Digital Commons Network^™

Exploratory Analysis Of The Spatial Distribution Of Adult Glioma Age-Adjusted County Incidence Rates, Nebraska Medicine, 2009-2019, Kendra Ratnapradipa, Amulya Yellala, Nicole Shonka

Journal Articles: Epidemiology

BACKGROUND: Central nervous system (CNS) cancers including gliomas have low incidence but high mortality. The age-adjusted incidence rate for CNS cancers is higher in Nebraska than nationally. This exploratory study was motivated by glioma patient inquiries about possible clustering of cases within the state to see if more in-depth investigation was warranted.

METHODS: Using electronic health records from Nebraska Medicine, we identified Nebraska adult (age ≥19) glioma patients diagnosed between January 1, 2009 and November 1, 2019. Patient residential addresses were geocoded, mapped, and combined with annual US Census data to compute age-adjusted incidence rates (AAIR) at the county level. …

Quality Of Life Among Cancer Survivors: Comparison Of Multiple Cancers Using Icare2, Shinobu Watanabe-Galloway, Rachael L. Schmidt, Kendra Ratnapradipa, Kristin Dickinson, Abbey Fingeret, Whitney Goldner

Manuscripts: Epidemiology

Background: The number of cancer survivors continues to increase due to dramatic improvements in cancer treatment, accounting for approximately 5% of the entire population. As cancer survivors continue to live longer, it is important to understand their quality of life (QoL) in order to maximize supportive care efforts.

Objectives: In this study, the quality of life (QoL) among patients with different types of cancer was examined. The objectives were to: 1) compare patient-reported outcome measures of QoL using the Short-Form (SF-36) Health Survey scores among patients of different cancer types and 2) identify demographic, oncologic, and clinical factors that are …

A Cross-Sectional Analysis Of Adverse Childhood Experience Exposure On Cancer Diagnosis Utilizing The 2022 Behavioral Risk Factor Surveillance Survey Data, Emma Zipperer

Capstone Experience

Objective: To determine the association between Adverse Childhood Experiences (ACEs) and cancer diagnosis based on ACE exposure levels.

Methods: We utilized data collected in the 2022 Behavioral Risk Factor Surveillance System (BRFSS) survey. The study population (n=54,148) was restricted to states that reported on the optional model of experiencing ACEs and those who responded about cancer diagnosis. A univariate analysis, bivariate analysis and a multivariate logistic regression were performed. Odds of cancer diagnosis among those with differing ACE exposure levels were calculated.

Results: High ACE exposure had 20% higher odds of cancer diagnosis when compared to low ACE exposure. White, …

Occupational Exposures Associated With Thyroid Cancer In The Thyroid Tumor And Cancer Collaborative Registry In The Integrated Cancer Center Repository For Cancer Research, James Buckley

Capstone Experience

Thyroid cancer is one of the fastest growing cancers in the United States, with the rate of new cases increasing from 5.2 per 100,000 in 1985 to 13.8 per 100,000 in 2019, with a peak of 14.5 per 100,000 in 2015. Increased thyroid cancer incidence is associated with certain occupations, including healthcare and agriculture. Most existing literature on occupational exposures and thyroid cancer evaluate their association in terms of occupation type and thyroid cancer, rather than specific occupational exposures and thyroid cancer. This study sought to utilize the wide range of occupational exposure data in the Integrated Cancer Center Repository …

Trends Of Human Papilloma Virus- Related Cancers And Hpv Vaccination In Nebraska From 2010 To 2018, Christelle Massumbu

Capstone Experience

Background:

Approximately 46,143 human papillomaviruses (HPV) related cancers are diagnosed annually in the United States. Although the HPV vaccine has been available in the United States since 2006, more than half of adolescents have not completed the HPV vaccine series. In Nebraska, the incidence rates of HPV-related cancers have increased from 2006 (5.7%) to 2018 (6.3%). Although cervical cancer has been highly studied, there is limited research and surveillance on head and neck, vaginal, vulvar, anal, and penile cancers in a state such as Nebraska, which experiences limited access to healthcare in its rural areas. Clarity about these aspects could …

A Walk In Two Worlds: An Indigenous Health Research Mentorship Model Developed From The Experiences Of Mentors And Mentees In A Cancer Research Education Program Aimed At Increasing Representation Of American Indians/Alaska Natives In Cancer Research And Healthcare Professions, Kiana Borengasser, Aislinn C. Rookwood, Joyce C. Solheim, Maurice Godfrey, Karen Taraszka Hastings, Keyonna King, Hannah Robbins, Mariah Abney, Rudy Smith Jr., Liliana Tamayo, Regina Emily Robbins

Capstone Experience

The National Cancer Institute promotes workforce development programs that aim to increase representation of American Indian/Alaska Natives in health science and research careers. One such program, Youth Enjoy Science at the University of Nebraska Medical Center, has employed American Indian/Alaska Native youth in mentored cancer research internships from 2017 to 2022. The primary purpose of this study was to examine mentor and mentee experiences of participation in Youth Enjoy Science research education internships to learn from their stories. We conducted semi-structured interviews with current and former Youth Enjoy Science mentees (n=8) and mentors (n=8). We analyzed and collectively re-storied the …

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 …

Functional Characterization Of Cancer-Associated Dna Polymerase Ε Variants, Stephanie R. Barbari

Theses & Dissertations

Replicative DNA polymerases ε (Polε) and δ (Polδ) achieve high fidelity DNA synthesis through a precise balance of polymerization and exonucleolytic proofreading. Errors that escape proofreading are corrected by DNA mismatch repair (MMR). Ultramutated human cancers with proficient MMR carry alterations in the exonuclease domain of Polε, which were initially predicted to abolish proofreading. However, functional studies in yeast of the most recurrent Polε-P286R variant suggested defects beyond a loss of exonuclease activity. Indeed, biochemical analysis of the yeast Polε-P286R analog revealed increased polymerization capacity in addition to decreased proofreading, which enables efficient mismatch extension and bypass of replication-blocking non-B …

Neutrophils In Pancreatic Cancer Progression, Paran Goel

Theses & Dissertations

Pancreatic cancer (PC) remains a challenge to modern-day cancer therapeutics, with a dismal five-year survival rate of 10%. Due to the pancreas's location and desmoplasia surrounding it, patients receive late diagnoses and fail to respond to chemotherapy regimens. Tumor-promoting inflammation, one of the emerging hallmarks of cancer, contributes to tumor cells' survival and proliferation. This inflammation is often the result of infiltrating leukocytes and pro-inflammatory cytokines released into the tumor microenvironment (TME).

Neutrophils, one of the most prominent immune cells in our body, play an essential role in sustaining this smoldering inflammation observed in the TME. Previously, our group has …

The Current Landscape Of Antibody-Based Therapies In Solid Malignancies, Ashu Shah, Sanchita Rauth, Abhijit Aithal, Sukhwinder Kaur, Koelina Ganguly, Catherine Orzechowski, Grish C. Varshney, Maneesh Jain, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies. The development of a therapeutic mAb with long-lasting clinical impact demands a prodigious understanding of target antigen, effective mechanism of action, gene engineering technologies, complex interplay between tumor and host immune system, and biomarkers for prediction of clinical response. This review discusses the various approaches used by mAbs for …

Dna Polymerase Ε: Replication Error Prevention And Consequences Of A Cancer-Associated Mutation, Chelsea R. Bulock

Theses & Dissertations

Genome integrity is necessary to prevent mutations and disease. During eukaryotic DNA replication, DNA polymerases ε (Polε) and δ (Polδ) synthesize the leading and lagging strand, respectively. Polε and Polδ also have exonuclease activity that acts in series with post-replicative mismatch repair (MMR) to remove replication errors. Defects in proofreading and MMR lead to an increase in mutations and cause cancer in humans. This dissertation focuses on several unresolved issues involving the relationship between Polε and Polδ in replication error avoidance. First, despite an abundance of data supporting the one-strand-one-polymerase replication fork model, defects in the fidelity of Polε have …

Neurolytic Celiac Plexus Blockade In Patients With Upper Intraabdominal Malignancies: An Evidence-Based Narrative Review, Kevin Wong, Apollo A. Stack, Madhuri Are

Graduate Medical Education Research Journal

Background: Cancer-related abdominal pain is a common symptom associated with upper intra-abdominal carcinoma, especially in patients with advanced disease and it has posed a significant therapeutic challenge to medical practitioners. Typically, cancer pain can be managed by following the World Health Organization 3-step analgesic ladder. However, analgesic use of opioids, the mainstay treatment for moderate-to-severe cancer-related pain, may be ineffective in a subset of cancer patients. Escalation of dosage may be limited by opioid-induced side effects. The aim of this study was to review the literature addressing the effect of neurolytic celiac plexus block (NCPB) on the palliation of pain …

Tobacco Cessation And Cancer Patients - Perspective Of An Ent Resident, Lauren Klute

Graduate Medical Education Research Journal

No abstract provided.

Genomic And Transcriptomic Alterations In Metabolic Regulators And Implications For Anti-Tumoral Immune Response, Ryan J. King

Theses & Dissertations

Metabolic and immune alterations are ubiquitous hallmarks of cancer that are established during the foundational mutations and are further selected upon to generate highly aggressive tumors. Recent evidence suggests that cancer cells employ an altered metabolism to induce immune evasion. To further discover the relationship between metabolism and immunity in cancer, this thesis aimed to discover potential candidates of interest by first examining the mucin family for differences, as they exert a wide range of activities in cancer, including altered metabolism and immune alterations. Unique differences lead to further profiling in pancreatic and esophageal cancer. In pancreatic cancer, CD73 was …

From Development To Therapy: A Panoramic Approach To Further Our Understanding Of Cancer, Brittany Poelaert

Theses & Dissertations

Solid tumors, such as pancreatic cancer, often result in dismally low survival outcomes for patients due to insufficient understanding of disease development and progression. Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and although oncogenic drivers (such as KRAS mutation or loss of tumor suppressor p53) and stages of disease development have been studied, further understanding of pancreatic cancer development is greatly needed. Studies from our laboratory have identified novel and varied functions of amyloid precursor-like protein 2 (APLP2) in the development and progression of pancreatic cancer. These functions include promoting cancer cell migration, …

Ligand-Installed Polymeric Nanocarriers For Combination Chemotherapy, Xinyuan Xi

Theses & Dissertations

Combination chemotherapy remains the mainstay of cancer treatment because such strategy targets different cell signaling pathways to decrease the likelihood of developing protective mechanisms by cancer cells, thereby delaying the onset of recurrence and prolonging the survival. The co-delivery of binary drug combination via a single nanocarrier provides benefits in reducing dose-limiting toxicities, improving the pharmacokinetic properties of the cargo, spatial-temporal synchronization of drug exposure, and synergistic therapeutic effects. Rational design of such regimen is crucial for maximizing the therapeutic effects since only certain drug ratios exposed to the target might be synergistic while other ratios exert additive or even …

The Role Of The Cxcr3 Signaling Axes In Pancreatic Ductal Adenocarcinoma, Andrew C. Cannon

Theses & Dissertations

Numerous cytokines promote pancreatic ductal adenocarcinoma (PDAC) progression and suppress anti-tumor immune response leading to poor prognosis in PDAC patients. Despite this, many cytokines, have not been investigated in PDAC. Bioinformatic analyses of PDAC microarray and RNA-Seq datasets were used to identify cytokines overexpressed in PDAC, confirm the expression of cognate receptors, determine the association of cytokines with patient survival and define key underlying molecular associations. Bioinformatic findings were validated using immunohistochemical (IHC) staining, comparative cytokine qPCR-array in Kras^LSL-G12D:TP53^LSL-R172H:Pdx1-Cre (KPC) and Kras^LSL-G12D:Pdx1-Cre (KC) PDAC models and multicolor immunofluorescence staining. Tail-vein injections of PDAC cells …

Development Of Hyaluronic Acid-Derived Macromolecular Agents For Multimodal Imaging Probes And Nanomedicine, William M. Payne

Theses & Dissertations

Cancer, one of the most challenging maladies facing modern medicine, is a complex family of diseases that requires a multifaceted treatment regime. In recent years, increased research effort has been placed on the development of nanoscale formulations as a potential method to improve therapeutic efficacy and offer better treatment. Both drug formulation and biomedical imaging has benefitted from the development of new, nanoscale agents. Hyaluronic Acid (HA), a naturally occurring glycosaminoglycan, is a promising platform for the development of new drug delivery systems. Furthermore, hyaluronic acid is the principal ligand for the cell surface receptor CD44, which is overexpressed on …

Neutrophils Are Mediators Of Metastatic Prostate Cancer Progression In Bone, Diane L. Costanzo-Garvey, Tyler Keeley, Adam J. Case, Gabrielle F. Watson, Massar Alsamraae, Yangsheng Yu, Kaihong Su, Cortney E. Heim, Tammy Kielian, Colm Morrissey, Jeremy S Frieling, Leah M. Cook

Journal Articles: Pathology and Microbiology

Bone metastatic prostate cancer (BM-PCa) significantly reduces overall patient survival and is currently incurable. Current standard immunotherapy showed promising results for PCa patients with metastatic, but less advanced, disease (i.e., fewer than 20 bone lesions) suggesting that PCa growth in bone contributes to response to immunotherapy. We found that: (1) PCa stimulates recruitment of neutrophils, the most abundant immune cell in bone, and (2) that neutrophils heavily infiltrate regions of prostate tumor in bone of BM-PCa patients. Based on these findings, we examined the impact of direct neutrophil-prostate cancer interactions on prostate cancer growth. Bone marrow neutrophils directly induced apoptosis …

Burden And Risk Of Non-Aids Defining Cancers In Hiv-Infected Persons Receiving Antiretroviral Therapy, Brittney L. Dickey

Theses & Dissertations

The burden of cancers not previously associated with an HIV infection, called non-AIDS defining cancers (NADCs), have increased in the years since highly active anti-retroviral therapy has been introduced. The studies in this dissertation attempted to quantify this burden via incidence and mortality compared to the general population. Further, an assessment of risk factors and creation of a predictive risk model, a nomogram, were utilized to better understand how factors associated with demographics, lifestyle, and immune response affected risk for an NADC diagnosis once therapy was initiated and HIV better controlled. Standardized incidence and mortality ratios showed that burden of …

Comorbidity Profile Of Head And Neck Cancer Patients With And Without Depression, Michaela Frenzel

Capstone Experience

This population-based retrospective study used SEER-Medicare data from 2002-2010 to assess depression, comorbidity, and substance use in the elderly head and neck cancer population. Out of 3,533 head and neck cancer patients, 10.6% had depression diagnoses two years prior to cancer diagnosis, 8.9% were newly diagnosed with depression within one year after cancer diagnosis, and 44.5% of those with preexisting depression had an additional depression diagnosis within one year following cancer diagnosis. Comorbid conditions (p<0.0001) and substance use (p=0.0017) showed associations with depression prior to cancer diagnosis yet, no significant associations with incidence of depression in this head and neck cancer population. This study affirms the need for continual depression screenings in head and neck cancer patients and suggests the need for increased research into the burden of comorbid conditions and substance use within the head and neck cancer population.

The Role Of Zyxin And Limd1 In Mitosis And Cancer, Jiuli Zhou

Theses & Dissertations

The Hippo signaling pathway, originally discovered in Drosophila, consists of a core kinase cascade and has been subsequently demonstrated to control tissue growth and tumorigenesis. The core of this pathway contains MST1/2 (Mammalian sterile 20-like kinase 1/2), LATS1/2 (large tumor suppressor 1/2) and downstream effector named Yes-associated protein (YAP) and PDZ-binding motif (TAZ). MST1/2 transduce their kinase activity mainly through directly phosphorylating LATS1/2. Once phosphorylated and activated, LATS1/2 subsequently phosphorylate and inhibit YAP/TAZ from translocating to nucleus, thereby suppressing the expression of downstream pro-growth and survival genes. While recent studies provide important insight into the tumor suppressor properties of …

Molecular Mechanisms Governing Muscle Wasting In Cancer, Aneesha Dasgupta

Theses & Dissertations

Pancreatic cancer is the third-leading cause of cancer-related deaths in the United States. About 80 percent of the pancreatic cancer patients suffer from cachexia and, about one-third die due to complexities related to the syndrome. Cachexia leads to a loss in body weight and cachectic patients are refractory to chemotherapy. Despite recent advances, the mechanisms of pancreatic cancer- cachexia and the potential therapeutic interventions remain poorly evaluated.

Sirtuins represent a class of proteins that are regulated by metabolic fluctuations in tissues. We observed a reduced expression of Sirt1 in spontaneous PDAC mice muscles, human pancreatic cancer muscles, and myotubes treated …

Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer

Theses & Dissertations

The Hippo pathway is conserved regulator of organ size through control of proliferation, apoptosis, and stem-cell self-renewal. In addition to this important function, many of the canonical signaling members have also been shown to be regulated during mitosis. Importantly, Hippo pathway components are frequently dysregulated in cancers and have attracted attention as possible targets for improved cancer therapeutics. Further exploration of Hippo-YAP (yes-associated protein) signaling has revealed new regulators and effectors outside the canonical signaling network and has revealed a larger non-canonical network of signaling proteins in which canonical Hippo pathway components crosstalk with important cellular homeostasis and apoptosis signaling …

Characterization Of Cancer Incidence In Chronic Kidney Disease Patients: A Single Center Study, 2008 – 2018, Jagadeesh Puvvula

Capstone Experience

Background: Chronic kidney disease (CKD) is an established risk factor for cardiovascular disease, but the significance of lower Glomerular filtration rate on incidence and mortality from cancer is uncertain. There is evidence that cancer risk and cancer mortality may be increased in individuals with End Stage Renal Disease (ESRD) requiring dialysis or after renal transplantation but whether less severe kidney disease is associated with cancer remains poorly understood.

Some studies indicate that these associations do appear to be organ specific. It has been reported that reduced renal function is associated with an increased risk of cancers of the kidney and …

A Pilot Partnership To Provide Health Information To Cancer Patients And Families, Christian I.J. Minter, Roxanne Cox, Mary Winter, Benjamin Simon, Rebecca Jackson

Posters and Presentations: Leon S. McGoogan Health Sciences Library

Objectives: McGoogan Library of Medicine at University of Nebraska Medical Center launched a pilot partnership with the new Resource and Wellness Center at Fred and Pamela Buffett Cancer Center in Omaha, NE. The goals of this pilot were to provide patients and families with easy access to quality health information, assess the health information needs of cancer patients and their families, and explore the demand for library services in the resource center.

Methods: From June 2017 through March 2018, library faculty and staff worked daily shifts at the Resource and Wellness Center and answered consumer health questions. Statistics were compiled …

Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson

Theses & Dissertations

Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …

The Survival And Treatment Refusal Of Lung Cancer Patients: Analyses Of National Cancer Registries, Poppy Deviany

Theses & Dissertations

Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer mortality of both genders in the United States. A recent report suggests that the relative five-year survival rate of lung cancer is only 18%. Studies indicate many factors are associated with the survival of lung cancer patients, including age at diagnosis. It is widely known as a disease of older people, but the literature shows a substantial number of young people have been diagnosed with lung cancer. The literature also indicates that the refusal of recommended treatment contributes to cancer-related death and poorer survival. The …

Matters Of Trust: Examination Of The Patient-Provider Relationship In Cancer Care, Krista A. Brown

Capstone Experience

Background: The intangible concept of trust is critical in the patient-provider relationship. Cancer patients may experience positive and negative impacts of trust in this relationship to a higher degree due to the inherently serious nature of their disease and the level of dependence upon treatment providers.

Objective: The goal of this study was to compare colorectal cancer patients’ levels of trust in their primary care physician and oncologist, along with examining trust differences associated with demographics and other characteristics.

Methods: Colorectal cancer patients (n=158) treated at Nebraska Medicine and consented into the Integrated Cancer Repository for Cancer Research IRB …

Development Of Neurotensin-Based Radiopharmaceuticals For Neurotensin-Receptor-1-Positive Tumors Targeting, Yinnong Jia

Theses & Dissertations

The neurotensin receptor 1 (NTR1) is overexpressed in many cancers, due to its role as a growth pathway. These NTR1-positive cancers include pancreatic, colon, prostate and breast cancers. In the radiopharmaceutical field, the overexpression of NTR1 in cancer has prompted the development of NTR1-targeted diagnostics and therapeutics. The neurotensin (NT) peptide exhibits low nanomolar affinity for NTR1 and has been the paradigm for NTR1-targeted agents. Since the 1980’s, radiolabeled NT analogs have been developed and evaluated for targeting NTR1-positive cancers. Since native NT is rapidly degraded in vivo by a variety of peptidases, a tremendous amount of effort has been …