Pharmacy and Pharmaceutical Sciences Commons^™

Prmt5 As A Key Driver Of Stemness And Metastatic Potential In Triple-Negative Breast Cancer, Jae Jin Jeong, Mauli Maniar, Shahrzad Ghane, Sakshi Deshpande, Claire Ellis, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Protein arginine methyltransferase 5 (PRMT5) mediates arginine methylation of a wide range of proteins and plays context-dependent oncogenic or tumor-suppressive roles. In cancer, PRMT5 represses several tumor suppressor genes, including E-cadherin, TP53BP1, ST7, PTEN, and RB (retinoblastoma). Elevated PRMT5 expression has been reported across multiple cancer types, notably triple-negative breast cancer (TNBC). In TNBC, high PRMT5 levels are associated with enhanced cancer stem cell self-renewal, increased tumor growth and metastasis, and reduced patient survival. Mechanistically, PRMT5 promotes breast cancer stem cell maintenance and proliferation through stabilization of the transcription factors KLF4 and KLF5. Disruption of the PRMT5-KLF4 axis results in …

Impact Of Dolutegravir-Based Regimens On Patient Satisfaction And Quality Of Life Among People Living With Hiv: A Systematic Review And Meta-Analysis, Mustapha Muhammed Abubakar, Christabel Ogechukwu Okoye, Ruth Jeminiwa, Ifeanyi Kanayo Ifeorah, Lotanna Ezeja, Yusuf Dauran, Sahabi Musa, Silas Usen Joel, Abdurrahman Murtala Bello, Amauche Pearl Ngige, Gabriel Ezenri, Abdulmuminu Isah, Ifunanya Ikhile, Blessing Onyinye Ukoha-Kalu

College of Pharmacy Faculty Papers

Background: Despite the global scale up of dolutegravir (DTG)-based regimens as the preferred first-line therapy for persons living with HIV (PLHIV), no comprehensive evidence exists on its effect on patient-reported outcomes such as Quality of Life (QoL) and patient satisfaction (PS). We conducted a systematic review and meta-analysis to provide the first comprehensive quantitative synthesis of the effect of DTG-based regimens on QoL and PS among PLHIV.

Method: We conducted literature search on PubMed, Scopus, Embase and Cochrane Library databases for peer-reviewed, primary studies published from January 2015 to January 2025. Studies using validated tools to evaluate QoL and PS …

Amyloid Β-Cholesterol Interplay: Removal Of Cholesterol From The Membranes To Catalyze Aggregation And Amyloid Pathology, Rishiram Baral, Ruan Van Deventer, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The interplay between the cholesterol metabolism and assembly of Aβ42 (the 42-residue form of the amyloid-β peptide) peptides in pathological aggregates is considered one of the major molecular mechanisms in the development of Alzheimer's disease (AD). Numerous in vitro studies led to the finding that high cholesterol levels in membranes accelerate the production of Aβ aggregates. The molecular mechanisms explaining how cholesterol localized inside the membrane bilayer catalyzes the assembly of Aβ aggregates above the membrane remain unknown. We addressed this problem by combining different AFM modalities, including imaging and force spectroscopy, with fluorescence spectroscopy. Our combined studies revealed that …

Early And Sustained Improvements In Sense Of Smell With Tezepelumab Treatment In Patients With Chronic Rhinosinusitis With Nasal Polyps (Waypoint), Joaquim Mullol, Joseph K. Han, Tanya M. Laidlaw, Claire Hopkins, Anju T. Peters, Oliver Pfaar, Martin Desrosiers, Stella E. Lee, Andrew P. Lane, Claudia Chen, Yun Chon, Sandhia S. Ponnarambil, Andrews Foster, Andrew W. Lindsley, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

Background

Loss of smell is a principal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP), affecting health-related quality of life and posing a safety hazard.

Methods

WAYPOINT (NCT04851964), a phase 3, multicenter trial in adults with uncontrolled CRSwNP, randomized patients 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline in biweekly mean Nasal Polyposis Symptom Diary (NPSD) loss of smell item, University of Pennsylvania Smell Identification Test (UPSIT), and 22-item Sino-Nasal Outcome Test (SNOT-22) loss of smell/taste item scores, as well as anosmia (UPSIT score ≤18) prevalence, were assessed over 52 …

Self-Assembly Of Anti-Inflammatory Peptide Amphiphiles For Mucosal Health, Maria José Gómara, Ignacio Pérez-Pomeda, Ramon Pons, Paul Ziprin, Carolina Herrera, Isabel Haro

CONRAD Publications

Broad spectrum anti-inflammatory peptide amphiphiles (AIF-PAs) have been developed as an innovative strategy for the treatment of chronic mucosal inflammation and the prevention of HIV transmission. Novel lipopeptides based on two linear sequences of anti-inflammatory peptides were obtained by solid-phase peptide chemistry. In a pilot study, ex vivo exposure of colorectal tissue explants from Crohn's disease patients to AIF-PAs induced a downregulation of the proinflammatory profile. Furthermore, the HIV inhibitory potency of AIF-PAs was evaluated ex vivo in colorectal tissue explants, obtaining sub-micromolar IC₅₀ values. Characterization of AIF-PAs self-aggregation in aqueous solution revealed that the net charge distribution within the …

Synergistic Sensitization Of Pancreatic Cancer Cells By Nanosecond Pulsed Electric Fields And Cold Atmospheric Plasma Via Amplifying Ros And Apoptotic Signaling, Zobia Minhas, Edwin A. Oshin, Lifang Yang, Chunqi Jiang, Siqi Guo

Bioelectrics Publications

Pancreatic cancer remains a highly lethal malignancy, with standard therapies offering limited benefits in advanced stages; thus, novel strategies that exploit specific cancer cell vulnerabilities are urgently needed. Building on our previous findings that nanosecond pulsed electric fields (nsPEF) combined with cold atmospheric plasma (CAP) produce enhanced cytotoxicity, this study investigates the molecular mechanisms underlying this synergy. Pan02 pancreatic cancer cells were subjected to nsPEF, CAP, or a combination of both. We assessed cell viability, reactive oxygen species (ROS) production, and mitochondrial integrity using metabolic assays, flow cytometry, and fluorescence microscopy. Apoptotic markers were evaluated via Western blotting and caspase …

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 …

Depemokimab: A Twice Yearly Anti-Il 5 Biologic For Chronic Rhinosinusitis With Nasal Polyps (Crswnp) - A Narrative Review, Marn Joon Park, Joseph K. Han, Kent K. Lam

Department of Otolaryngology (ENT) Faculty Publications

Depemokimab is a monoclonal antibody that targets interleukin-5 with enhanced binding affinity and an extended terminal elimination half‑life of 6-8 weeks. The unique pharmacodynamic features of depemokimab enable sustained suppression of type 2 inflammation with twice‑yearly subcutaneous dosing. This narrative review provides details of depemokimab's molecular profile, pharmacokinetics, and pharmacodynamics and results regarding the clinical efficacy and safety of depemokimab from recently published Phase 3 clinical trials for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP). In 528 severe adult CRSwNP patients (ANCHOR‑1/‑2 trials), depemokimab achieved Δ total endoscopic nasal polyp score by -0.70 (p <  .001) and Δ nasal obstruction verbal response scale by -0.24 (p = .003) at week 52, compared to placebo. Twice‑yearly 100 mg depemokimab provides durable eosinophil suppression and with a safety profile comparable to placebo in Phase 3 trials for CRSwNP. Future work should refine biomarkers and assess comparative cost‑effectiveness and long‑term adherence, safety, and effectiveness.

Formulation Development Of Topical Inserts Containing Doxycycline And Doxycycline Combined With Tenofovir Alafenamide And Elvitegravir For The Prevention Of Sexually Transmitted Infections, Vivek Agrahari, M. Melissa Peet, Jasmin Monpara, Rijo John, Sriramakamal Jonnalagadda, Pardeep K. Gupta, Meredith R. Clark, Gustavo F. Doncel

CONRAD Publications

Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 …

The Concise Guide To Pharmacology 2025/26: Catalytic Receptors, Stephen P. H. Alexander, Doriano Fabbro, Chloe J. Peach, Alasdair J. Gibb, Eamonn Kelly, Alistair A. Mathie, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Christopher Southan, Jamie A. Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C. Burnett, Richard W. Farndale, Andreas Friebe, John Garthwaite, Adrian J. Hobbs, Gavin E. Jarvis, Laura Kilpatrick, Doris Koesling, Michaela Kuhn, Birgit Leitinger, David Macewan, Tom P. Monie, Lincoln R. Potter, Michael Russwurm, Harald H. H. W. Schmidt, Johannes-Peter Stasch, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The Concise Guide to Pharmacology 2025/26 marks the seventh edition in this series of biennial publications in the British Journal of Pharmacology. Presented in landscape format, the guide provides a comparative overview of the pharmacology of drug target families. The concise nature of the Concise Guide refers to the style of presentation, being clear, accessible, and well-structured, rather than the scope of the content, which spans approximately 500 pages. The Concise Guide summarises the key pharmacological properties of around 1900 human drug targets, and nearly 7000 interactions, involving around 4400 ligands. While the content is a substantially condensed version of …

Mechanism Of Anticancer Action Of Bifidobacterium: Insights From Gut Microbiota, Hoang Do, Esther Asiamah, Mayanijesu Olorife, Arathi Pillai, Sakshi Patel, Ponniah Selvakumar, Sidhartha D Ray, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Bifidobacterium has captured major attention recently because of its health benefits and extensive research highlighting its potential in cancer treatment and prevention. Evidence suggests that bifidobacterium can actively fight against various types of cancer, including those of the colon, lungs, breast, and stomach. Research indicates that several species of bifidobacterium can potentiate the action of chemotherapy, immunotherapy and radiation therapy in battling tumors, and reducing their adverse effects. Bifidobacteria shows its multipronged effect by modulating various immunomodulatory and inflammatory signaling pathways, potentially leading to the suppression of tumor growth. Moreover, different species of bifidobacteria are known to regulate signaling molecules …

Validation Of A Risk Score For Cancer-Associated Thrombosis Using Nationwide Ehr Data, Ang Li, Omid Jafari, Barbara D Lam, Jun Y Jiang, Rock Bum Kim, Shengling Ma, Emily Zhou, Joyce W Tiong, Elizabeth C Chiang, Justine Ryu, Christopher I Amos, Jennifer La, Nathanael R Fillmore

Faculty, Staff and Student Publications

Importance: Venous thromboembolism (VTE) is associated with increased mortality and morbidity in patients with cancer. Existing risk prediction models are typically validated within individual sites, a fragmented approach that limits clinical adoption.

Objective: To validate the electronic health record cancer-associated thrombosis (EHR-CAT) score compared with the benchmark Khorana score in a contemporary cohort of patients with cancer across the nation, before and after treatment, excluding those at high risk of bleeding.

Design, setting, and participants: This prognostic study included patients in a nationwide longitudinal EHR database from January 2018 to December 2023 with follow-up continuing to April 2025. Patients with …

Real-World Impact Of Amiodarone On Apixaban Population Pharmacokinetics In Hospitalized Patients, Samantha Kolowrat, Chazmyn Riley, Kevin Lam, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite common coadministration in nonvalvular atrial fibrillation (NVAF), there is minimal evidence regarding the impact of concomitant amiodarone use on apixaban pharmacokinetics (PK). We described the population PK of apixaban (2.5 and 5mg twice daily) in 106 hospitalized patients with and without concomitant amiodarone administration at steady state. Apixaban PK was reasonably described by a one-compartment model with first-order absorption and linear elimination. Aside from the receipt of amiodarone, age was retained as a statistically significant covariate on apparent clearance. Model-based simulations depicted concomitant amiodarone use increasing AUCT for both 2.5mg (1.58, 90% CI [1.28, 1.87]) and 5mg (1.12, 90% …

Exploring Young Adults' Experiences And Beliefs In Asthma Medication Management: Pilot Qualitative Study Comparing Human And Multiple Ai Thematic Analysis, Ruth Ndarake Jeminiwa, Caroline Popielaski, Amber King

College of Pharmacy Faculty Papers

BACKGROUND: Young adults take their asthma maintenance medication 67% of the time or less. Understanding the specific needs and behaviors of young adults with asthma is essential for developing targeted interventions to improve disease self-management. Artificial intelligence (AI) has demonstrated its utility in summarizing and identifying patterns in qualitative research and may support or augment human coding efforts. However, there is pause literature to support this assertion.

OBJECTIVE: The objective of this study is to begin to explore the medication management-related needs of young adults with asthma via a pilot feasibility study. We aim to understand how to best assist …

Impact Of A Multi-Strain L. Crispatus-Based Vaginal Synbiotic On The Vaginal Microbiome: A Randomized Placebo-Controlled Trial, Jacques Ravel, Sheri Simmons, Eleni Greenwood Jaswa, Sara Gottfried, Miriam Greene, Susan Kellogg-Spadt, Dirk Gevers, Diane M. Harper

Institute of Emerging Health Professions Faculty Papers

A clinical trial of a multi-strain vaginal synbiotic (NCT05659745, registered 12/19/2022 at clinicaltrials.gov) led to an optimal vaginal microbiome dominated by L. crispatus (CST I). The synbiotic led to a significant increase in L. crispatus compared to placebo (p <  0.05), and conversion to CST I was significantly higher with the vaginal synbiotic than with placebo (90 vs 11%; p <  0.002). Mechanistically, the synbiotic reduced Gardnerella vaginalis and Candida, clinically important microbes.

Choline-An Essential Nutrient With Health Benefits And A Signaling Molecule, Brianne C. Burns, Jitendra D. Belani, Hailey N. Wittorf, Eugen Brailoiu, G. Cristina Brailoiu

College of Pharmacy Faculty Papers

Choline has been recognized as an essential nutrient involved in various physiological functions critical to human health. Adequate daily intake of choline has been established by the US National Academy of Medicine in 1998, considering choline requirements for different ages, sex differences and physiological states (e.g., pregnancy). By serving as a precursor for acetylcholine and phospholipids, choline is important for cholinergic transmission and the structural integrity of cell membranes. In addition, choline is involved in lipid and cholesterol transport and serves as a methyl donor after oxidation to betaine. Extracellular choline is transported across the cell membrane via various transport …

Therapeutic Hurdles In Acute Myeloid Leukemia: Leukemic Stem Cells, Inflammation And Immune Dysfunction, Bofei Wang, Patrick K Reville, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is an aggressive and highly heterogeneous hematological malignancy characterized by clonal expansion and differentiation arrest in myeloid progenitor cells. Despite advancements in chemotherapy, allogeneic hematopoietic stem cell transplantation, and post-remission maintenance therapies, the long-term survival remains unsatisfactory with high rates of relapse and refractory. These therapeutic challenges are mediated by multiple factors, including the complexity of the cellular hierarchies in AML, the interaction of leukemic stem cells (LSCs) with the bone marrow niche, inflammation, and immune evasion mechanisms. Further, the absence of specific surface markers that distinguish LSCs from normal hematopoietic stem cells, together with LSCs' …

A Review Of Mirvetuximab Soravtansine-Gynx In Folate Receptor Alpha-Expressing Platinum-Resistant Ovarian Cancer, Judith A Smith, Patrick Medina, Mary Miao, Kathleen N Moore

Faculty, Staff and Student Publications

Purpose: To evaluate the pharmacology, efficacy, safety, and dosing and administration considerations (including adjusted ideal body weight [AIBW] dosing) for mirvetuximab soravtansine-gynx, a first-in-class folate receptor alpha (FRα)-directed antibody-drug conjugate for platinum-resistant ovarian cancer (PROC).

Summary: A literature search was conducted in PubMed using the terms "ovarian cancer" and "mirvetuximab soravtansine" of articles published from inception to April 16, 2024. Relevant publications, abstracts, and clinical trials were reviewed. Mirvetuximab soravtansine-gynx is dosed at 6 mg/kg AIBW every 3 weeks and comprises an FRα-binding antibody, a hydrophilic disulfide linker, and a maytansinoid DM4 payload. Mirvetuximab soravtansine-gynx binds to FRα, which induces …

Catalytic Effect Of Amyloid-Β On Native Tau Aggregation At Physiologically Relevant Concentrations, Rakhi Chowdhury, Apu Chandra Das, Ruan Van Deventer, Luda S. Shlyakhtenko, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Alzheimer's disease (AD) is characterized by the accumulation and aggregation of tau and amyloid-β (Aβ). The pathophysiology and progression of AD are facilitated by the neurotoxic effects of these aggregated proteins, resulting in neurodegeneration and memory loss. In this context, the interaction between tau and Aβ42 is considered, but the mechanism underlying their pathogenic interplay remains unclear. Here, we addressed this question by studying the aggregation of full-length, unmodified tau and Aβ42 at physiologically low concentrations using atomic force microscopy (AFM). AFM imaging and data analyses demonstrate an increase in tau aggregation in the presence of Aβ42, characterized by increased …

The Ptp4a3 Inhibitor Kvx-053 Reduces Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Virulence, Inflammation, And Development Of Acute Lung Injury In K18-Hace2 Mice, Ruben M. L. Colunga-Biancatelli, Pavel A. Solopov, Caitlin M. Woodson, Irving Coy Allen, Ivan Akhrymuk, Maryna Akhrymuk, Brittany N. Heath, Hannah M. Ivester, Tierney Day, Dan E. Austin, Kylene Kehn-Hall, John S. Lazo, Elizabeth R. Sharlow, John D. Catravas

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global health crisis, marked by high transmissibility and virulence. Despite widespread vaccination efforts, effective treatments for COVID-19, particularly for severe cases leading to Acute Respiratory Distress Syndrome (ARDS), remain limited. This study investigates the efficacy of KVX-053, a protein tyrosine phosphatase type IVA (PTP4A3) small molecule inhibitor, in modulating SARS-CoV-2-induced inflammation and lung injury using in vitro cell models and in vivo K18-hACE2 transgenic mice. KVX-053 reduced in vitro pro-inflammatory cytokine expression, including TNFα, CXCL10, and CXCL11, without impacting viral replication or cell viability. K18-hACE2 mice treated with KVX-053 demonstrated …

Gramseq-Dta: A Grammar-Based Drug-Target Affinity Prediction Approach Fusing Gene Expression Information, Kasul Debnath, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

Drug–target affinity (DTA) prediction is a critical aspect of drug discovery. The meaningful representation of drugs and targets is crucial for accurate prediction. Using 1D string-based representations for drugs and targets is a common approach that has demonstrated good results in drug–target affinity prediction. However, these approach lacks information on the relative position of the atoms and bonds. To address this limitation, graph-based representations have been used to some extent. However, solely considering the structural aspect of drugs and targets may be insufficient for accurate DTA prediction. Integrating the functional aspect of these drugs at the genetic level can enhance …

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …

Changes In Cardiovascular Risk Factors And Health Care Expenditures Among Patients Prescribed Semaglutide, Yuan Lu, Yuntian Lu, Tedi Totojani, Chungsoo Kim, Rohan Khera, Hua Xu, John E. Brush Jr., Harlan M. Krumholtz, Jason Abaluck

Department of Medicine Faculty Publications

Importance Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored.

Objective To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts.

Design, Setting, and Participants This retrospective cohort study included 23 522 adults (≥18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System.

Exposure The first prescription of …

The Significance Of Aldehyde Dehydrogenase 1 In Cancers, Anh L. Nguyen, Caroline O. B. Facey, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The goal of this paper is to discuss the role of ALDH isozymes in different cancers, review advances in ALDH1-targeting cancer therapies, and explore a mechanism that explains how ALDH expression becomes elevated during cancer development. ALDH is often overexpressed in cancer, and each isoform has a unique expression pattern and a distinct role in different cancers. The abnormal expression of ALDHs in different cancer types (breast, colorectal, lung, gastric, cervical, melanoma, prostate, and renal) is presented and correlated with patient prognosis. ALDH plays a significant role in various cellular functions, such as metabolism, oxidative stress response, detoxification, and cellular …

Intracellular Islatravir-Triphosphate Half-Life Supports Extended Dosing Intervals, Xiaowei Zang, Wendy Ankrom, Walter K. Kraft, Ryan Vargo, S Aubrey Stoch, Marian Iwamoto, Randolph P Matthews

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Antiretroviral therapy has substantially reduced morbidity, mortality, and disease transmission in people living with HIV. Islatravir is a nucleoside reverse transcriptase translocation inhibitor that inhibits HIV-1 replication by multiple mechanisms of action, and it is in development for the treatment of HIV-1 infection. In preclinical and clinical studies, islatravir had a long half-life (t½) of 3.0 and 8.7 days (72 and 209 hours, respectively); therefore, islatravir is being investigated as a long-acting oral antiretroviral agent. A study was conducted to definitively elucidate the terminal t½ of islatravir and its active form islatravir-triphosphate (islatravir-TP). A single-site, open-label, non-randomized, single-dose phase 1 …

Combination Treatment Of Biochanin A And Atorvastatin Alters Mitochondrial Bioenergetics, Modulating Cell Metabolism And Inducing Cell Cycle Arrest In Pancreatic Cancer Cells, Vilas Desai, Satya Murthy Tadinada, Hoora Shaghaghi, Ross Summer, James C.K. Lai, Alok Bhushan

College of Pharmacy Faculty Papers

Background/Aim: Pancreatic cancer is an aggressive type of cancer, with a dismally low survival rate of <5%. FDA-approved drugs like gemcitabine have shown little therapeutic success, prolonging survival by a mere six months. Isoflavones, such as biochanin A and daidzein, are known to exhibit anti-cancer activity, whereas statins reportedly have anti-proliferative effects. This study investigated the effects of combination treatment of biochanin A and atorvastatin on pancreatic cancer cells.

Materials and Methods: Pancreatic cancer cells AsPC-1, PANC-1, and MIA PaCa-2 were procured from ATCC. The cell viability studies were carried out using MTT & cell count assays. Flow cytometry was used to study cell apoptosis whereas cell metabolism studies were carried out using the Seahorse Mito stress test and XF-PMP assay. The effects of treatment on cell signaling pathways & cell cycle associated proteins were investigated using western blot whereas invasiveness of cancer cells was evaluated using gelatin zymography.

Results: The combination treatment …

Ael Transformed From Post-Et Myelofibrosis With A Sinusoidal Pattern, Jak2 Mutation, And Biallelic Tp53 Inactivation, Qing Wei, M James You

Faculty, Staff and Student Publications

No abstract provided.

The Dual-Targeted Fusion Inhibitor Clofazimine Binds To The S2 Segment Of The Sars-Cov-2 Spike Protein, Matthew Freidel, Pratiti Vakhariya, Shalinder Sardarni, Roger Armen

College of Pharmacy Faculty Papers

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs that have been repurposed for the treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule bindings to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 Spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and its derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest-quality SPR data for binding with S2 over the …

Implementing Services For Pediatric Cystic Fibrosis Treatment In A Community Hospital., Paige Grube, Heather Nichols, Sarah Ferrell Pharmd, Denise Gilham Pnp, Allyson Gaylor Pharmd, Bcpps, Karen Dunkelberger Bs Pharm, Mshi, Cpps

Pharmacy Residency

This project aimed to describe how the pharmacy department prepared to care for pediatric patients with cystic fibrosis, a new population being cared for at the institution.

PURPOSE: Our community hospital was recently charged with providing care for pediatric people with cystic fibrosis (PwCF). Pediatric PwCF generally need a higher level of care than is required by other pediatric patients cared for at our institution. This project aimed to prepare the pharmacy department to care for this specialized population safely and efficiently.

SUMMARY: The implementation process was divided into 3 phases to accomplish the larger purpose. These phases were as …