Matching Items (154)
Description
Almost every form of cancer deregulates the expression and activity of anabolic glycosyltransferase (GT) enzymes, which incorporate particular monosaccharides in a donor acceptor as well as linkage- and anomer-specific manner to assemble complex and diverse glycans that significantly affect numerous cellular events, including tumorigenesis and metastasis. Because glycosylation is not template-driven, GT deregulation yields heterogeneous arrays of aberrant intact glycan products, some in undetectable quantities in clinical bio-fluids (e.g., blood plasma). Numerous glycan features (e.g., 6 sialylation, β-1,6-branching, and core fucosylation) stem from approximately 25 glycan “nodes:” unique linkage specific monosaccharides at particular glycan branch points that collectively confer distinguishing features upon glycan products. For each node, changes in normalized abundance (Figure 1) may serve as nearly 1:1 surrogate measure of activity for culpable GTs and may correlate with particular stages of carcinogenesis. Complementary to traditional top down glycomics, the novel bottom-up technique applied herein condenses each glycan node and feature into a single analytical signal, quantified by two GC-MS instruments: GCT (time-of-flight analyzer) and GCMSD (transmission quadrupole analyzers). Bottom-up analysis of stage 3 and 4 breast cancer cases revealed better overall precision for GCMSD yet comparable clinical performance of both GC MS instruments and identified two downregulated glycan nodes as excellent breast cancer biomarker candidates: t-Gal and 4,6-GlcNAc (ROC AUC ≈ 0.80, p < 0.05). Resulting from the activity of multiple GTs, t-Gal had the highest ROC AUC (0.88) and lowest ROC p‑value (0.001) among all analyzed nodes. Representing core-fucosylation, glycan node 4,6-GlcNAc is a nearly 1:1 molecular surrogate for the activity of α-(1,6)-fucosyltransferase—a potential target for cancer therapy. To validate these results, future projects can analyze larger sample sets, find correlations between breast cancer stage and changes in t-Gal and 4,6-GlcNAc levels, gauge the specificity of these nodes for breast cancer and their potential role in other cancer types, and develop clinical tests for reliable breast cancer diagnosis and treatment monitoring based on t-Gal and 4,6-GlcNAc.
ContributorsZaare, Sahba (Author) / Borges, Chad (Thesis director) / LaBaer, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Research supports that music therapy can be used in multiple aspects of care for patients living within different environments. There is a gap in the literature when it comes to the impact of music sessions for older adults who do not have a diagnosed disease, therefore this study analyzes this population specifically. This study examines music therapy and its effects on anxiety and depression in adults aged 65 or older living in independent living homes. The adults participated in a mixed-methods study over the span of one month examining music as an intervention to decrease anxiety and depression. Each subject consented into the study, completed a demographic survey, answered open-ended questions regarding their experience with anxiety/sadness and ways to cope, as well as Profile of Moods Scale (POMS) during the first session. On the last week of the study, the participants were asked to fill out the same POMS scale to evaluate whether music influenced anxiety and depression. There was limited evidence found in this study to support the use of music therapy as an intervention to decrease anxiety and depression in adults over the age of 65.
ContributorsWolfus, Sarah Ilyssa (Author) / Lee, Rebecca (Thesis director) / Larkey, Linda (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The Centers for Disease Control and Prevention in the United States announced that there has been roughly a 50% increase in the prevalence of food allergies among people between the years of 1997 - 2011. A food allergy can be described as a medical condition where being exposed to a certain food triggers a harmful immune response in the body, known as an allergic reaction. These reactions can range from mild to fatal, and they are caused mainly by the top 8 major food allergens: dairy, eggs, peanuts, tree nuts, wheat, soy, fish, and shellfish. Food allergies mainly plague children under the age of 3, as some of them will grow out of their allergy sensitivity over time, and most people develop their allergies at a young age, and not when they are older. The rise in prevalence is becoming a frightening problem around the world, and there are emerging theories that are attempting to ascribe a cause. There are three well-known hypotheses that will be discussed: the Hygiene Hypothesis, the Dual-Allergen Exposure Hypothesis, and the Vitamin-D Deficiency Hypothesis. Beyond that, this report proposes that a new hypothesis be studied, the Food Systems Hypothesis. This hypothesis theorizes that the cause of the rise of food allergies is actually caused by changes in the food itself and particularly the pesticides that are used to cultivate it.
ContributorsCromer, Kelly (Author) / Lee, Rebecca (Thesis director) / MacFadyen, Joshua (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Regional and geographical differences may explain variability in menopausal symptom occurrence due to development of climate-specific thermoneutral zones leading to population-specific hot flash frequencies. Limited information available regarding menopausal symptoms in underserved women living in extreme heat.
Understanding the perception of menopausal symptoms in underserved women living in extreme heat regions to identify if heat impacts perception of menopausal symptoms was the objective of this study. Women in free, low-income, and homeless clinics in Phoenix were surveyed during summer and winter months using a self-administered, written questionnaire including demographic, climate and menopause related questions, including the Green Climacteric Scale (GCS).
A total of 139 predominantly Hispanic (56 %), uninsured (53 %), menopausal (56 %), mid-aged (mean 49.9, SD 10.3) women were surveyed— 36% were homeless or in shelters. Most women were not on menopausal hormone therapy (98 %). Twenty-two percent reported hot flashes and 26% night sweats. Twenty-five percent of women reported previously becoming ill from heat. More women thought season influenced menopausal symptoms during summer than winter (41 % vs. 14 %, p = 0.0009). However, majority of women did not think temperature outside influenced their menopausal symptoms and that did not differ by season (73 % in winter vs. 60% in summer, p=0.1094). No statistically significant differences seen for vasomotor symptoms between winter and summer months.
Regional and geographical differences may be key in understanding the variability in menopausal symptoms. Regardless of season, the menopausal, underserved and homeless women living in Arizona reported few vasomotor symptoms. In the summer, they were more likely to report that the season influenced their menopausal symptoms rather than temperature suggesting an influence of the season on symptom perception.
ContributorsMukarram, Mahnoor (Author) / Hondula, David M. (Thesis director) / Kling, Juliana (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Hematopoietic stem cell transplantation (HSCT) is a unique but intense procedure used to save the lives of patients with hematopoietic malignancies. However, patients and caregivers undergoing HSCT can experience prolonged psychological distress due to an intense and distinctive transplant process. Types of psychological distress include anxiety, depression, social isolation, and post-traumatic stress disorder. Although this a significant healthcare problem, limited research has been conducted within the HSCT patient and caregiver population to investigate ways to improve their mental health. The purpose of this study was to examine the effects of an educational video intervention about post-transplant recovery in decreasing emotional distress and promoting emotional well-being in HSCT patients and caregivers. This pilot study utilized a quantitative single-group pretest-posttest design to examine the effect of educational videos on participant's emotional well-being. Four educational videos were developed using information gathered from several reliable bone marrow transplant and cancer websites. A convenience sampling method was used to recruit HSCT patient and caregiver participants. Eleven Caucasian, English-speaking individuals (6 patients, 5 caregivers; 54.5% female; M age= 43.7 years) across the United States were enrolled in the 60-90 minute online intervention. Participant responses were measured using pretest and posttest questionnaires. Results from the study found that the educational videos were effective in decreasing levels of depression and anxiety. Implications for nursing practice include the need to educate HSCT patients and caregivers about transplant recovery to decrease emotional distress. This study demonstrates the impact post-transplant education has on decreasing depression and anxiety in HSCT patients and caregivers.
ContributorsBosselman, Kate Elizabeth (Author) / Kim, Sunny (Thesis director) / Lee, Rebecca (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Disturbances in the protein interactome often play a large role in cancer progression. Investigation of protein-protein interactions (PPI) can increase our understanding of cancer pathways and will disclose unknown targets involved in cancer disease biology. Although numerous methods are available to study protein interactions, most platforms suffer from drawbacks including high false positive rates, low throughput, and lack of quantification. Moreover, most methods are not compatible for use in a clinical setting. To address these limitations, we have developed a multiplexed, in-solution protein microarray (MISPA) platform with broad applications in proteomics. MISPA can be used to quantitatively profile PPIs and as a robust technology for early detection of cancers. This method utilizes unique DNA barcoding of individual proteins coupled with next generation sequencing to quantitatively assess interactions via barcode enrichment. We have tested the feasibility of this technology in the detection of patient immune responses to oropharyngeal carcinomas and in the discovery of novel PPIs in the B-cell receptor (BCR) pathway. To achieve this goal, 96 human papillomavirus (HPV) antigen genes were cloned into pJFT7-cHalo (99% success) and pJFT7-n3xFlag-Halo (100% success) expression vectors. These libraries were expressed via a cell-free in vitro transcription-translation system with 93% and 96% success, respectively. A small-scale study of patient serum interactions with barcoded HPV16 antigens was performed and a HPV proteome-wide study will follow using additional patient samples. In addition, 15 query proteins were cloned into pJFT7_nGST expression vectors, expressed, and purified with 93% success to probe a library of 100 BCR pathway proteins and detect novel PPIs.
ContributorsRinaldi, Capria Lakshmi (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The City of Phoenix Street Transportation Department partnered with the Rob and Melani Walton Sustainability Solutions Service at Arizona State University (ASU) and researchers from various ASU schools to evaluate the effectiveness, performance, and community perception of the new pavement coating. The data collection and analysis occurred across multiple neighborhoods and at varying times across days and/or months over the course of one year (July 15, 2020–July 14, 2021), allowing the team to study the impacts of the surface treatment under various weather conditions.
ContributorsMiddel, Ariane (Author) / Vanos, Jennifer K. (Author) / Hondula, David M. (Author) / Kaloush, Kamil (Author) / Sailor, David (Author) / Medina, Jose R. (Jose Roberto) (Author) / Schneider, Florian (Author) / Ortiz, Johny Cordova (Author) / Campbell, Bill (Author) / Epel, Erin (Contributor) / Rice, Brendan (Contributor) / Garcia, Ruth (Contributor) / Phoenix (Ariz.). Street Transportation Department (Contributor) / City of Phoenix (Funder) / Industrial Development Authority of the County of Maricopa (Funder) / Julie Ann Wrigley Global Institute of Sustainability (Funder) / Arizona State University. Healthy Urban Environments Program (Contributor)
Created2021-09
Description
The TP53 tumor suppressor gene is the most frequently mutated gene in human cancers. In the highly aggressive triple negative breast cancer (TNBC), TP53 is mutated in 80% of cases. TNBC lacks viable drug targets, resulting in a low prognosis (12.2% 5 year survivability rate). As such, the discovery of druggable targets in TNBC would be beneficial. Mutated p53 protein typically occurs as a missense mutation and often endows cancer cells with gain of function (GOF) properties by dysregulating metabolic pathways. One of these frequently dysregulated pathways is the Hippo/Yes-associated protein-1 (YAP1)/WW Domain Containing Transcription Regulator 1 (TAZ) tumor suppressor pathway. This study therefore analyzed the involvement of the Hippo/YAP1/TAZ pathway in p53-mediated breast cancer cell invasion. From an RNA-seq screen in MCF10A cell lines harboring different TP53 missense mutations, each with a differing invasive phenotype, components of the Hippo pathway were found to correlate with cell invasion. To this end, the active and inactive forms of YAP1 and TAZ were studied. Phosphorylated (inactive) YAP1 and TAZ are retained in the cytoplasm and eventually degraded. Unphosphorylated (active) YAP1 and TAZ translocate to the nucleus to activate TEAD-family transcription factors, inducing cell survival and proliferation genes leading to increased cell invasion. Using quantitative western blot analysis, it was found that inactive TAZ expression was lower in the most invasive cell lines and higher in the least invasive cell lines (p = 0.003). Moreover, the ratio of inactive TAZ protein to total TAZ protein was also shown to be predominantly lower in the invasive cell lines compared to the non-invasive lines (p = 0.04). Finally, active TAZ expression was primarily higher in p53-mutant invasive cell lines and lower in non-invasive p53 mutant cells. Additionally, although YAP1 and TAZ are thought to be functionally redundant, the pattern seen in TAZ was not seen in the YAP1 protein. Taken together, the results demonstrated here suggest that TAZ holds a more dominant role in governing TNBC cell invasion compared to YAP1 and further highlights TAZ as a potential therapeutic target in TNBC.
ContributorsGrief, Dustin (Author) / LaBaer, Joshua (Thesis advisor) / Anderson, Karen (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2022
Description
Glioblastoma (GBM), the most common and aggressive primary brain tumor affecting adults, is characterized by an aberrant yet druggable epigenetic landscape. The Histone Deacetylases (HDACs), a major family of epigenetic regulators, favor transcriptional repression by mediating chromatin compaction and are frequently overexpressed in human cancers, including GBM. Hence, over the last decade there has been considerable interest in using HDAC inhibitors (HDACi) for the treatment of malignant primary brain tumors. However, to date most HDACi tested in clinical trials have failed to provide significant therapeutic benefit to patients with GBM. This is because current HDACi have poor or unknown pharmacokinetic profiles, lack selectivity towards the different HDAC isoforms, and have narrow therapeutic windows. Isoform selectivity for HDACi is important given that broad inhibition of all HDACs results in widespread toxicity across different organs. Moreover, the functional roles of individual HDAC isoforms in GBM are still not well understood. Here, I demonstrate that HDAC1 expression increases with brain tumor grade and is correlated with decreased survival in GBM. I find that HDAC1 is the essential HDAC isoform in glioma stem cells and its loss is not compensated for by its paralogue HDAC2 or other members of the HDAC family. Loss of HDAC1 alone has profound effects on the glioma stem cell phenotype in a p53-dependent manner and leads to significant suppression of tumor growth in vivo. While no HDAC isoform-selective inhibitors are currently available, the second-generation HDACi quisinostat harbors high specificity for HDAC1. I show that quisinostat exhibits potent growth inhibition in multiple patient-derived glioma stem cells. Using a pharmacokinetics- and pharmacodynamics-driven approach, I demonstrate that quisinostat is a brain-penetrant molecule that reduces tumor burden in flank and orthotopic models of GBM and significantly extends survival both alone and in combination with radiotherapy. The work presented in this thesis thereby unveils the non-redundant functions of HDAC1 in therapy- resistant glioma stem cells and identifies a brain-penetrant HDACi with higher selectivity towards HDAC1 as a potent radiosensitizer in preclinical models of GBM. Together, these results provide a rationale for developing quisinostat as a potential adjuvant therapy for the treatment of GBM.
ContributorsLo Cascio, Costanza (Author) / LaBaer, Joshua (Thesis advisor) / Mehta, Shwetal (Committee member) / Mirzadeh, Zaman (Committee member) / Mangone, Marco (Committee member) / Paek, Andrew (Committee member) / Arizona State University (Publisher)
Created2022
Description
Infrastructure systems are facing non-stationary challenges that stem from climate change and the increasingly complex interactions between the social, ecological, and technological systems (SETSs). It is crucial for transportation infrastructures—which enable residents to access opportunities and foster prosperity, quality of life, and social connections—to be resilient under these non-stationary challenges. Vulnerability assessment (VA) examines the potential consequences a system is likely to experience due to exposure to perturbation or stressors and lack of the capacity to adapt. Post-fire debris flow and heat represent particularly challenging problems for infrastructure and users in the arid U.S. West. Post-fire debris flow, which is manifested with heat and drought, produces powerful runoff threatening physical transportation infrastructures. And heat waves have devastating health effects on transportation infrastructure users, including increased mortality rates. VA anticipates the potential consequences of these perturbations and enables infrastructure stakeholders to improve the system's resilience. The current transportation climate VA—which only considers a single direct climate stressor on the infrastructure—falls short of addressing the wildfire and heat challenges. This work proposes advanced transportation climate VA methods to address the complex and multiple climate stressors and the vulnerability of infrastructure users. Two specific regions were chosen to carry out the progressive transportation climate VA: 1) the California transportation networks’ vulnerability to post-fire debris flows, and 2) the transportation infrastructure user’s vulnerability to heat exposure in Phoenix.
ContributorsLi, Rui (Author) / Chester, Mikhail V. (Thesis advisor) / Middel, Ariane (Committee member) / Hondula, David M. (Committee member) / Pendyala, Ram (Committee member) / Arizona State University (Publisher)
Created2022