| Modeling of Spatial and Temporal Dynamics in Biological Olfactory Systems |
21 SEP 2007 |
111 pages |
| Authors:
Jacek M. Zurada; Andy G. Lozowski; Mykola Lysetskiy; LOUISVILLE UNIV RESEARCH FOUNDATION INC KY OFFICE OF GRANTS MANAGEMENT
|
 | The olfactory system is a very efficient biological setup capable of odor information processing with neural signals. The nature of neural signals restricts the information representation to multidimensional temporal sequences of spikes. The information is contained in the inter-spike intervals in each individual neural signal and in inter-spike intervals between multiple signals. A mechanism of interactions between random excitations evoked by odorants in the olfactory receptors of the epithelium and ... |
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| Biochemical Characterization of Native Schwannonmin/Merlin |
SEP 2007 |
23 pages |
| Authors:
Athar Chrishti; ILLINOIS UNIV AT CHICAGO
|
| Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of bilateral vestibular and spinal schwamomas meningiomas, and ependymomas. The hF2 gene encodes a 595 amino acid polypeptide known as NF2 protein or Merlin or Schwanomin. The primary structure of the NF2 protein is homologous to the ERM family of peripheral membrane proteins, which includes Ezrin, Radixin, and Moesin. The founding member of the ERM superfamily is ... |
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| Optical Spectroscopy and Multiphoton Imaging for the Diagnosis and Characterization of Hyperplasias in the Mouse Mammary Gland |
SEP 2007 |
16 pages |
| Authors:
Melissa C. Skala; DUKE UNIV DURHAM NC
|
| In these studies, the potential of optical techniques for early breast cancer detection were tested in animal models and cell culture. Optical spectroscopy, in vivo and in vitro microscopy studies indicate that optical methods show great promise for the early diagnosis of cancer, and may potentially provide biologically relevant information that could aid in treatment decisions. The features extracted from diffuse reflectance spectra measured in vivo from the hamster cheek ... |
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| Bacillus Anthracis Spores of the bclA Mutant Exhibit Increased Adherence to Epithelial Cells, Fibroblasts, and Endothelial Cells but not to Macrophages |
SEP 2007 |
9 pages |
| Authors:
Jorl Bozue; Krishna L. Moody; Christopher K. Cote; Bradley G. Stiles; Arthur M. Friedlander; Susan L. Welkos; Martha L. Hale; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD DIV OF TOXINOLOGY AND AEROBIOLOGY
|
| Bacillus anthracis is the causative agent of anthrax, and the spore form of the bacterium represents the infectious particle introduced into a host. The spore is surrounded by an exosporium, a loose-fitting membrane composed of proteins and carbohydrates from which hair-like projections extend. These projections are composed mainly of BclA (Bacillus-collagen-like protein of B. anthracis). To date, exact roles of the exosporium structure and BclA protein remain undetermined. We examined ... |
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| Seladin-1: A Novel Tumor Suppressor Gene Involved in Breast Cancer? |
01 AUG 2007 |
8 pages |
| Authors:
Konstantin I. Galaktionov; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Seladin-1 maps to the human chromosome region 1p31-1p32 that shows frequent loss of heterozygosity (LOH) in human breast tumors. Publicly available data (Entrez, GEO) also show a significant variability between levels of Seladin-1 expression in breast cancer cell lines and normal breast epithelium. Is Seladin-1 a tumor suppressor on 1p31-1p32 that is involved in breast cancer? Our concept is that it is. In order to determine if Seladin-1 is a ... |
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| The Significance of Erythropoietin Receptor (EpoR) Acquisition by Breast Cancer Cells |
AUG 2007 |
21 pages |
| Authors:
Laurie Feldman; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Data from our lab and others indicate that normal breast cells do not express the erythropoietin receptor (EpoR); conversely breast cancer (Ca Br) cells express functional EpoR. Expression of EpoR appears greatest in poorly oxygenated tumor regions and in patients with negative estrogen receptor status a sign of more aggressive disease. Additionally one study demonstrated that the EpoR gene is overexpressed in patients with micrometastatic disease. The differential expression of ... |
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| Reversal of Breast Cancer Phenotype to Normal in Vitro by Transposon-Mediated Mutagenesis and Identification of Associated Genetic Changes |
AUG 2007 |
19 pages |
| Authors:
Anirban Datta; CALIFORNIA UNIV SAN FRANCISCO
|
| The highly organized architecture of cells in normal epithelial organs such as the mammary glands is lost in cancer cells. Both the normal as well as the neoplastic phenotypes can be recapitulated in 3- dimensional cell cultures in vitro. Our goal was to revert transformed breast cancer cell lines in vitro back to normal and identify the molecular and genetic changes required for this reversal. We have identified the Rho ... |
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| MicroRNA and Breast Cancer Progression |
AUG 2007 |
10 pages |
| Authors:
Konstantin Galaktionov; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| We hypothesized that certain miRNA species are differentially expressed in the normal breast epithelium and breast cancer cells. Our concept was that these miRNAs are involved in breast cancer progression by promoting either loss or alternatively an increase (in case of miRNA downregulation) in specific target mRNA translation or stability. In order to determine if certain miRNAs are involved in breast cancer we proposed to: 1. Identify the changes in ... |
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| Promotion of Epithelial to Mesenchymal Transformation by Hyaluronan |
01-Jul-2007 |
43 pages |
| Authors:
Silva Krause; TUFTS UNIV BOSTON MA
|
| The homeostasis observed in an organ is a consequence of a coordinated multidirectional communication between the epithelium and its microenvironment through physical and biochemical signals. An interruption of this communication can lead to the formation of cancer. One of the major components of mammary gland microenvironment, also called stroma, is hyaluronan (HA). It has been proposed that HA may induce malignant transformation in normal cells through interaction with its receptors. ... |
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| Breast Cancer and Early Onset Childhood Obesity: Cell Specific Gene Expression in Mammary Epithelia and Adipocytes |
JUL 2007 |
27 pages |
| Authors:
Ignacio G. Camarillo; Maxine Nichols; PURDUE UNIV LAFAYETTE IN
|
| Obesity has become a major health problem in children and adults and is associated with increased breast cancer incidence and mortality The epidemic of childhood obesity is recent and little information exists regarding its association with mammary tumongenesis Towards better understanding this relationship we have developed and characterized a new rat model of childhood onset Diet Induced Obesity (DIO) and breast cancer We have shown that young female rats fed ... |
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| The Role of DN-GSK3b in Mammary Tumorigenesis |
JUL 2007 |
31 pages |
| Authors:
Marganit D. Farago; BOSTON MEDICAL CENTER CORP MA
|
| Recent studies have implicated ectopic activation of the Wnt pathway in many human cancers, including breast cancer. beta-catenin is a critical co-activator in this signaling pathway, and is regulated in a complex fashion by phosphorylation, degradation, and nuclear translocation. Glycogen synthase kinase-3beta (GSK3beta) phosphorylation of the N-terminal domain of beta-catenin targets it for ubiquitination and proteosomal degradation. We hypothesized that expression of dominant negative (DN) GSK3beta in mammary glands would ... |
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| Allele Imbalance or Loss of Heterozygosity in Normal-Appearing Breast Epithelium as a Novel Marker to Predict Future Breast Cancer |
JUL 2007 |
6 pages |
| Authors:
Carol L. Rosenberg; BOSTON MEDICAL CENTER CORP MA
|
| The goal of this study is to determine whether the occurrence of AI/LOH in the DNA of histologically normal epithelium from non-cancerous breasts predicts future breast cancer development. If so, then AI/LOH would be an excellent candidate molecular marker of increased sporadic breast cancer risk: its incidence increases during cancer development, it can be quantified and standardized, it is likely to reflect dysregulation of genetic mechanisms that could be potential ... |
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| Smad Acetylation: A New Level of Regulation in TGF-Beta Signaling |
JUL 2007 |
24 pages |
| Authors:
Andrea W. Tu; CALIFORNIA UNIV BERKELEY
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| The transforming growth factor (TGF) signaling pathway is an essential pathway whose initiation results in cell growth arrest in most epithelial cells. Activation of TGF receptors leads to the phosphorylation and translocation of the Smad proteins, the major TGF intracellular signaling molecule, to the nucleus where transcription of TGF target genes occur. Many breast cancers contain aberrations in the regulation of Smad proteins demonstrating the importance of TGF signaling. Therefore, ... |
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| Lipid Peroxidation, Chronic Oxidative Stress and Breast Cancer Inci-dence: Implications for Breast Cancer Prevention |
JUL 2007 |
14 pages |
| Authors:
Judith Weisz; PENNSYLVANIA STATE UNIV COLL OF MEDICINE HERSHEY
|
| The experiments were based on the following interrelated hypotheses: a) Exposure of the mammary epithelium (ME) to chronic oxidative stress (OxS) underlies the high breast cancer (BC) incidence associated with Western industrialized environment/lifestyle and b) that there is a positive correlation between BC incidence within a population and the prevalence within that population of protein adducts of the well-documented marker of chronic OxS 4-hydroxy-2-nonenal (4HNE) that is a major breakdown ... |
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| Cells With Unique Properties in Prostate Cancer-Associated Storma Are Mesenchymal Stem Cells |
01-Jun-2007 |
8 pages |
| Authors:
Donna M Peehl; STANFORD UNIV CA
|
| Our objective was to explore the hypothesis that prostate cancer-associated stromal cells are derived, at least in part, from mesenchymal stem cells. Our objective was to show that cancer-derived stromal cells capable of anchorage-independent growth have characteristics of stem cells and convert nontumorigenic prostatic epithelial cells to tumorigenicity. We could not identify cells capable of anchorage-independent growth, so we sought other stem cell markers. We pinpointed CD90 as a marker ... |
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| The Nuclear Death Domain Protein p84N5; A Candidate Breast Cancer Susceptibility Gene |
MAY 2007 |
50 pages |
| Authors:
Andrew Godwin; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| Efforts to identify genes that contribute to breast cancer lead to the discovery of the human TREX complex, a group of proteins that work together to accurately process and transport messenger RNAs from the nucleus to the cytoplasm in a cell. A member of this complex, referred to as p84N5 (more recently named hTREX84) was found to be a culprit of aggressive human breast cancers. hTREX84 is expressed at very ... |
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| Signaling Crosstalk: A Live in Situ Analysis of the Temporal and Spatial Regulation of Key Pathways in Human Breast Cancer Progression |
MAY 2007 |
20 pages |
| Authors:
Aaron Boudreau; CALIFORNIA UNIV BERKELEY
|
| Signal transduction networks such as the PI3K-AKT and EGFR pathways are important regulators of cell fate decisions, including cell proliferation, differentiation, apoptosis, and homeostasis. Furthermore, these pathways integrate and influence one another when cells are within an appropriate microenvironment. Using a proteomic approach, we identify stratifin, a protein which regulates AKT and EGFR signaling as well as the cell cycle, to be upregulated in T4-2 cells cultured in 3D lrECM. ... |
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| Role of p53 in Mammary Epithelial Cell Senescence |
MAY 2007 |
62 pages |
| Authors:
Goberdhan P. Dimri; EVANSTON NORTHWESTERN HEALTHCARE RESEARCH INST IL
|
| The tumor suppressor p53 plays an important role in a variety of cancers including breast cancer. It inhibits the growth of malignant cells either by inducing G1 arrest, apoptosis or senescence. We are determining the role of p53 in human mammary epithelial cell (HMEC) senescence and the requirement of p53 inactivation in transformation of HMECs. In this report, we have found that p53 downregulation is required to overcome H-Ras induced ... |
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| Manipulation of NF-KappaBetta Activity in the Macrophage Lineage as a Novel Therapeutic Approach |
MAY 2007 |
22 pages |
| Authors:
Fiona E. Yull; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| Morphogenesis of the mammary gland is a highly complex process which when misregulated can result in tumorigenesis. It involves the interactions of multiple cell types in a highly regulated manner with complex signal transduction pathways coordinating the physiological processes. Interactions between epithelial and mesenchymal cells are known to be important. Recent studies highlight the importance of cell types, such as macrophages. The nuclear factorkappa B (NF-kB) family of transcription factors ... |
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| Clinical and Molecular Consequences of NF1 Microdeletion |
MAY 2007 |
43 pages |
| Authors:
Karen Stephens; WASHINGTON UNIV SEATTLE
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| We have developed rapid and sensitive assays for the detection and mapping of both the common 1.4 Mb NF1 microdeletion and novel microdeletions; our subjects carrying microdeletions have contributed to diverse collaborations including development of a mouse model of plexiform neurofibroma tunorigenesis and the conservation of recombination hotspots. Our hypothesis that genome instability occurs during NF1-tumorigenesis continues to be supported by our findings. First, somatic instability leading to uniparental isodisomy ... |
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| Targeting of CD151 in Breast Cancer and in Breast Cancer Stem Cells |
01-Apr-2007 |
34 pages |
| Authors:
Martin E Hemler; DANA-FARBER CANCER INST BOSTON MA
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| A mouse model for spontaneous breast cancer has been set up to analyze the role of CD151 during breast cancer progression. Using this model, which involves amplification of the ErbB2 oncogene, preliminary data was then obtained indicating that the absence of CD151 causes a substantial delay in the appearance of mouse mammary tumors. To confirm these preliminary results, we next set up a larger scale experiment to evaluate the role ... |
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| The Role & Action of Prohibition, an Antiproliferative Gene, in Ovarian Cancer |
APR 2007 |
10 pages |
| Authors:
Winston E. Thompson; MOREHOUSE SCHOOL OF MEDICINE ATLANTA GA
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| The experiments proposed in this application aim at understanding the mechanisms by which prohibitin induces growth arrest in ovarian cancer. We hypothesize that the prohibitin gene product will substantially induce arrest in ovarian cancer cells and enhance differentiation. Accordingly, we will characterize the expression pattern and function of this gene. In specific aim 1, we will define the spatial, temporal and stage specific cellular expression pattern of prohibitin in normal ... |
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| Regulation of Tumor Cell Growth by the Mesenchymal Environment of the Bone Marrow is Enhanced by a High-Fat Diet |
APR 2007 |
15 pages |
| Authors:
Colin Jefcoate; WISCONSIN UNIV-MADISON
|
| Obesity enhances prostate cancer (PC) metastasis to bone. Factors secreted from adipocytes enhance PC growth. We hypothesized that feeding a high fat diet to C57BL/6 mice would enhance bone marrow (BM) fibroblastic progenitor differentiation to adipocytes. Mice were fed isocaloric low (LFD) and high (HFD) fat diets for up to 11 weeks postweaning. BM cells were isolated and cultured in serum-free RPMI 1640 media (PC media), generating BM conditioned media ... |
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| Roles of Breast Cancer Susceptibility Genes BRCA's in Mammary Epithelial Cell Differentiation |
MAR 2007 |
26 pages |
| Authors:
Saori Furuta; CALIFORNIA UNIV IRVINE
|
| BRCA1 exerts transcriptional repression through interaction with CtIP in the C-terminal BRCT domain and ZBRK1 in the central domain. A dozen of genes including angiopoietin-1 (ANG1), a secreted angiogenic factor, are co-repressed by BRCA1 and CtIP based on microarray analysis of mammary epithelial cells in 3-D culture. BRCA1, CtIP and ZBRK1 form a complex that coordinately represses ANG1expression via a ZBRK1 recognition site in ANG1 promoter. Impairment of this complex ... |
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| Elucidating the Role of CKS Proteins in Breast Cancer by Combining the Disciplines of Molecular Biology, Pathology, and Biophysics |
MAR 2007 |
7 pages |
| Authors:
Sonia del Rincon; SIDNEY KIMMEL CANCER CENTER SAN DIEGO CA
|
| Breast cancer often occurs when the proteins that regulate normal epithelial cell division become dysregulated. This proposal examines the role of the cell cycle regulatory proteins, human cyclin-dependent kinase subunits (Cks1 and Cks2) in human breast cancer. The overexpression of Cks genes in breast tumor tissue and the role of Skp2 in tumorigenesis, suggests that Cks and Skp2 levels must be strictly regulated for proper cell cycling. We hypothesize that ... |
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| A Biophysico-Computational Perspective of Breast Cancer Pathogenesis and Treatment Response |
MAR 2007 |
245 pages |
| Authors:
Valerie M. Weaver; PENNSYLVANIA UNIV PHILADELPHIA
|
| Apoptosis resistance regulates breast transformation and treatment responsiveness, yet the mechanism(s) enhancing breast cancer cell survival remain unclear. We showed that malignant transformation is associated with increased matrix deposition, cross-linking and reorganization that correlate with a progressive stiffening of the gland. Organotypic culture experiments demonstrated that stiffening the extracellular matrix (ECM) destabilizes cell-cell junctions, enhances integrin-dependent adhesions, alters survival, and compromises mammary morphogenesis and the integrity of differentiated mammary tissues. ... |
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| Identify the Impact of TGF-Beta Signaling on the Stroma in the Progression of Prostate Cancer |
MAR 2007 |
11 pages |
| Authors:
Neil A. Bhowmick; VANDERBILT UNIV NASHVILLE TN
|
| As a result of androgen ablation TGF- 1 expression levels transiently elevate and regression of benign prostate hyperplasia as well asprostate cancer cells for the most part occur. Better understanding of prostate androgen responsiveness is critical in understanding and ultimately combating androgen-non-responsive prostate cancer. Studying the conditional TGF- type II receptor fibroblast knock out mouse model we developed (Tgfbr2fspko), we found that TGF- signaling in the prostate stromal fibroblasts regulate ... |
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| Regulation of Leukocyte Infiltration into Ovarian Cancer by Tumor-Stroma Interactions, a Microarray View of Cancer Microenvironment |
MAR 2007 |
59 pages |
| Authors:
Izhak Haviv; Mark Smyth; Carleen Cullinane; Michael Kershaw; Sarah Russell; MELBOURNE UNIV VICTORIA (AUSTRALIA)
|
| Despite compelling cell biological studies and histopathological observations incriminating stromal cells in tumorigenesis, our knowledge of the genes that mediate changes in the tumor microenvironment and interactions among various cell types in epithelial cancer and their role in tumorigenesis is limited. Here, we describe a comprehensive molecular characterization of stromal-epithelial cell interactions, using microarray analysis of co-cultured cell pairs. We further show that these gene expression changes indeed are common ... |
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| The Significance of Focal Basal Cell Layer Disruption-Induced Immuno-Cell Infiltration in Prostate Cancer Invasion |
MAR 2007 |
10 pages |
| Authors:
Yang-gao Man; AMERICAN REGISTRY OF PATHOLOGY WASHINGTON DC
|
| Using multidisciplinary approaches, our studies assessed the physical status of prostate basal cell layers and the impact of basal cells on the biological presentation of associated epithelial cells. Our studies showed that focally disrupted basal cell layers had the following unique features (1) significantly lower proliferation; (2) significantly lower p63 expression; (3) significantly higher apostosis; (4) significantly higher leukocyte infiltration and stromal reactions. |
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| Development of a Novel Therapeutic Paradigm Utilizing a Mammary Gland-Targeted, Bin-1 Knockout Mouse Model |
MAR 2007 |
51 pages |
| Authors:
Alexander J. Muller; LANKENAU INST OF MEDICAL RESEARCH WYNNEWOOD PA
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| Evidence of loss or attenuation of the Bin 1 gene in human breast cancers has implicated Bin 1 as a tumor suppressor or negative modifier gene in mammary gland epithelial cells. We have discovered that Bin 1 loss can promote tumorigenesis through an immune escape mechanism. This correlates with the negative regulatory impact that we have found Bin 1 to exert on the important immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Previously ... |
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| Decreased Expression of the Early Mitotic Gene CHFR Contributes to the Acquisition of Breast Cancer Phenotypes |
MAR 2007 |
37 pages |
| Authors:
Lisa M. Privette; MICHIGAN UNIV ANN ARBOR
|
| The purpose of this study was to determine if CHFR was biologically relevant to breast cancer characteristics and progression. Here we studied both breast cancer cell lines and primary samples from breast cancer patients to investigate CHFR as a relevant tumor suppressor in breast cancer and to associate CHFR expression with clinical and pathological variables. A large percentage of samples demonstrated negative or weak CHFR protein expression or staining. In ... |
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| Therapy Selection by Proteomic Profiling |
01 FEB 2007 |
8 pages |
| Authors:
Simon W. Hayward; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| The long term goal of this work is to develop a new prognostic tool with which to determine the response of a patient to a given therapy, with the view of providing the most appropriate treatments tailored to individual patients. The central hypothesis of this proposal is that a subset of the proteins expressed in a prostate tumor can be used to predict response to specific therapeutic regimens. The purpose ... |
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| Mechanisms and Chemoprevention of Ovarian Carcinogenesis |
FEB 2007 |
10 pages |
| Authors:
Christos Patriotis; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| Due to its asymptomatic development and frequent diagnosis at advanced stages ovarian cancer is the most deady among the gynecological cancers. A better understanding of the early molecular events leading to the disease is of utmost importance for the development of strategies for its efficient early diagnosis and prevention which could improve patient survival and quality of life. We have shown that DMBA-induced mutagenesis in the rat ovary combined with ... |
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| Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast |
FEB 2007 |
21 pages |
| Authors:
Jeffrey K. Griffith; NEW MEXICO UNIV ALBUQUERQUE
|
| We are using an innovative quantitative assay for telomere DNA content (TC) developed and characterized by the PI to test the hypothesis that TC predicts the likelihood of disease recurrence in women with DCIS. In Year One we collaborated to determine whether TC measured in bulk DCIS tumor tissue is comparable to that measured in tumor epithelial cells purified by laser-capture microscopy. In 7/10 instances TC in microdissected specimens was ... |
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| Modeling Human Epithelial Ovarian Cancer in Mice by Alteration of Expression of the BRCA1 and/p53 Genes |
FEB 2007 |
8 pages |
| Authors:
Denise Connolly; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| About one out of every ten cases of epithelial ovarian cancer (EOC) is inherited. The majority >90% of inherited cases of EOC are the result of mutations in the breast cancer associated gene I (BRCA1). This gene was originally identified based on genetic linkage to families with an increased risk of developing breast and ovarian cancer. It is involved in controlling normal cellular growth and is thought to suppress the ... |
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| Origin and Properties of Prostatic Stem Cells |
FEB 2007 |
32 pages |
| Authors:
E. L. Wilson; Rashmi Gupta; NEW YORK UNIV NY SCHOOL OF MEDICINE
|
| The aims of this proposal were to isolate and characterize prostatic epithelial stem cells and also to determine if bone marrow (BM) cells can differentiate into prostatic tissue. We show that the murine prostate contains a small population of cells ( |
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| BTG2 Antiproliferative Gene and Prostate Cancer |
FEB 2007 |
8 pages |
| Authors:
Paul D. Walden; NEW YORK UNIV NY SCHOOL OF MEDICINE
|
| Levels of the BTG2 tumor suppressor protein diminish during the transition of normal prostate epithelial cells into prostate cancer cells and restoration of BTG2 expression in prostate cancer cells significantly reduces cell proliferation and tumorigenicity. Our working hypothesis being tested is that the tumor suppressive activity of BTG2 is diminished as an early event in prostate carcinogenesis due to increased proteasomal degradation, leading to compromised cell cycle regulation, increased cell ... |
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| Development of a Mouse Model for Prostate Cancer Imaging and Study of Disease Progression |
JAN 2007 |
9 pages |
| Authors:
Isla Garraway; CALIFORNIA UNIV LOS ANGELES
|
| Prostate carcinogenesis is a multi-step process resulting in the transformation of prostatic epithelial cells into invasive carcinoma and metastasis. In recent years, mouse models have emerged that recapitulate salient features of prostate carcinogenesis found in human disease. These models illuminate the molecular events that result in transformation and disease progression. In addition, mouse models can be used to identify molecular targets and to test chemotherapeutic agents that may alter the ... |
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| Improved Wound Healing of Cutaneous Sulfur Mustard Injuries in a Weanling Pig Model |
08 NOV 2006 |
24 pages |
| Authors:
John S. Graham; Robert S. Stevenson; Larry W. Mitcheltree; Marcia Simon; Tracey A. Hamilton; Robin R. Deckert; Robyn B. Lee; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| OBJECTIVE: The objective was to examine the efficacy of several treatment regimens in improving wound healing of cutaneous sulfur mustard (HD) injuries. METHODS: Wound healing studies were conducted in weanling pigs. Superficial dermal HD injuries were debrided at 48 hours post-exposure using an erbium-doped yttrium aluminum garnet (Er:YAG) laser, followed by application of a treatment adjunct. A variety of noninvasive bioengineering methods were conducted during the post-surgical observation period to ... |
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| Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells |
01 NOV 2006 |
33 pages |
| Authors:
Radharaman Ray2 Gao1* Yan Xiao3; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
|
| Inhalation of sulfur mustard (SM) causes airway inflammation and injury. There is increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE) cells and bronchial/tracheal epithelial (BTE) cells. Cells were exposed to varying concentrations of SM with or without roxithromycin. ... |
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| Sensitive Bioanalytical Methods for Mustard Gas Exposure Diagnosis |
01 NOV 2006 |
8 pages |
| Authors:
Xiannu Jin; Radharaman Ray; Prabhati Ray; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
|
| Sulfur mustard (SM, 2, 2'-dichlorodiethyl sulfide) is an alkylating vesicating agent. The injuries resulting from SM exposure are mainly characterized by epithelial damage of the tissues through which it is absorbed, i.e., skin, eye, and respiratory tract. The skin blistering action of SM is not seen until about 12 24 hr after exposure. This time lag provides a window of opportunity for an early diagnosis of SM exposure and medical ... |
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| A Mouse Model to Investigate Postmenopausal Biology as an Etiology of Ovarian Cancer Risk |
NOV 2006 |
31 pages |
| Authors:
Xiangxi Xu; INSTITUTE FOR CANCER RESEARCH PHILADELPHIA PA
|
| This project is to use a unique mouse model to study the interaction of reproductive factors and genetic mutations in the development of ovarian cancer. Ovarian cancer often develops in women of peri-menopausal age. We found that the germ cell deficient Wv mice mimics postmenopausal biology and develop benign ovarian tumors. We plan to test the hypothesis that a synergy exists between oncogenic mutations such as p53, pten, or p27kip1 ... |
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| Telomere Length as a Predictor of Aggressive Prostate Cancer |
NOV 2006 |
10 pages |
| Authors:
Elizabeth A. Platz; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
|
| We are evaluating whether men with shorter telomere length in prostate cancer tissue and in normal appearing prostate tissue adjacent to adenocarcinoma have a higher risk of aggressive prostate cancer than men with longer telomere length. Since the last progress report (Nov 2005) the tissue microarrays were assembled by our Harvard collaborators. At Hopkins, we completed staining of the tissue microarrays for telomere length and are in the processing of ... |
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| Anti-Angiogenic Action of Neutral Endopeptidase |
NOV 2006 |
15 pages |
| Authors:
David Nanus; CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK
|
| Angiogenesis, or the formation of new blood vessels from existing vasculature is an important event in tumor progression. It results from a complex, multistep biochemical cascade that is initiated by the activation of endothelial cells in response to angiogenic factors. In prostate cancers, angiogenic factors are produced by epithelial and stromal cells, and are believed critical to prostate cancer growth and progression. One of the most important of these factors ... |
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| Protection Against the Vesicant Chemical Warfare Agent Sulfur Mustard: Therapeutics Utilizing Apoptosis Inhibitors |
NOV 2006 |
7 pages |
| Authors:
R. Ray; B. J. Benton; S. L. Hauck; C. Carpin; D. S. Rosenthal; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD RESEARCH DIVISION
|
| Sulfur mustard (SM, bis-(2-chloroethyl) sulfide), commonly called mustard gas, is a vesicant chemical warfare agent and a potential terrorism agent. SM is relatively easy to make and to deploy, which makes this chemical most likely to be used. SM exposure causes debilitating skin blisters (vesication) and injury to the eyes and the respiratory tract. Therefore, developing an effective medical countermeasure to protect against the dermal, ocular and airway injuries due ... |
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| Mouse Orthotopic Xenographs of Human Prostate Primary Tumors |
NOV 2006 |
9 pages |
| Authors:
Massimo Loda; DANA-FARBER CANCER INST BOSTON MA
|
| Currently, primary human tumor material is insufficient due to small size, multifocality and difficulty of visualization at macroscopic examination. This essentially prevents extensive studies aimed at distinguishing indolent and aggressive organ-confined prostate cancers. Understanding the molecular alterations governing tumorigenesis and cancer progression is the first step necessary for the design of effective and targeted therapies. For this reason, in recent years considerable efforts have been devoted to generate clinically relevant ... |
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| Identification of Sonic Hedgehog-Induced Stromal Factors That Stimulate Prostate Tumor Growth |
NOV 2006 |
69 pages |
| Authors:
Aubie Shaw; Wade Bushman; WISCONSIN UNIV-MADISON
|
| We will determine the mechanism by which Shh signaling accelerates prostate tumor growth, identify Shh targets in prostate tumor stroma, and test the effect of individual target genes on tumor growth. The purpose of the report is to evaluate the first year of research. Sonic hedgehog induces tumor growth by a paracrine mechanism using tumor stroma. Shh signaling independent of Shh ligand in tumor stroma accelerates tumor growth. We have ... |
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| Molecular Mechanism for Prostate Cancer Resistance to the Anti-tumor Activity of Vitamin D |
NOV 2006 |
51 pages |
| Authors:
Larisa Nonn; LELAND STANFORD JUNIOR UNIV STANFORD CA
|
| The original purpose of this research, as proposed in the statement of work, was to determine the mechanism by which prostate cancer (PCa) cells become resistant to the anti-tumor activity of vitamin D. The proposal focused on a PCa-specific deficiency in a key vitamin D metabolizing enzyme, 1alpha-hydroxylase (1alphaOH). During the first year, we encountered unforeseen difficulties with one of the key techniques in the original proposal. Therefore we decided ... |
|
| Biological Basis for Chemoprevention of Ovarian Cancer |
OCT 2006 |
60 pages |
| Authors:
Andrew Berchuck; DUKE UNIV MEDICAL CENTER DURHAM NC
|
| To achieve a better understanding of the etiology of ovarian cancer we have initiated a case-control study that considers genetic susceptibility epidemiologic risk factors and acquired genetic alterations. Subjects are interviewed in their homes and about 950 cases and 950 controls have been accrued thus far. Blood and cancer samples have been collected and molecular analyses of polymorphisms in single genes including most recently the androgen receptor have been performed. ... |
|
| Knockout AR in Prostate |
OCT 2006 |
8 pages |
| Authors:
Chawnshang Chang; ROCHESTER UNIV NY
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| Prostate cancer progresses from androgen-dependent to androgen-independent state. The androgen receptor (AR) is expressed throughout progression. We would like to understand the AR role in this progression. Using lox-Ore methodology we have generated mice in which AR function is abolished in the entire animal (ARKO) or tissue specific manner and generated mice with ARKO in prostate only or in different stages to be used to study prostate cancer (PCa) progresses. ... |
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