Oncology Commons^™

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 …

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 …

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 …

Improved Therapy For Medulloblastoma: Targeting Hedgehog And Pi3k-Mtor Signaling Pathways In Combination With Chemotherapy, Nagendra K. Chaturvedi, Matthew J. Kling, Don W. Coulter, Timothy R. Mcguire, Sutapa Ray, Varun Kesherwani, Shantaram S. Joshi, J. Graham Sharp

Journal Articles: Radiation Oncology

Aberrant activation and interactions of hedgehog (HH) and PI3K/AKT/mTOR signaling pathways are frequently associated with high-risk medulloblastoma (MB). Thus, combined targeting of the HH and PI3K/AKT/mTOR pathways could be a viable therapeutic strategy to treat high-risk patients. Therefore, we investigated the anti-MB efficacies of combined HH inhibitor Vismodegib and PI3K-mTOR dual-inhibitor BEZ235 together or combined individually with cisplatin against high-risk MB. Using non-MYC- and MYC-amplified cell lines, and a xenograft mouse model, the in vitro and in vivo efficacies of these therapies on cell growth/survival and associated molecular mechanism(s) were investigated. Results showed that combined treatment of Vismodegib and BEZ235 …

Aminoglycosides Rapidly Inhibit Nad(P)H Metabolism Increasing Reactive Oxygen Species And Cochlear Cell Demise, Danielle E. Desa, Michael G. Nichols, Heather Jensen Smith

Journal Articles: Eppley Institute

Despite causing permanent hearing loss by damaging inner ear sensory cells, aminoglycosides (AGs) remain one of the most widely used classes of antibiotics in the world. Although the mechanisms of cochlear sensory cell damage are not fully known, reactive oxygen species (ROS) are clearly implicated. Mitochondrial-specific ROS formation was evaluated in acutely cultured murine cochlear explants exposed to gentamicin (GM), a representative ototoxic AG antibiotic. Superoxide (O2·-) and hydrogen peroxide (H2O2) were measured using MitoSOX Red and Dihydrorhodamine 123, respectively, in sensory and supporting cells. A 1-h GM exposure significantly increased O2·- formation in IHCs and increased H2O2 formation in …

Microscale Gene Expression Analysis Of Tumor-Associated Macrophages, Kuldeep S. Attri, Kamiya Mehla, Surendra K. Shukla, Pankaj K. Singh

Journal Articles: Eppley Institute

Macrophages, apart from being the key effector cells of the innate immune system, also play critical roles during the development and progression of various complex diseases, including cancer. Tumor-associated macrophages, infiltrate tumors during different stages of cancer progression to regulate motility, invasion, and intravasation to metastatic sites. Macrophages can exist in different polarization states associated with unique function in tumors. Since tumor-associated macrophages constitute a very small proportion of tumor cells, analysis of gene expression pattern using normal extraction buffer-based methods remains a challenging task. Therefore, it is imperative to develop low-throughput strategies to investigate transcriptional regulations from a small …

Phosphoinositide 3-Kinase Signaling Pathway In Pancreatic Ductal Adenocarcinoma Progression, Pathogenesis, And Therapeutics, Divya Murthy, Kuldeep S. Attri, Pankaj K. Singh

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by its sudden manifestation, rapid progression, poor prognosis, and limited therapeutic options. Genetic alterations in key signaling pathways found in early pancreatic lesions are pivotal for the development and progression of pancreatic intraepithelial neoplastic lesions into invasive carcinomas. More than 90% of PDAC tumors harbor driver mutations in K-Ras that activate various downstream effector-signaling pathways, including the phosphoinositide-3-kinase (PI3K) pathway. The PI3K pathway also responds to stimuli from various growth factor receptors present on the cancer cell surface that, in turn, modulate downstream signaling cascades. Thus, the inositide signaling acts …

Met Receptor Inhibitor Su11274 Localizes In The Endoplasmic Reticulum, Edwin J. Wiest, Heather Jensen Smith, Michael A. Hollingsworth

Journal Articles: Eppley Institute

We discovered that SU11274, a class I c-Met inhibitor, fluoresces when excited by 488 nm laser light and showed rapid specific accumulation in distinct subcellular compartments. Given that SU11274 reduces cancer cell viability, we exploited these newly identified spectral properties to determine SU11274 intracellular distribution and accumulation in human pancreatic cancer cells. The aim of the studies reported here was to identify organelle(s) to which SU11274 is trafficked. We conclude that SU11274 rapidly and predominantly accumulates in the endoplasmic reticulum.