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- Creators: Arizona State University
- Creators: Chen, Angela
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
Description
Over the past several decades, there has been a growing interest in the use of fluorescent probes in low-cost diagnostic devices for resource-limited environments. This dissertation details the design, development, and deployment of an inexpensive, multiplexed, and quantitative, fluorescence-based lateral flow immunoassay platform, in light of the specific constraints associated with resource-limited settings.
This effort grew out of the need to develop a highly sensitive, field-deployable platform to be used as a primary screening and early detection tool for serologic biomarkers for the high-risk human papillomavirus (hrHPV) infection. A hrHPV infection is a precursor for developing high-grade cervical intraepithelial neoplasia (CIN 2/3+). Early detection requires high sensitivity and a low limit-of-detection (LOD). To this end, the developed platform (DxArray) takes advantage of the specificity of immunoassays and the selectivity of fluorescence for early disease detection. The long term goal is to improve the quality of life for several hundred million women globally, at risk of being infected with hrHPV.
The developed platform uses fluorescent labels over the gold-standard colorimetric labels in a compact, high-sensitivity lateral flow assay configuration. It is also compatible with POC settings as it substitutes expensive and bulky light sources for LEDs, low-light CMOS cameras, and photomultiplier tubes for photodiodes, in a transillumination architecture, and eliminates the need for expensive focusing/transfer optics. The platform uses high-quality interference filters at less than $1 each, enabling a rugged and robust design suitable for field use.
The limit of detection (LOD) of the developed platform is within an order of magnitude of centralized laboratory diagnostic instruments. It enhances the LOD of absorbance or reflectometric and visual readout lateral flow assays by 2 - 3 orders of magnitude. This system could be applied toward any chemical or bioanalytical procedure that requires a high performance at low-cost.
The knowledge and techniques developed in this effort is relevant to the community of researchers and industry developers looking to deploy inexpensive, quantitative, and highly sensitive diagnostic devices to resource-limited settings.
This effort grew out of the need to develop a highly sensitive, field-deployable platform to be used as a primary screening and early detection tool for serologic biomarkers for the high-risk human papillomavirus (hrHPV) infection. A hrHPV infection is a precursor for developing high-grade cervical intraepithelial neoplasia (CIN 2/3+). Early detection requires high sensitivity and a low limit-of-detection (LOD). To this end, the developed platform (DxArray) takes advantage of the specificity of immunoassays and the selectivity of fluorescence for early disease detection. The long term goal is to improve the quality of life for several hundred million women globally, at risk of being infected with hrHPV.
The developed platform uses fluorescent labels over the gold-standard colorimetric labels in a compact, high-sensitivity lateral flow assay configuration. It is also compatible with POC settings as it substitutes expensive and bulky light sources for LEDs, low-light CMOS cameras, and photomultiplier tubes for photodiodes, in a transillumination architecture, and eliminates the need for expensive focusing/transfer optics. The platform uses high-quality interference filters at less than $1 each, enabling a rugged and robust design suitable for field use.
The limit of detection (LOD) of the developed platform is within an order of magnitude of centralized laboratory diagnostic instruments. It enhances the LOD of absorbance or reflectometric and visual readout lateral flow assays by 2 - 3 orders of magnitude. This system could be applied toward any chemical or bioanalytical procedure that requires a high performance at low-cost.
The knowledge and techniques developed in this effort is relevant to the community of researchers and industry developers looking to deploy inexpensive, quantitative, and highly sensitive diagnostic devices to resource-limited settings.
ContributorsObahiagbon, Uwadiae (Author) / Blain Christen, Jennifer M (Thesis advisor) / Anderson, Karen S (Committee member) / Goryll, Michael (Committee member) / Smith, Barbara S. (Committee member) / Arizona State University (Publisher)
Created2018
DescriptionThis study aimed to: (a) examine adolescents' knowledge, attitudes and behavioral intention about HPV and vaccination in adolescent boys and girls aged 11-17; and (b) examine gender differences in responses given by adolescent boys and girls aged 11-17.
ContributorsReidhead, Whitney Brooke (Author) / Chen, Angela (Thesis director) / Stevens, Carol (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Recent studies have shown that human papillomavirus (HPV) plays a role in development of cancers, one of which is head and neck cancer. There is strong and consistent molecular evidence demonstrating that human papillomavirus (HPV) is an etiological cause of these oropharyngeal cancers. Despite the introduction of HPV vaccines, there is still an increase in human papillomavirus associated OPC (HPVOPC) and it is expected that the incidence of head and neck cancer, specifically oropharyngeal cancer (OPC) will increase. The aim of this study is to utilize human papillomavirus (HPV) seropositivity for rapid detection of HPV early specific antigen-antibodies using a lateral flow assay.
Human papillomavirus (HPV) 16 proteins of interest, E7, E6 and CE2 were expressed and purified in E. coli for detection of specific antibodies using lateral flow assay because viral and host factors impact the serologic responses to HPV early antigens in HPV-positive oropharyngeal cancer. 17 samples and 5 controls with already known antibody reactivity from ELISA analysis were selected for HPV serologic responses. The lateral flow strip was evaluated for its color band intensity using Image J software. Peak area was used to quantify the color intensity of the lateral flow strip. Out of the 17 samples, 11 (64.7%) showed high antibody levels to E7, 12 (70.6%) showed high Ab levels to E6 and 6 (35.3%) showed high Ab levels to CE2. Correlation coefficient between antibody detection by sight and ELISA for E7, CE2 and E6 were 0.6614, 0.4845 and 0.2372 respectively and correlation coefficient between lateral flow assay and ELISA for E7, CE2 and E6 were 0.3480, 0.1716 and 0.1644 respectively. This further proves patients or samples with HPV 16 oropharyngeal cancer have detectable antibodies to early E7, E6 and E2 proteins, which are potential biomarkers for HPV-associated oropharyngeal cancer.
Human papillomavirus (HPV) 16 proteins of interest, E7, E6 and CE2 were expressed and purified in E. coli for detection of specific antibodies using lateral flow assay because viral and host factors impact the serologic responses to HPV early antigens in HPV-positive oropharyngeal cancer. 17 samples and 5 controls with already known antibody reactivity from ELISA analysis were selected for HPV serologic responses. The lateral flow strip was evaluated for its color band intensity using Image J software. Peak area was used to quantify the color intensity of the lateral flow strip. Out of the 17 samples, 11 (64.7%) showed high antibody levels to E7, 12 (70.6%) showed high Ab levels to E6 and 6 (35.3%) showed high Ab levels to CE2. Correlation coefficient between antibody detection by sight and ELISA for E7, CE2 and E6 were 0.6614, 0.4845 and 0.2372 respectively and correlation coefficient between lateral flow assay and ELISA for E7, CE2 and E6 were 0.3480, 0.1716 and 0.1644 respectively. This further proves patients or samples with HPV 16 oropharyngeal cancer have detectable antibodies to early E7, E6 and E2 proteins, which are potential biomarkers for HPV-associated oropharyngeal cancer.
ContributorsLadipo, Evelyn (Author) / Anderson, Karen S (Thesis advisor) / Hogue, Brenda G (Committee member) / Hou, Ching-Wen (Committee member) / Arizona State University (Publisher)
Created2019
Description
The purpose of this study was to examine the effect of educational videos on Human Papillomavirus (HPV) vaccination intent among young adults aged 18-26. A two-group randomized control trial (RCT) is conducted among 156 individuals (control group n = 79, intervention group n= 77). Inclusion criteria were English-speaking young adults aged 18-26 who have not been vaccinated against HPV. Participants who met the inclusion criteria based on an online screening form were recruited via Amazon Mechanical Turk (MTurk) and invited to join the study. They first completed a pretest (T0) online via REDCap, randomly assigned to the intervention or control group, and completed a posttest (T1) after viewing their assigned intervention. Participants assigned to the intervention group watched two brief animated videos while participants assigned to the control group examined an HPV educational brochure created by the Centers for Disease Control and Prevention (CDC). Guided by the Theory of Planned Behavior, survey questions measured HPV-related knowledge, attitudes, perceived severity, perceived susceptibility, vaccination intent (T0 and T1), sociodemographic characteristics, and health history (T0 only) of participants. The results showed the intervention group had an increase in vaccination intent while the control group had a decrease in vaccination intent. This shows that video education methods are more effective than traditional written education methods at increasing vaccination intention among young adults.
ContributorsShinherr, Sophia (Author) / Vasquez, Savannah (Co-author) / Chen, Angela (Thesis director) / Reifsnider, Elizabeth (Committee member) / Scott, Jason (Committee member) / Han, SeungYong (Committee member) / Barrett, The Honors College (Contributor) / Edson College of Nursing and Health Innovation (Contributor)
Created2022-05
Description
Background: It is estimated that 50% of all mental illness arises prior to age 14, an incident attributed in part to disruptions and imbalances within the family system. Equine assisted learning is a complementary and alternative approach to family therapy which is being used increasingly to promote mental health in both adults and children. This study sought to build and deliver an evidence-based, family-centered equine assisted learning program aimed at promoting family function, family satisfaction and child social-emotional competence, and to measure its acceptability and preliminary effect.
Method: Twenty families with children 10 years and older were recruited to participate in a 3-week equine assisted learning program at a therapeutic riding center in Phoenix, Arizona. Sessions included groundwork activities with horses used to promote life skills using experiential learning theory. The study design included a mixed-method quasi-experimental one-group pretest posttest design using the following mental health instruments: Devereaux Student Strengths Assessment, Brief Family Assessment Measure (3 dimensions), and Family Satisfaction Scale to measure child social-emotional competence, family function, and family satisfaction, respectively. Acceptability was determined using a Likert-type questionnaire with open-ended questions to gain a qualitative thematic perspective of the experience.
Results: Preliminary pretest and posttest comparisons were statistically significant for improvements in family satisfaction (p = 0.001, M = -5.84, SD = 5.63), all three domains of family function (General Scale: p = 0.005, M = 6.84, SD = 9.20; Self-Rating Scale: p = 0.050, M = 6.53, SD = 12.89; and Dyadic Relationship Scale: p = 0.028, M = 3.47, SD = 7.18), and child social-emotional competence (p = 0.015, M = -4.05, SD 5.95). Effect sizes were moderate to large (d > 0.5) for all but one instrument (Self-Rating Scale), suggesting a considerable magnitude of change over the three-week period. The intervention was highly accepted among both children and adults. Themes of proximity, self-discovery, and regard for others emerged during evaluation of qualitative findings. Longitudinal comparisons of baseline and 3-month follow-up remain in-progress, a topic available for future discussion.
Discussion: Results help to validate equine assisted learning as a valuable tool in the promotion of child social-emotional intelligence strengthened in part by the promotion of family function and family satisfaction. For mental health professionals, these results serve as a reminder of the alternatives that are available, as well as the importance of partnerships within the community. For therapeutic riding centers, these results help equine professionals validate their programs and gain a foothold within the scientific community. Additionally, they invite future riding centers to follow course in incorporating evidence into their programs and examining new directions for growth within the mental health community.
Method: Twenty families with children 10 years and older were recruited to participate in a 3-week equine assisted learning program at a therapeutic riding center in Phoenix, Arizona. Sessions included groundwork activities with horses used to promote life skills using experiential learning theory. The study design included a mixed-method quasi-experimental one-group pretest posttest design using the following mental health instruments: Devereaux Student Strengths Assessment, Brief Family Assessment Measure (3 dimensions), and Family Satisfaction Scale to measure child social-emotional competence, family function, and family satisfaction, respectively. Acceptability was determined using a Likert-type questionnaire with open-ended questions to gain a qualitative thematic perspective of the experience.
Results: Preliminary pretest and posttest comparisons were statistically significant for improvements in family satisfaction (p = 0.001, M = -5.84, SD = 5.63), all three domains of family function (General Scale: p = 0.005, M = 6.84, SD = 9.20; Self-Rating Scale: p = 0.050, M = 6.53, SD = 12.89; and Dyadic Relationship Scale: p = 0.028, M = 3.47, SD = 7.18), and child social-emotional competence (p = 0.015, M = -4.05, SD 5.95). Effect sizes were moderate to large (d > 0.5) for all but one instrument (Self-Rating Scale), suggesting a considerable magnitude of change over the three-week period. The intervention was highly accepted among both children and adults. Themes of proximity, self-discovery, and regard for others emerged during evaluation of qualitative findings. Longitudinal comparisons of baseline and 3-month follow-up remain in-progress, a topic available for future discussion.
Discussion: Results help to validate equine assisted learning as a valuable tool in the promotion of child social-emotional intelligence strengthened in part by the promotion of family function and family satisfaction. For mental health professionals, these results serve as a reminder of the alternatives that are available, as well as the importance of partnerships within the community. For therapeutic riding centers, these results help equine professionals validate their programs and gain a foothold within the scientific community. Additionally, they invite future riding centers to follow course in incorporating evidence into their programs and examining new directions for growth within the mental health community.
ContributorsSolarz, Allison (Author) / Chen, Angela (Thesis advisor)
Created2019-05-02