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Isolation And Total Synthesis Of Sigma-2 Ligands From Marine Cyanobacteria, Andrea Hough

Electronic Theses and Dissertations

Cyanobacteria have been studied for over 50 years as a source of new antibiotics, antiviral, and anticancer drugs. The research described in this dissertation investigates marine cyanobacteria as a source of natural products with activity within the central nervous system and with cytotoxicity against breast cancer cells. Barbamide (1) is a known cyanobacterial metabolite that has been re-isolated from a variety of species and collection sites suggesting broad utility as a signaling molecule. Utilizing the psychoactive drug screening program, we screened barbamide for CNS activity and found that barbamide exhibited affinity for the kappa opioid receptor (KOR) and …

Targeting The Mek5, Mek1/2, And/Or Pi3k Pathways To Reverse Epithelial To Mesenchymal Transition And Enhance Chemotherapeutic Sensitivity In Breast And Brain Cancers, Akshita Bhatt

Electronic Theses and Dissertations

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer and accounts for 10-15% of breast cancer cases. Due to absence of estrogen, progesterone, and human epidermal growth factor receptors, there is lack of targeted therapies and chemotherapy remains the mainstay treatment. Moreover, drug resistance is a major problem associated specifically with TNBC. Similarly, while estrogen receptor positive (ER+) breast cancer can be treated with targeted therapies such as tamoxifen, 40% of patients develop resistance and resulting in recurrence of the disease.

There is a dire need for identifying novel targets and developing therapeutics to target triple-negative and …

Diagnosis Of Melanoma Disease State From Patient Blood Samples Using Photoacoustic Flow Cytometry, Jacob Salvatore

Electronic Theses and Dissertations

Approximately 1 in 50 Americans develop melanoma in their lifetime. Early detection of melanoma is pivotal to the survival of the patient, with a 99% survival rate for 5 or more years after an early diagnosis. Metastasis, or the spread of cancer, increases the chances of cancerous growth in other parts of the body. In this study, we propose the use of photoacoustic flow cytometry as a diagnostic of patient disease state, by closely monitoring the amount of circulating melanoma cells (CMCs) in a patient’s blood before and after chemotherapy treatments. Using this patient data, we were able to make …

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …

Treatment-Related Decisional Conflict, Quality Of Life, And Comorbid Illness In Older Adults With Cancer, Jeannette Kates

Electronic Theses and Dissertations

As the aging population the nation increases, cancer diagnoses in this age group will also increase. The many chronic medical conditions associated with older adults will be confounded by a diagnosis of cancer. Older adults with cancer are at risk for physical, psychological, and functional decline as a result of not only the cancer, but also the cancer treatment. This study utilized a cross-sectional, descriptive, correlational study design to explore the relationships between and among treatment-related decisional conflict, quality of life and comorbidity in older adults with cancer. An anonymous survey method was employed. The criteria for inclusion in this …

Synthesis And Molecular Modeling Studies Of Bicyclic Inhibitors Of Dihydrofolate Reductase, Receptor Tyrosine Kinases And Tubulin, Sudhir Raghavan

Electronic Theses and Dissertations

The results from this work are reported into two sections listed below:

Synthesis:

Following structural classes of compounds have been designed, synthesized and studied as inhibitors of pjDHFR, RTKs and tubulin:

1. 2,4-Diamino-6-(substituted-arylmethyl)pyrido[2,3-d]pyrimidines

2. 4-((3-Bromophenyl)linked)-6-(substituted-benzyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amines

3. 6-Methyl-5-((substitutedphenyl)thio)-7H-pyrrolo[2,3-d]pyrimidin-2-amines

A total of 35 new compounds (excluding intermediates) were synthesized, characterized and submitted for biological evaluation. Results from these studies will be presented in due course. Bulk synthesis of the potent lead compound 170 was carried out to facilitate in vivo evaluation.

Docking Studies

Docking studies were performed using LeadIT, MOE, Sybyl or Flexx for target compounds listed above and for other compounds …

Classification Tree Models For Predicting Cancer Status, Pu Chen

Electronic Theses and Dissertations

Early detection of cancers might improve the clinical outcomes. Multiple biomarkers with a novel LabMAP technology were used as the laboratory method to develop the diagnostic assay for ovarian, breast, endometrial, and lung cancer. To evaluate the accuracy of early stage detection, logistic regression (with forward selection) and classification tree models were applied as statistical methods. Furthermore, complexity parameters and the number of bootstrap samples were varied to assess the effect on sensitivity and specificity. The receiver operating characteristic curves reflected high sensitivities and specificities.

Retrospective Analysis Of A Breast Health Program On Routine Annual Mammography In Low-Income, Uninsured Women, Theresa Morrison

Electronic Theses and Dissertations

Problem: Detection of breast cancer in women of low socioeconomic status, lacking health insurance, can be improved by increasing annual mammography rates, yet little is known about their screening behavior.

Purpose: A retrospective subject-controlled study of an ongoing Breast Health Program, at a not-for-profit, non-government assisted, volunteer clinic, was undertaken to examine mammography usage and discovery variables.

Design and Methods: English and Spanish speaking women 40 years old and over who viewed in a 7-minute breast health DVD and were offered free mammography were eligible for the study (N= 223). The Health Belief Model (HBM) (Becker, 1974) provided the study …

The Lived Experience Of Lebanese Oncology Patients Receiving Palliative Care, Myrna Doumit

Electronic Theses and Dissertations

The purpose of this study was to uncover the lived experience of Lebanese oncology patients receiving palliative care. The study design was based on the Utrecht School of phenomenology based on the Dutch school of phenomenology. This study followed purposeful sampling in which ten participants six women and four men with a mean age of 54.4 years were selected. The proposed research was approved by the Institutional Review Boards at the American University of Beirut and Duquesne University. In-depth semi-structured interviews along with observation-field notes were used as the source for data collection. Data were analyzed using the hermeneutic phenomenological …

Theoretical Aspects Of Designing New Vaccines For Breast Cancer: Docking Studies Of Peptide/Hla-A2.1 Complexes, Tugba Kucukkal

Electronic Theses and Dissertations

HER2/neu is a transmembrane glycoprotein that is overexpressed in many tumors, including ovarian and breast cancers. The HER2/neu peptide IISAVVGIL (GP2) is recognized by tumor-specific cytotoxic T lymphocytes in the context of human class I major histocompatibility complex (MHC) HLA-A2.1. One limiting-factor for using GP2 as a tumor vaccine is its poor affinity for HLA-A2.1, even though it has the correct peptide-binding motif. The research aims are to develop an accurate docking method for the binding of GP2 to HLA-A2.1, to understand the molecular forces that give rise to strong binding, and to predict mutations that lead to new tumor …

Living With Life-Threatening Illness: An Inquiry Into Children's Experience Of Cancer, Kristy Novinski

Electronic Theses and Dissertations

Previous studies concerning children living with illness have been limited by (a) a narrow focus on the child's cognitive development, (b) reliance on sources outside of the child's experience, (c) reliance on methods based on the language and quantitative modes of measuring used by adults rather than the experience of the child, (d) models that emphasize methods of control in coping, and (e) a tendency to pathologize the responses of the child.

In contrast, the current study involved speaking directly with school-aged children living with a diagnosis of cancer. The qualitative method developed for this study involved a two-fold approach, …