Therapeutics Commons^™

Investigation Of The Effects Of Cobimetinib On Neurofibromatosis Type 2 Model Schwannoma Cells, Konstantin Brnjos

Honors Undergraduate Theses

Neurofibromatosis type two (NF2) is a genetic disorder predisposing those affected to the development of multiple benign tumors in their central and peripheral nervous systems. This is due to the absence of the tumor suppressor protein merlin, which is encoded by the NF2 gene. In nearly all NF2 cases, patients present with bilateral schwannomas of the vestibulocochlear nerve, in addition to other schwannomas throughout the central and peripheral nervous systems, as well as meningiomas and ependymomas. Currently, no therapeutic alternatives to surgical removal and radiation therapy are available for NF2 patients. This study investigated cobimetinib, an inhibitor of the often-deregulated …

Inactivation Of Endoplasmic Reticulum Stress And The Prevention Of Neurodegenerative Diseases, Ian James Martins

Research outputs 2014 to 2021

Biotherapeutics and nutritional therapy are essential for the treatment of endoplasmic reticulum (ER) stress in diabetes and neurodegenerative diseases. Oxidative stress and nutrient excess may induce ER stress associated with activation of the unfolded protein response and connected to cell death. The heat shock gene Sirtuin 1 (Sirt 1) is important to the heat shock response with amyloid beta aggregation associated with the induction of mitophagy and ER stress in neuron cells. Genomic medicine that activates nuclear Sirt 1 is essential for the prevention of mitochondrial apoptosis and ER stress. Inhibitors such as drugs, alcohol, excess caffeine and palmitic acid …

A Comparison Of Hamstring Injury Recovery Rates In Male And Female Athletes, Amanda Hall

Undergraduate Honors Theses

Excerpt from Introduction

Hamstring injuries are among the most common muscular injuries sustained by athletes across multiple levels of various sports (Askling et al). Most hamstring injuries occur during similar movements and under similar conditions, where the muscle is required to be explosive. Thus, athletes that participate in sports where “sprinting, kicking, or high-speed skilled movements” are required, experience an increased likelihood of suffering a hamstring injury (Erickson and Sherry). After injury, athletes are then subjected to different methods of rehabilitation to heal and strengthen the afflicted area. However, some athletes take longer than others to return and impatience may …

Drug Delivery With Light, Patrick S. Dupart

Theses and Dissertations

Cancer is responsible for about 25% of deaths in developed countries and for 15% of all deaths worldwide. Cancer is a devastating disease and while there have been great advances in the development of anticancer drugs, off-target toxicity is a major limitation with conventional cancer chemotherapy. The consequence of this form of treatment results in the killing of healthy and rapidly-growing non-cancerous cells including cells in the bone marrow; hair follicles; and cells in the mouth, digestive tract, and reproductive system. In addition to these general effects, certain anticancer drugs can have other associated toxicities. For instance, the anticancer drug …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …

The Unspoken Psychological Issues With Lesson Horses And How We Need To Address Them, Casey Clark

Murray State Theses and Dissertations

Every day all over the world horses provide much needed therapy and treatment to people in need. They provide physical, emotional, and mental training and healing. Humans depend on them for so much and we have a moral and ethical obligation to be good stewards of our equine companions. This close proximity can take a toll on horses physically and psychologically even in the realm of experienced equine professionals. So many times though it is the small lesson facility that sees hundreds of people each year and makes a profound difference in people’s lives. This can be at a 4-H …

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 …

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 …

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 …

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 …

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 …

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), …