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- All Subjects: Cancer
- All Subjects: Down syndrome
- Creators: School of Molecular Sciences
- Creators: College of Health Solutions
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
- Member of: Theses and Dissertations
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.
The goal of this project was to design and create a genetic construct that would allow for <br/>tumor growth to be induced in the center of the wing imaginal disc of Drosophila larvae, the <br/>R85E08 domain, using a heat shock. The resulting transgene would be combined with other <br/>transgenes in a single fly that would allow for simultaneous expression of the oncogene and, in <br/>the surrounding cells, other genes of interest. This system would help establish Drosophila as a <br/>more versatile and reliable model organism for cancer research. Furthermore, pilot studies were <br/>performed, using elements of the final proposed system, to determine if tumor growth is possible <br/>in the center of the disc, which oncogene produces the best results, and if oncogene expression <br/>induced later in development causes tumor growth. Three different candidate genes were <br/>investigated: RasV12, PvrACT, and Avli.
Down syndrome (DS) is a common genetic developmental disorder characterized by the trisomy of chromosome 21 (Hsa21). All individuals with DS have some kind of intellectual disability, associated with dysfunction in cognition-related structures, including the frontal cortex. Studies have examined developmental changes in the frontal cortex during prenatal stages in DS, however little is known about cortical lamination and neuronal differentiation in postnatal periods in this neurodevelopmental disorder. Therefore, we examined the quantitative and qualitative distribution of neuronal profiles containing the neuronal migration protein doublecortin (DCX), the non-phosphorylated high-molecular-weight neurofilament SMI-32, the calcium-binding proteins calbindin D-28K (Calb), calretinin (Calr), and parvalbumin (Parv), as well as human β-amyloid and APP (6E10), Aβ1-42, and phospho-tau (CP-13) in the supragranular (SG, II/III) and infragranular (IG, V/VI) layers in the DS postnatal frontal cortex compared to neurotypically developing (NTD) controls from ages 28 weeks to 196.4 weeks using immunohistochemistry. Furthermore, cortical lamination was evaluated using thionin, a Nissl stain. We found DCX-immunoreactive (-ir) cells in both the SG and IG layers in younger cases, but not in the oldest cases in both groups. Strong expression of SMI-32 immunoreactivity was observed in pyramidal cells in layers III and V in the oldest cases in both groups, however SMI-32-ir cells appeared much earlier in NTD compared to DS. We found small and fusiform Calb-ir cells in the younger cases (28 to 44 weeks), while in the oldest cases, Calb immunoreactivity was also found in pyramidal cells. Calr-ir cells appeared earlier in DS at 32 weeks compared to NTD at 44 weeks, however both groups showed large bipolar fusiform-shaped Calr-ir cells in the oldest cases. Diffuse APP/Aβ-ir plaque-like accumulations were found in the frontal cortex grey and white matter at all ages, but no Aβ1-42 immunoreactivity was detected in any case. Furthermore, neuropil (but not cellular) granular CP-13 immunostaining was seen in layer I only at 41 weeks NTD and 33 weeks DS. Cell counts show a significantly higher cell number in SG compared to IG for all the neuronal markers in both groups, except in Calb and SMI-32. In NTD, age and brain weight showed the strongest correlations with all cellular counts, except in thionin where DS had a stronger negative correlation with age and brain weight compared to NTD. In addition, height and body weight showed a strong negative correlation in NTD with the migration and neurogenesis marker DCX. These findings suggest that trisomy 21 affects the postnatal frontal cortex lamination, neuronal migration<br/>eurogenesis, and differentiation of projection pyramidal cells and interneurons, which contribute to the disruption of the local and projection inhibitory and excitatory circuitries that may underlie the cognitive disabilities in DS.
Brave Bears was a Barrett creative project that operated under local non-profit organizations, Amanda Hope Rainbow Angels and Arizona Women’s Recovery Center. Amanda Hope Rainbow Angels provides support and education for children fighting cancer and their families. Arizona Women’s Recovery Center provides rehabilitation programs for women fighting substance abuse and housing for the women and their children. The Brave Bears Project was focused on helping children in these situations cope with the trauma they are experiencing. The children received a teddy bear, which is a transitional object. In addition, a clay pendant with the word, “brave” pressed into it was tied around the bear’s neck with a ribbon. A poem of explanation and encouragement was also included.<br/><br/>The teddy bear provided comfort to children experiencing emotionally distressing situations as they receive treatment for their illness or as their mom undergoes rehabilitation. This can be in the form of holding the teddy bear when they feel frightened, anxious, lonely or depressed. The “brave” pendant and poem seek to encourage them and acknowledge their trauma and ability to persevere.
Down syndrome (DS) is caused by either an extra copy of chromosome 21 or by extra material on chromosome 21. This causes various levels of intellectual disability and issues with gross motor skill development which can prevent these individuals from participating in activities of daily living (ADL) such as getting dressed, self-care, or grocery shopping. People with DS have a decreased ability to balance, an abnormal and slower gait pattern, difficulty adapting to new environments, and a lack of improvement in these areas with growth and development when compared to their neurotypical peers. The objective of this study was to determine the immediate effects of resistance training (RT) and assisted cycle therapy (ACT) on adults with DS’s balance ability and gait speed. Each participant completed one session of RT, ACT (stationary cycling with the assistance of a motor to maintain a cadence of at least 35% greater than their voluntary cycling speed), and no training in a randomly selected order. Balance and gait speed were measured by a Clinical Test of Sensory Interaction on Balance (CTSIB) (i.e., eyes open firm surface, eyes closed firm surface, eyes open foam surface, eyes closed foam surface) on a Balance Tracking System Board (Btracks board) and by a Timed Up and Go (TUG) test. A total of ten participants’ data was used for analysis. The measures of total path length (cm), anterior-posterior (AP) excursion, and medial-lateral (ML) excursion were used to analyze the CTSIB. The average time was used to analyze the TUG test. The results showed that the eyes closed foam surface balance task was the most challenging balance task for every participant in every intervention. Furthermore, the most improvement was evident in the eyes closed foam surface balance task from pre to post intervention in all of the interventions. Post hoc tests also indicated statistically significant improvements of path length from pre to post in the RT intervention with the eyes closed foam surface balance task as well as with AP excursion in the ACT intervention with the eyes closed foam surface balance task. Possible explanations for improvements from pre to post in the eyes closed foam balance task across all interventions will be discussed with respect to the length of the intervention, and the effect of strength, social and learned factors on balance in adults with DS.