| The Role of eIF4E Activity in Breast Cancer |
Aug-2009 |
12 pages |
| Authors:
Thomas A Hughes; L A Coleman; S Satheesha; LEEDS UNIV (UNITED KINGDOM)
|
 | Increased eIF4E expression occurs in many breast cancers and makes fundamental contributions to carcinogenesis by stimulating expression of cancer-related genes at post-transcriptional levels. This key role is highlighted by the facts that eIF4E levels can predict prognosis and that eIF4E is an established therapeutic target. However, eIF4E activity is a complex function of expression levels and phosphorylation statuses of eIF4E and its regulatory proteins. Our hypothesis was that combined analyses ... |
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| Humanized Androgen Receptor Mice: A Genetic Model for Differential Response to Prostate Cancer Therapy |
Jul-2009 |
12 pages |
| Authors:
Diane M Robins; MICHIGAN UNIV ANN ARBOR
|
| In mice in which human androgen receptor (AR) replaces the endogenous murine gene, variation in the length of a polymorphic N-terminal polyglutamine tract affects initiation, progression and therapy response prostate tumors. This provides a genetic paradigm in which to dissect AR functions that determine response to therapy. We are studying the role of the AR Q tract in ligand-independent AR activation in vitro and in a mouse model with prostate ... |
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| Identification and Targeting of Upstream Tyrosine Kinases Mediating PI3 Kinase Activation in PTEN-Deficient Prostate Cancer |
Jun-2009 |
22 pages |
| Authors:
Steven P Balk; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Class IA PI3K p110 catalytic subunits are activated upon SH2 domain mediated binding of p85 regulatory subunits to tyrosine phosphorylated receptor tyrosine kinases (RTKs) or adaptor proteins. This activation can be enhanced by Ras, and is amplified by PTEN loss in the majority of advanced prostate cancers (PCa). We found that RTK inhibitors lapatinib and sorafenib could suppress PI3K in PTEN deficient PCa cells. However, analysis of p85 associated proteins ... |
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| Y Chromosome Regulation of Autism Susceptibility Genes |
Jun-2009 |
13 pages |
| Authors:
Chris L Yun-Fai; NORTHERN CALIFORNIA INST FOR RESEARCH AND EDUCATION SAN FRANCISCO
|
| Autism spectrum disorders (ASD) are a group of pervasive neurodevelopmental disorders with impairments in social interaction, language and range of interests. There is a significant sexual dimorphism with affected boy to girl ratios as high as 8:1. Recent studies in our laboratory demonstrated that the Y-located transcription factor, SRY, could possibly play a genetic modifier role in the expression of several significant autism susceptibility genes (ASGs). The major goal of ... |
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| Modification of Tamoxifen Effectiveness by Gene Polymorphisms and Other Drugs |
May-2009 |
43 pages |
| Authors:
Thomas P Ahern; TRUSTEES OF BOSTON UNIV MA
|
| In the first year of his predoctoral award, Thomas Ahern completed all coursework and qualifying examinations required for entry into the senior phase of doctoral study for the Doctor of Science degree in epidemiology at Boston University. Mr. Ahern submitted a dissertation research proposal to the Epidemiology Doctoral Committee in May 2008; the proposal was formally approved in October 2008. Mr. Ahern completed and published one of the three studies ... |
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| Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy |
Mar-2009 |
18 pages |
| Authors:
Peter S Nelson; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| The Purpose of this proposal is to exploit a molecular correlate of the Gleason grading system for prostate carcinoma in order to: a) develop improved outcome predictors; and b) identify therapeutic strategies. During this project period we have evaluated in excess of 25 prostate cancer antigens by Western blot and tissue-based assays and identified 3 with detectable levels in the plasma. We also determined that developmental genes involved with invasive ... |
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| The Role of Backup NHEJ Repair in Creating Genomic Instability in CML. Addendum |
Mar-2009 |
18 pages |
| Authors:
Feyruz Rassool; MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE
|
| The BCR-ABL1 fusion gene in Philadelphia (Ph)-+ve chronic myeloid leukemis (CML) encodes a constitutively active tyrosine kinase that causes uncontrolled cellular proliferation. BCR-ABL1 expression results in elevated levels of reactive oxygen species (ROS), an increased incidence of DNA double strand breaks (DSBs), error-prone repair and genomic instability. We recently demonstrated that an error-prone alternative (alt) NHEJ pathway involving DNA ligase IIIa/XRCC1 is upregulated in CML cells. Knockdown of alt NHEJ ... |
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| Maintenance of Glucose Homeostasis through Acetylation of the Metabolic Transcriptional Coactivator PGC1-alpha |
Feb-2009 |
12 pages |
| Authors:
Pere Puigserver; DANA-FARBER CANCER INST BOSTON MA
|
| The main purpose of this proposal is to test the hypothesis that acetylation of PGC-1alpha by GCN5 and associated proteins, Pc3 and WDR18, controls hepatic glucose production. The major findings of this Research Technical Report are in tasks 2, 4, 5 and 6. In task 2, we have further confirmed that Pc3 and WDR18 are part of the PGC-1alpha/GCN5 complex but are not required for its assembly. In task 4, ... |
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| Identification of Ovarian Cancer Susceptibility Genes Involved in Stromal-Epithelial Interactions |
Feb-2009 |
27 pages |
| Authors:
Georgia Chenevix-Trench; QUEENSLAND INST OF MEDICAL RESEARCH BRISBANE (AUSTRALIA)
|
| The purpose of this project was to identify ovarian cancer susceptibility genes involved in stromal- epithelial cross talk. We have now genotyped 2138 samples for 1536 tagging, ns and miRNA binding site SNPs in 174 genes. Following Quality Control exclusions, the final dataset comprised 1839 samples (675 cases and 1164 controls) with genotype information for 1292 SNPs in 174 genes. We also genotyped 22 SNPs in 2985 cases and 2932 ... |
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| Exploring the Mechanisms of Pathogenesis in Prostate Cancer Involving TMPRSS2-ERG (Or ETV1) Gene Rearrangement |
Jan-2009 |
11 pages |
| Authors:
Stuart H Orkin; CHILDREN'S HOSPITAL CORP BOSTON MA
|
| Recently, gene rearrangements involving ETS family transcription factors have been identified in 50% of prostate cancer cases. To address roles of these ETS factors, especially ERG, the most frequently rearranged ETS gene in prostate cancer, as well as in normal prostate development, we planned to, 1. Generate conditional knockin mouse models of prostate cancer based on the newly identified TMPRSS2-ERG (or ETV1) gene arrangements; 2 Explore roles of Erg during ... |
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| Identification of Novel Genes and Candidate Targets in CML Stem Cells |
Jan-2009 |
32 pages |
| Authors:
Connie Eaves; Yun Zhao; BRITISH COLUMBIA CANCER AGENCY VANCOUVER
|
| Chronic myeloid leukemia (CML) is believed to originate from a normal hematopoietc stem cell acquiring the BCR-ABL fusion gene whose protein product has hyperactive tyrosine kinase activity. Though imatinib mesylate(IM) that targets BCR-ABL kinase activity is now widely used, its curative potential as a single agent is not sure, moreover it is unlikely to eliminate the CML stem cells either, which highlights the necessity to elucidate the molecular mechanism operative ... |
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| Autologous Marrow-Derived Stem Cell-Seeded Gene-Supplemented Collagen Scaffolds for Spinal Cord Regeneration as a Treatment for Paralysis |
Jan-2009 |
16 pages |
| Authors:
Myron Spector; BOSTON VA RESEARCH INST MA
|
| The long-term objective of this research is to develop a device for treating spinal cord injury. The specific aims of the proposed study are to test new types of collagen biomaterials. Moreover we will be investigating the effects of incorporating genes from nerve growth factors into the collagen scaffolds and seeding the scaffolds with neurogenic cells. The standardized defect site is a 5-mm gap in the rat thoracic spinal cord. ... |
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| Epigenetic Characterization of Ovarian Cancer |
Dec-2008 |
105 pages |
| Authors:
Susan K Murphy; DUKE UNIV MEDICAL CENTER DURHAM NC
|
| The overall objective of this research was to identify genes that are aberrantly methylated in epithelial ovarian cancer. Our approach was to treat or mock treat primary normal or tumor cultured cells with drugs that inhibit DNA methyltransferase activity and then perform microarray analysis to identify genes that are likely to exhibit methylation-mediated silencing. We also employed similar analysis of 43 ovarian cell lines. Two major criteria identified genes likely ... |
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| Tumor Suppressor Activity of the EphB2 Receptor in Prostate Cancer |
Nov-2008 |
96 pages |
| Authors:
Elena B Pasquale; BURNHAM INST LA JOLLA CA
|
| Mutations have been recently identified in the EphB2 receptor gene in prostate cancer suggesting that EphB2, a member of the large Eph receptor tyrosine kinase family, is a tumor suppressor in prostate cancer. Consistent with a tumor suppressor activity, we found that EphB2 is more highly expressed in non-transformed BPH-1 prostate epithelial cells than in several prostate cancer cell lines. Furthermore, EphB2 expression was rapidly lost in stably transfected DU145 ... |
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| Function of Klotho and is MicroRNA in Prostate Cancer and Aging |
Oct-2008 |
7 pages |
| Authors:
Shao-Yao Ying; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| We have observed the expression of CD164, IGFR, and Klotho proteins in human prostate cancer tissue microarrays as determined by immunohistochemistry. A positive correlation between CD164, IGFR and stages of prostate cancer was observed whereas a negative correlation between Klotho and stages was detected. However, the expression of Klotho in terms of the age of patients was not conclusive due to a small number of older (65 years) patients. Previously, ... |
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| Molecular and Clinical Predictors of Aggressive Prostate Cancer |
01-Sep-2008 |
28 pages |
| Authors:
Lorelei A Mucci; BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
|
| While prostate cancer is an important cause of cancer mortality, most men diagnosed with early prostate cancer experience an indolent course. We evaluated molecular and clinical predictors to distinguish lethal and indolent prostate cancer. In a related project, we tested the predictive value of a previously identified multigene tumor signature, a 12-gene model. Risk classification based on the 12-gene model predicted development of lethal disease 20 years hence. The best ... |
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| Notch Signaling and Schwann Cell Transformation: Development of a Model System and Application to Human MPNSTs |
Sep-2008 |
19 pages |
| Authors:
Tom Kadesch; PENNSYLVANIA UNIV PHILADELPHIA PA RESEARCH SERVICES
|
| This is a final report that presents data obtained during the grant?s duration of funding. The grant addresses the potential role of Notch signaling in the malignant transformation of neurofibromas to MPNSTs in patients with NF1. Our previous work has shown that constitutive expression of Notch can transform rat Schwann cells and that at least on MPNST-derived human Schwann cell line (of three examined) signals via Notch. This report includes ... |
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| Identifying Breast Cancer Bone Metastasis Genes. Addendum |
Aug-2008 |
11 pages |
| Authors:
LuZhe Sun; TEXAS UNIV AT SAN ANTONIO
|
| Bone metastasis is one of the major causes of morbidity and mortality in breast cancer (BC) patients. However, only a few human BC cell lines can efficiently metastasize to bone whereas most BC cell lines cannot. Recently, it was shown that systemic administration of the conditioned medium by a melanoma cell line redirected the metastatic dissemination of a weakly metastatic lung carcinoma cell line to the organ sites that were ... |
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| Detection of Tumor Suppressor Gene Mutations on 17p in DCIS |
Aug-2008 |
9 pages |
| Authors:
Lesleyann Hawthorn; HEALTH RESEARCH INC BUFFALO NY
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| The most powerful indicator of the location of TSGs in sporadic breast tumors has come from LOH studies. The implication is that a recessive mutation in the gene is exposed because the normal gene has been lost. DCIS is considered a precursor lesion of infiltrating ductal carcinoma (IDC). LOH at 17p is a recurrent observation specific to grade III DCIS and Grade III IDC suggesting a role for these alterations ... |
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| A Search for New Therapeutic Targets: Using Yeast to Find the GEF for Rheb |
Jul-2008 |
6 pages |
| Authors:
Janet Leatherwood; STATE UNIV OF NEW YORK AT STONY BROOK RESEARCH FOUNDATION
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| The Tsc1/2 complex known as Hamartin/Tuberin is mutated in the human disease Tuberous Sclerosis and such mutation predisposes for cancer. Tsc1/2 complex has a clearly established chemical release a GTPase Activating Protein or GAP for the small GTPase Rheb. Rheb in turn regulates TOP. The Tor kinases and associated proteins are large complex units that integrate signals pertaining to nutrients and proliferation potential. Tor promotes growth and proliferation and thus ... |
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| Genomic Approaches for Detection and Treatment of Breast Cancer |
Jul-2008 |
25 pages |
| Authors:
Stephen J Elledge; BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
|
| A key part of our research plan has been the development and use of retroviral vectors expressing RNA interference RNAs to identify human genes involved in causing or restraining cancer. In our first progress reports we described our efforts to develop shRNA libraries and showed they could be used to identify tumor suppressors. Ultimately our goal is to screen of complex pools of shRNA expressing retroviruses each marked with a ... |
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| ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone |
Jul-2008 |
33 pages |
| Authors:
Guozhi Xiao; PITTSBURGH UNIV PA
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| During the last year of support (from July 1, 2007 to June 30, 2008), our studies have made significant progresses in all aspects of the study: i) we demonstrate that PTH increases ATF4 expression and activity and ATF4 is required for PTH induction of Ocn expression in osteoblasts. ATF4 is a novel downstream target of PTH signaling in osteoblasts; ii) we show that ATF4 is required for the anabolic actions ... |
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| Chemoprevention of Breast Cancer by Mimicking the Protective Effect of Early First Birth |
01-Jun-2008 |
64 pages |
| Authors:
Malcolm C Pike; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| We have successfully shown that in the rat estradiol, estradiol plus progesterone, and beta-HCG is protective against carcinogen-induced mammary tumorigenesis. Progesterone alone was not protective; perphenazine was partially protective. Treatment and pregnancy induced RNA gene expression changes have been identified. Work on finding the lowest effective dose of estrogen has started. We have continued to collect normal breast tissue from women undergoing elective reduction mammoplasty. Estrogen receptor, progesterone receptors and ... |
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| Cytochrome c Gene and Protein Expression: Developmental Regulation, Environmental Response, and Pesticide Sensitivity in Aedes aegypti |
May-2008 |
9 pages |
| Authors:
Kenneth J Linthicum; Julia W Pridgeon; Liming Zhao; James J Becnel; Gary G Clark; AGRICULTURAL RESEARCH SERVICE GAINESVILLE FL CENTER FOR MEDICAL AGRICULTURAL AND VETERINARY ENTOMOLOGY
|
| Cytochrome c is a highly conserved protein that is found in many multicellular and unicellular organisms. Cytochrome c is a critical intermediate in apoptosis: a controlled form of cell death that kills cells as part of their natural process of development and in response to environmental condition. To detect whether cytochrome c of the mosquito Aedes aegypti (L.) (AeaCytC) is developmentally regulated, we used quantitative real-time polymerase chain reaction (PCR) ... |
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| Hypermethylation of AP-2Alpha as a Prognostic Marker for DCIS |
May-2008 |
10 pages |
| Authors:
Stephen B Baylin; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
|
| This proposal was initially based on the IDEA award concept that the abnormal gene promoter DNA methylation status of the AP2 gene might predict which DCIS lesions in women would be at risk for the evolution of recurrence and/or emergence of invasive cancer. As the work progressed the concept was expanded to include the DNA methylation status of additional genes for this purpose and also for the purpose of predicting ... |
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| Genomic and Expression Profiling of Benign and Malignant Nerve Sheath Tumors in Neurofibromatosis Patients |
May-2008 |
33 pages |
| Authors:
Brian Rubin; Torsten Nielsen; Matt van de Rijn; STANFORD UNIV CA
|
| The goal of the study is to identify genes that will serve as molecular markers for progression of neurofibroma to MPNST, and to identify potential therapeutic targets. miRNA expression profiling was performed on 6 cases of MPNSTs, and 7 cases of synovial sarcomas. By using unsupervised hierarchical clustering most tumors were grouped together according to tumor type. Subsequent analyses using Significance Analysis of Microarrays (SAM) identified miRNAs that differentiate between ... |
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| Investigation of a Putative Estrogen-Imprinting Gene, Phosphodiesterase Type IV Variant (Pde4d4), in Determining Prostate Cancer Risk |
01-Apr-2008 |
74 pages |
| Authors:
Wan-Yee Tang; CINCINNATI UNIV OH
|
| Estrogens are known to play a role in the initiation and progression of prostate cancer. Recently, environmental factors such as xenoestrogens have been reported on their prevalence of prostate diseases or cancers. Estrogen imprinting of the prostate gland is believed to associate with an increased incidence of prostatic lesions including inflammation, epithelial hyperplasia, squamous metaplasia, dysplasia and adenocarcinoma. And DNA methylation may be one of the possible mechanisms of the ... |
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| Identification of Genes Regulating the Development of Breast Cancer |
01-Apr-2008 |
33 pages |
| Authors:
Hua Wang; WISCONSIN UNIV-MADISON
|
| We have identified four different modifiers of Apc(min) that affect mammary tumor number or mammary tumor latency (Mmom1-Mmom4). To further investigate the molecular mechanisms of mammary modifiers, Mmom1 and Mmmom2 congenic mice were produced and tested for the effect on mammary tumor number or mammary tumor latency. The effect of Mmom2 on mammary tumor latency was confirmed in the congenic mice and the region containing Mmom2 was narrowed into a ... |
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| Developing a Zebrafish Model of NF1 for Structure-Function Analysis and Identification of Modifier Genes |
01-Apr-2008 |
14 pages |
| Authors:
Jonathan A Epstein; PENNSYLVANIA UNIV PHILADELPHIA
|
| This progress report summarizes the first year of activity of this project focused on the identification and characterization of the zebrafish orthologs of the neurofibromatosis type 1 genes. This project involves work within the Epstein laboratory and collaboration with the laboratory of Dr. Thomas Look at the Dana Farber Cancer Institute as a sub-contract. This progress report summarized the collaborative work including results from both groups. During the first year, ... |
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| Characterization of Clinically Attenuated Burkholderia mallei by Whole-Genome Sequencing: Candidate Strain for Exclusion from Select Agent Lists |
01-Apr-2008 |
7 pages |
| Authors:
David DeShazer; Jacques Ravel; Steven E Schutzer; Linda R Schiater; Catherine M Ronning; Benjamin J Luft; John J Dunn; Claire M Fraser-Liggett; William C Nierman; UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEWARK
|
| Background: Burkholderia mallei is an understudied biothreat agent responsible for glanders which can be lethal in humans and animals. Research with this pathogen has been hampered in part by constraints of Select Agent regulations for safety reasons. Whole genomic sequencing (WGS) is an apt approach to characterize newly discovered or poorly understood microbial pathogens. Methodology/Principal Findings: We performed WGS on a strain of B. mallei, SAVP1, previously pathogenic, that was ... |
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| Detection of Genes Modifying Sensitivity to Proteasome Inhibitors Using a shRNA Library in Breast Cancer |
01-Mar-2008 |
9 pages |
| Authors:
Gregory J Hannon; COLD SPRING HARBOR LAB NY
|
| By virtue of their accumulated genetic alterations, tumor cells may acquire vulnerabilities that create opportunities for therapeutic intervention. We have devised a massively parallel strategy for screening short hairpin RNA (shRNA) collections for stable loss-of-function phenotypes. We assayed from 6000 to 20,000 shRNAs simultaneously to identify genes important for the proliferation and survival of five cell lines derived from human mammary tissue. Lethal shRNAs common to these cell lines targeted ... |
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| Characterizing Candidate Oncogenes at 8q21 in Breast Cancer |
01-Mar-2008 |
12 pages |
| Authors:
Jessica Y Kao; STANFORD UNIV CA
|
| Breast cancer carcinogenesis is caused by molecular genetic changes. These genetic changes ultimately affect the transcriptome. Copy number alterations of the genome is a cardinal feature of cancer and plays an important role in tumor progression by altering the gene expression program. These regions of alteration are associated with oncogenes and tumor suppressor genes of known and unknown identity. Characterization of both CNA's and gene expression profiles have been carried ... |
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| Decreased Expression of the Early Mitotic Gene, CHFR, Contributes to the Acquisition of Breast Cancer Phenotypes |
01-Mar-2008 |
61 pages |
| Authors:
Lisa M Privette; MICHIGAN UNIV ANN ARBOR
|
| CHFR is an E3 ubiquitin ligase that reportedly delays mitosis in response to microtubule-targeting drugs (i.e. nocodazole and taxanes). Loss of CHFR mRNA expression has been reported in many cancers, including breast cancer, but the relevance of this to tumorigenesis remains unknown. The purpose of this study was to determine if CHFR was biologically relevant to breast cancer characteristics, progression, and genomic stability. As previously reported, nearly 40% of breast ... |
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| The Role of Tumor Metastases Suppressor Gene, Drg-1, in Breast Cancer |
01-Mar-2008 |
48 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among women in the US. Because metastatic disease is the major cause of death it is crucial to understand the mechanism by which tumor cells metastasize to the distant organs so that we can identify a better therapeutic target. During this funding period we had a breakthrough finding that the metastasis suppressor gene NDRG1 ... |
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| New Advanced Technology for Muscular Dystrophy |
01-Mar-2008 |
132 pages |
| Authors:
Johnny Huard; CHILDREN'S HOSPITAL OF PITTSBURGH PA
|
| Researchers continue to investigate whether gene transfer to skeletal muscle can enable both the production of proteins that might be therapeutic for muscle disorders and the systemic delivery of non-muscle proteins. Although the engineering of new mutant vectors has reduced the problems associated with viral cytotoxicity and immune rejection after gene transfer, the inability of most viral vectors to efficiently transduce mature muscle fibers continues to impede gene transfer to ... |
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| Structural Basis for TSC-1 TSC-2 Complex Formation |
01 MAR 2008 |
26 pages |
| Authors:
John A. Ladias; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Tuberous sclerosis complex (TSC) is a neurological disorder characterized by the formation of hamartomas in brain skin kidney and other organs. The tumor suppressor genes TSCI and TSC2 encode the proteins hamartin and tuberin respectively. The tuberin(1-418) region interacts with hamartin(302-430) forming the TSC1-TSC2 complex that functions in cell growth regulation. Certain mutations in TSC patients disrupt the hamartin-tuberin interaction indicating that association of these proteins is required for their ... |
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| Studies of Kinesins and Axonal Transport in a Mouse Model of NF1 |
MAR 2008 |
|
| Authors:
Vinodh Narayanan; CATHOLIC HEALTHCARE WEST PHOENIX AZ
|
 | In this research project, we investigated the hypothesis that mutation of the NF1 gene might alter axonal and dendritic transport in neurons. This might provide new insights into the development of cognitive defects in patients with neurofibromatosis 1. The significant results of this pilot research project are all derived from functional studies done by sciatic nerve ligation in wild-type and Nf1-/+ mice. After nerve ligation, proximal and distal segments of ... |
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| Decreased Expression of the Early Mitotic Gene, CHFR, Contributes to the Acquisition of Breast Cancer Phenotypes |
MAR 2008 |
61 pages |
| Authors:
Lisa M. Privette; MICHIGAN UNIV ANN ARBOR
|
| CHFR is an E3 ubiquitin ligase that reportedly delays mitosis in response to microtubule-targeting drugs (i.e. nocodazole and taxanes). Loss of CHFR mRNA expression has been reported in many cancers, including breast cancer, but the relevance of this to tumorigenesis remains unknown. The purpose of this study was to determine if CHFR was biologically relevant to breast cancer characteristics, progression, and genomic stability. As previously reported, nearly 40% of breast ... |
|
| Biomarkers for Amyotrophic Lateral Sclerosis in Active Duty Military (BALSAM) |
22-Feb-2008 |
55 pages |
| Authors:
David E Milhorn; CINCINNATI UNIV OH
|
| Purpose: 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 ... |
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| Disruption of the Circadian Rhythms of Gene Expression and the Development of Breast Cancer |
01-Feb-2008 |
11 pages |
| Authors:
David J Kennaway; ADELAIDE UNIV (AUSTRALIA)
|
| This project uses a mouse model to examine the effects of rhythm disruption on the expression of genes, the growth of breast cancer xenografts and spontaneous mammary tumours. Task 2: Task has been completed except for some additional gene expression assays. Task 3: Collection of tissues from the PyMT transgenic mice has been partially completed. Second cohort of animals are currently growing under the control and shiftwork simulation conditions. Task ... |
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| CBP and p27KIP1 in Prostate Carcinogenesis |
FEB 2008 |
9 pages |
| Authors:
Haojie Hunag; MINNESOTA UNIV MINNEAPOLIS
|
| CBP and p27KIP1 are two genes that are highly relevant to human prostate cancer. The objective of this proposal is to test the hypothesis that deletion of both alleles of CBP, in conjunction with deletion of one allele of p27KIP1, will result in the development of high-grade tumor in the prostate. The specific aims are to create CBP/p27KIP1 double knockout mice, to determine whether they present enhanced tumor progression compared ... |
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| Prostate Specific or Enriched Genes as Composite Biomarkers for Prostate Cancer |
Feb-2008 |
17 pages |
| Authors:
Biaoyang Lin; 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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| PARK2, a Large Common Fragile Site Gene, is Part of a Stress Response Network in Normal Cells that is Disrupted During the Development of Ovarian Cancer |
01-Jan-2008 |
18 pages |
| Authors:
Yu Zhu; David I Smith; MAYO CLINIC ROCHESTER MN
|
| PARK2 (Parkin) is a common fragile site (CFS) gene. We examined Parkin in primary ovarian tumors and found that this gene was frequently inactivated. We also found that re-introduction of Parkin is associated with greater sensitivity to apoptotic induction in ovarian cancer cell lines. We also discovered an entire family of very large common fragile site genes. We measured the expression of Parkin and 13 other CFS genes in panels ... |
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| Genes Involved in Oxidation and Prostate Cancer Progression |
01-Jan-2008 |
11 pages |
| Authors:
Elizabeth A Platz; JOHNS HOPKINS UNIV BALTIMORE MD BLOOMBERG SCHOOL OF PUBLIC HEALTH
|
| We are evaluating whether polymorphisms in genes involved in the genesis of oxidative species, detoxification of oxidative species, or repair of oxidative DNA damage influence risk of prostate cancer progression in men with clinically organ-confined prostate cancer. We identified 524 men with who underwent radical prostatectomy in 1993-2004 and who subsequently experienced biochemical recurrence, development metastases, or died from their prostate cancer. Using incidence-density sampling, we selected 524 men matched ... |
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| Prostate Expression Databases: Gene Expression Resources for Comparative Studies of Prostate Carcinogenesis |
JAN 2008 |
61 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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| BTG2 Antiproliferative Gene and Prostate Cancer |
Jan-2008 |
16 pages |
| Authors:
Paul D Walden; NEW YORK UNIV NY SCHOOL OF MEDICINE
|
| Based on our preliminary findings, the working hypothesis tested in this study was that the tumor suppressive activity of the BTG2 protein is diminished as an early event in prostate carcinogenesis due to increased proteasomal degradation, leading to compromised cell cycle regulation and increased cell invasion. During this study we showed that BTG2 protein expression is lost as an early event in prostate carcinogenesis and that prostate cancer cells degrade ... |
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| Identification of Prostate Cancer Related Genes Using Inhibition of NMD in Prostate Cancer Cell Lines. Addendum |
JAN 2008 |
5 pages |
| Authors:
Yurij Ionov; ROSWELL PARK CANCER INST BUFFALO NY
|
| A strategy to identify mutant genes using inhibition of nonsense mediated decay (NMD) in cell lines has been proposed by others. Blocking translation with antibiotic emetine has been shown to inhibit the NMD. Stabilization of mutant mRNA following the inhibition of NMD with emetine can be detected using microarray technology, such as Affymetrix genechips, for example. Unfortunately, too many genes that do not contain any mutations show mRNA increase following ... |
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| The Role of c-FLIP(L) in Regulating Apoptotic Pathways in Prostate Cancer |
01-Dec-2007 |
19 pages |
| Authors:
Aria F Olumi; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| Abnormalities in programmed cell death (apoptosis) machinery play a crucial role in initiation progression and metastasis of prostate cancer. Therefore molecules that initiate pro-apoptotic pathways are excellent therapeutic agents in prostate cancer. However some prostate cancer cells develop resistance to pro-apoptotic agents. In this proposal we are examining the regulatory mechanisms of c-FLIP(L) which is an important modulator of apoptosis in prostate cancer. |
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| Gene Expression Profiling of Nonhuman Primates Exposed to Aerosolized Venezuelan Equine Encephalitis Virus |
DEC 2007 |
12 pages |
| Authors:
James Koterski; Nancy Twenhafel; Aimee Porter; Douglas S. Reed; Susan Martino-Catt; Bruno Sobral; Oswald Crasta; Thomas Downey; Luis DaSilva; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Host responses to Venezuelan equine encephalitis viruses (VEEV) were studied in cynomolgus macaques after aerosol exposure to the epizootic virus. Changes in global gene expression were assessed for the brain, lungs, and spleen. In the brain, major histocompatibility complex (MHC) class I transcripts were induced, while the expression of S100b, a factor associated with brain injury, was inhibited, as was expression of the encephalitogenic gene MOG. Cytokine-mediated signals were affected ... |
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| Identification of Novel Retinoid Targets in Prostate Cancer |
NOV 2007 |
11 pages |
| Authors:
F. J. Piedrafita; SIDNEY KIMMEL CANCER CENTER SAN DIEGO CA
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| Retinoids function upon binding to nuclear retinoid receptors (RARs, RXRs) and have shown promise for the chemoprevention and treatment of prostate cancer. Novel synthetic retinoid-related molecules (RRMs) that function as RAR gamma/beta-selective agonists (MX3350-1, CD2325) or antagonists (MX781) were discovered with strong anticancer activity. These RRMs induce apoptosis independently of RARs. The cellular targets that mediate RRM-anticancer activity are unknown and theie mechanism of action is currently under investigation. The ... |
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