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Biological SciencesBiochemistry

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Incidence Insulin-requiring Diabetes in the US Military Jan 2009 7 pages
Authors:  Edward D Gorham; Elizabeth Barrett-Connor; Robyn M Highfill-McRoy; Sharif B Mohr; Cedric F Garland; Frank C Garland; Camillo Ricordi; NAVAL HEALTH RESEARCH CENTER SAN DIEGO CA
The full text of this report is available for sale.Type 1 diabetes mellitus (T1DM) is a disease of concern in young adults and children. Further research would be desirable to define the role of race and seasonality in incidence of T1DM in young adults. Seasonality and racial disparities in incidence suggest that T1DM may be associated vitamin D inadequacy. If so, public health action to reduce its incidence may be feasible with supplementation and vitamin D fortification of foods. ...


Combining Chemoselective Ligation with Polyhistidine-Driven Self-Assembly for the Modular Display of Biomolecules on Quantum Dots Jan 2009 13 pages
Authors:  Duane E Prasuhn; Juan B Blanco-Canosa; Gary J Vora; James B Delehanty; Kimihiro Susumu; Bing C Mei; Philip E Dawson; Igor L Medintz; NAVAL RESEARCH LAB WASHINGTON DC OPTICAL SCIENCES DIV
The full text of this report is available for sale.One of the principle hurdles to wider incorporation of semiconductor quantum dots (QDs) in biology is the lack of facile linkage chemistries to create different types of functional QD-bioconjugates. A two-step modular strategy for the presentation of biomolecules on CdSe/ZnS core/shell QDs is described here which utilizes a chemoselective, aniline-catalyzed hydrazone coupling chemistry to append hexahistidine sequences onto peptides and DNA. This specifically provides them the ability to ratiometrically self-assemble ...


Effect of Physicochemical Anomalies of Soda-Lime Silicate Slides on Biomolecule Immobilization Jan 2009 8 pages
Authors:  Stella H North; Evgeniya H Look; Tiffany R King; James B Franek; Scott G Walton; Chris R Taitt; NAVAL RESEARCH LAB WASHINGTON DC CENTER FOR BIOMOLECULAR SCIENCE AND ENGINEERING
The full text of this report is available for sale.Glass microscope slides are considered by many as the substrate of choice for microarray manufacturing due to their amenability to various surface chemistry modifications. The use of silanes to attach various functional groups onto glass slides has provided a versatile tool for the covalent immobilization of many diverse biomolecules of interest. We recently noted a dramatic reduction in biomolecule immobilization efficiency on standard microscope slides prepared using a well-characterized silanization ...


Anger Expression and Psychophysiological Stress Responses in Military Men 29-Dec-2008 32 pages
Authors:  Marcus K Taylor; Lilianne R Mujica-Parodi; Eric G Potterat; Amanda E Markham; Genieleah A Padilla; Nausheen Dial Momen; Michael D Ward; Katherine E Evans; NAVAL HEALTH RESEARCH CENTER SAN DIEGO CA
The full text of this report is available for sale.Little is known of individual differences governing human responses to realistic stress. In this study, the authors examined the relationships of anger experience and expression to psychophysiological stress indices during daily living and in response to military survival training in 45 healthy, male, active-duty Navy personnel. Prior to participation in survival training, participants completed self-report measures of perceived stress and anger. Also, salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed ...


Uncoupling GP1 and GP2 Expression in the Lassa Virus Glycoprotein Complex: Implications for GPI Ectodomain Shedding 23-Dec-2008 18 pages
Authors:  Luis M Branco; Alex Matschiner; Joseph N Fair; Megan M Illick; Kerry A Illick; Randal Schoepp; Robert F Garry; Mary C Guttieri; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
The full text of this report is available for sale.Bacillus anthracis lethal toxin (LT) was characterized in plasma from infected African Green monkeys, rabbits, and guinea pigs. In all cases, during the terminal phase of infection only the protease-activated 63-kDa form of protective antigen (PA63) and the residual 20-kDa fragment (PA20) were detected in the plasma. No uncut PA with a molecular mass of 83 kDa was detected in plasma from toxemic animals during the terminal stage of infection. ...


Stability Improvements of DNA Photonic Devices 20-Dec-2008 16 pages
Authors:  Naoya Ogata; OGATA RESEARCH LAB HOKKAIDO (JAPAN)
The full text of this report is available for sale.Recent research results on DNA-lipid complexes have shown various attractive features on E/O or O/E devices, optical memories, switches and sensors by intercalating optical dye into DNA double helix、while DNA devices absorbed water under high humidity which led to decreases of optical functions. However, it is possible to improve the stability of DNA devices by encapsulating the DNA-lipid complexes into sol-gel materials or synthetic polymers so that water permeation is ...


Vitamin D Supplementation in Submarines 02-Dec-2008 25 pages
Authors:  Jeffrey Gertner; Wayne Horn; NAVAL SUBMARINE MEDICAL RESEARCH LAB GROTON CT
The full text of this report is available for sale.Vitamin D is primarily recognized for its role in calcium homeostasis. However, recent research has suggested that the functions of vitamin D may be more numerous and complex. This paper is a review of basic physiology of vitamin D, recent research, and how it applies to submarine crews. Epidemiological and cellular research indicate that vitamin D may play a role in autoimmune disorders and cancer formation. These studies are not ...


Single Molecule Effects of Osteogenesis Imperfecta Mutations in Tropocollagen Protein Domains 02 Dec 2008 9 pages
Authors:  Alfonso Gautieri; Simone Vesentini; Alberto Redaelli; Markus J Buehler; MASSACHUSETTS INST OF TECH CAMBRIDGE DEPT OF CIVIL AND ENVIRONMENTAL ENGINEERING
The full text of this report is available for sale.Osteogenesis imperfecta (OI) is a genetic disease characterized by fragile bones, skeletal deformities and, in severe cases, prenatal death that affects more than 1 in 10,000 individuals. Here we show by full atomistic simulation in explicit solvent that OI mutations have a significant influence on the mechanical properties of single tropocollagen molecules, and that the severity of different forms of OI is directly correlated with the reduction of the mechanical ...


Aptamer Selection Express: A Novel Method for Rapid Single-Step Selection and Sensing of Aptamers Dec-2008 10 pages
Authors:  Maomian Fan; Shelly Roper; Carrie Andrews; Amity Allman; John Bruno; Jonathan Kiel; CONCEPTUAL MINDWORKS INC SAN ANTONIO TX
The full text of this report is available for sale.This article describes a new DNA capture element (DCE) sensing system, based on the quenching and dequenching of a double-stranded aptamer. This system shows very good sensitivity and thermal stability. While quenching, dequenching, and separating the DCE systems made from different aptamers (all selected by SELEX), an alternative method to rapidly select aptamers was developed the Aptamer Selection Express (ASExp). This process has been used to select aptamers against different ...


Blood Chemistries Following Repeated Days of First Strike Ration or Meal, Ready-to-Eat consumption Dec-2008 28 pages
Authors:  Scott J Montain; John S Cuddy; Brent C Ruby; Dustin Slivka; Matthew R Ely; Susan M McGraw; Jennifer Rood; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA MILITARY NUTRITION DIV
The full text of this report is available for sale.To determine if the First Strike Ration (FSR) sustains nutritional and metabolic status as effectively as the Meals, Ready to Eat (MRE), blood chemistries were compared between Soldiers who consumed 1 FSR (2864 Kcal, 377 g CHO, 91 g PRO, 109 g Fat) per day or 2 MRE (2620 Kcal, 348 g CHO, 84 g PRO, 102 g Fat) per day while performing 3 days of wildland fire suppression. Eighteen ...


Telomere Length Polymorphisms: A Potential Factor Underlying Increased Risk of Prostate Cancer in African American Men and Familial Prostate Cancer Dec-2008 30 pages
Authors:  Alan K Meeker; JOHNS HOPKINS UNIV BALTIMORE MD
The full text of this report is available for sale.This project tests the hypothesis that inherited and/or acquired differences in telomere length unprostate cancer observed in African Americans compared to Caucasians and in affected members of hefamilies. To test this hypothesis, telomere content in genomic DNA isolated from blood samples of by quantitative PCR and the data assessed for associations with either racial background or prostathe period of this report we have isolated genomic DNA from 128 members from ...


Molecular Targets for the Prevention of Prostate Cancer Dec-2008 16 pages
Authors:  Ajit K Verma; WISCONSIN UNIV-MADISON
The full text of this report is available for sale.The objectives of this proposal are to determine whether protein kinase C epsilon (PKCe) is linked to the initiation and progression of Prostate cancer (PCa) and should be explored as a molecular target for the prevention of human PCa. PKCe, a calcium-insensitive PKC, is among the PKC isoforms expressed in both mouse and human prostate tissue. We plan to test the hypothesis that PKCe is linked to the onset, progression ...


Hyaluronan Tumor Cell Interactions in Prostate Cancer Growth and Survival Dec-2008 42 pages
Authors:  James B McCarthy; Eva Turley; MINNESOTA UNIV MINNEAPOLIS
The full text of this report is available for sale.Hyaluronan is a high molecular weight polyanionic polysaccharide that is increased in more advanced prostate cancers. Tumor cell interaction with this polysaccharide by specific receptors CD44 and RHAMM promote tumor growth, survival and invasion. Work during the last funding period have further defined the mechanism of action of each of these receptors. Studies show that extracellular RHAMM acts a co-receptor for CD44, and the combined action of this receptor complex ...


Fatty Acid Synthase Inhibitors Engage the Cell Death Program Through the Endoplasmic Reticulum Dec-2008 58 pages
Authors:  Steven J Kridel; WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF HEALTH SCIENCES
The full text of this report is available for sale.Fatty acid synthase (FAS), the enzyme that synthesizes the 16-carbon fatty acid palmitate, in highly expressed in prostate cancer. Because of a corresponding lack of expression in normal prostate, FAS is an attractive drug target. We have described the endoplasmic stress (ER) response as a critical mediator of the anti-tumor effects of FAS inhibitors. In this report we demonstrate the mechanism that drives the synergy between FASN inhibitors and the ...


Molecular Mechanisms and Treatment Strategies for Obesity-Associated Coronary Artery Disease, an Imminent Military Epidemic Dec-2008 90 pages
Authors:  Ira Tabas; Wai H Woo; COLUMBIA UNIV NEW YORK
The full text of this report is available for sale.There is an epidemic of obesity in the military. Obesity leads to type 2 diabetes, the most dangerous consequence of which is atherothrombotic vascular disease. We have made major progress on the key Tasks over the last year. We have gained more in-depth understanding on how the AngII targets CaMKII and NADPH oxidase trigger apoptosis in ER-stressed macrophages. Our knowledge of how PPARs and obesity affect advanced plaque progression was ...


Mobility, Geochemistry, and Speciation of Tungsten Dec-2008 8 pages
Authors:  A J Bednar; W T Jones; R E Boyd; R A Kirgan; M A Chappell; J L Clausen; ENGINEER RESEARCH AND DEVELOPMENT CENTER VICKSBURG MS ENVIRONMENTAL LAB
The full text of this report is available for sale.Tungsten metal is used in many industrial, military, and consumer applications, and interest in its biogeochemistry is increasing partially due to its potential mobility and biological effects. Recent studies have investigated the geochemistry of tungsten from the laboratory to field scale, to determine its mobility and toxicity. Tungsten exists in most environmental matrices as the soluble and mobile tungstate anion, although polymerization to form poly- and heteropoly- tungstates has been ...


Integration of the Bionanomaterial Bacteriorhodopsin and Single Electron Transistors Dec-2008 5 pages
Authors:  Paul L Bergstrom; Craig Friedrich; Karl A Walczak; Manoranjan Arcary; Donald R Lueking; MICHIGAN TECHNOLOGICAL UNIV HOUGHTON DEPT OF MECHANICAL ENGINEERING AND ENGINEERING MECHANICS
The full text of this report is available for sale.Innovation in sensing technology is necessary in order to decrease negative outcomes in the event of a chemical or biological exposure. The sensors currently used to detect chemical and biological agents are too bulky, complex, and costly. The thrusts of this research are to develop sensor technologies. The technologies developed would help create sensor arrays which are: lightweight, disposable, wireless, deployable by hand, and reconfigurable. This paper will present initial ...


Soil Microbial Activity Benchmarks (Provisional) for Ecological Risk Assessments at Explosives-Contaminated Sites: Promoting Range Sustainability Dec-2008 8 pages
Authors:  R G Kuperman; R T Checkai; C T Phillips; M Simini; S Dodard; J Hawari; S Rocheleau; M Joly; G I Sunahara; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD
The full text of this report is available for sale.The Army Strategy for the Environment applies an ecosystem approach to managing natural resources on Army installations. It incorporates the principles of sustainability across the Army into all functional areas. We conducted investigations to develop critical data required for successful management of Army installations in a sustainable manner and for the knowledge-based decision making. Assessment and protection of the terrestrial environment at Army testing and training ranges is being advanced ...


PRO-2-PAM: The First Therapeutic Drug for Reactivation of Organo-Phosphate-Inhibited Central (Brain) and Peripheral Cholinesterases Dec-2008 9 pages
Authors:  K; Farhat A Khan; Latoya A Hyson; Angela R Davis; James C DeMar; Ruthie H Ratchiffe; Roberta R Owens; Amy J Campbell; Richard Gordon; Madhusoodana P Nambiar; Elizabeth Marek; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
The full text of this report is available for sale.Due to the documented use of organophosphorus (OP) chemical agents in warfare and by terrorists around the globe, Federal, State, and local authorities need novel therapeutics to overcome their deleterious effects. OPs inhibit cholinesterases (ChE), leading to accumulation of the neurotransmitter acetylcholine (ACh). Potentially lethal effects begin with secretion, muscle fasciculation, and paralysis in the peripheral nervous system (PNS). Central nervous system (CNS) perturbations include epileptic seizures leading to neuronal ...


Chemical and Biological Sensing Utilizing Fused Bacteriorhodopsin Protein Hybrids Dec-2008 7 pages
Authors:  Donald R Lueking; Eric M Winder; Mark H Griep; Craig R Friedrich; MICHIGAN TECHNOLOGICAL UNIV HOUGHTON
The full text of this report is available for sale.This paper describes how monomeric bR can be overproduced in Escherichia coli and subsequently utilized as an integral component of a generic, nanoscale chemical sensing platform. The utility of this sensing platform is that it can be adapted for detection of a wide range of biological and chemical agents at, or below, nanomolar concentration levels. The gene encoding for bacteriorhodopsin has been successfully isolated from Halobacterium salinarum strain S9P using ...


Assembly of Proteorhodopsin for Bioinspired Alternative Energy Applications Dec-2008 3 pages
Authors:  C Nguyen; J Ingram; H Liang; G Stucky; MILITARY ACADEMY WEST POINT NY DEPT OF CHEMISTRY
The full text of this report is available for sale.Proteorhodopsin is an integral membrane protein that functions as a light-driven proton pump, which serves as the basis for an alternative energy device. While many membrane proteins are becoming understood, both structurally and mechanistically, little technology exists for the production and incorporation of this important class of molecules into useful devices. The advantage we have in working with proteorhodopsin is that it can be genetically modified and grown in the ...


An Environmental Sentinel Biomonitor System for Drinking Water Protection Dec-2008 7 pages
Authors:  M W Widder; D Trader; L Brennan; T R Shedd; Gargan; T P van der II; W H Schalie; N Salazar; Y R Vallejo; ARMY CENTER FOR ENVIRONMENTAL HEALTH RESEARCH FORT DETRICK MD
The full text of this report is available for sale.Toxic industrial chemicals (TICs) are a potential threat to field drinking water supplies, but capabilities for rapid field testing of water are limited to relatively few chemicals. The Environmental Sentinel Biomonitor (ESB) system will significantly augment current detection methods by rapidly identifying toxicity from chemicals that currently cannot be rapidly detected in water samples in the field. The ESB system utilizes two toxicity sensors - a cell based electrical impedance ...


Early Systemic Biomarkers of Acute Lung Injury: Application of Multiplex Proteomic Array Technology Dec-2008 8 pages
Authors:  Adolph Januszkiewicz; Jayasree Nath; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
The full text of this report is available for sale.The primary objectives of the present study were: 1) to set up a non-invasive animal model of 'inhalation injury', to monitor early changes in levels of pro-inflammatory cytokines in breath condensates of live rats, to delineate early biomarkers of pulmonary inflammation; 2) to further investigate the role of specific proinflammatory mediator(s) in acute lung inflammation/injury following exposure to toxic fire gases and/or BOP shockwave-mediated blunt trauma; 3) to monitor changes ...


Quantum Dot / Optical Protein Bio-Nano Hybrid System for Biosensing Applications Dec-2008 6 pages
Authors:  M Griep; D Lueking; R Mackay; G Mallick; S Karna; C Friedrich; MICHIGAN TECHNOLOGICAL UNIV HOUGHTON DEPT OF MECHANICAL ENGINEERING AND ENGINEERING MECHANICS
The full text of this report is available for sale.The unique energy transfer interaction between the optical protein bacteriorhodopsin (bR) and CdSe/ZnS quantum dots (QDs) provides a potential modulation mechanism for bio-nano electronic application. We have utilized ionic-self assembled monolayer (I-SAM) techniques to create a novel alternating monolayer system of QDs and bR on a conductive ITO substrate. Results demonstrate the ability to efficiently create bR/QD multilayer films along with the ability to control bR/QD spacing on the nanometer ...


Release of BMP-2 and Tobramycin from Injectable, Biodegradable Polyurethane Scaffolds for Enhanced Bone Fracture Healing Dec-2008 4 pages
Authors:  A E Hafeman; J O Hollinger; S A Guelcher; VANDERBILT UNIV NASHVILLE TN
The full text of this report is available for sale.Nonunions are a significant clinical problem for civilians and military personnel. A 2004 report (Capturing the Full Power of Biomaterials for Military Medicine)1 published by the National Research Council recognizes the potential for further development of bioactive materials that promote bone healing and decrease the incidence of non-unions. Military applications of bone graft materials incorporating bioactives that promote bone healing will be practical and realistic over the next 3 ? ...


Methylmercury-Induced Dysfunction of Blood Vessel Cells: Implications in Cardiovascular Diseases Dec-2008 9 pages
Authors:  A Shidham; N Parinandi; S Sherwani; UPPER ARLINGTON HIGH SCHOOL COLUMBUS OH
The full text of this report is available for sale.Methylmercury [MeHg] has long been known as a neurotoxic agent. Recent epidemiological research has also linked MeHg exposure to cardiovascular disease. However, the precise mechanisms linking MeHg toxicity to blood vessels at the cellular levels are lacking. Endothelial cells exist as a single monolayer of cells that form the inner lining of blood vessels and are crucial to the structure and function of blood vessels. It was proposed that these ...


Macrolide Antibiotics Improve Phagocytic Capacity and Reduce Inflammation In Sulfur Mustard-Exposed Monocytes Dec-2008 9 pages
Authors:  Radharaman Ray; Prabhati Ray; Xiugong Gao; Yan Xiao; Keiko Ishida; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
The full text of this report is available for sale.Sulfur mustard (SM) inhalation causes apoptosis and death of airway epithelial cells as well as inflammation in the airway. Efficient clearance of the cell debris by alveolar macrophages (AMs) is necessitated to reduce the inflammation. Macrolide antibiotics have been reported to have anti-inflammatory properties by modulating the production of proinflammatory cytokines and mediators, and by improving macrophage functions. The present study investigated the effects of four FDA-approved macrolide antibiotics, namely ...


Development of a Portable DNA Sensor System Dec-2008 11 pages
Authors:  J J Sumner; P Freudenthal; C D Meinhart; H T Soh; K W Plaxco; ARMY RESEARCH LAB ADELPHI MD
The full text of this report is available for sale.A fully-integrated, palmtop, field-portable DNA analyzer that is capable of responding within 30 minutes to a sample of as little as three strands of DNA will enhance the survivability of the warfighter. This technology has been sponsored through the Institute of Collaborative Biotechnologies and was lead by Nanex LLC with co-investigators from the US Army Research Laboratory and the University of California, Santa Barbara. This analyzer will not sacrifice selectivity ...


DNA-Based Chiral Composites with Enhancement of Chirooptic and NLO Effects for NIMS Applications 24-Nov-2008
Authors:  Marek Samoc; Anna Samoc; AUSTRALIAN NATIONAL UNIV CANBERRA
The full text of this report is not available and therefore is not for sale. This information is provided for reference purposes only.In March 2008 we started a new research program on enhancement of chirooptic and nonlinear optical properties in composites based on deoxyribonucleic acid (DNA) derived from marine sources (salmon roe). During the first half-year period of the project we worked on preparation and characterization of the hybrid composites that utilize DNA as a chiral template for assembling non-chiral organic conjugated molecules and noble metal nanoparticles. This combination could potentially lead ...


Prostate Cancer in African-American Men: Serum Biomarkers for Early Detection Using Nanoparticles 01-Nov-2008 18 pages
Authors:  Catherine M Phelan; H LEE MOFFITT CANCER CENTER AND RESEARCH INST TAMPA FL
The full text of this report is available for sale.We have blood samples from 40 African-American men with prostate cancer and 30 ethnically-matched control healthy men with questionnaire data on demographics, general health and cancer family history. Our total accrual goal is 100 cases and 200 controls. The use of nanoscale materials and devices has enhanced the lower limits of detection of proteins and other compounds in plasma and tissues. We have investigated using nanoparticles or quantum dots conjugated ...


Carbon Dioxide Corrosion and Acetate: A Hypothesis on the Influence of Microorganisms Nov-2008 7 pages
Authors:  Brenda J Little; Joseph M Suflita; Tommy J Phelps; NAVAL RESEARCH LAB STENNIS SPACE CENTER MS OCEANOGRAPHY DIV
The full text of this report is available for sale.It is our hypothesis that fermentative acetogenic, and sulfate-reducing bacteria residing in pipeline facilities can influence corrosion through the production of carbon dioxide and acetate under the prevailing anaerobic conditions. The exacerbation of carbon dioxide corrosion of carbon steel in the presence of acetic acid is a well-known phenomenon in the oil industry. Both chemical compounds can be produced and consumed by microorganisms during the anaerobic biodegradation of organic matter-- ...


The Role of Interleukin-6/GP130 Signaling in Prostate Cancer Progression and its Contribution to Bone Metastasis Morbidity Nov-2008 28 pages
Authors:  Richard P Redvers; MONASH UNIV CLAYTON (AUSTRALIA) INST OF MEDICAL RESEARCH
The full text of this report is available for sale.Prostate cancer (PrCa) is the leading cause of male cancer death in Western civilization. Interleukin-6 (IL-6) is a cytokine implicated in primary PrCa growth and survival post-androgen withdrawal. Moreover, IL-6 is strongly associated with bone metastasis, a major cause of morbidity in PrCa patients. This project aims to investigate the IL-6 axis in a novel in vivo PrCa xenograft model (BM18) of androgen-dependent growth (McCulloch et al., 2005) and osteosclerotic ...


The Role of HOX Proteins in Androgen-Independent Prostate Cancer Nov-2008 11 pages
Authors:  Sunshine Daddario; COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
The full text of this report is available for sale.HOX genes encode a large family of transcription factors involved in key developmental decisions, and are often aberrantly expressed in cancer. Our laboratory has previously shown that a subset of genes of the HOXC cluster are overexpressed in primary prostate tumors, metastases, and prostate cancer (PCa) cell lines1. Increasing transient expression of HOXC8 in LNCaP PCa cells as well as HPr-1 AR non-tumorigenic prostate epithelial cells results in a progressive ...


PIM1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer 31-Oct-2008 47 pages
Authors:  Michael Lilly; LOMA LINDA UNIV CA
The full text of this report is available for sale.The contract supports studies to define the role of the PIM1 kinase in acquired resistance to chemotherapy by prostate cancer cells. Data to date for specific aim #1 define a signaling pathway induced by docetaxel, involving sequential steps of STAT3 phosphorylation, expression of PIM1, and activation of NFkB signaling. Blockade of this pathway prevents drug-induced upregulation of NFkB activity, and sensitizes cells to docetaxel. Other studies (specific aim #2)focus on ...


PSMA-Targeted Nano-Conjugates as Dual-Modality (MRI/PET) Imaging Probes for the Non-Invasive Detection of Prostate Cancer Oct-2008 10 pages
Authors:  Xiankai Sun; TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
The full text of this report is available for sale.The goal of this project is to develop dual modality imaging probes for the detection of prostate cancer by doping radioisotopes to iron oxide nanoparticles, so that the sensitivity and specificity of prostate cancer diagnosis could be significantly improved. In the three years, a facile approach has been developed to prepare gamma- or positron emitting nuclides incorporated SPIO nanoparticles (NUSPIONs) for dual modality imaging of prostate cancer, where a size-exclusion ...


Function of Klotho and is MicroRNA in Prostate Cancer and Aging Oct-2008 7 pages
Authors:  Shao-Yao Ying; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
The full text of this report is available for sale.We have observed the expression of CD164, IGFR, and Klotho proteins in human prostate cancer tissue microarrays as determined by immunohistochemistry. A positive correlation between CD164, IGFR and stages of prostate cancer was observed whereas a negative correlation between Klotho and stages was detected. However, the expression of Klotho in terms of the age of patients was not conclusive due to a small number of older (65 years) patients. Previously, ...


Development of the C-Terminal Inhibitors of Heat Shock Protein 90 in the Treatment of Prostate Cancer Oct-2008 26 pages
Authors:  Jeffrey Holzbeierlein; KANSAS UNIV MEDICAL CENTER RESEARCH INST KANSAS CITY
The full text of this report is available for sale.To develop and evaluate novel compounds which inhibit the C-terminal portion of Hsp90 in prostate cancer models. To develop a library of novobiocin analogues to be tested in vitro initially and then in a mouse model. Major findings: we have tested over 220 analogues of the original parent compound (A-1) all of which have been tested in at least two commonly used prostate cancer cell lines LNCaP and PC3. Screening ...


Lysosome-mediated Cell Death and Autophagy-Dependent Multidrug Resistance in Breast Cancer Oct-2008 16 pages
Authors:  Victor V Levenson; NORTHWESTERN UNIV EVANSTON IL
The full text of this report is available for sale.The original Statement of Work called for analysis of proteins and organelles involved in autophagic cell death (Task 1); for analysis of expression profiles and identification of pathways affected by tamoxifen treatment in parental cells and in resistant derivatives (Task 2); and for functional testing of identified differentially regulated genes as potential components of regulatory pathways for autophagy-related cell death (Task 3). It is important to recognize that Tasks 1 ...


Targeting Fatty Acid Synthase Gene for Prostate Cancer Therapy Oct-2008 6 pages
Authors:  Kounosuke Watabe; Eiji Furuta; SOUTHERN ILLINOIS UNIV SPRINGFIELD
The full text of this report is available for sale.Fatty acid synthase (FAS) is significantly over-expressed in prostate tumor cells and inhibition of FAS results in apoptosis, suggesting that FAS is an ideal target for drug development. The overarching hypothesis of this project is that a specific inhibitor for FAS dimerization will block the function of this enzyme and cause apoptosis of the tumor cell. Our specific aims are (1) to characterize the apoptotic pathway induced by FAS inhibition, ...


The Impact of a Common Mdm2 SNP on the Sensitivity of Breast Cancer To Treatment Oct-2008 13 pages
Authors:  Jin-Ming Yang; Kim M Hirshfield; Bruce Haffty; ROBERT WOOD JOHNSON MEDICAL SCHOOL PISCATAWAY NJ
The full text of this report is available for sale.The discovery of a single nucleotide polymorphism (SNP) in the mdm2 promoter uncovered a previously unknown role of this SNP in predicting early onset of breast and the possibility that this germ line variation could decrease the effectiveness of treatment. These outcomes are likely due to the increased expression of mdm2 protein in SNP309 individuals, which blunts the p53-mediated apoptotic response to DNA damage. The objective of this proposal is ...


Mechanisms Down-Regulating Sprouty1, a Growth Inhibitor in Prostate Cancer Oct-2008 113 pages
Authors:  Bernard Kwabi-Addo; HOWARD UNIV WASHINGTON DC
The full text of this report is available for sale.The Sprouty gene family negatively regulates growth factor-induced receptor tyrosine kinase signaling in human prostate cancer (PCa). The purpose of this study was to investigate the expression of Sprouty1 in PCa, determine its biological function and elucidate the molecular mechanism(s) regulating its expression in PCa. RESULTS: Using immunohistochemical and quantitative RT-PCR analysis, I have shown that Sprouty1 is down-regulated in PCa tissues compared to matched normal prostate tissues. Transient forced ...


Assessment of GPR30, a Seven Transmembrane-Spanning Estrogen Receptor, as an Oncogene Oct-2008 9 pages
Authors:  Edward J Filardo; RHODE ISLAND HOSPITAL PROVIDENCE
The full text of this report is available for sale.Expression of the seven transmembrane-spanning receptor (7TMR), GPR30, in primary human breast tumors is positively associated with several tumor progression variables including extra mammary metastases (Filardo et al, 2006). Altered expression of 7TMRs is linked with a spectrum of disease phenotypes, including cancer, raising the possibility that GPR30 may function as an oncogene. To test this hypothesis, two lines of transgenic mice (T6-1A and T6-2E) were engineered with stably integrated ...


Bioremediation Approaches for Treating Low Concentrations of N-Nitrosodimethylamine in Groundwater Oct-2008 151 pages
Authors:  Jalal Hawari; Diane Fournier; Paul Hatzinger; SHAW ENVIRONMENTAL INC LAWRENCEVILLE NJ
The full text of this report is available for sale.NDMA is a potent carcinogen and an emerging groundwater pollutant. The objective of this SERDP project was to study NDMA biodegradation and to develop in situ and ex situ bioremediation strategies for the compound. A detailed summary of the relevant findings for this project is provided in the Executive Summary of this report.


Determination of Optimum Vitamin D Nutrition in Young Women Oct-2008 6 pages
Authors:  John C Gallagher; CREIGHTON UNIV OMAHA NE
The full text of this report is available for sale.The main objective of the current proposal is to study the effect of increasing doses of vitamin D3 in a group of young women with hypovitaminosis D (serum 25OHD 20 ng/ml) and an adequate calcium intake of 1200 -1400mg/day. This is a double blind randomized placebo controlled study .There will be 5 treatment arms, four vitamin D3 dose groups ,400, 800, 1600, and 2400 IU/day and placebo .Calcium citrate tablets ...


Therapeutic Implications of Progesterone Receptor-Mediated Regulation of Cell Cycle in Breast Cancer Oct-2008 15 pages
Authors:  Hilary Wade; DUKE UNIV DURHAM NC OFFICE OF SPONSORED PROGRAMS
The full text of this report is available for sale.Since the 2007 summary report, we have made significant progress in elucidating the novel mechanisms by which PR regulates expression of E2F1, a key regulator of cell cycle progression, in T47D breast cancer cells. In addition to a direct regulatory pathway involving recruitment of PR to the E2F1 promoter, we have identified several indirect modes of regulation. First, ligand-bound PR stimulates increased recruitment of E2F1 to its own promoter in ...


Total Xenoestrogen Body Burden in Relation to Mammographic Density, a Marker of Breast Cancer Risk Oct-2008 22 pages
Authors:  Amy Trentham-Dietz; WISCONSIN UNIV-MADISON BOARD OF REGENTS/RESEARCH SPONSORED PROGRAMS
The full text of this report is available for sale.Humans are also exposed to a large number of environmental chemicals which have estrogenic activity (xenoestrogens) and therefore may raise breast cancer risk. This study is evaluating the association of total xenoestrogen burden with mammographic breast density, which is a strong intermediate marker of breast cancer risk. All study procedures and manuals of operation for this study have been finalized, and IRB approval obtained. Subject recruitment is currently ongoing. 108 ...


Complement and Immunotherapy of Breast Cancer Oct-2008 7 pages
Authors:  Michelle Rapisardo; Stephen Tomlinson; MEDICAL UNIV OF SOUTH CAROLINA CHARLESTON
The full text of this report is available for sale.In general, monoclonal antibody immunotherapy for cancer has fallen short of clinical expectations. This is due, at least in part, to the over expression of membrane-bound complement inhibitors on the tumor cell surface. The authors proposed to prepare and investigate the effects of two novel recombinant proteins aimed at modulating complement to increase the immune response to breast tumors. During year two it was proposed to finish construction, expression, and ...


Mechanisms of Rerg-Mediated Tumor Suppression in Breast Cancer Oct-2008 14 pages
Authors:  Ariella B Hanker; Channing J Der; NORTH CAROLINA UNIV AT CHAPEL HILL
The full text of this report is available for sale.Rheb (Ras Homolog Enriched in Brain), a member of the Ras family of GTPases, has been implicated as an oncogene and may be involved in estrogen-dependent breast cancer. Rheb activity is induced by non-genomic estrogen signaling; activated Rheb leads to activation of the mTOR kinase and increased protein translation and cell cycle progression. Whether Rheb is required for estrogen-induced breast cancer growth and whether Rheb can promote tamoxifen resistance has ...


Identification of Substances for Ubiquitin-Dependent Proteolysis During Breast Tumor Progression Oct-2008 31 pages
Authors:  Charles H Spruck; SIDNEY KIMMEL CANCER CENTER SAN DIEGO CA
The full text of this report is available for sale.Ubiquitylation is post-translational modification in which a small and highly abundant protein called ubiquitin is attached to proteins. Ubiquitylation regulates several processes that are central to breast tumorigenesis, including cell division, inflammation, and angiogenesis. However, defining how ubiquitylation contributes to breast tumorigenesis has been technically limited. We developed an innovative methodology that utilizes protein microarrays as a platform to evaluate the ubiquitylation activity of breast tumor specimens on a proteome-wide ...


Molecular Basis for BRCA2-mediated DNA Repair and Breast Tumor Suppression Oct 2008 12 pages
Authors:  Julie Etchin; YALE UNIV NEW HAVEN CT
The full text of this report is available for sale.In eukaryotes, homologous recombination and the homology-directed repair of DNA double-strand breaks are mediated by the RAD51 recombinase. In catalyzing recombination reactions, RAD51 must first form a right-handed helical filament, termed the presynaptic filament, on single-stranded DNA. Emerging evidence indicates that BRCA2 acts a recombination mediator by promoting the assembly of the RAD51 presynaptic filament. BRCA2 binds DNA and associates with RAD51. Our laboratory has established biochemical systems to examine ...


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