| Physico-Chemical Prokaryote Models: Stand-Alone Modules and Karyote Integration |
MAR 2006 |
35 pages |
| Authors:
INDIANA UNIV AT BLOOMINGTON THEORETICAL CHEMISTRY LAB
|
 | At the Center for Cell and Virus Theory (CCVT) several types of systems biology modules were developed for the Bio- SPICE project. The cell modeling modules account for metabolic, proteomic and genomic kinetics and their spatially localized, multiple scale character. Modules for model development, calibration and multiplex (e.g. genome-wide expression) data interpretation are also provided. Models are made available via three complementary mechanisms: 1) the Bio-SPICE system; 2) open source ... |
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| Prevention of the Angiogenic Switch in Human Breast Cancer |
MAR 2006 |
28 pages |
| Authors:
Judah Folkman; CHILDREN'S HOSPITAL MEDICAL CENTER BOSTON MA
|
| The overall goal of this project is to determine if human breast cancer can be prevented from becoming angiogenic when it is still at a microscopic size (i.e., < 1 cubic millimeter). During the past year, from February 2005 to February 2006, the authors cloned three different human breast cancers that undergo the angiogenic switch at predictable times. They found that the angiogenic switch time is modified by host stroma; ... |
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| Nanoprobe Directed Tumor Imaging Using pH Activated Peptides as Contrast Agent Carriers |
MAR 2006 |
13 pages |
| Authors:
John E. Mata; Scout Gustafson; OREGON STATE UNIV CORVALLIS
|
| We characterized a class of modified peptides designed to activate in the extracellular space of tumors in which pH is below 7.0 in cell culture and in tumor bearing mice. These "molecular engines" change shape in a low pH environment, become lipophilic, and embed into the plasma membrane. Our studies suggest that a molecular engine with a pT of 6.8-6.9 will deliver an 8-carboxyfluoroscein ligand to the surface of tumor ... |
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| Role of CYP1B1 in PAH-DNA Adduct Formation and Breast Cancer Risk |
MAR 2006 |
10 pages |
| Authors:
Regine Goth-Goldstein; CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
|
| The cytochrome P450 enzyme CYP1B1 is a major enzyme involved in metabolizing polycyclic aromatic hydrocarbons (PAHs) to reactive intermediates. Given that exposure to carcinogenic PAHs may be a breast cancer risk factor, we have set out to investigate molecular mechanisms of the relationship between PAH exposure, CYP1B1 expression and breast cancer risk in a clinic-based case-control study. We have collected nontumor breast tissue from 43 women (32 cases and 11 ... |
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| Metastic Progression of Breast Cancer by Allelic Loss on Chromosome 18q21 |
MAR 2006 |
9 pages |
| Authors:
Sam Thiagalingam; BOSTON UNIV MA
|
| Genetic and epigenetic inactivation of SMAD4 are rare occurrences in breast tumors despite it is localized to chromosome 18q and serves as a frequent target for inactivation in advanced gastrointestinal cancers. On the other hand, our studies demonstrated that SMAD8 could be an alternate target gene which undergoes epigenetic silencing of gene expression in nearly 30% of breast cancers. These studies provided the first line of evidence for an alternate ... |
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| A Mouse Model to Investigate the Role of DBC2 in Breast Cancer |
MAR 2006 |
8 pages |
| Authors:
Valerie Boka; UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER FORT WORTH TX
|
| Sporadic breast cancer represents 90% of breast cancer patients. Mutations of both oncogenes and tumor suppressor genes often occur in spontaneous breast cancer. Specifically, tumor suppressor gene activity may be abrogated or decreased in cancer cells. Recently, a putative tumor suppressor gene, DBC2 (Deleted in Breast Cancer), was discovered that appears to be frequently mutated in sporadic breast cancer. DBC2 is suspected to be a tumor suppressor gene important for ... |
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| Identification of Novel Tumor Suppressor Genes for Breast Cancer |
MAR 2006 |
43 pages |
| Authors:
Chao Qi; NORTHWESTERN UNIV EVANSTON IL
|
| Chromosomal deletions are very common events in breast cancer. However, no TSGs have been identified from most of recurrent deletions and few identified TSGs do not account for the risk of majority of breast cancer. In additional to the classical TSGs, there are haplo-insufficient TSGs which defy the identification through mutation analysis and may be quite common. By using a new system to generate random chromosomal deletions, we identified a ... |
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| Genetic Epidemiology of Prostate Cancer |
MAR 2006 |
7 pages |
| Authors:
Susan L. Neuhausen; CALIFORNIA UNIV IRVINE
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| Prostate cancer results from complex interactions among genetic, endocrine, and environmental factors. Understanding genetic risk factors that contribute to the occurrence of prostate cancer is crucial to design both preventative and therapeutic strategies and to identify at-risk individuals. This knowledge could reduce the incidence of and death from this disease. The primary objective of this grant is to investigate changes in genes that directly and indirectly regulate levels of male ... |
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| Identification, Characterization, and Clinical Development of the New Generation of Breast Cancer Susceptibility Alleles |
MAR 2006 |
12 pages |
| Authors:
Nazneen Rahman; ROYAL CANCER HOSPITAL LONDON (UNITED KINGDOM) INST OF CANCER RESEARCH
|
| Breast cancer is a common disease in women but the causes are still largely unknown. There is considerable evidence to suggest that genetic factors play an important role in causing breast cancer, but the genes involved in the majority of breast cancers are currently unknown. Our aim is to identify genetic factors that increase the chance of breast cancer occurring. We have collected clinical information and samples from over 1500 ... |
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| Prostate Cancer Aggressiveness Genes in Hereditary Prostate Cancer |
MAR 2006 |
9 pages |
| Authors:
Kathleen A. Cooney; Colin Duckett; MICHIGAN UNIV ANN ARBOR
|
| The EZH2 transcriptional regulator, recently shown by to be overexpressed in prostate cancer specimens that are more likely to recur, maps to 7q35 and represents a candidate gene for inherited prostate cancer susceptibility. This statement is based on the identification of prostate cancer linkage to distal 7q markers in a recently completed genome-wide scan using hereditary prostate cancer families from the University of Michigan Prostate Cancer Genetics Project (PCGP). Relatively ... |
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| Multi-Timescale Complex Adaptation |
MAR 2006 |
72 pages |
| Authors:
James Schwaber; Raj Vadigepalli; Praveen Chakravarthula; THOMAS JEFFERSON UNIV PHILADELPHIA PA
|
| The overall goal of the project was to develop structured approaches to modeling complex gene regulation dynamics underlying cellular adaptation in mammalian systems. This involves integration of two erstwhile disjoint aspects: mathematical modeling and bioinformatics of high-throughput biological data. As part of a structured approach to tackle this problem, we have developed methods and software tools for identification of 1) robust patterns of gene expression using a meta-clustering approach, 2) ... |
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| Large Scale Single Nucleotide Polymorphism Study of PD Susceptibility |
MAR 2006 |
16 pages |
| Authors:
J. W. Langston; PARKINSONS INST SUNNYVALE CA
|
| Although genetic contributions of Parkinson's disease (PD) have gained support from the recent identification of eight genetic loci in the familial PD, the results of intensive investigations of polymorphisms in dozens of genes related to sporadic, late onset, typical PD have not shown consistent results. Recent rapid progress in the investigation of single nucleotide polymorphisms (SNPs) has provided a new tool for this area of research. Millions of SNPs have ... |
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| The Role of the POZ-ZF Transcription Factor Kaiso in Breast Cell Proliferation and Tumorigenesis |
MAR 2006 |
17 pages |
| Authors:
Abena Otchere; MCMASTER UNIV HAMILTON (ONTARIO)
|
| Kaiso is a new member of the POZ-ZF transcription factor family, which was first identified as a binding partner for the cell adhesion co-factor p120ctn. Preliminary work from our lab indicated that Kaiso is misexpressed in ~40% of human breast tumors and identified cyclin D1 as a putative Kaiso target gene. The purpose of this project is to elucidate the mechanisms by which Kaiso's transcriptional regulation of cyclin D1 affects ... |
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| The Role of TSC1 in the Formation and Maintenance of Excitatory Synapses |
MAR 2006 |
18 pages |
| Authors:
Bernardo L. Sabatini; HARVARD UNIV BOSTON MA
|
| Tuberous Sclerosis (TSC) is an autosomal dominant genetic disorder characterized by benign tumors of many organs. The majority of TSC patients are identified as children and most have neurological symptoms including mental retardation and epilepsy. Although it is known that TSC results from mutations in either the TSC1 or TSC2 genes, the pathogenesis of the neurological disorder is unclear. One possibility, inspired by gross pathological findings, is that the presence ... |
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| Roles of Breast Cancer Susceptibility Genes BRCA's in Mammary Epithelial Cell Differentiation |
MAR 2006 |
67 pages |
| Authors:
Saori Furuta; CALIFORNIA UNIV IRVINE
|
| We examined if BRCA1 is involved in MEC differentiation and how its dysfunction pertains to breast tumor pathogenesis. We demonstrated that BRCA1 mediates acinar differentiation of MEC using 3-D culture. Reduction of BRCA1 by RNAi impairs acinus formation but enhances proliferation. Such aberrations can be rescued by expression of wild-type BRCA1 as well as a mutant in the central domain but not in the C-terminal BRCT domain, suggesting that the ... |
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| In-Vivo Characterization of Mammalian Polarity Genes as Novel Tumor Suppressors Involved in Breast Cancer Development and Progression in a Mouse Model |
MAR 2006 |
8 pages |
| Authors:
Avi Z. Rosenberg; COLD SPRING HARBOR LAB NY
|
| The purpose of our study is to understand the role of novel polarity regulators mammary gland development and their ability to cooperate with oncogenes in tumorogenesis within this gland. We are using mouse systems as well as an analysis of cell lines to understand the role of a particular gene, Scribble, in this process. So far, I have been able to identify one human breast cancer cell line with little ... |
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| Derivation of Targeted Phage Vectors for Gene Therapy of Prostate Cancer |
MAR 2006 |
13 pages |
| Authors:
Victor Krasnykh; M D ANDERSON CANCER CENTER HOUSTON TX
|
| The subject of these studies is the development of targeted vector for selective infection and killing of prostate cancer cells. The resultant vector is to be administered to prostate cancer patients to find, infect and destroy tumor cells. Targeting of the vector to prostate tumors is to be accomplished via incorporation into its capsid of ligands, which selectively bind to prostate specific membrane antigen (PSMA). Research accomplishments: (i) two targets, ... |
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| Transcriptional Regulation by KLF6, A Novel Tumor Suppressor Gene in Prostate Cancer, Through Interaction with HATS and HDACS |
MAR 2006 |
79 pages |
| Authors:
Scott L. Friedman; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| KLF6 is a zinc finger transcription factor mutated in more than 50% of sporadic prostate cancers. Our studies have explored the role of acetylation of KLF6 and how its abrogation by mutation in human cancer may contribute to its dysregulation and emergence of prostate cancer. The KLF6 tumor suppressor protein normally inhibits cell growth by upregulating p21 (WAF1/CIP1) independent of p53 whereas most tumor derived mutations are no longer growth ... |
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| Role of Rad23 and Dsk2 in Nucleotide Excision Repair and Spindle Pole Body Duplication |
MAR 2006 |
17 pages |
| Authors:
Laura Diaz-Martinez; MINNESOTA UNIV MINNEAPOLIS
|
| The three yeast UBL-UBA proteins, Rad23, Ddi1 and Dsk2 bind both ubiquitin and the proteasome. They are not essential for viability and some redundancy in terms of stabilization of ubiquitinated substrates has been shown, suggesting that they may have overlapping functions. Here we showed that Rad23 is indeed redundant with both Ddi1 and Dsk2 for cell cycle related roles. Surprisingly, Ddi1 and Dsk2 do not show any redundancy but the ... |
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| Novel Gbeta Mimic Kelch Proteins Gpb1 and Gpb2 Connect G-Protein Signaling to Ras via Yeast Neurofibromin Homologs Ira 1 and Ira 2: A Model for Human NF1 |
MAR 2006 |
115 pages |
| Authors:
Joseph Heitman; DUKE UNIV DURHAM NC
|
| The Neurofibromatosis type 1 (NF1) gene encodes a large tumor suppressor protein, neurofibromin, which is a Ras GTPase-activating protein (RasGAP) activity. Although the NF1 gene was identified over a decade ago, the biological roles of neurofibromin in cellular processes remain unclear. Therefore it is crucial for therapy and developing new drugs for NF1 patients to elucidate how the RasGAP activity of neurofibromin is controlled. To achieve this goal, it is ... |
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| Ultrasensitive, Ultradense Nanoelectronic Biosensing with Nanoparticle Probes |
13 FEB 2006 |
18 pages |
| Authors:
Chad A. Mirkin; Mark Ratner; NORTHWESTERN UNIV EVANSTON IL DEPT OF CHEMISTRY
|
| A robust and effective model for determining the presence or absence of an analyte in a DPN-assembled gold nanoparticle/DNA conjugate structure in the limit of single molecule binding was developed. The capacitance picture of semi-classical mesoscopic transport provides both greater sensitivity and greater reproducibility than focusing on the charge transport within the DNA. Effectively, the capacitance model works well in the coulomb blockade limit that is relevant for such sensing ... |
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| Programme DNA Lattices: Design, Synthesis and Applications |
FEB 2006 |
74 pages |
| Authors:
John Reif; DUKE UNIV DURHAM NC OFFICE OF RESEARCH SUPPORT
|
| Programmable methods for construction of complex structured objects on the 10-100 nm scale. Self-assembled DNA nanostructures provide a methodology for bottom-up nanoscale construction of highly patterned systems, utilizing macromolecular DNA tiles" composed of branched DNA, self-assembled into periodic and aperiodic lattices. This methodology is programmable by choice of the set of DNA tiles, and can form any computable 2D or 3D pattern. Work was done by three leading research groups ... |
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| Role of Reactive Stroma in Prostate Cancer Progression |
FEB 2006 |
21 pages |
| Authors:
David R. Rowley; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| The purpose of this project is to determine the role of fibroblast growth factor (FGF) receptor 1 in reactive stroma during prostate tumorigenesis. The authors are using a novel approach to target transgene expression specifically to the reactive stroma of experimental prostate cancer. They are placing an inducible Cre recombinase (CrePR1) into the fibroblast activation protein (FAP) gene locus to target expression to reactive stroma. They will cross this mouse ... |
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| Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast |
FEB 2006 |
9 pages |
| Authors:
Jeffrey K. Griffith; NEW MEXICO UNIV ALBUQUERQUE
|
| The investigators employed an innovative, quantitative assay for telomere DNA content (TC) that was developed and characterized by the Principal Investigator to test the hypothesis that TC can be used to predict the likelihood of disease progression in women with Ductal Carcinoma in Situ (DCIS). The first step in this investigation was to determine whether TC measured in bulk DCIS tumor tissue is comparable to that measured in tumor epithelial ... |
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| Mechanisms and Chemoprevention of Ovarian Carcinogenesis |
FEB 2006 |
12 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 deadly 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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| Modeling Human Epithelial Ovarian Cancer in Mice by Alteration of Expression of the Expression of the BRCA1 and/p53 Genes |
FEB 2006 |
9 pages |
| Authors:
Denise C. 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 1 (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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| Functional Characterization of Two Novel Human Prostate Cancer Metastasis Related Genes |
FEB 2006 |
12 pages |
| Authors:
Asim B. Abdel-Mageed; Krishna C. Agrawal; Jr Crawford Byron; TULANE UNIV NEW ORLEANS LA
|
| We propose to identify the functional characterization of two novel cancer-specific, metastasis-related genes whose constitutive expression may be pivotal for prostate cancer progression. Work accomplished in the first year was performed based on the proposed statement of work. We have characterized the full-length cDNAs of the Seq1 and Seq2 genes using at least three 5 and 3 rapid amplification of cDNA ends (RACE) commercial kits (Invitrogen Carlsbad, CA, BD Bioscience ... |
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| BTG2 Antiproliferative Gene and Prostate Cancer |
FEB 2006 |
9 pages |
| Authors:
Paul D. Walden; NEW YORK UNIV SCHOOL OF MEDICINE NY
|
| Expression of the protein product of the BTG2 tumor suppressor is lost during the transition of normal prostate epithelial cells into prostate cancer cells. Restoration of BTG2 expression in BTG2 null prostate cancer cells significantly reduces cell proliferation and tumorigenicity. Steady state levels of BTG2 protein are regulated post-translationally in p53 positive prostate cells. Our working hypothesis being tested as part of our proposed studies is that the tumor suppressive ... |
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| Sonic Hedgehog Signaling Promotes Tumor Growth |
FEB 2006 |
61 pages |
| Authors:
Wade Bushman; WISCONSIN UNIV-MADISON
|
| We have shown that the Sonic hedgehog (Shh) signaling pathway is absolutely required for normal prostate development and our studies performed with the support of the DOD New Investigator award indicate that Shh signaling promotes tumor growth. This proposal addresses the hypothesis that Sonic hedgehog signaling promotes tumor growth by activating stromal cell gene expression. To address this hypothesis, we have developed the DLPlacZ-LNCaP xenograft, a model that provides us ... |
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| Control of Growth Within Drosophila Peripheral Nerves by Ras and Protein Kinase A |
FEB 2006 |
11 pages |
| Authors:
Michael Stern; RICE UNIV HOUSTON TX
|
| The long term goals of this research are to understand the mechanisms by which NF1 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 the first twelve months ... |
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| The Role of the Y-Located TSPY Gene in Prostatic Oncogenesis |
FEB 2006 |
74 pages |
| Authors:
Yun-Fai C. Lau; NORTHERN CALIFORNIA INST FOR RESEARCH AND EDUCATION SAN FRANCISCO
|
| The TSPY gene is the only functional gene within the critical region harboring the gonadoblastoma locus on the Y chromosome (GBY). Expression studies demonstrated that it is aberrantly expressed in prostate cancer. This project is designed to address the role of this putative oncogene on the Y chromosome in this male-specific cancer. The objectives are: 1) to identify the oncogenic or tumor promoting domain in TSPY, and 2)to correlate TSPY ... |
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| Development of Novel Bifunctional Compounds that Induce Apoptosis in Prostate Cancer Cells |
FEB 2006 |
|
| Authors:
John M. Essigmann; MASSACHUSETTS INST OF TECH CAMBRIDGE
|
 | We have designed and synthesized a novel compound (I ip) that efficiently triggers apoptosis in prostate cancer cells such as LNCaP. This bifunctional compound was designed to form DNA adducts that are camouflaged by the androgen receptor making them less readily repaired in AR+ prostate cancer cells. The aims of our studies are to investigate the mechanisms by which lip is able to trigger apoptosis in target cells. One approach ... |
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| The Role of the Neurofibromin-Syndecan-CASK Complex in the Regulation of Synaptic Ras-MAPK Signaling and Dendritic Spine Plasticity |
FEB 2006 |
10 pages |
| Authors:
Gang-Yi Wu; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| 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 objective of this proposal is to test the hypothesis that the newly identified NF1-Syndecan2-CASK signaling complex plays an essential role in the regulation of synaptic Ras-MAPK activity and dendritic spine maturation. Using ... |
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| ATM Heterozygosity and the Development of Radiation-Induced Erectile Dysfunction and Urinary Morbidity Following Radiotherapy for Prostate Cancer |
FEB 2006 |
40 pages |
| Authors:
Jamie A. Cesaretti; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| The goal of this training grant project is to determine whether the prevalence of ATM carriers among prostate cancer patients treated with radiotherapy that develop erectile dysfunction and urinary morbidity is greater than the prevalence of ATM heterozygosity among patients that do not develop this complication. Regardless of the scientific outcome of the proposal the PI will be left with a vast experience in translational research from which to form ... |
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| GKLF as a Novel Target in Selenium Chemoprevention of Prostate-Cancer |
FEB 2006 |
18 pages |
| Authors:
Yan Dong; HEALTH RESEARCH INC BUFFALO NY
|
| The present study investigated the functional significance of the zinc finger transcription factor gut-enriched kr ppel-like factor (GKLF) in mediating selenium action in the androgen receptor (AR)-null PC-3 human prostate cancer cells. We found that over-expression of GKLF enhances selenium inhibition of DNA synthesis and induction of apoptosis. Furthermore, knocking down the expression of GKLF greatly attenuates the growth suppressive and apoptosis inducing activities of selenium. Therefore, our data support ... |
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| Vasculature-Specific Adenovirus Vectors for Gene Therapy of Prostate Cancer |
FEB 2006 |
12 pages |
| Authors:
Victor Krasnykh; M D ANDERSON CANCER CENTER HOUSTON TX
|
| In Year 2 of the project we have completed Task 2 (as per approved Statement of Work) by characterizing the binding specificity of the Ad fiber proteins designed to bind IL-11Ralpha. In Task 3 of the project we identified the most promising fiber ligand constructs and designed Ad genomes that incorporate the genes for these proteins in addition to the reporter expressing gene cassettes. |
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| Molecular Engineering of Vector-Based Oncolytic and Imaging Approaches for Advanced Prostate Cancer |
FEB 2006 |
26 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 ... |
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| Inhibition of Androgen-Independent Growth of Prostate Cancer by siRNA-Mediated Androgen Receptor Gene Silencing |
FEB 2006 |
52 pages |
| Authors:
Benyi Li; KANSAS UNIV MEDICAL CENTER KANSAS CITY
|
| In current period, We first used a signal intra-tumoral injection of different amount of AAV particles to define a proper dosage for efficient virus distribution and knockdown of AR expression. The defined dose was 5.0 x 10^6 AAV particles per 100 mm^3 of tumor volume. Next, we used this dose to treat prostate cancer xenografts. We found that intra-tumoral injection of the ARHP8 but not GFP AAVs abolished tumor growth ... |
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| Mutagen Sensitivity, Apoptosis, and Polymorphism in DNA Repair as Measures of Prostate Cancer Risk |
FEB 2006 |
150 pages |
| Authors:
Radoslav Goldman; GEORGETOWN UNIV WASHINGTON DC
|
| Prostate cancer is the most common lethal tumor among US males but etiology of the disease remains unknown. We hypothesize that low DNA repair contributes to increased risk of having prostate cancer. To evaluate the hypothesis, we conducted a case-control study of prostate cancer evaluating association of mutagen sensitivity phenotype with cancer risk. We established a repository of fully annotated specimen of 63 prostate cancer cases and 109 controls frequency ... |
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| Temporal and Spatial Dynamics of DNA Topoisomerase I in Prostate Cancer |
01 JAN 2006 |
11 pages |
| Authors:
Randy M. Wadkins; MISSISSIPPI UNIV UNIVERSITY
|
| The purpose of this proposal was to investigate the response of prostate cancer to a series of camptothecin analogs, which are drugs that target DNA topoisomerase I. This final report summarizes the accomplishments toward the tasks outlined in the original proposal for this grant. The goal of the project was to try to understand why, despite the availability of topoisomerase I in prostate cancer, chemotherapeutic agents that target this enzyme ... |
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| C-met Induction in the Hippocampus of NF1-Null Mice |
01 JAN 2006 |
6 pages |
| Authors:
Larry S. Sherman; OREGON HEALTH SCIENCES UNIV PORTLAND
|
| Children and mice with one defective NF1 allele have learning disabilities linked to hippocampal deficits. Compared to wild-type mice, expression of the c-met receptor tyrosine kinase is elevated in the hippocampus of mice with astrocyte-targeted disruption of the Nf1 gene. Hippocampal neurons from these mutant mice still express neurofibromin, arguing that increased c-met expression is not due to non-specific targeting of neurons. Both c-met and its ligand, hepatocyte growth factor, ... |
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| An Essential Function of the N-Terminus of Ira/Neurofibromin |
01 JAN 2006 |
7 pages |
| Authors:
Vivianne Ding; CALIFORNIA UNIV SAN FRANCISCO
|
| The authors proposed to study a potentially new function of the yeast homolog of neurofibromin, Ira1. It is suggested from the literature that a complete deletion of Ira1 is lethal to yeast, while previous partial deletions of the same gene is viable. These seemingly conflicting results point to a possible essential function of the N-terminus of Ira1. However, the authors found that in their hands, a complete deletion of Ira1 ... |
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| Preconceptional Paternal Exposure to Embedded Depleted Uranium Fragments: Transmission of Genetic Damage to Offspring |
01 JAN 2006 |
26 pages |
| Authors:
Alexandra C. Miller; HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLE MD
|
| The Persian Gulf War resulted in friendly fire casualties among U.S. personnel injured by fragments of depleted uranium (DU) munitions. The demonstrated effectiveness of such weapons makes it likely that they may be used against U.S. forces in future conflicts. Uncertainty about how aggressively to remove fragments of the radioactive, chemically toxic DU has stimulated research into the long-term health consequences of embedded DU fragments. There has been no previous ... |
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| Generation of in Vitro Cellular Models of Lymphangioleiomyomatosis for the Development of Tuberous Sclerosis Therapeutics |
01 JAN 2006 |
11 pages |
| Authors:
Rachel Squillace; ROTHBERG INST FOR CHILDHOOD DISEASES GUILFORD CT
|
| The purposes of this work are three related objectives: to generate human TSC2-/- LAM cell lines; to generate matching inducible isogenic TSC2 knock-in cell lines; and to confirm the absence and rescue of TSC signaling in these LAM lines. We generated 400 immortalized LAM cell lines from two different LAM tissue sources and used immunoblot analysis to determine the loss of the TSC2 protein itself, or function as indicate by ... |
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| A Role for TACI in Prostate Neoplasia |
01-Jan-2006 |
5 pages |
| Authors:
Von; Gotz-Ulrich Bulow; INDIANA UNIV AT INDIANAPOLIS SCHOOL OF MEDICINE
|
| This research study proposed that TNF-family growth factors, BAFF and APRIL, play a role in prostate cancer. The investigators' hypothesis proposed that APRIL provides a proliferative signal to normal prostate epithelial cells by means of an unknown receptor. They postulated that TACI is an antagonist receptor that functions to regulate APRIL-mediated proliferation of cells by inducing apoptosis and thereby maintaining the normal glandular structure. The loss of TACI expression in ... |
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| Hyaluronic Acid and Hyaluronidase in Prostate Cancer: Evaluation of Their Therapeutic and Prognostic Potential |
JAN 2006 |
112 pages |
| Authors:
Vinata B. Lokeshwar; MIAMI UNIV FL
|
| Identification of accurate prognostic indicators could aid in individualization of treatment and better prediction of outcome or prostate cancer patients. Treatment modalities that target these molecules could effectively control CaP progression. The results of this project identify HYAL1 type hyaluronidase (HAase) as one such molecule. HA is a glycosaminoglycan and HAase is an enzyme that degrades HA into angiogenic fragments. Immunohistochemical analysis using archival radical prostatectomy CaP specimens from patients ... |
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| Prostate Expression Databases: Gene Expression Resources for Comparative Studies of Prostate Carcinogenesis |
JAN 2006 |
7 pages |
| Authors:
Peter S. Nelson; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| This proposal aims to test the hypothesis that integrating observations derived from mouse model systems with observations from human prostate cancers will define relevant and consistent molecular alterations critical to the development and progression of prostate carcinoma. The research accomplished to date has: 1) assembled the requisite mouse models to enable the generation of tumor gene expression data; 2) produced a second-generation mouse prostate microarray that will allow for deeper ... |
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| A Bioengineered Gene Therapy System with Potential to Heal War Wounds |
JAN 2006 |
48 pages |
| Authors:
John W. Harmon; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
|
| Wound healing is a controlled coordinated response to tissue injury leading to scar tissue formation. It involves complex interactions between cell types, matrix and soluble mediators. When one or more of these components is disrupted, wound healing is delayed or even halted. There has been some success with topical application of growth factors to improve healing in the face of sepsis and infection. However the effects have been modest. A ... |
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| Restoration of Wild-Type Activity to Mutant p53 in Prostate Cancer: A Novel Therapeutic Approach |
JAN 2006 |
8 pages |
| Authors:
James Manfredi; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| A summary is presented of research performed during the first year of a project to determine feasibility of approaches to restore wild-type transcriptional activity on mutant p53 proteins found in human prostate tumors. p53 mutant proteins that are specifically relevant to prostate cancer are being examined to determine whether they are suitable targets for such an approach. Three specific aims are being pursued. The first is characterizing the interaction of ... |
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| An Analysis of Rho-PKN Signaling in Prostate Cancer Using Drosophila Genetics |
JAN 2006 |
17 pages |
| Authors:
Martha E. Betson; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| The Rho effector protein kinase N (PKN) has been implicated in prostate cancer. To study the role of PKN andclosely related PRK2 in prostate cancer progression, lentiviral small hairpin RNA constructs have been obtained andwhich knock down expression of PKN and PRK2 in human cells. The constructs will be introduced into prostatecancer cells to study the role of PKN and PRK2 in cellular processes related to tumorigenesis. To identify novelcomponents ... |
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Genetic Engineering and Molecular Biology
