| Positional Cloning of an Ashkenzai Jewish Hereditary Prostate Cancer |
JAN 2006 |
25 pages |
| Authors:
Danielle Friedrichsen; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
 | The fellowship aimed to confirm the 7q11-21 linkage result, to identify the founder haplotype and to clone the disease- associated mutation. The final research accomplished has: 1) confirmed the 7q11-21 linkage result by analysis of additional microsatellite markers in the 37.6 cM region and a combined genome-wide scan of 36 Jewish HPC families (empirical P=O.006); 2) defined the minimal recombination region for the 18 PROGRESS Jewish families as a 5.7 ... |
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| Formulated Delivery of Enzyme/Prodrug and Cytokine Gene Therapy to Promote Immune Reduction of Treated and Remote Tumors in Mouse Models of Prostate Cancer |
JAN 2006 |
99 pages |
| Authors:
Pamela J. Russell; Aparajita Khatri; Yasmin Husaini; Jane Chapman; NEW SOUTH WALES UNIV SYDNEY (AUSTRALIA)
|
| Prostate cancer is the second highest cause of cancer death in men in Western society. Early disease is treatable by surgery or radiation, but once late stage disease becomes refractory to hormone removal, patient care is limited to pain management. New treatments are needed. We use gene therapy, alone and in combination with hormones called cytokines that stimulate the immune system. The concept is that delivering a cell-killing agent to ... |
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| A Novel Mechanism of Androgen Receptor Action |
JAN 2006 |
8 pages |
| Authors:
Jr Roberts Charles T.; OREGON HEALTH AND SCIENCE UNIV PORTLAND
|
| This project had as its original goal the elucidation of a novel mode of action of the androgen receptor that may be of importance in the initiation and progression of prostate cancer. Specifically, the authors had determined that the androgen receptor controls the expression of the cell-surface receptor for the hormone IGF-1 at the level of translation of the IGF-1 receptor mRNA in an androgen-independent fashion. In the course of ... |
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| Mechanism of Ovarian Epithelial Tumor Predisposition in Individuals Carrying Germline BRCA1 Mutations |
JAN 2006 |
25 pages |
| Authors:
Louis Dubeau; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Women with germline mutations in BRCA1 are strongly predisposed to cancers of the ovary and fallopian tubes. Given the strong link between menstrual activity and risk of ovarian cancer in the general population, we hypothesized that BRCA1 might predispose to ovarian cancer indirectly, by influencing ovarian granulosa cells, which play an important role in controlling menstrual cycle progression. We used the Cre-lox system to inactivate the mouse Brca1 gene in ... |
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| Assessment of the Genetic Variation in Bone Fracture Healing |
JAN 2006 |
84 pages |
| Authors:
Louis C. Gerstenfeld; TRUSTEES OF BOSTON UNIV MA
|
| The hypothesis of these studies is that genetic processes that lead to the variations in both structural and material properties of bone development will be recapitulated in the developmental mechanisms that control the bone quality during fracture healing. Two goals were set out in this proposal to test this hypothesis. the First was to determine how variations in basic bone quality in the three in bred strains of mice were ... |
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| Combinatorial Genetic Regulatory Network Analysis Tools for High Throughput Transcriptomic Data |
2006 |
18 pages |
| Authors:
Elissa J. Chesler; Michael A. Langston; OAK RIDGE NATIONAL LAB TN LIFE SCIENCES DIV
|
| Abstract: A series of genome-scale algorithms and high-performance implementations is described and shown to be useful in the genetic analysis of gene transcription. With them it is possible to address common questions such as: are the sets of genes coexpressed under one type of conditions the same as those sets co-expressed under another? A new noise-adaptive graph algorithm, dubbed paraclique, is introduced and analyzed for use in biological hypotheses testing. ... |
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| Molecular Analysis of the Caries Biofilm in Young Permanent Teeth |
2006 |
36 pages |
| Authors:
Stephen R. Gasparovich; OHIO STATE UNIV COLUMBUS
|
| Dental caries is the most common infectious disease in childhood. Only a small percentage of children will go through adolescence and not develop caries, and the disease typically is concentrated in children from poor socioeconomic backgrounds with limited access to routine dental care. 16S DNA based bacterial sequencing technology is beginning to make it possible to more accurately identify the pathogens responsible. Most of the previous research has only focused ... |
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| Stochastic Analysis of Gene Regulatory Networks using Finite State Projections and Singular Perturbation |
2006 |
8 pages |
| Authors:
Brian Munsky; Slaven Peles; Mustafa Khammash; CALIFORNIA UNIV SANTA BARBARA DEPT OF MECHANICAL ENGINEERING
|
| Considerable recent experimental evidence suggests that significant stochastic fluctuations are present in gene regulatory networks. The investigation of stochastic properties in genetic systems involves the formulation of a mathematical representation of molecular noise and devising efficient computational algorithms for computing the relevant statistics of the modeled processes. However, the complexity of gene regulatory networks poses serious computational difficulties and makes any quantitative prediction a difficult task. Monte Carlo based approaches ... |
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| Investigation of the Basis for Persistent Porin Serotypes of Neisseria Gonorrhoeae in Community Infections |
2006 |
84 pages |
| Authors:
Lotisha E. Garvin; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MICROBIOLOGY AND IMMUNOLOGY
|
| Neisseria gonorrhoeae porin (por), a major outer membrane protein, has been studied extensively and is the basis of many gonococcal typing schemes. Epidemiological studies which utilize the porin-based typing method called variable region (VR) typing have shown certain VR types of the porB1A allele occur more frequently. We examine the hypothesis that certain porin types give strains a functional advantage. Alternatively, porin may just be a marker of more fit ... |
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| Poly (ADP-Ribose) Polymerase (PARP) is Essential for Sulfur Mustard-Induced DNA Damage Repair, But Has No Role in DNA Ligase Activation |
2006 |
7 pages |
| Authors:
K. R. Bhat; Betty J. Benton; Radharaman Ray; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD RESEARCH DIVISION
|
| Concurrent activation of poly (ADP-ribose) polymerase (PARP) and DNA ligase was observed in cultured human epidermal keratinocytes (HEK) exposed to the DNA alkylating compound sulfur mustard (SM), suggesting that DNA ligase activation could be due to its modification by PARP. Using HEK, intracellular (3)H-labeled NAD+ ((3)H-adenine) was metabolically generated and then these cells were exposed to SM (1 mM). DNA ligase I isolated from these cells was not (3)H-labeled, indicating ... |
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| Dietary Fat, Fat Metabolizing Genes and Prostate Cancer Risk in African-Americans and Whites |
01-Dec-2005 |
8 pages |
| Authors:
Sue A Ingles; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Dietary fat has been implicated as a potential promotional factor leading to the progression of small, latent, nonmetastatic prostate tumors to invasive, metastatic lesions. One possible mechanism is conversion of the 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 ... |
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| Rapid Identification of Dengue Virus by Reverse Transcription-Polymerase Chain Reaction Using Field-Deployable Instrumentation |
DEC 2005 |
9 pages |
| Authors:
James C. McAvin; Elizabeth M. Escamilla; James A. Blow; Micahel J. Turell; Miguel Quintana; David E. Bowles; James A. Swaby; William J. Barnes; William B. Huff; Kenton L. Lahman; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Dengue virus universal and dengue serotype 1 to 4, fluorogenick probe hydrolysis (Taqman) reverse transcription-polymerase chain reaction assays were developed for screening and seroype identification of infected mosquito vectors and human sera using a field-deployable, fluorometric thermocycler. Dengue universal and dengue 1 to 4 seroype assay in vitro sensitivity and specificity results were 100% concordant when tested with nucleic acid extracts of multiple strains of dengue seroype 1 to 4, ... |
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| Differential Mechanisms of Androgen Resistance |
DEC 2005 |
17 pages |
| Authors:
Orla A. O'Mahony; MICHIGAN UNIV ANN ARBOR
|
| We proposed to study the mechanisms of androgen resistance by focusing on androgen receptor mutations that arise due to the selective pressures of antiandrogen treatment. In vitro we examined the mechanistic actions of bicalutamide and flutamide in transfection studies in a variety of cell lines and on different androgen responsive promoters. We have shown that flutamide exhibits agonist action in a cell specific manner. In vivo we utilized two models ... |
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| Identification of a Protein for Prostate-Specific Infection |
DEC 2005 |
6 pages |
| Authors:
Shen Pang; CALIFORNIA UNIV LOS ANGELES
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| In this proposal, the authors will identify and clone a protein that can be used to generate an infection-specific gene therapy vector. They expect that by using this protein to modify various gene therapy vectors, they can precisely deliver cytotoxic genes into prostate cancer cells using systemic treatment, and eventually eradicate the metastatic prostate cancer cells in patients. During the second year, they continue screening their cDNA library that they ... |
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| The Role of C-FLIP(L) in Regulating Apoptotic Pathways in Prostate Cancer |
DEC 2005 |
7 pages |
| Authors:
Aria Olumi; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Abnormalities in programmed cell death (apoptosis) machinery play a crucial role in the initiation, progression, and metastasis of prostate cancer. Therefore, molecules that initiate pro-apoptotic pathways are excellent therapeutic agents in prostate cancer. However, some prostate cancer cells develop resistance to pro-apoptotic agents. In this proposal, the authors are examining the regulatory mechanisms of c-FLIP(L), which is an important modulator of apoptosis in prostate cancer. |
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| Dendritic Cell-Based Genetic Immunotherapy for Ovarian Cancer |
DEC 2005 |
15 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 costimulatory molecules ... |
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| Genetic Screens in Yeast to Identify BRCA1 Modifiers |
DEC 2005 |
19 pages |
| Authors:
Sharon E. Plon; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Mutations in the BRCA1 checkpoint gene results in aneuploidy and an increased risk of breast cancer. The yeast RAD9 protein has similar functions and sequence motifs as BRCA1 and we proposed to identify haploinsufficient mutations at a second locus that alters the chromosome loss rate of our rad9-/- diploid strains. We created a rad9-delta/delta strain both a qualitative (sectoring colonies) and quantitative assay (canavanine resistance) sensitive enough to detect the ... |
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| HOXC5 as a Biomarker of Disease Presence in Tumor-Associated Normal Prostate |
DEC 2005 |
7 pages |
| Authors:
Steven K. Nordeen; COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
|
| Our preliminary data had suggested that HOXC5 gene expression was increased in prostate tumor and in tumor-associated normal epithelium compared to epithelium from normal prostate, raising hopes that HOXC5 could be a biomarker that could guide whether a patient with a negative biopsy should undergo a rebiopsy. We compared methods for preparation of RNA from formalin-fixed, paraffin embedded tissue and used the best method to prepare RNA from normal prostate ... |
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| Chemical Genetics of 14-3-3 Regulation and Role in Tumor Development |
NOV 2005 |
17 pages |
| Authors:
Garabet G. Toby; DANA-FARBER CANCER INST BOSTON MA
|
| The 14-3-3 proteins are central to cell growth and have been implicated in the regulation of tumor development. While much is known about their mode of function in that they bind to ligands and affect their cellular activity, the regulation of 14-3-3s is not clearly understood. For this we have developed a cell-based assay to screen for modulators of 14-3-3 functions. Specifically we have screened a chemical compound library, and ... |
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| Genetic and Functional Studies of Genes That Regulate DNA-Damage-Induced Cell Death |
NOV 2005 |
29 pages |
| Authors:
Zhou Songyang; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Studies have shown that apoptosis and survival pathways in response to DNA damage play a critical role in breast cancer development and progression. 90% of breast cancer cases are sporadic where mutations of BRCA1/2 have not been detected. Other breast cancer genes must exist. Our group has approached the issue in two ways, a genomic and a proteomic approach. We have established and utilized a novel retrovirus-based genetic screen system ... |
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| New Approaches for Early Detection of Breast Tumor Invasion or Progression |
NOV 2005 |
17 pages |
| Authors:
Yan-Gao Man; AMERICAN REGISTRY OF PATHOLOGY WASHINGTON DC
|
| To assess interactions between epithelial (EP) and myoepithelial (ME) cells in association with breast tumor progression and invasion, a double immunostaining technique with antibodies to smooth muscle actin (SMA) and estrogen receptor (ER) was used to elucidate the ME and EP cells in breast tissues harboring ductal carcinoma in situ (DCIS). Single or clusters of EP cells with a marked diminution or a total loss of the ER expression were ... |
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| Computational Genomics Tools for Copy-Number Fluctuations in Prostate Cancer |
NOV 2005 |
8 pages |
| Authors:
Bhubaneswar Mishra; NEW YORK UNIV NY
|
| The goal of this research was to produce a large, useful, open-access database of lesions in prostate cancer, organized in terms of segments of aberrant copy numbers for subsequent automated statistical analysis. The authors aimed to make this data base easily searched, so that users could find those genes likely to be causally related to the disease. They hoped to maximize the utility of the data base by optimizing the ... |
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| The Role of Siah1-Induced Degradation of Beta-Catenin in Androgen Receptor |
NOV 2005 |
10 pages |
| Authors:
Shu-ichi Matsuzawa; BURNHAM INST LA JOLLA CA
|
| The androgen receptor (AR) signaling-pathway plays crucial roles in the growth and progression of prostate cancer cells. Recent studies indicate that Beta-Catenin physically binds to AR and enhances its transcriptional activity in a ligand-dependent manner. P53 also has been implicated in AR signaling because of its ability to induce expression of Siah1, which binds and activates E3 ligase complexes that degrade Beta-Catenin. In this study, the authors demonstrated the biological ... |
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| Pandora's Box Opened Wide: UAVs Carrying Genetic Weapons |
NOV 2005 |
39 pages |
| Authors:
Daryl J. Hauck; AIR WAR COLL MAXWELL AFB AL CENTER FOR STRATEGY AND TECHNOLOGY
|
| A recent Rand report on chemical and biological weapons (CBW) identifies unmanned aerial vehicles(UAVs) as a feasible CBW delivery means by potential adversaries like North Korea. With significant concern regarding the ability to defend against a delivery vehicle several meters in size, imagine the difficulty in defending against a future scenario involving swarms of micro UAVs (MAVs) carrying genetic weapons with the potential to create powerful and precise political, economical, ... |
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| Undergraduate Training in Mammary Gland Biology and Breast Cancer |
19 OCT 2005 |
40 pages |
| Authors:
Mina J. Bissell; CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
|
| This report describes the second year of the BCRT undergraduate research training program in breast cancer. The program provides undergraduate trainees with exposure to areas of breast cancer research that focus on the role of microenvironment in mammary gland biology and neoplasia development. Trainees benefit from investigating issues at the forefront of breast cancer research: the intersection of hormones, growth factors, and extracellular matrix (ECM) signaling and remodeling during mammary ... |
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| The Nuclear Death Domain Protein p84N5; a Candidate Breast Cancer Susceptibility Gene |
19 OCT 2005 |
26 pages |
| Authors:
Andrew Godwin; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| Besides family history of cancer and an individual's age, no single etiologic factor can identify women at an increased risk for the disease. Approximately 10% of all cases of breast cancer exhibit a familial pattern of incidence. Efforts to identify the genetic basis of familial breast cancer reached fruition some years ago, when the breast cancer susceptibility genes, BRCA1 and BRCA2 were identified. However, recent studies have suggested that mutations ... |
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| Monitoring Cellular Interactions during T Cell Activation at the Single Molecule Level Using Semiconductor Quantum-Dots |
05 OCT 2005 |
8 pages |
| Authors:
Shimon Weiss; Owen Witte; Laurent Bentolila; Fabien Pinaud; James Tsay; Caius Radu; Lili Wang; CALIFORNIA UNIV LOS ANGELES DEPT OF CHEMISTRY AND BIOCHEMISTRY
|
| Enhanced peptide-coated quantum dots (with high brightness and high saturation intensity) were developed. Two high-affinity targeting "velcro-pairs" based on avidin-biotin and fluorescine-antibody interactions were demonstrated and used to specifically target single proteins in membranes of live cells. Single molecule spectroscopy and imaging of individual quantum dot-labeled lipid rafts receptors were performed. Software tools were developed to analyze individual diffusion and trafficking trajectories. These studies provide strong support for the lipid ... |
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| Molecular Characterization and Proposed Taxonomic Placement of the Biosimulant 'BG' |
01 OCT 2005 |
16 pages |
| Authors:
S. A. Burke; J. W. Wright; M. K. Robinson; B. Bronk; R. L. Warren; BATTELLE DUGWAY OPERATIONS DUGWAY UT
|
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| Detoxification of Chemical Warfare Agents by the Plant Cholinergic System |
01 OCT 2005 |
7 pages |
| Authors:
Suman S. Thakur; Gregory E. Garcia; Haim N. Leader; Deborah Moorad-Doctor; Rajendra Gupta; Richard K. Gordon; Bhupendra P. Doctor; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
|
| Plants have cholinesterases (pChEs), anti-ChEs, and activators of ChEs. We have isolated pChE from mung bean sprout. We investigated 300 plants and found that 75% of them contained anti- ChE that inhibited ChEs. Thirty-five percent contained activators of ChEs. An activator of ChE from wheat leaf, Tritiacche-T123 , activates fetal bovine serum AChE, equine BChE, and pChE. This non-oxime natural plant product may offer a new approach to the reactivation ... |
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| Transcriptional Inducers of Acetylcholinesterase Expression as Novel Antidotes for Protection Against Chemical Warfare Agents |
01 OCT 2005 |
19 pages |
| Authors:
Bryan F. Curtin; Lauren M. Tetz; Richard K. Gordon; Bhupendra P. Doctor; Madhusoodana P. Nambiar; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
|
| The biological effects of organophosphorous chemical warfare agents (CWAs) are exerted by inhibition of acetylcholinesterase (AChE), which blocks the hydrolysis of acetylcholine leading to hypercholinergy, seizures, status epilepticus, respiratory/ cardiovascular failure and death. Current investigations show that bio-scavenger therapy, using purified fetal bovine AChE and the more recently tested human BChE, is a promising treatment for protection against CWA exposure. Impediments such as the complex structure of AChEs, posttranslational modifications, ... |
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| Subacute Low Dose Nerve Agent Exposure Causes DNA Fragmentation in Guinea Pig Leukocytes |
01 OCT 2005 |
8 pages |
| Authors:
Jitendra R. Dave; John R. Moffett; Sally M. Anderson; Rebecca A. Price; Rebecca Whipple; Maurice L. Sipos; Anita V. Moran; Suzanne M. DeFord; Frank C. Tortella; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD DIVISION OF NEUROSCIENCE
|
| The objective of present study was to determine levels of DNA fragmentation in blood leukocytes from guinea pigs by 'Comet' assay after exposure to soman at doses ranging from 0.1LD50 to 0.4 LD50, once per day for 10 days. Post-exposure recovery periods were 0, 17 or 110 days. Leukocytes were imaged from each animal, and the images analyzed by computer. Data obtained for exposure to soman demonstrated significant increases in ... |
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| Regulation of AR and (Beta)-Catenin Signaling by Pin 1 in Prostate Cancer |
OCT 2005 |
50 pages |
| Authors:
Shaoyong Chen; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| This mid-term report is a summary of the work accomplished during the past research year. The majority of this work was included in the attached Manuscript. Additional data were also included. Together our data support a positive role of Pin1 in PCa progression. We demonstrated that Pin1 can enhance beta-catenin nuclear localization, TCF/beta-catenin dependent promoter activity, and c-Myc and Cyclin D1 expression, while disrupt AR-mediated suppression of TCF/beta-catenin signaling. We ... |
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| A Novel Membrane-Permeable Breast-Targeting Pro-Apoptotic Peptide for Treatment of Breast Cancer |
OCT 2005 |
5 pages |
| Authors:
Bin Guo; NORTH DAKOTA STATE UNIV FARGO
|
| In this project, the authors are trying to create a novel peptide with three properties: capable of membrane permeability, capable of targeting the breast, and capable of inducing apoptosis. The peptide is expected to be able to induce apoptosis specifically in breast cancer cells. It will be tested as a single therapeutic agent as well as in combination with chemotherapeutic drugs to treat breast cancer. In the first step of ... |
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| Selective Cytotoxic Phospholipids for Prostate Cancer |
OCT 2005 |
24 pages |
| Authors:
Duane D. Miller; TENNESSEE UNIV MEMPHIS
|
| The goal of this project is to build upon our discovery of two phospholipid lead compounds, serine amide phosphate (SAP) and serine diamide phosphate (SDAP), that have been shown to he selective in their cytotoxic actions in PC-3 and DU-145 prostate caner cells respectively. These agents were originally designed as part of a series of compounds to inhibit lysophosphatidic acid (LPA), a phospholid growth factor. After discovering the antiproliferation activity ... |
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| Chromokinesins: Possible Generators of Cancer-Associated Aneuploidy |
OCT 2005 |
16 pages |
| Authors:
David J. Sharp; Daniel W. Buster; ALBERT EINSTEIN COLL OF MEDICINE OF (YESHIVA UNIV) BRONX NY
|
| Aneuploidy occurs with high frequency in breast cancer cells, and an aneuploidy increase is positively correlated with the transition from pre-malignant to metastatic cancer. Chromokinesins, a family of chromosome-associated microtubule motors, are potential generators of aneuploidy since they are believed to participate in spindle morphogenesis and chromosome movements during mitosis. Our hypothesis is that inhibition of chromokinesin activity increases the aneuploid frequency in cultured cells. Five different chromokinesins were knocked-down ... |
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| Genetic Analysis of DNA Repair Deficiency in Novel Non-Tumor Adjacent and Tumor Cell Lines Suggests a New Paradigm of Breast Cancer Etiology |
OCT 2005 |
19 pages |
| Authors:
Jean J. Latimer; MAGEE-WOMEN'S HOSPITAL PITTSBURGH PA
|
| We have found that 75% of our NTA primary cultures (n= 42) and cell lines manifest the same deficiency of Nucleotide Excision Repair (NER) as the matching tumor culture. This subpopulation of breast cancers indicates that the loss of NER preceded the final mutations that led to full blown transformation. This hypothesis is in stark contrast to the hypothesis that cancer essentially arises in a vacuum and the NTA tissue ... |
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| Breast Cancer in African American Women: Molecular Analysis of Differences in Incidence and Outcomes |
OCT 2005 |
43 pages |
| Authors:
Agnes A. Day; John Stubbs; Rina Das; Marti Jett; HOWARD UNIV WASHINGTON DC
|
| The DOD funded HBCU/MI Partnership Training award entitled "Breast Cancer in African American Women: Molecular Analysis of Differences in Incidence and Outcomes" continues to provide quality research experiences to faculty and students and has developed into a highly rewarding collaboration that has expanded from the original 2 faculty at HUCC to include 6 experienced faculty and multiple students. At WRAIR, the original 2 has increased to include 3 new researchers ... |
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| Breast Cancer Specific Gene 1 is a Potential Novel Biomarker for Selected Application of Anti-Microtubule Drugs for the Treatment of Breast Cancer Patients |
OCT 2005 |
11 pages |
| Authors:
Jingwen Liu; VETERANS AFFAIRS PALO ALTO HEALTH CARE SYSTEM CA
|
| Anti-microtubule drugs that cause mitotic arrest and subsequent apoptosis of cancer cells are frequently used to treat breast cancer patients with advanced or metastatic diseases. However, patient response rates to this class of chemotherapeutic agents vary significantly. Identification of cellular and genetic factors that are associated with the sensitivity to anti-microtubule drug treatment would be of great clinic implications. Our previous studies have demonstrated that the neuronal protein synuclein-gamma (SNOG), ... |
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| Identification of the Molecular Determinants of Breast Epithelial Cell Polarity |
OCT 2005 |
22 pages |
| Authors:
Masahiko Itoh; CALIFORNIA UNIV BERKELEY
|
| Establishment of polarity is indispensable for normal glandular function. Conversely, loss of tissue polarity and increased growth are hallmarks of tumorigenesis. Many studies indicate that cell-cell and cell-extracellular matrix interactions are involved in regulation of both cell polarity and growth. Tight junctions, which are the most apical components of cell-cell junctional complexes, play critical roles in the establishment of polarity. However, the molecular pathways that integrate these adhesive interactions to ... |
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| Elucidation of the Molecular Mechanisms Underlying Lymph Node Metastasis in Prostate Cancer |
OCT 2005 |
22 pages |
| Authors:
Kaustubh Datta; MAYO CLINIC ROCHESTER MN
|
| Metastatic spread of prostate cancer is the second leading cause of death of men in the United States. Although there are many ways to treat non-metastatic forms of prostate cancer, only androgen-deprivation therapy is available for the later stages of the disease. Again, the cancer will often progress to an androgen-refractory (independent), metastatic stage. Recent reports have suggested that the expression of VEGF-C and its receptor VEGFR-3 are directly correlated ... |
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| Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress |
OCT 2005 |
11 pages |
| Authors:
Dana H. Bovbjerg; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| The purpose of the research supported by this IDEA grant award was to test the possibility that variability in the strength of immune surveillance mechanisms against cancer (operationally defined by assessment of natural killer cell activity, or NKCA) may be a factor in determining the penetrance of mutations in breast cancer susceptibility genes. The following hypotheses were investigated: Hypothesis 1 -- Women with family histories of breast cancer are more ... |
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| Hypoxia as a Driving Force for Genetic Instability During Breast Tumorigenesis |
OCT 2005 |
37 pages |
| Authors:
Robert T. Abraham; BURNHAM INST LA JOLLA CA
|
| The overall hypothesis that drives this project is that persistent replication stress generates mutational events in breast epithelial cells that fuel breast cancer (BCa) progression. Our model predicts that a major source of replicative stress in BCa is hypoxia, which stalls active replication forks, and selects for cells that have bypassed this S-phase checkpoint due to mutations in the ATR-hchkl pathway. The specific aims of this project are: (1) to ... |
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| Sage Gene Expression Profiles Characterizing Cure |
OCT 2005 |
51 pages |
| Authors:
William Hrushesy; Phillip Bulkhaults; Shaojin You; DORN RESEARCH INST INC COLUMBIA SC
|
| The menstrual cycle phase of breast cancer resection affects the frequency of cancer metastatic spread. Tumor metastases are 2-3 fold more frequent when the resection is performed during diestrus as compared to estrus. Tumor angiogenesis is essential for both cancer growth and lethal metastatic cancer spread. The balance between vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) modulates new blood vessel formation and blood vessel permeability. In ... |
|
| SERDP and ESTCP Expert Panel Workshop on Research and Development Needs for the Environmental Remediation Application of Molecular Biological Tools |
Oct-2005 |
65 pages |
| Authors:
Andrea Leeson; Syed Hashsham; Terry Hazan; Wen Tso-Liu; Frank Loeffler; Derek Lovley; Suresh Pillai; Alicia Shepard; Rob Steffan; Rolf Halden; Patrick Haas; Paul Johnson; Perry McCarty; Hans Stroo; Bruce Alleman; Darrell Chandler; James Cole; Elizabeth Edwards; Matthew Fields; Kent Sorenson; DEPUTY DIRECTOR OF DEFENSE RESEARCH AND ENGINEERING ARLINGTON VA STRATEGIC ENVIRONMENTAL RESEARCH AND DEVELOPMENT PROGRAM
|
| SERDP and ESTCP must determine how their limited research, development and demonstration funds can best be invested to improve DoD's ability to effectively address its requirements to remediate contaminated sites. The objectives of this workshop were to (1) examine the current state of the science and technology of molecular biological tools that are applicable to the cleanup of hazardous waste in the field, (2) assess the current operational usage of ... |
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| Molecular Engineering of Vector-Based Oncolytic and Imaging Approaches for Advanced Prostate Cancer |
28 SEP 2005 |
40 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 coupled non-invasive optical imaging to develop metastatic prostate cancer animal models, and vector-based diagnostic and therapeutic approaches. A highly potent and prostate-specific transcriptional regulatory system (TSTA) has been utilized to restrict the expression of our adenoviral vector specifically to prostate or prostate ... |
|
| Inducible Anti-Angiogenic Gene Therapy |
28 SEP 2005 |
14 pages |
| Authors:
Paul J. Higgins; ALBANY MEDICAL COLL NY
|
| Clinical studies indicate that high breast tumor levels of plasminogen activator inhibitor 1 (PAI-1) are associated with an increased metastatic risk, decreased survival, tumor angiogenesis; and overall poor prognosis. Since PAI-1 is required for tumor angiogenesis and inhibition of capillary regression, a targeted genetic approach was used to ablate PAI-1 synthesis in endothelial cells employing antisense PAI-1 and dominant-negative Constructs. Such targeting provided proof of principle that reduced PAI-1 synthesis ... |
|
| Studies of Neurofibromatosis-1 Modifier Genes |
28 SEP 2005 |
33 pages |
| Authors:
Andre Bernards; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| This project aims to collect NF1 patient DNAs required to identify neurofibroma burden modifier genes, to perform an allele association study for three classes of potential modifiers, and to evaluate more global approaches. Over four years we aim to collect 1200 DNAs from adult NF1 patients that represent the top and bottom 20% of dermal neurofibroma burden in various age cohorts. We will use these DNAs in a case-control allele ... |
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| Control of Growth Within Drosophila Peripheral Nerves by Ras and Protein Kinase A |
28 SEP 2005 |
11 pages |
| Authors:
Michael Stern; RICE UNIV HOUSTON TX
|
| The long term goals of this research are to understand the mechanisms by which NFl and its partners control growth using the Drosophila peripheral nerve as our assay system. This system is advantageous because we can apply a number of powerful molecular genetic methodologies that are not available in other systems. This project addresses four specific aspects of growth control, two of which were begun during these first twelve months ... |
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| Isolating of Target Genes for NKX3.1 in Prostate Carcinogenesis |
28 SEP 2005 |
42 pages |
| Authors:
Xuesong Ouyang; UNIVERSITY OF MEDICINE AND DENTISTRY OFNEW JERSEY PISCATAWAY
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| Nkx3.1 is a prostatic-specific tumor suppressor whose loss-of-function represents a critical step in prostate cancer initiation. However, the molecular basis is still largely unknown. We have been utilizing microarray analysis to pursue the gene expression profiling of prostatic lesions in the Nkx3.1 mutant mouse model relative to normal prostate epithelium. Our findings suggest that Nkx3.1 loss-of-function leads to deregulated secretory function of prostate which representing a defect differentiation of prostate ... |
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| Molecular Analysis of Olfactory Neural Circuits |
21 SEP 2005 |
4 pages |
| Authors:
Linda Buck; FRED HUTCHINSON RESEARCH CENTER WASHINGTON DC
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| The olfactory system detects odorants that elicit diverse odor perceptions as well as pheromones that stimulate instinctive behaviors. We previously identified a large family of odorant receptors and determined how signals derived from those receptors are organized in the nose and then the olfactory bulb and cortex. To explore neural circuits in higher brain areas that control olfactory perception and behavior, new technologies are needed. We took the first steps ... |
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Genetic Engineering and Molecular Biology
