| Understanding the Biosynthesis SF2575: A Potent Antitumor Compound With Novel Modes of Action |
Sep-2009 |
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| Authors:
Yi Tang; CALIFORNIA UNIV LOS ANGELES
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 | SF2575 is a tetracycline polyketide produced by Streptomyces sp. SF2575 and displays exceptionally potent anticancer activity. The structure is chemically complex and contains unusual angelate and salicylate tailoring groups. In this study, we identified, sequenced and functionally analyzed the ssf biosynthetic gene cluster. Intermediates were isolated from the SF2575 culture extract to suggest the order of pendant groups addition is C-9 glycosylation, C-4 salicylation and C-4' angelycylation. Cytotoxicity studies demonstrated ... |
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| tRNAs as Biomarkers and Regulators for Breast Cancer |
Aug-2009 |
19 pages |
| Authors:
Tao Pan; Marsha Rosner; M Pavon-Eternod; S Gomes; R Geslain; Q Dai; CHICAGO UNIV IL
|
 | tRNA reads mRNA codons in translation and is essential for protein synthesis. Like mRNA, tRNAs are also under stringent cellular control. Our proposal aims to determine the feasibility of using tRNA expression as biomarkers for breast cancer type and progression, and how tRNAs are used to regulate gene expression in breast cancer cells. We found that the expression of both nuclear and mitochondrial-encoded tRNAs can be useful as possible biomarkers ... |
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| In Silico Genome Mismatch Scanning to Map Breast Cancer Genes in Extended Pedigrees |
01-Jul-2009 |
89 pages |
| Authors:
Alun Thomas; UTAH UNIV SALT LAKE CITY
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| This project aims to map breast cancer genes using dense single nucleotide polymorphism assays in large extended pedigrees. Data has been collected using 1,000,000 SNP genotype assays for 25 women affected by breast cancer in three high risk Utah pedigrees. Analysis of control data from the HapMap project has been completed and methods that will model linkage disequilibrium for genome wide, dense, SNP data have been developed. Papers describing these ... |
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| Genomic Approaches for Detection and Treatment of Breast Cancer |
Jul-2009 |
28 pages |
| Authors:
Stephen J Elledge; BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
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| The experiments carried out under this Innovator award allowed us to set up a genetic system to identify genes through loss of function (RNAi) or gain of function (over-expression) functional screens that are capable of influencing cells to acquire tumorlike properties. In this way we have identified many novel tumor suppressors and oncogenes. Many of these are found to be altered in breast cancer and other cancer types. Importantly, we ... |
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| Age-Related DNA Methylation Changes and Neoplastic Transformation of the Human Prostate |
Jul-2009 |
22 pages |
| Authors:
Bernard Kwabi-Addo; HOWARD UNIV WASHINGTON DC
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| There is abundant evidence to suggest that DNA methylation changes may appear earlier during prostate cancer development than genetic changes, as well as more commonly and consistently. The purpose of the present study is to investigate whether aberrant methylation in normal prostate tissues may in itself be a pathologic event that increases with age. Using methylated CpG island amplification coupled with CpG promoter microarray, I have identified several novel genes ... |
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| Biochemical Characterisation of TSC1 and TSC2 Variants Identified in Patients with Tuberous Sclerosis Complex |
Jul-2009 |
74 pages |
| Authors:
Mark Nellist; ERASMUS MEDICAL CENTER ROTTERDAM (NETHERLANDS)
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| The key findings of the project during the research period (23/1/09 - 31/7/09) are as follows: 1. Derivation and testing of 31 unclassified TSC2 variants: 16 classified as pathogenic; 7 classified as neutral; 8 still unclassified/analysis not complete. 2. Derivation of 12 unclassified TSC1 variants: 3 classified as pathogenic; 7 classified as neutral; 2 still unclassified/analysis not complete. 3. Improved assay cost, throughput and reproducibility. 4. Idenbtification of variants with ... |
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| Functional Characterization of the Protein Product of the Prostate Carcinoma Gene Fusion TMPRSS2:ERG Using the Proteomic and Microarray Analyses |
Jul-2009 |
16 pages |
| Authors:
Larisa Litovchick; DANA-FARBER CANCER INST BOSTON MA
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| A recently identified TMPRSS2:ERG gene fusion is present in more than half of the prostate cancer cases and could contribute to the pathogenesis of CaP. The proposed research during the first year of performance was focused at identification of native protein complexes formed by ERG using large-scale immunoprecipitation and MudPIT proteomic analysis. During the performance period, experiments towards this aim were successfully completed. Conditions for semi-preparative purifications of the ERG-CTAP ... |
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| Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity |
Jul-2009 |
16 pages |
| Authors:
Betty Diamond; FEINSTEIN INST FOR MEDICAL RESEARCH MANHASSET NY
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| Systemic lupus erythematosus (SLE) is an autoimmune disease that occurs preferentially in women. In murine models of SLE, it is clear that increased or sustained high physiologic levels of estradiol can accelerate onset of disease and exacerbate disease severity. We have shown that estradiol alters B cell maturation in vivo but does so in a genetically restricted fashion. We have also shown that estradiol can act directly on B cells ... |
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| Roles for the DNA Damage Checkpoint Protein HUS1 in Breast Cancer |
Jul-2009 |
9 pages |
| Authors:
Stephanie A Yazinski; CORNELL UNIV NEW YORK
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| Cancer is aberrant, uncontrolled cellular proliferation arising from an accumulation of mutations in growth regulatory genes. Two mammalian DNA damage checkpoint pathways, the Atm and Atr pathways, act to suppress tumor formation by preventing mutation accumulation and inducing senescence in response to oncogenic stimuli. Roles for the Atr pathway in tumor suppression are less understood, as deletion of any member of this pathway, including Hus1, results in embryonic lethality. To ... |
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| Iron and Prochlorococcus |
Jun-2009 |
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| Authors:
Anne W Thompson; WOODS HOLE OCEANOGRAPHIC INSTITUTION MA
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| Iron and primary productivity in the oceans are linked through photosynthesis. At the global scale iron induces phytoplankton blooms during addition experiments. At the atomic scale, iron is involved in photosystem I, the most efficient light-harvesting complex in nature. Yet, we know little of how iron influences microbial diversity and distribution. Here, we assess the influence of iron on the ecology of Prochlorococcus. With its minimal genome and ubiquity in ... |
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| Iron Limitation and the Role of Siderophores in Marine Synechococcus |
Jun-2009 |
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| Authors:
Adam R Rivers; WOODS HOLE OCEANOGRAPHIC INSTITUTION MA
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| Marine cyanobacteria in the genus Synechococcus are widely distributed and contribute significantly to global primary productivity. In many parts of the ocean their growth is limited by a lack of iron, an essential nutrient that is virtually insoluble in seawater. To overcome this, Synechococcus have evolved a number of strategies to acquire iron. Gene distribution, metagenomics and a novel immunological flow cytometry assay in the Costa Rica Upwelling Dome were ... |
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| Genetic Dissection of the Role of Heparan Sulfate in Mammary Tumor Progression |
Jun-2009 |
14 pages |
| Authors:
Yu Yamaguchi; BURNHAM INST LA JOLLA CA
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| There is accumulating evidence that heparan sulfate (HS) controls various growth factor signaling events. There is also evidence that cellular HS production itself exerts strong influences on tumorigenesis, exemplified by the fact that mutations of Ext1, the gene encoding an HS synthesizing enzyme, cause multiple bone tumors. Furthermore, the level of HS degrading activity correlates with the aggressiveness of the tumor. Despite these longstanding observations, much less is known about ... |
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| Checkpoint Kinase-Dependent Regulation of DNA Repair and Genome Instability in Breast Cancer |
Jun-2009 |
29 pages |
| Authors:
Courtney A Lovejoy; VANDERBILT UNIV NASHVILLE TN
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| The DNA damage response (DDR) functions as a tumorigenesis barrier. It is activated in precancerous lesions, potentially as a consequence of aberrant DNA replication. The genetic alterations that create this genomic instability are poorly defined. Using a functional genomic screen in human cells we identified seventy-four genes that when silenced by RNAi activate the DDR. Using a series of secondary assays we determined that many have DNA replication-associated genome maintenance ... |
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| Advances in Breast Cancer Therapy |
Jun-2009 |
10 pages |
| Authors:
Holly Gallion; PRECISION THERAPEUTICS INC PITTSBURGH PA
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| PTI has received WIRB approval and the University of Pittsburgh IRB approval for this study. PTI has engaged 19 research sites in this research and four contracts have been successfully negotiated and executed. Another six research sites are determining clinical and budgetary feasibility. Pending the approval of the DoD and the WIRB of this first set of research sites submitted for approval, it is anticipated we will have the first ... |
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| High-Content FRET-FLIM Screening in Inhibitors of Oncogenic Transcription by C-Myc in Breast Cancer |
Jun-2009 |
31 pages |
| Authors:
David Andrews; Linda Penn; MCMASTER UNIV HAMILTON (ONTARIO)
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| To develop a novel high content screen to identify inhibitors that block Myc:TRRAP interaction, in the first year of this project we constructed several fluorescent fusion protein constructs of Myc and TRRAP, and evaluated their ability to bind and engage in fluorescence energy transfer (FRET) in vivo. All year-one tasks were completed in the first year of the grant. During the second year we discovered that expression of Myc-CFP was ... |
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| Beta-catenin/TCF Signaling and Castrate-Resistant Progression of Osteoblastic Bone Metastases |
Jun-2009 |
11 pages |
| Authors:
Nora M Navone; M D ANDERSON CANCER CENTER HOUSTON TX
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| In this project, we are studying the role of D32G-mutant beta-catenin in the expression of secretory genes by prostate cancer cells. We believe that D32G-mutant beta-catenin potently activates a subset of beta-catenin/wnt downstream target genes, thus providing a tool for identifying ?bone progression? factors activated by this pathway in prostate cancer. Results from the studies performed during this period indicate that activation of beta-catenin in prostate cancer cells stimulates a ... |
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| Mechanisms of Abnormal Growth Regulation in Prostatic Adenocarcinoma Using Abi1/Hssh3bp1 Conditional Knockout Mouse Model |
Jun-2009 |
70 pages |
| Authors:
Leszek Kotula; Xiaoling Xiong; NEW YORK BLOOD CENTER NY
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| Prostate cancer is the most common type of cancer found in American men. The American Cancer Society estimates that there will be about 190,000 new cases and 27,000 deaths of prostate cancer in the United States in 2009. Genetic alterations of tumor suppressor genes are one of the most common causes of prostate cancer tumorigenesis. Our group identified Abi1/Hssh3bp1 as candidate prostate tumor suppressor gene. To understand the role of ... |
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| Endocrine Therapy of Breast Cancer |
Jun-2009 |
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| Authors:
Robert Clarke; GEORGETOWN UNIV WASHINGTON DC
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| A controversy in the treatment of estrogen receptor positive (ER+) breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., 40% of tumors show cross resistance to TAM or an aromatase inhibitor on crossover. Only 50% of ... |
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| A Novel Anti-Beta2-Microglobulin Antibody Inhibition of Androgen Receptor Expression, Survival, and Progression in Prostate Cancer Cells |
31-May-2009 |
21 pages |
| Authors:
Wen-Chin Huang; EMORY UNIV ATLANTA GA
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| Beta2-microglobulin (beta2M) is a signaling and growth-promoting factor stimulating prostate cancer cell proliferation and progression. Blockade of the beta2M signaling axis resulted in the inhibition of androgen receptor (AR) and its target gene, prostate-specific antigen (PSA), and the induction of programmed death of prostate cancer cells through activation of a caspase-dependent pathway in vitro and in vivo. In this annual summary report, we identified a cis-acting element, sterol regulatory element-binding ... |
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| Identification and Functional Characterization of Somatic Mutations in Human MicroRNAs and their Responsive Elements in Target Genes in Ovarian Tumor Tissues |
May-2009 |
6 pages |
| Authors:
Hua Zhao; HEALTH RESEARCH INC BUFFALO NY
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| Epithelial ovarian cancer (EOC) continues to be the leading cause of the death among gynecological malignancies, owing to the lack of preventive strategies, early diagnostic methods or effective therapies. Detailed understanding of molecular changes, such as, somatic mutations, in ovarian cancer holds the promise of greatly contributing to the understanding of ovarian cancer pathogenesis, with obvious implications in development of new biomarkers, prevention strategies and therapy Micro-RNAs (miRNAs) are endogenous ... |
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| Inhibition of Ovarian Cancer by microRNA-mediated Regulation of Telomerase |
May-2009 |
51 pages |
| Authors:
Brittney-Shea Herbert; INDIANA UNIV INDIANAPOLIS
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| A hallmark of ovarian cancer is its limitless proliferative potential which is governed in part by elevated levels of human telomerase (hTERT) or telomerase activity. However, how telomerase can be regulated in normal cells, and how this regulation can be lost during cancer progression, is not completely understood. microRNAs (miRNAs) are evolutionarily conserved, small, non-coding, single-stranded, 19-23 nucleotide RNA molecules that are estimated to negatively regulate protein encoding genes including ... |
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| The Role of Estrogen-Related Receptor Alpha in Steroidogenesis in the Breast |
01-Apr-2009 |
75 pages |
| Authors:
Linda Grasfeder; DUKE UNIV DURHAM NC
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| This project has focused on the potential role of Estrogen-Related Receptor alpha (ERRalpha) in regulating steroidogenesis. ERRalpha is an orphan nuclear receptor closely related to the Estrogen Receptors (ERs), and while its expression correlates with unfavorable biomarkers and poor prognosis for breast cancer, its function in breast cancer biology is not known. This project was initiated because we observed that a primary coactivator of ERRalpha, PGC-1alpha, induces hepatic gene expression ... |
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| Development and Screening of Subtractive RNAi Libraries from Ovarian Cancer Cell Lines |
Apr-2009 |
6 pages |
| Authors:
Alexandre B Dimtchev; GEORGETOWN UNIV WASHINGTON DC
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| The Specific aims of this proposal are: (1) Construction of two subtractive RNAi libraries targeting mRNA transcripts predominantly present in an (a) advanced ovarian cancer cell line and (b) metastatic ovarian cancer cell line. (2) Screen for genes vitally important for survival and growth. The two malignant cell lines will be transfected with individual clones from the subtractive RNAi libraries and the effect on viability will be monitored. Clones from ... |
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| Genetic Association Study of Ancestry-Matched African American Prostate Cancer Cases and Control |
Apr-2009 |
10 pages |
| Authors:
William B Isaacs; JOHNS HOPKINS UNIV BALTIMORE MD
|
| African American men have the highest incidence and mortality from prostate cancer in the world. Multiple reasons have been postulated to explain these findings although the definitive reasons for this are unknown. While both environmental and genetic factors may contribute to prostate cancer susceptibility, results from multiple studies consistently implicate a strong genetic component of this cancer. However, a specific gene which is consistently and reproducibly associated with prostate cancer ... |
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| Modulators of Response to Tumor Necrosis-Related Apoptosis-Inducing Ligand (TRAIL) Therapy in Ovarian Cancer |
Apr-2009 |
18 pages |
| Authors:
Kian Behbakht; COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
|
| Ovarian Cancer is the leading cause of death from gynecologic cancers in the developed world. We have previously identified a homeobox gene, Six1, which is overexpressed in ovarian cancers as compared to normal ovarian surface epithelium. Overexpression of Six1 is associated with resistance to Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) based therapies. We have discovered that this resistance in ovarian cancers is likely related to over-expression of the TRAIL ... |
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| Profiling the Roles of Insulin Receptor Substrate Isoforms 1 and 2 in Breast Cancer |
Apr-2009 |
10 pages |
| Authors:
Marc A Becker; MINNESOTA UNIV MINNEAPOLIS
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| The insulin-like growth factor (IGF) system has been shown to play a role in breast cancer tumorigenesis and metastasis. Following IGF ligand stimulation, insulin receptor substrate (IRS) adaptor proteins are recruited to the IGF-1 receptor (IGF-1R) to mitigate downstream biochemical signaling namely via the MAPK and PI3K pathways. Data from our lab suggest that different isoforms (IRS-1 and IRS-2) exhibit a selective propensity for one of these signaling pathways to ... |
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| Inhibition of Rac GTPases in the Therapy of Chronic Myelogenous Leukemia |
Apr-2009 |
56 pages |
| Authors:
Jose Cancelas; CHILDREN'S HOSPITAL MEDICAL CENTER CINCINNATI OH
|
| Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) characterized by the expression of the p210-BCR/ABL fusion gene [1]. This gene is produced by the reciprocal translocation (9; 22) (q34; q11) that juxtaposes the 3end of Abelson leukemia virus (ABL) gene with the 5' end of the breakpoint cluster region (Bcr) gene on chromosome 22. The transcript formed as a result encodes for the BCR/ABL fusion protein with constitutively ... |
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| SXR, A Novel Target for Breast Cancer Therapeutics |
Apr-2009 |
31 pages |
| Authors:
Suman Verma; CALIFORNIA UNIV IRVINE
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| Many structurally and functionally distinct SXR activators inhibited the proliferation of MCF-7 and ZR-75-1 breast cancer cells by inducing cell cycle arrest at the G1/S phase followed by apoptosis. Decreased growth in response to SXR activation was associated with stabilization of p53 and up-regulation of cell cycle regulatory and pro-apoptotic genes such as p21, PUMA and BAX. These gene expression changes were preceded by an increase in inducible nitric oxide ... |
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| BRCA1 in Gene-specific Coordination of Transcription and DNA-Damage Response |
14-Mar-2009 |
9 pages |
| Authors:
Jianlong Sun; TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
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| BRCA1 is a tumor suppressor gene for hereditary breast and ovarian cancers. In collaborating with various binding partners, BRCA1 protein participates in multiple cellular functions. Characterization of these binding proteins of BRCA1 is therefore key to the complete understanding of BRCA1's role in tumor suppression. Cofactor of BRCA1 (COBRA1) is a novel BRCA1-interacting protein and shares several functional commonalities with BRCA1 in regulating expression of genes involved various types of ... |
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| Genome-Wide Analysis of Germline CNPs and SNPs in Prostate Cancer |
01-Mar-2009 |
42 pages |
| Authors:
Jianfeng Xu; Siqun L Zheng; Wennuan Liu; Jielin Sun; WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF HEALTH SCIENCES
|
| Prostate cancer (PCa) is the leading cancer among men in the United States, and is a disease with strong genetic susceptibility. The genetic susceptibility is due to the inheritance of altered germline DNA sequences, either in the form of point mutations such as single nucleotide polymorphisms (SNPs), or deletions/gains of a string of nucleotides such as copy number polymorphisms (CNPs). Most current genetic studies focus only on the role of ... |
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| The Functional Effect of an Amphiregulin Autocrine Loop on Inflammatory Breast Cancer Progression |
Mar-2009 |
9 pages |
| Authors:
Andrea Baillo; WAYNE STATE UNIV DETROIT MI
|
| Inflammatory breast cancer (IBC) is one of the most lethal forms of breast cancer. A strong correlation has been found between inflammatory breast cancer and high levels of the growth factor amphiregulin. Amphiregulin is known to activate the epidermal growth factor receptor (EGFR) which turns on genes involved in a number of functions including cell growth. Self-sustained activation of EGFR by amphiregulin is called an amphiregulin autocrine loop. An amphiregulin ... |
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| Interferon Antagonism as a Common Virulence Factor of Hemorrhagic Fever Viruses |
Feb-2009 |
19 pages |
| Authors:
Adolfo G Sastre; Connie S Schmaljohn; MOUNT SINAI MEDICAL CENTER OF THE CITY OF NEW YORK
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| We examined the ability of viruses in the Hantavirus and Nairovirus genera of the family Bunyaviridae to interfere with host signaling pathways involved in innate immunity. For the nairovirus, Crimean Congo hemorrhagic fever virus (CCHFV), we found that the viral polymerase gene contains a predicted ovarian tumor (OTU) protease domain that functions to deconjugate ubiquitin and interferon stimulated gene product 15 (ISG15) from host proteins. Both ubiquitin and ISG15 reversibly ... |
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| Prostate Specific or Enriched Genes as Composite Biomarkers for Prostate Cancer |
Feb-2009 |
7 pages |
| Authors:
Leroy Hood; Qiang Tian; INSTITUTE FOR SYSTEMS BIOLOGY SEATTLE WA
|
| Purpose and scope of research: To evaluate prostate specific genes such as WDR19, NDRG1, Transgelin 2 as diagnosis and prognosis markers for prostate cancers. Major findings: (1) Serum Samples collections: We have retrieved more than 200 prostate cancer, BPH and normal matched control serum samples from the University of Washington Urology serum bank. (2) WDR19 antibody production and ELISA assay development. We have generated Rabbit monoclonal antibodies against WDR19. We ... |
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| Biomarkers for Amyotrophic Lateral Sclerosis in Active Duty Military (BALSAM) |
Feb-2009 |
56 pages |
| Authors:
David Millhorn; John Schlager; CINCINNATI UNIV OH
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| To compare serum samples from individuals diagnosed with amyotrophic lateral sclerosis (ALS) to serum samples from matched individuals who did not develop ALS. In this study we aim to identify candidate serum biomarkers that are unique for ALS and identify a subset of diagnostic serum biomarkers for early detection of ALS prior to the appearance of overt symptoms. Scope: The significance of a positive identification of protein biomarkers for ALS ... |
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| Disruption of the Circadian Rhythms of Gene Expression and the Development of Breast Cancer |
Feb-2009 |
30 pages |
| Authors:
David J Kennaway; SOUTH AUSTRALIA UNIV ADELAIDE
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| This project investigated the effects of rhythm disruption in mice on the expression of a wide range of genes in mammary tissue, the growth of MCF-7 xenografts and the growth, metastasis and gene expression in spontaneous mouse mammary tumors. Subjecting mice to a simulated shiftwork schedule altered the pattern and level of expression of clock gene transcription factors and genes that are involved in the cell cycle. We have also ... |
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| Development of a Nature-Inspired Vector for Targeted Systemic Breast Cancer Gene Therapy |
Jan-2009 |
47 pages |
| Authors:
Arash Hatefi; WASHINGTON STATE UNIV PULLMAN
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| The purpose of this research was to develop a gene delivery system that can target breast cancer cells specifically and transfect them efficiently. A biomimetic vector was genetically engineered to contain at precise locations: a) an adenovirus micro peptide to condense pDNA into nanosize particles, b) a synthetic peptide to target breast cancer cells, c) a pH-responsive synthetic fusogenic peptide to disrupt endosome membranes and facilitate escape of the nanoparticles ... |
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| Novel Small Molecule Antagonists of the Interaction of the Androgen Receptor and Transcriptional Co-regulators |
Jan-2009 |
34 pages |
| Authors:
Clementine Feau; SAINT JUDE CHILDREN'S RESEARCH HOSPITAL MEMPHIS TN
|
| Androgens, mediated by the Androgen Receptor (AR), play a crucial role in prostate cancer. Current treatments are focused on anti-androgenic drugs competing with natural androgens and antagonizing the transcriptional activity of the AR. Although widely used, these drugs have shown significant side effects and in addition, tumors have become resistant suggesting mutations of the receptor. Regulation of gene expression by AR requires the binding to androgens or to its natural ... |
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| Development of a Mouse Model for Prostate Cancer Imaging and Study of Disease Progression |
Jan-2009 |
11 pages |
| Authors:
Isla Garraway; CALIFORNIA UNIV LOS ANGELES
|
| Prostate carcinogenesis is a multi-step process resulting in the transformation of prostatic epithelial cells into invasive carcinoma and metastasis. In recent years, mouse models have emerged that recapitulate salient features of prostate carcinogenesis found in human disease. These models illuminate the molecular events that result in transformation and disease progression. In addition, mouse models can be used to identify molecular targets and test chemotherapeutic agents that may alter the course ... |
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| Biological Impact of Senescence Induction in Prostate Cancer Therapy |
Jan-2009 |
48 pages |
| Authors:
David F Jarrard; WISCONSIN UNIV-MADISON
|
| Recently, it has been recognized that a distinct mechanism of terminal proliferation arrest after chemotherapy involves the reactivation of senescence. However, whether this phenotype occurs in vivo is unclear, as is the biological impact of senescence induction. We have previously identified pathways and genes involved in human senescence that may serve as senescence markers, and have demonstrated that senescence occurs in prostate cancer cell lines after chemotherapy. In this proposal, ... |
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| Identification and Characterization of Genomic Amplifications in Ovarian Serous Carcinoma |
Jan-2009 |
148 pages |
| Authors:
Tian-Li Wang; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
|
| The purpose of this proposed study is to apply genome-wide technologies to analyze ovarian cancer genome and transcriptome. We have accomplished all the proposed tasks as stated in the original grant. They include generating digital karyotyping libraries from ovarian carcinomas and perform transcirptome analysis in each amplicon. This effort leads us to identify at least two novel candidate oncogenes, Rsf1 and Notch3, which were up-regulated in both genomic DNA and ... |
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| Gene Expression Analysis of Circulating Hormone Refractory Prostate Cancer Micrometastases |
Jan-2009 |
32 pages |
| Authors:
Jonathan Rosenberg; CALIFORNIA UNIV SAN FRANCISCO
|
| This annual report for the Physician Research Training Award focuses on progress in the genetic analysis of circulating hormone refractory prostate cancer micrometastases. As metastatic tissue is often inaccessible in advanced prostate cancer patients, analysis of circulating tumor cells may provide understanding of the biology of hormone refractory prostate cancer as well as chemotherapy resistance. Oligonucleotide array comparative genomic hybridization allows the assessment of genetic changes that may occur in ... |
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| Evaluation of Genomic Instability in the Abnormal Prostate |
Dec-2008 |
94 pages |
| Authors:
Christina Haaland-Pullus; Jeffrey K Griffth; NEW MEXICO UNIV ALBUQUERQUE
|
| The aim of this study is to investigate field effect in prostate cancer, the relationship between tumor and nearby histologically normal tissues compared to truly disease free prostate tissue. Identification of changes within tumor adjacent tissues has two possible clinical implications: prognosis and diagnosis. Several tools are being used to investigate this effect, specifically the assessment of telomere length, allelic imbalance, and methylation status, all markers of genomic instability. Microarray ... |
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| Hyaluronan Tumor Cell Interactions in Prostate Cancer Growth and Survival |
Dec-2008 |
42 pages |
| Authors:
James B McCarthy; Eva Turley; MINNESOTA UNIV MINNEAPOLIS
|
| Hyaluronan is a high molecular weight polyanionic polysaccharide that is increased in more advanced prostate cancers. Tumor cell interaction with this polysaccharide by specific receptors CD44 and RHAMM promote tumor growth, survival and invasion. Work during the last funding period have further defined the mechanism of action of each of these receptors. Studies show that extracellular RHAMM acts a co-receptor for CD44, and the combined action of this receptor complex ... |
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| The Aged Microenvironment Influences Prostate Carcinogenesis |
Dec-2008 |
24 pages |
| Authors:
Daniella Bianchi-Frias; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| The greatest factor for the development of prostate adenocarcinoma is advanced age. Emerging evidence suggests that molecular alterations in the aged prostate microenvironment mediated by stromal aging and senescence are key factors regulating carcinogenesis and neoplastic progression. We used normal mouse prostate epithelial and adjacent stromal cells microdissected in situ from young and old animals, to identify factors altered by the aged stroma that may place the prostate gland at ... |
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| Chemical and Biological Sensing Utilizing Fused Bacteriorhodopsin Protein Hybrids |
Dec-2008 |
7 pages |
| Authors:
Donald R Lueking; Eric M Winder; Mark H Griep; Craig R Friedrich; MICHIGAN TECHNOLOGICAL UNIV HOUGHTON
|
| This paper describes how monomeric bR can be overproduced in Escherichia coli and subsequently utilized as an integral component of a generic, nanoscale chemical sensing platform. The utility of this sensing platform is that it can be adapted for detection of a wide range of biological and chemical agents at, or below, nanomolar concentration levels. The gene encoding for bacteriorhodopsin has been successfully isolated from Halobacterium salinarum strain S9P using ... |
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| Genome to Phenome: Integromic Approaches to Define Networks of Host-Pathogen Interactions and Vaccine Biomarker Discovery |
Dec-2008 |
7 pages |
| Authors:
Marti Jett; Rasha Hammamieh; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
|
| The rapid development of genomics, proteomics and high-throughput computing approaches to study diseases is now allowing us to apply an integrative systems biology work frame for drug and biomarker development. Understanding the symbiosis of pathogen and host at the molecular level requires a comprehension of the molecular/cellular events by which the pathogens can induce alterations in the host in order to invade, proliferate and overtake the host. Our research focuses ... |
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| A Novel Approach to Identify Genes that Modulate Response of Human Ovarian Cancer Cells to Chemotherapeutic Agents Using High-Throughput RNA Interference |
Dec-2008 |
11 pages |
| Authors:
David Azorsa; TRANSLATIONAL GENOMICS RESEARCH INST PHOENIX AZ
|
| The application of HT-RNAi represents an innovative functional genomic strategy to rapidly identify important genes involved in the response of cancer cells to the chemotherapeutic agents. We developed a novel HT-RNAi screening assay using a kinase siRNA library to identify genes that modulate the response of ovarian cancer cells to cisplatin and paclitaxel. HT-RNAi assays were conducted using the cell line SKOV-3 to identify genes that sensitize cells to low ... |
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| The Role of HOX Proteins in Androgen-Independent Prostate Cancer |
Nov-2008 |
11 pages |
| Authors:
Sunshine Daddario; COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
|
| HOX genes encode a large family of transcription factors involved in key developmental decisions, and are often aberrantly expressed in cancer. Our laboratory has previously shown that a subset of genes of the HOXC cluster are overexpressed in primary prostate tumors, metastases, and prostate cancer (PCa) cell lines1. Increasing transient expression of HOXC8 in LNCaP PCa cells as well as HPr-1 AR non-tumorigenic prostate epithelial cells results in a progressive ... |
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| Identification and Characterization of an X-Linked Familial Prostate Cancer Gene |
Nov-2008 |
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| Authors:
Brian Yaspan; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| Prostate cancer is the most commonly diagnosed non-skin malignancy in males, with as many as one in 5 males living in developed nations being diagnosed with prostate cancer in their lifetime. Despite the medical significance of prostate cancer our understanding of predisposition and progression in the disease remains rudimentary. Prostate cancer is estimated to have the largest heritable component of all common cancers. We will explicitly characterize ancestral versions of ... |
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| Prostate Cancer Progression and Serum Sibling (Small Integrin Binding N-Linked Glycoprotein) Levels |
01-Oct-2008 |
154 pages |
| Authors:
Neal S Fedarko; JOHNS HOPKINS UNIV BALTIMORE MD
|
| We have been studying a gene family termed SIBLINGs (for small integrin binding ligand N-linked glycoproteins) whose members include bone sialoprotein (BSP), osteopontin (OPN), dentin matrix protein-1 (DMP1), dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE). Our Specific Aims are to describe the distribution of serumbased measurements of SIBLINGs among (a) normal individuals, (b) individuals with benign prostatic disease, (c) individuals with clinically defined prostate cancer, and (d) longitudinal samples ... |
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Reports by Keyword(s)
GENES
