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ContributorsDaval, Charles (Performer) / ASU Library. Music Library (Publisher)
Created2018-03-26
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DescriptionThe purpose of this project is to explore the influence of folk music in guitar compositions by Manuel Ponce from 1923 to 1932. It focuses on his Tres canciones populares mexicanas and Tropico and Rumba.
ContributorsGarcia Santos, Arnoldo (Author) / Koonce, Frank (Thesis advisor) / Rogers, Rodney (Committee member) / Rotaru, Catalin (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Cancer is a disease that affects millions of people worldwide each year. The metastatic progression of cancer is the number one reason for cancer related deaths. Cancer preventions rely on the early identification of tumor cells as well as a detailed understanding of cancer as a whole. Identifying proteins specific

Cancer is a disease that affects millions of people worldwide each year. The metastatic progression of cancer is the number one reason for cancer related deaths. Cancer preventions rely on the early identification of tumor cells as well as a detailed understanding of cancer as a whole. Identifying proteins specific to tumor cells provide an opportunity to develop noninvasive clinical tests and further our understanding of tumor biology. Using liquid chromatography-mass spectrometry (LC-MS/MS) a short peptide was identified in pancreatic cancer patient plasma that was not found in normal samples, and mapped back to QSOX1 protein. Immunohistochemistry was performed probing for QSOX1 in tumor tissue and discovered that QSOX1 is highly over-expressed in pancreatic and breast tumors. QSOX1 is a FAD-dependent sulfhydryl oxidase that is extremely efficient at forming disulfide bonds in nascent proteins. While the enzymology of QSOX1 has been well studied, the tumor biology of QSOX1 has not been studied. To begin to determine the advantage that QSOX1 over-expression provides to tumors, short hairpin RNA (shRNA) were used to reduce the expression of QSOX1 in human tumor cell lines. Following the loss of QSOX1 growth rate, apoptosis, cell cycle and invasive potential were compared between tumor cells transduced with shQSOX1 and control tumor cells. Knock-down of QSOX1 protein suppressed tumor cell growth but had no effect on apoptosis and cell cycle regulation. However, shQSOX1 dramatically inhibited the abilities of both pancreatic and breast tumor cells to invade through Matrigel in a modified Boyden chamber assay. Mechanistically, shQSOX1-transduced tumor cells secreted MMP-2 and -9 that were less active than MMP-2 and -9 from control cells. Taken together, these results suggest that the mechanism of QSOX1-mediated tumor cell invasion is through the post-translational activation of MMPs. This dissertation represents the first in depth study of the role that QSOX1 plays in tumor cell biology.
ContributorsKatchman, Benjamin A (Author) / Lake, Douglas F. (Thesis advisor) / Rawls, Jeffery A (Committee member) / Miller, Laurence J (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2012
ContributorsKotronakis, Dimitris (Performer) / ASU Library. Music Library (Publisher)
Created2018-03-01
Description
Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. These vesicles play an important role in cellular communication by virtue of their protein, RNA, and lipid content, which can be transferred among cells. Peripheral blood is a rich source

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. These vesicles play an important role in cellular communication by virtue of their protein, RNA, and lipid content, which can be transferred among cells. Peripheral blood is a rich source of circulating EVs. An analysis of EVs in peripheral blood could provide access to unparalleled amounts of biomarkers of great diagnostic, prognostic as well as therapeutic value. In the current study, a plasma EV enrichment method based on pluronic co-polymer was first established and characterized. Plasma EVs from breast cancer patients were then enriched, profiled and compared to non-cancer controls. Proteins signatures that contributed to the prediction of cancer samples from non-cancer controls were created by a random-forest based cross-validation approach. We found that a large portion of these signatures were related to breast cancer aggression. To verify such findings, KIAA0100, one of the features identified, was chosen for in vitro molecular and cellular studies in the breast cancer cell line MDA-MB-231. We found that KIAA0100 regulates cancer cell aggression in MDA-MB-231 in an anchorage-independent manner and is particularly associated with anoikis resistance through its interaction with HSPA1A. Lastly, plasma EVs contain not only individual proteins, but also numerous molecular complexes. In order to measure millions of proteins, isoforms, and complexes simultaneously, Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT) platform was applied. ADAPT employs an enriched library of single-stranded oligodeoxynucleotides to profile complex biological samples, thus achieving a deep coverage of system-wide, native biomolecules. Profiling of EVs from breast cancer patients was able to obtain a prediction AUC performance of 0.73 when compared biopsy-positive cancer patient to healthy controls and 0.64 compared to biopsy-negative controls and such performance was not associated with the physical breast condition indicated by BIRAD scores. Taken together, current research demonstrated the potential of profiling plasma EVs in searching for therapeutic targets as well as diagnostic signatures.
ContributorsZhong, Zhenyu (Author) / Spetzler, David (Thesis advisor) / Yan, Hao (Thesis advisor) / Lake, Douglas (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2018
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Description

Past studies have shown that exercise in the form of high intensity interval training (HIIT) is the "ideal form of exercise to improve health and performance without overstressing the immune system" (Fisher et. al, 2011, p. 5). Additionally, HIIT has been found to promote cardiovascular health and immunity (Fisher et.

Past studies have shown that exercise in the form of high intensity interval training (HIIT) is the "ideal form of exercise to improve health and performance without overstressing the immune system" (Fisher et. al, 2011, p. 5). Additionally, HIIT has been found to promote cardiovascular health and immunity (Fisher et. al, 2011). The proposed study will evaluate the neuropsychological effects of HIIT on breast cancer patients undergoing anthracycline-based chemotherapy. The intervention group (n = 17) will receive a HIIT protocol concurrent with chemotherapy treatment. There will also be a control group (n= 17) to compare the effects of the intervention. Breast cancer survivorship is often ridden with various health and mental problems, the implementation of HIIT procedures could help to reduce these issues. It is expected that knowledge from this study will be useful in the healthcare setting to benefit breast cancer patients. This study will uniquely add to the limited research base by introducing an intervention for neuropsychological declines in breast cancer patients.

ContributorsNguyen, Ha Vi Song (Author) / Tran, Alisia (Thesis director) / Capco, David (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
The objective of this research was to create a 3D in vitro model to mimic the native breast tumor microenvironment. Polydimethylsiloxane (PDMS) stamps and micromolding techniques were utilized to develop collagen based 3D tumor model. Geometrical design was optimized for the PDMS stamp to compartmentalize the tumor and stromal region

The objective of this research was to create a 3D in vitro model to mimic the native breast tumor microenvironment. Polydimethylsiloxane (PDMS) stamps and micromolding techniques were utilized to develop collagen based 3D tumor model. Geometrical design was optimized for the PDMS stamp to compartmentalize the tumor and stromal region of the 3D model. Addition of tumor and stromal cells into the platform further demonstrated the successful fabrication of the 3D model which will be used to investigate the role of stromal components on tumor growth and progression. Atomic force microscopy will also be utilized to access stromal remodeling during active invasion.
ContributorsAssefa, Eyerusalem Dibaba (Author) / Nikkhah, Mehdi (Thesis director) / Saini, Harpinder (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description
Breast and other solid tumors exhibit high and varying degrees of intra-tumor heterogeneity resulting in targeted therapy resistance and other challenges that make the management and treatment of these diseases rather difficult. Due to the presence of admixtures of non-neoplastic cells with polyclonal cell populations, it is difficult to define

Breast and other solid tumors exhibit high and varying degrees of intra-tumor heterogeneity resulting in targeted therapy resistance and other challenges that make the management and treatment of these diseases rather difficult. Due to the presence of admixtures of non-neoplastic cells with polyclonal cell populations, it is difficult to define cancer genomes in patient samples. By isolating tumor cells from normal cells, and enriching distinct clonal populations, clinically relevant genomic aberrations that drive disease can be identified in patients in vivo. An in-depth analysis of clonal architecture and tumor heterogeneity was performed in a stage II chemoradiation-naïve breast cancer from a sixty-five year old patient. DAPI-based DNA content measurements and DNA content-based flow sorting was used to to isolate nuclei from distinct clonal populations of diploid and aneuploid tumor cells in surgical tumor samples. We combined DNA content-based flow cytometry and ploidy analysis with high-definition array comparative genomic hybridization (aCGH) and next-generation sequencing technologies to interrogate the genomes of multiple biopsies from the breast cancer. The detailed profiles of ploidy, copy number aberrations and mutations were used to recreate and map the lineages present within the tumor. The clonal analysis revealed driver events for tumor progression (a heterozygous germline BRCA2 mutation converted to homozygosity within the tumor by a copy number event and the constitutive activation of Notch and Akt signaling pathways. The highlighted approach has broad implications in the study of tumor heterogeneity by providing a unique ultra-high resolution of polyclonal tumors that can advance effective therapies and clinical management of patients with this disease.
ContributorsLaughlin, Brady Scott (Author) / Ankeny, Casey (Thesis director) / Barrett, Michael (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School for the Science of Health Care Delivery (Contributor)
Created2015-05
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Description
The purpose of this project was to identify proteins associated with the migration and invasion of non-transformed MCF10A mammary epithelial cells with ectopically expressed missense mutations in p53. Because of the prevalence of TP53 missense mutations in basal-like and triple-negative breast cancer tumors, understanding the effect of TP53 mutations on

The purpose of this project was to identify proteins associated with the migration and invasion of non-transformed MCF10A mammary epithelial cells with ectopically expressed missense mutations in p53. Because of the prevalence of TP53 missense mutations in basal-like and triple-negative breast cancer tumors, understanding the effect of TP53 mutations on the phenotypic expression of human mammary epithelial cells may offer new therapeutic targets for those currently lacking in treatment options. As such, MCF10A mammary epithelial cells ectopically overexpressing structural mutations (G245S, H179R, R175H, Y163C, Y220C, and Y234C) and DNA-binding mutations (R248Q, R248W, R273C, and R273H) in the DNA-binding domain were selected for use in this project. Overexpression of p53 in the mutant cell lines was confirmed by western blot and q-PCR analysis targeting the V5 epitope tag present in the pLenti4 vector used to transduce TP53 into the mutant cell lines. Characterization of the invasion and migration phenotypes resulting from the overexpression of p53 in the mutant cell lines was achieved using transwell invasion and migration assays with Boyden chambers. Statistical analysis showed that three cell lines—DNA-contact mutants R248W and R273C and structural mutant Y220C—were consistently more migratory and invasive and demonstrated a relationship between the migration and invasion properties of the mutant cell lines. Two families of proteins were then explored: those involved in the Epithelial-Mesenchymal Transition (EMT) and matrix metalloproteinases (MMPs). Results of q-PCR and immunofluorescence analysis of epithelial marker E-cadherin and mesenchymal proteins Slug and Vimentin did not show a clear relationship between mRNA and protein expression levels with the migration and invasiveness phenotypes observed in the transwell studies. Results of western blotting, q-PCR, and zymography of MMP-2 and MMP-9 also did not show any consistent results indicating a definite relationship between MMPs and the overall invasiveness of the cells. Finally, two drugs were tested as possible treatments inhibiting invasiveness: ebselen and SBI-183. These drugs were tested on only the most invasive of the MCF10A p53 mutant cell lines (R248W, R273C, and Y220C). Results of invasion assay following 30 μM treatment with ebselen and SBI-183 showed that ebselen does not inhibit invasiveness; SBI-183, however, did inhibit invasiveness in all three cell lines tested. As such, SBI-183 will be an important compound to study in the future as a treatment that could potentially serve to benefit triple-negative or basal-like breast cancer patients who currently lack therapeutic treatment options.
ContributorsZhang, Kathie Q (Author) / LaBaer, Joshua (Thesis director) / Anderson, Karen (Committee member) / Gonzalez, Laura (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
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Description
Breast cancer affects hundreds of thousands of women a year in the United States, and kills tens of thousands. African-American women experience a lower incidence of breast cancer, yet they die at twice the rate of Caucasian women. This disparity demonstrates the ineffectiveness of mammography at decreasing mortality in women

Breast cancer affects hundreds of thousands of women a year in the United States, and kills tens of thousands. African-American women experience a lower incidence of breast cancer, yet they die at twice the rate of Caucasian women. This disparity demonstrates the ineffectiveness of mammography at decreasing mortality in women at higher risk of late stage diagnosis. In this paper I argue that the continued support of the predominating idea that the benefits of mammograms strictly outweigh their negative effects may be a factor in the continued racial disparity in breast cancer mortality between African-American and Caucasian women. In addition, I will argue that mammograms are less effective for African American women because they are predisposed to later stage diagnosis and the accompanying poorer mortality prognosis due to higher-risk environments caused by varied socio-political status. My claims are supported by studies of incidence rates, survivorship versus mortality rates, screening usage rates, late stage and early stage diagnosis rate, tumor type, and the effects of socioeconomic status on stage of diagnosis. In particular, mortality rates have not decreased parallel with increased mammogram usage, especially in African-American women. Although early stage diagnosis has drastically increased, late stage-diagnosis remains unchanged and higher in African-American women. Tumor types vary by race, and African American women tend to have tumors that are highly prolific and more likely to be metastatic. Socioeconomic factors are more of a marker for breast cancer disparities than race, however race and socio-political structures that embody racism are often intersected.
ContributorsHuper-Holmes, Chloe Lynn (Author) / Lynch, John (Thesis director) / Brian, Jennifer (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor)
Created2015-05