAT) is an alternative option for clinicians to use for orthodontic treatment as opposed to fixed appliances. Many patients prefer clear aligner therapy due to its esthetic looks, removability, ease of oral hygiene, and comfort. Clear aligner companies boast to clinicians that it can be used more efficiently and effectively than fixed appliances in many orthodontic cases. Although these claims have been made, there is a lack of evidence to prove that clear aligner therapy is more efficient or effective. This research will focus on torque control. This project is designed around a new, pre-manufactured attachment …

Investigating The Influence Of Environmental Stressors To Exopolysaccharide Production In Soil Cyanobacteria: Genomic And Physiological Perspectives, Benjy Sedano-Herrera

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cyanobacteria are photosynthetic microbes with essential roles in Earth’s ecosystems. The secretion of long–chain polysaccharides, known as exopolysaccharides (EPS), is a key trait facilitating cyanobacterial adaptation to diverse ecosystems. Genomics studies have shown that aquatic cyanobacteria harbor multiple gene copies encoding EPS export proteins, likely conferring a selective advantage in lakes or oceans. In addition, physiological experiments showed that nutrient limitation in aquatic habitats influences EPS production, affecting cyanobacterial fitness. However, whether terrestrial cyanobacteria also harbor multiple EPS-related genes and how nutrient limitation impacts their EPS production is not well understood.In the first chapter of my thesis, we investigated the …

Peripheral Neuroimmune Mechanisms Of Chronic Back Pain, Aleyah Esther Goins

Biomedical Sciences ETDs

Chronic back pain (CBP) affects 1 in 10 people worldwide, reducing mobility, productivity, and quality of life. Despite its prevalence, non-addictive treatments remain limited due to an incomplete understanding of chronic pain mechanisms. This dissertation examines peripheral neuroimmune interactions in CBP using a urokinase-type plasminogen activator (uPA)-induced mouse model (uPA-CBP). uPA, a pro-inflammatory serine protease, was injected into the L2/L3 lumbar spinous ligament, inducing prolonged mechanical and cold hypersensitivity. Flow cytometry of dorsal root ganglia (DRG) showed increased CD45+CD11b+ myeloid cells in males and CD45+CD3+CD4+ lymphocytes in females. DRG neurons from male uPA-CBP mice exhibited heightened action potential firing. Pharmacological …

The Influence Of Intrinsic Foot Muscles In Modulating Foot Shape Relative To Substrate And The Efficacy Of Different Strengthening Approaches, Luke R. Lotsis

Masters Theses, 2020-current

Cross-sloped surfaces create an asymmetrical substrate for foot contact, introducing a slip force within the transverse plane and a gravitational pull within the coronal plane that increases the tendency to topple downslope. To maintain stability, the foot must make structural adjustments across the hindfoot, midfoot, forefoot, and hallux. In chapter 1, I investigated how IFMs respond to varying substrate conditions and balance demands, providing insight into their functional role in maintaining stability and adapting foot structure in static and dynamic locomotor tasks. Twenty-four healthy adults participated in a series of dynamic walking trials on flat, cross-sloped and sandy substrates and …

Ubiquitin-Conjugating Enzyme Ube2n Modulates Proteostasis In Immunoproteasome-Positive Acute Myeloid Leukemia, Chiharu Ishikawa, Laura Barreyro, Avery M Sampson, Kathleen M Hueneman, Kwangmin Choi, Sophia Y Philbrook, Issac Choi, Lyndsey C Bolanos, Mark Wunderlich, Andrew G Volk, Stephanie S Watowich, Kenneth D Greis, Daniel T Starczynowski

Faculty, Staff and Student Publications

Altered protein homeostasis through proteasomal degradation of ubiquitinated proteins is a hallmark of many cancers. Ubiquitination, coordinated by E1, E2, and E3 enzymes, involves up to 40 E2-conjugating enzymes in humans to specify substrates and ubiquitin linkages. In a screen for E2 dependencies in acute myeloid leukemia (AML), ubiquitin conjugating enzyme E2 N (UBE2N) emerged as the top candidate. To investigate UBE2N's role in AML, we characterized an enzymatically defective mouse model of UBE2N, revealing UBE2N's requirement in AML without an impact on normal hematopoiesis. Unlike other E2s, which mediate lysine-48 (K48) polyubiquitination and degradation of proteins, UBE2N primarily synthesizes …

Effects Of Altered Somatosensory Input On Gait Kinetics And Kinematics Via Different Footwear In Individuals With Chronic Post-Stroke Hemiparesis, Daniela Casillas, Lesley Ruiz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Purpose/Hypothesis: Individuals with post-stroke hemiparesis walk with significant asymmetries, leading to slow, effortful walking, and a high risk of falls. One contributing factor is altered sensation on the plantar surface. Studies examining altered somatosensory input via insoles, vibration and other tactile stimuli observed improvements in hemiparesis gait. This study investigates whether altering somatosensory input through different footwear can affect kinetics, kinematics and muscle activity during walking post-stroke. We hypothesized the barefoot conditions would have increased dorsiflexion (heel-strike, swing), increased plantarflexion during toe-off, increased muscle activity and kinetics, compared to memory foam conditions.

Participants: 13 individuals with chronic post-stroke hemiparesis (4F/9M, …

The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna

Faculty, Staff and Student Publications

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, …

G-Quadruplex Stabilizer Cx-5461 Effectively Combines With Radiotherapy To Target Α-Thalassemia/Mental Retardation X-Linked-Deficient Malignant Glioma, Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse

Faculty, Staff and Student Publications

Background: Inactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models.

Methods: Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the …

Long-Term Efficacy Of Pembrolizumab And The Clinical Utility Of Ctdna In Locally Advanced Dmmr/Msi-H Solid Tumors, Michael Lapelusa, Wei Qiao, Bryan Iorgulescu, Francis San Lucas, Keyur Patel, Deepak Bhamidipati, Jane Varkey Thomas, Nancy You, Wai Chin Foo, Dipen Maru, Selvi Thirumurthi, Van Morris, Scott Kopetz, Michael Overman, Kaysia Ludford

Faculty, Staff and Student Publications

Neoadjuvant immunotherapy can induce pathologic complete response (pCR) in patients with localized deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors. The long-term outcomes of these patients are unknown, as is the clinical utility of measuring circulating tumor DNA (ctDNA). Follow-up was evaluated in patients enrolled in a phase II trial (NCT04082572) that evaluated the efficacy and safety of pembrolizumab in patients with localized dMMR/MSI-H tumors. The primary outcomes of this trial have previously been reported. 3-year EFS and OS rates were 80% (95% CI: 66% - 93%) and 94% (95% CI: 86% - 100%). Patients without detectable ctDNA after pembrolizumab had …

The Effects Of Sugar Alcohols On The Growth Of Cariogenic Bacteria, Jake Sanders Boone

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study was to examine the potential of sugar alcohols, commonly used as sugar substitutes to reduce the activity of dental caries causing bacteria. Specifically, the sugar alcohols xylitol, erythritol, sorbitol, and mannitol were placed into the growth media of Streptococcus mutans and Lactobacillus acidophilus. The effects on their bacterial growth were observed. 10% xylitol, 10% erythritol, 10% sorbitol, 10% mannitol, 5% xylitol + 5% erythritol, and 3.3% erythritol + 3.3% xylitol + 3.3% sorbitol combinations were compared to the control groups for differences in bacterial growth. S. mutans samples were significantly inhibited by all groups except …

Emerging Adult Gamers: Nutritional Insights On Dietary Intake, Physical Well-Being, And Occupational Performance, Justine Dualan Tuason

UNLV Theses, Dissertations, Professional Papers, and Capstones

This study aimed to gather insights from Emerging Adult (EA) gamers (between 18 and 24) regarding their nutritional literacy, dietary patterns, and its potential impacts on their occupational performance and physical well-being. There is a need to gather gamers' perspectives to identify the specific facilitators and barriers regarding their ability to discern appropriate dietary choices, as it provides more information regarding preventative and client-centered measures for future healthcare professionals. Occupational Therapists (OTs) are uniquely equipped to address this population's needs, as the profession's holistic principles allow for a well-rounded and sustainable approach. Additionally, growing emphasis is placed on preventative rather …

Welcome To The Journal Of Integrative Physiology, Maurie J. Luetkemeier

The Journal of Integrative Physiology

The Journal of Integrative Physiology is dedicated to the development of you, the student researcher as you learn to publish your scholarly works via the peer review process. We welcome your physiology related research studies that you conduct in conjuction with your faculty mentor.

Early Hematopoietic Differentiation Of An Inducible Pluripotent Stem Cell Model Of Infant Lymphoblastic Leukemia, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Priyanka Kumar, Jay L. Vivian, John M. Perry

Research Days

This abstract describes our work regarding the differentiation of human inducible pluripotent stem cells into hematopoietic stem and progenitor cells as the groundwork for the development of a genomics driven inducible pluripotent stem cell model of KMT2A rearranged infant acute lymphoblastic leukemia.

Molecular Characterization And Predictors Of Relapse In Patients With Ph + All After Frontline Ponatinib And Blinatumomab, Nicholas J Short, Hagop Kantarjian, Ken Furudate, Nitin Jain, Farhad Ravandi, Omer Karrar, Sanam Loghavi, Lewis Nasr, Fadi G Haddad, Jayastu Senapati, Rebecca Garris, Koichi Takahashi, Elias Jabbour

Faculty, Staff and Student Publications

Background: Several studies have suggested that chemotherapy-free regimens consisting of blinatumomab and a BCR::ABL1 tyrosine kinase inhibitor are highly effective in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, the clinical and molecular characteristics that predict for relapse with these chemotherapy-free regimens are largely unknown.

Methods: We conducted a prospective phase II clinical trial of the combination of blinatumomab and ponatinib in 76 patients with newly diagnosed Ph + ALL. Patients received 12-15 doses of intrathecal chemotherapy as central nervous systemic (CNS) prophylaxis. The patterns of relapse and the clinical and molecular predictors of relapse were analyzed.

Results: With …

Immunotherapy With Nebulized Pattern Recognition Receptor Agonists Restores Severe Immune Paralysis And Improves Outcomes In Mice With Influenza-Associated Pulmonary Aspergillosis, Jezreel Pantaleón García, Sebastian Wurster, Nathaniel D Albert, Uddalak Bharadwaj, Keerthi Bhoda, Vikram K Kulkarni, Mbaya Ntita, Paris Rodríguez Carstens, Madeleine Burch-Eapen, Daniela Covarrubias López, Jania Foncerrada Lizaola, Katherine E Larsen, Lauren M Matula, Seyed J Moghaddam, Yongxing Wang, Dimitrios P Kontoyiannis, Scott E Evans

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a potentially deadly superinfection in patients with influenza pneumonia, especially those with severe disease, underlying immunosuppression, corticosteroid therapy, or requiring intensive care support. Given the high mortality of IAPA, adjunct immunomodulatory strategies remain a critical unmet need. Previously, the desensitization of pattern recognition pathways has been described as a hallmark of IAPA pathogenesis and a predictor of mortality in IAPA patients. Therefore, we studied the impact of nebulized Toll-like receptor 2/6/9 agonists Pam2 CSK4 (Pam2) and CpG oligodeoxynucleotides (ODNs) on infection outcomes and pulmonary immunopathology in a corticosteroid-immunosuppressed murine IAPA model. Mice with IAPA receiving …

Clinical And Fundamental Research Progressions On Tumor-Infiltrating Lymphocytes Therapy In Cancer, Jiandong Hu, Mengli Jin, Weihong Feng, Barbara Nassif-Rausseo, Alexandre Reuben, Chunhua Ma, Gregory Lizee, Fenge Li

Faculty, Staff and Student Publications

Malignant tumors represent a significant threat to human health. Among the various therapeutic strategies available, cancer immunotherapy-encompassing adoptive cell transfer (ACT) and immune checkpoint blockade therapy-has emerged as a particularly promising approach following surgical resection, radiotherapy, chemotherapy, and molecular targeted therapies. This form of treatment elicits substantial antigen-specific immune responses, enhances or restores anti-tumor immunity, thereby facilitating the control and destruction of tumor cells, and yielding durable responses across a range of cancers, which can lead to the eradication of tumor lesions and the prevention of recurrence. Tumor-infiltrating lymphocytes (TILs), a subset of ACT, are characterized by their heterogeneity and …

Theta Oscillons In Behaving Rats, M S Zobaer, Nastaran Lotfi, Carli M Domenico, Clarissa Hoffman, Luca Perotti, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Recently discovered constituents of the brain waves—the oscillons—provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional θ-waves. The resemblances between θ-oscillons and the conventional θ-waves are manifested primarily at the ballpark level—mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms’ structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled …

Chronic Inflammation: The Link Between A High Added Sugar Diet And Disease, Anna Collins

Senior Honors Theses

The modern diet includes many processed foods that contain added sugars, resulting in a significant increase in daily glucose and fructose consumption. Considering this, there is an increased effort to uncover the effects of excess sugar intake on the body’s health and metabolism. Strong evidence supports the connection between a high added sugar diet and the presence of chronic, low-grade inflammation due to cellular distress and metabolic dysfunction. Prolonged inflammatory responses are linked to tissue damage and the development of various metabolic diseases that are prevalent in modern society, such as obesity, fatty liver disease, cardiovascular disease, and type 2 …

Investigating Undergraduate Conditioned Place Preference Utilizing Virtual Alcohol Stimuli, Nikole A. Rodriguez Torres, Robert Astur, Jeffrey Divino

Honors Scholar Theses

Alcohol use remains a major concern among college students, with binge drinking linked to serious physical and mental health problems. But how much does the environment influence these addictive behaviors? The relationship between environmental cues and alcohol related behaviors is a critical area of study, particularly understanding reward and motivation mechanisms. Binge drinking, common among college students, is associated with a range of negative outcomes such as physical harm, legal issues, poorer overall health, sleep problems, depression, anxiety, and severe thoughts of suicide. In our study, college undergraduates were exposed to two VR rooms: one with alcohol-related stimuli and one …

Ogg1s326c Variant Frequent In Human Populations Facilitates Inflammatory Responses Due To Its Extended Interaction With Dna Substrate, Jinling Han, Meichen Zhang, Jiakun Ge, Zhihua Ji, Jianyi Zhao, Yinchao Hu, Chunshuang Li, Yaoyao Xue, Xining Li, Haiwang Zhao, Zixu Cui, Miaomiao Tian, Xu Zheng, Dapeng Wang, Jing Wang, Min Wei, Zsolt Radak, Yusaku Nakabeppu, Istvan Boldogh, Xueqing Ba

Faculty, Staff and Student Publications

8-oxoguanine (8-oxoGua) is one of the most frequent forms of oxidative DNA base lesions, repaired by 8-oxoguanine DNA glycosylase 1 (OGG1) via base excision repair (BER) pathway to maintain genome fidelity. The human allelic variant hOGG1^S326C, prevalent in Caucasians and Asians, has been regarded as a susceptibility factor for various diseases, yet its pathogenic mechanism remains elusive. In this study, we demonstrate that Ogg1^S326C/S326C mice exhibit increased and sustained airway inflammation compared with wild-type (WT) Ogg1^S326/S326 mice. Mechanistically, in response to inflammatory stimulation, OGG1S326C undergoes reactive oxygen species-induced dimerization, which impairs its base excision function, but …

A Pharmacokinetic And Safety Study Of Oral Arsenic Trioxide In Patients With Acute Promyelocytic Leukemia, Farhad Ravandi, Sravanti Rangaraju, Hagop Kantarjian, Guillermo Garcia-Manero, Musa Yilmaz, Kristen Baker, Terence Hall, Joy Grabenstein, Pourab Roy, Beth A Zamboni, William C Zamboni, Erica Warlick, Michael Kelly, David A Roth, Gabriel Ghiaur

Faculty, Staff and Student Publications

SY-2101 is a novel oral formulation of arsenic trioxide (ATO). Although IV ATO in combination with all trans retinoic acid is highly efficacious in treating acute promyelocytic leukemia (APL), there remains a significant unmet need due to the treatment burden associated with receiving daily ATO infusions for nearly a year and the risk of complications associated with indwelling central catheters. The pharmacokinetics (PK), safety, and tolerability of SY-2101 and ATO IV after single- and multiple-dose administration and the impact of food on PK for SY-2101 were evaluated in this phase 1 study in 15 participants with APL. SY-2101 in the …