Medicine and Health Sciences Commons^™

Genome-Scale Precision Proteomics Identifies Cancer Signaling Networks And Therapeutic Vulnerabilities, Hong Wang

Theses and Dissertations (ETD)

Mass spectrometry (MS) based-proteomics technology has been emerging as an indispensable tool for biomedical research. But the highly diverse physical and chemical properties of the protein building blocks and the dramatic human proteome complexity largely limited proteomic profiling depth. Moreover, there was a lack of high-throughput quantitative strategies that were both precise and parallel to in-depth proteomic techniques. To solve these grand challenges, a high resolution liquid chromatography (LC) system that coupled with an advanced mass spectrometer was developed to allow genome-scale human proteome identification. Using the combination of pre-MS peptide fractionation, MS2-based interference detection and post-MS computational interference correction, …

Managing Variant Discrepancy In Hereditary Cancer: Clinical Practice, Barriers, And Desired Resources, Ellen Zirkelbach

Dissertations and Theses (Open Access)

Variants are changes in the DNA whose phenotypic effects may or may not be definitively understood. Because variant interpretation is a complex process, sources sometimes disagree on the classification of a variant, which is called a variant discrepancy. This study aimed to determine the practice of genetic counselors regarding variant discrepancies and to identify the barriers to counseling a variant discrepancy in hereditary cancer genetic testing. This investigation was unique because it was the first to address variant discrepancies from a clinical point of view. An electronic survey was sent to genetic counselors in the NSGC Cancer Special Interest Group. …

Peptide Vaccine Formulation Controls The Duration Of Antigen Presentation And Magnitude Of Tumor‐Specific Cd8+ T Cell Response, Hiep Khong

Dissertations and Theses (Open Access)

Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that the duration of antigen presentation critically affected the quantity and quality of T cell response and subsequent anti‐tumor efficacy. Here we describe L‐tyrosine amino acid‐based microparticles as a novel peptide vaccine adjuvant for the induction of tumor‐specific T cells. L‐tyrosine microparticles did not induce inflammasome activation, but instead extended antigen presentation time. The consequent prolongation in antigen presentation translated into prolonged T cell proliferation and superior numbers and anti‐tumor function of vaccination‐induced CD8+ T cells. Indeed, prolonging antigen presentation by repeated injection …

Ultrasound Monitoring Of Extant Adnexal Masses In The Era Of Type 1 And Type 2 Ovarian Cancers: Lessons Learned From Ovarian Cancer Screening Trials, Eleanor L. Ormsby, Edward J. Pavlik, John P. Mcgahan

Obstetrics and Gynecology Faculty Publications

Women that are positive for an ovarian abnormality in a clinical setting can have either a malignancy or a benign tumor with probability favoring the benign alternative. Accelerating the abnormality to surgery will result in a high number of unnecessary procedures that will place cost burdens on the individual and the health delivery system. Surveillance using serial ultrasonography is a reasonable alternative that can be used to discover if changes in the ovarian abnormality will occur that favor either a malignant or benign interpretation. Several ovarian cancer screening trials have had extensive experiences with changes in subclinical ovarian abnormalities in …

Low Molecular-Weight Heparin Is Better Than Warfarin For Prevention Of Recurrent Venous Thromboembolism In Cancer Patients, Sarah Choi

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lee AYY, Levin MN, Bake RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146-153. doi: 10.1056/NEJMoa025313

The Role Of Metastasis Suppressor Cd82 In The Deactivation Of The C-Met Signaling Pathway In Prostate Cancer, Katie L. Uhl

Masters Theses

BACKGROUND AND PURPOSE: Prostate cancer is the second leading cause of cancer deaths among men in the United States. Metastasis plays a major role in patient prognosis and treatment options. One of the factors that influences metastasis is the activation of the c-Met signaling pathway. Activation of the growth factor c-Met results in cytoskeletal rearrangement, migration, and invasion. Previous studies have shown CD82 to act as an active metastatic suppressor in normal, healthy cells and is downregulated in various forms of cancer. When CD82 is re-expressed in cancer cells, the cells no longer express metastatic characteristics. The purpose of this …

Ten Important Considerations For Ovarian Cancer Screening, Edward J. Pavlik

Obstetrics and Gynecology Faculty Publications

The unique intricacies of ovarian cancer screening and perspectives of different screening methods are presented as ten considerations that are examined. Included in these considerations are: (1) Deciding on the number of individuals to be screened; (2) Anticipating screening group reductions due to death; (3) Deciding on the duration and frequency of screening; (4) Deciding on an appropriate follow-up period after screening; (5) Deciding on time to surgery when malignancy is suspected; (6) Deciding on how screen-detected ovarian cancers are treated and by whom; (7) Deciding on how to treat the data of enrolled participants; (8) Deciding on the most …

Gastrointestinal Stromal Tumor Induced Hypercalcemia, Aram Barbaryan, Stefania Bailuc, Padma Poddutoori, Aida Richardson, Aibek E. Mirrakhimov

Internal Medicine Faculty Publications

Hypercalcemia in patients with cancer is a common laboratory finding affecting up to 44% of that patient population. 1,25-Dihydroxyvitamin D₃ mediated hypercalcemia is one of the rare mechanisms of this endocrine emergency in cancer patients. It is even rarer for solid organ neoplasms to present with hypercalcemia mediated through the production of 1,25-dihydroxyvitamin D₃. We report a case of a 77-year-old female who presented to the hospital with hypercalcemia and later was found to have metastatic gastrointestinal stromal tumor. There have been only 5 cases of gastrointestinal stromal tumor described in literature resulting in hypercalcemia. In our …

Cancer As A Metabolic Disease, Javaria Haseeb

Honors Senior Capstone Projects

Despite decades of intensive scientific and medical efforts to develop efficient and effective treatments for cancer, it remains one of the prime causes of death today. For example, in 2016, there will be an estimated 1,685,210 new cases of cancer and 595,690 deaths due to cancer in the United States alone (National Cancer Institute). Worldwide in 2012, there were an estimated 14 million new cases of cancer and 8.2 million deaths due to cancer. In order to come up with better methods of detection and more successful modes of treatment, it is crucial that scientists understand the depth of not …

Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto

GW Research Days 2016 - 2020

While BRAF is among the most well-established oncogenes in human cancers, more recently it has garnered attention for its role in suppressing antitumor immunity, especially in melanoma. Because tumor-infiltrating lymphocyte (TIL) density is strongly prognostic in colorectal cancer (CRC)⁷, we decided to investigate the connection between TIL density and the BRAF-activating V600E mutation in CRC.

We used ESTIMATE to quantify immune infiltrate in samples from the TCGA colon adenocarcinoma (COAD) dataset (n = 216). This is an algorithm that uses the gene-expression signature of 141 immune-related genes to infer the presence of immune cells in the tumor infiltrate. …

Persistent Organic Pollutants And Mortality In The United States, Kristiann Fry, Melinda Power

GW Research Days 2016 - 2020

Background/Objectives: Persistent organic pollutants (POPs) are environmentally and biologically persistent chemicals that include polybrominated diphenyl ethers (PBDEs), per- and polyfluoroalkyl Substances (PFASs), polychlorinated biphenyls (PCBs), and organochlorine (OC) pesticides. Currently, there is limited data on the association between exposure to POPs and the risk of mortality in the general US population. The objective of this study was to determine if higher exposure to POPs are associated with greater risk of all-cause, cancer, heart/cerebrovascular disease, or other-cause mortality in persons aged 60 years and older.

Methods: The analyses included participants aged 60 years and older from the 1999-2006 National Health and …

Quality Of Life And Its Determinants In Adult Cancer Patients Undergoing Chemotherapy Treatment In Pakistan., Parveen Chagani, Yasmin Parpio, Raisa B. Gul, Adnan Jabbar

School of Nursing & Midwifery

Objective:

Cancer is a leading cause of death worldwide. Likewise, in Pakistan, it is a major health problem, with an approximate increase each year. Cancer treatment, particularly chemotherapy, produces a detrimental effect on individuals' well-being. Since the past few years, quality of life (QOL) is considered as the primary goal of cancer treatment in patients' survival. This study aimed to assess the QOL and its determinants in adult cancer patients undergoing chemotherapy treatment.

Methods:

An analytical cross-sectional design was employed to achieve the study objectives, utilizing consecutive sampling technique. A total of 150 adult (>19 years) cancer patients were …

Natural Killer (Nk) Cells And Their Involvement In Different Types Of Cancer. Current Status Of Clinical Research, Isadora Zaharescu, Adina D. Moldovan, Cristiana Tanase

Journal of Mind and Medical Sciences

Natural killer cells are the main agents of innate immunity. Since 1970, various studies have repeatedly confirmed their involvement in decreasing local tumor growth and also decreasing the risk of metastasis, due to their cytotoxic effects and also through the release of immunostimulatory cytokines such as IFN-gamma. In the 1990s, several studies demonstrated the existence of certain inhibiting and stimulating receptors of these cells, leading to the concept of “induced self”, thus explaining why tumors with MHC-1 are destroyed and autologous cells without it are saved out. Recognition and destruction of tumor cells by the NK cells are the result …

Applications Of Next-Generation Sequencing In Cancer Research And Molecular Diagnosis, Kesheng Wang, Chun Xu

Health & Biomedical Sciences Faculty Publications

Next-generation sequencing (NGS) technologies including DNA sequencing and RNA sequencing provide “omics” approaches to reveal genomic, transcriptomic, and epigenomic landscapes of individual cancers. A variety of genomic aberrations can be screened simultaneously, such as common and rare variants, structural variations (e.g. insertions and deletions), copy-number variation, and fusion transcripts. NGS technologies together with bioinformatics analysis, which expand our knowledge, are increasingly used to simultaneously analyze multiple genes in a cost and time-effective manner and have been applied in analyzing clinical cancer samples and offering NGS-based molecular diagnosis. Therefore, NGS is increasingly valuable as a tool for diagnosis for a number …

Complications From Surgeries Related To Ovarian Cancer Screening, Lauren A. Baldwin, Edward J. Pavlik, Emma Ueland, Hannah E. Brown, Kelsey M. Ladd, Bin Huang, Christopher P. Desimone, John R. Van Nagell, Frederick R. Ueland, Rachel W. Miller

Obstetrics and Gynecology Faculty Publications

The aim of this study was to evaluate complications of surgical intervention for participants in the Kentucky Ovarian Cancer Screening Program and compare results to those of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. A retrospective database review included 657 patients who underwent surgery for a positive screen in the Kentucky Ovarian Cancer Screening Program from 1988–2014. Data were abstracted from operative reports, discharge summaries, and office notes for 406 patients. Another 142 patients with incomplete records were interviewed by phone. Complete information was available for 548 patients. Complications were graded using the Clavien–Dindo (C–D) Classification of Surgical …

Patients Receiving Androgen Deprivation Therapy For Prostate Cancer Have An Increased Risk Of Depressive Disorder, Shiu-Dong Chung, Li-Ting Kao, Herng-Ching Lin, Sudha Xirasagar Mbbs., Ph.D., Chung-Chien Huang, Hsin-Chien Lee

Publications

Androgen deprivation therapy (ADT) results in testosterone suppression, a hypothesized mechanism linking ADT to depressive symptoms. This study investigated the relationship between ADT and the risk of subsequently being diagnosed with depressive disorder (DD) during a 3-year follow-up period. The patient sample for this population-based, retrospective cohort study was retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We included all 1714 patients aged over 40 years with a first-time diagnosis of prostate cancer (PC) during 2001 to 2010 who did not have an orchiectomy. Among them, we defined 868 patients who received ADT during the 3-year follow-up period as …

Using A Conformal Water Bolus To Adjust Heating Patterns Of Microwave Waveguide Applicators, Paul R. Stauffer, Dario B. Rodrigues, Randolph Sinahon, Lyndsey Sbarro, Valeria Beckhoff, Mark Hurwitz

Department of Radiation Oncology Faculty Papers

Background: Hyperthermia, i.e., raising tissue temperature to 40-45°C for 60 min, has been demonstrated to increase the effectiveness of radiation and chemotherapy for cancer. Although multi-element conformal heat applicators are under development to provide more adjustable heating of contoured anatomy, to date the most often used applicator to heat superficial disease is the simple microwave waveguide. With only a single power input, the operator must be resourceful to adjust heat treatment to accommodate variable size and shape tumors spreading across contoured anatomy. Methods: We used multiphysics simulation software that couples electromagnetic, thermal and fluid dynamics physics to simulate heating patterns …

Quantification Of Two Isomeric Flavones In Rat Colon Tissue Using Reverse Phase High Performance Liquid Chromatography, Crystal L. Whitted, Victoria E. Palau, Ruben D. Torrenegra, Oscar E. Rodriguez, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Background: Antineoplastic activity has been previously shown for two isomeric flavones, 5,7-dihydroxy-3,6,8-trimethoxy flavone (flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy flavone (flavone B), against colon cancer cell lines (Thomas et al. in PLoS ONE 7:e39806, 5). Here, we present modified methods for the extraction and quantification of flavones A and B in rat colon tissue after intravenous dosing via high performance liquid chromatography, from the originally described procedure for extraction and quantification in rat plasma (Whitted et al. in J Chromatogr B Analyt Technol Biomed Life Sci 1001:150–155, 7).

Results: Modifications included tissue homogenization (1 g tissue: 2 mL water), filtration …

Biological Functions Of Cdk5 And Potential Cdk5 Targeted Clinical Treatments., Alison Shupp, Mathew C. Casimiro, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Cyclin dependent kinases are proline-directed serine/threonine protein kinases that are traditionally activated upon association with a regulatory subunit. For most CDKs, activation by a cyclin occurs through association and phosphorylation of the CDK's T-loop. CDK5 is unusual because it is not typically activated upon binding with a cyclin and does not require T-loop phosphorylation for activation, even though it has high amino acid sequence homology with other CDKs. While it was previously thought that CDK5 only interacted with p35 or p39 and their cleaved counterparts, Recent evidence suggests that CDK5 can interact with certain cylins, amongst other proteins, which modulate …

Breast Cancer: What Young Women Need To Know, Franki Hubbard

Student Brochures

No abstract provided.

Steroid-Induced Hyperglycemia In Patients With Malignancies: Healthcare Team Adaptation To A Paradigm Shift, Miriam Ingrid Silva

Student Theses, Dissertations and Capstones

Background: Caring for patients with malignancies and presenting hyperglycemia has been an ongoing problem that needed to be addressed. The Endocrinologist Society and the Joint British Diabetes Societies for Inpatient Care suggested a change in the process by which patients in this population are managed. Purpose: The purpose of this project was to implement evidence-based practice guidelines for managing steroid-induced hyperglycemia focusing on the interdisciplinary team and adaptation of nurses who care for patients with malignancies. Theoretical Framework: The theoretical framework selected for this project was Roy’s Adaptation Model. Methods: This project used a mixed method approach, with a triangulation …

Cancer Care Annual Report 2016-2017, Children's Mercy Hospital

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Hospital, Kansas City MO, a pediatric medical center. This report has a focus on sarcomas.

The Effect Of K562-Il21-2 Plasma Membrane Particles On The Proliferation Of Natural Killer Cells To Fight Cancer, Michelle Prophete

Honors Undergraduate Theses

Immunotherapy has emerged as a current and future paradigm of cancer treatment, which utilizes the body’s immune system to eradicate cancer. Natural Killer (NK) cells as part of the innate immune system have immense potential in their anti-tumor cytotoxic activities and host cell surveillance properties. NK cells comprise approximately five to fifteen percent of peripheral blood lymphocytes and can be proliferated in vitro using recently developed methods with co-cultures with feeder cells (derived from engineered tumor cells) or plasma membrane (PM) particles, produced from the fore mentioned feeder cells, in combination with soluble cytokines. For efficient growth and maintenance of …

Components In Aqueous Hibiscus Rosa-Sinensis Flower Extract Inhibit In Vitro Melanoma Cell Growth, Karina H. Goldberg, Ariel C. Yin, Archana Mupparapu, Edward P. Retzbach, Gary S. Goldberg, Catherine F. Yang

College of Science & Mathematics Departmental Research

Skin cancer is extremely common, and melanoma causes about 80% of skin cancer deaths. In fact, melanoma kills over 50 thousand people around the world each year, and these numbers are rising. Clearly, standard treatments are not effectively treating melanoma, and alternative therapies are needed to address this problem. Hibiscus tea has been noted to have medicinal properties, including anticancer effects. Extracts from Hibiscus have been shown to inhibit the growth of a variety of cancer cells. In particular, recent studies found that polyphenols extracted from Hibiscus sabdariffa by organic solvents can inhibit melanoma cell growth. However, effects of aqueous …

Developing A Peer-To-Peer Mhealth Application To Connect Hispanic Cancer Patients, Jennifer R. Banas, David Victorson, Sandra Gutierrez, Evelyn Cordero, Judy Guitleman, Niina Haas

Health Sciences and Physical Education Faculty Publications

Purpose: Cancer and its treatment can significantly impact health-related quality of life (HRQOL) [29, 4], particularly for Hispanics [8, 17]. Moreover, providers of cancer support for this population may encounter unique challenges. Grounded in social capital theory, this study identified Spanish-speaking, Hispanic breast cancer survivor support needs and preferences for a mHealth intervention. Methods: A user-centered, community-engaged research design was employed, consisting of focus groups made up of constituents from a local Hispanic-serving, cancer support organization. Focus group audio-recordings, translated into English, were coded using a grounded theory analytic approach. First, lead researchers read the complete transcripts to obtain a …

Exploring The Relationship Between Symptom Management And Distress In Pediatric Oncology Nurses, Amanda M. Schultz

Honors Undergraduate Theses

Pediatric oncology is known to be a stressful work environment due to the difficult aspects regarding patient care. This known stress related to work and caring for pediatric oncology patients can negatively impact nurses, patients, and families. The purpose of this study is to examine: relationships between patient symptom management and nurse distress; strategies used by nurses to manage symptoms in pediatric patients with cancer; nurse perceptions of the effectiveness of non-pharmacologic or nursing interventions; and nurse distress related to managing symptoms in pediatric patients with cancer. Registered nurses (N=13) at a local children’s hospital participated in an online survey. …

No One Fights Alone: Exploring Social Participation Of Young Adults With Cancer, Susan Blake Hodgson

Online Theses and Dissertations

Background: Young adults are relatively understudied and often misrepresented in oncology research and practice, as they are often overlooked or clumped in with pediatric or older adult patients. There is a gap in literature for young adults with cancer and this study was done in an effort to help bridge that gap while exploring social participation along with peer support. Social participation is the interweaving of occupations to support desired engagement in community and family activities as well as those involving peers and friends (American Occupational Therapy Association, 2014). This will not only elicit a better understanding of the impact …

Frontiers In Precision Medicine Ii: Cancer, Big Data And The Public, Emily Coonrod, Jorge L. Contreras, Willard Dere, Jeffrey Botkin, Leslie Francis, Jim Tabery

Utah Law Faculty Scholarship

Precision medicine is being developed within a complex landscape of public policy, science, economics, law, and regulation. In these and other policy areas, the goal of developing individually-tailored therapies poses novel challenges for health care research, delivery and policy. In this symposium, a range of experts in genetics, medicine, bioinformatics, intellectual property, health economics and bioethics identified and discussed many of the pressing questions raised by the development and practice of precision medicine. These and other issues will need to be taken into account as precision medicine moves ahead and becomes the standard of medical practice and care in the …

Application Of The Misclassification Simulation Extrapolation (Mc-Simex) Procedure To Log-Logistic Accelerated Failure Time (Aft) Models In Survival Analysis, Varadan Sevilimedu

College of Graduate Studies: Theses & Dissertations

Survival analysis is the study of time to event outcomes. Accelerated Failure Time models (AFT) serve as a useful tool in survival analysis to study the time of occurrence of an event and its relation to the covariates of interest. The accuracy of estimation of parameters in a model depends upon the correct measurement of covariates. Considering that perfect measurement of covariates is highly unlikely, it is imperative that the performance of the existing bias-correction methods be analyzed in AFT models. However, certain areas of bias-correction in AFT models still remain unexplored. One of these unexplored areas, is a situation …

A Prospective Follow-Up Of Quality Of Life, Depression, Andanxiety In Children With Lymphoma And Solid Tumors, Ni̇hal Sargin Yildirim, Meti̇n Demi̇rkaya, Betül Berri̇n Sevi̇ni̇r, Sali̇h Güler, Ayşe Pinar Vural, Candan Demi̇röz, Arzu Çirpan Kantarcioğlu

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was the determination and prospective follow-up of quality of life, depression, and anxiety in pediatric patients with cancer under chemotherapy, as well as the evaluation of related factors. Materials and methods: Fifty newly diagnosed pediatric cancer patients and their parents were prospectively monitored before, during, and after therapy, and tests were used. Results: Significantly lower quality of life scores were recorded during treatment, in the group with CNS tumors, in the group receiving chemotherapy plus radiotherapy plus surgery, in the inpatient-only treatment group, in the group receiving treatment for longer than 6 months, and …