| PSMA-Activated Imaging Agents for Prostate Cancer |
Jul 2009 |
10 pages |
| Authors:
Samuel R Denmeade; JOHNS HOPKINS UNIV BALTIMORE MD
|
 | In preliminary studies, a potent TG analog (12ADT) was coupled to a series of pentapeptides composed of varying combinations of Asp and Glu to create PSMA-activated prodrugs. One of these prodrugs with the sequence 12ADT-Asp-Glu*Glu*Glu*Glu was efficiently hydrolyzed by PSMA and resulted in accumulation of high levels of the cleaved product in tumor tissue compared to normal tissue. The goal of this study is to take advantage of this selective ... |
|
| Investigation of the Spectroscopy and Kinetics of Transient Intermediates of Importance in the Decomposition of Energetic Materials |
27-May-2009 |
6 pages |
| Authors:
Paul J Dagdigian; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Infrared (IR) laser spectroscopy has been employed for both the spectroscopic and kinetic study of transient intermediates of importance in the decomposition of energetic materials using cavity ring-down spectroscopy (CRDS) and for the detection of organic residues, including energetic materials, by laser-induced breakdown spectroscopy (UBS) with infrared laser irradiation. CRDS in the hydride stretching region of the IR was employed to study the thermal decomposition of methyl azide to form ... |
|
| Isolation and Growth of Prostate Stem Cells and Establishing Cancer Cell Lines from Human Prostate Tumors |
May-2009 |
35 pages |
| Authors:
Donald Vander Griend; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The objective of this proposal was to isolate, grow, and characterize normal prostate stem cells and establish new prostate cancer cell lines from fresh human prostate tissues. The hypothesis is that prostate stem cells express defined stem cell markers, self-renew, and require the use of a feeder layer which is necessary for the establishment of prostate cancer cell lines from primary tumors. The goal of Specific Aim I was to ... |
|
| 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 ... |
|
| Self Managing the Consequences of Major Limb Trauma |
01-Mar-2009 |
15 pages |
| Authors:
Ellen J MacKenzie; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The objective of this research is to develop and evaluate the efficacy of a computer-based self management program (heretofore referred to as NextSteps Program) for reducing secondary conditions and improving function following major lower limb trauma. The intervention will build on widely accepted self-management programs developed for persons with arthritis as well as components of a face-to-face self-management program for civilians with long-standing limb loss. It will be necessary, however, ... |
|
| Telomere Length Polymorphisms: A Potential Factor Underlying Increased Risk of Prostate Cancer in African American Men and Familial Prostate Cancer |
Dec-2008 |
30 pages |
| Authors:
Alan K Meeker; JOHNS HOPKINS UNIV BALTIMORE MD
|
| This project tests the hypothesis that inherited and/or acquired differences in telomere length unprostate cancer observed in African Americans compared to Caucasians and in affected members of hefamilies. To test this hypothesis, telomere content in genomic DNA isolated from blood samples of by quantitative PCR and the data assessed for associations with either racial background or prostathe period of this report we have isolated genomic DNA from 128 members from ... |
|
| Development of Antigen Presenting Cells for Adoptive Immunotherapy in Prostate Cancer |
Dec-2008 |
15 pages |
| Authors:
Mathias Oelke; JOHNS HOPKINS UNIV BALTIMORE MD
|
| While adoptive immunotherapy holds promise as a treatment for cancer and infectious diseases, development has been impeded by the lack of reproducible methods for generating therapeutic numbers of antigen-specific CD8+ CTL. As a result, there are only limited reports of expansion of antigen-specific CTL to levels required for clinical therapy. Therefore, our groups has previously developed artificial Antigen-Presenting Cells (aAPC), made by coupling soluble HLA-Ig and anti-CD28 to beads. These ... |
|
| 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 ... |
|
| Outpatient Workload (RVU) Predictors: Age, Gender & Beneficiary Category |
15-Jun-2008 |
47 pages |
| Authors:
Charles Moniz; JOHNS HOPKINS UNIV BALTIMORE MD
|
| This retrospective study examines 1,529 data observations based on eligible beneficiaries who received outpatient care primary and specialty) within the catchment areas of three military treatment facilities located at Nellis AFB, Langley AFB and Travis AFB during fiscal year 2006. Data was collected from the Military Health System Management Analysis and Reporting Tool (M2). Univariate analysis of variance was used to determine the difference between workload, measured in relative value ... |
|
| Malonyl-CoA Decarboxylase (MCD) as a Potential Therapeutic Target for Breast Cancer |
May-2008 |
11 pages |
| Authors:
Francis P Kuhajda; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Fatty acid synthase (FAS) inhibition initiates selective apoptosis of cancer cells both in vivo and in vitro, which may involve malonyl-CoA metabolism. These findings led to exploration of malonyl-CoA decarboxylase (MCD) as a potential novel target for cancer treatment. MCD regulates the levels of cellular malonyl-CoA through the decarboxylation of malonyl-CoA to acetyl-CoA. Malonyl-CoA is both a substrate for FAS and an inhibitor of fatty acid oxidation acting as a ... |
|
| Prostate Cancer Detection by Molecular Urinalysis |
Apr-2008 |
81 pages |
| Authors:
Christian P Pavlovich; David Y Chan; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States. The goal of this training grant is to develop urinary makers for prostate cancer detection and prognostication and to train two physicians in clinical research. In this year, we continue to evaluate the feasibility of detection of prostate cancer by molecular urinalysis. We have found HGF along with IL18Bpa were ... |
|
| MURI Real Time, Explosive Specific Chemical Sensors: Spectroscopic and Time-Domain Detection of Trace Explosives in Condensed and Vapor Phases |
27 MAR 2008 |
31 pages |
| Authors:
James B. Spicer; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Under this MURI, research into the use of terahertz spectroscopy, femtosecond laser-induced breakdown spectroscopy, infrared spectroscopy, laser ionization-mass spectrometry and cavity ring-down spectroscopy for explosives detection was pursued. Fundamental studies have been completed that contribute to our understanding of explosives and how they behave when being sensed using the techniques selected for study. The highest level conclusion reached in this program is that all of the techniques have the ability ... |
|
| Self Managing the Consequences of Major Limb Trauma |
01-Mar-2008 |
15 pages |
| Authors:
Ellen J MacKenzie; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The objective of this research is to develop and evaluate the efficacy of a computer-based self management program (heretofore referred to as NextSteps Program) for reducing secondary conditions and improving function following major lower limb trauma. The intervention will build on widely accepted self-management programs developed for persons with arthritis as well as components of a face-to-face self-management program for civilians with long-standing limb loss. It will be necessary, however, ... |
|
| Robotic Prostate Biopsy in Closed MRI Scanner |
FEB 2008 |
68 pages |
| Authors:
Gregory Fischer; JOHNS HOPKINS UNIV BALTIMORE MD
|
| MRI possess many of the capabilities that TRUS is lacking for prostate brachytherapy and biopsy, with high sensitivity for detecting prostate tumors, high spatial resolution, excellent soft tissue contrast, and volumetric imaging capabilities. However, closed-bore high-field MRI has not been widely adopted for prostate interventions because strong magnetic fields and confined physical space present formidable challenges. This work enables prostate brachytherapy and biopsy procedures in standard high-field diagnostic MRI scanners ... |
|
| CDK5 as a Therapeutic Target in Prostate Cancer Metastasis |
JAN 2008 |
12 pages |
| Authors:
Barry D. Nelkin; JOHNS HOPKINS UNIV BALTIMORE MD
|
| We have recently found that CDK5 is active in prostate cancer cell lines and in almost all human metastatic prostate cancers, and inhibition of CDK5 activity resulted in reduction of spontaneous metastases by 79%. This suggests that CDK5 is a novel potential therapeutic target to limit prostate cancer metastasis. Based on our finding that CDK5 activity is present in prostate cancer and is important for metastasis, we intend to develop ... |
|
| Neurofibromatosis and the Painful Neuroma |
JAN 2008 |
28 pages |
| Authors:
Allan J. Belzberg; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Pain is a common and distressing symptom that impacts the quality of life of many patients with neurofibromatosis. The pain is often due to the formation of a neuroma. To understand better how neuromas cause pain and what treatments may be provided, we have developed an animal model of a painful neuroma. The tibial neuroma transposition (TNT) model has been confirmed as a model of neuropathic pain. The TNT model ... |
|
| Proof of Concept for Systematic Collection of Optimal Molecular Quality Anatomically Oriented Normal Prostate From Diverse Age and Race Transplant Donors |
DEC 2007 |
9 pages |
| Authors:
G. S. Bova; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The lack of availability of high-quality whole normal human prostate tissue from subjects of various ages and races impedes prostate cancer research in several ways. It prevents examination of prostate molecular pathologic changes on a time continuum, thus preventing the establishment of a definition of what the range of normal cellular activity is in a human male prostate for any one age or race. Just as important, the lack of ... |
|
| Evaluation of Fibroblast Activation Protein-Alpha (FAP) as a Diagnostic Marker and Therapeutic Target in Prostate Cancer |
DEC 2007 |
21 pages |
| Authors:
Nathaniel Brennen; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Our goal is to evaluate FAP expression patterns and enzymatic activity in both normal prostate tissue and at various stages of oncogenic transformation (i.e. PIA, PIN, Localized and Advanced Cancer) to determine tumor stage in which FAP expression may play a role. A second objective is to exploit this expression in the treatment of prostate cancer by developing therapies targeted for activation by FAP. This will be accomplished by identifying ... |
|
| Development of Antigen Presenting Cells for Adoptive Immunotherapy in Prostate Cancer |
DEC 2007 |
13 pages |
| Authors:
Mathias Oelke; JOHNS HOPKINS UNIV BALTIMORE MD
|
| While adoptive immunotherapy holds promise as a treatment for cancer and infectious diseases, development has been impeded by the lack of reproducible methods for generating therapeutic numbers of antigen-specific CD8+ CTL. As a result, there are only limited reports of expansion of antigen-specific CTL to levels required for clinical therapy. Therefore, our groups has previously developed artificial Antigen-Presenting Cells (aAPC), made by coupling soluble HLAIg and anti-CD28 to beads. These ... |
|
| Prostate Cancer Progression and Serum SIBLING (Small Integrin Binding N-Linked Glycoprotein)Levels |
OCT 2007 |
11 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 serum-based measurements of SIBLINGs among (a) normal individuals, (b) individuals with benign prostatic disease, (c) individuals with clinically defined prostate cancer, and (d) longitudinal samples ... |
|
| Pilot Comparison of Stromal Gene Expression Among Normal Prostate Tissues and Primary Prostate Cancer Tissues in White and Black Men |
SEP 2007 |
9 pages |
| Authors:
G. S. Bova; JOHNS HOPKINS UNIV BALTIMORE MD
|
| This hypothesis development project tested the feasibility of identification, laser capture microdissection, and expression analysis of prostate-stroma specific cells in normal and cancerous prostates, and aims to develop preliminary data sufficient to identify potential differences in stromal RNA expression in normal and cancerous prostate tissue. Our studies found that it is difficult but not impossible to histologically identify prostate zones with an acceptable degree of confidence in frozen tissues, eliminating ... |
|
| Characterization of Odin, a Novel Inhibitory Molecule, in EGF Receptor Signaling |
APR 2007 |
13 pages |
| Authors:
Jun Zhong; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Protein phosphorylation plays a key role in the regulation of the function of the proteins and the control of wild range of cellular process. Odin, one of signaling molecules identified in EGF receptor signaling pathway, functions as a negative regulator of growth factor receptor signaling pathways. To dissect the molecular mechanism of Odin in signaling pathway and its biological function, we employed SILAC methodology to identify 36 interacting proteins of ... |
|
| Prostate Cancer Detection by Molecular Urinalysis |
APR 2007 |
12 pages |
| Authors:
Christian P. Pavlovich; David Y. Chan; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States. The most common DNA alteration associated with prostate cancer is hypermethylation in the regulatory region of certain genes, particularly in the promoter of the pi-class glutathione- 5-transferase (GSTP1) gene. Analysis of hypermethylation of other gene promoters in combination has demonstrated high sensitivity and specificity for prostate cancer diagnosis. In this ... |
|
| Wireless Intrusion Detection |
MAR 2007 |
138 pages |
| Authors:
Albert A. Tomko; Christian J. Rieser; Louis H. Buell; David R. Zaret; William M. Turner; JOHNS HOPKINS UNIV BALTIMORE MD
|
| This report describes a Wireless Intrustion Detection (WIND) system that utilized physical layer features, derived from individual radio frequency packets, to identify network intrustions. The features considered include those intrinsic to the packet source, as well as those related to the propagation path between the source and a network access point. It is shown that the statistics of a set of packet features can be used to fingerprint each packet ... |
|
| Maintenance of Glucose Homeostasis through Acetylation of the Metabolic Transcriptional Coactivator PGC-1alpha |
FEB 2007 |
10 pages |
| Authors:
Pere Puigserver; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The purpose of this proposal is to test the hypothesis that acetylation of PGC-1alpha by the Acetyl Transferase GCN5 associated proteins, Pc3 and WDR18, is a key regulatory modification that controls hepatic glucose production. This investigation has a define scope to specifically test how these proteins control the acetylation status of PGC-1alpha and what is the functional effect in blood glucose levels. The major findings of this Research Technical Report ... |
|
| Neurofibromatosis and the Painful Neuroma |
JAN 2007 |
24 pages |
| Authors:
Allan J. Belzberg; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Pain is a common and distressing symptom that impacts the quality of life of many patients with neurofibromatosis. The pain is often due to the formation of a neuroma. To understand better how neuromas cause pain and what treatments may be provided, we have attempted to develop an animal model of a painful neuroma. We have completed the first of the three specific aims in this research project. The tibial ... |
|
| CDK5 as a Therapeutic Target in Prostate Cancer Metastasis |
JAN 2007 |
9 pages |
| Authors:
Barry Nelkin; JOHNS HOPKINS UNIV BALTIMORE MD
|
| We have recently found that CDK5 is active in prostate cancer cell lines and in almost all human metastatic prostate cancers, and inhibition of CDK5 activity resulted in reduction of spontaneous metastases by 79%. In this project, we intend to develop CDK5 as a novel therapeutic target. Therefore, we proposed to characterize a series of small molecule CDK5 inhibitors for specificity in cell culture, and for their effect on xenograft ... |
|
| Prostate Cancer Gene Discovery Using ROMA |
DEC 2006 |
7 pages |
| Authors:
William B. Isaacs; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The authors hypothesize that a subset of men who develop prostate cancer do so as a result of an inherited chromosomal deletion or amplification, affecting the function of one or more critical prostate cancer susceptibility genes. These chromosomal abnormalities, and the affected gene(s) can be identified using the novel technique, ROMA. Together with their collaborators at Cold Spring Harbor, they have now performed ROMA analysis of 90 prostate cancer patients, ... |
|
| Interactions between Dietary Factors and Inflammation in Prostate Carcinogenesis |
DEC 2006 |
15 pages |
| Authors:
Angelo M. DeMarzo; JOHNS HOPKINS UNIV BALTIMORE MD
|
| We are investigating whether inflammation can enhance prostate carcinogenesis in a rat model of dietary charred meat carcinogen induced cancers, and, whether antioxidant and other chemopreventative compounds can reduce prostate cancer in this model. We published a manuscript of some of the key data used for preliminary data in the original grant proposal. We completed part of aim 1 by treating PhIP treated Fisher rats with broccoli tea extract and ... |
|
| Intra-Operative Dosimetry in Prostate Brachytherapy |
NOV 2006 |
92 pages |
| Authors:
Ameet Jain; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Favorable outcome in prostate brachytherapy critically depends on the accurate placement of radioactive sources in their planned locations. Unfortunately, there is variety of mechanical factors that cause the seeds to divert from their planned locations. While this problem has been known to brachytherapists, current technology does not allow for reliable localization of the implanted sources, thereby prohibiting the prediction and modification of seed distribution intra-operatively. The Research Objective of the ... |
|
| Restoration of Transforming Growth Factor Beta Signaling by Histone Deacetylase Inhibitors in Human Prostate Carcinoma |
OCT 2006 |
11 pages |
| Authors:
Zheng D. Qian; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The goal of the current grant is to investigate the potential antitumor activity of histone deacetylase inhibitor MS-275 along with the activation of TGFb signaling pathway with the restoration of TGFb receptor II. As presented in our initial proposal prostate cancer cell line LNCaP has reduced expression in TGFbRII which is due to the promoter histone deacetylation. Subsequent treatment with chromatin remodeling agent MS-275 was able to restore the expression ... |
|
| Collaborative Research Program on Advanced Metals and Ceramics for Armor and Anti-Armor Applications Dynamic Behavior of Non-Crystalline and Crystalline Metallic Systems |
SEP 2006 |
36 pages |
| Authors:
K. T. Ramesh; James W. McCauley; JOHNS HOPKINS UNIV BALTIMORE MD
|
| This collaborative research program emphasized collaborative research between Johns Hopkins University and the U.S. Army Research Laboratory (ARL) towards well-defined common goals: the understanding and development of advanced metallic systems for armor and anti-armor applications. The Johns Hopkins side of the collaboration was operated through a science driven, problem-directed Center the Center for Advanced Metal and Ceramic Systems. The Center provides a tight integration of the University with ARL, providing ... |
|
| Multifunctional Magnetic Nanowires for Biomagnetic Interfacing Concepts |
14 JUL 2006 |
27 pages |
| Authors:
D. H. Reich; C. S. Chen; C. L. Chien; G. J. Meyer; K. Leong; P. C. Searson; G. Xiao; JOHNS HOPKINS UNIV BALTIMORE MD
|
| A technique of increasing importance in biotechnology is the manipulation of cells and biomolecules with small magnetic particles. In this research program, we developed a new type of carrier particle, multifunctional magnetic nanowires, which possess tunable magnetic and chemical properties. These nanowires can carry out multiple tasks e.g. binding multiple types of molecules, probing chemical activity in specific regions of a cell, and responding to light as well as to ... |
|
| Bone Sialoproteins and Breast Cancer Detection |
JUL 2006 |
75 pages |
| Authors:
Neal S. Fedarko; JOHNS HOPKINS UNIV BALTIMORE MD
|
| We have been studying a family of proteins that we have termed SIBLINGs for Small Integrin Binding Llgand N-linked Glycoproteins that share similar structural domains human chromosomal location normal synthesis by skeletal tissue and abnormal expression by neoplasms . The goal of our research is to test whether SIBLINGs might be informative markers for breast cancer detection. To accomplish this goal we have developed competitive enzyme-linked immunosorbent assays (ELISAs) for ... |
|
| Energetics and Structure Prediction of the Network of Homo- and Hetero-Oligomers Formed by the Transmembrane Domains of the ErbReceptor Family of Proteins |
JUN 2006 |
77 pages |
| Authors:
Karen G. Fleming; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The erbB/HER receptor proteins use a single transmembrane domain to mediate growth factor induced signal transduction across membranes. A complex network of both homo- and hetero-oligomeric interactions exists for the members of this receptor family. The goals of our research are to examine the role played by the transmembrane domain in this network of interactions. We have measured the energetics of homo- and hetero-oligomerization for the four human erbB transmembrane ... |
|
| Scalability, Accountability and Instant Information Access for Network-Centric Warfare |
JUN 2006 |
55 pages |
| Authors:
Yair Amir; JOHNS HOPKINS UNIV BALTIMORE MD
|
| This project focused on one main problem: How to scale intrusion tolerant replication to wide area networks while considerably improving performance. During the last few years, there has been considerable progress in the design of intrusion-tolerant (Byzantine) replication systems. The state of the art before this project performed well on small scale systems that were usually confined to local area networks. The project developed the first hierarchical Byzantine replication architecture ... |
|
| Corrective 111 In Capromab Pendetide SPECT Image Reconstruction Methods for Improved Detection of Recurrent Prostate Cancer |
JUN 2006 |
30 pages |
| Authors:
Benjamin M. Tsui; JOHNS HOPKINS UNIV BALTIMORE MD
|
| It is generally recognized that 111In capromab pendetide (PS) scans are technically challenging to perform and interpret, particularly with regard to pelvic SPECT studies used to detect possible disease in the prostate fossa and pelvic lymph node (LN). The hypothesis of this proposal is that the superior spatial resolution, high image contrast, and much reduced image artifacts that result from the corrective SPECT image reconstruction methods would substantially aid in ... |
|
| Selective Inhibition of T Cell Tolerance as a Means of Enhancing Tumor Vaccines in a Mouse Model of Breast Cancer |
JUN 2006 |
8 pages |
| Authors:
Jonathan Powell; JOHNS HOPKINS UNIV BALTIMORE MD
|
| To determine if the addition of Go6976 to vaccine protocols will inhibit neu specific tolerance and enhance immunotherapy for breast cancer. Scope: In the Her-2/neu model of spontaneous breast cancer the immune system of these transgenic mice are tolerant to the neu protein. While immunity to neu can be demonstrated in the neu-transgenic mice (partial breaking of tolerance), this immunity is inadequate to prevent the spontaneous development of tumors and ... |
|
| Akt Rescue in Cardiomyocytes but not Breast Cancer Cells After Doxorubicin and Anti-erB2 Treatment |
MAY 2006 |
14 pages |
| Authors:
Kathleen L. Gabrielson; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The proposed study will first evaluate the role of Akt, in protection against doxorubicin and anti-erbB2-cardiomyocyte toxicity, using adenoviral expression of active Akt, pharmacological inhibitors of this pathway, and two peptides that activate Akt, cardiotrophin-1 and urocortin. Since these peptides have not been reported expressed in breast tissues or cancer, to confirm this, we will evaluate the expression of both peptides and their receptors in six commonly studied breast cancer ... |
|
| Rational Inhibitors of DNA Base Excision Repair Enzymes: New Tools for Elucidating the Role of BER in Cancer Chemotherapy |
MAY 2006 |
22 pages |
| Authors:
Daniel J. Krosky; JOHNS HOPKINS UNIV BALTIMORE MD
|
| In this funding period we have extended our studies outlined in Tasks 1 and 2 of the approved Statement of Work with the development of a novel and versatile strategy to synthesize focused chemical libraries against DNA repair enzymes. A high-throughput screen of this focused library yielded several potent and specific inhibitors of human uracil DNA glycosylase. Investigations into the effects of inhibiting uracil DNA glycosylase with these small molecules ... |
|
| Identification of Breast Cancer Specific Proteolytic Activities for Targeted Prodrug Activation |
MAY 2006 |
15 pages |
| Authors:
Samuel R. Denmeade; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The underlying hypothesis of this proposal is that a breast tissue/cancer proteolytic activity can be identified by screening the extracellular fluid from human breast cancers with a fluorescence quenched random peptide library. The peptide substrate(s) identified from this screening could be used to produce prodrugs that are targeted for specific activation by proteolytic activity present in extracellular fluid of breast cancers while avoiding systemic toxicity. In the first year we ... |
|
| Role of Polyamine Oxidase (PAOh1/SMO) in Human Breast Cancer |
APR 2006 |
17 pages |
| Authors:
Allison Pledgie; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The induction of polyamine catabolism and its production of H2O2 have been implicated in the response to specific anti-tumor polyamine analogues. This project evaluates the ability of Bis(ethyl)norspermine (BENSpm) to induce the polyamine catabolic enzymes in human breast cancer cell lines and examines the role of their induction in the overall response of breast cancer cell lines to BENSpm treatment. To examine the role of the catabolic enzymes in the ... |
|
| Prostate Cancer Detection by Molecular Urinalysis |
APR 2006 |
8 pages |
| Authors:
Christian P. Pavlovich; David Y. Chan; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States. The most common DNA alteration associated with prostate cancer is hypermethylation in the regulatory region of certain genes, particularly in the promoter of the pi-class glutathione-S-transferase (GSTP1) gene. Analysis of hypermethylation of other gene promoters in combination has demonstrated high sensitivity and specificity for prostate cancer diagnosis. In this project, ... |
|
| Structure and Machanism-Base Design of ErbB Receptor Inhibitors |
SEP 2005 |
11 pages |
| Authors:
Daniel J. Leahy; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The work proposed for this award involved using the crystal structures of the extracellular domains of the EGF receptor (EGFR) and its homologs HER2/Neu/ErbB2, HER3/ErbB3, and HER4/ErbB4, which were recently determined in my lab and elsewhere, to design a new class of inhibitors of this family of receptors. These structures had shown that ligands bind to two separate surfaces in these receptors that are normally far apart in the absence ... |
|
| Pilot Comparison of Stromal Gene Expression Among Normal Prostate Tissues and Primary Prostate Cancer Tissues in White and Black Men |
SEP 2005 |
9 pages |
| Authors:
G. S. Bova; JOHNS HOPKINS UNIV BALTIMORE MD
|
| This critical hypothesis development project is still underway and we have requested a deadline extension without additional funding to allow us to complete the work. The two sources of the delay are 1) histological analysis of all tissues available for study took longer than expected but is now complete and 2) we have been working (using other sources of funding) to get a lab database ready to handle the data ... |
|
| Molecular Epidemiology of Breast Cancer in Korean Women |
AUG 2005 |
6 pages |
| Authors:
Edward W. Gabrielson; JOHNS HOPKINS UNIV BALTIMORE MD
|
| This project is testing the hypothesis that populations of women with significantly different demographic characteristics may not only have different incidences of breast cancers, but also different types of breast cancers. We are testing this hypothesis by examining gene expression profiles of breast cancers from two populations that differ apparently by only a single major variable: age. Specifically, we are measuring gene expression profiles by gene array technology and by ... |
|
| 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 ... |
|
| Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment |
AUG 2005 |
34 pages |
| Authors:
Robert J. Kurman; Ie-Ming Shih; Richard Roden; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The purpose of this study is to elucidate the pathogenesis of serous carcinoma by identifying the molecular genetic changes and preferentially expressed genes of different histological types of serous neoplasms. We hypothesize that the development of serous carcinoma proceeds along two main pathways: one is rapid progression from ovarian surface epithelium to high-grade serous carcinoma without well-established morphological precursors ( de novo pathway) and the other is a gradual development ... |
|
| Proton MR Spectroscopic Imaging in NF-1 |
01 JUL 2005 |
11 pages |
| Authors:
Peter B. Barker; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Neurofibromatosis Type 1 (NF-1) is the most common autosomal dominant genetic disorder, affecting the skin, central (CNS) and peripheral nervous systems. Children with NF-1 have an increased risk of developing significant learning disability (LD), cognitive impairment, and optic or brain stem gliomas. Cerebral magnetic resonance imaging (MRI) in NF-1 reveals regions of high signal intensity (often called "unidentified bright objects", or UBOs). The pathophysiology of UBOs is poorly understood, and ... |
|
| Endourethral MRI Guidance for Prostatic RF Ablation |
JUN 2005 |
120 pages |
| Authors:
Ergin Atalar; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Prostate cancer constitutes a major health problem. Although the medical techniques currently in use to diagnose prostate cancer are successful, the methods to stage the cancer and visualize the invasion and spread of the cancer are inadequate. MRI is known to be the best method for staging but it does not offer image resolution that is acceptable, especially for detecting disease in the anterior prostate. In the first year of ... |
|
Reports by Corporate Author
