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- All Subjects: Physical Activity
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
Hispanic children have the highest prevalence of obesity versus other ethnic groups. This leaves this population susceptible to many adverse health risks, including hypertension, cardiovascular disease, and high blood pressure. Unfortunately, little research has been done investigating the contributing cause to this issue, specifically common sedentary behaviors in children that limit physical activity and it’s purpose in expending energy. Amongst these behaviors, amount of time spent on electronic devices has proven to have increased drastically in recent years. The relationship between screen time and electronic device use, specifically with television, video games, and computer usage, and physical activity levels, and how those affect cardiometabolic disease risk factors, were explored in this study. Participants of this study were elementary school-aged children from Maricopa County, AZ. Electronic device usage, physical activity amounts, and presence of the specific devices in the child’s were collected from the participants’ parents through self-reported survey questions. Anthropometric and biochemical markers of cardiometabolic disease risk were directly measured. The average time spent engaged in physical activity per day by these participants was 20.02 ± 21.1 minutes and the average total screen time per day was 655 ± 605 minutes. Findings showed strong significance between total screen time and computer and video game use (r=0.482; p=0.01 and r=0.784; p=0.01, respectively). Video game time in the group of children with a video game in their room (350.66 ± 445.96 min/day) was significantly higher than the sample of kids without one in their room (107.19 ± 210.0 min/day ; p=0.000). Total screen time was also significantly greater with children who had a video game system in their room (927.56 ± 928.7 min/day) versus children who did not (543.14 ± 355.11 min/day; p=0.006). Additionally, significance was found showing children with a computer in the bedroom spent more time using the computer per day (450.95 ± 377.95 min/day), compared to those children who did not have a computer in their room (333.5 ± 395.6 min/day; p=0.048). No significant association was found between metabolic markers and screen time. However, HDL-cholesterol, triglycerides, and insulin proved to be dependent on BMI percentile (r=-0.582; p=0.01, r=0.476; p=0.01, r=0.704; p=0.01 respectively). Our data suggest further research needs to be done investigating other potential sources that limit physical activity so that strategies can focus on reducing obesity incidence and the associated health risks. Future studies should use larger sample sizes to be more representative of this population, and develop more direct observations instead of self-reported values to limit bias.
ContributorsGaines, Michael Anthony (Author) / Vega-Lopez, Sonia (Thesis director) / Crespo, Noe (Committee member) / School for the Science of Health Care Delivery (Contributor) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05