Medicine and Health Sciences Commons^™

Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang

Dissertations & Theses (Open Access)

Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important …

Influences On Self-Care In Women With Heart Failure: A Pilot Study, Joy Corcione

Dissertations & Theses (Open Access)

Background: Heart Failure self-care becomes exceedingly difficult to perform as the disease progresses; therefore social support becomes important in facilitating heart failure self-care. Woman with heart failure represent a significant and growing vulnerable population. Women tend to have lower self-confidence in providing self-care, experience greater negative emotions, decreased social support, experience more adverse psychosocial factors affecting self-care and experience greater psychosocial adversity than do men. Self-care is vital in managing heart failure and social support greatly facilitates self-care behaviors.

Purpose: The purpose of this pilot study was to gain a deeper understanding about the sources of perceived social support and …

Repetitive, Pre-Anesthetic Fasting And Malnutrition In A Pediatric Oncology Population Undergoing Radiation Therapy, Laura P. Santibáñez

Dissertations & Theses (Open Access)

Background: Pediatric oncology patients often experience nutritional status changes, particularly malnutrition, which may adversely affect their outcomes. Although the consequences of malnutrition are elucidated, its causes remain unclear. A possible cause of malnutrition in pediatric oncology patients is repetitive, pre-anesthetic fasting prior to non-invasive procedures and treatments, such as anesthesia-assisted radiation therapy (AART). This exploratory study investigated the association between repetitive, pre-anesthetic fasting and non-fasting days and malnutrition in pediatric oncology patients receiving AART.

Procedure: A retrospective cohort of 138 pediatric oncology patients (£ 10 years of age) who received any type of radiation therapy (RT) with or without anesthesia …

Epigenetic Modulation In Braf Mutated Metastatic Colorectal Cancer, Van Morris

Dissertations & Theses (Open Access)

Introduction: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer (mCRC). Unlike other tumors with the same mutation, BRAF inhibitors are ineffective as monotherapy. CRC tumors with BRAF V600E mutations are associated with global hypermethylation, which may turn off tumor suppressor gene expression. We studied demethylation in BRAF V600E mCRC to restore sensitivity to BRAF inhibitors.

Methods: Tumor databanks were investigated for genes differentially expressed according to BRAF mutation status to identify genes which may be particularly susceptible to epigenetic influence. Mouse xenograft models of BRAFV600E mCRC were treated with vemurafenib or azacitidine, alone …

Regulation Of Breast Cancer Initiation And Progression By 14-3-3zeta, Chia-Chi Chang

Dissertations & Theses (Open Access)

14-3-3ζ is a ubiquitously expressed family member of proteins that have been implicated to have oncogenic potential through its interactions and involvement in cancer initiation and progression. 14-3-3ζ belongs to the highly conserved 14-3-3ζ protein family and modulates numerous pathways in cancer. Overexpression of 14-3-3ζ is an early event, occurs in more than 40% of human breast cancer cases, and is associated with disease recurrence and poor prognosis. Metabolic reprogramming is a hallmark of cancer. Cancer cells elevate aerobic glycolysis to produce metabolic intermediates and reducing equivalents, thereby facilitating cellular adaptation to the adverse environment and sustaining fast proliferation. Interestingly, …

Cll Metabolism Is Regulated By Prognostic Factors, Modulated By Stroma And Abrogated By Pi3k Inhibition, Hima Vangapandu

Dissertations & Theses (Open Access)

Metabolism of chronic lymphocytic leukemia (CLL), a disease characterized by the relentless accumulation of mature B cells has been little explored. Bone marrow stromal cells provide a survival benefit to CLL cells, in part through PI3K/AKT pathway. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in quiescent malignant B lymphocytes from CLL patients. Glycolysis (extracellular acidification rate, ECAR) was consistently low in CLL samples, but oxygen consumption (OCR) varied considerably. Higher OCR was associated with poor prognostic factors such as ZAP 70 positivity, unmutated IgVH, high β2M levels, and higher Rai stage. Co-culture with the …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations & Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Psychometric Performance Of The Arabic Versions Of The Cancer Behavior Inventory‐Brief And The Functional Assessment Of Cancer Therapy‐Breast In Saudi Arabia, Maaidah M. Algamdi Msn

Dissertations & Theses (Open Access)

Background: Arabic is the mother tongue of 26 countries, including Saudi Arabia where cancer is the fourth leading cause of death. Cancer is a sensitive issue in the Arabic population and a clear understanding of patients’ perceptions of self-efficacy for coping with cancer and quality of life helps assess interventions designed to facilitate optimal patient outcomes. In preliminary studies, the Cancer Behavior Inventory-Brief (CBI-B) was translated and back translated between English and Arabic, and reviewed for translational validity by an expert panel. The Arabic version of the CBI-B (CBI-BA) had acceptable evidence of translational validity with an overall translational validity …

Clinical And Demographic Variables Associated With Cognitive Deficits, Symptom Severity, And Duration After Concussive Injury In Adolescents: A Retrospective Study, Seema S. Aggarwal

Dissertations & Theses (Open Access)

Background: Concussions in adolescents are a public health concern with the growing popularity of high school sports. Recent legislation mandates that athletes who are suspected of a concussion be cleared to return-to-play by a clinician. More research is needed to develop a concussion predictive model to identify populations at risk for more severe and prolonged symptoms and long-term neurologic deficits.

Aims: The aims of this study were to (1) examine the effect of race and gender on neurocognitive and symptom scores and (2) determine which clinical (e.g., number of concussions, migraine history, learning disabilities/ attention deficit disorders) and demographic factors …

Poly (Adp) Ribose Polymerase Inhibitors For The Treatment Of Malignant Peripheral Nerve Sheath Tumor, Christine M. Kivlin

Dissertations & Theses (Open Access)

Malignant peripheral nerve sheath tumor (MPNST) is a rare subtype of soft tissue sarcoma. Surgical excision has remained the standard of care for this highly aggressive malignancy for over a decade. Conventional chemotherapy and radiotherapy have shown limited efficacy in MPNST; therefore, it is imperative that targeted treatment be identified to improve the outcome for MPNST patients. Poly (ADP) ribose polymerase (PARP) inhibitors were first reported over a decade ago to have substantial anti-tumorigenic effects in malignancies with defective DNA repair, specifically those with BRCA1/2 (breast cancer, early onset 1/2) mutations. Further evaluation of these inhibitors has shown multiple mechanisms …