Medicine and Health Sciences Commons^™

Transcriptional, Epigenetic, And Signal Events In Antifolate Therapeutics, Alexandra Racanelli

Theses and Dissertations

A targeted approach to the development of antifolate therapies has been sought for many years. Central to the success of such development is an understanding of the molecular mechanisms dictating the sensitivity of cells to antifolates and the fundamental differences of these processes between normal and neoplastic phenotypes. This dissertation addressed transcriptional mechanisms and cell-signaling events responsible for the efficacy of antifolate therapies. Transcriptional processes and cell signaling pathways are often aberrant in neoplastic tissues, providing a potential point of distinction between a normal and neoplastic cellular state. Folylpolyglutamate synthetase (FPGS) catalyzes the formation of poly-γ-glutamate derivatives of folates and …

Old Disease, New Targets--Part-I, Solid Malignancies, Shiyam Kumar, Nehal Masood, Asim Jamal Shaikh

Department of Radiation Oncology

Targeted agents are now an integral part of treatment regimens for some cancers. Trastuzumab is established in treatment of human epidermal receptor 2 (Her2) positive breast cancers, with improvements in both, the disease free and over all survival. Monoclonal antibody (MoAB) against vascular growth factor receptor (VEGF), bevacizumab and cetuximab a MoAB against epidermal growth factor receptor (EGFR) are establishing their role in a many cancers after making their mark in colorectal cancer. Sorafenib and sunitinib have success stories in renal carcinoma. The Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial has established sorafenib role in advanced hepatocellular carcinoma, while …

Does Unemployment Decrease Cancer Mortality?, Benjamin Torres Galick

Economics Honors Projects

Recent research indicates that healthier lifestyles during recessions decrease the most common U.S. mortalities, but not cancer. However, they combine specific cancer mortalities with different progressions into one, possibly obscuring cancer’s link to unemployment. This paper estimates a fixed-effects regression model on unemployment and the nine most prevalent cancers between 1988 and 2002 using state-level panel data. Five cancers and total cancer are procyclical, and suggest that unemployment affects both incidence and gestation for some cancers. Consistent with the medical literature, this paper contradicts previous economic research and suggests that behavioral factors significantly impact cancer mortality.

Pax5 Haploinsufficiency Cooperates With Bcr-Abl1 To Induce Acute Lymphoblastic Leukemia, Christopher B. Miller

Theses and Dissertations (ETD)

Acute lymphoblastic leukemia (ALL) is the commonest pediatric malignancy and comprises several distinct subtypes each with its own unique pathogenesis, clinical behavior, and response to therapy. Chromosomal aberrations are a hallmark of ALL but alone fail to induce leukemia. Pediatric ALLs can be divided into several categories based on the expression of several genetically conserved chromosomal translocations including the t(9,22)[BCR-ABL1], t(1,19)[TCF3-PBX1], t(12,21)[ETV6-RUNX1], MLLrearranged leukemia’s, hyperdiploid and hypodiploid karyotypes, and T-lineage leukemia. Each translocation confers a characteristic transforming phenotype within the cell in which it originates but is alone insufficient to induce overt leukemia. …

Diffusion Tensor Imaging In Pediatric Brain Tumor Patients, Nicholas S. Phillips

Theses and Dissertations (ETD)

In this dissertation, we outline our efforts to introduce an advanced MRI imaging technique called Diffusion Tensor Imaging (DTI) to the pediatric brain tumor population. We discuss the theory and application of DTI as it was performed in a series of translational investigations at St. Jude Children’s Research Hospital. We present evidence of how the introduction of this technique impacted diagnosis, and treatment. And finally, we demonstrate how DTI was used to investigate cognitive morbidities associated with cancer treatment and how this research provided insight into the underlying pathophysiology involved in the development of these treatment sequela.

This research has …

Basement Membrane Proteoglycans: Modulators Par Excellence Of Cancer Growth And Angiogenesis., Renato V. Iozzo, Jason J. Zoeller, Alexander Nyström

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proteoglycans located in basement membranes, the nanostructures underling epithelial and endothelial layers, are unique in several respects. They are usually large, elongated molecules with a collage of domains that share structural and functional homology with numerous extracellular matrix proteins, growth factors and surface receptors. They mainly carry heparan sulfate side chains and these contribute not only to storing and preserving the biological activity of various heparan sulfate-binding cytokines and growth factors, but also in presenting them in a more "active configuration" to their cognate receptors. Abnormal expression or deregulated function of these proteoglycans affect cancer and angiogenesis, and are critical …

Therapeutic Drugs In Cancer And Resistance., Aditi Pandya Martin

Theses and Dissertations

We investigated the mechanism of toxicity and resistance development of small molecule tyrosine kinase inhibitor lapatinib in HCT 116 colon cancer cells. Lapatinib mediated cell death in HCT 116 cells was caspase independent and involved cytosolic release of apoptosis inducing factor. Treatment of HCT 116 cells with 10µM Lapatinib lead to the outgrowth of lapatinib resistant HCT 116 cells. Our studies show that alterations in the expression and activation of Bcl-2 family proteins allow lapatinib resistant HCT 116 cells to resist cytotoxic effects of lapatinib as well as of other commonly used chemotherapeutic agents. In hepatoma and pancreatic cancer cells, …

Cancer Of The Penis: Case Report, D. K. Kiptoon, P. M. Ngugi, F. S. Rana

Pathology, East Africa

Two patients with penile carcinoma are presented after management at a district hospital in Kenya. Both had undergone ritual circumcision as teenagers and presented late. HR was a 73 year old who presented with a fungating penile mass for which a partial penectomy was performed after wedge biopsy confirmed malignancy. He thereafter declined to have the surgical specimen sent for histology and took the amputated stump for burial in his compound to avoid bad omen. GK was 25 years old and presented with a fungating mass and underwent partial penectomy after a histological diagnosis was made. He absconded from follow-up …

Cardiorespiratory Fitness And Digestive Cancer Mortality: Findings From The Aerobics Center Longitudinal Study (Acls), J. Brent Peel, Xuemei Sui, Charles E. Matthews, Swann Arp Adams, James R. Hébert, James W. Hardin, Timothy S. Church, Steven N. Blair

Faculty Publications

Although higher levels of physical activity are inversely associated with risk of colon cancer, few prospective studies have evaluated overall digestive system cancer mortality in relation to cardiorespiratory fitness (CRF). The authors examined this association among 38,801 men aged 20−88 years and who performed a maximal treadmill exercise test at baseline in the Aerobics Center Longitudinal Study (Dallas, Texas) during 1974−2003. Mortality was assessed over 29 years of follow-up (1974−2003). 283 digestive system cancer deaths occurred during a mean 17-year of observation. Age-adjusted mortality rates per 10,000 person-yrs according to low, moderate, and high CRF groups were 6.8, 4.0, and …

Factors Influencing Early Detection Of Breast Cancer In African American Women, Tamrah Joy Parker

Nursing Theses and Capstone Projects

Background. African American women are more likely to have breast cancer diagnosed at a later stage than Caucasian women and with a five year death rate 1.5 times greater than Caucasian women. Mammography screening detects breast cancer in its early stages and can reduce mortality.

Objective. To examine factors influencing early detection of breast cancer for African American women.

Methods. A convenience sample of 39 African American women 50 years of age and older was selected from two local Baptist churches in eastern North Carolina. Eligibility criteria included ability to read and write in English with no prior or present …

Demographics, Clinical Presentations And Outcomes Of Cancer Patients Admitting To Emergency Department., Nuri̇ Bozdemi̇r, Oktay Eray, Cenker Eken, Yeşi̇m Şenol, Mehmet Artaç, Mustafa Samur

Turkish Journal of Medical Sciences

Aim: The development of new treatment strategies for cancer patients resulted in an increase of cancer patient visits to emergency departments (EDs). The purpose of this study is to determine clinical characteristics, causes, and predictors of short term prognosis of cancer patient admissions to the ED. Materials and Methods: This prospective, clinical, and observational study was carried out in an adult ED of a tertiary hospital with an annual census of 55,000. All cancer patients visiting the ED within the 6-month period were enrolled into the study and followed up at the 1st and 3rd months afterwards. Records were based …

Human Ribosomal Rna Gene Clusters Are Recombinational Hotspots In Cancer, Dawn Michelle Stults

University of Kentucky Master's Theses

The gene that produces the precursor RNA transcript to the three largest ribosomal RNA molecules (rDNA) is present in multiple copies and organized into gene clusters. They represent 0.5% of the diploid human genome but are critical for cellular viability. The individual genes possess very high levels of sequence identity and are present in high local concentration, making them ideal substrates for genomic rearrangement driven by dysregulated homologous recombination. Our laboratory has developed a sensitive physical assay capable of detecting recombination-mediated genomic restructuring in the rDNA by monitoring changes in lengths of the individual clusters. In order to determine whether …

Oncology Nurses’ Perceptions Of Obstacles And Supportive Behaviors In End-Of-Life Care, Renea L. Beckstrand, A. Elaine Bond, Lynn Clark Callister, Josie Moore

Faculty Publications

Cancer accounts for one in four deaths in the United States. Oncology nurses care for dying patients on a daily basis. Research on specific obstacles that impede and supportive behaviors that help the delivery of end-of-life (EOL) care is limited.

The Peptidyl-Prolyl Isomerase Pin1 Promotes Nf-Kappab And Stat3 Signaling In Glioblastoma, George Prescott Atkinson

All ETDs from UAB

Glioblastoma (GBM) is an incurable tumor of the central nervous system (CNS). Over the past 50 years, little progress has made in improving the quality of life and median lifespans of patients who are diagnosed with this devastating disease. However, new insights into the aberrant signaling pathways at the root of GBM pathology are providing new targets for next generation cancer therapies. Two signaling pathways that are commonly upregulated in GBM are NF-kappaB and STAT3. Importantly, tumor models in which NF-kappaB and STAT3 signaling are inhibited have demonstrated the importance of these pathways to GBM growth and proliferation. Therefore, better …

Mouse Modeling Of Pancreatic Ductal Adenocarcinoma (Pdac); Search For Early Diagnostic Markers And Therapeutic Targets, Kyoko Kojima

All ETDs from UAB

PDAC is a highly malignant neoplasm that carries a very poor prognosis. PDAC development is a multistage transformation process that involves multiple genetic alterations that include activation of EGFR/HER2 and KRAS, and loss-of-function mutations in INK4A/ARF, p53 and SMAD4. In recent years, several genetically engineered mouse models that accurately recapitulate human pancreatic neoplasia have been developed. Histological characterizations of those models have revealed possible roles for the mutated RAS, INK4a/ARF and p53 in pancreatic tumorigenesis. However, the role of SMAD4 mutation, which is associated with late stages of tumor progression, has yet to be explored. Additionally, those models that would …

Review Of Cancer Among Indigenous Peoples, Sasha Stumpers, Neil Thomson

Research outputs pre 2011

This review provides a comprehensive synthesis of population-level cancer statistics and other key information for Aboriginal and Torres Strait Islander people alongside comparative figures for non-Indigenous Australians. It includes general information on the extent of cancer, including: incidence, hospitalisation and mortality. The review also provides information on the extent of cancer for specific cancers: lung, cervical, breast, prostate, liver, pancreatic and colorectal (bowel). Finally, the review discusses issues surrounding Aboriginal and Torres Strait Islander people’s use of cancer services.

Synthesis Of Marine Chemicals And Derivatives As Potential Anti-Cancer Drugs., Laude Bannerman-Akwei

Electronic Theses and Dissertations

Two natural marine compounds, 3-bromo-4,5-dihydroxybenzaldehyde 2 and 2,3-dibromo-4,5-dihydroxybenzaldehyde 5 together with two novel derivatives, 3-bromo-5-(tert-butyl-dimethyl-silanyloxy)-4-hydroxybenzaldehyde 3 and 1-bromo-2,3-dimethoxy-5-nitrooxy-methylbenzene 9, were synthesized. Compounds 2, 3, and 5 were evaluated for their biological activity towards the inhibition of prostate cancer cell growth using staurosporine a a positive control. All three compounds have shown significant inhibition of prostate cancer cell growth. Compound 9 is yet to be evaluated.

Breast Cancer Fatalism: The Role Of Women's Perceptions Of The Health Care System, Allyson G. Hall, Amal J. Khoury, Ellen D.S. Lopez, Nedra Lisovicz, Amanda Avis-Williams, Amal K. Mitra

Faculty Publications

Cancer fatalism, which can be understood as the belief that cancer is a death sentence, has been found to be a deterrent to preventive cancer screening participation. This study examines factors associated with breast cancer fatalism among women. We analyzed data from a 2003 survey of women 40 years of age. The survey collected information about respondents' knowledge and attitudes regarding breast health. Analyses compared the characteristics of women who reported and those who did not report a fatalistic attitude. Women with a fatalistic attitude were more likely to be African American, to have a family history of breast cancer, …

Ford, Sandra Young, 1944-1998 (Sc 1752), Manuscripts & Folklife Archives

Manuscript Collection Finding Aids

Finding aid only for Manuscripts Small Collection 1752. Items related to Sandra Young Ford's battle with cancer and her ultimate death.

Acute Exercise Protects Against Doxorubucin Cardiotoxicity, Karen Y. Wonders, David S. Hydock, Carole M. Schneider, Reid Hayward

School of Sport & Exercise Science Faculty Publications

Numerous methods have been used to minimize the cardiotoxic effects of the chemotherapeutic agent doxorubicin (DOX), and most have had limited success. Chronic endurance exercise has been shown to protect against DOX cardiotoxicity, but little is known regarding the effects of acute exercise on DOX-induced cardiac dysfunction. Purpose. The purpose of this study was to determine the effects of a single bout of acute endurance exercise on the cardiac dysfunction associated with DOX treatment. Methods. Male Sprague-Dawley rats either performed an acute exercise bout on a motorized treadmill for 60 minutes at a maximal speed of 25 m/min with a …

Incidence Of Cancers Of The Oral Cavity And Pharynx Among American Indians And Alaska Natives, 1999–2004, Marsha E. Reichman, Janet J. Kelly, Carol L. Kosary, Steven S. Coughlin, Melissa Jim, Anne P. Lanier

United States Public Health Resources

BACKGROUND. Previous studies identified disparities in incidence rates of cancers of the oral cavity and pharynx between American Indians/Alaska Natives (AI/AN) and non-Hispanic whites (NHW) and differences between various AI/AN populations. Reporting among AI/AN has been hampered by: 1) heterogeneity among various anatomic sites of oral cavity and pharyngeal cancers obscuring unique patterns of individual anatomic sites; 2) race misclassification and under-reporting of AI/AN; and 3) sparseness of data needed to identify regional variations.

METHODS. To improve race classification of AI/AN, data from US central cancer registries were linked with Indian Health Service (IHS) records. AI/AN incidence data …

Cancer In American Indian And Alaska Native Young Adults (Ages 20–44 Years): Us, 1999–2004, Hannah K. Weir, Melissa Jim, Loraine D. Marrett, Temeika L. Fairley

United States Public Health Resources

BACKGROUND. An examination of cancer incidence patterns in American Indians and Alaska Native (AI/AN) young adults may provide insight into their present and future cancer burden.

METHODS. To reduce racial misclassification, incidence data were linked with the Indian Health Service (IHS) patient services database. Age-adjusted cancer incidence rates per 100,000 (AAR) and corresponding rate ratios (RR) for young adults (ages 20-44 years) were compared across IHS regions and for selected cancers within Contract Health Service Delivery Area counties by race (AI/AN vs non-Hispanic whites [NHW]) and sex.

RESULTS. The all-sites cancer incidence rate was lower for AI/ANs …

Gastric Cancer Among American Indians And Alaska Natives In The United States, 1999–2004, Charles Wiggins, David G. Perdue, Jeffrey A. Henderson, Michael G. Bruce, Anne P. Lanier, Janet J. Kelly, Brenda F. Seals, David K. Espey

United States Public Health Resources

BACKGROUND. Gastric cancer incidence rates for American Indians and Alaska Natives (AI/ANs) historically have exceeded those for non-Hispanic whites (NHWs). Previous reports may have underestimated the true burden of gastric cancer in AI/AN populations because of misclassification of AI/AN race in cancer registries.

METHODS. Population-based cancer registry data from 1999 through 2004 were used to describe gastric cancer incidence in AI/ANs and NHWs in the US. To address misclassification of race, registry data were linked with Indian Health Service administrative records, and analyses were restricted to residents of Contract Health Service Delivery Areas (CHSDA). Disease patterns were assessed …

The Relationship Between Perceived Personal Risk Of Getting Prostate Cancer And Prostate-Specific Antigen (Psa) Screening, Yeatoe G. Mcintosh

Theses and Dissertations

Abstract Title: The Relationship between Perceived Personal Risk of getting Prostate cancer and Prostate-Specific Antigen (PSA) Screening Yeatoe G. McIntosh, MPH Candidate Advisor: Emmanuel Anum, MBChB, MPH, PHD Preceptor: Emmanuel Anum, MBChB, MPH, PHD Background: Prostate cancer is one of the most common cancer diagnoses in the United States. The American Cancer Society estimates that in 2008 28,660 deaths would be attributed to prostate cancer, projecting it to be the leading cause of cancer deaths in U.S. men. Despite the potential threat this cancer presents to men and the potential for improved disease outcomes from early detection, guidelines for screening …

Malignant Neoplasm Of The Lower Respiratory Tract At King Chulalongkorn Memorial Hospital: A Retrospective Study On Histological Diagnoses Of 1,464 Cases From 2000 To 2006, A. Kulwongthanaroj, C. Chantranuwat

Chulalongkorn Medical Journal

No abstract provided.

Treg Depletion Inhibits Efficacy Of Cancer Immunotherapy: Implications For Clinical Trials., James Curtin, Marianela Candolfi, Tamer Fakhouri, Chunyan Liu, Anderson Alden, Matthew Edwards, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Regulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients. FINDINGS: Using a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs …

Nucleoplasmic And Cytoplasmic Degradation Of Telomerase: Implications Toward Telomerase-Based Cancer Therapy, Binh Nguyen

Theses and Dissertations

Telomerase is a ribonucleoprotein that is reactivated in cancer cells to allow for continuous cellular division and indefinite growth. With telomerase being expressed in more than 85% of all cancer, it is imperative that we understand how to selectively inactivate and degrade this unique DNA polymerase. In doing so, we can specifically target tumor cells to erode their telomeres so that they will undergo apoptosis or senescence. Through this research, we have learned that telomerase can be degraded in the nucleoplasm by Hsp90 chaperone inhibition and in the cytoplasm by the dominant negative mutant, D712A V713I. These findings should guide …

Management Of Oral Mucositis In Patients With Cancer, Rajesh V. Lalla, Douglas E. Peterson

UCHC Articles - Research

Oral mucositis refers to erythematous and ulcerative lesions of the oral mucosa observed in patients with cancer being treated with chemotherapy, and/or with radiation therapy to fields involving the oral cavity. Lesions of oral mucositis are often very painful and compromise nutrition and oral hygiene as well as increase risk for local and systemic infection. Mucositis can also involve other areas of the alimentary tract; for example, gastrointestinal (GI) mucositis can manifest as diarrhea. Thus, mucositis is a highly significant and sometimes dose-limiting complication of cancer therapy.

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Impaired Clearance Of Methotrexate In Organic Anion Transporter 3 (Slc22a8) Knockout Mice: A Gender Specific Impact Of Reduced Folates, Adam L. Vanwert, Douglas H. Sweet

Pharmaceutics Publications

Purpose

To elucidate the role of the renal basolateral transporter, Oat3, in the disposition of methotrexate.

Materials and Methods

Chinese hamster ovary cells expressing mouse Oat3 were used to determine kinetics and specificity of inhibition of methotrexate transport. Methotrexate clearance was then examined in vivo in wildtype and Oat3 knockout mice.

Results

NSAIDs, ß-lactams, and uremic toxins inhibited mOat3-mediated methotrexate uptake by 70–100%, while folate, leucovorin, and 5-methyltetrahydrofolate inhibited transport by 25–50%. A Km of 60.6±9.3 μM for methotrexate transport was determined. Oat3 knockout mice exhibited reduced methotrexate-to-inulin clearance ratios versus wildtype. Male wildtype mice, but not knockouts or …

2007 Cancer Care Annual Report, Children's Mercy Hospital

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Hospital, Kansas City MO, a pediatric medical center.