Medicine and Health Sciences Commons^™

The Role Of Mtorc1 In Autophagy As It Relates To Cancer, Olivia Robinson

Senior Honors Theses

The mammalian target of rapamycin complex 1, mTORC1, is composed of several subunit proteins with many cellular responsibilities including participation in a complex cell signaling cascade leading to autophagy, which is the regulated degradation of cell components. mTORC1 is frequently mutated or dysregulated within human cancer. Normally, mTORC1 functions to provide efficient regulation of autophagy according to intracellular levels of growth factors, amino acids, nutrients, oxygen levels, and more that can either inhibit mTORC1 and upregulate autophagy or activate mTORC1 and downregulate autophagy. A better understanding of mTORC1 is imperative to preparing cancer therapy treatments. Various cancerous tissue types require …

Mediator Kinase Inhibitors For Breast Cancer Therapy, Xiaokai Ding

Theses and Dissertations

Breast cancers (BrCa) that overexpress oncogenic tyrosine kinase receptor HER2 are treated with HER2-targeting antibodies (such as trastuzumab) or small-molecule kinase inhibitors (such as lapatinib). However, most patients with metastatic HER2+ BrCa have intrinsic resistance and nearly all eventually become resistant to HER2-targeting therapy. Resistance to HER2-targeting drugs frequently involves transcriptional reprogramming associated with constitutive activation of different signaling pathways. We have investigated the role of CDK8/19 Mediator kinase, a regulator of transcriptional reprogramming, in the response of HER2+ BrCa to HER2-targeting drugs. Selective CDK8/19 inhibitors (senexin B and SNX631) showed synergistic interactions with lapatinib and trastuzumab in a panel …

Survivorship Research For People With Metastatic Or Advanced Cancer: A Time For Action, Andrea L. Smith, Nicolas H. Hart, Michael Jefford, Raymond J. Chan

Research outputs 2022 to 2026

Over recent decades, survival outcomes for people diagnosed with cancer have changed dramatically, with approximately 20% improvement in five-year relative survival rates in high-income countries including the United States and Australia. Regardless of regions, there is a decrease in overall cancer mortality rate of about 1% per year. Likewise, the cancer disease trajectory has changed. The traditional linear cancer trajectory in which a patient moves from cancer diagnosis through to a binary outcome (cure or death)—is no longer applicable and does not adequately describe the complexity of experience for many people. Indeed, the availability of targeted therapies and immunotherapies has …

Origin And Epigenetic Regulation Of Cutaneous T Cell Lymphoma, Carly M. Harro

USF Tampa Graduate Theses and Dissertations

The pathogenesis of Cutaneous T cell lymphoma (CTCL) remains unclear. Using conditional knockout mice, we found that ablation of the genomic organizer Special AT-rich sequence-binding protein-1 (Satb1) caused malignant transformation of mature, skin-homing, Notch-activated CD4+ and CD8+ T cells into progressively fatal lymphoma. Mechanistically, Satb1 restrained Stat5 phosphorylation and the expression of skin-homing chemokine receptors in mature T cells. H3K27 and H3K9 trimethylation occluded the SATB1 promoter in Sézary cells, while inhibition of SUV39H1/2 methyltransferases (unlike EZH2 inhibition), restored protective SATB1 expression and selectively abrogated the growth of primary Sézary cells more effectively than romidepsin. Additionally, using single-cell RNA/TCR sequencing …

The Incidence And The Type Of Stomatognathic Disorders In Patients With Gardner Syndrome. A Systematic Review, Olga Preuss, Aleksandra Jaron, Anna Grzywacz, Magda Aniko-Wlodarczyk, Grzegorz Trybek

Baltic Journal of Health and Physical Activity

Background: Diseases of genetic origin are very often associated with oral disorders. One of them is Gardner syndrome (GS) a rare variant of familial adenomatous polyposis (FAP), whose main manifestation is colon cancer. Its most common oral cavity symptoms include osteomas, odontomas and impacted or supernumerary teeth. Material and methods: Medline (PubMed), Medline (Ebsco), Scopus and Google Scholar databases were searched oral manifestations of Gardner Syndrome.Results: Thirty-eight articles met inclusion criteria. The most frequently mentioned oral changes included osteomas, impacted teeth, supernumerary teeth and odontomas. Conclusion: This review provides evidence for associating FAP with oral disorders. Dentists can be the …

Sportsman’S Authority In The Perspective Of Man’S Weakness, Marcin Pasek

Baltic Journal of Health and Physical Activity

Background: History of glory and fall of the cyclist Lance Armstrong refers to the issues from the borderline of sociology, psychology, pharmacology and qualified sport. It stirs many emotions and extreme opinions in which human attitudes are focused on phenomena impossible to be interpreted unequivocally. The purpose of this research was to learn opinions on the life path of Lance Armstrong, regarding his struggle both with cancer and his rivals in the peloton, but at the same time marked with forbidden doping. Material and methods: The research was carried out using the survey method, which asked one question about the …

Editorial: Anticancer Potential Of Artemisia Annua, Jill M. Kolesar, Peter H. Seeberger

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Challenges And Opportunities For Immunotherapeutic Intervention Against Myeloid Immunosuppression In Glioblastoma, Mark A Exley, Samantha Garcia, Amelia Zellander, Jenny Zilberberg, David W. Andrews

Department of Neurosurgery Faculty Papers

Glioblastoma multiforme (GBM), the most common and deadly brain cancer, exemplifies the paradigm that cancers grow with help from an immunosuppressive tumor microenvironment (TME). In general, TME includes a large contribution from various myeloid lineage-derived cell types, including (in the brain) altered pathogenic microglia as well as monocyte-macrophages (Macs), myeloid-derived suppressor cells (MDSC) and dendritic cell (DC) populations. Each can have protective roles, but has, by definition, been coopted by the tumor in patients with progressive disease. However, evidence demonstrates that myeloid immunosuppressive activities can be reversed in different ways, leading to enthusiasm for this therapeutic approach, both alone and …

Dna-Pkcs: A Targetable Protumorigenic Protein Kinase., Emanuela Dylgjeri, Karen E Knudsen

Department of Cancer Biology Faculty Papers

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a pleiotropic protein kinase that plays critical roles in cellular processes fundamental to cancer. DNA-PKcs expression and activity are frequently deregulated in multiple hematologic and solid tumors and have been tightly linked to poor outcome. Given the potentially influential role of DNA-PKcs in cancer development and progression, therapeutic targeting of this kinase is being tested in preclinical and clinical settings. This review summarizes the latest advances in the field, providing a comprehensive discussion of DNA-PKcs functions in cancer and an update on the clinical assessment of DNA-PK inhibitors in cancer therapy.

Choosing To Thrive: An Autoethnographic Journey Of Cancer, Companionship, And Carrots, Bruce Lilyea

The Qualitative Report

In this autoethnography, I explore the companionship experience of someone supporting a cancer patient who is endeavoring to thrive in the face of this disease. A wide range of studies has been conducted on the emotional and social issues relating to cancer and specifically to breast cancer. Appropriately, most of the research relating to the personal narrative focuses on the stories of the person who has been diagnosed with cancer, and limited research has highlighted the perspective and experiences of their companions. My primary goals for this autoethnographic research are to: (1) Begin to answer the question: What role do …

Risk Factors For Hospitalizations Among Older Adults With Gastrointestinal Cancers, Daneng Li, Can-Lan Sun, Rebecca Allen, Christiana J Crook, Abrahm Levi, Richard Ballena, Heidi D Klepin, Rawad Elias, Supriya G Mohile, William P Tew, Cynthia Owusu, Hyman B Muss, Stuart M Lichtman, Cary P Gross, Andrew Chapman, Ajeet Gajra, Harvey J Cohen, Vani Katheria, Arti Hurria, William Dale

Department of Medical Oncology Faculty Papers

Background: Older adults (≥65 years) with gastrointestinal (GI) cancers who receive chemotherapy are at increased risk of hospitalization caused by treatment-related toxicity. Geriatric assessment (GA) has been previously shown to predict risk of toxicity in older adults undergoing chemotherapy. However, studies incorporating the GA specifically in older adults with GI cancers have been limited. This study sought to identify GA-based risk factors for chemotherapy toxicity-related hospitalization among older adults with GI cancers.

Patients and methods: We performed a secondary post hoc subgroup analysis of two prospective studies used to develop and validate a GA-based chemotherapy toxicity score. The incidence of …

Positive Selection And Enhancer Evolution Shaped Lifespan And Body Mass In Great Apes, Daniela Tejada-Martinez, Roberto A Avelar, Inês Lopes, Bruce Zhang, Guy Novoa, João Pedro De Magalhães, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body …

Examining Rural-Urban Differences In Fatalism And Information Overload: Data From 12 Nci-Designated Cancer Centers, Jakob D Jensen, Jackilen Shannon, Ronaldo Iachan, Yangyang Deng, Sunny Jung Kim, Wendy Demark-Wahnefried, Babalola Faseru, Electra D Paskett, Jinxiang Hu, Robin C Vanderpool, Deann Lazovich, Jason A Mendoza, Sanjay Shete, Linda B Robertson, Rajesh Balkrishnan, Katherine J Briant, Benjamin Haaland, David A Haggstrom, Bernard F Fuemmeler, Rural Workgroup Of The Population Health Assessment In Cancer Center Catchment Areas Consortium

Faculty, Staff and Student Publications

BACKGROUND: Rural populations experience a disproportionate cancer burden relative to urban populations. One possibility is that rural populations are more likely to hold counterproductive cancer beliefs such as fatalism and information overload that undermine prevention and screening behaviors.

METHODS: Between 2016 and 2020, 12 U.S. cancer centers surveyed adults in their service areas using online and in-person survey instruments. Participants (

RESULTS: Compared with urban residents, rural residents were more likely to believe that (i) everything causes cancer (OR = 1.29; 95% CI, 1.17-1.43); (ii) prevention is not possible (OR = 1.34; 95% CI, 1.19-1.51); and (iii) there are too …

A Narrative Review Of The Evidence For Variations In Serum 25-Hydroxyvitamin D Concentration Thresholds For Optimal Health, William B. Grant, Fatme Al Anouti, Barbara J. Boucher, Erdinç Dursun, Duygu Gezen-Ak, Edward B. Jude, Tatiana Karonova, Pawel Pludowski

All Works

Vitamin D3 has many important health benefits. Unfortunately, these benefits are not widely known among health care personnel and the general public. As a result, most of the world’s population has serum 25-hydroxyvitamin D (25(OH)D) concentrations far below optimal values. This narrative review examines the evidence for the major causes of death including cardiovascular disease, hypertension, cancer, type 2 diabetes mellitus, and COVID-19 with regard to sub-optimal 25(OH)D concentrations. Evidence for the beneficial effects comes from a variety of approaches including ecological and observational studies, studies of mechanisms, and Mendelian randomization studies. Although randomized controlled trials (RCTs) are generally considered …

Neutralizing Interleukin-6 In Tumor-Bearing Mice Does Not Abrogate Behavioral Fatigue Induced By Lewis Lung Carcinoma, Kiersten Scott, Thien Trong Phan, A Phillip West, Cullen M Taniguchi, Robert Dantzer

Faculty, Staff and Student Publications

Tumor growth is associated with metabolic reprogramming of various organs including the liver. This metabolic reprogramming is responsible for the development of behavioral fatigue represented by decreased voluntary wheel running in a murine model of lung cancer. To determine whether interleukin (IL-)6 induced by the tumor is responsible for the metabolic reprogramming, mice injected with Lewis lung carcinoma cells in the flank were treated with an anti-mouse IL-6 monoclonal neutralizing antibody using a 2 × 2 factorial design (+/- tumor and +/- anti-IL-6 antibody). Endpoints were represented by behavioral, metabolic and immune phenotypes. Despite its ability to abrogate the increase …

Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara

Articles

Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects. This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with …

Cancer Care Annual Report 2020-2021, Children's Mercy Kansas City

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Kansas City, a pediatric medical center. This year’s report focuses on Hodgkin Lymphoma.

The Efficacy Of The Role Of Therapeutic Play In Alleviating Pain Or Anxiety In Pediatric Cancer Patients, Savannah B. Duke

Honors Undergraduate Theses

Aim: To evaluate the efficacy of therapeutic play in alleviating pain or anxiety in the pediatric cancer patient.

Background: Therapeutic play is an intervention often incorporated within the care of pediatric cancer patients and children with other disease processes to promote well-being. Even though play therapy is supported by research, nurses have the option to implement nursing care interventions in a play-like manner. Therapeutic play is an individualized technique that provides an intentional opportunity for children to express their emotional responses in a controlled environment.

Method: The databases used in this search included CINAHL, MEDLINE, APA PsycINFO, ERIC, and Education …

Increasing Cancer Survivorship Knowledge Through Individualized Cancer Survivorship Packets, Ashley Atkins

Doctor of Nursing Practice Projects

This project was developed with the aim of formulating an individualized educational packet that would improve patients’ knowledge of their initial cancer diagnosis and provide additional information to facilitate a smooth transition from treatment to remission. Using a pretest and posttest, quantitative data was collected pertaining to 10 different types of patient education. The pretest survey collected eight questions that related to gathering information about their cancer diagnosis, resources, and knowledge level. The DNP Project Leader secured a Cancer Survivorship Guide through the American Society of Clinical Oncology that was added to the initial cancer survivorship education for all patients. …

The Factors Urban African American Men Perceive As Preventing Early Prostate Cancer Screening, Joel Mongo

Walden Dissertations and Doctoral Studies

Prostatic carcinoma, or prostate cancer, is the leading cause of death among adult males in the United States. The highest rate of prostate cancer is found in males of African American ethnicity, as males within this cohort are 50% more likely to develop prostate cancer than other ethnicities. African Americans men are 1.6 times more likely to develop prostate cancer and 2.4 times more likely to die from it than Caucasians. The purpose of this qualitative study was to examine the perceptions of urban African American men about factors that prevent them from seeking and receiving prostate cancer screening, and …

Therapeutic Music Effectiveness In Managing Anxiety And Depression Feelings In Cancer Patients, Aida L. Ramos

Walden Dissertations and Doctoral Studies

AbstractWith the emergence of advances in health care technology, increased life expectancy has exacerbated the manifestation of chronic disease states such as cancer. The side effects of cancer treatments can lead to feelings of depression and anxiety, which can be as devastating as disease process. Many studies have provided evidence supporting the practice problem, therapeutic music effectiveness in managing anxiety and depression feelings in cancer patients. Available pharmacological treatments may result in additional side effects that may outweigh the benefits of their use. Current systematic reviews of literature demonstrating the effectiveness of therapeutic music use as a non-pharmacological thera-peutic adjunct …

Liquid Biopsy: A Step Closer To Transform Diagnosis, Prognosis And Future Of Cancer Treatments, Saife N. Lone, Sabah Nisar, Tariq Masoodi, Mayank Singh, Arshi Rizwan, Sheema Hashem, Wael El-Rifai, Davide Bedognetti, Surinder K. Batra, Mohammad Haris, Ajaz A. Bhat, Muzafar A. Macha

Journal Articles: Biochemistry & Molecular Biology

Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly …

Analyzing The Relationship Between The Quality Of Life And Race Of Lung Cancer Survivors, Alina S. Wise

Honors Undergraduate Theses

Purpose: The relationship between racial disparities and the health-related quality of life (HRQoL) of lung cancer patients is not well understood. The purpose of this study was to quantify the overall HRQoL of lung cancer patients and compare differences in HRQoL among racial groups in the United States.

Methods: We analyzed data from the Behavioral Risk Factors Surveillance System (BRFSS), a population-based national cross-sectional study conducted by the Centers for Disease Control and Prevention. The BRFSS is conducted annually in all 50 states and collects information on demographics, health behaviors, health-related experiences, health conditions, use of medications, and use of …

European Epidemiological Patterns Of Cannabis- And Substance-Related Congenital Cardiovascular Anomalies: Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

As prenatal and community cannabis exposures have recently been linked with congenital heart disease (CHD), it was of interest to explore these associations in Europe in a causal framework and space-time context. Congenital anomaly data from Eurocat, drug-use data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Countries with rising daily cannabis use had in general higher congenital anomaly rates over time than those without (time: status interaction: β-Est. = 0.0267, P = 0.0059). At inverse probability-weighted panel regression, cannabis terms were positive and significant for CHD, severe CHD, atrial septal defect, …

"It’S Just Another Thing”: Perceptions Of Well Water Quality And Barriers In An Arsenic Hot Spot, Linzy Rosen

Honors Theses

Privately owned water is the primary source of drinking water for 43 million Americans. Although residential or private wells are susceptible to a variety of contaminants, the Safe Drinking Water Act of 1974 positions individuals as responsible for the testing, remediation, and management of this water. Despite the elevated presence of arsenic in Maine, which is linked to various cancers, cardiovascular disease, and neurological damage, little is known about how private well owners perceive the safety and quality of their own water.

This study takes a qualitative approach to understanding concerns and opinions by conducting semi - structured interviews with …

Changes In Physical Activity And Relationships To Submaximal Exercise Capacity And Cardiac Function During Breast Cancer Therapy, Moriah P. Bellissimo

Theses and Dissertations

Background: Breast cancer (BC) survivors are at high risk for heart failure due to curative cancer therapies. In non-cancer populations, physical activity is a first line treatment for preventing cardiovascular disease. This study examined whether more physical activity was associated with better submaximal exercise capacity and cardiac function during the first three months of cancer therapy.

Methods: Participants included 223 women with stage I-III BC before therapy and after three months of undergoing treatment and 126 controls. Leisure time physical activity was reported using the Godin Sheppard leisure time exercise questionnaire. Cardiac function was assessed by cardiac magnetic resonance, and …

Regulation, Targets And Functions Of Chk, Shudong Zhu, Rong Sun, Xialing Guo, Yuanwu Bao, Dianzheng Zhang

PCOM Scholarly Works

Src family kinases (SFKs) play pivotal roles in multiple signaling pathways (Yeatman, 2004). SFK activity is inhibited by phosphorylation at its C-terminal tyrosine, by CSK (C-terminal Src kinase) and CHK (CSK-homologous kinase). CHK expression is restricted to normal hematopoietic cells, brain, and colon tissues. Downregulation of CHK in brain and colon tumors contributes to tumorigenicity in these tissues. CHK does not phosphorylate Src efficiently, however, in contrast to CSK, CHK inhibits Src kinase activity allosterically. Although the functions of CHK are still largely unknown, potential substrates of CHK including β-synuclein, α-tubulin, α-spectrin, 14-3-3, and Hsp90 have been identified. CHK is …

A Review Of Monte Carlo Methods And Their Application In Medical Physics For Simulating Radiation Transport, Joe Shields

Honors Theses and Capstones

Monte Carlo methods are used to calculate statistical behavior through the use of random number generators and probability density functions. They have been used extensively in medical physics for research in radiotherapy, designing technology, dosimetry, and advanced clinical applications. This paper provides a background on Monte Carlo methods and a review of radiation therapy physics and dosimetry. Additionally, there is a discussion of the different ways Monte Carlo methods are used in medical physics as well as a review of current research related to Monte Carlo methods. The final portion of this paper contains my own Monte Carlo simulation using …

Validation Of The Knowledge Of Genome Sequencing (Kogs) Scale In Cancer Patients, P Butow, C Napier, R Campbell, N Bartley, Megan Best, M L. Ballinger

IES Papers and Journal Articles

Introduction: The Knowledge of Genome Sequencing (KOGS) questionnaire was recently developed to measure knowledge of genomic sequencing (GS), with preliminary psychometric data supporting its reliability and validity. The aim of this study was to test the reliability and validity of the KOGS in a larger sample, and to confirm its utility in a cancer setting.

Methods: The Genetic Cancer Risk in the Young (RisC) study recruits participants with a personal history of cancer, to investigate heritable cancer causes and future cancer risk using germline GS. Participants (n = 261) in a psychosocial substudy of RisC completed a questionnaire after consent …

Interferon-Β Activity Is Affected By S100b Protein, Alexey S. Kazakov, Alexander D. Sofin, Nadezhda V. Avkhacheva, Eugenia I. Deryusheva, Victoria A. Rastrygina, Maria E. Permyakova, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov

Molecular Medicine Faculty Publications

Interferon-β (IFN-β) is a pleiotropic cytokine secreted in response to various pathological conditions and is clinically used for therapy of multiple sclerosis. Its application for treatment of cancer, infections and pulmonary diseases is limited by incomplete understanding of regulatory mechanisms of its functioning. Recently, we reported that IFN-β activity is affected by interactions with S100A1, S100A4, S100A6, and S100P proteins, which are members of the S100 protein family of multifunctional Ca2+-binding proteins possessing cytokine-like activities (Int J Mol Sci. 2020;21(24):9473). Here we show that IFN-β interacts with one more representative of the S100 protein family, the S100B protein, involved in …