Chemical Actions and Uses Commons^™

Assessing The Efficacy Of Prolonged Doxycycline Pep Use In High-Risk Populations For Sti Prevention, Lam Doan, Pearl Joslyn, Lizann Sung, Timothy Breiner, Sarah Marotta, Shikhar Rastogi

Rowan-Virtua Research Day

First recommended in October 2022, doxycycline post-exposure prophylaxis (DoxyPEP) has been increasingly used as a treatment for multiple sexually transmitted infections (STIs). To evaluate the efficacy of prolonged DoxyPEP use in high risk populations - men who have sex with men (MSM) and transgender women - for STIs, different sources addressing various aspects of DoxyPEP, its efficacy in STI prevention, and the potential consequences of its widespread use in terms of antimicrobial resistance were examined. Across 9 studies, DoxyPEP was found to decrease the incidence of bacterial STIs, specifically, syphilis, chlamydia, and gonorrhea with varying efficacy, especially for gonorrhea. Furthermore, …

Cardiovascular Effects Of Glp-1 Receptor Agonists In Non-Diabetic Adults With Obesity: A Systematic Literature Review, Mariam Abdeen

Rowan-Virtua Research Day

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with obesity. GLP-1 receptor agonists, initially developed for glycemic control in diabetes, are now approved for weight loss in non-diabetic populations. Recent clinical trials suggest these agents may also offer direct cardiovascular benefits.

Objective: This literature review aims to evaluate the cardiovascular effects of GLP-1 receptor agonists, specifically semaglutide, liraglutide, and tirzepatide, in non-diabetic adults with overweight or obesity.

Methods: A systematic search was conducted in January 2025 using PubMed as the primary database, supplemented by Google Scholar and Embase. Clinical trials were selected based on …

A Rare Case Of Diffuse Alveolar Hemorrhage In The Setting Of Iga Nephropathy, Vasculitis And Atypical Hemolytic Uremic Syndrome In A Previously Healthy Young Adult, Karl Schlicht, Nancy Kaura

Rowan-Virtua Research Day

IgA Nephropathy, also known as Berger disease, can precipitate acute renal failure in patients. IgA Nephropathy (IgAN) is deposition of protein from IgA into the renal tissue with subsequent renal dysfunction. IgA vasculitis (IgAV) is another condition where similarly the protein of IgA is deposited into the vessels. There are some cases of co-existing atypical hemolytic uremic syndrome (aHUS) with IgAN. However, rare combinations seen with all three IgAN, IgAV, and aHUS without any pre-existing conditions nor medical history. Patients that develop any one of these conditions are looking at life long changes with hemodialysis (HD) and organ transplants being …

Alcohol And Cannabis Use For Pain Management: Translational Findings Of Relative Risks, Benefits, And Interactions, Sumin Lee, Scott Edwards

School of Medicine Faculty Publications

Chronic pain affects over 20% of the global population and contributes to the vast burden of psychiatric illness. While effective treatments for chronic pain remain limited, both alcohol and cannabis have been used for centuries to manage pain and closely associated negative affective symptoms. However, persistent misuse of alcohol and/or cannabis in such a negative reinforcement fashion is hypothesized to increase the risk of severity of substance use disorders (SUDs). The current review describes neurobiological evidence for the analgesic efficacy of alcohol and primary cannabis constituents and how use or co-use of these substances may influence SUD risk.

Glucagon-Like Peptide-1 Receptor Agonists Improve Metabolic Dysfunction-Associated Steatotic Liver Disease Outcomes, Brandon Havranek, Rebecca Loh, Beatriz Torre, Rachel Redfield, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard …

An Open-Label Study To Determine The Maximum Tolerated Dose Of Oral Esk-440 Administered As A Single Agent In Patients With Advanced Or Metastatic Solid Tumors, Russell J. Schilder, Drew Rasco, Manish R. Sharma

Kimmel Cancer Center Faculty Papers

PURPOSE: Anaplastic lymphoma kinase (ALK) dysregulation is implicated in numerous cancers. Tyrosine kinase inhibitors (TKIs) targeting ALK have improved disease outcomes, but resistance mechanisms are common. This first-in-human trial evaluates ESK-440, a dual inhibitor of ALK and focal adhesion kinase, as a novel strategy for cancers with resistance to ALK-targeting TKIs.

METHODS: This phase 1, open-label, dose-finding study evaluated the maximum tolerated dose (MTD), safety, efficacy, and pharmacokinetics of ESK-440 in participants with advanced or metastatic solid tumors (ClinicalTrials.gov: NCT01922752). A 3 + 3 dose-escalation design, with daily doses ranging from 25 to 700 mg/day of ESK-440 for each 28-day …

Durable Responses To Immune Checkpoint Inhibitor-Based Regimens For Metastatic Clear Cell Renal Cell Carcinoma Stratified By Imdc Risk Groups: A Pooled Analysis Of Four Randomized Phase 3 Trials, Albert Jang, Jeffrey Y. Zhong, Hamsa L.S. Kumar, Kevin K. Zarrabi, Alec Zhu, Abby L. Grier, Adam Calaway, Jonathan E. Shoag, Laura Bukavina, Angela Y. Jia, Prateek Mendiratta, Iris Y. Sheng, Santosh Rao, Jason R. Brown, Jorge A. Garcia, Seunghee Margevicius, Pingfu Fu, Pedro C. Barata

Department of Medical Oncology Faculty Papers

Background: An immune checkpoint inhibitor (ICI) backbone is a standard of care for frontline metastatic clear cell renal cell carcinoma, involving either ICI doublet or tyrosine kinase inhibitor (TKI) with ICI. These phase 3 trials used a sunitinib control arm. The optimal regimen is uncertain. Objective: To compare long-term responders of these trials using extended follow-up data stratified by International Metastatic RCC Database Consortium risk group. Methods: Phase 3 trial data (CheckMate 214, KEYNOTE-426, CheckMate 9ER, and CLEAR) with a minimum follow-up of four years was used. Pseudo individual patient data (IPD) was obtained from Kaplan-Meier curves using the graph …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Management Of Hip Fracture Patients On Direct Oral Anticoagulants: A Survey Of Orthopaedic Trauma Surgeons, Systematic Review, And Meta-Analysis, Clay Spitler, Robert Rutz, Nigel Blackwood, Meghan Wally, Joseph Johnson, Peter Krause, Jaimo Ahn, Zuhair Mohammed, Mark Mcclure, Rebecca Billings, Ziqing Yu, Matthew Yeager

School of Medicine Faculty Publications

OBJECTIVES: This systematic review examined the literature regarding management of fracture patients who take direct oral anticoagulant (DOAC) medications, with a focus on delay in surgical treatment, and need for transfusions. In addition, a survey of orthopaedic trauma surgeons was conducted to gain insight on current practices. DATA SOURCES: A review of PubMed, Cochrane, Embase, and Scopus databases was performed from inception through March 2024, including English language publications. STUDY SELECTION: Studies were included if they reported time to surgery and transfusion rates among fracture patents who were taking DOAC medications. Additional data points were collected on an "if-reported" basis, …

Residual Traditional Risk In Non-Traditional Atherosclerotic Diseases, Federico Biscetti, Giorgia Polito, Maria Margherita Rando, Maria Anna Nicolazzi, Luis H. Eraso, Paul J. Dimuzio, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

Individuals with chronic inflammatory and immune disorders are at an increased risk of atherosclerotic events and premature cardiovascular (CV) disease. Despite extensive literature exploring the relationship between "non-traditional" atherosclerotic conditions and CV risk, many aspects remain unresolved, including the underlying mechanisms promoting the "non-traditional CV risk", the development of an innovative and comprehensive CV risk assessment tool, and recommendations for tailored interventions. This review aims to evaluate the available evidence on key "non-traditional" CV risk-enhancer conditions, with a focus on assessing and managing CV risk factors. We conducted a comprehensive review of 412 original articles, narrative and systematic reviews, and …

Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer

Kimmel Cancer Center Faculty Papers

BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. …

Emcreg-International Multidisciplinary Consensus Panel On Management Of Hyperkalemia In Chronic Kidney Disease And Heart Failure, Natalie Kreitzer, Nancy M. Albert, Alpesh N. Amin, Craig J. Beavers, Richard C. Becker, Gregg Fonarow, W. Brian Gibler, Katherine W. Kwon, Robert J. Mentz, Biff F. Palmer, Charles V. Pollack, Iliana L. Piña

Division of Cardiology Faculty Papers

BACKGROUND: Hyperkalemia, generally defined as serum potassium levels greater than 5.0 mEq/L, poses significant clinical risks, including cardiac toxicity and muscle weakness. Its prevalence and severity increase in patients with chronic kidney disease (CKD), diabetes mellitus, and heart failure (HF), particularly when compounded by medications like angiotensin converting inhibitors, angiotensin receptor blockers, and potassium sparing diuretics. Hyperkalemia arises from disruptions in potassium regulation involving intake, excretion, and intracellular-extracellular distribution. In CKD and acute kidney injury, these regulatory mechanisms are impaired, leading to heightened risk. The management of chronic hyperkalemia presents a challenge due to the necessity of balancing effective cardiovascular …

Lrtm Left-Right Transition Matrices For Molecular Interaction Prediction, Kaitlin Zheng, Guihua Duan, Mengyun Yang, Wei Wu, Yao-Hang Li, Jianxin Wang

Computer Science Faculty Publications

Molecular interactions are central to most biological processes. The discovery and identification of potential associations between molecules can provide insights into biological exploration, diagnostic and therapeutic interventions, and drug development. So far many relevant computational methods have been proposed, but most of them are usually limited to specific domains and rely on complex preprocessing procedures, which restricts the models’ ability to be applied to other tasks. Therefore, it remains a challenge to explore a generalized approach to accurately predicting potential associations. In this study, We propose Left-Right Transition Matrices (LRTM) for molecular interaction prediction. From the perspective on the diffusion …

Chronic Administration Of A Cannabis-Derived Mixture At An Antihyperalgesic Dose Does Not Significantly Enhance Hepatotoxicity Or The Development Of Metabolic Dysfunction-Associated Steatohepatitis In Male Mice, Kim B. Pedersen, Tomislav Jelesijevic, Tamara M. Morris, Sarah M. Melton, Ashley S. Henderson, John F. Glenn, Gregory J. Davenport, Martin J.J. Ronis, Peter J. Winsauer

School of Medicine Faculty Publications

Cannabis and cannabinoid mixtures have been linked to a variety of health benefits including pain mitigation, suppression of nausea produced by chemotherapeutic agents, anti-inflammatory effects, and effects on energy homeostasis, glucose, and lipid metabolism. The latter properties have led to the suggestion that these products could have therapeutic effects on the development of metabolic dysfunction-associated steatohepatitis (MASH) - a severe type of liver pathology in obese and diabetic patients. However, varying agonist and antagonistic properties of different cannabinoids on the endogenous cannabinoid system make prediction regarding hepatic effects and diet interactions difficult. The current study was designed to examine hepatic …

The Complexity And Significance Of Fibroblast Growth Factor (Fgf) Signaling For Fgf-Targeted Cancer Therapies, Anh Nguyen, Caroline Facey, Bruce Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 …

Glucagon-Like Peptide-1 Receptor Agonist Mediated Weight Loss And Diabetes Mellitus Benefits: A Narrative Review, Alan D. Kaye, Nathan Lien, Christopher Vuong, Matthew H. Schmitt, Yusra Soorya, Bushirat A. Abubakar, Luke Muiznieks, Noah Embry, Harish Siddaiah, Adam M. Kaye, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Obesity and type 2 diabetes mellitus (T2DM) are chronic diseases with increasing prevalence, underscoring the urgent need for effective treatment and management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an essential class of drugs for managing both obesity and T2DM, offering additional benefits for cardiovascular and kidney health. GLP-1 RAs work by targeting GLP-1 receptors, mimicking the effects of the natural hormone GLP-1 to regulate blood glucose levels, promote weight loss, and provide potential benefits for cardiovascular health. This narrative review evaluates the mechanisms of action, clinical efficacy, and broader roles of GLP-1 RAs in promoting weight …

Takeout Or Delivery? Reoperation Rates In Lower Extremity Long Bone Osteomyelitis Treated With Debridement And Local Antibiotic Delivery Systems, Nolan M. Reinhart, Jackson P. Tate, Jacob S. Budin, Julianna E. Winter, Olivia C. Lee, William F. Sherman

School of Medicine Faculty Publications

BACKGROUND: Early diagnosis and treatment of osteomyelitis is essential to prevent potential complications including sepsis, extensive bone resection, amputation, and death. Despite current treatment strategies for management of osteomyelitis, recurrence rates reported in the literature are upwards of 25 %. Current evidence comparing the efficacy of differing surgical treatments of osteomyelitis is inconclusive. The purpose of this study is to compare rates of re-debridement and amputation in patients who receive either debridement alone or debridement with placement of local antibiotic delivery systems as initial treatment for lower extremity long bone osteomyelitis. METHODS: A retrospective cohort study was performed to investigate …

Clinical Practice Guideline-Inconsistent Chemotherapy-Induced Vomiting Prophylaxis In Pediatric Cancer Patients In Community Settings: A Children's Oncology Group Study, Aaron J. Sugalski, Allison C. Grimes, Michelle M. Nuño, Subhash Ramakrishnan, Melissa P. Beauchemin, Paula D. Robinson, Nancy Santesso, Alexandra M. Walsh, Andrea R. Wrightson, Lolie C. Yu, Susan K. Parsons, Lillian Sung, L. Lee Dupuis

School of Medicine Faculty Publications

Background: This study aimed to determine the proportion of patients receiving clinical practice guideline (CPG)-inconsistent care related to chemotherapy-induced vomiting (CIV) prophylaxis, and to describe the association between CPG-inconsistent care and site size. The association between delivery of CPG-inconsistent care and patient outcomes (CIV control, admission prolongation, and unplanned healthcare visits) was also described. Methods: This was a retrospective study conducted at Children's Oncology Group (COG) National Cancer Institute Community Oncology Research Program (NCORP) sites. Eligible patients received highly (HEC) or moderately emetogenic chemotherapy (MEC) as inpatients from January 2014 through December 2015, and were previously enrolled in a COG …

Successful Treatment Of A Chronic Recurrent Expanding Hematoma Of The Thigh, Gianfranco Galantini, Bakhtawar Mushtaq, Jesse Ottaway, Charles Long

Abington Jefferson Health Papers

Chronic expanding hematoma (CEH) is a rare entity that poses diagnostic and therapeutic challenges due to persistent growth, risk of recurrence, and potential for blood loss anemia. The most common etiologies of CEH are trauma or surgery. It is thought to occur due to irritant effects of blood breakdown products, causing bleeding from capillaries in chronic granulation tissue. Although treatment of CEH is variable, complete surgical excision of the hematoma and its pseudocapsule is the gold standard. We present a case of a 15-year CEH that was initially treated with limited evacuation of the hematoma and cavity decortication, resulting in …

The Potential Anti-Arrhythmic Effect Of Sglt2 Inhibitors, Hong-Yi Duan, Hector Barajas-Martinez, Charles Antzelevitch, Dan Hu

Department of Medicine Faculty Papers

Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) were initially recommended as oral anti-diabetic drugs to treat type 2 diabetes (T2D), by inhibiting SGLT2 in proximal tubule and reduce renal reabsorption of sodium and glucose. While many clinical trials demonstrated the tremendous potential of SGLT2i for cardiovascular diseases. 2022 AHA/ACC/HFSA guideline first emphasized that SGLT2i were the only drug class that can cover the entire management of heart failure (HF) from prevention to treatment. Subsequently, the antiarrhythmic properties of SGLT2i have also attracted attention. Although there are currently no prospective studies specifically on the anti-arrhythmic effects of SGLT2i. We provide clues from …

Hairy Tongue Associated With The Use Of Baricitinib Therapy For Ophiasis Pattern Alopecia Areata, Anthony Gaspari

Department of Dermatology and Cutaneous Biology Faculty Papers

We report a case of hairy tongue that developed in a young Caucasian
/="/">woman during systemic baricitinib therapy for severe alopecia areata.
/="/">Because she experienced good clinical regrowth of her hair during
/="/">treatment, she did not want to interrupt therapy. We recommended she
/="/">use a toothbrush to debride her tongue on a daily basis, which was
/="/">successful. Hairy tongue most commonly occurs in elderly, debilitated
/="/">males with poor oral hygiene. It is thought to occur because of overgrowth
/="/">of chromogenic bacteria and/or yeast on the tongue. This unusual side
/="/">effect during baricitinib …

Increased Usage Of Doxycycline For Young Children With Lyme Disease, Amy Thompson, Desiree Neville, Laura Chapman, Fran Balamuth, Meagan Ladell, Anupam Kharbanda, Rachael Aresco, Lise Nigrovic

Department of Emergency Medicine Faculty Papers

Background: The 2018 Infectious Disease Committee of the American Academy of Pediatrics stated that up to 3 weeks or less of doxycycline is safe in children of all ages. Our goal was to examine trends in doxycycline treatment for children with Lyme disease.

Methods: We assembled a prospective cohort of children aged 1 to 21 years with Lyme disease who presented to one of eight participating Pedi Lyme Net centers between 2015 and 2023. We defined a Lyme disease case with an erythema migrans (EM) lesion or positive two-tier Lyme disease serology categorized by stage: early-localized (single EM lesion), early-disseminated …

The Impact Of Vitamin Supplementation (D, B12, B9) On Behaviors Associated With Autism Spectrum Disorder, Rohan Mehra

Rowan-Virtua Research Day

Background: One in 36 children in the United States are diagnosed with Autism Spectrum Disorder (ASD). Although heritability of the condition ranges from 40 to 80%, other factors such as vitamin levels, may have a significant impact on the risk of development. These vitamins include D, B12, and B9.

Purpose: To assess the impact vitamin supplementation has on behaviors associated with ASD, and to determine which specific aspects of ASD may be improved with vitamin supplementation.

Methods: A literature review was performed. The search was utilized PubMed, JSTOR and Web of Science. Keyword strings included: “Vitamin D B12 B9 folate …

Advancing Treatment In Atopic Dermatitis: A Comprehensive Review Of Clinical Efficacy, Safety, And Comparative Insights Into Corticosteroids, Calcineurin Inhibitors, And Phosphodiesterase-4 Inhibitors As Topical Therapies, Tyler D. Hernandez, Sarah J. Aleman, Maria Bao-Loc-Trung, Michael V. Forte, William Brandt, Catherine Armstrong, Jeffrey Howard, Chizoba N. Mosieri, Shahab Ahmadzadeh, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Atopic dermatitis (AD) is a pervasive and multifaceted dermatological disorder causing daily distress to afflicted individuals worldwide. This comprehensive review synthesizes the historical and contemporary advancements in therapeutic strategies, offering a critical analysis of their efficacy, safety profiles, and adaptability. The enduring role of topical corticosteroids in managing AD is examined, acknowledging their potent anti-inflammatory properties alongside their potential adverse side effects, particularly in extended usage. The article explores the utilization of topical calcineurin inhibitors like tacrolimus and pimecrolimus, highlighting their novel anti-inflammatory pathways while also scrutinizing concerns over potential malignancies that relegate them to second-line therapy. The present investigation …

Stevens-Johnson Syndrome From Combined Allopurinol And Angiotensin-Converting Enzyme Inhibitors: A Narrative Review, Isabella M. Fabian, Kirsten Maddox, Cameron Robicheaux, Rahib K. Islam, Ahmed Anwar, Bradley Dorius, Christopher L. Robinson, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Stevens-Johnson syndrome (SJS) is a severe and potentially debilitating skin reaction frequently related to medication use. Allopurinol and angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for prevalent health conditions worldwide, and their interaction associated with SJS warrants further investigation. A comprehensive literature search was performed to investigate cases as studies related to SJS occurring in patients with concomitant use of allopurinol and ACE inhibitors. We identified case reports and studies detailing hypersensitivity reactions, including SJS, attributed to a combination of allopurinol and ACE inhibitors. Despite the drug-drug interactions or lack thereof seen in patient populations, there is no definitive …

Topiramate (Topamax): Evolving Role In Weight Reduction Management: A Narrative Review, Irza Wajid, Alexis Vega, Katherine Thornhill, Jack Jenkins, Chandler Merriman, Debbie Chandler, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye

School of Medicine Faculty Publications

Obesity has emerged as a widespread disease with epidemic proportions, necessitating effective management to enhance the overall health outcomes of patients. Medical intervention for weight loss becomes necessary when diet and exercise prove ineffective, and topiramate emerges as a potential treatment option for this global problem. Currently approved as an anti-epileptic and migraine prophylaxis medication, topiramate is frequently utilized as adjunctive therapy for patients with mood and eating disorders, as well as for alcohol use disorders. Its multifaceted mechanisms of action contribute to reducing neuronal excitation and enhancing neuronal inhibition. Given its variety of mechanisms, topiramate shows several off-label outcomes, …

Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased …

High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …

Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun

School of Medicine Faculty Publications

Background: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …

Comparison Of Clinical And Radiographic Efficacy Of Particles Versus Nbca/Onyx In Middle Meningeal Artery Embolization For Chronic Subdural Hematoma, Jane Khalife, Mohamed Salem, Victoria Wong Murray, Allen Karimov, Brian Jankowitz, Jan Karl Burkhardt, Hamza Shaikh, Daniel Tonetti, Pratit Patel, Tudor Jovin, Ajith Thomas

Rowan-Virtua Research Day

Different embolic materials are utilized in MMA embolization of chronic subdural hematoma per operators’ discretion. We aim to compare the clinical and radiographic efficacy of different embolic materials in a pooled retrospective cohort of two US centers.