Oncology Commons^™

A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey

Arts & Sciences Electronic Theses and Dissertations

The implementation of next-generation genomic sequencing has exploded over the past dozen years. Large consortia, such as The Cancer Genome Atlas (TCGA); the International Cancer Genetics Consortium (ICGC); and the Pediatric Cancer Genome Projects (PCGP), made great strides in democratizing big data for the scientific community. These data sets provide a rich resource to build tools for somatic variant discovery and exploratory analysis. Public repositories hold the answer to many novel biological and clinical revelations i.e., the discovery of complex indels, splice creating mutations, alternative super enhancer binding sites, machine learning models to predict mutation impact, and cancer subtype classification …

Shoulder-Specific Patient Reported Outcome Measures For Use In Patients With Head And Neck Cancer:An Assessment Of Reliability, Construct Validity, And Overall Appropriateness Of Test Score Interpretation Using Rasch Analysis, Melissa Michelle Eden

Department of Physical Therapy Student Theses, Dissertations and Capstones

Context: Medical management for head and neck cancer (HNC) often includes neck dissection surgery, a side effect of which is shoulder dysfunction. There is no consensus for which patient-reported outcome measure (PRO) is most appropriate to quantify shoulder dysfunction in this population.

Objective: The aims of this research study were to: (1) use Rasch methodologies to assess construct validity and overall appropriateness of test score interpretation of Disability of the Arm, Shoulder and Hand (DASH), QuickDASH, Shoulder Pain and Disability Index (SPADI) and Neck Dissection Impairment Index (NDII) in the HNC population; (2) determine appropriateness of use of University of …

Care Of Adult Cancer Survivors, Kelsey Kloosterman

Doctoral Projects

As innovative cancer treatments emerge, more people are surviving cancer. Cancer survivors have multiple and unique healthcare needs due to their cancer and cancer treatments. Communication among those treating the cancer, primary care providers, and cancer survivors is necessary to coordinate care once treatment is finished. The development of a survivorship care plan that is reviewed with the cancer survivor is intended to facilitate communication among all stakeholders. This quality improvement project examined current practice in a survivorship clinic in a Midwestern health system cancer center that cares for a variety of types of cancer patients. By reviewing evidence in …

Genetic Evolution And Prognostic Determinants Of Pancreatic Cancer On Longitudinal Liquid Biopsies, Vincent Bernard

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates amongst solid tumors. As early detection of PDAC is unusual and typically incidental, most patients present with locally advanced and metastatic disease where effective therapeutic strategies remain a significant unmet need. Specifically, surrogate biomarkers for tumor monitoring of PDAC may lead to improved elucidation of clinical actionability and prognostic potential. On the other hand, tumor tissue is rarely sampled in patients presenting with de novo or recurrent metastatic PDAC, apart from a fine needle aspiration or a core needle biopsy performed for diagnosis. This precludes the opportunity for …

Actinomycin D And Telmisartan Combination Therapy Targets Lung Cancer Stem Cells, Ryan Green

USF Tampa Graduate Theses and Dissertations

The failure of lung cancer treatments has been attributed partly to the development of drug resistance, however the underlying cellular and molecular mechanisms are poorly understood. It has been suggested that a very small group of specific cells within the heterogeneous tumors, cancer initiating stem cells (CSC), develop resistance to treatment, survive and later initiate the growth of new tumors. Due to their pivotal role in maintenance and relapse of tumors following the acquisition of drug resistance, we reasoned that novel drugs targeting cancer cells and CSC might provide the most effective treatments, if not a cure. To this end, …

Elucidating Mechanisms Of Innate And Acquired Resistance To Pi3ka Inhibition In Head And Neck Squamous Cell Carcinoma, Kara M. Ruicci

Electronic Thesis and Dissertation Repository

The phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signalling pathway is aberrantly activated in most head and neck squamous cell carcinomas (HNSCCs). PI3K signalling drives cellular proliferation, protein synthesis and cell survival. Although numerous targeted agents are available to inhibit PI3K signalling, results have been variable and factors influencing response to PI3K inhibition (e.g. genomic aberrations, pathway interconnectivity, acquired drug resistance) are not well defined. In this thesis, we employ a multifaceted approach to elucidate the molecular underpinnings of biomarkers of response and mediators of resistance to PI3K inhibition in HNSCC. We began by combining a large panel of HNSCC …

Impact Of Feeding Tube Status On Health Outcomes For Individuals With Oropharyngeal Cancer, Nedeljko Jovanovic

Electronic Thesis and Dissertation Repository

Abstract

This study investigated differences in outcomes related to health, swallowing, and quality of life (QoL) for individuals with oropharyngeal squamous cell carcinoma (OPSCC) receiving either radiotherapy (RT) alone, or concomitant chemoradiotherapy (CRT). Differences were assessed based on whether patients received a feeding tube (FT group) or not (NFT group). Measures including the Functional Oral Intake Scale (FOIS), Performance Status Scale for Head and Neck Cancer (PSS-HN), M.D. Anderson Dysphagia Inventory (MDADI), and weight were collected for 126 individuals at baseline, and at 3, 6, and 12 months post-treatment. Data were analyzed to identify potential prognostic differences between the groups, …

A Multi-Level Assessment Of Healthcare Facilities Readiness, Willingness, And Ability To Adopt And Sustain Telehealth Services, Jamie Larson

Theses & Dissertations

Telehealth technologies are becoming more pervasive throughout the healthcare system as a way to provide services to patients that would otherwise have difficulty with access. Currently, little is known about the current state of telehealth use within clinics and hospital in the US. Most studies evaluating telehealth programs are feasibility or small patient outcome studies from one location. Utilizing a hybrid framework combining the levels of complex socio-technical systems with the theory of ready, willing and able. The theory of ready, willing, and able is founded on the basis that these three preconditions need to be met for a change …

Kdm6b Is Required For Self-Renewal Of Normal And Leukemic Mouse Stem Cells Under Proliferative Stress, Cates Mallaney

Arts & Sciences Electronic Theses and Dissertations

KDM6B (JMJD3) is one of two known epigenetic modifiers responsible for the removal of the repressive histone mark, histone-3 lysine-27 trimethylation (H3K27me3), and has been shown to play a role in development, differentiation, and inflammatory stress response. Unlike the other H3K27me3 demethylase, UTX (KDM6A), which is frequently mutated in hematopoietic malignancies, KDM6B is upregulated in a myriad of blood disorders. This suggests that it may have important functions in the pathogenesis of hematopoietic cancers. Here, we examined the role of Kdm6b in hematopoietic stem cell (HSC) fate decisions under normal and malignant conditions to evaluate its potential as a therapeutic …

Analytical Models Of Neutron Spectral Fluence, Kerma And Absorbed-Dose For Proton Therapy, Suman Shrestha

LSU Master's Theses

Abstract

Purpose: The accurate prediction of stray neutron dose has become increasingly important as it increases the risk of second cancer development after proton therapy. Previously reported analytical models predicted the quantity dose equivalent, which includes physical and biological considerations but does not explicitly take into account material dependence and variation in the radiation quality. The purpose of this study was to investigate the feasibility of an analytical model of absorbed dose to water from stray neutrons in proton therapy.

Methods: To calculate neutron absorbed dose and kerma in water, the authors developed analytical models of neutron spectral fluence and …

Design, Fabrication, And Validation Of 3d Printed, Patient-Specific Compensators For Postmastectomy Radiation Therapy, Daniel Craft

Dissertations & Theses (Open Access)

The purpose of this study was to use 3D printed, patient-specific tissue compensators to overcome the 3D planning limitations for postmastectomy radiation therapy (PMRT). Tissue compensators can be used to reduce dose heterogeneity, hot and cold spots at field junctions, and treatment complexity, but are currently seldom used due to the difficulty in designing, fabricating, and validating them.

To produce compensators using 3D printing technology, suitable materials had to be found and characterized. Several materials were found to be promising, but previously unreported material uncertainties were also discovered that must be carefully controlled for in 3D printing studies. A new …

Development And Commissioning Of An Independent Peer Review System For A Small Animal Irradiator, Mary Peters

Dissertations & Theses (Open Access)

Dosimetry for small animal irradiators lacks the standardization of clinical radiotherapy practice, yet plays a central translational role in human trial design. The purpose of this work was to improve the dosimetric accuracy and consistency of animal studies by developing an independent peer review system to verify dose delivery from animal irradiators. This study focused on the development of a mouse phantom and characterization of the thermoluminescent dosimetry system for a commonly used small animal irradiator.

First, a mouse model and irradiation stand were designed with the purpose of being used in a mailable audit. Two mouse phantoms were machined …

Equipment To Address Infrastructure And Human Resource Challenges For Radiotherapy In Low-Resource Settings, Rachel Mccarroll

Dissertations & Theses (Open Access)

Millions of people in low- and middle- income countries (LMICs) are without access to radiation therapy and as rate of population growth in these regions increase and lifestyle factors which are indicative of cancer increase; the cancer burden will only rise. There are a multitude of reasons for lack of access but two themes among them are the lack of access to affordable and reliable teletherapy units and insufficient properly trained staff to deliver high quality care. The purpose of this work was to investigate to two proposed efforts to improve access to radiotherapy in low-resource areas; an upright radiotherapy …

Wnt/Β-Catenin Mediated Cancer Stem Cell Activation In Hepatocellular Carcinoma., Harshulkumar M. Pandit

Electronic Theses and Dissertations

Hepatocellular carcinoma (HCC) is one of the deadliest cancers, with variable presentation, high chemotherapy resistance and early tumor recurrence. In this dissertation, we have systematically enriched, identified and characterized HCC cancer stem cells (CSCs) from 3 different HCC cell lines (Hepa1-6, HepG2, and Hep3B) using in vitro serum-free culture method. Enriched spheroids acquired CSC properties, primarily self-renewal capability, spheroid formation ability, and drug resistance. Heterogeneous CSCs enriched from Hepa1-6 cells demonstrated higher tumor initiation and proliferation capability in vivo, compared to control HCC cells in orthotopic immunocompetent mouse model. EpCAM+ CSCs were significantly enriched within heterogeneous Hepa1-6 CSC spheroids. Consequently, …

Omics Approaches To Uncover Germline And Somatic Variation Underlying Inherited Sarcomagenesis, Justin Wong

Dissertations & Theses (Open Access)

Sarcomas are rare mesenchymal tumors, making up 15% of all childhood and 1% of all adult tumors. They account for a disproportionate share of mortality in young adults, and if left untreated, are highly likely to metastasize. However, sarcoma etiology is poorly understood, and having numerous histological subtypes has complicated elucidation. To better understand factors underlying sarcomagenesis, we leveraged two rare inherited cancer predisposition syndromes, Li-Fraumeni Syndrome (LFS), and LFS-like (LFSL), both with a high incidence of sarcomas. LFS is caused by mutations in the tumor suppressor gene TP53 (p53), but has variable and incomplete penetrance, suggesting additional acquired …

Investigation Of Stereotactic Body Radiation Therapy Delivery Accuracy On An Elekta Linear Accelerator, Addie Barron

LSU Master's Theses

Purpose: This work investigated the delivery accuracy of high-dose lung and spine stereotactic treatments delivered with the Elekta Infinity and Versa HD platforms. The accuracy of these platforms will be used for consideration in implementing a spine stereotactic radiosurgery (SSRS) program at Mary Bird Perkins Cancer Center.

Methods: A geometric phantom was used to perform Winston-Lutz type tests that assessed the relevant degrees of freedom (gantry, collimator, and couch) of the delivery system. A lung stereotactic body radiation therapy (SBRT) and spine SRS treatment plan were generated for use in end-to-end testing. Delivery accuracy was tested using a novel diode …

Fatigue-Related Symptom Clusters And Their Relationship With Depression, And Functional Status In Older Adults Hospice Patients With Cancer., Suzan Fouad Abduljawad

USF Tampa Graduate Theses and Dissertations

The hospice care population with cancer are often older adults who report many cancer-related symptoms experienced often in clusters. Most prevalent of these symptoms is fatigue and often it co-occurs with depressive symptoms and poor physical functioning. This dissertation examined fatigue, symptom clusters, depression, physical activity, and functional status in older adults with cancer. The aims of the literature review were to understand the relationship among physical functioning, cancer fatigue, fatigue-related symptom clusters, and their relationship with functional status In older adults. The literature related to these associations is insufficient and inconclusive. The methods section aimed to investigate the reliability …

Inference And Analysis Of Multilayered Mirna-Mediated Networks In Cancer, Duc Do

Dissertations (1934 -)

MicroRNAs (miRNAs) are small noncoding transcripts that can regulate gene expression, thereby controlling diverse biological processes. Aberrant disruptions of miRNA expression and their interactions with other biological agents (e.g., coding and noncoding transcripts) have been associated with several types of cancer. The goal of this dissertation is to use multidimensional genomic data to model two different gene regulation mechanisms by miRNAs in cancer. This dissertation results from two research projects. The first project investigates a miRNA-mediated gene regulation mechanism called competing endogenous RNA (ceRNA) interactions, which suggests that some transcripts can indirectly regulate one another's activity through their interactions with …

Electron Monte Carlo Dose Calculation Model Dependency On Optional Applicator Specific 1d Profiles, Ryan Sharp

UNLV Theses, Dissertations, Professional Papers, and Capstones

The accuracy of a calculated dose distribution compared to the actual dose administered to a patient undergoing electron radiation treatment is dependent upon the configured electron dose calculation algorithm in the treatment planning system (TPS). Configuration of the electron Monte Carlo (eMC) algorithm in the Eclipse TPS requires a variety of beam scan data. One of the required data sets is the inclusion of optional in air crossplane (CP) and inplane (IP) profiles. It is unknown if the inclusion of the optional profiles into the eMC algorithm greatly influences the output of the TPS. Two eMC algorithms were configured in …

Increasing Ph In Cancer: Enabling A New Therapeutic Paradigm Using Novel Carbonate Nanoparticles, Avik Som

McKelvey School of Engineering Theses & Dissertations

Enormous progress has been made to treat cancer, and yet the mortality rate of cancer remains unacceptably high. High clinical resistance to molecularly targeted therapeutics has pushed interest again towards inhibiting universal biochemical hallmarks of cancer. Recent evidence suggests that malignant tumors acidify the local extracellular environment to activate proteases for degrading the tumor matrix, which facilitates metastasis, and explains why more aggressive tumors are more acidic. Current therapies have only focused on using the low pH for enhancing drug release in tumors, thereby still relying on the traditional paradigm of intracellular inhibition of pathways, a method that continues to …

Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar

Arts & Sciences Electronic Theses and Dissertations

Paired tumor-normal sequencing of thousands of patient’s exomes has revealed millions of somatic mutations, but functional characterization and clinical decision making are stymied because biologically neutral ‘passenger’ mutations greatly outnumber pathogenic ‘driver’ mutations. Since most mutations will return negative results if tested, conventional resource-intensive experiments are reserved for mutations which are observed in multiple patients or rarer mutations found in well-established cancer genes. Most mutations are therefore never tested, diminishing the potential to discover new mechanisms of cancer development and treatment opportunities. Computational methods that reliably prioritize mutations for testing would greatly increase the translation of sequencing results to clinical …

Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer

Arts & Sciences Electronic Theses and Dissertations

Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are …

Functional Signature Ontology-Based Identification And Validation Of Novel Therapeutic Targets And Natural Products For The Treatment Of Cancer, Beth Neilsen

Theses & Dissertations

Multiple studies have revealed that Ras-driven tumors acquire vulnerabilities by adapting cellular mechanisms that promote uncontrolled proliferation and suppress apoptosis. Kinase Suppressor of Ras 1 (KSR1) modulates ERK activation downstream of oncogenic Ras, and knockdown of KSR1 selectively kills malignant, Ras-driven cancer cells, but does not kill immortalized, non-transformed human colon epithelial cells (HCECs). KSR1^-/- mice are fertile and phenotypically normal, but resistant to Ras-driven tumor formation suggesting KSR1 represents a vulnerability in cancer cells.

To identify additional vulnerabilities in cancer, a screening approach termed Functional Signature Ontology (FUSION) was used to screen 14,355 genes and 1,200 natural product …

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 …

Treating Breast Cancer With Light: The Creation Of Two Photodynamic Therapy Agents, Victoria Lackey

Honors Theses

Photodynamic therapy (PDT) is a treatment for a wide display of diseases, including cancer, that has become gradually widespread. The procedure requires the usage of photosynthesizing agents, which are activated in the presence of light. One quite successful photodynamic therapy agent is an aromatic structure made up of four pyrrole rings called a porphyrin. This research focused on producing the water-soluble porphyrins, H2TPP-3-PEG-OH and H2TPP-PiperMe-OH, through the attachment of the starting porphyrin, H2TPPC, with 3-polyethyleneglycol and 3-piperidinemethanol, respectively. The novel, water-soluble agent was purified and characterized by infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR), and UV-vis spectroscopy. Purity was …

Development Of 3d-Printed Patient Specific Bolus For Clinical Use In Total Scalp Irradiation, Garrett Baltz

Dissertations & Theses (Open Access)

Total scalp irradiation (TSI) is a specialized radiation therapy technique that aims to deliver a uniform dose to the entire scalp. Original electron-based TSI techniques had limited homogeneity due to hot and cold spots created at field junctions due to the multiple matched fields that were required to treat the entire scalp. The transition to photon volumetric-modulated arc therapy based TSI techniques has improved homogeneity, to the point where non-conformal bolus is now a limiting factor. Bolus is required to build-up full dose to the scalp surface in total scalp irradiation. Creating bolus that is conformal to the scalp is …

Patient Attitudes Toward Genetic Testing For Inherited Predispositions To Hematologic Malignancies, Taylor Beecroft

Dissertations & Theses (Open Access)

Although inherited predispositions to hematologic malignancies have previously been considered extremely rare, approximately 12 causative genes have been implicated in the last decade. Since individuals diagnosed with leukemia have not historically been considered for evaluation of inherited predispositions, genetic testing is underperformed in this population. This study used focus group discussions to explore the attitudes, motivations, and barriers to genetic testing for 23 patients with leukemia. Participants generally exhibited a positive regard for the utility of genetic testing, and were primarily motivated by concern for their family and a sense of altruism toward all leukemia patients. While drawbacks and barriers …

Quantification Of Tumor-Associated Macrophages Following Immunomodulation Therapy In A Murine Allograft Model Of Colorectal Carcinoma, Caroline Spainhour

Biomedical Engineering Undergraduate Honors Theses

Colorectal Carcinoma (CRC) is one of the deadliest cancers in the world, with 150,000 new cases annually in the United States. Traditional treatments include chemotherapy and invasive surgery; however, research has shown that only 25% of patients that undergo traditional treatment have a positive result. Immunotherapy is an emerging form of cancer treatment that utilizes the patients’immune system to fight cancer cells by targeting inflammation, which plays a large role in the proliferation and metastasis of cancer cells.

Tumor-associated macrophages (TAMs) are immune cells that affect the inflammatory microenvironment of tumors. TAMs are M1 in the early stages of tumors, …

Symptom Clusters And Quality Of Life Trajectories In Breast Cancer Patients Before And After Chemotherapy, Gaurav Kumar

Capstone Experience

Context. Breast cancer patients experience multiple concurrent symptoms before and after chemotherapy (CTX). Physical and psychological symptoms may persist after treatment and reduce the quality of life (QOL) of survivors.

Objectives. Identify differences in prevalence and severity of symptoms at three times within 1- year of starting CTX; and identify symptom cluster and QOL trajectories over these times in breast cancer patients.

Methods. Symptoms were identified in breast cancer patients (N=219) before the start of CTX (baseline), 30 days after the last CTX, and 1-year after the first CTX. Hospital Anxiety and Depression Scale and Symptom Experience Scale …

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 …