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Description
Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and

Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic in vitro models with physiologically relevant (i.e. in vivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions.
ContributorsPeela, Nitish (Author) / Nikkhah, Mehdi (Thesis director) / LaBaer, Joshua (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description
Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and

Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and includes chemotherapy, radiation therapy, and surgical removal if the tumor is surgically accessible. Treatment seldom results in a significant increase in longevity, partly due to the lack of precise information regarding tumor size and location. This lack of information arises from the physical limitations of MR and CT imaging coupled with the diffusive nature of glioblastoma tumors. GBM tumor cells can migrate far beyond the visible boundaries of the tumor and will result in a recurring tumor if not killed or removed. Since medical images are the only readily available information about the tumor, we aim to improve mathematical models of tumor growth to better estimate the missing information. Particularly, we investigate the effect of random variation in tumor cell behavior (anisotropy) using stochastic parameterizations of an established proliferation-diffusion model of tumor growth. To evaluate the performance of our mathematical model, we use MR images from an animal model consisting of Murine GL261 tumors implanted in immunocompetent mice, which provides consistency in tumor initiation and location, immune response, genetic variation, and treatment. Compared to non-stochastic simulations, stochastic simulations showed improved volume accuracy when proliferation variability was high, but diffusion variability was found to only marginally affect tumor volume estimates. Neither proliferation nor diffusion variability significantly affected the spatial distribution accuracy of the simulations. While certain cases of stochastic parameterizations improved volume accuracy, they failed to significantly improve simulation accuracy overall. Both the non-stochastic and stochastic simulations failed to achieve over 75% spatial distribution accuracy, suggesting that the underlying structure of the model fails to capture one or more biological processes that affect tumor growth. Two biological features that are candidates for further investigation are angiogenesis and anisotropy resulting from differences between white and gray matter. Time-dependent proliferation and diffusion terms could be introduced to model angiogenesis, and diffusion weighed imaging (DTI) could be used to differentiate between white and gray matter, which might allow for improved estimates brain anisotropy.
ContributorsAnderies, Barrett James (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Stepien, Tracy (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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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 examine the viability of protein biomarkers in pre-symptomatic detection of lung cancer. Regular screening has been shown to vastly improve patient survival outcome. Lung cancer currently has the highest occurrence and mortality of all cancers and so a means of screening would be

The purpose of this project was to examine the viability of protein biomarkers in pre-symptomatic detection of lung cancer. Regular screening has been shown to vastly improve patient survival outcome. Lung cancer currently has the highest occurrence and mortality of all cancers and so a means of screening would be highly beneficial. In this research, the biomarker neuron-specific enolase (Enolase-2, eno2), a marker of small-cell lung cancer, was detected at varying concentrations using electrochemical impedance spectroscopy in order to develop a mathematical model of predicting protein expression based on a measured impedance value at a determined optimum frequency. The extent of protein expression would indicate the possibility of the patient having small-cell lung cancer. The optimum frequency was found to be 459 Hz, and the mathematical model to determine eno2 concentration based on impedance was found to be y = 40.246x + 719.5 with an R2 value of 0.82237. These results suggest that this approach could provide an option for the development of small-cell lung cancer screening utilizing electrochemical technology.
ContributorsEvans, William Ian (Author) / LaBelle, Jeffrey (Thesis director) / Spano, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Engineering is a heavily male-dominated field and females are significantly less likely to choose an engineering-related major or career path. At the age of six years old, females start believing that their male peers are smarter than them, leading them to pursue less ambitious careers. The children's book Lyla B.

Engineering is a heavily male-dominated field and females are significantly less likely to choose an engineering-related major or career path. At the age of six years old, females start believing that their male peers are smarter than them, leading them to pursue less ambitious careers. The children's book Lyla B. An Engineering Legacy was created to encourage more young girls to discover their own potential and pursue engineering as a career. To explore the efficacy of the book on its target consumers, a pilot study was performed with first and second grade children. The participants' engineering knowledge; fixed and failure mindset beliefs; STEM (Science, Technology, Engineering, and Math) interest, competency, and career aspirations; and stereotype beliefs were evaluated before and after being read the book to determine if the story has a positive impact on children. Additionally, the satisfaction of the participants towards both the book and main character were analyzed quantitatively and qualitatively. Overall, the results of the study suggest that the book has a positive impact on the interest and competency of STEM fields and the stereotype beliefs that the children had towards engineers. The study also suggests that the book decreases fixed and failure mindsets and that the participants were satisfied with the overall concept of the book and main character, Lyla.
ContributorsPiatak, Catherine (Co-author) / Seelhammer, Marissa Leigh (Co-author) / Torrence, Kelly (Co-author) / Miller, Cindy (Thesis director) / Jordan, Shawn (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor with a median prognosis of 14 months. Human hairless protein (HR) is a 130 kDa nuclear transcription factor that plays a critical role in skin and hair function but was found to be highly expressed in neural tissue as well. The

Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor with a median prognosis of 14 months. Human hairless protein (HR) is a 130 kDa nuclear transcription factor that plays a critical role in skin and hair function but was found to be highly expressed in neural tissue as well. The expression of HR in GBM tumor cells is significantly decreased compared to the normal brain tissue and low levels of HR expression is associated with shortened patient survival. We have recently reported that HR is a DNA binding phosphoprotein, which binds to p53 protein and p53 responsive element (p53RE) in vitro and in intact cells. We hypothesized that HR can regulate p53 downstream target genes, and consequently affects cellular function and activity. To test the hypothesis, we overexpressed HR in normal human embryonic kidney HEK293 and GBM U87MG cell lines and characterized these cells by analyzing p53 target gene expression, viability, cell-cycle arrest, and apoptosis. The results revealed that the overexpressed HR not only regulates p53-mediated target gene expression, but also significantly inhibit cell viability, induced early apoptosis, and G2/M cell cycle arrest in U87MG cells, compared to mock groups. Translating the knowledge gained from this research on the connections between HR and GBM could aid in identifying novel therapies to circumvent GBM progression or improve clinical outcome.
ContributorsBrook, Lemlem Addis (Author) / Blattman, Joseph (Thesis director) / Hsieh, Jui-Cheng (Committee member) / Goldstein, Elliott (Committee member) / Harrington Bioengineering Program (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
In this creative project, our goal was to establish a student lead service organization dedicated to raising money and awareness for a selected medical issue through an interactive carnival event. In doing so, we were able to identify the potential obstacles and pathways that are required for service organizations within

In this creative project, our goal was to establish a student lead service organization dedicated to raising money and awareness for a selected medical issue through an interactive carnival event. In doing so, we were able to identify the potential obstacles and pathways that are required for service organizations within Arizona State University. Our experience provides a guideline for future students looking to organize charitable events on campus. This paper discusses several essential skills for running a charitable student organization, including establishing a brand, managing finances, cultivating business relationships, and marketing the cause. It is our hope that future students can learn from our experience and find success in similar endeavors.
ContributorsStoddard, Stacy Dawn (Co-author) / Wong, Brittney (Co-author) / Hultsman, Wendy (Thesis director) / Holland-Malcom, Jan (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique

Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique growth pattern. Consequently it is difficult for neurosurgeons to anticipate where the tumor will spread in the brain, making treatment planning difficult. Archival patient data including MRI scans depicting the progress of tumors have been helpful in developing a model to predict Glioblastoma proliferation, but limited scans per patient make the tumor growth rate difficult to determine. Furthermore, patient treatment between scan points can significantly compound the challenge of accurately predicting the tumor growth. A partnership with Barrow Neurological Institute has allowed murine studies to be conducted in order to closely observe tumor growth and potentially improve the current model to more closely resemble intermittent stages of GBM growth without treatment effects.
ContributorsSnyder, Lena Haley (Author) / Kostelich, Eric (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Spending time outdoors can have a positive impact on the physical and mental health of individuals. These physiological and psychological benefits were comprehensively reviewed, accompanied by a brief history of these views in American society and how modern programs are promoting outdoor activity. Some of the populations targeted in this

Spending time outdoors can have a positive impact on the physical and mental health of individuals. These physiological and psychological benefits were comprehensively reviewed, accompanied by a brief history of these views in American society and how modern programs are promoting outdoor activity. Some of the populations targeted in this research include children, veterans, the elderly, and the clinically ill. A guidebook for Arizona outdoor adventures \u2014 containing original landscape photography \u2014 was created to encourage ASU students to explore local hikes, campsites, and other outdoor opportunities near the city of Phoenix. Each entry contained a brief description of the area or trail, along with the distance from the ASU Tempe campus and information on the length and difficulty of the hike, if applicable. A section at the end of the book was aimed at education readers on basic outdoor survival protocol, as many people venture into the wild with very little understanding of the dangers associated with their activities. A website was made that mirrors the guidebook, but was intended to be a more accessible method of sharing our information. The final component of the project involved maintaining a social media account over the course of the year, allowing us to expand our reach to people beyond ASU and this community. Over the course of the project, the account gained a large following, and several posted photos went on to be featured on prominent regional accounts. By combining the four components described previously, several resources were created for people, particularly students attending ASU, to gain a better understanding of the outdoor adventures available to them, and the benefits that spending time surrounded by nature can have.
ContributorsSwitzer, Hannah (Co-author) / Weinstein, Casey (Co-author) / Smith, Andrew (Thesis director) / Lefler, Scott (Committee member) / Kozakiewicz, Scott (Committee member) / Harrington Bioengineering Program (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The goal of this creative project is to document my grandmother’s traditional Gujarati recipes with the hopes of preserving her life and passion for cooking. This process included library research to investigate the history of Indian and Gujarati cuisine, spending time in the kitchen documenting the recipes in their entirety,

The goal of this creative project is to document my grandmother’s traditional Gujarati recipes with the hopes of preserving her life and passion for cooking. This process included library research to investigate the history of Indian and Gujarati cuisine, spending time in the kitchen documenting the recipes in their entirety, practicing them on my own, writing the cookbook and including passages that weave in the history, my grandmother’s stories, and techniques and tools. After completing this process, the significant findings related to my grandmother’s life and her journey from birth to now. Her marriage to my grandfather at a young age, her journey and those who influenced her ability to cook, and her impact on my family were all effects that I had understood and known during my experiences with my grandmother. In this journey, I learned more about her thoughts and experiences that I never knew before. Our relationship has deepened ten-fold and while she may not be with me forever, I now have a tangible part of her that I can keep with me for the rest of my life.
ContributorsPatel, Ekta (Author) / Graff, Sarah (Thesis director) / Jacobs, Mark (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05