Digital Commons Network^™

Phosphorylation Of Cdk2 At Threonine 39 By Akt Facilitates Cyclin-Cdk2 Activation, Thiago Bezerra Gaspar Carvalho Da Silva

Open Access Dissertations

Cdk2 importantly regulates G1 progression. Cdk2 activation requires cyclin binding and phosphorylation at T160 by CAK. Here we describe a novel Cdk2 site whose Akt dependent phosphorylation appears to facilitate cyclin-Cdk2 assembly Cdk2 bears a Akt consensus motif containing threonine 39 (T39) immediately preceding the PSTAIRE helix. Cellular Cdk2 co-precipitated with Akt and Akt phosphorylated Cdk2 in vitro. Treatment of quiescent cells with serum leads to activation of the Akt pathway, followed by phosphorylation of Cdk2T39. This phosphorylation preceded the formation of cyclin-Cdk2 complexes and the phosphorylation at Cdk2T160. PI3K inhibition caused cyclin E dissociation from Cdk2, loss of CAK …

In The Middle, Nicole Pugh

University of New Orleans Theses and Dissertations

A woman just getting settled in New Orleans with her fiancé is uprooted by Hurricane Katrina. She spends the two months after the hurricane in various parts of Louisiana trying to pick up the pieces of her uprooted reality. Along the way, she encounters ordinary people who act as inspirations and is also reminded of her deceased Chinese grandmother, whom she was care-giver to before she died and whose stories about life in China and the US parallel the woman´s own life during the post-Katrina months of vulnerability and change.

Structural Insights Into Dna Replication And Lesion Bypass By Y Family Dna Polymerases, Kevin N. Kirouac

Electronic Thesis and Dissertation Repository

Y family DNA polymerases are specialized enzymes for replication through sites of DNA damage in the genome. Although the DNA damage bypass activity of these enzymes is important for genome maintenance and integrity, it is also responsible for DNA mutagenesis due to the error-prone nature of the Y family. Understanding how these enzymes select incoming nucleotides during DNA replication will give insight into their role in cancer formation, aging, and evolution. This work attempts to mechanistically explain, primarily through X-ray crystallography and enzymatic activity assays, how Y family polymerases select incoming nucleotides in various DNA replication contexts. Initially, we sought …

Obesity And Acute Lymphocytic Leukemia, Jacob Michael Taylor

Electronic Theses and Dissertations

Obesity rates for pediatric acute lymphocytic leukemia (ALL) survivors vary from 11%-57%. The purpose of this study was to evaluate the relationship between caloric and macronutrient intake on the incidence of obesity in survivors of pediatric ALL. A retrospective study of 137 participants using existing data collected from the Bone II study was evaluated. Participants were grouped into categories based on BMI for adults and CDC growth charts for children. Data was collected from 24 hour food recalls at time of enrollment. No statistical significance was found between BMI groups. Forty percent of participants were overweight or obese, but 69% …

Poeta Power: The Poetic Journey Of La Erika: Poems, Erika Marie Garza-Johnson

Theses and Dissertations - UTB/UTPA

This is a collection of poetry set in the borderlands of deep South Texas. The poems take as their subject Chican@ identity, family, the Rio Grande Valley of South Texas, Edcouch-Elsa, Texas, cancer, sexuality, Chicana feminism, childbirth and children, marriage, education, folklore, epithets, among others. As a cycle, they represent the poet‘s development through key stages in her life, including childbirth, marriage, and death of a parent. Many poems in this collection also reflect the linguistic diversity of the U.S.-Mexico border through the poet’s use of code-switching and Tex Mex.

Antimicrobial And Anticancer Activity Of Essential Oils From Guatemalan Medicinal Plants, Andrew B. Miller

Theses and Dissertations

Guatemalan medicinal plants were collected and screened for the presence of essential oils using steam distillation. Oil was found in 63 species from 24 families and was tested in tube dilution assays for activity against Escherichia coli, Staphylococcus aureus, Streptococcus mutans, Lactobacillus acidophilus and Candida albicans. Several essential oils were highly active with 20 instances of oils inhibiting the microbes at an MIC of 0.31 µl/ml. Oils were also tested against cancerous and established cell lines using a 15% (v/v) agar-media which was developed to improve essential oil solubility. Assays were performed against three cancer lines: …

Antifolate Modulators Of Amp-Activated Protein Kinase Signaling As Cancer Therapeutics, Scott Rothbart

Theses and Dissertations

Since its discovery, it was appreciated that the antifolate pemetrexed had multiple targets within folate metabolism. This laboratory was instrumental in showing that pemetrexed elicited its primary action as a thymidylate synthase inhibitor. Unusual for an antifolate, pemetrexed showed significant clinical activity against malignant pleural mesothelioma and non-small cell lung cancer. Accordingly, the FDA recently issued first-line approvals for pemetrexed in these diseases, leading us to question whether the effects of pemetrexed on other folate-dependent targets could explain this atypical clinical activity of the drug. Studies in this dissertation showed that in addition to thymidylate synthase inhibition, pemetrexed was also …

Synthesis Of A Water Soluble Resveratrol Derivative As A Potential Anti-Cancer Drug., Augustine Essel

Electronic Theses and Dissertations

Research on development of water soluble anti-cancer drugs is one of the great challenges of modern medicinal chemistry. Resveratrol (Res) is one of the many phytoalexins producing stilbenoids present in several medicinal plants, grape skin, peanuts, and red wine. It has been found to exhibit anti-cancer, anti-inflammatory, and anti-oxidant properties. Water solubility and bioavailability are some of the setbacks of this interesting compound. In view of this, effort has been made to synthesize amino acid derivative of resveratrol to improve its bioavailability and solubility in water. Methyl 4-{-[(1E)-2-(3, 5-dihydroxyphenyl)-ethenyl] - phenoxy} butyrate (7), a novel ester intermediate, has been synthesized …

Characterizing The Role Of Dna Repair Proteins In Telomere Length Regulation And Maintenance: Fanconi Anemia Complementation Group C Protein And 8-Oxoguanine Dna Glycosylase, David Beomjin Rhee

Doctoral Dissertations

Telomeres are the chromosome end structures consisting of telomere-associated proteins and short tandem repeat sequences, TTAGGG, in humans and mice. Telomeres prevent chromosome termini from being recognized as broken DNA ends. The structural integrity of DNA including telomeres is constantly threatened by a variety of DNA damaging agents on a daily basis. To counteract the constant threats from DNA damage, organisms have developed a number of DNA repair pathways to ensure that the integrity of genome remains intact. A number of DNA repair proteins localize to telomeres and contribute to telomere maintenance; however, it is still unclear as to what …

A Case Study On The Use Of Athletic Performance Strategies In An Elite Athlete’S Management Of Pancreatic Cancer, Brooke Elisabeth Harris

Boise State University Theses and Dissertations

In 2007, 11.7 million people in the United States were living with a cancer diagnosis. Specifically, 12 in every 100,000 Americans are diagnosed with pancreatic cancer each year. The five year survival rate of pancreatic cancer in the United States is only 5.6% (National Cancer Institute, 2007). In addition to traditional pharmacological treatments, physical activity has been increasingly used to help individuals successfully cope with cancer. One area that has not been studied extensively is the use of sport psychology techniques to help athletes cope with cancer. It is possible that these techniques, learned by elite athletes during their careers, …

Sa-4-1bbl As A Modulator Of T Effector To T Regulatory Cell Conversion., Shravan Madireddi 1980-

Electronic Theses and Dissertations

The immune system is of profound importance for host survival due to its ability to clear many acquired diseases. In case of infections and cancer, disease arises due to under-performance of immune system. Whereas in autoimmunity and transplantation, deleterious immunity to normal self-antigens and allogeneic antigens arises due to enhanced immune responses. Regulatory T (Treg) cells play a critical role in immune homeostasis in health and disease. Treg cells are important in the development and maintenance of immune tolerance towards self or transplantation antigens. However, Treg cells also play an obstructive role in cancer-related immunity by suppressing various effector cells. …

Understanding Acquired Resistance To Lapatinib In Breast Cancer Cells, Jen-Te Tseng

Dissertations & Theses (Open Access)

Signaling through epidermal growth factor receptor (EGFR/ErbB) family members plays a very important role in regulating proliferation, development, and malignant transformation of mammary epithelial cells. ErbB family members are often over-expressed in human breast carcinomas. Lapatinib is an ErbB1 and ErbB2 tyrosine kinase inhibitor that has been shown to have anti-proliferative effects in breast and lung cancer cells. Cells treated with Lapatinib undergo G1 phase arrest, followed by apoptosis. Lapatinib has been approved for clinical use, though patients have developed resistance to the drug, as seen previously with other EGFR inhibitors. Moreover, the therapeutic efficacy varies significantly within the patient …

Cell Death And Sustained Senescence Arrest In Colon Carcinoma And Melanoma Tumor Cells In Response To The Novel Microtubule Poison, Jg-03-14, Jonathan Biggers

Theses and Dissertations

Previous studies from this and other laboratories have shown that the novel microtubule poison, JG-03-14, which binds to the colchicine binding site of tubulin, has the capacity to promote both autophagy and apoptosis in breast tumor cells, as well as interfering with endothelial cell function and potentially disrupting tumor vasculature. The current work was designed to investigate the interaction between JG-03-14 and cell culture models of colon carcinoma and melanoma, specifically HCT116 human colon carcinoma cells and B16F10 murine melanoma cells. In both cases, JG-03-14 promoted death in the bulk of the treated population. FACS analysis, DAPI and TUNEL staining …

A Comparative Study Of Knowledge Of Pain Management In Certified And Non-Certified Oncology Nurses, Sherrie A. Lalande

USF Tampa Graduate Theses and Dissertations

Over 1.4 million people are diagnosed with cancer annually. Of those people, 70-90% experience some form of pain. Numerous efforts have been made to educate nurses in the management of pain, yet 30-50% of cancer patients report that their pain is poorly managed. It is not clear whether nurses who obtain certification in Oncology are better equipped to manage this patient population regarding their pain issues. This study compared the knowledge of Oncology Certified Nurses (OCN) and Non-Certified Oncology Nurses (NCON) regarding pain management.

The sample of 41 oncology nurses included 19 who were certified in oncology and 22 who …

Balancing Effector And Regulatory T Cell Responses In Cancer And Autoimmunity, Taylor H. Schreiber

Open Access Dissertations

Activation of immunity to self-antigens is the goal in cancer immunotherapy, whereas blocking such responses is the goal in autoimmune disease. Thus, it is not surprising that investigation into cancer immunotherapy might also produce insights for the treatment of autoimmune disease. Heat shock protein, gp96, based therapies lead to the robust activation of CD8+ cytotoxic T cells that can slow tumor growth in 60-70% of mice, but only lead to the elimination of tumors in 30-40% of animals. The primary goal of the current studies was to understand why vaccination with a secreted gp96 vaccine was not efficacious in a …

A Nonlinear Ode Model Of Tumor Growth And Effect Of Immunotherapy And Chemotherapy Treatment In Colorectal Cancer, Hannah P. Savage

HMC Senior Theses

Colorectal cancer will kill approximately 50,000 people in the United States this year. Current treatment options, including surgery, chemotherapy, and radiation, are often able to force the cancer into remission, but better treatments are needed to help those who don't respond to current treatments. A new and promising treatment option, monoclonal-antibody therapy, has the potential to help reduce the deaths caused by colorectal cancer, but most monoclonal-antibody drugs are currently still in trial phases, and the variations in the dosing schedule of those currently approved for use have not been heavily explored. We have modified a nonlinear ODE tumor/treatment model …

Surviving Cancer In Appalachia: A Qualitative Study Of Family Cancer Communication And Changing Personal Identities Through The Cancer Journey., Kathryn L. Duvall

Electronic Theses and Dissertations

The Appalachian region is known for its beautiful mountains, close-knit communities, and health care disparities including higher rates of cancer and premature mortality. Being diagnosed with cancer in the region may present a unique experience for survivors in regards to family cancer communication and changing personal identities. In a multiphasic study, the stories of 29 female Appalachian cancer survivors were collected through either a day-long modified story circle event (n=26) or an in-depth interview (n=3). Qualitative content analysis was used to identify emergent themes in the data. The analysis revealed 5 types of family cancer communication and five barriers to …

Functional Analysis Of Chromodomain Helicase Dna Binding Protein 2(Chd2) Mediated Genomic Stability, Sangeetha Rajagopalan

Doctoral Dissertations

Histone modifying enzymes and chromatin remodeling complexes play an important regulatory role in chromatin dynamics that dictate the interaction of regulatory factors involved in processes such as DNA replication, recombination, repair and transcription, with DNA template. The CHD (Chromodomain Helicase DNA Binding Protein) family of proteins is known to be involved in the regulation of gene expression, recombination and chromatin remodeling via their chromatin specific interactions and activities. Phenotypic analysis of the Chd2 mutant mouse model developed by our laboratory indicates that the Chd2 protein plays a critical role in tumor suppression as the heterozygous mutant mice develop spontaneous lymphomas. …

Pain Management In Nursing Home Residents With Cancer And Dementia With And Without Hospice Services, Todd Bryant Monroe

Theses and Dissertations (ETD)

Aims: We sought to identify differences in pain management between two groups; nursing home residents with malignant cancer and dementia with and without hospice services.

Methods: Decedent records from 2003-2009 were assessed for diagnosis of dementia and cause of death as cancer. Ten malignant cancer diagnoses were determined a priori from the CDC 2004 data on the top 10 malignant cancers for all races and genders. Fifty-five decedents from 10 nursing homes were included in the final sample. Four instruments were used: Minimum Data Set (MDS) a standardized assessment tool required of most U.S. nursing homes. A large …

Understanding Posttraumatic Growth Among Individuals With Cancer: The Role Of Social Support And Unsupportive Interactions, Wendy Balliet

Theses and Dissertations

The experience of being diagnosed with and treated for cancer is an extremely stressful experience for most individuals. Historically, the literature on stress and coping has focused on negative outcomes, such as depression and anxiety, in relation to one‘s experience with cancer. Under-represented in the literature has been a theoretical framework that examines positive and transformative experiences that may occur throughout the cancer experience. The current study assessed interpersonal variables that rarely have been investigated in relation to one‘s experience with cancer (i.e., received social support and unsupportive interactions) and their association with depressive symptoms, positive emotion, and posttraumatic growth …

A Randomized Trial Of Bilevel Positive Airway Pressure Device And High Flow Oxygen For Persistent Dyspnea In, David Hui

Dissertations & Theses (Open Access)

Background: Dyspnea is a common and distressing symptom among patients with advanced cancer. The role of bilevel positive airway pressure (BIPAP) and Vapotherm in the relief of dyspnea have not been well defined. We aimed to determine and to compare the efficacy of BIPAP and VapoTherm for cancer related dyspnea.

Methods: In this randomized, open-label, crossover study, we randomly assigned advanced cancer patients with persistent dyspnea >=3/10 to either Vapotherm for 2 hours followed by BiPAP for 2 hours, or BiPAP followed by Vaptherm. A variable washout period was instituted between interventions. The primary end point was change in numeric …

Effective And Compassionate Communication Between Hospital Staff And Parents Of Children With Newly Diagnosed Cancer, Natalie Volz

Regis University Student Publications (comprehensive collection)

This study was conducted to determine the most effective and compassionate modes of communication for hospital staff at The Children's Hospital to use when conveying information to parents of children with cancer. Twelve parents whose children were four to twelve weeks post diagnosis were interviewed. Parents were asked a series of eleven open-ended questions addressing their experience with hospital staff's communication skills. Recurring themes resulting from the interviews include delivery of diagnosis, value of information, receptiveness to questions and availability of hospital staff. These themes reveal that parents value thorough and complete explanations of their child's diagnosis and treatment plans, …

Activation Of Non-Muscle Myosin Iib Helps Mediate Tnf-Alpha Cell Death Signaling, Patrick G. Flynn

Open Access Dissertations

TNF-alpha can stimulate a variety of kinases with the ability to activate non-muscle myosin II. As a result, increases in actin filament formation and actomyosin contractility (AMC) have been reported in response to TNF-alpha. These events are thought to play an important role in mediating TNF-alpha induced apoptosis but how they do so is unclear. In this study we prevented non-muscle myosin II activation in response to TNF-alpha by treating cells with the myosin light chain kinase (MLCK) inhibitor ML-7 or through isoform specific siRNA knockdown of myosin IIA and IIB. We found that treatment with ML-7 or knockdown of …

The Role Of Igf-1 And Notch Signaling In Thoracic Malignancies., Sandra Eliasz

Dissertations

Thoracic malignancies are one of the deadliest of all cancers, being the leading cause of cancer death in the Western world. Thoracic malignancies arise from different tissues; however the most common are of epithelial (commonly referred to as non-small cell lung cancer, or NSCLC), neuroendocrine (small cell lung cancer, or SCLC) and mesothelial origin (malignant mesothelioma, or MM). The DNA oncogenic virus Simian Virus 40 (SV40) has been shown to cooperate with environmental oncogenic fibers in the onset of MM. Insulin like growth factor-1 (IGF-1) signaling plays a central role in all thoracic malignancies and in the process of SV40-mediated …

Molecular Mechanisms Of Pressure-Stimulated Cancer Cell Signaling, Christina Downey

Wayne State University Dissertations

ABSTRACT

MOLECULAR MECHANISMS OF PRESSURE-STIMULATED CANCER CELL SIGNALING

by

CHRISTINA DOWNEY

June 2010

Advisor: Dr. Marc Basson, MD, PhD

Major: Cancer Biology

Degree: Doctor of Philosophy

Increased extracellular pressure stimulates cancer cell adhesion by a mechanism that is dependent upon beta-1-integrin activation, an intact cytoskeleton, and FAK and Src activation. By a different mechanism, increased extracellular pressure modulates cancer cell proliferation in a manner that is regulated by protein kinase C, but not Src or an intact cytoskeleton. Previous studies from our laboratory have shown that paxillin is a necessary mediator in the pathway by which pressure stimulates adhesion; however, …

Quantification Of Vascular Parametric Indices Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging, Areen Khaled Al.Bashir

Wayne State University Dissertations

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive method used to evaluate the biological activity in early clinical trials of novel drugs targeting the tumor vasculature using gadolinium-DTPA (Gd) as a contrast agent. However, it has some limitations, such as reproducibility, data acquisition times, the presence of noise, extracting contrast concentration, estimating T1 relaxation and estimating pharmacokinetic parameters.

In this work, a new approach to used fixed T1(0) which provides more reproducible DCE results has been introduced. Using this new algorithm to quantify the vascular changes in DCE-MRI, a pre-clinical renal cell carcinoma (RCC) tumor model was used to …

Genetic And Environmental Factors Suggest That Dietary Fatty Acid Content, Lipid Metabolism, And Bone Properties Are Key Regulators Of Myeloid Progenitor Cell Frequency, Melinda E. Varney

Theses, Dissertations and Capstones

Acute myelogenous leukemia (AML) and its precursors are the result of the dysregulation of hematopoiesis. Hematopoiesis proceeds in a stepwise manner, beginning with hematopoietic stem cells, continuing to develop into various stages of progenitor cells, and finally becoming fully functional blood cells. As this process goes awry, immature, functionless cells of the myeloid lineage proliferate out of control. Discerning how myeloid progenitor frequency is regulated allows for a better understanding of how the process may lose control. Hematopoiesis has been shown to depend on genetic and environmental factors. In this work, I have added to this knowledge base by providing …

Structural Investigation Of Atp-Utilizing Enzymes: Structures Involved In H+ Homeostasis And The Proliferation Of Hormone-Dependent Cancers, Zacariah Louis Hildenbrand

Open Access Theses & Dissertations

ATP is a multifunctional nucleotide considered to be the "molecular unit of currency" of intracellular energy transfer. ATP is utilized ubiquitously for the transport of chemical energy within the cell in addition to acting as a substrate in the regulation of many metabolic and signaling transduction pathways such as kinase-mediated signaling cascades. Interestingly, the functional mechanisms of many enzymes require the binding of ATP to trigger key structural and conformational changes that ultimately result in enzyme-directed catalysis. Two of the most omnipresent ATPases within the cell include the V-ATPase rotary proton pump and the Hsp90 protein-folding chaperone. Structural and biochemical …

Synthesis Of A Potentially Insulin-Mimetic, Lipid-Linked Inositol Glycan, Meenakshi Goel

Master's Theses

Inositol glycans (IGs) are naturally occurring oligosaccharides that can stimulate insulin sensitive cells. Several synthetic IG analogues have been shown to activate the insulin-signaling pathway, including the stimulation of the enzyme pyruvate dehydrogenase (PDH) phosphatase that can further stimulate aerobic metabolism in cells. Cancer cells shift to anaerobic metabolism in order to escape intrinsic apoptosis (Warburg Effect). IG's ability to stimulate aerobic metabolism might provide a method to reverse the Warburg Effect and thereby induce apoptosis in the cancer cells. One specific palmitoylated IG analogue has been shown to selectively kill cancer cells while having no adverse effect on normal …

Structural Instability Of Human Ribosomal Rna Gene Clusters, Dawn Michelle Stults

University of Kentucky Doctoral Dissertations

The human ribosomal RNA genes are critically important for cell metabolism and viability. They code for the catalytic RNAs which, encased in a housing of more than 80 ribosomal proteins, link together amino acids by peptide bonds to generate all cellular proteins. Because the RNAs are not repeatedly translated, as is the case with messenger RNAs, multiple copies are required. The genes which code for the human ribosomal RNAs (rRNAs) are arranged as clusters of tandemly repeated sequences. Three of four catalytic RNAs are spliced from a single transcript. The genes are located on the short arms of the five …