Matching Items (22)
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- All Subjects: Cancer
- Creators: Harrington Bioengineering Program
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 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
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 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
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 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
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 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
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 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
Description
Cardiopulmonary resuscitation (CPR) is an emergency course of action developed to sustain oxygenated blood flow in persons suffering from cardiac arrest by manually compressing the heart in the chest and providing rescue ventilations. The best-selling CPR manikins, an integral part of training, lack biofidelic characteristics in appearance, feel, and response, and as a result, the rescuer's learning experience suffers. The objective of this thesis was to test the compressibility properties of different foams and thermoplastics in order to determine which material would most accurately imitate a human chest response. The results suggested that styrene-ethylene/butylene-styrene (SEBS) was the best choice, because its increasing stiffness under increasing compression was characteristic of a human chest cavity. Further testing must be done to determine the best composition of SEBS, analyze its response under cyclic compressions, and improve its durability.
ContributorsWalsh, Alex Bradley (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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 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
Nutritional support offered before and during chemotherapy treatment is proven to improve the outcomes of treatment (Bernhardson, 2016). This project seeks to examine current forms of nutritional support offered to patients, as well as the models of care and support teams in cancer treatment centers. The basis for this project incorporated personal experiences at M.D. Anderson Cancer Center in Gilbert, Arizona as well as research into the work of clinical oncology dietitians. An intense interest in food videos and blogs also informed this project, and was incorporated in the hope of providing chemotherapy patients a platform to discover recipes specific to their unique situation. The combination of this research was utilized to create several videos which demonstrated specific recipes beneficial for patients as well as creating a platform for this particular population. While nutritional support can take multiple forms, the focus of nutritional support surrounds symptom management. The common side effects of chemotherapy such as nausea, mucositis (mouth sores), and extreme weight loss were taken into account. Recipes were formulated to directly address these conditions and each recipe was broken down into the benefits of both macronutrients and micronutrients. In addition to formulating specific recipes and videos, barriers to proper nutritional support were examined and explained. These barriers include understaffing of clinical dietitians at cancer treatment centers, a patient's lack of transportation to and from treatments, as well as an overwhelming viewpoint that nutritional support is only required for extreme cases of malnutrition. Combatting these barriers and offering more forms of nutritional support will help to increase a patient's positive response to treatment, manage their symptoms, and improve their overall quality of life.
ContributorsMonteilh, Christina Eleanor (Author) / Levinson, Simin (Thesis director) / Martinelli, Sarah (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
The millennial generation is quickly solidifying its place as the dominate generation within the workforce. As millennials transition through workplace hierarchy it is essential organizations understand how to properly develop incoming talent. This is especially important within sales as the opportunity cost for hiring and developing new sales professionals is much higher compared to other professions. Downward trends in millennial retention rates is also a strong contributing factor to the importance of understanding the millennial generation. This paper aims to identify key concepts and elements employers should incorporate into their sales training programs in order to better develop millennials entering sales roles. Through an analysis of each generation and sales training a clear framework will be identified to achieve this goal. Analyzing millennials unique strengths and weaknesses will provide the basis for the key areas employers need to focus on when designing their sales development programs. The framework identified is easily adaptable within any organizations as the concepts discussed can be universally applied.
ContributorsStensland, Zachary William (Author) / Montoya, Detra (Thesis director) / Schlacter, John (Committee member) / Department of Marketing (Contributor) / Department of Information Systems (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Injury Prevention of Young Adult Competitive Athletes Abstract: This literature review covers many aspects of health and injury prevention that affects the young adult population. This review will begin to formulate a general guideline for sustaining performance while minimizing the incidence for injury. This population is specifically narrowed down to competitive athletes between the ages of 16-22. Some of the topics covered in this paper are the effects of macro-nutrients and micro-nutrients such as iron, calcium, vitamin D and vitamin C, on the body. Along with relating nutrition to lowering the risk of injury, there are also other topics covered such as sleep, stress relief in the form of binaural sounds, training and over-training. Nutrition topics include carbohydrates, proteins and fats, which are then split into their respective roles inside the body. These macro-nutrients are also associated with recovery and the timing and quantity consumed can be at optimal levels for competitive athletes based on gender, age and size. The vitamins and minerals discussed are also important factors in injury prevention related to bone, ligament and muscle strength. These micro-nutrients are also related to hormone regulation and immune system response which are necessary in mitigating the risk of injury in the population being analyzed. Finally, there is a training section of this literary review which covers monitoring external and internal loads experienced by the athletes, movement patterns as well as flexibility, and how to respond to over-training syndrome and overreaching in young adult athletes. Creating a balance between all aspects covered will result in a high likelihood of reducing the risk for injury in the young adult population.
ContributorsMark, Colby Jordan (Author) / Levinson, Simin (Thesis director) / Feser, Erin (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12