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- All Subjects: Nutrition
- All Subjects: Cancer
- Creators: School of Life Sciences
- Creators: Vega-Lopez, Sonia
- Status: Published
Description
Glioblastoma (GB) is one of the deadliest cancers and the most common form of adult primary brain tumors. SGEF (ARHGEF26) has been previously shown to be overexpressed in GB tumors, play a role in cell invasion/migration, and increase temozolomide (TMZ) resistance.[3] It was hypothesized parental LN229 cell lines with SGEF knockdown (LN229-SGEFi) will show decreased metabolism in the MTS assay and decreased colony formation in a colony formation assay compared to parental LN229 cells after challenging the two cell lines with TMZ. For WB and co-immunoprecipitation (co-IP), parental LN229 cells with endogenous SGEF and BRCA were expected to interact and stain in the BRCA1:IP WB. LN229-SGEFi cells were expected to show very little SGEF precipitated due to shRNA targeted knockdown of SGEF. In conditions with mutations in the BRCA1 binding site (LN229-SGEFi + AdBRCAm/AdDM), SGEF expression was expected to decrease compared to parental LN229 or LN229-SGEFi cells reconstituted with WT SGEF (LN229-SGEFi + AdWT). LN229 infected with AdSGEF with a mutated nuclear localization signal (LN229-SGEFi + AdNLS12m) were expected to show BRCA and SGEF interaction since whole cell lysates were used for the co-IP. MTS data showed no significant differences in metabolism between the two cell lines at all three time points (3, 5, and 7 days). Western blot analysis was successful at imaging both SGEF and BRCA1 protein bands from whole cell lysate. The CFA showed no significant difference between cell lines after being challenged with 500uM TMZ. The co-IP immunoblot showed staining for BRCA1 and SGEF for all lysate samples, including unexpected lysates such as LN229-SGEFi, LN229-SGEFi + AdBRCAm, and LN229-SGEFi + AdDM. These results suggested either an indirect protein interaction between BRCA1 and SGEF, an additional BRCA binding site not included in the consensus, or possible detection of the translocated SGEF in knockdown cells lines since shRNA cannot enter the nucleus. Further optimization of CO-IP protocol, MTS assay, and CFA will be needed to characterize the SGEF/BRCA1 interaction and its role in cell survival.
ContributorsNabaty, Natalie Lana (Author) / Douglas, Lake (Thesis director) / Loftus, Joseph C. (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into how evolutionary history has shaped mechanisms of cancer suppression by examining how life history traits impact cancer susceptibility across species. Here, we perform multi-level analysis to test how species-level life history strategies are associated with differences in neoplasia prevalence, and apply this to mammary neoplasia within mammals. We propose that the same patterns of cancer prevalence that have been reported across species will be maintained at the tissue-specific level. We used a combination of factor analysis and phylogenetic regression on 13 life history traits across 90 mammalian species to determine the correlation between a life history trait and how it relates to mammary neoplasia prevalence. The factor analysis presented ways to calculate quantifiable underlying factors that contribute to covariance of entangled life history variables. A greater risk of mammary neoplasia was found to be correlated most significantly with shorter gestation length. With this analysis, a framework is provided for how different life history modalities can influence cancer vulnerability. Additionally, statistical methods developed for this project present a framework for future comparative oncology studies and have the potential for many diverse applications.
ContributorsFox, Morgan Shane (Author) / Maley, Carlo C. (Thesis director) / Boddy, Amy (Committee member) / Compton, Zachary (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Mexican Americans have an increased risk for type 2 diabetes and premature cardiovascular disease (CVD). The association of hyperglycemia with traditional CVD risk factors in this population has been established, but there is limited data regarding other non-traditional CVD risk factors. Thus, this cross-sectional study was conducted to evaluate CVD risk among Mexican Americans by measuring concentrations of lipids, high-sensitivity C-reactive protein (hsCRP), and cholesterol in low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) subfractions. Eighty overweight/obese Mexican-American adults participating in the Maricopa Insulin Resistance Initiative were randomly selected from each of the following four groups (n = 20 per group): nomolipidemic
ormoglycemic controls (NC), dyslipidemic
ormoglycemic (DN), dyslipidemic/prediabetic (DPD) and dyslipidemic/diabetic (DD). Total cholesterol (TC) was 30% higher among DD than in NC participants (p<0.0001). The DPD group had 27% and 12% higher LDL-C concentrations than the NC and DN groups, respectively. Similarly, LDL-C was 29% and 13% higher in DD than in NC and DN participants (p=0.013). An increasing trend was observed in %10-year CVD risk with increasing degree of hyperglycemia (p<0.0001). The NC group had less cholesterol in sdLDL particles than dyslipidemic groups, regardless of glycemic status (p<0.0001). When hyperglycemia was part of the phenotype (DPD and DD), there was a greater proportion of total and HDL-C in sHDL particles in dyslipidemic individuals than in NC (p=0.023; p<0.0001; respectively). Percent 10-year CVD risk was positively correlated with triglyceride (TG) (r=0.384, p<0.0001), TC (r=0.340, p<0.05), cholesterol in sdLDL(r=0.247; p<0.05), and TC to HDL-C ratio (r=0.404, p<0.0001), and negatively correlated with HDL-C in intermediate and large HDL(r=-0.38, p=0.001; r=0.34, p=0.002, respectively). The TC/HDL-C was positively correlated with cholesterol in sdLDL particles (r=0.698, p<0.0001) and HDL-C in sHDL particles (r=0.602, p<0.0001), and negatively correlated with cholesterol in small (r=-0.35, p=0.002), intermediate (r=-0.91, p<0.0001) and large (r=-0.84, p<0.0001) HDL particles, and HDL-C in the large HDL particles (r=-0.562, p<0.0001). No significant association was found between %10-year CVD risk and hsCRP. Collectively, these results corroborate that dyslipidemic Mexican-American adults have higher CVD risk than normolipidemic individuals. Hyperglycemia may further affect CVD risk by modulating cholesterol in LDL and HDL subfractions.
ormoglycemic controls (NC), dyslipidemic
ormoglycemic (DN), dyslipidemic/prediabetic (DPD) and dyslipidemic/diabetic (DD). Total cholesterol (TC) was 30% higher among DD than in NC participants (p<0.0001). The DPD group had 27% and 12% higher LDL-C concentrations than the NC and DN groups, respectively. Similarly, LDL-C was 29% and 13% higher in DD than in NC and DN participants (p=0.013). An increasing trend was observed in %10-year CVD risk with increasing degree of hyperglycemia (p<0.0001). The NC group had less cholesterol in sdLDL particles than dyslipidemic groups, regardless of glycemic status (p<0.0001). When hyperglycemia was part of the phenotype (DPD and DD), there was a greater proportion of total and HDL-C in sHDL particles in dyslipidemic individuals than in NC (p=0.023; p<0.0001; respectively). Percent 10-year CVD risk was positively correlated with triglyceride (TG) (r=0.384, p<0.0001), TC (r=0.340, p<0.05), cholesterol in sdLDL(r=0.247; p<0.05), and TC to HDL-C ratio (r=0.404, p<0.0001), and negatively correlated with HDL-C in intermediate and large HDL(r=-0.38, p=0.001; r=0.34, p=0.002, respectively). The TC/HDL-C was positively correlated with cholesterol in sdLDL particles (r=0.698, p<0.0001) and HDL-C in sHDL particles (r=0.602, p<0.0001), and negatively correlated with cholesterol in small (r=-0.35, p=0.002), intermediate (r=-0.91, p<0.0001) and large (r=-0.84, p<0.0001) HDL particles, and HDL-C in the large HDL particles (r=-0.562, p<0.0001). No significant association was found between %10-year CVD risk and hsCRP. Collectively, these results corroborate that dyslipidemic Mexican-American adults have higher CVD risk than normolipidemic individuals. Hyperglycemia may further affect CVD risk by modulating cholesterol in LDL and HDL subfractions.
ContributorsNeupane, Srijana (Author) / Vega-Lopez, Sonia (Thesis advisor) / Shaibi, Gabriel Q (Committee member) / Johnston, Carol S (Committee member) / Arizona State University (Publisher)
Created2011
Description
Studies have demonstrated that anthocyanins can function as antioxidants, reduce inflammation, and improve dyslipidemia. Tart cherries are anthocyanin-rich, making them particularly attractive as a functional food to improve cardiovascular disease (CVD) risk. There have been few published studies to date examining the impact of tart cherries on biomarkers of dyslipidemia and inflammation, particularly in overweight and obese individuals at high risk for these conditions. This study evaluated the effect of consuming 100% tart cherry juice daily on blood lipids including total cholesterol, low-density lipoprotein cholesterol (LDL-C), calculated very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and the CVD risk ratios, as well as the inflammatory biomarkers interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), and erythrocyte sedimentation rate (ESR) following a 4-week period. Based on the high anthocyanin content of tart cherries, it was hypothesized that the lipid and inflammatory profiles would be significantly improved following the intervention. A total of 26 men and women completed this 4-week randomized, single-blind, placebo-controlled, crossover study. Participants were randomized to drink either 8 ounces of placebo beverage or tart cherry juice daily for 4 weeks. Following a 4-week washout period, the alternate beverage was consumed. Ultimately, this investigation demonstrated no statistically significant alterations in any of the lipid or inflammatory biomarkers when analyzed across time and between interventions (p > 0.05). As expected, glucose and insulin parameters remained stable over the duration of the study, as well as self-reported physical activity level, total calorie consumption, and macronutrient intake. However, trans-fat was reported to be significantly higher during the cherry arm of the study as compared to the placebo arm (p < 0.05), potentially confounding other results. Although the results of this study were equivocal, it is feasible that a higher dose, longer treatment duration, or more susceptible target population may be required to elicit significant effects. Consequently, further investigation is necessary to clarify this research.
ContributorsColes, Katie (Author) / Martin, Keith R. (Thesis advisor) / Traustadottir, Tinna (Committee member) / Vega-Lopez, Sonia (Committee member) / Arizona State University (Publisher)
Created2012
Description
Among the general US population, cardiovascular disease (CVD) is the main cause of mortality for Mexican-Americans. CVD is less prevalent among Mexican-Americans than non-Hispanic Whites or African Americans. However, there is limited research regarding the factors associated with increased CVD risk among Mexican-Americans. Thus, this cross-sectional study was conducted to evaluate the effects of non-biological factors (income, education, employment, acculturation) and diet on CVD risk factors in 75 Mexican-American adults (26 males, 49 females; age=37.6±9.3 y, BMI=28.9±5.3 kg/m2, systolic BP=117±11 mmHg, diastolic BP=73±9 mmHg, LDL cholesterol=114±32 mg/dL, HDL cholesterol=44±11 mg/dL, triglycerides=115±61 mg/dL, serum glucose=92±7 mg/dL). Aside from collecting anthropometric measurements, blood pressure, and measuring fasting blood lipids, glucose, and insulin, information about participants' socioeconomic status, income, employment, education, and acculturation were gathered using a survey. Diet data was collected using the Southwestern Food Frequency Questionnaire. Weight, BMI, and waist circumference were significantly greater for those with a monthly income of <$3000 than for those earning >$3000 (81±15 kg vs. 71±15 kg; 29.8±4.6 kg/m2 vs. 26.5±5.1 kg/m2; 98±12 cm vs. 89±14 cm; respectively) and with an education level of high school graduate or less than for those with some college (84±16 kg vs. 72±14 kg; 30.6±4.2 kg/m2 vs. 26.9±4.9 kg/m2; 100±11 cm vs. 91±13 cm; respectively). HDL-C was higher for those with a monthly income of >$3000 than those earning <$3000 (49±12 mg/dL vs. 41±10 mg/dL), those with some college education than those with high school or less (47±10 mg/dL vs. 37±9 mg/dL), and for those employed than those not employed (46±10 mg/dL vs. 40±12 mg/dL). There was no association between acculturation and CVD risk factors. Percent of energy consumed from fat was greater and percent of energy from carbohydrates was lower in those earning <$3000 monthly than those earning >$3000 (32±5% vs. 29±3%; 52±8% vs. 56±4%; respectively). Greater acculturation to the Anglo culture was negatively correlated with body fat percentage (r=-0.238, p=0.043) and serum glucose (r=-0.265, p=0.024). Overall, these results suggest that factors related to sociocultural and socioeconomic status may affect cardiometabolic disease risk in Mexican-Americans living in the Phoenix metropolitan area.
ContributorsFarr, Kristin Jennette (Author) / Vega-Lopez, Sonia (Thesis advisor) / Shaibi, Gabriel Q (Committee member) / Mayol-Kreiser, Sandra N (Committee member) / Arizona State University (Publisher)
Created2011
Description
Cardiovascular disease is one of the most deadly outcomes of end stage renal disease. Bioelectrical impedance is a intriguing, yet unproven method of measuring fluid buildup in the heart, and is marketed as a early diagnostic tool for onset of cardiovascular disease. In this study, selenium supplements were given to a cohort of dialysis patients in the Phoenix metro area and their fluid tolerance was measured with thoracic biolectrical impedance. BNP was used as a correlate to see if bioelectrical impedance was correlated with heart disease. The study found no correlation between BNP and bioelectrical impedance and thus was not an accurate diagnostic tool in a medical setting.
ContributorsBrown, Patrick Michael (Author) / Johnston, Carol (Thesis director) / Orchinik, Miles (Committee member) / Tingey, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor)
Created2013-05
Description
The Western Pattern diet has been characterized by having greater than 50 percent consumption coming from fat and sugar. This macronutrient allocation has been shown to have deleterious effects on endothelial function and metabolic markers of cardiovascular disease. Exercise has been shown to improve vascular reactivity and metabolic markers related to cardiovascular health. The objective of the study was to determine if exercise training can prevent the anticipated deleterious effects of a fat-sugar supplemented diet on endothelial function and blood markers of cardiovascular risk in young men. Twenty-one, healthy college-aged males were randomly assigned to either the doughnut + exercise or doughnut only groups. Both groups were fed 2 doughnuts per day, 6 days per week, for three weeks, while maintain their current diet. The exercise group completed 4 exercise training sessions per week consisting of 2 high intensity interval training bouts (up to 95% VO2peak) on a cycle ergometer and two moderate intensity, steady-state bouts (at 75% VO2peak) on a treadmill. Changes in body weight and composition, markers of endothelial function, oxidative stress, serum lipids, and blood glucose were measured in each group. As expected, cardiovascular fitness increased significantly in the doughnut-supplemented + exercise group as compared to the doughnut-supplemented (p=0.005). Significant increases in body weight (p=0.036), fat mass (p=0.013), and body fat percentage (p=0.014) were seen in the doughnut only group as compared to the doughnut + exercise group. The doughnut + exercise group showed significant improvements in fasting serum triglycerides (p=0.036), plasma insulin (p=0.039) and insulin sensitivity (HOMA; p=0.05) as compared to the doughnut only group. The doughnut + exercise group saw a significant improvement in nitric oxide availability whereas the doughnut only group experienced a significant decline (p=0.014). There were no significant changes in other markers. Despite the addition of a fat/sugar supplement of ~11,600 kcal over three weeks, 4 exercise sessions per week were sufficient to prevent a gain in body weight and fat mass, and also improve some measures of cardiometabolic risk. These results suggest that exercise may be necessary to prevent some adverse health outcomes associated with transient periods of excessive energy consumption.
ContributorsBlack, Laurie (Author) / Gaesser, Glenn (Thesis advisor) / Cataldo, Donna (Committee member) / Sweazea, Karen (Committee member) / Vega-Lopez, Sonia (Committee member) / Swan, Pamela (Committee member) / Arizona State University (Publisher)
Created2013
Description
Background: Evidence about the purported hypoglycemic and hypolipidemic effects of nopales (prickly pear cactus pads) is limited. Objective: To evaluate the efficacy of nopales for improving cardiometabolic risk factors and oxidative stress, compared to control, in adults with hypercholesterolemia. Design: In a randomized crossover trial, participants were assigned to a 2-wk intervention with 2 cups/day of nopales or cucumbers (control), with a 2 to 3-wk washout period. The study included 16 adults (5 male; 46±14 y; BMI = 31.4±5.7 kg/m2) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-c] = 137±21 mg/dL), but otherwise healthy. Main outcomes measured included: dietary intake (energy, macronutrients and micronutrients), cardiometabolic risk markers (total cholesterol, LDL-c, high density lipoprotein cholesterol [HDL-c], triglycerides, cholesterol distribution in LDL and HDL subfractions, glucose, insulin, homeostasis model assessment, and C-reactive protein), and oxidative stress markers (vitamin C, total antioxidant capacity, oxidized LDL, and LDL susceptibility to oxidation). Effects of treatment, time, or interactions were assessed using repeated measures ANOVA. Results: There was no significant treatment-by-time effect for any dietary composition data, lipid profile, cardiometabolic outcomes, or oxidative stress markers. A significant time effect was observed for energy, which was decreased in both treatments (cucumber, -8.3%; nopales, -10.1%; pTime=0.026) mostly due to lower mono and polyunsaturated fatty acids intake (pTime=0.023 and pTime=0.003, respectively). Both treatments significantly increased triglyceride concentrations (cucumber, 14.8%; nopales, 15.2%; pTime=0.020). Despite the lack of significant treatment-by-time effects, great individual response variability was observed for all outcomes. After the cucumber and nopales phases, a decrease in LDL-c was observed in 44% and 63% of the participants respectively. On average LDL-c was decreased by 2.0 mg/dL (-1.4%) after the cucumber phase and 3.9 mg/dL (-2.9%) after the nopales phase (pTime=0.176). Pro-atherogenic changes in HDL subfractions were observed in both interventions over time, by decreasing the proportion of HDL-c in large HDL (cucumber, -5.1%; nopales, -5.9%; pTime=0.021) and increasing the proportion in small HDL (cucumber, 4.1%; nopales, 7.9%; pTime=0.002). Conclusions: These data do not support the purported benefits of nopales at doses of 2 cups/day for 2-wk on markers of lipoprotein profile, cardiometabolic risk, and oxidative stress in hypercholesterolemic adults.
ContributorsPereira Pignotti, Giselle Adriana (Author) / Vega-Lopez, Sonia (Thesis advisor) / Gaesser, Glenn (Committee member) / Keller, Colleen (Committee member) / Shaibi, Gabriel (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2013
Description
Objectives Through a cross-sectional observational study, this thesis evaluates the relationship between food insecurity and weight status, eating behaviors, the home food environment, meal planning and preparation, and perceived stress as it relates to predominantly Hispanic/Latino parents in Phoenix, Arizona. The purpose of this study was to address gaps in the literature by examining differences in "healthy" and "unhealthy" eating behaviors, foods available in the home, how time and low energy impact meal preparation, and the level of stress between food security groups. Methods Parents, 18 years or older, were recruited during two pre-scheduled health fairs, from English as a second language classes, or from the Women, Infants, and Children's clinic at a local community center, Golden Gate Community Center, in Phoenix, Arizona. An interview, electronic, or paper survey were offered in either Spanish or English to collect data on the variables described above. In addition to the survey, height and weight were collected for all participants to determine BMI and weight status. One hundred and sixty participants were recruited. Multivariate linear and logistic regression models, adjusting for weight status, education, race/ethnicity, income level, and years residing in the U.S., were used to assess the relationship between food security status and weight status, eating behaviors, the home food environment, meal planning and preparation, and perceived stress. Results Results concluded that food insecurity was more prevalent among parents reporting lower income levels compared to higher income levels (p=0.017). In adjusted models, higher perceived cost of fruits (p=0.004) and higher perceived level of stress (p=0.001) were associated with food insecurity. Given that the sample population was predominately women, a post-hoc analysis was completed on women only. In addition to the two significant results noted in the adjusted analyses, the women-only analysis revealed that food insecure mothers reported lower amounts of vegetables served with meals (p=0.019) and higher use of fast-food when tired or running late (p=0.043), compared to food secure mothers. Conclusion Additional studies are needed to further assess differences in stress levels between food insecure parents and food insecure parents, with special consideration for directionality and its relationship to weight status.
ContributorsVillanova, Christina (Author) / Bruening, Meg (Thesis advisor) / Ohri-Vachaspati, Punam (Committee member) / Vega-Lopez, Sonia (Committee member) / Arizona State University (Publisher)
Created2014
Description
Introduction: Human papillomavirus (HPV) infection is seen in up to 90% of cases of cervical cancer, the third leading cancer cause of death in women. Current HPV screening focuses on only two HPV types and covers roughly 75% of HPV-associated cervical cancers. A protein based assay to test for antibody biomarkers against 98 HPV antigens from both high and low risk types could provide an inexpensive and reliable method to screen for patients at risk of developing invasive cervical cancer. Methods: 98 codon optimized, commercially produced HPV genes were cloned into the pANT7_cGST vector, amplified in a bacterial host, and purified for mammalian expression using in vitro transcription/translation (IVTT) in a luminescence-based RAPID ELISA (RELISA) assay. Monoclonal antibodies were used to determine immune cross-reactivity between phylogenetically similar antigens. Lastly, several protein characteristics were examined to determine if they correlated with protein expression. Results: All genes were successfully moved into the destination vector and 86 of the 98 genes (88%) expressed protein at an adequate level. A difference was noted in expression by gene across HPV types but no correlation was found between protein size, pI, or aliphatic index and expression. Discussion: Further testing is needed to express the remaining 12 HPV genes. Once all genes have been successfully expressed and purified at high concentrations, DNA will be printed on microscope slides to create a protein microarray. This microarray will be used to screen HPV-positive patient sera for antibody biomarkers that may be indicative of cervical cancer and precancerous cervical neoplasias.
ContributorsMeshay, Ian Matthew (Author) / Anderson, Karen (Thesis director) / Magee, Mitch (Committee member) / Katchman, Benjamin (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05