Therapeutics Commons^™

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are currently …

Systemic Blood Pressure Trends And Antihypertensive Utilization Following Continuous-Flow Left Ventricular Assist Device Implantation: An Analysis Of The Interagency Registry For Mechanically Assisted Circulatory Support, Adham Elmously, Andreas R. De Biasi, Donald A. Risucci, Berhane Worku, Evelyn M. Horn, Arash Salemi

NYMC Faculty Publications

Background: Elevated systemic blood pressure (SBP) has been linked to complications in Continuous-flow left ventricular assist devices (CF-LVADs), including stroke and pump thrombosis. We queried Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) to describe the response of SBP to CF-LVAD implantation and to delineate contemporary trends in antihypertensive (AH) utilization for patients with these pumps. Methods: We identified all CF-LVAD implantations in patients older than 18 years from 2006-2014, excluding those whose durations were less than 30 days. Pre-implant patient demographics and characteristics were obtained for each record. SBPs [i.e., mean arterial pressures (MAPs)], AH-use data, and vital status …

Paclitaxel Enhances Oncolytic Potential Of Herpes Simplex Virus Type-1 In Cancer Cells, Misagh Naderi

LSU Master's Theses

Taxanes are spindle poisons that bind to and stabilize microtubules resulting in mitotic arrest. Herpes simplex Typ-1 (HSV-1) virions utilize the microtubular network for intracellular transport during both virus entry and virus egress from infected cells. It has been reported previously that taxanes may synergize with oncolytic herpes simplex viruses in the treatment of experimental prostate and breast tumors in mice. Other reports have indicated that taxanes may inhibit viral replication in infected cells. In this study the previously characterized Oncolytic Herpes Simplex Virus type 1 (OSVP), which was constructed in Kousoulas lab was used in conjugation with paclitaxel (taxol) …

Transitioning To The Role Of A Professional Physical Therapist Through Community Engagement, Brittany L. Wentzel

VA Engage Journal

This article recounts the author's experiences observing and interning with physical therapists in a variety of settings.The hands-on experiences the author describes allowed the author to learn the specific procedures and requirements in a typical day as a Physical Therapist, and to gain knowledge on the protocol for different injuries, the muscles that each exercise strengthens, and how to properly perform exercises to prevent further injuries. The author also explores how these experiences fostered observational and interpersonal skills and solidified the decision to pursue Physical Therapy as a career.

Oncology Section Edge Task Force On Cancer: Measures Of Cancer-Related Fatigue—A Systematic Review, Mary Insana Fisher, Claire Davies, Hannah Lacy, Deborah Doherty

Physical Therapy Faculty Publications

Background: Cancer-related fatigue (CRF) is one of the most common side effects of cancer and cancer treatment. Being able to accurately screen for and assess CRF will improve access to and prescriptions for interventions. Valid and reliable measures to screen for and assess CRF need to be identified.

Purpose: To identify and recommend reliable, valid, and clinically useful tools to screen for and assess CRF among those treated for cancer.

Methods: A systematic review of the literature was conducted to assess the published psychometric properties and clinical feasibility of each method identified. Task force members independently reviewed each measure using …

Genetic Variants In Hsd17b3, Smad3, And Ipo11 Impact Circulating Lipids In Response To Fenofibrate In Individuals With Type 2 Diabetes, Daniel M. Rotroff, Sonja S. Pijut, Skylar W. Marvel, John R. Jack, Tammy M. Havener, Aurora Pujol, Agatha Schluter, Gregory A. Graf, Henry N. Ginsberg, Hetal S. Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C. Mychaleckyi, Howard L. Mcleod, John B. Buse, Michael J. Wagner, Alison A. Motsinger-Reif, Accord/Accordion Investigators

Pharmaceutical Sciences Faculty Publications

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin‐treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed‐up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10^‐6). Rare variant and gene expression changes …

Discovery And Effects Of Pharmacological Inhibition Of The E3 Ligase Skp2 By Small Molecule Protein-Protein Interaction Disruptors, John K. Morrow

Dissertations and Theses (Open Access)

Skp2 (S-phase kinase-associated protein 2), one component of the SCF E3 ubiquitin ligase complex, directly interacts with Skp1 and indirectly associates with Cullin1 and Rbx1 to bridge the E2 conjugating enzyme with its protein substrate to execute its E3 ligase activity. Skp2 is an Fbox protein (due to it containing an Fbox domain) and it is the rate-limiting component of the SCF complex. Skp2 targets several cell-cycle regulatory proteins for ubiquitination and degradation; most notable and significant for cancer are the cyclin-dependent kinase inhibitor, p27. Skp2 is an oncogene and studies have shown that over-expression of Skp2 leads to increased …

Aging Exacerbates Development Of Cerebral Microbleeds In A Mouse Model, Rachita K. Sumbria, Mher Mahoney Grigoryan, Vitaly Vasilevko, Annlia Paganini-Hill, Kelley Kilday, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationships among inflammation, aging, and CMH development are not well-defined. In the current study, we hypothesized that the pathogenesis of inflammation-induced CMH in mice differs by age.

Methods: We studied young (3 months, n = 20) and old (18 months, n = 25) C57BL/6 mice injected with low-dose lipopolysaccharide (LPS; 1 mg/kg, i.p.) or saline at 0, 6, and 24 …

A Delayed Diagnosis Of Tarsometatarsal Ligament (Lisfranc) Sprain In A Female College Soccer Athlete And Foot Rehabilitation, Boyoung Park

UNO Student Research and Creative Activity Fair

A Delayed Diagnosis of Tarsometatarsal Ligament (Lisfranc) Sprain in a Female College Soccer Athlete and Foot Rehabilitation

Park B*, Nicola M*, Wilkins S*: *University of Nebraska at Omaha, Omaha, NE

Objective: To emphasize the importance of the correct treatment protocol and the proper rehabilitation exercises based on the patient’s injury condition and healing process. Background: A 22-year-old female division I soccer athlete underwent tarsometatarsal ligament repair to stabilize midfoot. The patient started feeling pain in the dorsal aspect of her left 1st and 2nd metatarsals at the beginning of the season, however, she reported no specific mechanism of injury …

Inactivation Of Myeloma Cancer Cells By Helium And Argon Plasma Jets: The Effect Comparison And The Key Reactive Species, Zeyu Chen, Qingjie Cui, Chen Chen, Dehui Xu, Dingxin Liu, H. L. Chen, Michael G. Kong

Bioelectrics Publications

In plasma cancer therapy, the inactivation of cancer cells under plasma treatment is closely related to the reactive oxygen and nitrogen species (RONS) induced by plasmas. Quantitative study on the plasma-induced RONS that related to cancer cells apoptosis is critical for advancing the research of plasma cancer therapy. In this paper, the effects of several reactive species on the inactivation of LP-1 myeloma cancer cells are comparatively studied with variable working gas composition, surrounding gas composition, and discharge power. The results show that helium plasma jet has a higher cell inactivation efficiency than argon plasma jet under the same discharge …

Relationships Between Clinical Scales And Binge Eating Days In Adults With Moderate To Severe Binge Eating Disorder In Two Phase Iii Studies, Leslie L. Citrome, Judith C. Kando, Caleb Bliss

NYMC Faculty Publications

OBJECTIVES:

In two Phase III studies, lisdexamfetamine dimesylate (LDX) reduced binge eating (BE) days/week in adults with moderate to severe binge eating disorder (BED) and was associated with improvement based on the Clinical Global Impressions-Improvement (CGI-I) scale. In this study, post hoc analyses examined the relationships between clinical observations and clinical rating scales in individuals with BED.

CLINICAL TRIAL REGISTRATION:

NCT01718483 (ClinicalTrials.gov/ct2/show/NCT01718483); NCT01718509(ClinicalTrials.gov/ct2/show/NCT01718509).

METHODS:

Two 12-week, double-blind, placebo-controlled studies randomized (1:1) adults meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, BED criteria and with protocol-defined moderate to severe BED (study …

Development Of Methods To Modulate Natural Killer Cells, Kari A. Shaver

Honors Undergraduate Theses

Natural Killer (NK) cell based immunotherapies have demonstrated success against malignancies and hematological cancers. However, tumors have developed mechanisms to evade detection by and suppress the immune system, commonly through altering the expression of cell-surface proteins. Overexpression of human leukocyte antigen-E (HLA-E), which binds to the inhibitory NKG2A on NK cells, protects malignant cells from lysis. Downregulating the NKG2A receptor on NK cells should release NK cell inhibition, but proves challenging as NK cells are difficult to transfect and no good methods currently exist. This project is designed to investigate the use of exosomes – small vesicles and natural carriers …

Targeted Delivery Of A Therapeutic Protein For The Treatment Of Alzheimer's Disease, Heather Holman

Honors Undergraduate Theses

Neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease are linked to mitochondrial dysfunction and the underexpression of TOM40, a protein with chaperone-like qualities that is responsible for transporting precursor proteins into the mitochondria. Overexpression of TOM40 is reported to partially restore mitochondrial dysfunction and decrease the accumulation of neurotoxic aggregates of α-synuclein. Our goal is to develop an effective method for delivery of TOM40 protein to the brain.

Previous studies have used lentiviruses to carry TOM40 into the hippocampus of α-synuclein transgenic mice. The disadvantage of lentiviral transfection is the random insertions of the target gene into the host …

Effects Of Energy-Based Therapies On Postoperative Recovery: An Integrative Review Of The Literature, Emily M. Wooten

Honors Undergraduate Theses

Associated with health care reform, there has been a growing interest among healthcare professionals regarding use of energy-based therapies as a complementary therapeutic intervention. The purpose of this integrative literature review was to examine the impact of energy-based therapies (i.e. healing touch, reiki, therapeutic touch) on patients’ postoperative recovery. The methodology included identifying appropriate peer-reviewed, English-language research articles on the topic area that were published between 2006 to 2018. Following a search in select data bases, articles focusing on the topic were critiqued, analyzed and synthesized by the researcher. Consistent and inconsistent findings along with gaps in the literature are …

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 …

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 …

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 …

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 …

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 …