Pharmacy and Pharmaceutical Sciences Commons^™

Pharmacogenomic Precision Medicine: Best Practice Toolkit For Improving Patient Screening For Adult Metastatic Cancer Patients, Rena L. Stewart

Student Scholarly Projects

Precision medicine utilizes pharmacogenomic testing as a therapeutic approach. Genomic testing can assess the impact of an individual's genome on their reaction to specific medications. The main objective is to find variants that may affect an individual's response to a given medication. The implementation of pharmacogenomics in oncology facilitates informed decision-making by clinicians in drug selection and dosage determination.

Liposome Synthesis And Evaluation In The Hek-293 Cell Line, Christine Skibinski

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Liposomes were synthesized using the thin film method. A lyophilized power of egg-derived phosphatidylcholine, stearylamine, and cholesterol were added to ethanol and dried under argon to form a lipid cake. The lipid cake was rehydrated with dPBS and sonicated at 60°C forming a heterogenous batch of liposomes. Our results revealed the average size of the liposomes, determined by Dynamic Light Scattering, was approximately 223.1nm, while demonstrating a weakly positive zeta-potential of 1.9± 8.07mv. Next, we tested the antitumor action of the liposomes in the HEK-293 cell line via an MTT assay. We observed that the liposomes were able to inhibit …

Improving Pharmacist-Led Pediatric Patient Education On Oral Chemotherapy At Home, Anika Patel, Christopher M. Nguyen, Kristin Willins, Elsabella Y. Wang, Grace Magedman, Sun Yang

Pharmacy Faculty Articles and Research

Oral chemotherapy (OC) has been increasingly used in pediatric patients diagnosed with cancer, which is primarily managed in the outpatient setting. Different from adults, pediatric patients face unique challenges in administering these hazardous medications at home. Because of the complexity of pediatric pharmaceutical care and the hazardous nature of chemotherapy agents, comprehensive patient education is imperative to mitigate the potential safety risks associated with OC administration at home. Pharmacists play a vital role in patient education and medication consultations. However, the lack of practice guidelines and limited resources supporting OC counseling are noted. Additional barriers include insufficient knowledge and training …

Pharmacoeconomics Of Metastatic Colorectal Cancer Treatment With Targeted Therapies Guided By Companion Molecular Diagnostics, Luis E. Fernández-Garza, Hector Sánchez-Ibarra, Daniela Treviño-Sáenz, Hugo A. Barrera-Saldaña

Research Symposium

Background: To guide the treatment with monoclonal antibodies (MAbs) against the epidermal growth factor receptor (EGFR) of metastatic colorectal cancer (mCRC), the FDA recommends prior companion molecular diagnosis (CMDx). It initially recommended screening for mutations in exon 2 of the KRAS gene, and most recently to extend to screening to exons 2, 3, and 4 of KRAS and 2, 3, and 4 of NRAS genes; furthermore, to evaluate the BRAF exon 15 mutation status (including V600E). To date, no studies have been done to compare the cost-benefit of these different CMDXs.

Methods: We have compared the cost of treatment without …

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …

Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC₅₀ values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC₅₀ values of 5a–d …

Application Of Informatics Tools To Facilitate The Practice Of Precision Medicine With Genomic Testing And Clinical Data, Michael Sayer

Pharmaceutical Sciences (PhD) Dissertations

The practice of precision medicine considers a variety of sources of information to optimize patient care. Factors such as patient demographics, clinical history, and lab test values have well understood effects on treatment outcomes and influence decision making. However, effective inclusion of biomolecular data such as protein expression and DNA sequencing data within the practice of precision medicine needs continued study. Informatics tools offer solutions to allow these complex data sources to be effectively embraced. Utilization of informatics tools to visualize data pertaining to the gene selection practices of pharmacogenomic (PGx) tests effectively communicated large amounts of information into concise …

Rapid Hepatomegaly From Ruxolitinib Discontinuation Syndrome, Ryan Jansen Van Rensburg, Shayna Hale, Anna Calara, Kulveer Dabb, Uday Dandamudi, Parth Desai

HCA Healthcare Journal of Medicine

Introduction

Ruxolitinib (RUX) is a Food and Drug Administration-approved Janus Kinase (JAK) inhibitor shown to be effective in improving hypercatabolic symptoms and splenomegaly in patients with myelofibrosis (MF). RUX therapy provides symptomatic benefits for MF patients but is often discontinued for various reasons including worsening cytopenias. Ruxolitinib Discontinuation Syndrome (RDS) involves an acute cytokine-storm rebound phenomenon that can manifest as an acute relapse of symptoms, worsening splenomegaly, respiratory distress, systemic inflammatory response syndrome, or disseminated intravascular coagulopathy.

Case Presentation

We present the case of a patient with JAK2-positive post-polycythemia vera MF, whose RUX therapy was discontinued due to an active …

Predicting Survival Of Nsclc Patients Treated With Immune Checkpoint Inhibitors: Impact And Timing Of Immune-Related Adverse Events And Prior Tyrosine Kinase Inhibitor Therapy, Michael R. Sayer, Isa Mambetsariev, Kun-Han Lu, Chi Wah Wong, Ashley Duche, Richard Beuttler, Jeremy Fricke, Rebecca Pharaon, Leonidas Arvanitis, Zahra Eftekhari, Arya Amini, Marianna Koczywas, Erminia Massarelli, Moom Rahman Roosan, Ravi Salgia

Pharmacy Faculty Articles and Research

Introduction: Immune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.

Objective: To investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.

Methods: A single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI …

Long-Term Prescription Opioid Use, Cancer Stage, And Economic Burden Among Older Cancer Survivors With Non-Cancer Chronic Pain Conditions, Rudi Safarudin

Graduate Theses, Dissertations, and Problem Reports

Opioids are commonly prescribed to treat pain conditions, which are highly prevalent among older adults (≥65 years). Recent evidence shows that opioids may have carcinogenic effects through immunosuppression and free-radical pathways, which could promote cancer growth. Two population-based studies have reported an association of opioid use with incident cancer. Many individuals with non-cancer chronic pain conditions (NCPCs) may use opioids for a long term. However, the association of long-term prescription opioid (LPO) use with cancer stage at diagnosis is still unknown. Furthermore, evidence suggests that individuals with cancer and pre-existing NCPCs may persistently use opioids, even in the absence of …

Testing The Efficacy And Synergistic Components Of Sesamol And Black Rice Extract On Human Colon Cancer Cells, Sera Lim, Philip M. Gerk

Undergraduate Research Posters

Purpose: Systemic treatment of colorectal cancer involves chemotherapeutic agents which elicit serious and negative side effects from the toxicity of the drug. To address this issue, we are testing dietary supplements for their efficacy against human colon cancer cell lines and also their potential synergistic effects when combined with conventional chemotherapy. Dietary supplements (specifically sesamol and black rice extract) exhibit anticancer, anti-inflammatory, and chemo-preventive properties. Meanwhile, one of the cancer resistance mechanisms is the upregulation of drug elimination mechanisms, leading to multi-drug resistance. We hypothesize that dietary compounds will act as chemo-enhancers, thus enhancing potency of the chemotherapy drug(s) on …

Optimization Of Orally Bioavailable Inhibitors Of Defective In Cullin Neddylation 1 (Dcn-1), Leah Kovalic

Theses and Dissertations--Pharmacy

Ubiquitin (UB) and ubiquitin-like protein (UBL) pathways have emerged as important targets for oncology drug discovery based on the success of proteasome inhibitors (bortezomib or carfilzomib), E3 inhibitors, and the NEDD8 E1 inhibitor pevonedistat (MLN42924). Chemical inhibitors have also proven to be useful probes for identifying and dissecting multifactor UB and UBL regulatory networks. Toward this end, we have pursued approaches to target NEDD8 ligation to Cullins, through developing small molecule inhibitors of DCN1 (defective in Cullin Neddylation 1). DCN1 was discovered as a potentiating RBX1-dependent NEDD8-ligation, through recognizing the acetylated N-terminal methionine of the NEDD8 E2s UBE2M and UBE2F. …