Therapeutics Commons^™

Nanomedicine For Immunosuppressive Therapy: Achievements In Pre-Clinical Research, Hanan Al-Lawati, Hamidreza Montazeri Aliabadi, Behzad Sharif Makhmalzadeh, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Introduction: Immunosuppression is the mainstay therapy in organ transplantation and autoimmune diseases. The effective clinical application of immunosuppressive agents has suffered from the emergence of systemic immunosuppression and/or individual drug side effects. Nanotechnology approaches may be used to modify the mentioned shortcomings by enhancing the delivery of immunosuppressants to target cells of the immune system, thus reducing the required dose for function, and/or reducing drug distribution to non-target tissues.

Areas covered: We provide an overview on the development of nanotechnology products for the most commonly used immunosuppressive agents. At first, the rationale for the use of nanoparticles as …

Cancer Survivorship: Promoting A Lifetime Of Health, Janelle Coleman-Smith

Master's Projects and Capstones

Abstract

Introduction Cancer survivors can face post-cancer treatment effects that need addressing throughout their care trajectory. Education provided to stakeholders and patients will be beneficial in preventing fragmented care, increasing patient satisfaction, and expanding ongoing supportive clinical survivorship care. Methods An adapted Dr. Joanne Lester survivorship needs survey was given to n=7 post-cancer treatment patients within a northern California cancer patient advisory committee. The survey results were analyzed to identify common underserved chronic long-term survivorship needs. Based on the data, an evidence-based educational component was included within a booklet to enhance future survivorship care. Additional surveys were sent to stakeholders …

Retrieval Analysis Of Necropsy Total Hip Replacements: Considerations Beyond The Implant, Julie Alyse Lowell

Theses and Dissertations (ETD)

Introduction. Total hip arthroplasty (THA) surgery is one of the most commonly performed and successful orthopedic procedures in the United States. More than 300,000 primary THAs and 40,000 revision THAs performed in the United States every year. While the need for revision surgeries can stem from a variety of causes, there have been, to the author’s knowledge, no studies attempting to correlate the concentrations of certain inflammatory cytokines to metal ion concentrations found in the tissue surrounding the implant, amount of polyethylene wear, or strength of the interface of the modular taper. The purpose of this study was to begin …

Effects Of Lower Extremity Aerobic Exercise And Conditioned Pain Modulation On Evoked Shoulder Pain, Logan Lumpkins, Craig Wassinger

Undergraduate Honors Theses

Background: Emerging evidence suggests that aerobic exercise and conditioned pain modulation may be advocated in treating patients with musculoskeletal pain. The effects of lower extremity aerobic exercise and conditioned pain modulation on evoked shoulder pain are not known.

Purpose: To determine the acute effects of lower extremity aerobic exercise and conditioned pain modulation on outcomes of evoked shoulder pain from pain pressure threshold measurements.

Study Design: Repeated measures.

Methods: Thirty (30) healthy volunteers were tested over the course of two sessions. Session 1 consisted of collecting pain pressure threshold measurements over the infraspinatus before and immediately following a conditioned pain …

The Effects Of Continuous Insulin Pump Therapy On Glycemic Control In Pregnant Type 1 Diabetics, Kimberly Kelsey

Senior Theses

Type 1 Diabetics have various ways of managing their diabetes that have been studied for their effectiveness. Pregnancy in the Type 1 Diabetic has been understudied. It is known that Diabetics in general have poorer pregnancy outcomes because of poor glycemic control. This coupled with the fact that the body needs 3-4 times more insulin as pregnancy comes to an end makes managing blood glucose levels challenging for diabetics (Lowdermilk, 2016, p. 689). For the Type 1 Diabetic, there are two main ways to control diabetes: multiple daily injections using at least two type of insulin and continuous subcutaneous insulin …

Evaluating The Therapeutic Efficacy Of Restoring Wild-Type P53 Activity In P53-Mutant Tumors, Connie A. Larsson

Dissertations and Theses (Open Access)

The p53 transcription factor is the most frequently altered in human cancers usually via missense mutations that undermine its transcriptional activity. Clinically, TP53 mutations have been shown to be remarkably predictive of refractoriness to treatment, resulting in poor outcome. Consequently, the development of p53 pathway activating agents is rapidly evolving and gaining more attention in cancer therapeutics research, with several small molecule compounds currently in preclinical and clinical trials. However, it remains largely unknown what types or proportions of p53-mutant tumors will respond to p53 restoration-based therapies.

Using a mouse model of Li Fraumeni syndrome, we genetically restored wild-type …

Sustained Sensitizing Effects Of Tumor Necrosis Factor Alpha On Sensory Nerves In Lung And Airways, Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 hours later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and …

Memory Potential, Molecular Characterization, And Translational Applications Of The Novel Theo/Tceo T Cell Phenotype, Todd Bartkowiak, Todd Bartkowiak

Dissertations and Theses (Open Access)

T cells comprise a substantial arm of the immune system and are exquisitely adapted to combat pathogens and tumors. The inflammatory environment largely dictates the nature of T cell response. A hallmark of T cell-mediated immunity is formation of immunological memory; the ability to respond more potently to re-encounter with pathogens. The immune system is also capable of recognizing tumors as foreign, much like viral or bacterial pathogens. Tumors have evolved, though, to generate an immunosuppressive environment to avoid destruction. The field of immunotherapy seeks to overcome immune suppression, in part by targeting T cell co-receptors on the cell surface …

Size, Shape, And Sequence-Dependent Immunogenicity Of Rna Nanoparticles, Sijin Guo, Hui Li, Mengshi Ma, Jian Fu, Yizhou Dong, Peixuan Guo

Center for Research on Environmental Disease Faculty Publications

RNA molecules have emerged as promising therapeutics. Like all other drugs, the safety profile and immune response are important criteria for drug evaluation. However, the literature on RNA immunogenicity has been controversial. Here, we used the approach of RNA nanotechnology to demonstrate that the immune response of RNA nanoparticles is size, shape, and sequence dependent. RNA triangle, square, pentagon, and tetrahedron with same shape but different sizes, or same size but different shapes were used as models to investigate the immune response. The levels of pro-inflammatory cytokines induced by these RNA nanoarchitectures were assessed in macrophage-like cells and animals. It …

Decreasing Time To Broad Spectrum Antibiotics For Septic Patients In The Emergency Department, Joseph J. Zieminski, Emily E. Bryant

Journal of Patient-Centered Research and Reviews

Background: Timely administration of broad spectrum antibiotics has been shown to be directly correlated with decreased mortality for patients with severe sepsis and septic shock. As such, both the Surviving Sepsis Campaign and the SEP-1 CMS measure recognize timely antibiotic administration as a cornerstone of therapy for patients with severe sepsis or septic shock.

Purpose: Decrease time to broad spectrum antibiotic administration for septic patients in the emergency department (ED) of Aurora St. Luke’s Medical Center.

Methods: An alert within the electronic medical record was created to more rapidly identify potentially septic patients in the ED. After receiving the alert, …

Mtor Kinase Inhibition Effectively Decreases Progression Of A Subset Of Neuroendocrine Tumors That Progress On Rapalog Therapy And Delays Cardiac Impairment, Melissa A. Orr-Asman, Zhengtao Chu, Min Jiang, Mariah Worley, Kathleen Lesance, Sheryl E. Koch, Vinicius S. Carreira, Hanan M. Dahche, David R. Plas, Kakajan Komurov, Xiaoyang Qi, Carol A. Mercer, Lowell B. Anthony, Jack Rubinstein, Hala E. Thomas

Internal Medicine Faculty Publications

Inhibition of mTOR signaling using the rapalog everolimus is an FDA-approved targeted therapy for patients with lung and gastroenteropancreatic neuroendocrine tumors (NET). However, patients eventually progress on treatment, highlighting the need for additional therapies. We focused on pancreatic NETs (pNET) and reasoned that treatment of these tumors upon progression on rapalog therapy, with an mTOR kinase inhibitor (mTORKi), such as CC-223, could overcome a number of resistance mechanisms in tumors and delay cardiac carcinoid disease. We performed preclinical studies using human pNET cells in vitro and injected them subcutaneously or orthotopically to determine tumor progression and cardiac function in mice …

Understanding The Patient Experience With Carcinoid Syndrome: Exit Interviews From A Randomized, Placebo-Controlled Study Of Telotristat Ethyl, Lowell B. Anthony, Claire Ervin, Pablo Lapuerta, Matthew H. Kulke, Pamela Kunz, Emily Bergsland, Dieter Hörsch, David C. Metz, Janice Pasieka, Nick Pavlakis, Marianne Pavel, Martyn Caplin, Kjell Öberg, John Ramage, Emily Evans, Qi Melissa Yang, Shanna Jackson, Karie Arnold, Linda Law, Dana B. Dibenedetti

Markey Cancer Center Faculty Publications

Purpose: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in TELESTAR, a Phase III study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview substudy was conducted to provide insight into the patient experience in TELESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful.

Methods: Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at …

Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie

Molecular and Cellular Biochemistry Faculty Publications

Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were performed in multiple breast cell lines. The mentioned nanoparticles were constructed following the standard molecular cloning …

Perceived Stress Levels May Impact Upper Extremity Function Among Women Treated For Breast Cancer, Mary Insana Fisher, Anne Fleischer, Lynn Hendricks, Megan Mcclure, Kim Parent, Renee Roberts

Physical Therapy Faculty Publications

Purpose/Hypothesis: Women treated for breast cancer report ongoing upper extremity disability with functional limitations; however, objective measures do not appear to explain the extent of perceived dysfunction. The purpose of this study was to investigate the relationship between perceived stress level, fear of physical activity, self-reported upper extremity function, and objective measures of upper extremity function including range of motion (ROM), strength, and muscular endurance, among women treated for breast cancer.

Number of Subjects: 25

Materials/Methods: Women diagnosed with stage I-III breast cancer in the past 12-60 months were evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH), …

Influence Of Β-Lactam Infusion Strategy On Acute Kidney Injury, Sarah E. Cotner, Wilbur Cliff Rutter, Donna R. Burgess, Katie L. Wallace, Craig A. Martin, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Limited literature is available assessing nephrotoxicity with prolonged β-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged β-lactam infusion or an intermittent infusion. This was a retrospective, matched-cohort study at an academic medical center from July 2006 to September 2015. Adult patients who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated. Patients were excluded for preexisting renal dysfunction or pregnancy. The primary outcome was difference in incidence of AKI evaluated using the RIFLE (risk, injury, failure, loss, and end-stage) criteria. Patients in the intermittent group …

Rehabilitation Of An Injured Golden Eagle (Aquila Chrysaetos): A Case Study, Fida Muhammad Khan, Fakhar-I- Abbas, Abu Ul Hassan Faiz

Journal of Bioresource Management

Habitat destruction and anthropogenic activities cause wild birds to migrate towards urban areas in search of food and sometimes nesting in high-roof buildings, where they are caught by local people using different techniques and are further used for hunting or recreational purposes. An injured Golden Eagle (Aquila chrysaetos) was found entangled in bushes near the vicinity of Balkasar Research Complex, Chakwal, Pakistan. After complete physical examination, a wound on the right wing and closed leg fracture was diagnosed. The successful treatment was done by anti-parasitic and anti-bacterial drugs with careful monitoring. Splint was adjusted after aligning the fractured …

Reframing Outcome Measures For Thrombolytics In Acute Ischemic Stroke, Brandon Baker, Charles W. Kropf, Nicholus Yee, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent conversation examining relevant research and discussing the potential benefits and harms of thrombolytic therapy in acute stroke.

Anticoagulation Increases Survival In Patients With Idiopathic Pulmonary Arterial Hypertension, Marvin L. Kajy

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Olsson KM, Delcroix M, Ghofrani HA, et al. Anticoagulation and survival in pulmonary arterial hypertension: Results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA). Circulation, 2014;129(1):57-65. doi: 10.1161/CIRCULATIONAHA.113.004526

Investigation Of The Safety Of Focused Ultrasound-Induced Blood-Brain Barrier Opening In A Natural Canine Model Of Aging, Meaghan Anne O'Reilly, Ryan Matthew Jones, Edward Barrett, Anthony P. Schwab, Elizabeth Head, Kullervo Hynynen

Sanders-Brown Center on Aging Faculty Publications

Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits.

Methods: Aged dogs naturally accumulate plaques and show …

Biomechanical Testing Of An Exercise For Strengthening The Proximal Femur., Alyssa Osbourne

Electronic Theses and Dissertations

Based on the principles of cutting edge bone remodeling research, a unique therapeutic exercise device was designed specifically to improve bone quality at the most critical location of the proximal femur prone to fracture: the superior-lateral femoral neck where the fracture first initiates during a fall. The exercise/device is intended to work by inducing enough strain in the bone to stimulate the body’s natural bone remodeling mechanisms to increase bone density in the proximal femur and consequently prevent a fracture from arising if a fall to the side does occur.

In order to test the proposed exercise, experiments simulating the …