Matching Items (121)
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 is the most aggressive and lethal brain tumor, due to its resistance to current conventional therapy. The resistance to chemo- and radiotherapy has been attributed to a special population of cells known as glioma stem cells. Previous literature has shown the importance of a Central Nervous System-restricted transcription factor OLIG2 in maintaining the tumor-propagating potential of these glioma stem cells. OLIG2's function was further elucidated, with its pro-mitogenic function due to its ability to negatively regulate the p53 pathway by suppressing the acetylation of the p53 protein's C terminal domain. Past work in our lab has confirmed that one of OLIG2's partner proteins is Histone Deacetylase 1 (HDAC1). In vitro experiments have also shown that targeting HDAC1 using hairpin RNA in glioma stem cells negatively impacts proliferation. In a survival study using a murine glioma model, targeting Hdac1 using hairpin RNA is shown to reduce tumor burden and increase survival. In this paper, we demonstrate that silencing Hdac1 expression reduces proliferation, increases cell death, likely a result of increased acetylation of p53. Olig2 expression levels seem to be unaffected in GSCs, demonstrating that the Hdac1 protein ablation is indeed lethal to GSCs. This work builds upon previously collected results, confirming that Hdac1 is a potential surrogate target for Olig2's pro-mitotic function in regulating the p53 pathway.
ContributorsLoo, Vincent You Wei (Author) / LaBaer, Joshua (Thesis director) / Mehta, Shwetal (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
CREB3L1 has been previously shown to auto-acetylate itself when prepared from HeLa cell based in vitro protein expression lysates. To circumvent the concerns of the contamination of co-purified human proteins from HeLa lysates, the protein was purified through insect cell transfection in vitro. The objective of this study was to assay the auto-acetylation activity of CREB3L1 prepared from insect cells using the baculovirus expression vector system (BEVS). To this end, His-tagged CREB3L1 was affinity purified from Hi5 cells using an IMAC column and used for acetylation assay. Samples were taken different time points and auto-acetylation was by western using antibodies specific to acetylated lysines. Auto-acetylation activity was observed after overnight incubation. Future experiments will focus on the improvement of purification yield and the identification of the substrates and interacting proteins of CREB3L1 to better understand the biological functions of this novel acetyltransferase.
ContributorsSchwab, Anna (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Abstract Objective: The purpose of this study was to determine the feasibility (e.g., practicality and demand) of a 4-week series of yoga classes in a homeless shelter. Participants: Five current residents of Central Arizona Shelter Services (CASS) and the Chief of Programming at CASS. Methods: Each shelter resident participated in a 5-minute interview answering questions regarding the demand of implementing a yoga program at CASS. The Chief of Programming participated in a 30-minute interview answering questions regarding the practicality of implementing a 4-week series yoga program at the homeless shelter. Results: CASS residents reported a strong desire to attend a yoga program. The Chief of Programming at CASS reported that implementing a yoga program would conflict with the overall goal of the shelter. Conclusion: Implementing a 4-week series yoga program is not feasible at CASS although there is a strong demand for a yoga program among the homeless population of the Phoenix metro area.
ContributorsSamuels, Jasmyne Angelique (Author) / Hart, Teresa (Thesis director) / Huberty, Jennifer (Committee member) / Pearl, Julia (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Recent research has confirmed and revealed many physical and mental benefits of yoga. The practice of yoga has spread throughout the western world, where it is widely used for the purpose of exercise and fitness. Due to its rise in popularity, there is a need for research regarding the energy expenditure required for different types of yoga. The majority of the literature cites yoga as being an effective exercise for light intensity activity, but there are not as many studies attempting to determine if there are postures and sequences that can meet the requirements for moderate physical activity. In addition, there is a need to validate mobile devices with which to measure energy expenditure (EE) that are compatible with the dynamic movements that occur during yoga. The purpose of this study was to measure energy expenditure of twenty-two yoga practitioners of varying experience during a 30-minute Vinyasa flow yoga practice and from this data collection determine: if an ashtanga-based vinyasa yoga class meets the criteria for moderate intensity physical activity, the reliability between the Actigraph and Oxycon Mobile and the validity of an Actigraph GT3X device worn on the hip in estimating energy expenditure for ashtanga-based vinyasa flow yoga. The Actigraph GT3X and the Oxycon mobile were used to measure energy expenditure. Mean values for energy expenditure recorded by the Oxycon and Actigraph were 3.19 ± 0.42 METs and 1.16 ± 0.23 METs respectively, exhibiting a significant difference in data collection. There was no correlation between the values recorded by the two devices, indicating that the Actigraph was not consistent with the Oxycon Mobile (previously validated for measurement of EE). Results of this study indicate that this Vinyasa flow yoga sequence does satisfy the criteria for moderate intensity physical activity as defined by ACSM with an average EE of 3.19 ± 0.42 METs, and that the Actigraph GT3X is not an accurate device for measurement of EE for yoga.
ContributorsHand, Lindsay Gabrielle (Author) / Huberty, Jennifer (Thesis director) / Buman, Matthew (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Objective: To investigate current HCP stillbirth aftercare practices and use findings to inform suggestions for stillbirth aftercare guidelines. Study Design: Participants (n=18) were HCPs (MDs, DOs, or NPs) in the field of Obstetrics and Gynecology or Maternal Fetal Medicine. Focus groups and surveys were conducted. A phenomenological approach was used to explore and understand current stillbirth aftercare practices and thoughts about protocols for stillbirth aftercare. Descriptive statistics were used to analyze demographics of participants and prevalence of references to stillbirth aftercare topics. Results: Sixteen obstetric HCPs (medical doctors and nurse practitioners in the fields of obstetrics and gynecology and/or maternal and fetal medicine) participated in Focus Groups and two obstetric HCPs alternatively completed surveys. Current stillbirth aftercare practices and perceptions related to stillbirth aftercare protocols and guidelines were clustered around the following themes: recommendations made to mothers after stillbirth, subsequent pregnancy care, perceptions and use of protocols for stillbirth aftercare, and responsibilities of nurses and nurse practitioners after stillbirth. Conclusion: Findings were used to develop a list of stillbirth aftercare practice suggestions and may be used to help design future research related to HCPs' stillbirth aftercare practices and the need for training on existing guidelines and development of further protocols or guidelines.
ContributorsMartinez, Lauren Ann (Author) / Huberty, Jennifer (Thesis director) / Coursen, Cristi (Committee member) / Leiferman, Jennifer (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Almost every form of cancer deregulates the expression and activity of anabolic glycosyltransferase (GT) enzymes, which incorporate particular monosaccharides in a donor acceptor as well as linkage- and anomer-specific manner to assemble complex and diverse glycans that significantly affect numerous cellular events, including tumorigenesis and metastasis. Because glycosylation is not template-driven, GT deregulation yields heterogeneous arrays of aberrant intact glycan products, some in undetectable quantities in clinical bio-fluids (e.g., blood plasma). Numerous glycan features (e.g., 6 sialylation, β-1,6-branching, and core fucosylation) stem from approximately 25 glycan “nodes:” unique linkage specific monosaccharides at particular glycan branch points that collectively confer distinguishing features upon glycan products. For each node, changes in normalized abundance (Figure 1) may serve as nearly 1:1 surrogate measure of activity for culpable GTs and may correlate with particular stages of carcinogenesis. Complementary to traditional top down glycomics, the novel bottom-up technique applied herein condenses each glycan node and feature into a single analytical signal, quantified by two GC-MS instruments: GCT (time-of-flight analyzer) and GCMSD (transmission quadrupole analyzers). Bottom-up analysis of stage 3 and 4 breast cancer cases revealed better overall precision for GCMSD yet comparable clinical performance of both GC MS instruments and identified two downregulated glycan nodes as excellent breast cancer biomarker candidates: t-Gal and 4,6-GlcNAc (ROC AUC ≈ 0.80, p < 0.05). Resulting from the activity of multiple GTs, t-Gal had the highest ROC AUC (0.88) and lowest ROC p‑value (0.001) among all analyzed nodes. Representing core-fucosylation, glycan node 4,6-GlcNAc is a nearly 1:1 molecular surrogate for the activity of α-(1,6)-fucosyltransferase—a potential target for cancer therapy. To validate these results, future projects can analyze larger sample sets, find correlations between breast cancer stage and changes in t-Gal and 4,6-GlcNAc levels, gauge the specificity of these nodes for breast cancer and their potential role in other cancer types, and develop clinical tests for reliable breast cancer diagnosis and treatment monitoring based on t-Gal and 4,6-GlcNAc.
ContributorsZaare, Sahba (Author) / Borges, Chad (Thesis director) / LaBaer, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Background: The purpose of this study was to determine the acceptability of a survey for MPN patients about: a) how patients with MPN cancer perceive information relayed from their healthcare providers in regards to integrative medicine and b) how patients use integrative medicine modalities to cope with their symptom burden (i.e. fatigue, headaches, abdominal discomfort). Additionally, we assessed what MPN patients thought about the survey (i.e., questions asked, how it could be modified, acceptability). This paper presents the patient's assessment of the survey. This information will be used to finalize the survey and distribute nationally to address integrative medicine and symptom burden in MPN patients. Methods: The survey was taken by 366, English speaking patients previously diagnosed with essential thrombocythemia, polycythemia vera, or myelofibrosis (primary and post polycythemia vera/post essential thrombocythemia) and ages 18 or older. The survey had XX questions and took approximately 20 minutes to complete. Acceptability questions were qualitatively analyzed and used to construct recurring themes and modifications for the final MPN Integrative Survey. Results: The following themes were recurrent in the acceptability responses; MPN symptom burden comments, views on healthcare, comments about demographics, and requests for survey modifications. When asked which Integrative Therapies have been used to treat symptom burden, participants most commonly named guidance therapy (i.e. counseling, prayer), physiotherapy ,and supplements administered orally, intravenously, intramuscularly, and topically. Conclusions: These results suggest this survey is an acceptable and feasible tool for MPN patients to assess how patients with MPN cancer perceive information relayed from their healthcare providers in regards to integrative medicine, and how patients use integrative medicine modalities to cope with their symptom burden. These findings also provide a better understanding of what facilitates and prevents MPN patients from using Integrative Medicine to treat MPN symptoms, as well as suggests useful survey modifications to inform the final MPN Integrative Survey.
ContributorsLebowitz, Nicole (Author) / Huberty, Jennifer (Thesis director) / Gowin, Krisstina (Committee member) / School of Nutrition and Health Promotion (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Objective: The purpose of this study was to determine the feasibility (i.e., acceptability) of a yoga intervention implemented within a preschool with typically and atypically developing children.
Participants: 29 children between the ages of three and five years that are currently attending the Mary Lou Fulton Teacher’s College Preschool.
Methods: Children participated in eight ~15-20-minute yoga sessions consisting of an opening circle, breathing, mindful movement, and a closing circle with relaxation time. Parents completed weekly homework assignments and surveys about the homework. Parents and teachers both completed daily behavior logs to track their child’s number of outbursts, mention of yoga, and use of yoga. Additionally, parents completed a post-intervention survey to determine overall satisfaction.
Results: The Preschool Behavior Questionnaire paired t-test results did not demonstrate any significant differences in pre-intervention (M=13.00, SD±7.55) and post-intervention (M=11.95, SD±6.92) scores, t(17)=0.94, p=0.36. There were no visible correlations between outbursts and use of yoga as reported by parents, but the use of yoga increased with the number of outbursts as reported by parents. Overall, parents felt the sessions had a positive effect on their child’s behavior and felt their children enjoyed the sessions.
Conclusion: Implementing classroom-based yoga programs could be an acceptable, realistic option to manage and prevent negative behaviors in preschool children.
Participants: 29 children between the ages of three and five years that are currently attending the Mary Lou Fulton Teacher’s College Preschool.
Methods: Children participated in eight ~15-20-minute yoga sessions consisting of an opening circle, breathing, mindful movement, and a closing circle with relaxation time. Parents completed weekly homework assignments and surveys about the homework. Parents and teachers both completed daily behavior logs to track their child’s number of outbursts, mention of yoga, and use of yoga. Additionally, parents completed a post-intervention survey to determine overall satisfaction.
Results: The Preschool Behavior Questionnaire paired t-test results did not demonstrate any significant differences in pre-intervention (M=13.00, SD±7.55) and post-intervention (M=11.95, SD±6.92) scores, t(17)=0.94, p=0.36. There were no visible correlations between outbursts and use of yoga as reported by parents, but the use of yoga increased with the number of outbursts as reported by parents. Overall, parents felt the sessions had a positive effect on their child’s behavior and felt their children enjoyed the sessions.
Conclusion: Implementing classroom-based yoga programs could be an acceptable, realistic option to manage and prevent negative behaviors in preschool children.
ContributorsColeman, Lindsey Katlin (Author) / Huberty, Jennifer (Thesis director) / Rotheram-Fuller, Erin (Committee member) / Mullady, Allison (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Background: The purpose of this study was to determine the feasibility of using Facebook as compared to a discussion board in an online, web-based intervention, Fit Minded College Edition-Podcasts (FMCEP), to improve physical activity and self-worth in female college students.
Methods: Participants (n=55) were randomly assigned to either a private Facebook group (FB) or the Fit Minded discussion board (DB) to participate in discussion of health and wellness related podcasts. FMCEP was a 6-week intervention guided by the self-determination theory (SDT) to target autonomy, relatedness and competence. Each week participants were instructed to complete three tasks: (1) listen to an assigned podcast, (2) complete a workbook assignment, and (3) participate in FB or DB online discussion. Participants completed assessments at baseline and post-intervention (6-weeks).
Results: Self-reported physical activity (p=0.032, η2= 0.193) and physical self-worth (p<0.001, η2=0.747) increased significantly over time, but no difference was seen between the groups for both physical activity (p=0.266, η2= 0.056) and physical self-worth (p=0.485, η2=0.024). Website use (measured by mean number of engagements per day, each week) declined across the 6-week intervention in the DB group but was consistent in the FB group.
Conclusion: These findings suggest web-based interventions, guided by SDT, can improve physical activity and physical self-worth among female college students, and the Facebook group may be more feasible and effective. Future studies are needed to optimize web-based physical activity interventions in college females.
Methods: Participants (n=55) were randomly assigned to either a private Facebook group (FB) or the Fit Minded discussion board (DB) to participate in discussion of health and wellness related podcasts. FMCEP was a 6-week intervention guided by the self-determination theory (SDT) to target autonomy, relatedness and competence. Each week participants were instructed to complete three tasks: (1) listen to an assigned podcast, (2) complete a workbook assignment, and (3) participate in FB or DB online discussion. Participants completed assessments at baseline and post-intervention (6-weeks).
Results: Self-reported physical activity (p=0.032, η2= 0.193) and physical self-worth (p<0.001, η2=0.747) increased significantly over time, but no difference was seen between the groups for both physical activity (p=0.266, η2= 0.056) and physical self-worth (p=0.485, η2=0.024). Website use (measured by mean number of engagements per day, each week) declined across the 6-week intervention in the DB group but was consistent in the FB group.
Conclusion: These findings suggest web-based interventions, guided by SDT, can improve physical activity and physical self-worth among female college students, and the Facebook group may be more feasible and effective. Future studies are needed to optimize web-based physical activity interventions in college females.
ContributorsSorteberg, Samantha Fern (Author) / Huberty, Jennifer (Thesis director) / Bruening, Meg (Committee member) / Mailey, Emily (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05