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The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]Pyrimidine Antifolates", Shermaine Kimberly Mitchell-Ryan

Wayne State University Dissertations

Ovarian Cancer is the fifth leading cause of cancer-related death of women in the United States. Epithelial Ovarian Cancer (EOC) constitutes 85-90% of malignancies within the ovary, with an alarming majority of these cases diagnosed at advanced stage. While most patients are initially highly responsive to the current treatment standard, there is a very high probability that they will recur with a drug resistant fatal disease. Currently there is no validated comprehensive model of disease progression for ovarian cancer, although tremendous progress has been made in understanding the origin of this disease and a putative precursor lesion has been identified …

Tps Mutational Status Is A Potential Marker For Risk Stratification In Wilms Tumour With Diffuse Anaplasia, Mariana Maschietto, Richard D. Williams, Tasnim Chagtai, Sergey D. Popov, Neil J. Sebire, Gordan Vujanic, Elizabeth Perlman, James R. Anderson, Paul Grundy, Jeffrey S. Dome, Kathy Pritchard-Jones

Pediatrics Faculty Publications

Purpose

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whetherTP53 mutational status confers additional prognostic information.

Patients and Methods

We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. …

Nuclear And Mitochondrial Trna-Lookalikes In The Human Genome., Aristeidis G Telonis, Phillipe Loher, Yohei Kirino, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

We are interested in identifying and characterizing loci of the human genome that harbor sequences resembling known mitochondrial and nuclear tRNAs. To this end, we used the known nuclear and mitochondrial tRNA genes (the "tRNA-Reference" set) to search for "tRNA-lookalikes" and found many such loci at different levels of sequence conservation. We find that the large majority of these tRNA-lookalikes resemble mitochondrial tRNAs and exhibit a skewed over-representation in favor of some mitochondrial anticodons. Our analysis shows that the tRNA-lookalikes have infiltrated specific chromosomes and are preferentially located in close proximity to known nuclear tRNAs (z-score ≤ -2.54, P-value ≤ …

Epoxide-Mediated Differential Packaging Of Cif And Other Virulence Factors Into Outer Membrane Vesicles, A. E. Ballok, L. M. Filkins, J.. M. Bomberger, B. A. Stanton, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa produces outer membrane vesicles (OMVs) that contain a number of secreted bacterial proteins, including phospholipases, alkaline phosphatase, and the CFTR inhibitory factor (Cif). Previously, Cif, an epoxide hydrolase, was shown to be regulated at the transcriptional level by epoxides, which serve as ligands of the repressor, CifR. Here, we tested whether epoxides have an effect on Cif levels in OMVs. We showed that growth of P. aeruginosa in the presence of specific epoxi

The End Of Alzheimer's Disease - From Biochemical Pharmacology To Ecopsychosociology: A Personal Perspective, Peter J. Whitehouse

Faculty Scholarship

The future of the Alzheimer's disease (AD) field involves a more complete understanding not only the state of current scientific approaches, but also the linguistic and cultural context of preclinical and clinical research and policy activities. The challenges surrounding dementia are large and growing but are only part of broader social and health concerns. In this latter context, the current state of research in the AD area is reviewed together with necessary priorities in moving forward. Creating a more optimistic future will depend less on genetic and reductionist approaches and more on environmental and intergenerative approaches that will aid in …

Current Pathophysiological Concepts In Cerebral Small Vessel Disease., Fred Rincon, Clinton B Wright

Department of Neurology Faculty Papers

The association between cerebral small vessel disease (SVD) - in the form of white matter lesions, infarctions, and hemorrhages - with vascular cognitive impairment (VCI), has mostly been deduced from observational studies. Pathological conditions affecting the small vessels of the brain and leading to SVD have suggested plausible molecular mechanisms involved in vascular damage and their impact on brain function. However, much still needs to be clarified in understanding the pathophysiology of VCI, the role of neurodegenerative processes such as Alzheimer's disease, and the impact of aging itself. In addition, both genetic predispositions and environmental exposures may potentiate the development …

An Ethnobotanical, Ecological And Lc-Ms-Based Chemometric Investigation Of Phaleria Nisidai, A Traditional Adaptogen Containing Diterpene Esters From Palau, Micronesia, Daniel Kulakowski

Dissertations, Theses, and Capstone Projects

An ethnobotanical, ecological and LC-MS-based chemometric investigation of Phaleria nisidai, a traditional adaptogen containing diterpene esters from Palau, Micronesia

Palau is a country with a rich heritage of traditional medicine still being practiced. One of the most popular and respected remedies in Palau is a tea made from fresh leaves of Phaleria nisidai Kaneh. (Thymelaeaceae). Interviews conducted to determine the use of this plant revealed that it is employed non-specifically to treat a variety of general health concerns. Its use as a prophylactic to keep away sickness, as a 'system cleaner', as well as for strength and energy indicate …

Layered Long Term Co-Culture Of Hepatocytes And Endothelial Cells On A Transwell Membrane: Toward Engineering The Liver Sinusoid, Young Bok (Abraham) Kang, Siddhartha Rawat, Joseph Cirillo, Michael Bouchard, Hongseok (Moses) Noh

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

This paper presents a novel liver model that mimics the liver sinusoid where most liver activities occur. A key aspect of our current liver model is a layered co-culture of primary rat hepatocytes (PRHs) and primary rat liver sinusoidal endothelial cells (LSECs) or bovine aortic endothelial cells (BAECs) on a transwell membrane. When a layered co-culture was attempted with a thin matrigel layer placed between hepatocytes and endothelial cells to mimic the Space of Disse, the cells did not form completely separated monolayers. However, when hepatocytes and endothelial cells were cultured on the opposite sides of a transwell membrane, PRHs …

Disruption Of Drosophila Melanogaster Lipid Metabolism Genes Causes Tissue Overgrowth Associated With Altered Developmental Signaling., Takeshi Sasamura, Kenji Matsuno, Mark E Fortini

Department of Biochemistry and Molecular Biology Faculty Papers

Developmental patterning requires the precise interplay of numerous intercellular signaling pathways to ensure that cells are properly specified during tissue formation and organogenesis. The spatiotemporal function of many developmental pathways is strongly influenced by the biosynthesis and intracellular trafficking of signaling components. Receptors and ligands must be trafficked to the cell surface where they interact, and their subsequent endocytic internalization and endosomal trafficking is critical for both signal propagation and its down-modulation. In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase. …

Altered Cholesterol Metabolism In Human Cancers Unraveled By Label-Free Spectroscopic Imaging, Shuhua Yue

Open Access Dissertations

Despite tremendous scientific achievements, cancer remains the second leading cause of death in the United States. Metabolic reprogramming has been increasingly recognized as a core hallmark of cancer. My dissertation work identified novel diagnostic markers and therapeutic targets for human cancers through the study of cholesterol in cancer cells.

Enabled by label-free Raman spectromicroscopy, we performed the first quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases, but not in normal prostate, benign prostatic hyperplasia, or …

Adoptive T Cell Therapy For Metastatic Colorectal Cancer, Shauna Ebanks

Summer Training Program in Cancer Immunotherapy

Colorectal cancer is the second leading cause of cancer-related death in US (1). Most of the mortality reflects local, regional and distant metastatic tumors. Cancers that are confined within the wall of the colon are often curable with surgery while tumor cells that have spread into other organs like liver and lung has low curable possibility, even though the chemotherapies and monoclonal antibodies can extend the person's life and improve quality of life(2, 3). Surgery is the main treatment for primary colorectal tumors but recurrence can happen and develop into metastasis. In addition, colorectal cancer …

Relationship Between Serum And Brain Carotenoids, Α-Tocopherol, And Retinol Concentrations And Cognitive Performance In The Oldest Old From The Georgia Centenarian Study, Elizabeth J. Johnson, Rohini Vishwanathan, Mary Ann Johnson, Dorothy B. Hausman, Adam Davey, Tammy M. Scott, Robert C. Green, L. Stephen Miller, Marla Gearing, John Woodard, Peter T. Nelson, Hae-Yun Chung, Wolfgang Schalch, Jonas Wittwer, Leonard W. Poon

Sanders-Brown Center on Aging Faculty Publications

Oxidative stress is involved in age-related cognitive decline. The dietary antioxidants, carotenoids, tocopherols, and vitamin A may play a role in the prevention or delay in cognitive decline. In this study, sera were obtained from 78 octogenarians and 220 centenarians from the Georgia Centenarian Study. Brain tissues were obtained from 47 centenarian decedents. Samples were analyzed for carotenoids, α-tocopherol, and retinol using HPLC. Analyte concentrations were compared with cognitive tests designed to evaluate global cognition, dementia, depression and cognitive domains (memory, processing speed, attention, and executive functioning). Serum lutein, zeaxanthin, and β-carotene concentrations were most consistently related to better cognition …

Effect Of Doping On Β-Tricalcium Phosphate Bioresorbable Bulk Material And Thin Film Coatings, Suhaila Abdalla

Dissertations

Magnesium has emerged as a revolutionary biodegradable metal for use as an orthopedic material, it has several advantages over the permanent metallic materials currently in use, including eliminating the effects of stress shielding, improving biocompatibility and degradation properties, thus removing the requirement of a second surgery for implant removal. Due to the rapid degradation of magnesium, it is necessary to control the corrosion rates of the materials to match the rates of bone healing. This dissertation reports on the effect of doping on the properties of β-tricalcium phosphate (β-TCP). It also reports on its application as a thin film coating …

The Complex Transcriptional Landscape Of The Anucleate Human Platelet., Paul F. Bray, Steven E. Mckenzie, Leonard Edelstein, Srikanth Nagalla, Kathleen Delgrosso, Adam Ertel, Joan Kupper, Yi Jing, Eric R. Londin, Phillipe Loher, Huang-Wen Chen, Paolo Fortina, Isidore Rigoutsos

Cardeza Foundation for Hematologic Research

BACKGROUND: Human blood platelets are essential to maintaining normal hemostasis, and platelet dysfunction often causes bleeding or thrombosis. Estimates of genome-wide platelet RNA expression using microarrays have provided insights to the platelet transcriptome but were limited by the number of known transcripts. The goal of this effort was to deep-sequence RNA from leukocyte-depleted platelets to capture the complex profile of all expressed transcripts.

RESULTS: From each of four healthy individuals we generated long RNA (≥40 nucleotides) profiles from total and ribosomal-RNA depleted RNA preparations, as well as short RNA (<40 >nucleotides) profiles. Analysis of ~1 billion reads revealed that coding …

Spinal Tuberculosis: Diagnosis And Management., Mohammad R Rasouli, Maryam Mirkoohi, Alexander R Vaccaro, Kourosh Karimi Yarandi, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

The spinal column is involved in less than 1% of all cases of tuberculosis (TB). Spinal TB is a very dangerous type of skeletal TB as it can be associated with neurologic deficit due to compression of adjacent neural structures and significant spinal deformity. Therefore, early diagnosis and management of spinal TB has special importance in preventing these serious complications. In order to extract current trends in diagnosis and medical or surgical treatment of spinal TB we performed a narrative review with analysis of all the articles available for us which were published between 1990 and 2011. Althoug h the …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Synergistic Effect Of Subnanosecond Pulsed Electric Fields And Temperature On The Viability Of Biological Cells, James Thomas Camp

Electrical & Computer Engineering Theses & Dissertations

Pulsed electric fields have been used to induce a biological response in cells, and at sufficient energy, can cause cell death. By reducing the pulse duration from presently used nanosecond to subnanosecond ranges, the electric field can be delivered to biological tissue non-invasively by the use of an antenna instead of electrodes, such as needles. Studies have previously been completed in which the aim was to determine the energy density (electric field strength, number of pulses) required to induce cell death with 800 ps pulses. Based on this data, it was concluded that for pulse durations of 200 ps, with …

A Role For Reactive Oxygen Species In Photodynamic Therapy, Michael Price

Wayne State University Dissertations

Photodynamic therapy (PDT) is based on the ability of certain photosensitizing agents to selectively localize in neoplastic cells and their vasculature. Subsequent irradiation at a wavelength corresponding to a photosensitizer absorbance band excites the photosensitizer molecules, leading to energy transfer reactions and fluorescence. It was initially concluded that the phototoxic effect occurred when energy from the excited state of the photosensitizer was transferred to dissolved oxygen to form singlet oxygen. This product has a very brief half-life and will cause cellular damage only in the immediate vicinity of its formation. But an excited-state photosensitizer can also interact with oxygen to …

2011 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.

2009 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. This report has a focus on acute lymphoblastic leukemia.

Central Role Of Tau Protein In Alzheimer»S Disease And Related Tauopathies, Khalid Iqbal, Omar Chohan, Inge Grundke-Iqbal

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Research Annual Report 2007, Children's Mercy Hospital

Research Annual Reports

Annual report of the research at Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

Frequency Of Abnormal Pap Smears And Assessment Of Risk Factors For Cervical Cancer In An Out-Patient Clinic, Firdous Jahan, Naheed Nabi, Waris Qidwai, Iqbal Azam

Department of Family Medicine

No abstract provided.

Oncolog Volume 53, Number 10, October 2008, Joe Munch, Sunita Patterson

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Pancreatic Cancer: The Prognosis Is Changing
• Delivering “The Guardian of the Genome”
• House Call: “Seeing” Cancer from the Outside
• Catching Pancreatic Cancer Early

Transcriptional Regulatory Network Analysis During Epithelial-Mesenchymal Transformation Of Retinal Pigment Epithelium., Craig H Pratt, Rajanikanth Vadigepalli, Praveen Chakravarthula, Gregory E Gonye, Nancy J Philp, Gerald B Grunwald

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

PURPOSE: Phenotypic transformation of retinal pigment epithelial (RPE) cells contributes to the onset and progression of ocular proliferative disorders such as proliferative vitreoretinopathy (PVR). The formation of epiretinal membranes in PVR may involve an epithelial-mesenchymal transformation (EMT) of RPE cells as part of an aberrant wound healing response. While the underlying mechanism remains unclear, this likely involves changes in RPE cell gene expression under the control of specific transcription factors (TFs). Thus, the purpose of the present study was to identify TFs that may play a role in this process.

METHODS: Regulatory regions of genes that are differentially regulated during …

Energizing Mirna Research: A Review Of The Role Of Mirnas In Lipid Metabolism, With A Prediction That Mir-103/107 Regulates Human Metabolic Pathways, Bernard R. Wilfred, Wang-Xia Wang, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are powerful regulators of gene expression. Although first discovered in worm larvae, miRNAs play fundamental biological roles-including in humans-well beyond development. MiRNAs participate in the regulation of metabolism (including lipid metabolism) for all animal species studied. A review of the fascinating and fast-growing literature on miRNA regulation of metabolism can be parsed into three main categories: (1) adipocyte biochemistry and cell fate determination; (2) regulation of metabolic biochemistry in invertebrates; and (3) regulation of metabolic biochemistry in mammals. Most research into the 'function' of a given miRNA in metabolic pathways has concentrated on a given miRNA acting upon …

Spontaneous Intracranial Arterial Dissection In The Young: Diagnosis By Ct Angiography, William C. Robertson, Curtis A. Given

Neurology Faculty Publications

BACKGROUND: Spontaneous carotid artery dissections have been rarely reported in children. Diagnosis has traditionally been confirmed by catheter arteriography. More recently diagnosis has been made by magnetic resonance imaging and magnetic resonance angiography; however the sensitivity of these techniques has yet to be determined. The authors are unaware of reports of carotid dissection confirmed by dynamic computed tomography (computerized tomographic arteriography) in the young.

CASE PRESENTATION: We recently evaluated a fourteen year-old male following the development of transient neurologic symptoms. There was no antecedent illness or trauma. Dynamic computed tomography revealed an intracranial dissection involving the supraclinoid segment of the …

Small B Cell Non-Hodgkins Lymphoma In Pakistan, Kanwal Aftab, Yasmin Bhurgri, Shahid Pervez

Department of Pathology and Laboratory Medicine

Objective: To study the pattern of small B cell lymphomas in Pakistan.

Methods: This descriptive study was carried out at the Aga Khan University Hospital pathology department including 1721 cases of Non-Hodgkins Lymphoma (NHL) diagnosed during a period of five years (1998-2002) and classified according to REAL/WHO classification. The antibodies used included Leukocyte Common Antigen (LCA), Pan B (CD20, CD79a), Pan T (UCHL-1), Bcl 2, Mib 1(Ki 67) and Cyclin D1 (Dako, Denmark).

Results: Out of the 1721 NHL cases, only 140 (8.1%) could be categorized as small B-cell NHL. The study group comprised small lymphocytic lymphoma/chronic lymphocytic leukemia (58 …

Differences In Peripheral Noradrenergic Function Among Actively Drinking And Abstinent Alcohol-Dependent Individuals., Ashwin A. Patkar, Charles A. Marsden, Prakash C. Naik, David A. Kendall, Raman Gopalakrishnan, Michael J. Vergare, Stephen P. Weinstein

Department of Psychiatry and Human Behavior Faculty Papers

We examined whether excessive alcohol consumption was related to changes in plasma levels of noradrenaline (NA) and whether these changes recover following abstinence. We also explored whether there were differences in NA levels between Type I and Type II alcoholics and controls during active drinking and abstinence. Plasma concentrations of NA were determined in (1) 27 Caucasian men with alcohol dependence who were regularly drinking (active drinkers) within 24 hours of hospitalization, (2) 29 Caucasian alcohol-dependent men who were in remission (abstinent for a minimum of three months), and (3) 28 race- and gender-matched healthy controls. NA concentrations were significantly …

Ionizing Radiation Induces A Stress Response In Primary Cultures Of Rainbow Trout Skin, Fiona Lyng, M. Lyons-Alcantara, P. Owell, Sharon Ni Shuilleabhain, Colin Seymour, D. Cottell, Carmel Mothersill

Articles

Fish skin is very vulnerable to damage from physical and chemical pollutants because it is in direct contact with the aquatic environment. In this study, the effect of g radiation on primary cultures of rainbow trout skin was investigated. Primary cultures containing two cell types, epidermal cells and goblet mucous cells, were exposed to doses ranging from 0.5–15 Gy 60Co g radiation. Expression of PCNA, c-myc and BCL2 was investigated as well as growth and levels of apoptosis and necrosis. Morphological and functional changes were also studied. The irradiated cultures showed evidence of a dose-dependent increase in necrosis and enhanced …