Medicine and Health Sciences Commons^™

Car T Cells As A Patentable Therapeutic, Mckenzie List

Honors Program Theses

The development of a therapeutic to treat a particular disease is a complicated process that incorporates numerous components such as drug discovery, clinical trials, FDA approval and patentability. In the last two decades, cancer research and development has shifted from identifying small molecule therapeutic agents to focusing research on a novel approach designated as immunotherapy. Today, immunotherapy has progressed from a twentieth century scientific theory into an innovative treatment to cancer. In particular, CAR T cells have demonstrated therapeutic properties for certain types of cancers, but these living cells are not compatible with the traditional therapeutic model. First, the drug …

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

A 3d Bioprinter Platform For Mechanistic Analysis Of Tumoroids And Chimeric Mammary Organoids, John A. Reid, Xavier-Lewis Palmer, Peter A. Mollica, Nicole Northam, Patrick C. Sachs, Robert D. Bruno

School of Medical Diagnostics & Translational Sciences Publications

The normal mammary microenvironment can suppress tumorigenesis and redirect cancer cells to adopt a normal mammary epithelial cell fate in vivo. Understanding of this phenomenon offers great promise for novel treatment and detection strategies in cancer, but current model systems make mechanistic insights into the process difficult. We have recently described a low-cost bioprinting platform designed to be accessible for basic cell biology laboratories. Here we report the use of this system for the study of tumorigenesis and microenvironmental redirection of breast cancer cells. We show our bioprinter significantly increases tumoroid formation in 3D collagen gels and allows for precise …

The Cost Of Treating Human Papillomavirus-Related Oropharyngeal Cancer, Karla Smalley Houston

Walden Dissertations and Doctoral Studies

Human papillomavirus (HPV) is a sexually transmitted infection contributing to 70% of oropharyngeal cancers in the United States. The incidence of HPV-related oropharyngeal cancers is greater in Kentucky's population than in any other state. Research has demonstrated the cost of treating oropharyngeal cancer on a national level, but little information exists as to state-specific costs. The purpose of this quantitative study was to examine radiation therapy costs for treating HPV-related oropharyngeal cancer in Kentucky in relation to age, gender, race, and insurance. A theory by Aday and Andersen was applied to explain the relationship between the independent and dependent variables. …

Benefits Of Hpv Vaccination In Adolescent Males, Budd Theriot

Physician Assistant Scholarly Project Posters

HPV is the most common sexually transmitted infection in the United States, affecting approximately 75-80% of young adults at some point in their lives, and it is also known to be directly related to several forms of cancer including cervical, vaginal, penile, anal, oral, and oropharyngeal cancer. Vaccination against several high-risk strains of HPV first became available in the U.S. in June of 2006 and has been proven to be effective in creating antibodies against several strains of high-risk HPV, potentially decreasing and preventing more than 30,000 new cases of HPV related cancers each year. Despite this fact, HPV vaccination …

Association Of Adaptive Early Phase Study Design And Late Phase Study Results In Oncology, Donna Elise Levy

Walden Dissertations and Doctoral Studies

This quantitative study assessed the association of the design methods used for early phase oncology studies (adaptive versus traditional) and the outcome of late stage clinical trials. Differences by cancer type and by drug classification were also assessed. The theoretical and conceptual frameworks used were the general systems theory and the design and evaluation of complex interventions, respectively. Units of analysis were individual oncology studies in the ClinicalTrials.gov database and Bayesian logistic modeling was applied on a random sample of 381 studies initiated after November 1999 to December 2016. When assessing study design and outcome, there were lower odds of …

The Stimulation Of Dendritic Cells By Cationic Lipids, John Peyton Bush

Theses and Dissertations--Medical Sciences

The discovery that cationic lipids can independently stimulate the immune system has generated interest in their potential as vaccine adjuvants. Here, we show that the cationic lipid R-DOTAP can independently stimulate type 1 interferon production in dendritic cells in both primary culture and immortalized cell culture. Levels of type 1 interferon production are cell line-dependent and limited in vitro by lipid-induced cell death. We show that cationic lipids can independently activate TLR-7 and TLR-9, suggesting a mechanism for type 1 interferon induction. This TLR-stimulatory activity is not restricted to R-DOTAP and can be extended to other similar cationic lipids in …

The Development Of Novel Proteasome Inhibitors For The Treatment Of Multiple Myeloma And Alzheimer’S Disease, Min Jae Lee

Theses and Dissertations--Pharmacy

Over a decade, proteasome inhibitors (PIs), bortezomib, carfilzomib (Cfz) and ixazomib, have contributed to a significant improvement in the overall survival for multiple myeloma (MM) patients. However, the response rate of PI was fairly low, leaving a huge gap in MM patient care. Given this, mechanistic understanding of PI resistance is crucial towards developing new therapeutic strategies for refractory/relapsed MM patients.

In this dissertation work, we found H727 human bronchial carcinoid cells are inherently resistant to Cfz, yet susceptible to other PIs and inhibitors targeting upstream components of the ubiquitin-proteasome system (UPS). It indicated H727 cells may serve as a …

The Current Burden Of Cancer Attributable To Occupational Exposures In Canada, France Labrèche, Joanne Kim, Chaojie Song, Manisha Pahwa, Calvin B. Ge, Victoria H. Arrandale, Christopher B. Mcleod, Cheryl E. Peters, Jérôme Lavoué, Hugh W. Davies, Anne-Marie Nicol, Paul A. Demers

Études primaires

Exposure to occupational carcinogens is often overlooked as a contributor to the burden of cancer. To estimate the proportion of cancer cases attributable to occupational exposure in Canada in 2011, exposure prevalence and levels of 44 carcinogens were informed by data from the Canadian carcinogen exposure surveillance project (CAREX Canada). These were used with Canadian Census (between 1961 and 2011) and Labour Force Survey (annual surveys between 1976 and 2013) data to estimate the number of workers ever exposed to occupational carcinogens. Risk estimates of the association between each carcinogen and cancer site were selected mainly from published literature reviews. …

The Association Between Hysterectomy And Ovarian Cancer Risk: A Population-Based Record-Linkage Study, Suzanne C. Dixon-Suen, Penelope M. Webb, Louise F. Wilson, Karen Tuesley, Louise M. Stewart, Susan J. Jordan

Health Sciences Papers and Journal Articles

Background: Recent studies have called into question the long-held belief that hysterectomy without oophorectomy protects against ovarian cancer. This population-based longitudinal record-linkage study aimed to explore this relationship, overall and by age at hysterectomy, time period, surgery type, and indication for hysterectomy.

Methods: We followed the female adult Western Australian population (837 942 women) across a 27-year period using linked electoral, hospital, births, deaths, and cancer records. Surgery dates were determined from hospital records, and ovarian cancer diagnoses (n¼1640) were ascertained from cancer registry records.We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the …

Advances In Chimeric Antigen Receptor T-Cell Therapies For Solid Tumors., Trevor R. Baybutt, John C. Flickinger, Ellen M. Caparosa, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

In 2017, the US Food and Drug Administration approved the first two novel cellular immunotherapies using synthetic, engineered receptors known as chimeric antigen receptors (CARs), tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), expressed by patient-derived T cells for the treatment of hematological malignancies expressing the B-cell surface antigen CD19 in both pediatric and adult patients. This approval marked a major milestone in the use of antigen-directed "living drugs" for the treatment of relapsed or refractory blood cancers, and with these two approvals, there is increased impetus to expand not only the target antigens but also the tumor types that can be …

Most Cancers Are Caused By Bad Luck Mutations: Scientific Explanation?, Shahid Pervez

Department of Pathology and Laboratory Medicine

No abstract provided.

Wireless Technologies (4g, 5g) Are Very Harmful To Human Health And Environment: A Preliminary Review, Victor Christianto, Robert N. Boyd, Florentin Smarandache

Branch Mathematics and Statistics Faculty and Staff Publications

The intent of this article is to show that wireless technology is, without remedy other than termination, one of the most devastating environmental and health threats and threats to personal liberty ever created. It is becoming widely known that 4G and 5G technologies cause many harms to human health. Cancer is only one problem, and one that is easily solved. 4G and 5G cause 720! (factorial) different maladies in human beings, and can kill everything that lives but some forms of micro organisms. Some pathogens and certain parasites are made more virulent by selected frequencies of RF. Insects and birds …

Generation, Identification And Characterization Of Novel Monoclonal Antibodies Against Ctla-4, Pd-1 And Btla For The Treatment Of Cancer, Rosabril Acuna

Open Access Theses & Dissertations

Members of the CD28 co-inhibitory receptor family, Cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4), Program death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) are type I transmembrane proteins expressed on a variety of immune cells. Co- inhibitory receptors deliver "off" signals that play an important role in down regulating immune cell activation. Manipulation of inhibitory signals have shown to be a powerful strategy in the treatment of autoimmune diseases, infectious diseases and various forms of cancer. In fact, the FDA (Food and Drug Administration) has approved the use of monoclonal antibodies against CTLA-4 (Ipilimumab) for the treatment of metastatic melanoma, against …

Semisynthetic Aurones: A Family Of Newly Discovered Tubulin Inhibitors As Antineoplastic Agents, Yanqi Xie

Theses and Dissertations--Molecular and Cellular Biochemistry

Aurones belong to an uncommon class of plant flavonoids that provide the bright yellow coloration of some ornamental flowers and that possess a range of biological activities. Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the biologically active analogs developed in the course of this dissertation work were (Z …

Nut And Peanut Butter Consumption And Risk Of Prostate Cancer In The Nih-Aarp Diet And Health Study, Mimi (Trucmai) Nu Ton

Public Health Theses

Background: While nuts and their related nutrients have been inversely associated with some cancers, the association between nut consumption and prostate cancer has been inconsistent.

Methods: We conducted an analysis of the association between nut and peanut butter consumption and risk of incident prostate cancer among 173,243 men in the prospective NIH-AARP Diet and Health Study. There was a total of 18,619 incident prostate cancer cases during the 16 years of follow-up. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression for intake of nuts, peanut butter, and total nuts (nuts plus peanut butter), …

Using Fundamental Properties Of Light To Investigate Photonic Effects In Condensed Matter And Biological Tissues, Laura A. Sordillo

Dissertations and Theses

Light possesses characteristics such as polarization, wavelength and coherence. The interaction of light and matter, whether in a semiconductor or in a biological sample, can reveal important information about the internal properties of a system. My thesis focuses on two areas: photocarriers in gallium arsenide and biomedical optics. Varying the excitation wavelength can be used to study both biological tissue and condensed matter. I altered the excitation wavelengths to be in the longer near-infrared (NIR) optical windows, in the shortwave infrared (SWIR) range, a wavelength region previously thought to be unusable for medical imaging. With this method, I acquired high …

Leptin Level Variance In Adults With And Without Cancer, Vilisa Chatman-Terry

Walden Dissertations and Doctoral Studies

Abstract

In 2018, health statistics revealed that, despite the many preventive measures established,

cancer was the second leading cause of death in the United States and the leading cause

of death in 22 states, exceeded only by heart disease. With obesity/leptin levels reaching

pandemic levels worldwide, and cancer having a well-known association with obesity,

both chronic diseases represent a large proportion of public health challenges. Guided by

the social ecological model, the purpose of this cross-sectional, quantitative study was to

examine if a significant difference exists in leptin levels among adults with different

types of obesity-associated and common cancers and …

Hpv And Hsv Associated Clinical Conditions Among People Living With Hiv-1 Infection, Yuanfan Ye

All ETDs from UAB

This dissertation research focuses on investigating health burdens of HPV- and HSV- associated clinical conditions (CC) in people living with HIV-1 infection (PLWH) in the Southeastern United States. I designed a retrospective study using the UAB 1917 HIV Clinic Cohort. Electronic health records of PLWH attending the clinic for HIV-care between January 2006 and March 2019 were obtained and reviewed. I first examined incidence rates and trends of anogenital HPV- and HSV-associated CC. Then I adopted a new algorithm to group longitudinal CD4 cell counts based on their trajectories. I compared it with nadir and median CD4 cell counts in …

Non-Contact Trapping And Stretching Of Biological Cells Using Dual-Beam Optical Stretcher On Microfluidic Platform, Aotuo Dong, Balaadithya Uppalapati, Shariful Islam, Brandon Gibbs, Ganesan Kamatchi, Sacharia Albin, Makarand Deo

Electrical & Computer Engineering Faculty Publications

Optical stretcher is a tool in which two counter-propagating, slightly diverging, and identical laser beams are used to trap and axially stretch microparticles in the path of light. In this work, we utilized the dual-beam optical stretcher setup to trap and stretch human embryonic kidney (HEK) cells and mammalian breast cancer (MBC) cells. Experiments were performed by exposing the HEK cells to counter-propagating laser beams for 30 seconds at powers ranging from 100 mW to 561 mW. It was observed that the percentage of cell deformation increased from 16.7% at 100 mW to 40.5% at 561 mW optical power. The …

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …

Subjective And Objective Assessment Of Taste And Smell Sensation In Advanced Cancer, Niamh Mcgettigan, Pauline Uí Dhuibhir, Michelle Barrett, Jessica Sui, Lucy Balding, Stephen Higgins, Norma O'Leary, Aileen Kennedy, Declan Walsh

Articles

Context: Taste and smell abnormalities (TSA) occur throughout the cancer trajectory regardless of cancer primary site and contribute to cancer-associated malnutrition. TSA etiology is poorly understood. Tumor-related inflammation is a possible cause. Objective: This study examined the prevalence, characteristics, and severity of TSA in advanced cancer and explored the relationship between TSA and nutritional status. No previous study combined subjective and objective measures for both taste and smell assessment in this population. Method: Consecutive advanced cancer hospice patients were recruited. A modified version of the “Taste and Smell Survey” assessed subjective TSA. Validated taste strips and “Sniffin’ …

Exercise And Patient Populations: A Community-Based Exercise Intervention On Cancer And Type 2 Diabetes, Cynthia Villalobos

University of the Pacific Theses and Dissertations

Cancer and diabetes are the second and seventh leading causes of death in the United States, respectively (Kochanek et al., 2017). When including prediabetes and the entire cancer continuum, both diseases affect over 150 million individuals in the United States each year (Bullard et al., 2018; Siegel et al., 2019). Furthermore, there exists an alarming rise in patients presenting with both type 2 diabetes and obesity-related cancers concurrently, as both diseases share similar risk factors (Vigneri et al., 2009). An aging adult population, physical inactivity and unhealthy eating habits are continuing to rise, and the prevalence of individuals with obesity-related …

Evaluation Of The Attitudes Of Veterinary Students Towards Cancer In Animals Using A Cancer Attitude Scale For Animals, İbrahi̇m Kiliç, İbrahi̇m Demi̇rkan, Aysun Çevi̇k Demi̇rkan, Si̇nan Saraçli

Turkish Journal of Veterinary & Animal Sciences

The aim of this descriptive study was to examine the attitudes of veterinary undergraduate students towards cancer in animals with cognitive, affective, and behavioral dimensions by a new cancer attitude scale for animals approach. Questionnaires, as data collection tools, were applied to 205 students training to be veterinary surgeons at Afyon Kocatepe University, Faculty of Veterinary Medicine, who were selected by systematic random sampling method. Validity-reliability analysis and t-test as well as ANOVA were used in addition to descriptive statistics for the data analysis. The students? general attitudes to cancer were (X = 3.65) greater than the midscore, 3, according …

Systematic Review And Meta-Analysis Of Patient Reported Outcomes For Nurse-Led Models Of Survivorship Care For Adult Cancer Patients, Leanne Monterosso, Violet Platt, Max Bulsara, Melissa Berg

Nursing Papers and Journal Articles

Purpose: This systematic review aimed to determine the effectiveness of nurse-led cancer survivorship care, compared with existing models of care, on patient reported outcomes for cancer survivors.

Methods: Randomised and non-randomised controlled trials and controlled before-after studies published in English between 1 January 2007 and 28 July 2017 were identified in bibliographic databases including Medline, Pubmed and PsychINFO. Included studies described nurse-led cancer care after treatment to adults (age ≥18 years) <2 years post treatment completion. Risk of bias was assessed using Joanna Briggs Institute’s tools and meta-analysis was undertaken.

Results: Twenty one publications were included describing 15 tumour-specific trials involving 3278 survivors of breast (n = 5), gynecological (n = 3), head and neck (n = 2), colorectal …

Modulation Of Autophagy And Senescence To Enhance The Response To Therapy In Triple Negative Breast Cancer, Liliya Tyutyunyk-Massey

Theses and Dissertations

Abstract

Although great strides have been made over the decades in development and optimization of anti-cancer therapies, even highly effective drugs often fail to completely eliminate tumors. Residual tumor cells can enter into a state of dormancy for prolonged periods of time but eventually are able to regain proliferative capacity and reemerge as chemotherapy-resistant disease. Because recurrent disease is a leading contributor to patient’s mortality, it is paramount to identify strategies for effectively destroying residual tumor cells.

Cytotoxic drugs and ionizing radiation are used as standard therapies in a variety of cancers. These modalities induce apoptosis, autophagy and senescence. Senescence …

Examining Sleep And Family Functioning In Pediatric Craniopharyngioma Using Ecological Momentary Assessment, Nour Al Ghriwati

Theses and Dissertations

Craniopharyngiomas are among the most common brain tumors in children and are associated with greater rates of sleep problems compared to other pediatric cancers. However, research examining sleep among youth with craniopharyngioma has been limited by a reliance on retrospective reports or sleep studies. Families also play a crucial role in children’s adjustment following a pediatric cancer diagnosis, yet remarkably little is known about transactional associations between family functioning and sleep in pediatric cancer. This study examined cross-sectional and daily associations among family functioning, affect, and sleep difficulties for youth with pediatric craniopharyngioma using retrospective reports and ecological momentary assessment …

The Exercise And Sports Science Australia Position Statement: Exercise Medicine In Cancer Management, Sandra C. Hayes, Robert U. Newton, Rosalind R. Spence, Daniel A. Galvao

Research outputs 2014 to 2021

Objectives: Since Exercise and Sports Science Australia (ESSA) first published its position statement on exercise guidelines for people with cancer, there has been exponential growth in research evaluating the role of exercise pre-, during and post-cancer treatment.

Design and Methods: The purpose of this report is to use the current scientific evidence, alongside clinical experience and exercise science principles to update ESSA’s position statement on cancer-specific exercise prescription.

Results: Reported in this position statement is a summary of the benefits accrued through exercise following a cancer diagnosis and the strengths and limitations of this evidence-base. An exercise prescription framework is …

Sport Medicine In The Prevention And Management Of Cancer, Hao Luo, Daniel A. Galvão, Robert U. Newton, Ciaran M. Fairman, Dennis R. Taaffe

Research outputs 2014 to 2021

Physical inactivity is a major concern in cancer patients despite the established preventative and therapeutic effects of regular physical exercise for this patient group. Sport not only plays an important role in supporting the development and maintenance of a physically active lifestyle but also is increasingly used as a health promotion activity in various populations. Nevertheless, the potential of sport as an effective strategy in the prevention and management of cancer has gained little attention. Based on the scant evidence to date, participation of cancer patients in supervised, well-tailored sport programs appears to be safe and feasible and is associated …

Implantable Biomaterials To Provide Local Immunotherapy Following Surgical Resection., Michael J Gough, Jason R Baird, R Bryan Bell

Articles, Abstracts, and Reports

No abstract provided.