Medicine and Health Sciences Commons^™

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 …

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 …

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 …

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, …

Nursing Home Organizational Characteristics And Utilization Of Cancer-Related Medical Services, Chun-Chieh Lin

Theses and Dissertations

Cancer is the second leading cause of death in the U.S and is more common among the elderly. Since frailty and other age related conditions put the elderly at risk for nursing home care, nursing homes may be the site of care and death for many elderly cancer patients. However, there is a large gap in knowledge concerning cancer treatment of elderly nursing home residents. Since residents rely heavily on their nursing facilities, nursing homes might influence them in their treatment decisions. After controlling for resident and nursing home market characteristics, this study applies Andersen’s Behavioral Model to examine whether …

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 …

Development And Validation Of A Palliative Care Needs Assessment Instrument-English/Arabic Versions (Pcna-Eav), For Use With Patients With Advanced Cancer, Susan Edith Volker

All ETDs from UAB

The aim of this study was to develop and translate a psychometrically valid and reliable, population-based, needs assessment instrument, the PCNA-EAV, to measure the health care and support needs of patients with advanced cancer. The cross-sectional study design combined qualitative and quantitative methods, to test instrument reliability and validity, and to examine the association between sample characteristics and health care and support needs. The 116-item, PCNA-EAV, comprised 10 domains of need: physical/functional; social; psychological/emotional; information; communication; helpful resources; financial; religious/spiritual; priority of need; and preference for care The target population was all cancer patients in the department of oncology at …

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 …

The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon

All ETDs from UAB

Glioma-associated oncogene homolog 1 (Gli1) is a well-known oncogene and a transcription factor that mediates several signaling pathways important for tumor progression, such as hedgehog, TGFß, Ras, and EGFR. Although Gli1 is known to play an important role in cancers of brain, skin, prostate, and the pancreas, the role of Gli1 in breast cancer was not previously well-defined. Therefore, this dissertation focuses on defining the role of Gli1 and the mechanism underlying Gli1-mediated transcription in breast cancer. Interestingly, the major findings of the dissertation clearly indicate that Gli1 promotes cell survival and is predictive of a poor outcome in Estrogen …

Preclinical Pharmacology Of Novel Synthetic Iminoquinones As Anticancer Agents, Scharri Ezell

All ETDs from UAB

Prostate cancer is the most common male malignancy and the second leading cause of cancer related death in the United States. Despite recent advances in the detection, diagnosis, and treatment of prostate cancer, there is a need for more effective therapies. Unfortunately, most conventional therapeutic modalities, such as androgen ablation therapy, frequently result in androgen-independent cancers. These cancers are typically more aggressive, metastatic, and resistant to chemotherapeutic agents than androgen-dependent prostate cancer. Therefore, agents that are effective against both androgen-sensitive and androgen-independent, as well as genetically diverse cancers are critically needed. The objective of the dissertation research was to address …

Identification Of A Tumor-Targeting-Peptide And Development Of A Tumor-Targeted-Cytokine Vector For Systemic Treatment Of Primary And Metastatic Malignancies, Jeffry Cutrera

LSU Doctoral Dissertations

Advances in cancer therapies continue to be improved, yet cancer continues to be one of the deadliest diseases in the world. Harnessing the power of the body’s immune system to attack cancer is a promising strategy that can further improve therapies for neoplastic diseases. As part of this strategy, cytokines such as interleukin (IL) 2 and interferon á are currently accepted cancer treatments, and other cytokines such as IL12 and GM-CSF also show potential as new treatments. Clinical trials with these cytokines have shown less than acceptable therapeutic efficacy and toxicities, but tumor-targeting motifs can improve these effects. Both antibodies …

Molecular Mechanisms Of Breast Cancer Metastasis: Gap Junction Intercellular Communication And The Bone Microenvironment, Thomas Morgan Bodenstine

All ETDs from UAB

Metastatic disease accounts for the overwhelming majority of cancer related deaths. More specifically, breast cancer remains one of the leading causes of death in women and breast cancer cells metastasize to bone more than any other secondary site. Upon arriving within the bone microenvironment, breast cancer cells interact with bone marrow cells, leading to changes in bone biology that favor growth of the cancer cells. Additionally, some cancer cells are capable of direct cellular communication with cells at metastatic sites via dysregulation of a family of proteins known as connexins. This direct, physical communication is known as gap junctional intercellular …

The Effects Of Weight Reduction On Obesity-Related Cancer Biomarkers And In Vitro Cancer Cell Growth, Maria Azrad

All ETDs from UAB

Obesity increases the risk for breast and endometrial cancers while weight loss reduces the risk for these cancers. One aim of this dissertation was to determine the effects of weight loss from an overweight state [body mass index (BMI) 27-30] to a normal weight state on several obesity-related cancer biomarkers in African-American (AA) and European-American (EA) premenopausal women. We also sought to determine whether the method of weight loss, caloric restriction alone (CR) or combined with exercise resulted in similar changes in cancer biomarkers. The biomarkers of interest were urinary estrogen metabolites, and serum adiponectin, leptin, insulin-like growth factor (IGF)-1, …

Fiber Modification Of Adenoviral Vectors For Cancer Gene Therapy, Miho Murakami

All ETDs from UAB

Cancer still remains a major public health concern despite improvements in primary prevention, early detection and advanced treatments. Cancer gene therapy using human adenovirus serotype 5 (HAdV-5) as a vector has been explored as a new therapeutic approach. HAdV-5 infection is initiated by binding to the coxsackie virus and adenovirus receptor (CAR), its primary cellular receptor. However, the levels and patterns of expression of CAR vary greatly in clinical tumor tissue samples, and the expression lev-els tend to decrease as the tumors progress. The low level expression of CAR in target cancer cells diminishes the utility of HAdV-5 as a …

Brms1 Coordinately Regulates Microrna To Suppress Breast, Mick D. Edmonds

All ETDs from UAB

The majority of cancer related mortality is attributed to complications associated with metastatic disease. Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple cancer types in vivo and loss of nuclear BRMS1 is associated with ER-negative cancers and a high rate of proliferation. Many groups have shown BRMS1 to regulate the expression of multiple metastatic genes, yet until now no one has been able to account for how these many changes in gene expression occur. In this work, we report that BRMS1 regulates a select set of genes called microRNA (miRNA), and these miRNA themselves can regulate metastasis. Using …

Optimization And Toxocologic Effects Of Cancer Immuno-Electrogene Therapy Using A Tumor-Targeted Interleukin-12 Gene Construct, Scott Douglas Reed

LSU Doctoral Dissertations

This dissertation includes a comprehensive current review of reversible electroporation (EP) and other related physical gene transfection techniques; an overview of results of electrochemogene therapy (ECGT) used to treat naturally occurring spontaneous neoplasms in dogs; and the results of comprehensive, pre-clinical toxicology testing of electrogene therapy (EGT) of a tumor-targeted version of interleukin-12 (IL-12) in mice. Intralesional bleomycin (BLM) and feline interleukin-12 (fIL-12) DNA injection combined with trans-lesional EP resulted in complete cure of two recurrent oral squamous cell carcinomas and an acanthomatous ameloblastoma in a series of six cases of spontaneous neoplasia in pet dogs. The three remaining dogs, …