| The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness |
Jan-2009 |
126 pages |
| Authors:
Owen P Hamill; Rosario Maroto; TEXAS UNIV MEDICAL BRANCH AT GALVESTON
|
 | Our patch clamp studies indicate MscCa is expressed by the invasive prostate tumor cell PC-3. Anti-MscCa agents, Gd3+, GsmTx-4, and an anti-TRPC1 antibody block PC-3 cell migration. MscCa activity can be recorded over the surface of the PC-3 cell but is expressed at higher density on the rear compared with the front of the cell. This channel density gradient combined with a higher density of thapsigargin-sensitive Ca2+ stores in the ... |
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| DNA Methylation as an Epigenetic Factor in the Development and Progression of Polycythemia Vera |
Oct-2008 |
34 pages |
| Authors:
Jean-Pierre Issa; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Polycythemia vera (PV) is the most common myeloproliferative disorder with a yearly incidence of 28 per 1 million people and a slightly higher prevalence in males. PV is characterized by clonal expansion of erythroid, myelomonocytic, and megakaryocytic lineages, erythrocytosis being the most prominent clinical manifestation of PV. The disease is associated with a significant morbidity and mortality, including thrombotic and/or hemorrhagic events, and a risk of an evolution into myelofibrosis ... |
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| Fowlpox as Decontamination Simulant for Variola Major |
01-Sep-2008 |
21 pages |
| Authors:
Amanda E Chambers; Steven P Harvey; Melissa M Dixon; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD RESEARCH AND TECHNOLOGY DIR
|
| Variola major, the causative agent of the disease smallpox, is the most deadly member of the poxvirus family. Although eradicated from nature, stocks of variola major still exist; thus, there is a need for relevant decontamination studies. However, studies with variola major must be performed under Biosafety Level 4 conditions. Previous studies have shown a similarity in the response of vaccinia virus and variola major to various decontaminants. This study ... |
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| DNA Methylation as an Epigenetic Factor in the Development and Progression of Polycythemia Vera |
NOV 2007 |
54 pages |
| Authors:
Jean-Pierre Issa; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Polycythemia vera (PV) is the most common myeloproliferative disorder with a yearly incidence of 28 per 1 million people and a slightly higher prevalence in males PV is characterized by clonal expansion of erythroid, myelomonocytic, and megakaryocytic lineages, erythrocytosis being the most prominent clinical manifestation of PV The disease is associated with a significant morbidity and mortality, including thrombotic and/or hemorrhagic events, and a risk of an evolution into myelofibrosis ... |
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| X Chromosome Inactivation and Breast Cancer: Epigenetic Alteration in Tumor Initiation and Progression |
SEP 2007 |
29 pages |
| Authors:
Barbara Panning; CALIFORNIA UNIV SAN FRANCISCO
|
| We tested whether reactivation of the inactive X chromosome in the mouse mammary gland contributes to tumorigenesis in vivo and whether that reactivation of the inactive X can cooperate with the MYC oncogene in tumor progression. We found no evidence for a role of reactivation of the inactive X in tumor initiation or progression. We also examined whether the inactive X was reactivated in a number of different mouse breast ... |
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| Legubicin, a Tumor-Activated Prodrug for Breast Cancer Therapy |
APR 2007 |
55 pages |
| Authors:
Cheng Liu; SCRIPPS RESEARCH INST LA JOLLA CA
|
| Legumain is a recently discovered and only known asparaginyl endopeptidase that is well conserved throughout the biologic kingdoms. We have demonstrated that legumain is highly and inappropriately expressed in 100% human breast cancer specimens as well as murine breast cancer models. We demonstrated that an inactive prototype doxorubicin derived prodrug incorporating a succinyl blocked substrate peptide removable by legumain was effectively activated and tumoricidal in human breast cancer models. We ... |
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| The Scaffold Attachment Factor SAFB1: A New Player in G2/M Checkpoint Control |
APR 2007 |
18 pages |
| Authors:
Adrian Lee; Steffi Oesterreich; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Loss of G2/M checkpoint plays an important role in tumorigenesis, however, few genes involved in this checkpoint control have been shown to be deregulated in human breast tumors. SAFB1 is a multifunctional protein which maps to a locus of high LOH, and mutations have been identified inboth breast cancer cell lines and tumors. Our preliminary data show that inactivation of SAFB1 in MEFs result in loss of G2/M checkpoint control, ... |
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| Targeting Breast Cancers Featuring Activating Mutations in PIK3CA by Generating a Lethal Dose of PIP3 |
FEB 2007 |
7 pages |
| Authors:
Jean J. Zhao; DANA-FARBER CANCER INST BOSTON MA
|
| Our research described here is relevant to the pathogenesis and a potential novel therapy for breast cancers. The PIK3CA is the most commonly mutated oncogene in breast cancer and loss of the tumor suppressor PTEN occurs frequently in patients suffering from this disease. The most significant accomplishment during the first year of funding is the generation of the oncogenic PIK3CA transgenic animal model which will allow us to determine the ... |
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| Military Personnel: Additional Actions Needed to Improve Oversight of Reserve Employment Issues |
FEB 2007 |
81 pages |
| Authors:
GOVERNMENT ACCOUNTABILITY OFFICE WASHINGTON DC
|
| DOD has made progress capturing employment information on its reservists since August 2005, but several challenges remain. In August 2004, DOD changed employer reporting by reservists from voluntary to mandatory. The number of reservists reporting employer information to DOD increased from 60 percent in August 2005 to about 77 percent in August 2006. However, we found that reservists have not fully reported civilian employment information, reported employment data are not ... |
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| Stathmin: A "Relay Protein" in the Development of Prostate Cancer and a Potential Target for Anticancer Therapy |
NOV 2006 |
14 pages |
| Authors:
Ritwik Ghosh; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| The long term goal of this work is to determine weather stathmin can be targeted as an effective therapy in the clinic against prostate cancer. The central hypothesisof this proposal is that overexpression of stathmin promotes prostate cancer development and blocking stathmin expression sensitizes prostate cancer cells to anticancer therapies such as Taxotere and Erbitux. The purpose of this work is to i) correlate stathmin overexpression with progression of prostate ... |
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| FGF Signaling and Dietary Factors in the Prostate |
SEP 2006 |
131 pages |
| Authors:
Fen Wang; TEXAS A AND M UNIV COLLEGE STATION HEALTH SCIENCE CENTER
|
| Purpose: To study the FGF signaling axis in prostate homeostasis and tumorigenesis, to evaluate dietary factors in modulating FGF signals in the prostate. Scope: To develop mouse models resembling human prostate tumor progressions for screening therapeutic strategies for prostate cancers and evaluating dietary factors in prostate cancer prevention. Major Finding: Ectopic expression of the constitutively-active FGFR1 (caFGFR1) in the prostate induces high-grade prostatic intraepithelial neoplasia (PIN) in transgenic mice in ... |
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| Genomic Patterns of Pathogen Evolution Revealed by Comparison of Burkholderia pseudomallei, the Causative Agent of Melioidosis, to Avirulent Burkholderia thailandensis |
26 MAY 2006 |
19 pages |
| Authors:
Yiting Yu; H. S. Kim; Hui H. Chua; Chi H. Lin; Siew H. Sim; Daoxun Lin; Alan Derr; Reinhard Engels; David DeShazer; Bruce Birren; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| The Gram-negative bacterium Burkholderia pseudomallei (Bp) is the causative agent of the human disease melioidosis. To understand the evolutionary mechanisms contributing to Bp virulence, we performed a comparative genomic analysis of Bp K96243 and B. thailandensis (Bt) E264, a closely related but avirulent relative. RESULTS: We found the Bp and Bt genomes to be broadly similar, comprising two highly syntenic chromosomes with comparable numbers of coding regions (CDs), protein family ... |
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| Comparison of Bacillus Anthracis to the Surrogate Bacillus Atrophaeus for Spore Inactivation on a Novel Antimicrobial Fabric |
MAY 2006 |
7 pages |
| Authors:
Christopher C. Thornburg; Jon J. Calomiris; HENRY M JACKSON FOUNDATION ABERDEEN PROVING GROUND MD
|
| Military fabric amended with an antimicrobial compound may reduce the viability of biological threat agents that could be encountered in contaminated environments. Bacillus atrophaeus (formerly Baclllus sub tills var. niger) is typically employed in the evaluation of antimicrobial compounds and has been reported to be less susceptible to disinfection than Baclllus anthracis, and thus is commonly used as a surrogate whenever direct evaluation with B. anthracis may not be feasible. ... |
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| Killing Breast Cancer Cells With a VEGF-Triggered Cell Death Receptor |
01-Apr-2006 |
16 pages |
| Authors:
Timothy Quinn; CALIFORNIA UNIV SAN FRANCISCO
|
| Many breast cancers overexpress the tumor angiogenesis factor VEGF (vascular endothelial growth factor). Consequently numerous VEGF inhibitors are being studied. Some such as bevacizumab extend progression-free survival but have not yet been shown to extend overall survival in breast cancer patients. We are pursuing a totally different approach to targeting VEGF: rather than inhibit VEGF our goal is to convert VEGF to act as a cell death factor. Toward this ... |
|
| Legubicin a Tumor-Activated Prodrug for Breast Cancer Therapy |
APR 2006 |
156 pages |
| Authors:
Cheng Liu; SCRIPPS RESEARCH INST LA JOLLA CA
|
| Legumain is a recently discovered and only known asparaginyl endopeptidase that is well conserved throughout the biologic kingdoms. We have demonstrated that legumain is highly and inappropriately expressed in 100% human breast cancer specimens as well as murine breast cancer models. We demonstrated that an inactive prototype doxorubicin derived prodrug incorporating a succinyl blocked substrate peptide removable by legumain was effectively activated and tumoricidal in human breast cancer models. We ... |
|
| The Scaffold Attachment Factor SAFB1: A New Player in G2/M Checkpoint Control |
APR 2006 |
10 pages |
| Authors:
Steffi Oesterreich; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Loss of G2/M checkpoint plays an important role in tumorigenesis, however, few genes involved in this checkpoint control have been shown to be deregulated in human breast tumors. SAFB1 is a multifunctional protein which maps to a locus of high LOH, and mutations have been identified from both breast cancer cell lines and tumors. Our preliminary data show that inactivation of SAFB1 in MEFs result in loss of G2/M checkpoint ... |
|
| Financial Management: Internal Controls Over Compiling and Reporting Environmental Liabilities Data |
15 MAR 2006 |
40 pages |
| Authors:
OFFICE OF THE DEPUTY INSPECTOR GENERAL FOR AUDITING OF THE DEPARTMENT OF DEFENSE ARLINGTON VA
|
| Who Should Read This Report and Why? DoD civilians and unifbn%ed officers responsible for envfrorn%ental cost estimating and financial reporting should read this report. It discusses internal controls over compiling and reporting cost%o-complete estimates for envfrorn%ental liabilities included in the Air Force annual financial statements. Background. This audit is required by Public Law 101-576, Chief Financial Officers Act of 1990, as amended by the Federal Financial Management Act of 1994. ... |
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| Endometase in Androgen-Repressed Human Prostate Cancer |
MAR 2006 |
192 pages |
| Authors:
Qing-Xiang A. Sang; FLORIDA STATE UNIV TALLAHASSEE
|
| This project investigated a biomedical problem related to human prostate cancer invasion and a possible biomarker for cancer diagnosis. We reported the identification and characterization of human matrix metalloproteinase-26 (MMP- 26/endometase/matrilysin-2). We have tested three specific hypotheses: 1) The expression levels of MMP-26 is correlated with the metastatic potentials and the degrees of malignancy of human prostate cells; 2)MMP-26 has unique structure and enzymatic function; 3) MMP-26 enhances prostate cancer ... |
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| Suppression of Prostate Cancer by PTEN and p18INK4c |
FEB 2006 |
17 pages |
| Authors:
Feng Bai; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| The Rb pathway suppresses tumorigenesis by constraining G1 cell cycle progression. Functional inactivation or reduction of this pathway is a common event found in many types of human tumors. To test how the Rb pathway interacts with other cellular pathways in tumor suppression, we characterized mice with combined mutations in the CDK inhibitor p18 (exp Ink4c) and the lipid phosphatase PTEN, which regulates cell growth and survival. The p18(exp -/-) ... |
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| Breast Cancer Metastasis to Bone Affects Osteoblast Differentiation |
28 SEP 2005 |
77 pages |
| Authors:
Robyn R. Mercer; PENNSYLVANIA STATE UNIV UNIVERSITY PARK
|
| Breast cancer fatally metastasizes to bone and activates osteoclasts, cells that resorb bone, resulting in the formation of osteolytic lesions. Certain drugs, bisphosphonates, slow the action of osteoclasts, however, the bone lesions are not repaired. The osteoblasts should be able to repair the lesions by synthesizing new bone matrix. Instead, these cells appear to be inactivated by breast cancer, and the lesions do not heal. The purpose of this proposal ... |
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| The Mechanism of Tetinoblastoma Protein-Mediated Terminal Cell Cycle Arrest |
SEP 2005 |
29 pages |
| Authors:
Hasan Rajabi; DANA-FARBER CANCER INST BOSTON MA
|
| A prognostic feature of many human cancers is a high mitotic index and the inability to maintain a terminal cell cycle arrest (TCCA). The Rb gene product retinoblastoma protein has been implicated in the maintenance of a terminal cell cycle arrest. Likewise the inactivation of retinoblastoma gene (Rb) is observed in several human cancers including those of the breast. However, in contrast to our knowledge of how pRb regulates proliferation ... |
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| Use of In Situ-Generated Dimethyldioxirane for Inactivation of Biological Agents |
08 JUL 2005 |
6 pages |
| Authors:
APPLIED RESEARCH ASSOCIATES INC TYNDALL AFB FL
|
|
| Evaluation of the Role of the Metastasis-Suppressor Gene MKK4/SEK1 in Transgenic Models of Prostate Cancer |
JUN 2005 |
38 pages |
| Authors:
Carrie W. Rinker-Schaeffer; CHICAGO UNIV IL
|
| Metastasis-suppressor genes suppress the growth of metastases without affecting tumor growth. We have been studying the role of inactivation of one such metastasis suppressor gene, Map Kinase Kinase 4 (MKK4) in the process of metastatic colonization. Work proposed in this application was aimed at extending our ongoing studies in the AT6.1 model system into established transgenic models of prostate cancer and the use of transgenic approaches to test further MKK4's ... |
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| Amplification of Anti-Tumor Immunity Without Antoimmune Complications |
MAY 2005 |
10 pages |
| Authors:
Wei-Zen Wei; WAYNE STATE UNIV DETROIT MI
|
| The hypothesis is that inactivation of Treg cells accompanied by Neu DNA vaccination will overcome tolerance in BALB NeuT mice and inhibit spontaneous matnmarytunorigenesis or reject an established s.c. tumor. The anticipated tumor growth inhibition maybe achieved at the risk of developing autoimmunity. Thyroiditis will be measured to indicate the level of risk. We further hypothesize that DNA vaccines encoding both Neu and GlTRligand will stimulate effectorT cells via conventional ... |
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| The Scaffold Attachment Factor SAFB1P: A New Player in G2/M Checkpoint Control |
APR 2005 |
8 pages |
| Authors:
Steffi Oesterreich; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Loss of G2/M checkpoint plays an important role in tumorigenesis, however, few genes involved in this checkpoint control have been shown to be deregulated in human breast tumors. SAFB1 is a multifunctional protein which maps to a locus of high LOH, and mutations have been identified from both breast cancer -cell lines and tumors. Our preliminary data show that inactivation of SAFB1 in MEFs result in loss of G2/M checkpoint ... |
|
| Induction of Apoptosis by Targeting the Microtubule Network: Using HIV Tat as a Model System |
APR 2005 |
8 pages |
| Authors:
Zhiyuan Yang; Qiang Zhou; CALIFORNIA UNIV BERKELEY
|
| The transcriptionally active P-TEFb that phosphorylates RNA Polymerase II to stimulate general and HIV-specific transcriptional elongation is presumed to exist in a free cyclin T1/CDK9 heterodimer. About half of cellular cyclin T1/CDK9 are also found in an inactive complex containing the 7SK snRNA and the HEXIM1 protein. In this research, I show that the remaining half are associated with Brd4, a bromodomain protein that binds to acetylated histones. In stress-induced ... |
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| Role of ei24/PIG8, A Putative Pro-Apoptotic Tumor Suppressor, in Breast Cancer Development and Resistance to Drug Therapy |
MAR 2005 |
13 pages |
| Authors:
Remco A. Spanjaard; BOSTON UNIV MA
|
| EI24/PIG8 is regulated by p53 in response to genotoxic damage and was shown to be genetically inactivated in aggressive breast cancers with frequent loss-of-heterozygosity. In addition, it was shown that ectopic expression of EI24/P108 resulted in apoptosis, whereas suppression of E124/PIO8 expression resulted in increased survival after treatment with an apoptotic retinoid. We hypothesizid that genetic inactivation of EI24/PIO8 is a major contributing factor to breast cancer development and resistance ... |
|
| Suppression of Prostate Cancer by PTEN and p18(INK4C) |
FEB 2005 |
16 pages |
| Authors:
Feng Bai; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| The Rb pathway suppresses tumorigenesis by constraining G1 cell cycle progression. Functional inactivation or reduction of this pathway is a common event found in many types of human tumors. To test how the Rb pathway interacts with other cellular pathways in tumor suppression, we characterized mice with combined mutations in the CDK inhibitor p18 (sub Ink4c) and the lipid phosphatase Pten, which regulates cell growth and survival. Thep18-/-;Pten +/-double mutant ... |
|
| Structural Studies on Intact Clostridium Botulinum Neurotoxins Complexed with Inhibitors Leading to Drug Design |
FEB 2005 |
54 pages |
| Authors:
Subramanyam Swaminathan; BROOKHAVEN NATIONAL LAB UPTON NY
|
| In this third annual report we present our progress on two different areas. We have identified two ganglioside binding sites in tetanus toxin. While one is common to botulinum toxins, the other is unique for tetanus. The second unique site also binds a tri-peptide which suggests that this peptide could be used as an inhibitor for tetanus, at least. We have determined the structure of the C fragment of botulinum ... |
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| Clinical Use of Plasma and Plasma Fractions Chapter: Viral Inactivation Techniques |
26 JAN 2005 |
26 pages |
| Authors:
Joesph P. Pelletier; YALE UNIV NEW HAVEN CT
|
| Even though the blood supply is very safe, concerns regarding transmission of transfusion-related pathogens exist. Risks are reduced by donor screening, arm-preparation techniques, first aliquant diversion, screening for pathogens and, in many countries, pathogen reduction/eradication technology. The risk for viral infection from transfusion is now reported at 1:2,135,000 for HIV, 1:138,700-233,000 for HBV, 1:1935,000 for HCV, 1:250,000 for HTLV 1 and 2 (after screening peripherally), 1:1,000,000 HAV, 1:10,000 for parvovirus ... |
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| The Use of Gene Knockout Mice in Thermoregulation Studies |
JAN 2005 |
17 pages |
| Authors:
Lisa R. Leon; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA THERMAL AND MOUNTAIN MEDICINE DIVISION
|
| As the use of gene knockout models in thermoregulation studies has gained popularity, the reported incidence of redundant or discrepant phenotypes between studies has also increased, Several gene knockout models mimic human processes and have provided valuable insight into the role of endogenous mediators in thermoregulatory processes. There are also many examples of mutant strains expressing virtually identical phenotypes as their wild-type controls, causing concern regarding the appropriateness of these ... |
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| An Anti-Oncogenic Role for Decorin in Mammary Carcinoma |
OCT 2004 |
35 pages |
| Authors:
Renato V. Iozzo; THOMAS JEFFERSON UNIV PHILADELPHIA PA
|
| A significant proportion of human breast cancers overexpress ErbB2, a member of the receptor tyrosine kinase gene family that also includes the epidermal growth factor receptor (EGFR). Overexpression of ErbB2 correlates with increased metastatic potential and poorer prognosis. Agents that antagonize the activity of ErbB family members have obvious clinical implications. We have previously demonstrated that decorin is a novel ligand for the EGFR, whose interaction with EGFR/ErbB family members ... |
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| Activation of P13K/PKB Signaling in Breast Cancer may Inhibit TGFB-Induced G1 Arrest through Changes in p27 Function |
OCT 2004 |
61 pages |
| Authors:
Jiyong Liang; SUNNYBROOK AND WOMENS COLL HEALTH SCIENCES CENTER TORONTO (ONTARIO)
|
| TGF-Beta1 plays a pivotal role in maintaining homeostasis of normal tissues including mammary epithelial cell growth, in which TGF-Beta1 induces cell cycle arrest through activating cdk inhibitors including p15(exp INK4B) and p27(expKiP1). Loss of p27(exp KiP1), seminally described in breast cancers, has been found in a plethora of human malignancies. The Slingerland (my mentor) lab found that p27 is subject to complex post-translational regulation, e.g. phosphorylation. To elucidate the mechanisms ... |
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| Molecular Identification of the Schwannomatosis Locus |
JUL 2004 |
9 pages |
| Authors:
Mia M. MacCollin; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| Schwannomatosis is a recently recognized third major type of neurofibromatosis. Our preliminary studies of the NF2 gene in tumors from schwannomatosis patients reveal a pattern of tumor suppressor gene inactivation not previously reported in any other human disease. The objective of this project is to clone the locus responsible for familial schwannomatosis. We are exploring two competing hypotheses which address both the non random distribution of LOH observed in schwannomatosis ... |
|
| Angiogenesis Inhibitors in Breast Cancer |
APR 2004 |
10 pages |
| Authors:
Alfonso Luque; Luisa Iruela-Arispe; CALIFORNIA UNIV LOS ANGELES
|
| ADAMTSl/METHl is a secreted protease that belongs to the metallospondin/ADAMTS sub-family of the zinc-metalloprotease superfamily. This family is characterized by proteins that contain a modular structure that includes A, Disintegrin-like, Metalloprotease, and type-1 ThromboSpondin domains. ADAMTSl has been shown to inhibit both endothelial cell proliferation in vitro, as well as angiogenesis in vivo. We have investigated the role of ADAMTSl and its proteolytic activity, through the creation of a catalytically ... |
|
| An Anti-Oncogenic Role for Decorin in Mammary Carcinoma |
OCT 2003 |
6 pages |
| Authors:
Renato V. Iozzo; THOMAS JEFFERSON UNIV PHILADELPHIA PA
|
| A significant proportion of human breast cancers overexpress ErbB2, a member of the receptor tyronsine kinase gene family that also includes the epidermal growth factor receptor (EGFR). Overexpression of ErbB2 correlates with increased metastatic potential and poorer prognosis. Agents that antagonize the activity of ErbB family members have obvious clinical implications. We have previously discovered that decorin causes a functional inactivation of the oncogenic ErbB2 in mammary carcinoma cells overexpressing ... |
|
| Evaluation of DNA Methylation as a Target for Intraductal Therapy for Ductal Carcinoma In Situ of the Breast |
AUG 2003 |
4 pages |
| Authors:
Kristin A. Skinner; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Ductal carcinoma in situ(DCIS), the preinvasive form of infiltrating ductal breast cancer, accounts for 20-30% of breast cancers and is treated surgically. In DCIS, the malignant cells are confined within the basement membrane. DCIS is a local disease, and so an ideal candidate for local therapies. DNA methylation is one mechanism for tumor suppressor gene inactivation. It is an early event in the course of malignant progression. Because methylation is ... |
|
| Counter Terrorism Measures to Combat Yersinia pestis With Selenium Pharmaceuticals |
01 JUL 2003 |
8 pages |
| Authors:
Ted W. Reid; Phat Tran; Julian Spallholz; Joe A. Fralick; TEXAS TECH UNIV HEALTH SCIENCES CENTER LUBBOCK
|
| The purpose of this study is to produce selenium labeled peptides and phage (bacterial viruses) that can selectively bind to the surface of the pathogenic bacteria Yersinia pestis (the plague) and inactivate it through the generation of superoxide radicals on its surface, similar to the way that it is inactivated by superoxide in macrophage. The results show that phage specific for a given bacteria can be obtained from phage expression ... |
|
| Comparative Biology of Brea2 Gene Expression in Caucasian and African American Female Breast Cells |
JUN 2003 |
20 pages |
| Authors:
Gautam Chaudhuri; MEHARRY MEDICAL COLL NASHVILLE TN
|
| The overall goal of this proposed project is to understand the mechanism of regulation of human BRCA2 gene expression in order to explore the possibility of epigenetic malfunction in this mechanism, which may lead to sporadic breast cancer. The majority (>95%) of human breast cancer happens sporadically and caused by mutations in a variety of genes (1-5). On the other hand, the familial breast cancers are caused by the defects ... |
|
| Breast Cancer Metastasis to Bone Affects Osteoblast Differentiation |
MAY 2003 |
8 pages |
| Authors:
Robyn R. Mercer; Andrea M. Mastro; PENNSYLVANIA STATE UNIV UNIVERSITY PARK
|
| Breast cancer fatally metastasizes to bone and activates osteoclasts, cells that resorb bone, resulting in the formation of osteolytic lesions. Certain drugs, bisphosphonates, slow the action of osteoclasts, however, the bone lesions are not repaired. The osteoblasts should be able to repair the lesions by synthesizing new bone matrix. Instead, these cells appear to be inactivated by breast cancer, and the lesions do not heal. The purpose of this proposal ... |
|
| Molecular Biology Basis for the Response of Poly(ADP-ribose) Polymerase and NAD Metabolism to DNA Damage Caused by Mustard Alkylating Agents |
MAY 2003 |
31 pages |
| Authors:
Mark E. Smulson; GEORGETOWN UNIV WASHINGTON DC
|
| PARP is a chromatin bound enzyme, which is pivotal in the recovery of cells from DNA strand break damage. SM confers damage to cells causing DNA strand breaks. In collaboration with intramural scientists of USAMRICD, we recently demonstrated that SM, in part, causes cellular pathology and death via initiating apoptosis, and in primary PARP (+/+) fibroblasts by causing such an extensive depletion of ATP and NAD that the skin cells ... |
|
| Procathepsin D Stimulation of Human Breast Cancer Cell Growth |
NOV 2002 |
47 pages |
| Authors:
Vaclav Vetvicka; LOUISVILLE UNIV RESEARCH FOUNDATION INCKY OFFICE OF GRANTS MANAGEMENT
|
| The long-term objective of this project is to develop a new treatment for breast cancer based on blockade of the autocrine growth factor activity of procathepsin D, the enzymatically inactive precursor of common enzyme cathepsin D. This precursor has been found to be overexpressed and actively secreted from various breast tumor cells. For this project it is important to realize that the aspartic proteinase cathepsin D is generated by removal ... |
|
| Role of Oocyte Loss in Ovarian Surface Mesothelial Cell Transformation |
NOV 2002 |
10 pages |
| Authors:
Jonathan L. Tilly; Grant R. MacGregor; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| Three Specific Aims (SA) were proposed to test in mice the hypothesis that accelerated oocyte loss caused by Bclw deficiency or Bax gain-of-function drives ovarian surface mesothelial cell (OSMC) transformation: 1) characterize preneoplastic changes in OSMC of between mice with increasing age; 2) determine if disruption of the gene encoding Bax, a Bclw interacting partner required for oocyte apoptosis, rescues the compromised oocyte survival and the OSMC transformation phenotype observed ... |
|
| Role of TGF-1B1-Mediated Down Regulation of NF-kB/Rel Activity During Growth Arrest of Breast Cancer Cells |
NOV 2002 |
31 pages |
| Authors:
Shangqin Guo; BOSTON UNIV MA
|
| NF-kB/Rel is a family of transcription factors, which are expressed in all cells; however, in most non-B cells, they are sequestered in the cytoplasm in inactive complexes with specific inhibitory proteins, termed IKBs We have recently shown that NF-kB/Rel factors are aberrantly activated in breast cancer, and function to promote tumor cell survival Specifically, mammary tumors induced upon carcinogen treatment of Sprague-Dawley (S-D) rats, human breast tumor cell lines, and ... |
|
| Molecular Beam Studies of Reactions Between Stratospheric Gases and Supercooled Sulfuric Acid |
12 AUG 2002 |
9 pages |
| Authors:
Gilbert M. Nathanson; John R. Morris; Peter M. Behr; Jennifer Splan; Samuel Glass; WISCONSIN UNIV-MADISON DEPT OF CHEMISTRY
|
| Sulfuric acid aerosols in the stratosphere contribute to the destruction of the ozone layer by converting inactive gases like HCl and HBr into molecules that fall apart into chlorine and bromine atoms, which catalytically destroy ozone. The first step in these reactions is the transport of gaseous HCl and HBr into the acid droplet, where they dissolve and dissociate. We find that the entry of HCl and HBr into sulfuric ... |
|
| Behavioral Neurophysiology of Ethanol |
JUL 2002 |
47 pages |
| Authors:
Patricia H. Janak; ERNEST GALLO CLINIC AND RESEARCH CENTEREMERYVILLE CA
|
| This research project is designed to further our knowledge on the neural basis of alcohol addiction. Alcohol consumption by humans can be modeled in the rat using operant behavioral procedures in which an arbitrary response, such as a lever press, is reinforced by the presentation of small amounts of orally consumed ethanol solutions; this paradigm is termed ethanol self- administration. In the studies in this project simultaneous recording of ensembles ... |
|
| "The Total Force Concept," Asserting Jurisdiction Over Air Reserve Component Forces |
APR 2002 |
51 pages |
| Authors:
Leslie D. Long; AIR COMMAND AND STAFF COLL MAXWELL AFB AL
|
| Today's Air Force relies heavily upon the Air Reserve Component (ARC) forces to meet mission requirements. As ARC forces are integrated into the force structure, commanders and judge advocates must have a clear understanding of a commander's authority to discipline members of the ARC force. The two reserve components that make up the Air Reserve Components are the Air Force Reserve (AFRES) and the Air National Guard of the United ... |
|
| Stimulus Simplification and Object Representation: A Modeling Study |
MAR 2002 |
9 pages |
| Authors:
Ulf Knoblich; Maximilian Riesenhuber; MASSACHUSETTS INST OF TECH CAMBRIDGE COMPUTER SCIENCE AND ARTIFICIAL INTELLIGENCE LAB
|
| Tsunoda et al. [20] recently studied the nature of object representation in monkey inferotemporal cortex using a combination of optical imaging and extracellular recordings. In particular, they examined IT neuron responses to complex natural objects and simplified versions thereof. In that study, in 42% of the cases, optical imaging revealed a decrease in the number of activation patches in IT as stimuli were simplified . However, in 58% of the ... |
|
| Bin1, Apoptosis, and Prostate Cancer |
FEB 2002 |
11 pages |
| Authors:
Frank K. Rauscher; WISTAR INST OF ANATOMY AND BIOLOGY PHILADELPHIA PA
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| Progress is summarized on our project to investigate the diagnostic and therapeutic potential for Bin1 in prostate cancer. We have successfully generated 9 new monoclonal antibodies capable of recognizing all Bin1 splice isoforms that have been identified in cells. These antibodies are currently being tested and optimized for staining of fixed tissues. In Aim 2, we proposed to perform immunohistochemical studies. To date, we have analyzed 30 cases of frozen ... |
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| PET-FDG Imaging in Metastatic Breast Cancer Treated with High Dose Chemotherapy and Stem Cell Support |
FEB 2002 |
29 pages |
| Authors:
Abass Alavi; PENNSYLVANIA UNIV PHILADELPHIA
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| The purpose of our study was to evaluate the effectiveness of PET-FDG in patients with metastatic breast cancer who were also being treated with high dose chemotherapy and stem cell rescue. The hypotheses of the study were as follow: 1) Active tumor sites shown by anatomical imaging methods will be associated with high levels of metabolic activity while inactive sites will be reflected by low levels of FDG uptake. 2) ... |
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