Therapeutics Commons^™

A Comparison Of The Safety And Efficacy Of Tapinarof And Roflumilast Topical Therapies In The Management Of Mild-To-Moderate Plaque Psoriasis, Hira Ghani, Alicia Podwojniak, Isabella J Tan, Aarushi K Parikh, Bianca Sanabria, Babar Rao

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Psoriasis is an immune-mediated inflammatory skin disease. First-line topical treatments include steroids, calcineurin inhibitors, vitamin D analogs, and anthralin. Recently, novel topical therapeutics like tapinarof and roflumilast have emerged with unique anti-inflammatory mechanisms and promising efficacy profiles.

MATERIALS AND METHODS: This review utilized PubMed, SCOPUS, and Web of Science databases to identify recent studies on tapinarof and roflumilast. Criteria focused on efficacy, safety profiles, and therapeutic roles in psoriasis treatment.

RESULTS: Four primary literature articles were identified for tapinarof and five for roflumilast. Both drugs demonstrated strong efficacy with minimal adverse events in treating mild-to-moderate plaque psoriasis. Tapinarof showed …

Exploring Perinatal Ketamine For Postpartum Depression Following Cesarean Section: A Systematic Review, Jaylyn Thompson, David F Lo, Alexis Foschini, Suvan Sundaresh

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The aim of this study was to explore the use of perinatal ketamine to see if it can be used for the reduction of postpartum depression (PPD) following cesarean section (C-section). PubMed, Cochrane, and Web of Science were the primary databases used for this review. Search terms used on January 5, 2024 incorporated "ketamine," "C-section," "postpartum depression," and related synonyms. The criteria for inclusion centered on studies published between January 1, 2008 and January 5, 2024. The final selection of articles was screened based on extraction criteria leaving eight randomized control trials in the final review. The selected data from …

Inflammation, Physical Activity, And Disease-Free Survival In Stage Iii Colon Cancer: Calgb/Swog 80702 (Alliance), Justin C. Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M. Goldberg, Eileen M. O'Reilly, Anthony F. Shields, Jeffrey A. Meyerhardt

School of Medicine Faculty Publications

Background: Both inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown. Methods: This cohort study was nested within the CALGB/SWOG 80702 (Alliance) randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free survival. Results: The 3-year disease-free survival rate was 88.4% among patients with low inflammation and …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …

Recurrent Inflammatory Myofibroblastic Tumor Of Larynx Harboring A Novel Thbs1::Alk Fusion, Namra Ajmal, Stacey Gargano, Ujwala Gosavi, Madalina Tuluc

Computational Medicine Center Faculty Papers

Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue tumor primarily occurring in the abdominopelvic region of young patients, and it is characterized by spindle-shaped myofibroblasts, or fibroblasts surrounded by inflammatory infiltrate. Herein, we report a case of a 24-year-old male with a firm submucosal mass in the anterior right vocal fold diagnosed as an IMT that recurred 14 months later. The tumor demonstrated a novel THBS1::ALK fusion containing Exons 1-7 of the thrombospondin 1 (THBS1) gene fused to Exon 19 of the anaplastic lymphoma kinase (ALK) gene via next-generation sequencing with the NextSeq sequencer. The fusion of THBS1 to …

Enpp1 Enzyme Replacement Therapy Improves Ectopic Calcification But Does Not Rescue Skeletal Phenotype In A Mouse Model For Craniometaphyseal Dysplasia, Ernst Reichenberger, Kevin O'Brien, Ayano Hatori, Thomas Carpenter, Koen Van De Wetering, Lisa Flaman, Jennifer Howe, Daniel Ortiz, Yves Sabbagh, I-Ping Chen

Jefferson Institute of Molecular Medicine Papers and Presentations

Craniometaphyseal dysplasia (CMD) is a rare genetic bone disorder, characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. Craniofacial hyperostosis leads to the obstruction of neural foramina and neurological symptoms such as facial palsy, blindness, deafness, or severe headache. Mutations in ANKH (mouse ortholog ANK), a transporter of small molecules such as citrate and ATP, are responsible for autosomal dominant CMD. Knock-in (KI) mice carrying an ANK_F377del mutation (Ank^KI/KI) replicate many features of human CMD. Pyrophosphate (PPi) levels in plasma are significantly reduced in Ank^KI/KI mice. PPi is a potent inhibitor of …

Non-Receptor Tyrosine Kinases: Their Structure And Mechanistic Role In Tumor Progression And Resistance, Abdulaziz M. Eshaq, Thomas W. Flanagan, Sofie Yasmin Hassan, Sara A. Al Asheikh, Waleed A. Al-Amoudi, Simeon Santourlidis, Sarah Lilly Hassan, Maryam O. Alamodi, Marcelo L. Bendhack, Mohammed O. Alamodi, Youssef Haikel, Mossad Megahed, Mohamed Hassan

School of Graduate Studies Faculty Publications

Protein tyrosine kinases (PTKs) function as key molecules in the signaling pathways in addition to their impact as a therapeutic target for the treatment of many human diseases, including cancer. PTKs are characterized by their ability to phosphorylate serine, threonine, or tyrosine residues and can thereby rapidly and reversibly alter the function of their protein substrates in the form of significant changes in protein confirmation and affinity for their interaction with protein partners to drive cellular functions under normal and pathological conditions. PTKs are classified into two groups: one of which represents tyrosine kinases, while the other one includes the …

High-Dose Intravenous Vitamin C Combined With Docetaxel In Men With Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase Ii Trial, Channing Paller, Marianna Zahurak, Adel Mandl, Nicole Metri, Aliya Lalji, Elisabeth Heath, William Kelly, Christopher Hoimes, Pedro Barata, Jason Taksey, Dominique Garrison, Kartick Patra, Ginger Milne, Nicole Anders, Julie Nauroth, Jennifer Durham, Catherine Marshall, Mark Markowski, Mario Eisenberger, Emmanuel Antonarakis, Michael Carducci, Samuel Denmeade, Mark Levine

Department of Medicine Faculty Papers

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate …

Functional Contribution Of Epithelial To Mesenchymal Transition Program On Krasg12d Targeting Efficacy In Pancreatic Cancer, Ana S. Maldonado

Dissertations and Theses (Open Access)

Functional contribution of epithelial to mesenchymal transition program on KRAS^G12D targeting efficacy in pancreatic cancer

Ana S. Maldonado, BS

Advisory Professor: Raghu Kalluri, M.D., Ph.D.

Pancreatic Ductal Adenocarcinoma (PDAC), a highly aggressive, metastatic, and therapeutically resistant form of pancreatic cancer has been projected to become the second-leading cause of cancer related mortality in the United States. This is driven by its detection difficulty, treatment efficacy, and asymptomatic nature, among other factors. PDAC is driven predominantly by KRAS^G12D mutations, which are responsible for the initial development of pancreatic intraepithelial neoplasia (Pan-IN) lesions, that are further maintained and progressed until …

Nanoparticle-Based Approaches To Brain Injury And Studies For Improved Detectability Toward Better Delivery Characterization, Hunter A. Miller

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

The clinical translation of nanoparticle (NP) therapeutics for brain injury has been slow despite preclinical promise. The causes of disconnect between preclinical and clinical outcomes is multifactorial, but insufficient delivery is noteworthy. Preclinical delivery characterization often lacks, obscuring mechanisms of failure, slowing development. Multimodal imaging is a promising strategy to improve delivery characterization, combining the strengths of various modalities. Magnetic resonance imaging (MRI) and luminescence imaging are a suitable combination for multimodal imaging, expanding the spatial and temporal resolution of either alone, but further material development is needed to enhance detectability. One problem is the interference of cellular autofluorescence in …

Differential Effect Of An Evolving Amyloid And Tau Pathology On Brain Phospholipids And Bioactive Lipid Mediators In Rat Models Of Alzheimer-Like Pathology, Sonia Do Carmo, Marie Audrey I. Kautzmann, Surjyadipta Bhattacharjee, Bokkyoo Jun, Carolyn Steinberg, Joshua T. Emmerson, Janice C. Malcolm, Quentin Bonomo, Nicolas G. Bazan, A. Claudio Cuello

School of Graduate Studies Faculty Publications

Background: Brain inflammation contributes significantly to the pathophysiology of Alzheimer’s disease, and it is manifested by glial cell activation, increased production of cytokines/chemokines, and a shift in lipid mediators from a pro-homeostatic to a pro-inflammatory profile. However, whether the production of bioactive lipid mediators is affected at earlier stages, prior to the deposition of Aβ plaques and tau hyperphosphorylation, is unknown. The differential contribution of an evolving amyloid and tau pathology on the composition and abundance of membrane phospholipids and bioactive lipid mediators also remains unresolved. Methods: In this study, we examined the cortical levels of DHA- and AA-derived bioactive …

Potential Targeting Mechanisms For Bone-Directed Therapies, Betul Celik, Andrés Leal, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. However, none of these strategies fully corrects skeletal dysfunction, particularly in growth plate-related ones. Although direct recombinant enzymes (e.g., Vimizim for Morquio, Cerezyme for Gaucher, Elaprase for Hunter, Mepsevii for …

Transcriptomic Features Associated To Neoadjuvant Chemotherapy Response In Four Molecular Breast Cancer Subtypes, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos Alberto Orozca, Alejandro Mejia-Garcia, Jovanny Zabaleta, Liliana Lopez-Kleine, Alba Lucia Combita-Rojas

School of Medicine Faculty Publications

12th Annual Symposium on Global Cancer Research, Virtual, May 5 - 9, 2024

The Value Of Using Validated Competency-Based Assessments Across The Career Span Of An Athletic Trainer, Matthew Drescher, Lindsey Eberman

Clinical Practice in Athletic Training

No abstract provided.

Perceptions And Use Of The Athletic Training Milestones In Education: A Report From The Aate Research Network, Cailee E. Welch Bacon, Barton E. Anderson, Julie M. Cavallario, Bonnie L. Van Lunen, Lindsey E. Eberman

Clinical Practice in Athletic Training

The Athletic Training Milestones (AT Milestones) were developed as an evaluation tool to capture the breadth and depth of athletic training knowledge, skills, and behavior. However, it is unclear whether athletic training programs are implementing this tool or how they are implementing it to gauge the clinical progression of students or residents in athletic training. We aimed to explore the perceptions and use of the AT Milestones among educators in athletic training programs. We used a cross-sectional, web- based survey with open-ended questions to collect data from athletic training programs on if and how they implement the AT Milestones at …

Standardized Patient Evaluation Tool: A Valid Measure Of The Core Competencies, Lindsey E. Eberman, Jessica Edler Nye

Clinical Practice in Athletic Training

No abstract provided.

The Development, Implementation, And Value Of The Athletic Training Milestones For Assessing Progressive Clinical Behaviors, Hollie Walusz, Eric Sauers, Mark Laursen, Forrest Pecha

Clinical Practice in Athletic Training

No abstract provided.

Enhancing Neoadjuvant Virotherapy's Effectiveness By Targeting Stroma To Improve Resectability In Pancreatic Cancer, Khandoker Usran Ferdous, Mulu Z. Tesfay, Aleksandra Cios, Randal S. Shelton, Conner Hartupee, Alicja Urbaniak, Jean Christopher Chamcheu, Michail N. Mavros, Emmanouil Giorgakis, Bahaa Mustafa, Camila C. Simoes, Isabelle R. Miousse, Alexei G. Basnakian, Omeed Moaven, Steven R. Post, Martin J. Cannon, Thomas Kelly, Bolni Marius Nagalo

School of Medicine Faculty Publications

About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering …

The Evolving Use Of Gold Nanoparticles As A Possible Reversal Agent For The Symptoms Of Neurodegenerative Diseases: A Narrative Review, Alan D. Kaye, Kelly R. Sala, Drew Dethloff, Matthew Norton, Corey Moss, Michael J. Plessala, Alyssa G. Derouen, Yair Lopez Torres, Julian Kim, Sridhar Tirumala, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Neurodegenerative diseases are broadly hallmarked by impaired energy metabolism and toxic intracellular accumulations such as damaged organelles or reactive oxygen species (ROS). Gold nanoparticles readily cross the blood-brain barrier and increase nicotinamide adenine dinucleotide + hydrogen (NADH) oxidation to nicotinamide adenine dinucleotide (NAD+), which is vital for intracellular energy generation, cellular repair, and protection from ROS. Thus, the use of gold nanoparticles to treat and potentially reverse cellular injury seen in neurodegenerative disease has been an area of ongoing research. This systematic review explores current literature regarding the use of gold nanoparticle therapy in the treatment of neurodegenerative diseases such …

Effect Of Transcranial Direct Current Stimulation And Narrow-Band Auditory Stimulation On The Intraoperative Electroencephalogram: An Exploratoratory Feasibility Study, Oliver G. Isik, Tuan Z. Cassim, Meah T. Ahmed, Matthias Kreuzer, Alice M. Daramola, Paul S. Garcia

SKMC Student Presentations and Publications

INTRODUCTION: During general anesthesia, frontal electroencephalogram (EEG) activity in the alpha frequency band (8-12 Hz) correlates with the adequacy of analgesia. Transcranial direct current stimulation (tDCS) and auditory stimulation, two noninvasive neuromodulation techniques, can entrain alpha activity in awake or sleeping patients. This study evaluates their effects on alpha oscillations in patients under general anesthesia.

METHODS: 30 patients receiving general anesthesia for surgery were enrolled in this two-by-two randomized clinical trial. Each participant received active or sham tDCS followed by auditory stimulation or silence according to assigned group (TDCS/AUD, TDCS/SIL, SHAM/AUD, SHAM/SIL). Frontal EEG was recorded before and after neuromodulation. …