| The Role of the Y-Located TSPY Gene in Prostatic Oncogenesis |
21 SEP 2005 |
33 pages |
| Authors:
Yun-Fai C. Lau; NORTHERN CALIFORNIA INST FOR RESEARCH AND EDUCATION SAN FRANCISCO
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 | 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: l) to identify the oncogenic or tumor promoting domain in TSPY, and 2) to correlate ... |
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| Role of Mitochondrial DNA Mutations in Cellular Vulnerability to Mitochondria-Specific Environmental Toxins |
14 SEP 2005 |
17 pages |
| Authors:
Etienne C. Hirsch; INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) PARIS (FRANCE)
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| In recent years, growing evidence has shown that mutations of mitochondrial DNA (mtDNA) are an important cause of mitochondrial disorders in humans, and have been associated with common neurodegenerative disorders, aging and cancers. In line with this, it has been proposed that those mutations could genetically predispose an individual to some environmental factors thereby initiating the disease process. To test such a hypothesis in Parkinson's disease we proposed to: 1) ... |
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| BRCA1 Protein Complexes: Dynamic Changes and Functions Important in Breast Cancer |
14 SEP 2005 |
11 pages |
| Authors:
Andrew A. Horwitz; HARVARD MEDICAL SCHOOL BOSTON MA
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| In the past year, I have made substantial progress towards completion of the tasks outlined in my Statement of Work. I have established a variety of stable cell lines, conducted preliminary purifications, and tested the functions of the BRCA1/BARD1 complex in in vitro assays for ubiquitination and transcription. |
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| Genome-Wide Chromosomal Targets of Oncogenic Transcription Factors |
14 SEP 2005 |
17 pages |
| Authors:
Vishwanath R. Iyer; TEXAS UNIV AT AUSTIN
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| The overall objective of this Idea Award was to develop a novel method for identifying the direct transcriptional targets of oncogenic transcription factors that are important in breast cancer. We have developed STAGE (Sequence Tag Analysis of Genomic Enrichment) as a novel genome-wide method for identifying the chromosomal targets of DNA binding proteins in any sequenced genome. STAGE is based on high-throughput sequencing of concatamerized tags derived from DNA associated ... |
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| Expression Profiling of Cell Lines Expressing Regulated NP2 Transcripts |
14 SEP 2005 |
19 pages |
| Authors:
Stefan M. Pulst; CEDARS-SINAI MEDICAL CENTER LOS ANGELESCA
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| Expression profiling is a powerful novel technique to examine changes in the expression of a large number of genes at the same time. Different phenotypic states of a cell can be translated into specific gene expression signatures. As a complement to yeast two hybrid studies we proposed using gene expression profiling to determine changes in gene expression as a function of expression of the neurofbromatosis-2 (NF2) gene in schwannoma cells. ... |
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| Roles of Osteonectin in Breast Cancer Metastasis to Bone |
14 SEP 2005 |
21 pages |
| Authors:
Dianalee A. Campo; PENNSYLVANIA STATE UNIV UNIVERSITY PARK
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| The focus of this study is to gain insight into the role(s) of osteonectin in the preferential metastasis of breast cancer cells to bone. Osteonectin was isolated from conditioned media of several cell lines including breast cancer (MDA-MB-435, MDA-MB-468), osteoblasts (hFOB1.19), non-neoplastic breast epithelial (hTERT-HME1), and vascular endothelial cells isolated from bone biopsies (HBME-1). Analysis of translational and post-translational properties of osteonectin from these five sources revealed that a unique ... |
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| The Roles of the BLM Helicase in Homologous Recombination and DNA Repair |
14 SEP 2005 |
8 pages |
| Authors:
Wendy L. Bussen; TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
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| In humans, homologous recombination (HR) represents a major pathway for the repair of DNA double strand breaks (DSBs), harmful lesions that can lead to genomic instability, cell death, or tumorigenesis. There is an emerging role in the HR pathway for the RecQ family of helicases. Mutation of the BLM protein, one of five RecQ helicases in humans, causes Bloom's syndrome, a rare autosomal recessive disease in which patients are predisposed ... |
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| Structural Studies of the BRCA1-Associated Human SWI/SNF Complex |
14 SEP 2005 |
12 pages |
| Authors:
Marc A. Holbert; PENNSYLVANIA UNIV PHILADELPHIA WISTAR INST
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| Mutations in the tumor suppressor gene, BRCA1, account for 45% of families with a high incidence of breast cancer and the majority of families with high incidences of both breast and ovarian cancers. Recent data has shown BRCA1 to be associated to be associated with a human SWI/SNF complex, serving to link breast cancer to chromatin remodeling (3). Current evidence points to the idea that BRCA1 works through SWI/SNF; therefore, ... |
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| Combined Biology and Bioinformatics Approaches to Breast Cancer |
14 SEP 2005 |
21 pages |
| Authors:
Zhongxian Lu; CALIFORNIA UNIV IRVINE
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| We identified a novel transcription factor LMO4 and found that LMO4 is highly expressed in breast epithelial cells and is related to cell proliferation and/or invasion in vivo. Because these cellular features are associated with breast carcinogenesis and because LMO4 is overexpressed in more than 50% of breast cancer cases, we hypothesize that LMO4 may play roles in oncogenesis of breast epithelial cells by regulating proliferation, invasion and/or other cellular ... |
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| DNA Damage and Genomic Instability Induced by Inappropriate DNA Re-Replication |
14 SEP 2005 |
37 pages |
| Authors:
Brian M. Green; CALIFORNIA UNIV SAN FRANCISCO
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| Chromosomal rearrangements and changes in copy number at various genomic loci are hallmarks of cancer cells and may be very early steps in tumorigenesis. The origins of genomic insults are poorly understood and this proposal aims to characterize one potential source of genomic instability, inappropriate DNA re-replication. In a normal eukaryotic cell cycle, the chromosomal DNA of a cell is replicated once, and only once, during S phase to ensure ... |
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| Interaction of BRCA1 with the DNA-Dependent Protein Kinase |
01-Sep-2005 |
14 pages |
| Authors:
Sandeep Burma; CALIFORNIA UNIV BERKELEY
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| The DNA-dependent protein kinase (DNA-PK) plays a very important role in the repair of DNA double-strand breaks generated by ionizing radiation (IR). The activation of DNA-PK in response to IR involves multiple autophosphorylations at S/TQ residues of the catalytic subunit, DNA-Pkcs. We find that the activation of DNA-PKcs is attenuated during the S/G2 phases of the cell cycle, phases during which Brca1 is expressed. We found that DNA-Pkcs interacts with ... |
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| Non-Invasive Gene Therapy of Experimental Parkinson's Disease |
SEP 2005 |
18 pages |
| Authors:
William M. Pardridge; CALIFORNIA UNIV LOS ANGELES
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| The present research has developed a non-viral gene targeting technology, whereby the effects of a neurotoxin on the brain can be reversed shortly after the intravenous injection of a therapeutic gene medicine without the use of viral vectors. The brain gene targeting technology developed in this work creates an "artificial virus" which is comprised of non-immunogenic lipids and proteins, wherein the therapeutic gene is packaged in the interior of the ... |
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| Prediction of Breast Cancer Risk by Whole Genome Profiling |
SEP 2005 |
8 pages |
| Authors:
SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
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| The purpose of this Concept Award project was to determine the feasibility of genotyping a population of Ashkenazi Jewish (AJ) breast cancer cases and controls using high density single nucleotide polymorphism (SNP) microarrays, with the eventual goal of testing the hypothesis that most or all of breast cancer cases represent a complex polygenic disease, susceptibility to which can be assessed using high density SNP genetic profiling. Work under this award ... |
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| Discovery of Novel Mammary Developmental and Cancer Genes Using ENU Mutagenesis |
SEP 2005 |
22 pages |
| Authors:
Christopher Ormandy; GARVAN INST OF MEDICAL RESEARCH SYDNEY (AUSTRALIA)
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| This project sought to discover new genes involved in mammary gland carcinogenesis using ENU mutagenesis. The initial approach involved screening ENU mutagenisized mice for mammary tumors. Screening of 1100 mice by mammary whole mount histology identified a number of pedigrees with mammary tumors attributable to ENU-induced recessive mutation. The authors failed in all cases to recapitulate the original phenotype in subsequent rounds of breeding, indicating the influence of environmental mutagenic ... |
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| Breast Cancer in Three Dimensions: Revealing Telomere Dysfunction in Breast Cancer |
SEP 2005 |
10 pages |
| Authors:
William D. Foulkers; Sabine Mai; MONTREAL GENERAL HOSPITAL (QUEBEC) RESEARCH INST
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| Forty three paraffin fixed tissue samples from anonymous hereditary and non-hereditary breast cancer cases were selected for the study. Five mum histological sections were prepared on microscopic slides for processing and analyses. All of the 43 tissue samples (11 nonhereditary; 17 with a BRCA1 mutation; 15 with a BRCA2 mutation) were hybridized and imaged for telomere and centromere. Data recording on telomere organization and distribution are in progress. This work ... |
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| Ovarian Cancer Risk and Survival in BRCA 1/2 Carriers |
SEP 2005 |
37 pages |
| Authors:
Francesmary Modugno; PITTSBURGH UNIV PA
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| Our research efforts to date suggest that both OC use and childbearing are protective in BRCA1/2 carriers and non-carriers. Our findings also suggest that there are unknown genetic and/or environmental factors that alter the risk of ovarian cancer, especially among BRCA1/2 carriers. It is possible that genetic variations in the inflammation pathway may be one such genetic factor and that exposure to inflammation-associated factors may be one such environmental factor. ... |
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| A Novel Functional Screen for New Breast Cancer Genes |
SEP 2005 |
25 pages |
| Authors:
Mary-Claire King; Piri L. Welcsh; SEATTLE UNIV WA
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| Genetic instability is a hallmark of tumor development. Mechanisms for maintenance of genomic stability are heterogeneous and identification of the genes responsible a critical goal of cancer biologists. The very large number of genetic alterations in breast tumors and genetic heterogeneity, even within a single breast tumor, strongly suggests that some mutator mechanism must be involved in breast tumorigenesis. Our hypothesis is that a mutator mechanism contributes to the development ... |
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| Modulation of Anaplastic Lymphoma Kinase Upon Tumor-Stroma Interaction and Its Implications for Tumor Growth and Metastasis in Breast Cancer |
SEP 2005 |
17 pages |
| Authors:
Elly-Gerald Stoica; GEORGETOWN UNIV WASHINGTON DC
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| Induction of neovascularization is needed for a growing tumor as well as for its metastasis. Angiogenic and growth promoting factors like Pleiotrophin (PTN) act on endothelial and epithelial cells and on fibroblasts. We identified the receptor for PTN as anaplastic lymphoma kinase(ALK). In individual tissues the presence of ALK is elevated in tumor stroma (endothelium) while adjacent normal tissue lacked ALK. In cultured endothelial cells or human fibroblasts ALK is ... |
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| Test for Sensitive Detection and Accurate Assignment of TP53 Variants in Tumor DNA |
SEP 2005 |
16 pages |
| Authors:
Cheryl A. Telmer; SPECTRAGENETICS LLC PITTSBURGH PA
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| Accurate, sensitive assessment of the mutational status of tumors enables genotype/phenotype studies and increases the understanding of tumor etiology, progression, recurrence and response to therapy. Preliminary Peptide Mass Signature Genotyping (PMSG) results using bacterial cultures indicated tremendous potential and proof of concept experiments demonstrated that the PMSG process could be converted to an in vitro test. Expansion of proof of concept protocols will provide a mutation detection process suitable for ... |
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| BRCC36, A Novel Subunit of a BRCA1/2 E3 Ubiquitin Ligase Complex: Candidate Breast Cancer Susceptibility Gene |
SEP 2005 |
12 pages |
| Authors:
Andrew K. Godwin; FOX CHASE CANCER CENTER PHILADELPHIA PA
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| liBesides 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 in ... |
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| In Vivo p53 Signaling in Breast Epithelial Cells After Oncogenic Stimulus |
SEP 2005 |
18 pages |
| Authors:
Jamie M. Hearnes; Jennifer Pietenpol; VANDERBILT UNIV MEDICAL CENTER ATLANTA GA
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| One of the most frequent alterations in breast cancer is deregulation of the p53 tumor suppression signaling pathways. The tumor suppressor p53 is a sequence-specific transcription factor that is activated in response to various cellular stresses. It has been predicted that there are over 1500 consensus p53 binding sites present in the human genome. However, only a subset of p53 binding sites and correlated target genes have been identified to ... |
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| Role of the 5HT3 Receptor in Alcohol Drinking and Aggression Using A Transgenic Mouse Model |
SEP 2005 |
37 pages |
| Authors:
Andrea M. Allan; NEW MEXICO UNIV HEALTH SCIENCES CENTER ALBUQUERQUE HEALTH SCIENCES CENTER
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| We hypothesized that over-expression of 5-HT3 receptors decreases alcohol consumption because the presence of an increased number of 5-HT3 receptors increased the potentiation of dopamine release at lower alcohol concentrations. Thus, the animal requires less alcohol to obtain the same behavioral effect. Thus, the lower level of alcohol consumption seen in the 5-HT3 receptor over-expressing mice may be the result of increased inhibitory control over alcohol consumption We found that ... |
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| Genetic and Biochemical Characterization of Peptidoglycan Synthesis in Chlamydia |
SEP 2005 |
253 pages |
| Authors:
Andrea J. McCoy; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MICROBIOLOGY AND IMMUNOLOGY
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| The Chlamydiaceae family of bacteria are obligate, intracellular pathogens that cause significant diseases world-wide in both humans and animals. Despite having a cell envelope that resembles other gram-negative bacteria, the presence of peptidoglycan in the Chlamydia cell envelope has long been debated. Unlike other wall-less bacteria, chlamydiae synthesize penicillin-binding proteins, are sensitive to antibiotics that inhibit cell wall synthesis, and encode a nearly complete pathway for the synthesis of peptidoglycan. ... |
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| Searching the Epigenome for Novel Breast Cancer Tumor Suppressors |
SEP 2005 |
8 pages |
| Authors:
Greg J. Hannon; COLD SPRING HARBOR LAB NY
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| Our initial proposal focused on developing technologies to uncover epigenetic changes that contribute to tumor development. Our initial attempts towards developing genome wide approaches to identify new genes silenced by epigenetic mechanisms encountered problems; however, our efforts to exploit epigenetic mechanisms of gene silencing to study tumor suppressor gene function have been very successful (see below). We have built upon these successes both to push the development of broadly useful ... |
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| Epidermal Growth Factor (EGF) Receptor Intron 1 CA Repeat Polymorphisms in African-American and Caucasian Males: Influence on Prostate Cancer Risk or Disease Progression and Interaction with Androgen Receptor CAG Repeat Polymorphisms |
SEP 2005 |
30 pages |
| Authors:
David K. Moscatello; COURTER PRODUCTS BOYNE CITY MI
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| We are investigating the effect of a polymorphic epidermal growth factor receptor(EGFR) gene intron 1 CA repeat on prostate cancer(CaP) development, alone or in combination with a known androgen receptor gene CAG repeat polymorphism. We will characterize these repeats in DNA from African-American and Caucasian men with CaP. The data will be analyzed for any correlation using both parameters with clinical outcome (age of onset, rapid progression, or metastasis. The ... |
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| Modeling Human Epithelial Ovarian Cancer in Mice by Alteration of Expression of the BRCA1 and/or P53 Genes |
31 AUG 2005 |
10 pages |
| Authors:
Denise C. Connolly; FOX CHASE CANCER CENTER PHILADELPHIA PA
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| About 1 out of every 10 cases of epithelial ovarian cancer is inherited. Unlike non-hereditary (sporadic) ovarian cancer, some of the underlying genetic causes of hereditary ovarian cancer are well understood. The majority, more than 90%, of inherited cases are the result of inherited mutations in the breast cancer associated gene 1 (BRCA1). In addition to mutations of BRCA1, mutations of the p53 gene are often found in patients with ... |
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| Mechanisms and Chemoprevention of Ovarian Carcinogenesis |
31 AUG 2005 |
28 pages |
| Authors:
Christos F. Patriotis; FOX CHASE CANCER CENTER PHILADELPHIA PA
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| 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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| Relationship Between Network Topology and Dynamics: Concepts from Genome-Wide Regulation of Cell States |
24 AUG 2005 |
7 pages |
| Authors:
Sui Huang; CHILDREN'S HOSPITAL MEDICAL CENTER BOSTON MA
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| Despite accumulating data about the topology ("wiring diagram") of genome-wide gene regulatory networks little is known about the system behavior of such complex networks which produce the genome-wide molecular profiles that now can be measured with new genomic technologies. Using gene expression profiling to monitor multiple trajectories in genome-wise expression state space it was shown experimentally for the first time that a cell fate, in this case, neutrophil differentiation in ... |
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| Melanopsin Polymorphisms in Seasonal Affective Disorder |
17 AUG 2005 |
65 pages |
| Authors:
Kathryn A. Roecklein; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MEDICAL AND CLINICAL PSYCHOLOGY
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| Seasonal affective disorder (SAD) is characterized by winter depressive episodes and springtime remission. SAD may result from a genetically mediated abnormal response to low light availability during winter. One candidate gene for SAD is melanopsin, a non-visual, circadian photopigment. The present study determined the frequency of a genetic polymorphism in melanopsin (P10L) in individuals with SAD (n=36) compared to two groups: gender-matched controls with no history of depression and minimal ... |
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| Pregnancy Specific Glycoprotein 17 Binds to the Extracellular Loop 2 of Its Receptor, CD9, and Induces the Secretion of IL-10, IL-6, PGE2, and TGFBeta1 in Murine Macrophages |
17 AUG 2005 |
142 pages |
| Authors:
Cam Thi Ha; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
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| Pregnancy specific glycoproteins (PSGs) are a family of proteins produced by primate and rodent placentas and secreted into the maternal circulation. In humans PSGs are detected in maternal serum from the time of implantation, and their concentration increases when pregnancy progresses, reaching 200-400 microgram/ml at term. The correlation between low levels of PSGs and poor pregnancy outcomes suggests PSGs play a role in the regulation of maternal immunity to the ... |
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| Molecular Epidemiology of Epidemic Severe Malaria Caused by Plasmodium vivax in the State of Amazonas, Brazil |
17 AUG 2005 |
330 pages |
| Authors:
Patricia D. Santos-Ciminera; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF PREVENTIVE MEDICINE AND BIOMETRICS
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| Malaria in South America is a major public health problem. In Brazil, most of the cases occur in the Amazon Region, particularly in the State of Amazonas. In Manaus, the capital of Amazonas, atypical cases of Plasmodium vivax infections, including patients presenting with severe thrombocytopenia and bleeding, led to the hypothesis that severe disease could be related to a particular, emergent, and more pathogenic genotype of P. vivax. The authors ... |
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| Characterization of a Plasmid-Encoded Type IV Secretion System in Campylobacter jejuni 81-176 |
17 AUG 2005 |
128 pages |
| Authors:
Joseph Larsen; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MICROBIOLOGY AND IMMUNOLOGY
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| The Gram-negative bacterium Campylobacter jejuni is major cause of diarrheal illness in both the United States and the world abroad. One strain of C. jejuni, 81-176, is a particularly virulent strain that invades epithelial cells at levels higher than most C. jejuni isolates. This strain possesses two plasmids, designated pVir and pTet, both of which contain genes with homology to type IV secretion systems (TFSS). TFSS are systems capable of ... |
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| Cooperative Relational Database Initiative for Threat Reduction |
17 AUG 2005 |
5 pages |
| Authors:
Michelle Sheahan; Luther E. Lindler; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| In order to create a resource for basic and clinical research in biological threat reduction, we have developed an annotated relational database. This database is comprised of gene sequences from public databases and researchers' laboratory results, the Bioterrorism Defense Database runs on Microsoft SQL platform and is accessible on a password-protected Internet site. The Biodefense database project is a collaborative effort between the Walter Reed Army Institute of Research, the ... |
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| Development of a Genome Fingerprint Database to Identify Genetically Engineered Microbes |
10 AUG 2005 |
12 pages |
| Authors:
Luther E. Lindler; Xiaozhe Huang; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC DIV OF COMMUNICABLE DISEASE AND IMMUNOLOGY
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| The development of recombinant DNA technology and the current state of bioscience has for the first time made the laboratory creation of new biological weapons a real possibility. A critical part of any countermeasures is the ability to identify strains that are unlike previous strains that have been isolated, i.e. are "outside the box" of known genetic variability for the organism. A database of this type will help medical care ... |
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| Genetic Influence on Toxicity and Prognosis in Women Treated with Breast-Conserving Surgery and Radiation Therapy |
01 AUG 2005 |
15 pages |
| Authors:
Christine B. Ambrosone; Jenny Chang-Claude; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
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| Women with earlier stage breast cancer who receive breast conserving surgery and radiation therapy have a generally good prognosis. However, among 15-20% of these women, breast cancer recurs, and a similar proportion of women also experience severe toxicity with radiation therapy. It is possible that inter-individual differences in the capability of both tumor and normal cells to protect themselves from radiation-induced damage, and to repair that damage if it does ... |
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| Molecular Engineering of Surfaces for Sensing and Detection |
AUG 2005 |
95 pages |
| Authors:
Shaoyi Jiang; WASHINGTON UNIV SEATTLE DEPT OF CHEMICAL ENGINEERING
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| There are three challenges in the development of surfaces for sensing and detection: sensitivity (i.e., low detection limit), specificity (i.e., false positives and negatives), and robustness (simultaneous detection of multiple analytes). These three issues are addressed in this work with the main focuses on control of protein orientation and creation of protein arrays. The ability to control, probe, and predict protein orientation will facilitate the development of biosensors with high ... |
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| Characterization of Two Novel Oncogenic Pathways Collaborating With Loss of P53 or Activated Neu in Mouse Models of Breast Cancer |
AUG 2005 |
16 pages |
| Authors:
Jianrong Lu; Philip Leder; HARVARD MEDICAL SCHOOL BOSTON MA
|
| Cancer develops through accumulation of multiple genetic mutations. Loss of tumor suppressor gene p53 and activation of oncogene Neu/ErbB2 are among the most frequent genetic alterations in human breast cancer. We performed a retroviral insertional mutagenesis screen to identify genes that may contribute to mammary tumor formation in conjunction with deregulated p53 or Neu. Multiple proviral insertions from independent tumors were identified to be located within introns of the F-box ... |
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| Targetable Endolytic Protein-Based Polymers for Systemic Breast Cancer Gene Therapy |
AUG 2005 |
62 pages |
| Authors:
Hamid Ghandehari; MARYLAND UNIV BALTIMORE
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| Using recombinant techniques the first prototype polymer-protein fusion was biosynthesized to mediate transgene expression in mammalian cell lines. The carrier was designed to have the structure of (KHKHKHKHKK)6-FGF2 where Lysine (K) residues would allow complexation with plasmid DNA by electrostatic interactions, basic Fibroblast Growth Factor (FGF2) to target cells over-expressing FGF2 receptors (FGFR), and Histidine (H) residues to facilitate escape from the endosomoal compartments due to proton sponge effect. The ... |
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| Alpha-V Integrin Targeted PET Imagining of Breast Cancer Angiogenesis and Lose-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy |
AUG 2005 |
94 pages |
| Authors:
Xiaoyuan Chen; LELAND STANFORD JUNIOR UNIV STANFORD CA
|
| The overall objective of this project is to develop I 18F-labeled RGD peptide derivatives for breast cancer imaging with prolonged tumor retention and improved in vivo kinetics to visualize and quantify av-integrin expression and subsequently evaluate the metronomic anti angiogenic chemotherapy efficacy on tumor regression, necrosis, and angiogenesis. Specific Aims: (1) To optimize 18F-labeled RGD peptide tracer for breast cancer imaging with prolonged tumor retention and improved in vivo kinetics. ... |
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| The Analysis of Cell Population Dynamics in Mammary Gland Development and Tumorigenesis |
AUG 2005 |
31 pages |
| Authors:
Bryan E. Welm; CALIFORNIA UNIV SAN FRANCISCO
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| The mammary gland is made up of several epithelial cell populations including luminal, myoepithelial, stem and progenitor cells. The experiments in this proposal investigate the role of mammary epithelial cell differentiation processes during development and tumorigenesis. Using FACS, mammary epithelial cell (MEC) populations from tumors and wildtype tissue will be investigated for their outgrowth potential or tumorigenic capacity. MECs with enhanced outgrowth or tumorigenic potential will be further characterized by ... |
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| Mechanisms of Matrix Metalloproteinase-Mediated p53 Regulation |
AUG 2005 |
25 pages |
| Authors:
Jimmie Fata; CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
|
| Cell contraction and membrane blebbing are evolutionarily conserved events that occur during the execution phase of apoptosis. Several members of the TNF-ligand superfamily, which are associated with the promotion of a number of pathological processes, including inflammation and cancer are also capable of inducing membrane blebbing in some cell types. Most of these ligands are transmembrane bound but can be shed from the cell surface through proteolytic processing where soluble ... |
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| MMP-8: A Breast Cancer Bone Metastasis Suppressor Gene |
AUG 2005 |
21 pages |
| Authors:
Nagarajan Selvamurugan; UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY PISCATAWAY
|
| In order to study the role of MMP-8 on inhibition of cancer growth and progression, we initiated our work to clone the human MMP-8 cDNA and express it in vitro. The pcDNA3.1 contains the following elements: human cytomegalovirus (CMV) immediate-early promoter/enhancer that permits efficient, high-level expression of recombinant protein and V5 epitope that allows detection of recombinant protein with anti-V5 antibody. The MMP-8 cDNA with a V5-epitope tag was cloned ... |
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| A Tissue Engineering Approach to Study the Progression of Breast Tumor Metastasis in Bone |
AUG 2005 |
6 pages |
| Authors:
Mingxin Che; Daotai Nie; WAYNE STATE UNIV DETROIT MI
|
| Most patients dying of breast cancer suffer painful bone metastasis. It is our hypothesis that the invasive growth and progression of breast metastatic lesions in bone requires the participation of various constituents from "soil". A reconstitution of such "soil" for the growth of breast metastatic cells will provide tremendous insights into factors critical for breast cancer growth in bone. We will firstly use our basic calcium minerals to reconstitute the ... |
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| Development of a Mouse Model for Determination of the Role of the Catechol Metabolites of Estradiol in Mammary Tumorigenesis |
AUG 2005 |
6 pages |
| Authors:
James D. Yager; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The goal was to develop a catechol-o-methyltransferase knockout (COMTKO)-estrogen receptorlwnt-I (ERKOANnt-I) mouse model to study the role of estrogen catechol metabolites in mammary tumorigenesis. The aims were: Through a complex genetic crossing, introduce the COMTKO genotype into the ERCOIWnt-I mice; Initiate studies to determine the effects of the absence of COMT on several biochemical end points and on mammary gland development and tumorigenesis in the resulting COMTKO/ERCOlWnt-1 female mice. ERKOlWnt-1 ... |
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| Vectors for Treatment of Metastatic Breast Cancer |
AUG 2005 |
156 pages |
| Authors:
Albert B. Deisseroth; SIDNEY KIMMEL CANCER CENTER SAN DIEGO CA
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| The objective is to design, build and study vectors which would be able to break tolerance to breast cancer associated TAA and be used to suppress the recurrence of metastatic breast cancer following surgical resection. The hypothesis is that by fusing the CD40 ligand stripped of its transmembrane domain and intracytoplasmic domains to a breast cancer TAA such as the extracellular domain of the her-2-neu receptor, or the extracellular tandem ... |
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| Identification of New EGR1 Target Genes that Regulate Radiation Responses in Prostate Cancer Cells |
AUG 2005 |
10 pages |
| Authors:
Shilpi Arora; BURNHAM INST LA JOLLA CA
|
| My work this year was in two parts. I completed a study started by others in the laboratory, on the DNA repair gene GADD45, that is induced by the Egr1 transcription factor (TF), as well as other TFs. Egr1 transcription ally induced GADD45 expression as shown by an GADD45-promoter luciferase reporter construct combined with the use of mutated Egr1 binding sites in the promoter. This work was submitted for publication ... |
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| Role of Rad51-Mediated Interactions in Recombination |
AUG 2005 |
9 pages |
| Authors:
Steven Raynard; YALE UNIV NEW HAVEN CT
|
| Mutations in the BRCA2 gene are linked to familial and sporadic breast cancer, yet the molecular function of BRCA2 protein remains largely obscure. BRCA2 protein physically interacts with the Rad51 recombinase, a member of the RAD52 epistasis group of proteins that mediate homologous recombination (HR), a major mechanism that repairs chromosomes damaged by ionizing radiation and genotoxic agents. Accordingly, BRCA2-deficient cell lines exhibit impaired HR and sensitivity to genotoxic agents. ... |
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| Posttranscriptional Regulation of the Neurofibromatosis 2 Gene |
AUG 2005 |
118 pages |
| Authors:
Long-Sheng Chang; CHILDREN'S HOSPITAL COLUMBUS OH
|
| Neurofibromatosis type 2 (NF2) is associated with a homozygous inactivation of the neurofibromatosis 2 (NF2) gene. Despite intense study of the NF2 gene the mechanism by which the NF2 tumor suppressor acts to prevent tumor formation is not well understood. The goal of this research is to examine the role of posttranscriptional regulation of the NF2 gene. During this reporting penod we have confirmed our findings that vestibular schwannomas express ... |
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| Neural Protein Synuclein (SNCG) in Breast Cancer Progression |
AUG 2005 |
11 pages |
| Authors:
Yangfu Jiang; LONG ISLAND JEWISH MEDICAL CENTER LAKE SUCCESS NY
|
| Synucleins are emerging as central players in the formation of pathologically insoluble deposits characteristic of neurodegenerative diseases. However, synuclein-gamma (SNCG), previously identified as a breast cancer specific gene (BCSG1), is also highly associated with breast cancer progression. Using transgenic mouse model, we demonstrated a role of SNCG in induction of highly proliferative pregnancy-like phenotype of mammary epithelial cells, branching morphology, and mammary hyperplasia. SNCG participated in the heat shock protein-based ... |
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| Nuclear Dynamics of BRCA1-Dependent Transcription Regulation |
AUG 2005 |
8 pages |
| Authors:
Zelton D. Sharp; TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
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| BRCA1 coordinates cellular responses to DNA damage. It functions as a co-repressor of GADD45atranscription through interactions with a DNA-binding protein termed ZBRK1. Our goal is to develop a biosensor system to visualize transcription control by ZBRK1 and BRCA1 in single living and/or fixed cells. The rationale is to use integrated DNA binding sites to obtain real time, multiplex-based data. The reportable outcomes for the period are: 1) UAS and ZREarray-bearing ... |
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Genetic Engineering and Molecular Biology
