| The Regulation of JAB1 and Its Role in Breast Cancer |
MAR 2007 |
9 pages |
| Authors:
Terry J. Johnson; M D ANDERSON CANCER CENTER HOUSTON TX
|
 | The purpose of the research done has been to determine the mechanism for overexpression of JAB1 through transcription factor analysis and FISH as well as the role of JAB1 in resistance. The major findings thus far are 1) The promoter region of JAB1 was analyzed and key transcription factors were identified that may drive JAB1 expression, CEBP alpha and GATA1 2) We have performed FISH on a number of breast ... |
|
| Prostate Cancer Aggressiveness Gene in Hereditary Prostate Cancer |
MAR 2007 |
21 pages |
| Authors:
Kathleen Cooney; MICHIGAN UNIV ANN ARBOR
|
 | This is the final report of our CDMRP-funded research grant. Our study comprised of two research aims to examine the role of EZH2 and prostate cancer. In the first of these aims, we have explored and developed data indicating that a polymorphism in EZH2, Asp146His, may contribute to aggressive prostate cancer, and we are currently conducting validation studies to determine if our findings may be used to predict whether men ... |
|
| Uncovering Design Principles of Intermediate Filaments, a Self-Assembling Biomaterial: Lessons in Nanoscale Materials Design |
21 FEB 2007 |
18 pages |
| Authors:
David H. Lee; TUFTS UNIV MEDFORD MA DEPT OF CHEMISTRY
|
 | Our broad long-term objective is to create novel biomaterials that advance the technical capabilities of the U.S. Army. In the short term, we seek to design self-assembling biomaterials that are adaptable in their structure and function. To do so, we must understand the molecular physicochemical aspects of biomaterials design, and we use three different systems to study this issue: 1) intermediate filaments, a class of protein with a broad range ... |
|
| Molecular Engineering of Vector-Based Oncolytic and Imaging Approaches for Advanced Prostate Cancer |
01-Feb-2007 |
57 pages |
| Authors:
Lily Wu; CALIFORNIA UNIV LOS ANGELES
|
 | Hormone refractory and metastatic prostate cancer are not well understood. Better animal models, diagnostic and treatment modalities are sorely needed for these advanced stages of disease. We have developed metastatic prostate cancer animal models that can be monitored by molecular imaging. To target metastatic disease, we have incorporated a highly potent and prostate-specific transcriptional regulatory system (TSTA) in adenoviral vectors such that the expression of imaging reporter gene and therapeutic ... |
|
| Role of Reactive Stroma in Prostate Cancer Progression |
FEB 2007 |
46 pages |
| Authors:
David R. Rowley; BAYLOR COLL OF MEDICINE HOUSTON TX
|
 | The purpose of this project is to determine the role of FGF receptor 1 in reactive stroma during prostate tumorigenesis. We are using a novel approach to target transgene expression specifically to the reactive stroma of experimental prostate cancer. Using a modified approach, we are placing an inducible Cre recombinase behind the FAP gene promoter to target expression to reactive stroma. We will cross this mouse with Fgfr1flox mice (LoxP ... |
|
| Mechanism of Tumor Metastasis Suppression by the KA11 Gene |
FEB 2007 |
13 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
 | KAI1 is a tumor metastases suppressor gene which is capable of blocking the metastatic process without affecting the primary tumorigenesis. Based on our preliminary data, we hypothesize that the KAI1 protein on tumor cells interacts with gp-Fy on the endothelial cells, which activates a signal pathway of the KAI1 molecule, and that this activation eventually leads to cell growth arrest of tumor cells. To test this hypothesis, we will examine ... |
|
| Genetic and Molecular Analysis of the Mechanisms by Which TSC Regulates Neuronal Differentiation |
FEB 2007 |
20 pages |
| Authors:
Helen McNeill; MOUNT SINAI HOSPITAL TORONTO (ONTARIO)
|
 | We have previously shown that loss of TSC pathway components alters the timing of neuronal differentiation in the Drosophila eye and wing imaginal disc. To determine the mechanisms underlying this regulation of neuronal differentiation, we have 1) further defined the subtypes of photoreceptors that respond to loss of TSC, 2) tested in silico candidates for the regulation of differentiation in the eye, and 3) optimized conditions for an RNAi screen. ... |
|
| Maintenance of Glucose Homeostasis through Acetylation of the Metabolic Transcriptional Coactivator PGC-1alpha |
FEB 2007 |
10 pages |
| Authors:
Pere Puigserver; JOHNS HOPKINS UNIV BALTIMORE MD
|
 | The purpose of this proposal is to test the hypothesis that acetylation of PGC-1alpha by the Acetyl Transferase GCN5 associated proteins, Pc3 and WDR18, is a key regulatory modification that controls hepatic glucose production. This investigation has a define scope to specifically test how these proteins control the acetylation status of PGC-1alpha and what is the functional effect in blood glucose levels. The major findings of this Research Technical Report ... |
|
| 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 ... |
|
| 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 ... |
|
| The Role of the Neurofibromin-Syndecan-Cask Complex in the Regulation of Synlaptic RAS-MAPK Signaling and Denoritic Spine Plasticity |
FEB 2007 |
15 pages |
| Authors:
Gang-Yi Wu; BAYLOR COLL OF MEDICINE HOUSTON TX
|
 | Neurofibromatosis type 1 (NF1) is a common dominant genetic disorder characterized by multiple benign and malignant tumors of neural origin and often cognitive deficits in children. How mutations in the NF1 gene lead to severe learning deficits is largely unknown. The protein encoded by NF1 neurofibromin contains a GAP domain known to inhibit Ras-mediated signal transduction. The objective of this proposal is to test the hypothesis that the newly identified ... |
|
| Molecular Targeting of the PI3K/Akt Pathway to Prevent the Development of Hormone Resistant Prostate Cancer |
FEB 2007 |
5 pages |
| Authors:
Jonathan Walker; ARIZONA UNIV TUCSON
|
 | Recently, the PI3K/Akt pathway has been found to be a significant factor in the development and progression of prostate cancer. It is the authors' belief that the PI3K/Akt pathway is the critical pathway that is maintaining survival by blocking apoptosis in the absence of hormonal stimulation. They will use molecular targeting to inhibit the phosphorylation of Akt. Celecoxib is a FDA approved COX-2 inhibitor. What is unique to celecoxib is ... |
|
| Molecular Genetic and Gene Therapy Studies of the Musculoskeletal System |
Feb-2007 |
223 pages |
| Authors:
Subburaman Mohan; LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION CA
|
 | The proposed research projects focuses on bone health, including relevance to the musculoskeletal system in battlefield performance and in battlefield injury. We have utilized state-of-the-art molecular genetic and gene therapy technologies to address fundamental questions in bone biology with particularly emphasis on attempting to clarify gene function for those genes that are involved in digit tip regeneration, bone size, skeletal repair and anabolic response to mechanical loading. The molecular genetic ... |
|
| Copine-I: Modulator of NF-kappa B Transcription and Prostate Cancer Survival |
01-Jan-2007 |
7 pages |
| Authors:
Marty W Mayo; Carl Creutz; VIRGINIA UNIV CHARLOTTESVILLE
|
 | NF-kB is a dynamic transcription factor that regulates important biological processes involved in cancer initiation and progression. This is especially true in prostate cancer (PCa) where dysregulated NF-kB activity is directly associated with PCa relapse. Identifying regulators that control the half-life of NF-kB is important to understanding molecular processes that control the duration of transcriptional responses. In this the initial funding period, we identify Copine-I, a calcium phospholipid binding protein, ... |
|
| Identification of Prostate Cancer-Related Genes Using Inhibition of NMD in Prostate Cancer Cell Lines |
JAN 2007 |
30 pages |
| Authors:
Yurij Ionov; HEALTH RESEARCH INC BUFFALO NY
|
 | A strategy to identify mutant genes using inhibition of nonsense mediated decay (NMD) in cell lines has been proposed by others. Blocking translation with antibiotic emetine has been shown to inhibit the NMD. Stabilization of mutant mRNA following the inhibition of NMD with emetine can be detected using microarray technology, such as Affymetrix genechips, for example. Unfortunately, too many genes that do not contain any mutations show mRNA increase following ... |
|
| 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 ... |
|
| Gene Expression Analysis of Circulating Hormone Refractory Prostate Cancer Micrometastases |
JAN 2007 |
13 pages |
| Authors:
Jonathan Rosenberg; CALIFORNIA UNIV SAN FRANCISCO
|
 | This annual report for the Physician Research Training Award focuses on progress in the genetic analysis of circulating hormone refractory prostate cancer micrometastases. As metastatic tissue is often inaccessible in advanced prostate cancer patients, analysis of circulating tumor cells may provide understanding of the biology of hormone refractory prostate cancer as well as chemotherapy resistance. Oligonucleotide array comparative genomic hybridization allows the assessment of genetic changes that may occur in ... |
|
| Identification of Risk Factors for Exertional Heat Illness: A Brief Commentary on Genetic Testing |
Jan-2007 |
6 pages |
| Authors:
Sheila Muldoon; Rolf Bunger; Patricia Deuster; Nyamkhishing Sambuughin; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF ANESTHESIOLOGY
|
 | This commentary discusses known links between Exertional Heat Illness (EHI), Malignant Hyperthermia (MH), and other hereditary diseases of muscle. Genetic and functional testing is also evaluated as measures of fitness to return to duty/play. Data Sources: Reviews and research articles from Sports Medicine, Applied Physiology, and Anesthesiology. Data Extraction: Detailed comparisons of existing literature regarding clinical cases of EHI and MH and the potential utility of genetic testing, specifically the ... |
|
| A Molecular Beam Deposition of DNA Nanometer Films |
Jan-2007 |
10 pages |
| Authors:
James G Grote; Andrew J Steckl; Joshua A Hagen; Hans Spaeth; Wei-Xin Li; CINCINNATI UNIV OH NANOELECTRONICS LAB
|
 | The development of novel photonic devices which incorporate biological materials is strongly tied to the development of thin film forming processes. Solution-based (wet) processes when used with biomaterials in device fabrication suffer from dissolution of underlying layers, incompatibility with clean environment, inconsistent film properties, etc. We have investigated ultra-high-vacuum molecular beam deposition of surfactant-modified deoxyribonucleic acid (DNA). We have obtained effective deposition rates of 0.1-1 A/s, enabling reproducible and controllable ... |
|
| Control of DNA Dehybridization via Nanoparticle Antennas for Antisense Gene Therapy |
2007 |
|
| Authors:
Kimberly Hamad-Schifferli; MASSACHUSETTS INST OF TECH CAMBRIDGE
|
 | The goal of this proposal is to develop the use of a nanoscale interface to protein translation machinery to control translation. External magnetic fields excite the nanoscale interface and thus switch on translation of a protein. This technique would enable time-specific control of protein expression, and would enable new techniques in disease diagnosis and therapy. These objectives are in line with the original proposal. |
|
| Exertional Heat Illness and Human Gene Expression |
2007 |
27 pages |
| Authors:
L.A. Sonna; M. N. Sawka; C. M. Lilly; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA THERMAL AND MOUNTAIN MEDICINE DIVISION
|
 | Microarray analysis of gene expression at the level of RNA has generated new insights into the relationship between cellular responses to acute heat shock in vitro, exercise, and exertional heat illness. Here we discuss the systemic physiology of exertional hyperthermia and exertional heat illness, and compare the results of several recent microarray studies performed in vitro on human cells subjected to heat shock and in vitro on samples obtained from ... |
|
| Biotechnology Industry |
2007 |
31 pages |
| Authors:
Kyle D. Campbell; Gene Clemen; Paul Denham; Greg Dodson; Denise Flanagan; Dale Goble; Deirdre Mahon; Joanne Martin; Rick Merrill; Mike Milford; INDUSTRIAL COLL OF THE ARMED FORCES WASHINGTON DC
|
 | Biotechnology is a diverse and promising industry, but it is not without challenges. The impact on our lives is already being felt, and all indications point to a future of unprecedented changes. Genetically modified (GM) organisms are being used to increase crop production, bacteria to remediate contaminated areas, and even fetal calf skin to grow human soft tissues. Concurrently our nation is seeking biotechnology answers for a variety of national ... |
|
| Dietary Fat, Fat Metabolizing Genes, and Prostate Cancer Risk in African-Americans and Whites |
01 DEC 2006 |
8 pages |
| Authors:
Sue Ann Ingles; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
 | Dietary fat has been implicated as a potential promotional factor leading to progression of small, latent, non-metastatic prostate tumors to invasive, metastatic lesions. One possible mechanism is conversion of n-6 polyunsaturated fatty acids to inflammatory compounds produced by the lipoxygenase (LOX) family of enzymes. The authors are examining whether genetic variants in the n-6 fatty acid LOX pathways are associated with the risk of prostate cancer in a population-based, case-control ... |
|
| DNA Conforming Dynamics and Protein Binding |
DEC 2006 |
8 pages |
| Authors:
Andreas Hanke; TEXAS UNIV AT BROWNSVILLE AND TEXAS SOUTHMOST COLLEGE
|
 | Recent advances in single%molecule force spectroscopy of DNA make it possible to study the thermodynamics and kinetics of DNA binding proteins under a wide range of conditions. A biophysical model for the DNA binding T4 gene 32 protein has been developed to study the kinetics of DNA protein binding to transient single-stranded DNA regions due to thermal fluctuations. The model is used to analyze recent single-molecule spectroscopy data of this ... |
|
| Program Project on the Pathogenesis and Treatment of Parkinson's Disease |
DEC 2006 |
211 pages |
| Authors:
Serge Przedborski; COLUMBIA UNIV NEW YORK
|
 | This proposal represents the authors' continuing efforts to investigate the molecular mechanisms of Parkinson's disease (PD), a progressive neurodegenerative disorder that affects about 1 million people in the United States alone. Recent evidence suggests that inflammation plays a major role in the progressive nature of this disease. Thus, they are investigating the contributions of several pro-inflammatory enzymes that they found up-regulated in microglia following the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP), the ... |
|
| Prostate Cancer Gene Discovery Using ROMA |
DEC 2006 |
7 pages |
| Authors:
William B. Isaacs; JOHNS HOPKINS UNIV BALTIMORE MD
|
 | The authors hypothesize that a subset of men who develop prostate cancer do so as a result of an inherited chromosomal deletion or amplification, affecting the function of one or more critical prostate cancer susceptibility genes. These chromosomal abnormalities, and the affected gene(s) can be identified using the novel technique, ROMA. Together with their collaborators at Cold Spring Harbor, they have now performed ROMA analysis of 90 prostate cancer patients, ... |
|
| Dendritic Cell-Based Genetic Immunotherapy for Ovarian Cancer |
DEC 2006 |
17 pages |
| Authors:
James M. Mathis; LOUISIANA STATE UNIV IN SHREVEPORT HEALTH SCIENCE CENTER
|
 | Adenovirus (Ad)-mediated transduction of dendritic cells (DCs) is inefficient because of the lack of the primary Ad receptor CAR. CD40 is a surface marker expressed by DCs that plays a crucial role in their maturation and subsequent stimulation of T cells. DC infection with Ad targeted to the CD40 results in increased gene transfer. Cells transduced with CD40-targeted Ad5-SV40-TAg vector showed increased expression of transgene and expression of co-stimulatory molecules ... |
|
| Functional Characterization of a Novel Pro-Apoptotic Transcription Regulatory Protein in Ovarian Cancer |
DEC 2006 |
66 pages |
| Authors:
Viji Shridhar; MAYO CLINIC ROCHESTER MN
|
 | In an effort to identify genetic changes involved in ovarian cancer (OvCa) development, we performed differential display-PCR, cDNA microarray and suppression subtraction hybridization analyses (SHH) to identify early genetic alterations associated with OvCa. These studies resulted in identification of several genes differentially expressed in OvCa, including a novel gene encoding a transcription elongation-like protein with the ability to induce apoptosis and suppress cancer cell growth. We named the protein ProApoptotic ... |
|
| Generation of Constructs for DNA-Directed RNA Interference of Venezuelan Equine Encephalitis Virus Genes |
DEC 2006 |
|
| Authors:
H. S. Bhogal; S. J. Jager; L. J. McLaws; DEFENCE RESEARCH AND DEVELOPMENT SUFFIELD (ALBERTA)
|
 | Venezuelan equine encephalitis (VEE) virus is an important human and veterinary pathogen with n6 effective treatment or prophiaxis. One strategy that has shown promise as an anti viral is a mechanism of gene silencing known as RNA interference. Although conventional RNA interference involves the use of dsRNA molecules, here we describe the generation of a panel of DNA cassettes which encode sIRNA sequences. Three different VEE virus genes encoding E2 ... |
|
| Gene Knockdown of Venezuelan Equine Encephalitis Virus E2 Glycoprotein Using DNA-Directed RNA Interference |
DEC 2006 |
|
| Authors:
H. S. Bhogal; L. J. McLaws; S. J. Jager; DEFENCE RESEARCH AND DEVELOPMENT SUFFIELD (ALBERTA)
|
 | Venezuelan equine encephalitis virus is an important veterinary and human pathogen that also has the potential to be used as a bioterrorist agent. Since there are no approved vaccines or antiviral drugs for this virus, it is prudent that antiviral strategies be developed. RNA interference, an evolutionarily conserved but only recently discovered biological phenomenon, may be an effective gene manipulation tool to combat viruses. The ability of RNA interference to ... |
|
| Unraveling the BvgAS Phosphorelay |
01-Nov-2006 |
|
| Authors:
Sotiria Lampoudi; Robin Hulbert; Peggy Cotter; Linda Petzold; CALIFORNIA UNIV SANTA BARBARA INSTITUTE FOR COLLABORATIVE BIOTECHNOLOGIES
|
 | Bacteria sense and respond to environmental stimuli using pairs of proteins called two-component systems. These are composed of a histidine kinase sensor protein, which autophosphorylates in the presence of the signal being sensed, and a response regulator protein, which is typically involved in binding DNA and controlling gene transcription. The information that a signal is being sensed is relayed from the sensor to the response regulator via a phosphotransfer step. ... |
|
| Amplification of Type II Cadherins in Prostate Cancer |
NOV 2006 |
25 pages |
| Authors:
Teresa L. Johnson-Pais; TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
|
 | Genomic alterations of chromosome 18q have been observed in prostate cancer. This research focuses on analyzing the role of increased gene copy number at chromosome 18q22.1 in prostate cancer. We believe the key genes in this region are the type II cadherins. We are studying the role of overexpression of these genes, particularly cadherin 7 (CDH7), on the tumorigenicand invasive potential of prostate cancer cells. We have shown the minimal ... |
|
| A Morpholino Strategy to Assess TSC Gene Function in Zebrafish |
NOV 2006 |
37 pages |
| Authors:
Scott C. Baraban; CALIFORNIA UNIV SAN FRANCISCO
|
 | Tuberous sclerosis complex (TSC) is a genetic disorder associated with severe neurological symptoms including mental retardation, autism, infantile spasms, and epilepsy. Seizures occur in the majority of TSC patients and are often refractory to antiepileptic drugs. Cortical tubers, the primary neuropathology in these patients, were identified as epileptogenic in several clinical studies. However, the contribution of TSC gene inactivation to altered excitability (in the absence of tuber formation) is not ... |
|
| Identification and Characterization of an X-Linked Familial Prostate Cancer Gene |
NOV 2006 |
8 pages |
| Authors:
Brian Yaspan; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
 | There is a significant heritable component of prostate cancer. Increased familial relative risk is observed across multiple populations (European, Asian-American, African-American and Caucasian). Male first degree relatives of prostate cancer patients have a two- to three-fold increased risk. Segregation analyses support genetic rather than shared environmental risk. Twin cancer concordance studies reveal a higher heritable risk for prostate cancer than for any other common cancer. A Scandinavian study of 44,788 ... |
|
| Selenoproteins and Prostate Cancer |
NOV 2006 |
17 pages |
| Authors:
Veda Diwadkar-Navsariwala; ILLINOIS UNIV AT CHICAGO
|
 | For this postdoctoral fellowship the specific role of selenoproteins (SP) in prostate cancer (PCa) was investigated. First the response of varying allelic identitiesin the SP glutathione peroxidase (GPx-1) to selenium (Se) supplementation was determined. GPx-1 has either a leucine (leu) or proline (pro) amino acid at thei9S codon and cancer risk has been shown to vary depending on the allelic identity. Our investigation showed that the prostate cell line LNCaP ... |
|
| Chemical Genetics of 14-3-3 Regulation and Role in Tumor Development |
NOV 2006 |
17 pages |
| Authors:
Garabet G. Toby; Pamela Silver; DANA-FARBER CANCER INST BOSTON MA
|
 | The 14-3-3 proteins are a family of adaptor proteins that bind to more than 200 protein partners and affect their biological function by altering their stability, catalytic activity and subcellular localization. While the structure or 14-3-3 is well studied and the biology of the 14-3-3 interaction with their partners is understood, the regulation of these proteins remains debatable. Specifically, the mode of export of 14-3-3 proteins from the nucleus is ... |
|
| Generation of Recombinant Human AChE OP-Scavengers with Extended Circulatory Longevity |
NOV 2006 |
144 pages |
| Authors:
Avigdor Shafferman; ISRAEL INST FOR BIOLOGICAL RESEARCH NESS ZIONA
|
 | We demonstrate that chemical conjugation of polyethylene glycol (PEG) moieties to recombinant human acetylcholinesterase (rHuAChE) gives rise to OP bioscavenger species which reside for very long periods of time in the circulation of mice, regardless of their post-translation-modification state, and that circulatory elimination of AChE via specific amino acid-related epitopes can also be efficiently overcome by enzyme PEGylation. Taken together, these findings indicate that the circulatory residence is dictated primarily ... |
|
| TSC2 Happloinsufficiency Leads to a Mutator Phenotype |
NOV 2006 |
8 pages |
| Authors:
John D. Short; M D ANDERSON CANCER CENTER HOUSTON TX
|
 | Tuberous Sclerosis Complex (TSC) patients develop tumors of the brain, kidney, skin and heart upon loss of either the TSC1 or TSC2 gene, and we are interested in elucidating early molecular events that contribute to loss of TSC2 and in understanding how TSC2 heterozygosity might contribute to this process. Our lab uses the Eker rat, which possesses an inactivating retroviral insertion in one Tsc2 allele (Tsc2Ek/+), as a model to ... |
|
| Chromatin Structure and Breast Cancer Radiosensitivity |
01 OCT 2006 |
10 pages |
| Authors:
Tej K. Pandita; WASHINGTON UNIV ST LOUIS MO
|
 | The hMOF protein is a chromatin-modifying factor. Chromatin structure plays a critical role in gene expression. Since hMOF has a chromodomain region as well as acetyl transferase activity, its inactivation can influence modification of chromatin during DNA metabolism. The proposed experiments of this grant proposal will determine functions of hMOF gene. This will be achieved by generating isogenic cells with and without hMOF function. Both in vivo and in vitro ... |
|
| Geneways for Biocomputing |
OCT 2006 |
37 pages |
| Authors:
Andrey Rzhetsky; COLUMBIA UNIV NEW YORK
|
 | The immense growth in the volume of research literature and experimental data in the field of molecular biology calls for efficient automatic methods to capture and store information. In recent years, several groups have worked on specific problems in this area, such as automated selection of articles pertinent to molecular biology, or automated extraction of information using natural-language processing, information visualization, and generation of specialized knowledge bases for molecular biology. ... |
|
| Miniature and Molecularly Specific Optical Screening Technologies for Breast Cancer |
OCT 2006 |
21 pages |
| Authors:
Nimmi Ramanujam; DUKE UNIV DURHAM NC
|
 | The goal of this proposal is to harness the power of light to create "miniature and molecularly specific optical technologies" for breast cancer diagnosis and detection. The miniature technologies will leverage on millimeter scale silicon detectors and LEDs to make compact devices that can be used in a practical clinical setting for breast cancer detection. The features that will be exploited for optical detection/diagnosis of breast cancer will include the ... |
|
| Methods, Knowledge Support, and Experimental Tools for Modeling |
OCT 2006 |
20 pages |
| Authors:
Roger Brent; Larry Lok; MOLECULAR SCIENCES INST BERKELEY CA
|
 | Our goal was to provide software and experimental abilities to support quantitative modeling of eukaryotic systems and thus to help enable new kinds of molecular logic. The most significant accomplishments were the development of two programs. One was a collaborative annotation, MONOD. MONOD embodied a number of genuinely novel ideas, particularly in the data structure, which constituted a middle ground between the highly structured relations of objects in a relational ... |
|
| Modeling, Analysis, Simulation, and Synthesis of Biomolecular Networks |
OCT 2006 |
18 pages |
| Authors:
Harvey Ruben; Vijay Kumar; Oleg Sokolsky; PENNSYLVANIA UNIV PHILADELPHIA
|
 | This project under the DARPA BIOCOMP program integrated fundamental scientific investigations in the field of molecular systems biology, algorithm development for biomolecular modeling, and open source, object based software implementation. Major accomplishments were 1) experimental gene knockout strain investigations of the V.fisheri quorum sensing system that yielded a mathematical model of its regulatory proteins, 2) a model of stringent response in E.coli and M.tuberculosis describing the role of enzyme RelMtb, ... |
|
| Androgen Receptor-Mediated Escape Mechanisms from Androgen Ablation Therapy |
OCT 2006 |
18 pages |
| Authors:
Gerhard A. Coetzee; Judd Rice; Li Jia; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
 | Too many prostate-cancer treatments, especially those relying on the suppression of androgen, eventually fail to slow the advance of the disease. One explanation for this situation is the absence of any systematic knowledge on the role and function of the androgen receptor (AR) in the course of prostate cancer development. Recent findings indicate that the AR is the key master regulator (transcription factor) that determines disease progression to androgen independence, ... |
|
| Sage Gene Expression Profiles Characterizing Cure |
OCT 2006 |
61 pages |
| Authors:
William Hrushesy; Phillip Bulkhaults; Shaojin You; DORN RESEARCH INST INC COLUMBIA SC
|
 | The timing of breast cancer resection within the estrous cycle of the cycling C3H mouse and the menstrual cycle of the premenopausal woman determines to some extent whether the disease is cured in the mouse and the ten-year disease free survival of the woman. Two metaanalyses have demonstrated the positive effect of timing breast cancer resection as near to midcycle (early luteal phase) as possible. A third study has estimated ... |
|
| Genetic Factors in Breast Cancer: Center for Interdisciplinary Biobehavioral Research |
OCT 2006 |
45 pages |
| Authors:
Dana H. Bovbjerg; Christine Ambrosone; Heiddis Valdimarsdottir; Lina Jandorf; Margaret McGovern; Jim Godbold; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
 | The Behavioral Center has three primary Objectives: 1) To support an integrated, interdisciplinary Program of Research consisting of three synergistic Research Projects each of which addresses an important issue in breast cancer genetic research with African American women that entails critical psychological or behavioral issues. Thus, our first purpose is to do outstanding research, with implications for our understanding of the etiology of breast cancer, as well as for our ... |
|
| A New Paradigm for African American Breast Cancer Involving Stem Cell Differentiation in a Novel Cell Culture System |
OCT 2006 |
32 pages |
| Authors:
Jean J. Latimer; PITTSBURGH UNIV MEDICAL CENTER PA
|
 | Our laboratory has published a novel culture system for Human Mammary Epithelial Cells (HMEC), both normal and malignant. This system allows for unusually long-term establishment of normal primary cultures that begin as three-dimensional "mammospheres," which subsequently differentiate into complex organotypic branching ducts and lobules that demonstrate Epithelial Specific Antibody (ESA) staining, lumen, polarized nuclei, desmosomes along the lateral surfaces of the cells, and microvilli on the apical surfaces. We hypothesize ... |
|
| Mechanisms Down-Regulating Sprouty1, a Growth Inhibitor in Prostate Cancer |
OCT 2006 |
62 pages |
| Authors:
Bernard Kwabi-Addo; BAYLOR COLL OF MEDICINE HOUSTON TX
|
 | The Sprouty gene family negatively regulates growth factor-induced receptor tyrosine kinase signaling with a potential tumor suppressor function in cancer. I have demonstrated that Sprouty1 is down-regulated in human prostate cancer (PCa). The purpose of the present study is to characterize the molecular mechanisms regulating Sprouty1 expression in the human PCa. Results. I have carried out deletion analysis coupled with reporter gene assays to characterize Sprouty1 promoter activity. Electrophoretic mobility ... |
|
| Regulation of AR and (beta)-Catenin Signaling by Pin 1 in Prostate Cancer |
OCT 2006 |
20 pages |
| Authors:
Shaoyong Chen; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
 | One part of the Final report was included in the attached Manuscript, demonstrating a positive role of Pin1 in PCa progression. The mechanisms include that Pin1 can enhance beta-catenin nuclear localization, TCF/beta-catenin dependent Topflash activity, and c-Myc and Cyclin D1 expression, and disrupt AR-mediated suppression of TCF/beta-catenin signaling. We provided additional data suggesting Pin1 reduces AR transcriptional activity and PSA expression, mediated by repression of the N-C interaction. We also ... |
|
| Tumor Suppression by BRCA-1: A Critical Role at DNA Replication Forks |
OCT 2006 |
7 pages |
| Authors:
Jean Gautier; COLUMBIA UNIV NEW YORK
|
 | BRCA1 is the major breast cancer susceptibility gene. It forms heterodimers with BARD1. Inactivation of either gene results in identical phenotypes suggesting that these proteins function primarily as a complex. BRCA1 deficiencies are associated with cellular phenotypes consistent with a DNA replication defect. We wished to test the hypothesis that BRCA1/BARD1 function during DNA replication supporting DNA transactions at replication forks. We are using cell-free extracts derived from Xenopus laevis ... |
|