Matching Items (48)
Description
Patients with malignant brain tumors have a median survival of approximately 15 months following diagnosis, regardless of currently available treatments which include surgery followed by radiation and chemotherapy. Improvement in the survival of brain cancer patients requires the design of new therapeutic modalities that take advantage of common phenotypes. One such phenotype is the metabolic dysregulation that is a hallmark of cancer cells. It has therefore been postulated that one approach to treating brain tumors may be by metabolic alteration such as that which occurs through the use of the ketogenic diet (KD). The KD is high-fat, low-carbohydrate diet that induces ketosis and has been utilized for the non-pharmacologic treatment of refractory epilepsy. It has been shown that this metabolic therapy enhances survival and potentiates standard therapy in mouse models of malignant gliomas, yet the anti-tumor mechanisms are not fully understood.
The current study reports that KetoCal® (KC; 4:1 fat:protein/carbohydrates), fed ad libitum, alters hypoxia, angiogenic, and inflammatory pathways in a mouse model of glioma. Tumors from animals maintained on KC showed reduced expression of the hypoxia marker carbonic anhydrase 9 (CA IX), a reduction in hypoxia inducible factor 1-alpha (HIF-1α) and decreased activation of nuclear factor kappa B (NF-κB). Animals maintained on KC also showed a reduction in expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased microvasculature in their tumors. Further, peritumoral edema was significantly reduced in animals fed the KC and protein analysis showed significantly altered expression of the tight junction protein zona occludens-1 (ZO-1) and the water channeling protein aquaporin-4 (AQP4), both of which have been implicated in malignant processes in glioma, including the formation of peritumoral edema in patients. Taken together the data suggests that KC alters multiple processes involved in malignant progression of gliomas. A greater understanding of the effects of the ketogenic diet as an adjuvant therapy will allow for a more rational approach to its clinical use.
The current study reports that KetoCal® (KC; 4:1 fat:protein/carbohydrates), fed ad libitum, alters hypoxia, angiogenic, and inflammatory pathways in a mouse model of glioma. Tumors from animals maintained on KC showed reduced expression of the hypoxia marker carbonic anhydrase 9 (CA IX), a reduction in hypoxia inducible factor 1-alpha (HIF-1α) and decreased activation of nuclear factor kappa B (NF-κB). Animals maintained on KC also showed a reduction in expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased microvasculature in their tumors. Further, peritumoral edema was significantly reduced in animals fed the KC and protein analysis showed significantly altered expression of the tight junction protein zona occludens-1 (ZO-1) and the water channeling protein aquaporin-4 (AQP4), both of which have been implicated in malignant processes in glioma, including the formation of peritumoral edema in patients. Taken together the data suggests that KC alters multiple processes involved in malignant progression of gliomas. A greater understanding of the effects of the ketogenic diet as an adjuvant therapy will allow for a more rational approach to its clinical use.
ContributorsWoolf, Eric C (Author) / Scheck, Adrienne C (Thesis advisor) / Lake, Douglas F (Committee member) / LaBaer, Joshua (Committee member) / Arizona State University (Publisher)
Created2014
Description
While obesity rates have plateaued within the last decade,
two-thirds of the United States
population is currently classified as overweight (defined a
s a body mass index [BMI] of
25-29.9 kg/m²) or obese (a BMI greater than 30 kg/m²). Bariatric
surgical interventions
are not only more effective than behavioral treatments
in the short term but are the only
form of obesity intervention with evidence of consisten
t long-term effectiveness.
However, even among bariatric surgery patients, weight
loss often stabilizes and it is
estimated that more than 20% of bariatric surgery patient
s will regain a significant
amount of weight that was initially lost long-term. Li
ttle research to date has been
conducted on physical activity in post bariatric surgery pati
ents. More specifically, there
have been no studies to date examining the effects of Me
ditative Movement (MM)
programs on body composition in bariatric patients. A s
tudy using an 8-week Tai Chi
Easy program was conducted in female gastric bypass patient
s to explore feasibility of
MM in the bariatric population as well as pre- and post-in
tervention changes in weight,
mindfulness, eating behaviors, body awareness, physical a
ctivity patterns, dietary quality
and mood. Data analysis revealed that there were no s
ignificant changes in weight or
physical activity patterns; however, significant changes w
ere observed in anxiety, overall
body awareness and cognitive restraint in eating. Addit
ionally, a significant decrease in
processed meat consumption and a weak trend towards increa
sed consumption of fruits
may suggest an overall improvement in dietary quality.
two-thirds of the United States
population is currently classified as overweight (defined a
s a body mass index [BMI] of
25-29.9 kg/m²) or obese (a BMI greater than 30 kg/m²). Bariatric
surgical interventions
are not only more effective than behavioral treatments
in the short term but are the only
form of obesity intervention with evidence of consisten
t long-term effectiveness.
However, even among bariatric surgery patients, weight
loss often stabilizes and it is
estimated that more than 20% of bariatric surgery patient
s will regain a significant
amount of weight that was initially lost long-term. Li
ttle research to date has been
conducted on physical activity in post bariatric surgery pati
ents. More specifically, there
have been no studies to date examining the effects of Me
ditative Movement (MM)
programs on body composition in bariatric patients. A s
tudy using an 8-week Tai Chi
Easy program was conducted in female gastric bypass patient
s to explore feasibility of
MM in the bariatric population as well as pre- and post-in
tervention changes in weight,
mindfulness, eating behaviors, body awareness, physical a
ctivity patterns, dietary quality
and mood. Data analysis revealed that there were no s
ignificant changes in weight or
physical activity patterns; however, significant changes w
ere observed in anxiety, overall
body awareness and cognitive restraint in eating. Addit
ionally, a significant decrease in
processed meat consumption and a weak trend towards increa
sed consumption of fruits
may suggest an overall improvement in dietary quality.
ContributorsSmith, Lisa L. (Author) / Larkey, Linda K (Thesis advisor) / Ainsworth, Barbara (Committee member) / Chisum, Jack (Committee member) / Ohri-Vachaspati, Punam (Committee member) / McClain, Darya (Committee member) / Arizona State University (Publisher)
Created2014
Description
ABSTRACT The purpose of this study was to determine the energy cost of four modes of resistance training (push-ups, pull-ups, curl-ups, lunges). Twelve well trained men aged 23.6 (SD=2.84) years were recruited to participate in the study. Each of the 12 men completed three trials of each of the four exercises on one visit to the laboratory lasting slightly over one hour (M=72 min, SD=5.9 min). The oxygen consumption of the men was monitored constantly throughout the trial and data was recorded every five seconds. Mean VO2 values were calculated for each exercise. The values for push-ups (M=11.57 ml/kg/min, SD=1.99), curl-ups (M=10.99 ml/kg/min, SD=1.48), pull-ups (M=10.87 ml/kg/min, SD=2.51), and lunges (M=14.18 ml/kg/min, SD=1.78) were converted to METs (Metabolic Equivalents). The MET values (3.31, 3.14, 3.11, and 4.05 respectively) all fall within the range of moderate intensity activity. The findings of this study show that a single set of any of the above exercises will qualify as a moderate intensity activity and can be used to meet recommendations on daily physical activity.
ContributorsVezina, Jesse (Author) / Ainsworth, Barbara (Thesis advisor) / Campbell, Kathryn (Committee member) / Woodruff, Larry (Committee member) / Arizona State University (Publisher)
Created2011
Description
Introduction: Several faith-based or faith-placed programs have focused on the physical dimension of wellness in efforts to improve health by increasing physical activity and improving diet behaviors. However, these programs were not designed to intervene on the mental dimension of wellness which is critical for stress reduction and health behavior change. Purpose: To evaluate the feasibility of a spirituality-based stress reduction and health behavior change intervention using the Spiritual Framework of Coping (SFC) model. Methods: This study was a quasi-experimental one group pretest posttest design. The study was a total of eight weeks conducted at a non-denominational Christian church. Participants were recruited from the church through announcements and flyers. The Optimal Health program met once a week for 1.5 hours with weekly phone calls during an additional four week follow-up period. Feasibility was assessed by the acceptability, demand, implementation, practicality, integration, and limited efficacy of the program. Analysis: Frequencies for demographics were assessed. Statistical analyses of feasibility objectives were assessed by frequencies and distribution of responses to feasibility evaluations. Limited efficacy of pretest and posttest measures were conducted using paired t-test (p <.05). Results: The Optimal Health Program was positively accepted by participants. The demand for the program was shown with average attendance of 78.7%. The program was successfully implemented as shown by meeting session objectives and 88% homework completion. The program was both practical for the intended participants and was successfully integrated within the existing environment. Limited efficacy changes within the program were mostly non-significant. Conclusion: This study tested the feasibility of implementing the Optimal Health program that specifically targeted the structural components of the Spiritual Framework of Coping Model identified to create meaning making and enhance well-being. This program may ultimately be used to help individuals improve and balance the spiritual, mental, and physical dimensions of wellness. However, length of study and limited efficacy measures will need to be reevaluated for program success.
ContributorsWalker, Jenelle R (Author) / Swan, Pamela (Thesis advisor) / Ainsworth, Barbara (Committee member) / Chisum, Jack (Committee member) / Fleury, Julie (Committee member) / Hooker, Steven (Committee member) / Arizona State University (Publisher)
Created2012
Description
The health enhancing effects of physical activity are well documented in the literature. However, women continue to report lower participation in exercise and physical activity (PA) compared to men. As women age an overall trend in decreased activity is observed. The primary place of activity reported in women is the home and one of the most commonly reported reasons for lack of physical activity is the lack of time. Few instruments have been developed that focus on the activity patterns of women. The Cross Cultural Physical Activity Study that this study was based on targeted women of color to assess the types of activity and constraints to activity experienced by African American and Native American women over 40 years old. This secondary data analysis focused on the psychometric properties of two scales used in the above study, The Physical Recreation Questionnaire (PRQ) and The Typical Week Physical Activity Survey (TWPAS). An exploratory factor analysis (EFA) was conducted on the 18 items from the Physical Recreation Questionnaire (PRQ) which focused on constraints to PA. The results of the EFA were a poor fit of a two factor model. The three factor model had a favorable fit in the EFA. Confirmatory factor analysis (CFA) was then conducted on the 18 items in the PRQ. Results of the CFA supported the presence of three latent variables: enjoyment of PA, constraints to PA, and negotiation of constraints to PA. The Typical Week Physical Activity Survey (TWPAS) is a 35 item measure of moderate PA that includes the activities most often reported by women. The purpose of the TWPAS was to capture habitual PA that might not be recorded in other PA questionnaires. The TWPAS was correlated with criterion measures of PA records, treadmill, accelerometer, and BMI. Although correlations were small, they were in the expected direction with the criterion measures. The evaluation of the instruments supported the presence of the construct of constraints to PA in the PRQ and the measurement of moderate intensity PA in the TWPAS.
ContributorsBishop, Jewel (Author) / Ainsworth, Barbara (Thesis advisor) / Komnenich, Pauline (Committee member) / Arizona State University (Publisher)
Created2012
Description
Features of the built environment (BE) are related to a wide range of health factors, including leisure-time physical activity (PA) and active forms of transportation. For working adults, worksite neighborhood is likely an important BE to better understand the impact of various factors on PA patterns. Compared to home neighborhood walkability research, worksite walkability has received relatively less attention. The objective of this project was to identify if worksite walkability was significantly associated with PA behavior.
Aims: to evaluate 1) the PA variation explained by work walkability, 2) the moderating effects of person-level characteristics to the relationship between PA and work walkability, and 3) the differences in the rate of change in PA over time by worksite walkability.
Methods: self-report and accelerometer measured PA at baseline (aim 1, 2); longitudinal accelerometer PA during the initial 56 days of a behavioral intervention (aim 3). Adults were generally healthy and reported part- or full-time employment with a geocodeable address outside the home. Geographic Information Systems (GIS) measured walkability followed established techniques (i.e., residential, intersection, and transit densities, and land-use-mix).
Results: On average, worksite walkability did not show direct relationships with PA (aim 1); yet certain person-level characteristics moderated the relationships: sex, race, and not having young children in the household (aim 2). During 56 days of intervention, the PA rate of change over time showed no evidence of a moderating effect by worksite walkability.
Discussion: Worksite walkability was generally not shown to relate to the overall PA. However, specific subgroups (women, those without young children) appeared more responsive to their worksite neighborhood walkability. Prior literature shows certain demographics respond differently with various BE exposures, and this study adds a potentially novel moderator of interest regarding young children at home. Understanding who benefits from access to walkable BE may inform targeted interventions and policy to improve PA levels and foster health equity.
Aims: to evaluate 1) the PA variation explained by work walkability, 2) the moderating effects of person-level characteristics to the relationship between PA and work walkability, and 3) the differences in the rate of change in PA over time by worksite walkability.
Methods: self-report and accelerometer measured PA at baseline (aim 1, 2); longitudinal accelerometer PA during the initial 56 days of a behavioral intervention (aim 3). Adults were generally healthy and reported part- or full-time employment with a geocodeable address outside the home. Geographic Information Systems (GIS) measured walkability followed established techniques (i.e., residential, intersection, and transit densities, and land-use-mix).
Results: On average, worksite walkability did not show direct relationships with PA (aim 1); yet certain person-level characteristics moderated the relationships: sex, race, and not having young children in the household (aim 2). During 56 days of intervention, the PA rate of change over time showed no evidence of a moderating effect by worksite walkability.
Discussion: Worksite walkability was generally not shown to relate to the overall PA. However, specific subgroups (women, those without young children) appeared more responsive to their worksite neighborhood walkability. Prior literature shows certain demographics respond differently with various BE exposures, and this study adds a potentially novel moderator of interest regarding young children at home. Understanding who benefits from access to walkable BE may inform targeted interventions and policy to improve PA levels and foster health equity.
ContributorsHurley, Jane Cathleen (Author) / Adams, Marc A (Thesis advisor) / Todd, Mike (Committee member) / Hooker, Steven P (Committee member) / Ohri-Vachaspati, Punam (Committee member) / Ainsworth, Barbara (Committee member) / Arizona State University (Publisher)
Created2019
Description
CD8+ T-lymphocytes (CTLs) are central to the immunologic control of infections and are currently at the forefront of strategies that enhance immune based treatment of a variety of tumors. Effective T-cell based vaccines and immunotherapies fundamentally rely on the interaction of CTLs with peptide-human leukocyte antigen class I (HLA-I) complexes on the infected/malignant cell surface. However, how CTLs are able to respond to antigenic peptides with high specificity is largely unknown. Also unknown, are the different mechanisms underlying tumor immune evasion from CTL-mediated cytotoxicity. In this dissertation, I investigate the immunogenicity and dysfunction of CTLs for the development of novel T-cell therapies. Project 1 explores the biochemical hallmarks associated with HLA-I binding peptides that result in a CTL-immune response. The results reveal amino acid hydrophobicity of T-cell receptor (TCR) contact residues within immunogenic CTL-epitopes as a critical parameter for CTL-self
onself discrimination. Project 2 develops a bioinformatic and experimental methodology for the identification of CTL-epitopes from low frequency T-cells against tumor antigens and chronic viruses. This methodology is employed in Project 3 to identify novel immunogenic CTL-epitopes from human papillomavirus (HPV)-associated head and neck cancer patients. In Project 3, I further study the mechanisms of HPV-specific T-cell dysfunction, and I demonstrate that combination inhibition of Indoleamine 2, 3-dioxygenase (IDO-1) and programmed cell death protein (PD-1) can be a potential immunotherapy against HPV+ head and neck cancers. Lastly, in Project 4, I develop a single-cell assay for high-throughput identification of antigens targeted by CTLs from whole pathogenome libraries. Thus, this dissertation contributes to fundamental T-cell immunobiology by identifying rules of T-cell immunogenicity and dysfunction, as well as to translational immunology by identifying novel CTL-epitopes, and therapeutic targets for T-cell immunotherapy.
onself discrimination. Project 2 develops a bioinformatic and experimental methodology for the identification of CTL-epitopes from low frequency T-cells against tumor antigens and chronic viruses. This methodology is employed in Project 3 to identify novel immunogenic CTL-epitopes from human papillomavirus (HPV)-associated head and neck cancer patients. In Project 3, I further study the mechanisms of HPV-specific T-cell dysfunction, and I demonstrate that combination inhibition of Indoleamine 2, 3-dioxygenase (IDO-1) and programmed cell death protein (PD-1) can be a potential immunotherapy against HPV+ head and neck cancers. Lastly, in Project 4, I develop a single-cell assay for high-throughput identification of antigens targeted by CTLs from whole pathogenome libraries. Thus, this dissertation contributes to fundamental T-cell immunobiology by identifying rules of T-cell immunogenicity and dysfunction, as well as to translational immunology by identifying novel CTL-epitopes, and therapeutic targets for T-cell immunotherapy.
ContributorsKrishna, Sri (Author) / Anderson, Karen S (Thesis advisor) / LaBaer, Joshua (Committee member) / Jacobs, Bertram L (Committee member) / Lake, Douglas F (Committee member) / Arizona State University (Publisher)
Created2017
Description
Valley Fever (VF), is a potentially lethal fungal pneumonia caused by Coccidioides spp., which is estimated to cause ~15-30% of all community-acquired pneumonias in the highly endemic Greater Phoenix and Tucson areas of Arizona. However, an accurate antigen-based diagnostic is still lacking. In order to identify protein and glycan antigen biomarkers of infection, I used a combination of genomics, proteomics and glycomics analyses to provide evidence of genus-specific proteins and glycosylations. The next goal was to determine if Coccidioides-specific glycans were present in biological samples from VF patients. Urine collected from 77 humans and 63 dogs were enriched for glycans and evaluated by mass spectrometry for Coccidioides-specific glycans and evaluated against a panel of normal donor urines, urines from patients infected with other fungi, and fungal cultures from closely related pneumonia-causing fungi. A combination of 6 glycan biomarkers was 100% sensitive and 100% specific in the diagnosis of human VF subjects, while only 3 glycan biomarkers were needed for 100% sensitivity and 100 specificity in the diagnosis of dog VF subject. Additionally, a blinded trial of 23 human urine samples was correctly able to classify urine samples with 93.3% sensitivity and 100% specificity. The results of this research provides evidence that Coccidioides genus-specific glycosylations have potential as antigens in diagnostic assays.
ContributorsMitchell, Natalie M (Author) / Lake, Douglas F (Thesis advisor) / Bean, Heather D (Committee member) / Grys, Thomas E (Committee member) / Magee, Dewey M (Committee member) / Arizona State University (Publisher)
Created2019
Description
Urinary sucrose and fructose has been suggested as a predictive biomarker of total sugars intake based on research involving UK adults. The purpose of this study was to determine the association between total sugars consumption and 24-hour urinary sucrose and fructose (24uSF) in US adult population and to investigate the effect of physical activity on this association. Fifty seven free-living healthy subjects 20 to 68 years old, participated in a 15-day highly controlled feeding study, consuming their habitual diet, provided by the research metabolic kitchen. Dietary sugars were estimated using Nutrition Data System for Research (NDSR). Subjects collected eight 24-hour urine samples measured for urinary sucrose and fructose. Physical activity was assessed daily using a validated 15-day log that inquired about 38 physical activities across six domains; home activities, transportation, occupation, conditioning, sports and leisure. The mean total sugars intake and added sugars intake of the sample was 112.2 (33.1) g/day and 65.8 (29.0) g/day (9.7%EI), respectively. Significant moderate positive correlation was found between 15-d mean total sugars intake and 8-day mean 24uSF (r = 0.56, p < 0.001). Similarly, added sugars were moderately correlated with 24uSF (r = 0.56, p < 0.001), while no correlation was found between naturally-occurring sugars and 24uSF (r = 0.070, p < 0.001). In a linear multiple regression, total and added sugars each explained 30% of variability in 24uSF (Adjusted R2, p value; total sugars: 0.297, 0.001; added sugars: 0.301, p < 0.001). Physical activity had no effect on the association between dietary and urinary sugars in neither the correlation nor the linear regression analysis. 24uSF can be used as a biomarker for total and added sugars consumption in US adults, although its predictability was weaker compared to findings involving UK adults. No evidence was found showing that physical activity levels affect the association between 24uSF and total sugars intake in US adults. More detailed investigation through future feeding studies including subjects with wide range of sugars intake and of different ethnic/racial backgrounds are needed to better understand the characteristics of the biomarker and its uses.
ContributorsMohan, Chitra (Author) / Tasevska, Natasha (Thesis advisor) / Ainsworth, Barbara (Committee member) / Johnston, Carol (Committee member) / Arizona State University (Publisher)
Created2019
Description
Biomarkers find a wide variety of applications in oncology from risk assessment to diagnosis and predicting and monitoring recurrence and response to therapy. Developing clinically useful biomarkers for cancer is faced with several challenges, including cancer heterogeneity and factors related to assay development and biomarker performance. Circulating biomarkers offer a rapid, cost-effective, and minimally-invasive window to disease and are ideal for population-based screening. Circulating immune biomarkers are stable, measurable, and can betray the underlying antigen when present below detection levels or even no longer present. This dissertation aims to investigate potential circulating immune biomarkers with applications in cancer detection and novel therapies. Over 600,000 cancers each year are attributed to the human papillomavirus (HPV), including cervical, anogenital and oropharyngeal cancers. A key challenge in understanding HPV immunobiology and developing immune biomarkers is the diversity of HPV types and the need for multiplexed display of HPV antigens. In Project 1, nucleic acid programmable protein arrays displaying the proteomes of 12 HPV types were developed and used for serum immunoprofiling of women with cervical lesions or invasive cervical cancer. These arrays provide a valuable high-throughput tool for measuring the breadth, specificity, heterogeneity, and cross-reactivity of the serologic response to HPV. Project 2 investigates potential biomarkers of immunity to the bacterial CRISPR/Cas9 system that is currently in clinical trials for cancer. Pre-existing B cell and T cell immune responses to Cas9 were detected in humans and Cas9 was modified to eliminate immunodominant epitopes while preserving its function and specificity. This dissertation broadens our understanding of the immunobiology of cervical cancer and provides insights into the immune profiles that could serve as biomarkers of various applications in cancer.
ContributorsEwaisha, Radwa Mohamed Emadeldin Mahmoud (Author) / Anderson, Karen S (Thesis advisor) / LaBaer, Joshua (Committee member) / Lake, Douglas F (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2018