Pharmacy and Pharmaceutical Sciences Commons^™

Local Lung Targeting Of Tumor Associated Macrophages Combined With Cytoreductive Therapy Decrease Tumor Burden In A Secondary Lung Cancer Model, Sulaiman Alhudaithi, Hanming Zhang, Rashed Almuqbil, Wei Du, Fatemah Sunbul, Paula Bos, Sandro Da Rocha

Graduate Research Posters

Backgrounds. The efficacy of a locally administered small molecule colony stimulating factor 1 receptor inhibitor (CSF-1Ri), PLX3397, alone or in combination with cytoreductive therapy (paclitaxel) in reducing the tumor burden of an in vivo model of secondary lung cancer was investigated in this work. Local administration of immunotherapy to the lungs may enhance lung biodistribution of such therapies and reduce potential unwanted off-target toxicity. In addition, combination of such therapy with low dose standard of care chemotherapy may offer improved anti-tumor effects.

Methods. Murine breast cancer cells (4T1, known to be highly metastasized to the lungs) were transduced to …

Dendrimer Conjugation Enhances Tumor Penetration And Cell Kill Of Doxorubicin In 3d Coculture Lung Cancer Models, Rashed Almuqbil, Rodrigo S. Heyder, Elizabeth R. Bielski, Mikhail Durymanov, Joshua J. Reineke, Sandro R. P. Da Rocha

Graduate Research Posters

Background: Doxorubicin (DOX) is a potent chemotherapeutic widely used for solid tumors (1). Despite high efficacy in 2D cell culture, DOX efficacy does not translate to in vivo lung cancer models (2). Major side effects such as cardiotoxicity may be alleviated with nano-based drug delivery systems (nanoDDS). However, tumor penetration of DOX and DOX-nanoDDS is largely unknown and is an additional barrier to effective clinical therapy (3). Here we describe a nanoDDS capable of enhancing the penetration of DOX.

Methods: DOX was conjugated to generation 4 poly(amido-amine) dendrimers through (GFLG) tumor- liable bond. G4SA-GFLG-DOX was synthesized/characterized. spheroids were formed of …

Development Of An R Script For Simple Lipidomic And Metabolomic Data Analysis, Suad Alshammari, Joshua M. Morriss, Daniel Contaifer, Dayanjan S. Wijesinghe, Monther Alsultan

Graduate Research Posters

Background: Metabolomic and lipidomic studies generate vast quantities of data that are often analysed in a closed software environment with little to no access to the underlying algorithms. As a result, data processed via different software pipelines yield different results thus leading to a widespread problem of low reproducibility within these fields. To address this problem, we are developing LipidAnalyst; an R based lipidomics software pipeline. As a part of this project, we are creating a simple statistical analysis and graphing module in R to generate accurate, reproducible, high-resolution figures.

Methods: R scripts were developed under version 3.5.3 with the …

A Pre-Transplant Blood-Based Lipid Signature For Prediction Of Antibody-Mediated Rejection In Kidney Transplant Patients, Monther Al Sultan, Daniel Contaifer Jr., Joshua Morriss, Suad Alshammari, Jeffrey Stern, Sindhura Bobba, Pamela Kimball, Anne King, Dhiren Kumar, Marlon Levy, Gaurav Gupta, Dayanjan Wijesinghe

Graduate Research Posters

Purpose. The aim of this study is to demonstrate the potential of the pre-transplant lipidome to predict post-transplant antibody-mediated rejection (AMR) in kidney transplant patients.

Methods. Patients were selected from a prospective observational cohort of a single-center adult kidney transplant center in the United States. The study included 16 kidney transplant patients who develop AMR within 2 years post-transplant and 29 stable control (SC) kidney transplant patients who did not develop AMR at any time within the post-transplant follow up. Selection of group differences on the day of transplant was determined by t-test analysis. Stepwise forward method was used to …

Molecular Predictors Of Anakinra Treatment Success In Heart Failure Patients With Reduced Ejection Fraction, Joshua Morriss, Daniel Contaifer Jr, Leo F. Buckley, George Wohlford, Monther Alsultan, Suad Alshammari, Asanga D. Ranasinghe, Salvatore Carbone, Justin M. Canada, Cory Trankle, Elvin T. Price, Antonio Abbate, Benjamin W. Van Tassell, Dayanjan S. Wijesinghe

Graduate Research Posters

Background. Kineret (Anakinra) is an interleukin-1 antagonist that is under investigation for its novel clinical application treating patients that have heart failure with reduced (<50%) ejection fraction (HFrEF). A prior study from our group indicated that Anakinra may restore heart function by addressing dysregulations in HFrEF metabolic pathways. Herein, we attempt to elicit Anakinra’s effects on both metabolome and lipidome.

Methods. Lipids and metabolites that had previously been quantified by mass spectrometry (MS) from patients (n=49) who had ≥2 mg/L of high-sensitivity C-reactive protein (hs-CRP) were mTIC normalized and transformed. We conducted a stepwise Linear Discriminant Analysis (r- LDA) to test Anakinra (2 and 12 weeks) vs placebo for separation from combined baseline. Metabolic pathway analysis was performed with Fisher’s exact test algorithm for detection of over-represented and enriched analytes. Univariate analysis (one tailed t-test …

Introducing A Model And A Framework To Unify The Pharmaceutical Quality System Enablers Quality Risk Management & Knowledge Management, Martin J. Lipa, Kevin O'Donnell, Anne Greene

Articles

An organization that effectively manages knowledge should be able to recognize and proactively apply new learnings to better anticipate risks. This is particularly important in the manufacture of medicinal products. Since the publication of ICH Q10 in 2010, Quality Risk Management (QRM) and Knowledge Management (KM) have been positioned as co-enablers to the Pharmaceutical Quality System. The authors of this paper present a Knowledge Management process model to foster greater practical understanding of the practice of knowledge management. This model when joined with the familiar ICH Q9 process model for QRM, should enable a company to better manage their knowledge …

Multicellular Spheroids Of A549 And A549-Irfp As An In Vitro Model Of Lung Cancer, Xinyu Pei

University of the Pacific Theses and Dissertations

Lung cancer is the second most common cancer in both men and women around the world, and 85% of it is non-small cell lung cancer (NSCLC). It is estimated that in 2020, there will be 228,820 cases of lung cancer and 135,720 deaths from lung (American Cancer Society, 2020). The prognosis of lung cancer is poor (

Traditionally, the most commonly used in vitro method for screening therapeutic drugs is monolayer cell cultures, which are reproducible, convenient and of low cost. However, monolayer cell culture models are unable to reproduce many properties of in vivo solid tumors such as the …

Variability In Antibacterial Activity In The Caribbean Sponge Amphimedon Compressa, Mackenzie Reilly

Honors Theses

Coral reefs are essential ecosystems that provide an abundance of natural resources. Sponges, common reef inhabitants, produce a diversity of secondary metabolites that are known to serve as chemical defenses. Secondary metabolites often have ecological functions, such as antipredator and antibacterial activities. I studied the common Caribbean sponge species, Amphimedon compressa, which is known to be chemically defended. Samples were collected from three sites in Belize, two sites in Grand Cayman, and three sites in St. Croix, U.S. Virgin Islands. To determine whether antibacterial activity varied across broad or local geographic scales, sponge extracts were tested against four bacterial strains …

The Interplay Of Progestins, Matrix Metalloproteinases, And The Aging Brain, Keyana Nicole Porter

Graduate Theses, Dissertations, and Problem Reports (ETD)

Progestins are synthetic hormones that are designed to mimic the biological actions of progesterone. They, however, possess other pharmacological actions and properties, in addition to their progestational activities. Medroxyprogesterone Acetate (MPA) is a progestin used globally in the hormonal contraceptive, Depo Provera®, by women in their reproductive prime and is a major compound found in hormone therapy (HT) formulations used by menopausal women. MPA is used by approximately 1 in 5 adolescents and adult women in the United States who are sexually active. Globally, nearly 48 million women utilize injectable contraceptives to prevent pregnancy, with most users utilizing MPA as …

Applications Of Machine Learning Methods In Health Outcomes Research: Heart Failure In Women, Khalid Abdullah Alhussain

Graduate Theses, Dissertations, and Problem Reports (ETD)

There is robust evidence that heart failure (HF) is associated with substantial mortality, morbidity, poor health-related quality of life, healthcare utilization, and economic burden. Previous research has revealed that there are sex differences in the epidemiology, etiology, and disease burden of HF. However, research on HF among women, especially postmenopausal women, is limited. To fill the knowledge gap, the three related aims of this dissertation were to: (1) identify knowledge gaps in HF research among women, especially postmenopausal women, using unsupervised machine learning methods and big data (i.e., articles published in PubMed); (2) identify emerging predictors (i.e., polypharmacy and some …

Asthma-Copd Overlap: Economic Burden And Medication Adherence, Mona Nili

Graduate Theses, Dissertations, and Problem Reports (ETD)

In many older adults, asthma and chronic obstructive pulmonary disease (COPD) coexist as “Asthma-COPD overlap” (ACO). This dissertation pursued three Aims: 1) estimate the economic burden of ACO and its contributory factors; 2) evaluate the association of ACO to “cost-related medication nonadherence” (CRN); and 3) identify adherence trajectory patterns and examine the impact of initial maintenance therapies (IMT) type (inhaled corticosteroids monotherapy (ICS) vs. fixed-dose combination of ICS and long-acting beta agonist (ICS/LABA)) on adherence trajectory patterns among older adults Medicare Beneficiaries. The first and second Aims were cross-sectional studies by using Medicare Current Beneficiary Survey data. For the third …

Multimorbidity, Immune Checkpoint Inhibitor Use, And Healthcare Expenditures Among Older Patients With Late-Stage Melanoma, Pragya Rai

Graduate Theses, Dissertations, and Problem Reports (ETD)

With decades of unchanged cancer care with no added survival benefit, immune checkpoint inhibitors (ICI) changed the treatment landscape of late-stage melanoma in 2011. A key factor in determining the use of ICIs is the presence of pre-existing chronic conditions, which can influence the outcome. However, the prevalence of multimorbidity (defined as presence of two or more chronic conditions) among older patients with late-stage melanoma remains unknown. It also remains unknown if the presence of multimorbidity factors into the use of ICIs. Hospital-related factors associated with ICI use have been studied. Yet, patient-level factors, such as age, sex, marital status, …

Naming Convention, Interchangeability, And Patient Interest In Biosimilars, Mariana P. Socal, Jace B. Garrett, William B. Tayler, Ge Bai, Gerard F. Anderson

Faculty Publications

Although biosimilars may offer cost savings over their comparable biologics, use of biosimilars in the United States remains relatively low. This study investigates two barriers to uptake of biosimilars in the United States. First, the U.S. Food and Drug Administration requires that four-letter suffixes be added to the nonproprietary names of all biosimilars, as well as to the nonproprietary names of all biologics approved after March 2020. Second, biosimilars are not interchangeable with their reference biologic product at the pharmacy counter; a new prescription is needed for the biosimilar to be dispensed in place of the biologic. We conducted two …

Tubular Adenoma Of Breast, Diksha Dadlani

Digital Journal of Clinical Medicine

No abstract provided.

Kikuchi-Fujimoto Disease, Rohan Karkra

Digital Journal of Clinical Medicine

No abstract provided.

Macular And Optic Disc Drusenoid Deposits With Hemifield Defects In A Patient With Iga Nephropathy: New Findings, Dr. Prabhakar S K

Digital Journal of Clinical Medicine

No abstract provided.

A Case Of Megaloblastic Anemia With Suspected Gilbert Syndrome, Nair A, Prasad R, Dr. Ravikumar S, Dr. Prasanna Kumar

Digital Journal of Clinical Medicine

No abstract provided.

A Case Of Recurrent Pregnancy Loss Due To Bicornuate Uterus, Chandran S

Digital Journal of Clinical Medicine

No abstract provided.

A Case Of Right Lower Lobe Lung Abscess With Stage Iii Empyema, Dey Sauparna, Dr. Ravi M D

Digital Journal of Clinical Medicine

No abstract provided.

Uterine Prolapse, Nimisha Sinha, Sakshi Anurika, Dr. Anu Prerana

Digital Journal of Clinical Medicine

No abstract provided.