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Design And Development Of A Novel Class Of Cell Cycle Cdk Inhibitors Targeting The Cyclin Binding Groove Utilizing The Replace Strategy, Padmavathy Nandha Premnath

Theses and Dissertations

Inhibition of CDK2 activity in G1 and S phases of the cell cycle can promote selective apoptosis of cancer cells through the E2F1 pathway. Currently available CDK inhibitors target the ATP binding pocket and result in lack of specificity for the cell cycle vs. the transcriptional CDKs. It has been shown that a peptide HAKRRLIF derived from the tumor suppressor p21 binds to the cyclin binding groove (CBG) and selectively inhibits cell cycle CDKs (CDK2/Cyclin A, CDK2/Cyclin E and CDK4/Cyclin D). The CBG is unique to cell cycle CDKs hence targeting this site avoids the inhibition of transcriptional CDKs can …

A Three-Dimensional-Engineered Matrix To Study The Microenvironment Of Cancer Stem Cells, Samaneh Kamali Sarvestani

Theses and Dissertations

Maintenance of cancer stem cells (CSCs) is regulated by their microenvironment. As cancer cells are affected by many factors in their microenvironment, a major challenge is to isolate the effect of a specific factor on CSCs while keeping other factors unchanged. We developed a synthetic inert 3D Poly Ethylene Glycol Di-Acrylate (PEGDA) gel culture system as a unique tool to study the effect of microenvironmental factors on CSCs response. Synthetic hydrogels provide the flexibility to design three-dimensional (3D) matrices to isolate and study individual factors in the tumor microenvironment. The first objective of this work was to investigate the effect …

Geographic Disparities In Cancer Mortality To Incidence Ratios, Kyle Buck

Theses and Dissertations

While cancer rates have shown promising trends over the last few decades, not all populations have experienced the same levels of decrease in cancer incidence in mortality rates. Identifying populations suffering from the impacts of the disparities has become a major goal in cancer research.

Most research has focused on the influence of single variables on cancer disparities or on small-scale case studies. Using the information from these analyses, the research conducted in this dissertation tests the relationship of selected variables to an outcome measure, the mortality to incidence ratio (MIR) in search of spatial relationships between the indicators and …

Role Of Chronic Inflammation On Liver Function During Cachexia Progression In The ApcMin/+ Mouse Model, Aditi Narsale

Theses and Dissertations

Cachexia is a multifactorial syndrome that manifests during the advanced stage of chronic diseases and is characterized by a progressive loss of body mass sustained by underlying inflammation. The ApcMin/+ mouse is an established model of cachexia that exhibits a gradual loss of body mass correlating with increasing tumor burden and plasma IL – 6 levels. Moreover it also mimics other secondary characteristics observed in cachectic patients like splenomegaly, elevated plasma endotoxin levels, gut barrier dysfunction, hypogonadism and an overall hypermetabolic state. Liver controls the energy metabolism in the body by regulating glucose and lipid metabolism, glycogen storage, filtration of …

Identification Of Microrna Biomarkers In Her2-Positive Breast Cancer, Hossam Tashkandi

Theses and Dissertations

Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 30% of breast cancer patients with poor prognosis. In addition, microRNAs are small non-coding RNA that have been linked to many cancers. Here we investigate which miRNAs are differentially regulated by HER2 overexpression. Using quantitative reverse-transcription prolymerase chain reaction (QRT-PCR) and matching it with the clinical data acquired from Dvinge, we find five candidate miRNAs. When comparing the miRNAs’ effect on patient survival, only three miRNAs stand as good predictors of patient survival outcome. These miRNAs are miR-146a-5p, miR-181d, and miR-195-5p. When miR-146a-5p is up-regulated, which is the case …

I Wish I Had Known This!: Impact Of Age On Life Choices And Testing Satisfaction For Brca1/2 Mutation Carriers Who Underwent Genetic Testing By Age 25, Sarah Elaine King

Theses and Dissertations

Objective: To examine if BRCA1/2 mutation carriers who received their positive genetic test result by age 25 were satisfied with their decision to undergo genetic testing and with the choices made regarding family planning, surveillance, and surgery. Methods: 72 participants recruited via social media completed a survey hosted by SurveyMonkey.com. Sixty-three met study criteria and were asked 40 quantitative and qualitative questions designed to assess family planning, surveillance, and surgery needs of young BRCA carriers, which included a six question Satisfaction with Decision Scale. Results: Regardless of age, participants were very satisfied with the decision to undergo genetic testing. Recommendations …

Role Of Micro Rna 148/152 Family In Cancer Progression, Anusha Chaparala

Theses and Dissertations

Micro RNA are small single stranded RNA that regulate the expression of various genes. MiRNA guide the mRNA disintegrating RISC complex to the complimentary sequence in the target mRNA. Each micro RNA has multiple targets and can play a different biological role depending on the population of targets at the particular stage of the cell or a physiological state. Several miRNA show elevated or decreased levels of expression in various cancers because of their role in tumor initiation and progression. MiRNA belonging to mir148/152 family are examples of such MicroRNA. This family includes miR148a, miR148b and miR152. MiR148a and miR152 …

Stress Management For Cancer Survivors Using A Technologically Adapted Psychosocial Intervention: A Randomized Trial Determining The Effect Of Expressive Writing On Psychoneuroimmunology Based Outcomes, Utkarsh B. Subnis

Theses and Dissertations

Patients with cancer transitioning from completing their final cancer treatments to survivorship are particularly at risk for experiencing psychosocial stress, and the Institute of Medicine (IOM) has referred to these cancer patients as “lost in transition.” In this study, patients with cancer in their transition phase after completing their final radiation treatment were defined as cancer survivors (CS). CS must deal with chronic stressors such as the fear of cancer recurrence as well as the resumption of their roles in their family and work lives. Chronic stress impacts the nervous system and increases secretion of stress hormones (e.g. cortisol) from …

The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence

Theses and Dissertations

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells. The affected cytokines …