| Military and Veterans' Benefits: Analysis of VA Compensation Levels for Survivors of Veterans and Servicemembers |
Nov-2009 |
33 pages |
| Authors:
Daniel Bertoni; Kyle C Adams; Beverly Ross; Walter K Vance; Kirsten B Lauber; Gregory D Whitney; Daniel R Concepcion; Paul R Schearf; Melissa H Emrey-Arras; Susan L Aschoff; GOVERNMENT ACCOUNTABILITY OFFICE WASHINGTON DC
|
 | We study the local reactivity of molecular oxygen with bimetallic substrates of a platinum trimer island supported on nanotips of CoPt, Pt, Co, Ni, and Fe. Because of the reduced interatomic distances and varying interaction strengths with the substrates, the supported island interaction with oxygen can be tuned from stronger to weaker relative to the interaction of a freestanding island with oxygen despite that there is no well-behaved trend with ... |
|
| High-Voltage Poling of a Bulk Sample of Disperse Red 1 Polymethylmethacrylate Guest-Host Polymer for U.S. Army Electro-Optical Applications |
Jul-2009 |
20 pages |
| Authors:
Stephen Fallis; Warren Herman; Andrew P Chafin; Matthew C Davis; Geoffrey A Lindsay; Timothy Pritchett; Robert C Hoffman; George R Martin; Joseph M Dougherty; Adam M Rawlett; Robert H Lambeth; Nicole E Zander; Joshua A Orlicki; Andrew G Mott; Jan Andzelm; Dong Park; ARMY RESEARCH LAB ABERDEEN PROVING GROUND MD WEAPONS AND MATERIALS RESEARCH DIRECTORATE
|
| The U.S. Army Research Laboratory is currently developing novel materials with high-bulk electro-optic (EO) activities that are transparent in the visible and/or near infrared regions of the spectrum. This multi-defense laboratory collaboration is a highly interactive and multispectral research effort (with expertise spanning from molecular modeling, materials development and processing, and system fabrication and testing), which is operating toward the development of fast EO shutters. A computational effort to predict ... |
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| Regulatory Role of the NF-kB Pathway in Lymphangiogenesis and Breast Cancer Mestatasis |
Jul-2009 |
33 pages |
| Authors:
Michael Flister; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| The concept of inflammation-induced lymphangiogenesis (i.e., formation of new lymphatic vessels) has long been recognized, but the molecular mechanisms remained largely unknown. The two primary mediators of lymphangiogenesis are vascular endothelial growth factor receptor-3 (VEGFR-3) and Prox1. The key factors that regulate inflammation-induced transcription are members of the NF-kB family; however, the role of NF-kB in regulation of lymphatic-specific genes has not been defined. Here, we identified VEGFR-3 and Prox1 ... |
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| Identification of the Mechanisms Underlying Antiestrogen Resistance: Breast Cancer Research Partnership between FIU-UM Braman Family Breast Cancer Institute |
Jun-2009 |
13 pages |
| Authors:
Deodutta Roy; FLORIDA INTERNATIONAL UNIV MIAMI
|
| This research proposal has two primary objectives which are to (1) increase FIU investigators' research expertise and competitive ability to succeed as independent breast cancer researchers; and (2) to execute research with the promise of identifying molecular causes of breast tumor resistance to anti-estrogen therapy. This research is of significant merit because of its clinical relevance to breast cancer. Secondly, the research accomplishments through the FIU/BFBCI training program will lead ... |
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| Regulation and Action of SKP2 in Cell and Tumor Models: Mechanisms Underlying Aggressive Growth in Basel-Like Breast Cancer |
Jun-2009 |
6 pages |
| Authors:
Katerina Fagan-Solis; MASSACHUSETTS UNIV AMHERST
|
| The objective of this research is to further our understanding of the molecular mechanisms underlying the aggressive growth of estrogen receptor (ER)-negative, basal-like breast tumors. My goal is to determine if SKP2 is a viable new therapeutic target to specifically treat patients who have tumors that are independent of ER signaling. The most significant finding during this research period is that SKP2 protein was expressed in 60% (21 of 35) ... |
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| PROSPECT (Profiling of Resistance Patterns & Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification |
Jun-2009 |
427 pages |
| Authors:
Wuan K Hong; M D ANDERSON CANCER CENTER HOUSTON TX
|
| We will develop a high throughput therapeutic-target focused (TTF) profiling platform and will combine this with tumor genome wide mRNA profiling and with serum or plasma profiling of phosphopeptides and DNA. We will use these molecular profiles to help define how various molecular factors alone and in combination relate to resistance to therapy, to prognosis, and to metastatic patterns at relapse. Using tumor and blood samples from non-small cell lung ... |
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| Chemical Reactivity as a Probe of Ionic-Liquid Surfaces |
30-Apr-2009 |
18 pages |
| Authors:
Kenneth McKendrick; Carla Waring; Paul A Bagot; Matthew L Costen; HERIOT-WATT UNIV EDINBURGH (UNITED KINGDOM)
|
| This report results from a contract tasking Heriot-Watt University as follows: The work will be similar to that which the group has pioneered in related studies of the reactions of O(3P) atoms with hydrocarbon liquids. It is based on laser-photolysis of a low pressure of a suitable O(3P) precursor (NO2 at 355 nm) above the surface of the liquid. This produces O(3P) atoms with a relatively broad, superthermal kinetic energy ... |
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| Molecular Connections Between Arousal and Metabolic Disease: Orexin and Modafinil |
Apr-2009 |
19 pages |
| Authors:
Stephen C Benoit; CINCINNATI UNIV OH
|
| Metabolic diseases are known to be tightly linked to arousal-sleep cycles and impact cognitive function. Importantly, the armed forces represent a population at significant risk for increased stress and disrupted arousal-sleep cycles. Because the incidence of metabolic disease and obesity is increasing, even in these physically fit individuals, understanding the interactions between these systems is highly significant. Further, some anti-fatigue pharmacologies (e.g.,modafinil) are already used in military settings, though their ... |
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| Molecular Identification of Human Fungal Pathogens |
01-Mar-2009 |
125 pages |
| Authors:
Brian L Wickes; TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
|
| This proposal focuses on the development of a system for the molecular identification of human fungal pathogens using a biocurated database of DNA sequences. While common fungi can be easily identified by clinical microbiologists, identification of non-routine fungi from clinical specimens cannot be reliably done without specific training in mycology. Unfortunately, individuals with this training are in short supply in both civilian and military hospitals. The objective of this study ... |
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| Demonstration and Verification of a Broad Spectrum Anomalous Dispersion Effects Tool for Index of Refraction and Optical Turbulence Calculations |
Mar-2009 |
119 pages |
| Authors:
J J Cohen; AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH GRADUATE SCHOOL OF ENGINEERING AND MANAGEMENT
|
| An atmospheric optical turbulence strength model with a broad wavelength range of 355nm (ultraviolet) to 8.6m (radio frequencies) has been created at AFIT and implemented into the High Energy Laser End-to-End Operational Simulation tool (HELEEOS). This modeling and simulation tool is a first principles atmospheric propagation and characterization model. Within HELEEOS lies the High-Resolution Transmission Molecular Absorption (HITRAN) database, containing 1,734,469 spectral lines for 37 different molecules as of version ... |
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| Development of Non-Uniform Radiation Solution Methods for Atmospheric Re-entry Using Detailed Thermal Modeling |
Mar-2009 |
68 pages |
| Authors:
Jeffrey R Komives; AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH GRADUATE SCHOOL OF ENGINEERING AND MANAGEMENT
|
| The line-by-line accurate spectral radiation solver SPRADIAN was integrated with the multi-temperature hypersonic flow-solver NH7Air for the purpose of predicting the radiation incident on the surface of a hypersonic re-entry vehicle. Atomic and molecular radiation mechanisms are considered for chemical species present in an Earth atmosphere re-entry. A new numerical method of radiation propagation is presented that is capable of accurately predicting the radiation propagation through a non-uniform radiation field. ... |
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| p63 in Development and Maintenance of the Prostate Epithelium |
Mar-2009 |
18 pages |
| Authors:
Sabina Signoretti; BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
|
| The purpose of this project is to define the role of p63 in the development and maintenance of the prostate epithelium by utilizing both in vivo and in vitro models. In the first two years of work, we have constructed the targeting vector for the generation of the p63-Cre-ERT2 knock-in mice. The p63-Cre-ERT2 vector has been electroporated in the ES cells. p63-Cre-ERT2 ES clones with successful targeting events have been ... |
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| Molecular Basis of Autophagic Cell Death in Prostate Cancer |
Mar-2009 |
28 pages |
| Authors:
Ramesh Kaini; NEW MEXICO UNIV ALBUQUERQUE
|
| To understand the molecular basis of autophagy in prostate cancer, I am trying to isolate pure autophagosomes from autophagic cell survival and autophagic cell death Prostate cancer cell model and profile proteins and lipids to identify autophagy abundant/specific proteins and lipid molecule that are essential for functional autophagy in prostate cancer. I established EGFP.LC3 stably expressing LNCaP cell line and characterized the autophagic activity by western blot, translocation assay and ... |
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| Molecular Mechanisms in Compromised Endothelial Barrier during Breast Cancer Metastasis |
Mar-2009 |
10 pages |
| Authors:
Teng-Leong Chew; NORTHWESTERN UNIV CHICAGO IL
|
| We have successfully devised a 3D tumor invasion assay that integrates 3D tissue engineering and FRET imaging to provide us with a means with which we could directly monitor, in real-time, the endothelial signaling event during tumor intravasation. Using this novel assay, we have demonstrated that breast cancer cells induce endothelial cell myosin light chain kinase (MLCK) activation at the site of tumor invasion, and that this transient MLCK activation ... |
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| The BESCT Lung Cancer Program (Biology, Education, Screening, Chemoprevention, and Treatment) |
Mar-2009 |
27 pages |
| Authors:
Waun K Hong; Fadlo R Khuri; M D ANDERSON CANCER CENTER HOUSTON TX
|
| BESCT program aims to define molecular abnormalities contributing to lung cancer initiation and progression and to develop innovative therapeutic approaches for this cancer. Our specific aims are 1) to understand molecular alterations in lung cancer, 2) to develop chemoprevention strategies for lung cancer, and 3) to implement experimental molecular therapeutic approaches for lung cancer treatment. |
|
| Mechanisms and Chemoprevention of Ovarian Carcinogenesis |
Feb-2009 |
38 pages |
| Authors:
Dusica Cvetkovic; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| Ovarian cancer is the most fatal gynecological malignancy. The understanding of the early molecular events leading to ovarian cancer is important for the development of strategies for early detection and prevention. We have demonstrated that DMBA induced mutagenesis in the rat ovary, combined with gonadotropin hormone-mediated enhanced mitogenesis of the ovarian surface epithelium, produces lesions ranging from preneoplastic, early neoplastic to advanced ovarian tumors, resembling human disease. The goal of ... |
|
| Accurate Methods for Large Molecular Systems (Preprint) |
06-Jan-2009 |
75 pages |
| Authors:
Jerry A Boatz; Mark S Gordon; Jonathan M Mullin; Spencer R Pruitt; Luke B Roskop; Lyudmila V Slipchenko; IOWA STATE UNIV AMES DEPT OF CHEMISTRY
|
| Three exciting new methods that address the accurate prediction of processes and properties of large molecular systems are discussed. The systematic fragmentation method (SFM) and the fragment molecular orbital (FMO) method both decompose a large molecular system (e.g., protein, liquid, zeolite) into small subunits (fragments) in very different ways that are both designed to retain the high accuracy of the chosen quantum mechanical level of theory while greatly reducing the ... |
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| The Function of PTP1B in Neuroendocrine Differentation of Prostate Cancer |
Jan-2009 |
37 pages |
| Authors:
Jiaoti Huang; ROCHESTER UNIV NY
|
| The goal of the project is to identify the molecular mechanisms responsible for therapeutic failure in prostate cancer patients receiving hormonal therapy Scope: The scope of the project is to use prostate cancer cell lines in in-vitro cell culture systems to study the complex signal transduction pathways that may be responsible for the neuroendocrine differentiation of prostate cancer cells, particularly the relationship of PTP1B to IL-8 signaling through its receptors ... |
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| 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
|
| 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 ... |
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| Metastable Polymeric Nitrogen From N2H2 Alloys |
Dec-2008 |
9 pages |
| Authors:
Jennifer A Ciezak; Timothy A Jenkins; ARMY RESEARCH LAB ABERDEEN PROVING GROUND MD
|
| Studies of high-density binary mixtures of simple molecular solids have uncovered a new aspect of high pressure chemistry. In contrast 10 the many previous studies on relatively inert mixtures, here we show that high pressures can lead 10 unexpected behavior in reactive compounds. Raman studies were performed on nitrogen and hydrogen binary alloys al room temperature to 83 GPa To pressures of 30 GPa, large vibron deviations from those of ... |
|
| Enzyme, Antibody, and Photocatalytically Active Nanoscale Scavengers and Sensors for CW and Biological Agents |
10-Jun-2008 |
9 pages |
| Authors:
Yates; John T Jr; Alan Russell; PITTSBURGH UNIV PA
|
| Thin films consisting of photoactive TiO2 and enzyme-functionalized polymer were studied for their activity against chemical agent simulants. The photochemistry of TiO2 was quantitatively studied for several molecules, including the activation of molecular oxygen which then oxidizes organic molecules. An important discovery is that the rate of the photoprocess is proportional to the square root of the ultraviolet light flux. The enzyme functionalized polymer films were produced to incorporate an ... |
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| A Disruption of ctpA Encoding Carboxy-Terminal Protease Attenuates Burkholderia mallei and Induces Partial Protection in CD1 Mice |
03-Jun-2008 |
11 pages |
| Authors:
David DeShazer; Aloka B Bandara; Thomas J Inzana; Nammalwar Sriranganathan; Gerhardt G Schurig; Stephen M Boyle; VIRGINIA-MARYLAND REGIONAL COLL OF VETERINARY MEDICINE BLACKSBURG VA
|
| Burkholderia mallei is the etiologic agent of glanders in solipeds (horses, mules and donkeys), and incidentally in carnivores and humans. Little is known about the molecular mechanisms of B. mallei pathogenesis. The putative carboxy-terminal processing protease (CtpA) of B. mallei is a member of a novel family of endoproteases involved in the maturation of proteins destined for the cell envelope. All species and isolates of Burkholderia carry a highly conserved ... |
|
| Prostate Cancer Detection by Molecular Urinalysis |
Apr-2008 |
81 pages |
| Authors:
Christian P Pavlovich; David Y Chan; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States. The goal of this training grant is to develop urinary makers for prostate cancer detection and prognostication and to train two physicians in clinical research. In this year, we continue to evaluate the feasibility of detection of prostate cancer by molecular urinalysis. We have found HGF along with IL18Bpa were ... |
|
| Molecular Identification of Human Fungal Pathogens |
01-Mar-2008 |
17 pages |
| Authors:
Brian L Wickes; TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
|
| The focus of the work during this funding period mainly centered around Task 2, which consisted of developing standardized protocols for PCR and sequencing template preparation. The two major subtasks, development of a universal DNA extraction strategy and development of a universal PCR reaction, were initiated during the first funding period and have been completed. These accomplishments now allow us to utilize a standard DNA extraction method and a standard ... |
|
| The BESCT Lung Cancer Program (Biology, Education, Screening, Chemoprevention, and Treatment) |
01-Mar-2008 |
77 pages |
| Authors:
Waun K Hong; Fadlo R Khuri; M D ANDERSON CANCER CENTER HOUSTON TX
|
| BESCT program aims to define molecular abnormalities contributing to lung cancer initiation and progression and to develop innovative therapeutic approaches for this cancer. Our specific aims are 1) to understand molecular alterations in lung cancer, 2) to develop chemoprevention strategies for lung cancer, and 3) to implement experimental molecular therapeutic approaches for lung cancer treatment. |
|
| Molecular Mechanisms in Compromised Endothelial Barrier during Breast Cancer Metastasis |
01-Mar-2008 |
10 pages |
| Authors:
Teng-Leong Chew; NORTHWESTERN UNIV EVANSTON IL
|
| In this funding period (second of three years), we have completed the first specific as scheduled. We have successfully devised a novel assay system comprise of an engineered 3D vasculature network stably expressing a FRET-based biosensor for myosin light chain kinase (MLCK) activity. This set-up thus offers a very powerful assay system to directly study tumor invasion of the vascular system from the perspective of the endothelial cells. Using this ... |
|
| p63 in Development and Maintenance of the Prostate Epithelium |
MAR 2008 |
16 pages |
| Authors:
Sabina Signoretti; BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
|
| The purpose of this project is to define the role of p63 in the development and maintenance of the prostate epithelium by utilizing both in vivo and in vitro models. In the first two years of work, we have constructed the targeting vector for the generation of the p63-Cre-ERT2 knock-in mice. The p63-Cre-ERT2 vector has been electroporated in the ES cells. p63-Cre-ERT2 ES clones with successful targeting events have been ... |
|
| Maintenance of Genome Stability and Breast Cancer: Molecular Analysis of DNA Damage-Activated Kinases |
Mar-2008 |
66 pages |
| Authors:
Mark Ehrhardt; Daniel Mordes; David Cortez; Heather L Ball; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| Genomic instability is a hallmark of breast cancer cells. DNA damage checkpoints are critical for the prevention of genomic instability and breast cancer. The ATR checkpoint kinase is activated in response to exogenous and endogenous DNA damage, and phosphorylates downsteam substrates such as BRCA1 and p53 to promote cell cycle arrest DNA repair, and apoptosis. ATR exists in a complex with ATR-interacting protein (ATRIP). In response to DNA damage, the ... |
|
| Genetic and Molecular Analysis of the Mechanisms by which TSC regulates Neuronal Differentiation |
01-Feb-2008 |
61 pages |
| Authors:
Helen McNeill; MOUNT SINAI HOSPITAL TORONTO (ONTARIO)
|
| We have shown that TSC plays a key role in controlling the timing of neuronal differentiation in Drosophila through the conserved insulin receptor (InR)/Tor kinase signaling pathway (Bateman & McNeill, 2004). The goal of our current research is to determine the mechanism by which TSC regulates the timing of neuronal differentiation. To uncover the pathway(s) downstream of TSC in the temporal control of neuronal differentiation we are taking complementary approaches. ... |
|
| Very High Performance Organic Photonic Devices |
15 JAN 2008 |
82 pages |
| Authors:
Stephen Forrest; PRINCETON UNIV NJ DEPT OF ELECTRICAL ENGINEERING
|
| The objective was to demonstrate very high efficiency, low cost organic solar cells on flexible substrates based on vapor-deposited thin film organic semiconductors. Our goal is to obtain solar power conversion efficiencies of >10% -- a value without precedent in over 30 years of science and engineering targeted at achieving practical organic solar energy conversion devices. A further objective is to demonstrate an electrically pumped organic thin film laser, again ... |
|
| Cell Cycle Dependence of TRIAL Sensitivity in Prostate Cancer Cells |
01-Nov-2007 |
50 pages |
| Authors:
David J McConkey; M D ANDERSON CANCER CENTER HOUSTON TX
|
| The proteasome inhibitor bortezomib (PS-341, Velcade) synergizes with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) acts via a p21- dependent mechanism to induce high levels of apoptosis in prostate cancer cells. Our further investigation into the molecular mechanisms underlying the effects of bortezomib implicated endoplasmic reticular (ER) stress in its anti-tumoral effects. These effects also provide us with a molecular mechanism to explain the observed anti-angiogenic effects of bortezomib in prostate ... |
|
| Molecular Genetic Studies of Bone Mechanical Strain and of Pedigrees with Very High Bone Density |
NOV 2007 |
41 pages |
| Authors:
Subburaman Mohan; LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION REDLANDS CA
|
| The primary goal of the proposed work on bone mechanical strain focuses on identifying the genes and their functions involved in mediating the anabolic skeletal response to mechanical stress. Two hypotheses have been proposed: I) Quantitative trait loci analysis using the four point bending technique in two strains of mice exhibiting extreme differences in loading response will lead to identification of chromosomal locations of genes involved in variation in skeletal ... |
|
| The Role of Siah1-Induced Degradation of beta-Catenin in Androgen Receptor Signaling |
NOV 2007 |
27 pages |
| Authors:
Shu-ichi Matsuzawa; BURNHAM INST LA JOLLA CA
|
| The androgen receptor (AR) signaling-pathway plays crucial roles in the growth and progression of prostate cancer cells. Recent studies indicate that beta-Catenin physically binds to AR and enhances its transcriptional activity in a ligand dependent manner. p53 has also been implicated in AR signaling because of its ability to induce expression of Siah1, which binds and activates E3 ligase complexes which degrade beta-Catenin. In this study, we demonstrated the biological ... |
|
| Molecular Mechanisms of Nonlinearity in Response to Low Dose Ionizing Radiation |
12 OCT 2007 |
43 pages |
| Authors:
Zelanna Goldberg; David M. Rocke; CALIFORNIA UNIV DAVIS
|
| In this very new project we have begun a systematic evaluation of the molecular mechanisms of radiation adaptation. We have developed a wound-healing model that will provide a functional assessment of the promitogenic effects of low dose radiation exposure. We have begun detailed cell cycle analysis of low dose radiation exposure on human keratinocytes and fibroblasts as well as survival as says following priming and challenge doses of ionizing radiation. ... |
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| XIAP as a Molecular Target for Therapeutic Intervention in Prostate Cancer |
OCT 2007 |
76 pages |
| Authors:
Colin S. Duckett; MICHIGAN UNIV REGENTS ANN ARBOR DIV OF RESEARCH DEVELOPMENT AND ADMINISTRATION
|
| This is the final report of our CDMRP-funded research grant. Our study comprised of two research aims to validate and examine the therapeutic potential of targeting XIAP for the treatment of prostate cancer. In the first of the two Aims, we generated cell lines in which XIAP was suppressed, using lentiviral-based RNA interference delivery system. Additionally, we reconstituted these lines with a panel of XIAP variants lacking either the caspase ... |
|
| Hypoxia and Prx1 in Malignant Progression of Prostate Cancer |
SEP 2007 |
51 pages |
| Authors:
Young-Mee Park; ROSWELL PARK CANCER INST BUFFALO NY
|
| Hypoxia has been proposed to function as a microenvironmental pressure to select for a subset of cancer cells with an increased ability to survive and proliferate. The activation of Nrf2 and the up-regulation of prx1 expression by changes of oxygenation are likely to contribute to the malignant progression of cancer and to modify the treatment response of cancer cells. The information provided in the current study suggests that the Nrf2-Prx1 ... |
|
| Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy |
SEP 2007 |
17 pages |
| Authors:
Chung-Ying Huang; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| Patients with high-risk localized prostate cancer have a high recurrence rate following primary therapy. Neoadjuvant chemotherapy has been shown to be beneficial in reducing recurrence rates in some tumor types but has yet to be of proven benefit in prostate cancer. Further current clinical pathological and molecular markers poorly predict the response and resistance of chemotherapy and the molecular mechanisms of chemotherapy resistance are largely unknown. We utilized tissue resources ... |
|
| A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induce Apoptosis |
SEP 2007 |
302 pages |
| Authors:
Jordan Virgil C.; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| To discover the mechanism of estrogen induced breast cancer cell apoptosis and establish the clinical value of short-term low dose estrogen treatment to cause apoptosis in antihormone resistance breast cancer. To achieve the goal, we have created an optimal collaborative network to study laboratory models of the regulation of estrogen-induced growth and apoptosis in breast cancer. The molecular mechanisms of estrogen action (ER) mediated regulation are being deciphered by the ... |
|
| Role of Heterochromatin Epigenetic Factors in CML |
AUG 2007 |
11 pages |
| Authors:
Sergei A. Grigoryev; PENNSYLVANIA STATE UNIV HERSHEY
|
| During the reported period, our main goal was to test and further develop a hypothesis that structural modifications and/or interference between two heterochromatin proteins: MNEI and HP1 lead to abnormal gene regulation and impaired myeloid differentiation, CML acceleration, blast crises and/or secondary acute leukemia. In specific aim 1, we isolated monomeric and high molecular forms of MNEI by chromatography and gel electrophoresis and determined their primary structure by mass spectroscopy ... |
|
| Role of Rac GTPasas in Chemokine-Stimulated Breast Carcinoma Metastasis |
JUL 2007 |
15 pages |
| Authors:
Marc Symons; NORTH SHORE HOSPITAL MANHASSET NY
|
| CXCR4 is highly expressed in breast carcinoma cells and is essential for breast cancer metastasis to the lung. CXCR4 is the receptor for CXCL12 a chemokine that is enriched in organs that are targeted by metastatic breast cancer such as lung and liver. The molecular mechanisms of CXCR4-mediated breast cancer metastasis however are poorly understood. In this project we test the hypothesis that Rac proteins are essential for CXCR4-mediated breast ... |
|
| Propagation of High Energy Laser Beams in Various Environments |
08 JUN 2007 |
61 pages |
| Authors:
Phillip Sprangle; Joseph Penano; Bahman Hafizi; NAVAL RESEARCH LAB WASHINGTON DC
|
| We report the results of our theoretical study on the key physical processes that affect the propagation of nigh energy lasers in the atmosphere. The main objective of this study is to discuss the optimum laser wavelength and power for efficient propagation in maritime, desert, rural and urban atmospheric environments. The theoretical/numerical model used in this study includes the effects of aerosol and molecular scattering, aerosol heating and vaporization, thermal ... |
|
| Endocrine Therapy of Breast Cancer |
JUN 2007 |
65 pages |
| Authors:
Robert Clarke; GEORGETOWN UNIV WASHINGTON DC
|
| A recent controversy in the treatment of estrogen receptor positive (ER+) breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ~40% of tumors show crossresistance to TAM or an aromatase inhibitor on crossover. Only 50% of ... |
|
| Chemical Probes of Rapid Estrogen Signaling in Breast Cancer Treatment and Chemoprevention |
01 APR 2007 |
52 pages |
| Authors:
Rose V. Weatherman; PURDUE UNIV LAFAYETTE IN
|
| The goal of this project was to design new chemical tools to selectively probe the molecular mechanisms of action of rapid estrogen receptor action and their relevance to breast cancer drugs like tamoxifen. Over the course of the project, we synthesized and tested approximately 15 new estrogen receptor modulators, some with novel activity in terms of both classic transcriptional and rapid response modulation. We discovered that the structure activity relationship ... |
|
| BATTLE: Biomarker-Based Approaches of Targeted Therapy for Lung Cancer Elimination |
APR 2007 |
104 pages |
| Authors:
Waun K. Hong; Roy Herbst; Li Mao; Edward Kim; M D ANDERSON CANCER CENTER HOUSTON TX
|
| The Program BATTLE (Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination) seeks to establish individualized targeted therapy by prospectively examining patients? tumor biomarker profiles and assigning them to corresponding targeted therapies with the expectation to yield a better clinical outcome. This novel approach will be a proof-of-principle experiment to test the benefit of molecular-based individualized targeted therapy for lung cancer patients. Specifically, the objectives of the BATTLE program are: ... |
|
| Experimental and Theoretical Investigation of Collisional Energy Transfer in Free Radicals of Atmospheric Importance |
25 MAR 2007 |
|
| Authors:
Millard H. Alexander; Paul J. Dagdigian; MARYLAND UNIV COLLEGE PARK DEPT OF CHEMISTRY AND BIOCHEMISTRY
|
 | Collisional relaxation of the atmospherically important free radicals OH and NO by open-shell atoms have been studied in a coordinated theoretical and experimental investigation. A quantum statistical method has been employed to describe collisional processes proceeding through a strongly bound collision complex, such as occur in the interaction of many free radicals with atoms. This theory has been used to compute rotationally and vibrationally inelastic collision rates for collisions of ... |
|
| Maintenance of Genome Stability and Breast Cancer: Molecular Analysis of DNA Damage-Activated Kinases |
MAR 2007 |
50 pages |
| Authors:
Heather L. Ball; Mark Ehrhardt; Daniel Mordes; David Cortez; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| The ATR (ATM and Rad3-Related) kinase is essential to maintain genomic integrity. ATR is recruited to DNA lesions in part through its association with ATR-interacting protein (ATRIP), which in turn interacts with the single-stranded DNA binding protein RPA (Replication Protein A). In this study, a conserved checkpoint protein recruitment domain (CRD) in ATRIP orthologs has been identified by biochemical mapping of the RPA binding site in combination with NMR, mutagenesis ... |
|
| p63 in Development and Maintenance of the Prostate Epithelium |
MAR 2007 |
13 pages |
| Authors:
Sabina Signoretti; BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
|
| The purpose of this project is to define the role of p63 in the development and maintenance of the prostate epithelium by utilizing both in vivo and in vitro models. In our first year of work, we have the successful constructed the targeting vector for the generation of the p63-Cre-ERT2 knock-in mice to be used for genetic lineage tracing. The p63-Cre-ERT2 vector has been transferred to the DFCI Gene Targeting ... |
|
| Novel Gbeta Mimic Kelch Proteins (Gpb1 and Gpb2 Connect G-Protein Signaling to Ras via Yeast Neurofibromin Homologs Ira1 and Ira2. A Model for Human NF1 |
MAR 2007 |
19 pages |
| Authors:
Joseph Heitman; Toshiaki Harashima; DUKE UNIV DURHAM NC
|
| The Neurofibromatosis type 1 (NF1) gene encodes a large tumor suppressor protein neurofibromin which is a Ras GTPase-activating protein (RasGAP) activity. Although the NF1 gene was identified over a decade ago the biological roles of neurofibromin in cellular processes remain unclear. Therefore it is crucial for therapy and developing new drugs for NF1 patients to elucidate how the RasGAP activity of neurofibromin is controlled. To achieve this goal it is ... |
|
| A MicroRNA Cluster as a Potential Breast Cancer Oncogene |
MAR 2007 |
8 pages |
| Authors:
Gregory J. Hannon; COLD SPRING HARBOR LAB NY
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| microRNAs (miRNAs) are small, regulatory RNAs that silence target genes by repressing translation and destabilizing mRNAs (1). Recent studies have demonstrated the importance of miRNAs in molecular mechanisms for the oncogenic and tumor suppressor pathways (2) (3) (4). We have identified a novel oncogenic miRNA polycistron, mir17-92, as a potential human oncogene in B-cell lymphomas (5). Since mir17-92 is overexpressed in a subset of breast tumor samples, we explored the ... |
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| Molecular Mechanisms in Compromised Endothelial Barrier during Breast Cancer Metastasis |
MAR 2007 |
7 pages |
| Authors:
Teng-Leong Chew; NORTHWESTERN UNIV EVANSTON IL
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| In this funding period (first of three years) we have fulfilled the scheduled tasks of (1) standardizing the condition for engineering the 3D vasculature network that can consistently produce lumen; (2) generating various viral constructs that can deliver the FRET sensors to 100% of the endothelial cells used in vasculature formation; (3) determining the fluid exchange rate within the 3D collagen matrix that will be critical for any subsequent drug ... |
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