| Generation of Recombinant Human AChE OP-Scavengers with Extended Circulatory Longevity |
NOV 2006 |
144 pages |
| Authors:
Avigdor Shafferman; ISRAEL INST FOR BIOLOGICAL RESEARCH NESS ZIONA
|
 | We demonstrate that chemical conjugation of polyethylene glycol (PEG) moieties to recombinant human acetylcholinesterase (rHuAChE) gives rise to OP bioscavenger species which reside for very long periods of time in the circulation of mice, regardless of their post-translation-modification state, and that circulatory elimination of AChE via specific amino acid-related epitopes can also be efficiently overcome by enzyme PEGylation. Taken together, these findings indicate that the circulatory residence is dictated primarily ... |
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| A Mouse Model to Investigate Postmenopausal Biology as an Etiology of Ovarian Cancer Risk |
NOV 2006 |
31 pages |
| Authors:
Xiangxi Xu; INSTITUTE FOR CANCER RESEARCH PHILADELPHIA PA
|
| This project is to use a unique mouse model to study the interaction of reproductive factors and genetic mutations in the development of ovarian cancer. Ovarian cancer often develops in women of peri-menopausal age. We found that the germ cell deficient Wv mice mimics postmenopausal biology and develop benign ovarian tumors. We plan to test the hypothesis that a synergy exists between oncogenic mutations such as p53, pten, or p27kip1 ... |
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| Anti-Angiogenic Action of Neutral Endopeptidase |
NOV 2006 |
15 pages |
| Authors:
David Nanus; CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK
|
| Angiogenesis, or the formation of new blood vessels from existing vasculature is an important event in tumor progression. It results from a complex, multistep biochemical cascade that is initiated by the activation of endothelial cells in response to angiogenic factors. In prostate cancers, angiogenic factors are produced by epithelial and stromal cells, and are believed critical to prostate cancer growth and progression. One of the most important of these factors ... |
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| Mouse Orthotopic Xenographs of Human Prostate Primary Tumors |
NOV 2006 |
9 pages |
| Authors:
Massimo Loda; DANA-FARBER CANCER INST BOSTON MA
|
| Currently, primary human tumor material is insufficient due to small size, multifocality and difficulty of visualization at macroscopic examination. This essentially prevents extensive studies aimed at distinguishing indolent and aggressive organ-confined prostate cancers. Understanding the molecular alterations governing tumorigenesis and cancer progression is the first step necessary for the design of effective and targeted therapies. For this reason, in recent years considerable efforts have been devoted to generate clinically relevant ... |
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| Development of STEAP-based Vaccines for the Treatment of Prostate Cancer |
NOV 2006 |
16 pages |
| Authors:
Maria de la L. Garcia-Hernandez; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Immunotherapy may provide an alternative treatment for cancer patients, especially when tumors over-expantigens that can be recognized by immune cells. The identification of markers and therapeutic targets that are up regulated in prostate cancer been important to design new potential treatments for prostate cancer. Among them, the recently identified six-transmembrane epithelial antigethe prostate (STEAP) is considered an attractive target, due to its over-expression in human prostate cancer tissues. Previously we ... |
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| A Novel Therapeutic Vaccine for Metastatic Mammary Carcinoma: Focusing MHC/Peptide Complexes to Lipid Rafts |
NOV 2006 |
90 pages |
| Authors:
Brian P. Dolan; MARYLAND UNIV BALTIMORE COUNTY BALTIMORE MD
|
| Genetic engineering of tumor cells to express MHC class ll and subsequent use of said cells for treatment of established and metastatic tumors has yielded promising results in animal models for treatment of breast cancer. It is widely believed that the vaccine efficacy is due to the ability of such tumor cells to present tumor-specific antigens to 004+ T helper cells which activate the immune system to eradicate tumors. Next ... |
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| The Role of CRELD1 Isoform 9b in the Pathogenesis of Breast Cancer |
OCT 2006 |
7 pages |
| Authors:
Cheryl L. Maslen; OREGON UNIV PORTLAND
|
| The goal is to develop a mouse model that expresses isoform 9b in mammary tissues, and to determine if CRELD1-9b causes or predisposes the mice to develop breast tumors, or participates in cancer progression. Scope: This study will determine if expression of CRELD1-9b contributes to the cause and/or progression of breast cancer. Information from this study will be used to better understand the relationship of CRELD1-9b to breast cancer tumor ... |
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| Identification of Genes Involved in Breast Tumor Invasion Utilizing a Ubiquitin-Mediated Proteolysis in Vitro Screen |
OCT 2006 |
9 pages |
| Authors:
Charles H. Spruck; SIDNEY KIMMEL CANCER CENTER SAN DIEGO CA
|
| In this proposal, we explored the potential use of ubiquitin-dependent proteolysis as a reverse genetics tool in functional genomics studies. We developed a retroviral-based system that artificially targets random cellular proteins to the proteolytic machinery for degradation. To achieve this, a randomized peptide library was linked to a segment of the F-box motif of beta- TrCP, the F-box protein that mediates the ubiquitination of I(kappa)B(alpha) and (beta)-catenin via the multimeric ... |
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| Preclinical Mouse Models of Neurofibromatosis |
OCT 2006 |
44 pages |
| Authors:
Kevin Shannon; CALIFORNIA UNIV SAN FRANCISCO
|
| This report describes the sixth year of research, and the first under this award, by a Consortium of investigators who have been continuously funded by this Program to develop, characterize, and utilize strains of mice that accurately model tumors found in persons with NF1 and NF2. This Consortium has generated many novel models of NF1 and NF2-associated tumors and has exploited these strains to investigate biologic and preclinical questions. In ... |
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| Knockout AR in Prostate |
OCT 2006 |
8 pages |
| Authors:
Chawnshang Chang; ROCHESTER UNIV NY
|
| Prostate cancer progresses from androgen-dependent to androgen-independent state. The androgen receptor (AR) is expressed throughout progression. We would like to understand the AR role in this progression. Using lox-Ore methodology we have generated mice in which AR function is abolished in the entire animal (ARKO) or tissue specific manner and generated mice with ARKO in prostate only or in different stages to be used to study prostate cancer (PCa) progresses. ... |
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| XIAP as a Molecular Target for Therapeutic Intervention in Prostate Cancer |
OCT 2006 |
21 pages |
| Authors:
Colin S. Duckett; MICHIGAN UNIV REGENTS ANN ARBOR DIV OF RESEARCH DEVELOPMENT AND ADMINISTRATION
|
| We have made very significant progress towards the completion of the goals proposed in this award. In the first of the two Aims, we proposed to generate cell lines in which we stably suppressed XIAP using lentiviral-based RNA interference, and subsequently to constitute XIAP expression using mutants which are incapable of suppressing caspases. While we have achieved these goals using PC-3 cells, we have encountered some issues of non-specificity when ... |
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| Genome Sequence Alterations Detected upon Passage of Burkholderia mallei ATCC 23344 in Culture and in Mammalian Hosts |
05 SEP 2006 |
12 pages |
| Authors:
Claudia M. Romero; David DeShazer; Tamara Feldblyum; Jacques Ravel; Donald Woods; H. S. Kim; Yan Yu; Catherine M. Ronning; William C. Nierman; INSTITUTE FOR GENOMIC RESEARCH ROCKVILLE MD
|
| Background: More than 12,000 simple sequence repeats (SSRs) have been identified in the genome of Burkholderia mallei ATCC 23344. As a demonstrated mechanism of phase variation in other pathogenic bacteria, these may function as mutable loci leading to altered protein expression or structure variation. To determine if such alterations are occurring in vivo, the genomes of various single-colony passaged B. mallei ATCC 23344 isolates, one from each source, were sequenced ... |
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| Mouse Model of Human Breast Cancer Initiated by a Fusion Oncogene |
SEP 2006 |
14 pages |
| Authors:
Stuart H. Orkin; CHILDREN'S HOSPITAL CORP BOSTON MA
|
| In this study, we generated a novel mouse model of human breast cancer based on a recurrent chromosomal translocation that produces the TEL-NTRK3 fusion oncogene, as the initiating mutation in human secretory breast carcinoma. In this model, we created a Ore-lox conditional knockin allele (TN) to express the TN fusion protein from the endogenous Tel locus in a tissue-specific manner. When TN is activated in mammary glands by whey acidic ... |
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| Effects of Extracellular Matix on DNA Repair in Vivo |
SEP 2006 |
9 pages |
| Authors:
Aylin Rizki; CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
|
| DNA damage in the form of double-strand breaks is caused by exposure to endogenous factors as well as in response to radiation therapy in breast cancer patients. Double-strand breaks can be repaired by homologous recombination or nonhomologous end joining pathways, both of which can lead to error-prone repair. Errors in repair lead to accumulation of mutations that may accelerate the process of tumorigenesis and malignant transformation. Apart from cell cycle ... |
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| Optical Spectroscopy and Multiphoton Imaging for the Diagnosis and Characterization of Hyperplasias in the Mouse Mammary |
SEP 2006 |
53 pages |
| Authors:
Melissa C. Skala; DUKE UNIV DURHAM NC
|
| The purpose of the first part of this project is to develop a method to diagnose mammary gland hyperplasias in an animal model in vivo using optical spectroscopy, so that the progression of benign lesions could be studied over time. The absorption and scattering parameters extracted from diffuse reflectance spectra measured in vivo were used to differentiate normal tissue (n=23) and benign lesions (n=16) in the mammary glands of ENU-treated ... |
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| Modulation of T Cell Tolerance in a Murine Model for Immunotheraphy of Prostatic Adenocarcinoma |
SEP 2006 |
28 pages |
| Authors:
Arthur A. Hurwitz; TRUE RESEARCH FOUNDATION SAN ANTONIO TX
|
| The goal of this project is to characterize T cell tolerance to prostate tumor antigens and to identify the role of costimulatory receptors in overcoming this tolerance. Identification of these processes will assist in the development of novel therapeutic approaches for treating prostate cancer. We use the TRAMP model a transgenic mouse line that develops primary prostatic tumors due to expression of the SV4O T antigen (TAg) under the transcriptional ... |
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| Dietary Fish Oil in Reducing Bone Metastasis of Breast Cancer |
SEP 2006 |
8 pages |
| Authors:
Nandini Ghosh-Choudhury; TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
|
| In a study of the mechanism behind the inhibitory effect of fish oil on the growth of breast cancer cells, the authors reported that fish oil, or w-3 polyunsaturated fatty acids (PUFAs), did the following: (1) increased the level of tumor suppressor protein PTEN; (2) inhibited the activity of PI 3 kinase, thus blocking a potent growth promoting signaling pathway; and (3) increased gene expression of BMP-2. In their final ... |
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| Efficient and Rapid Development of Transgenic Hamster Models of TSEs Using a Radical New Technology |
SEP 2006 |
8 pages |
| Authors:
Robert G. Rohwer; Irena Alexeeva; Marie Bugin; BALTIMORE RESEARCH AND EDUCATION FOUNDATION INC MD
|
| The development of blood-based or other diagnostic tests for the TSE diseases should be greatly facilitated by an integrated set of compatible resources: 1) a susceptible large animal (sheep) to provide blood or other substrates, 2) susceptible transgenic rodents that can be used as a sensitive bioassay, 3) standard reference samples of brain, blood, and plasma of sufficient volume to be used by the TSE community. We are breeding a ... |
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| Neurotrophin Therapy of Neurodegenerative Disorders with Mitochondrial Dysfunction |
SEP 2006 |
10 pages |
| Authors:
Linda L. Bambrick; MARYLAND UNIV BALTIMORE
|
| This research program will determine whether accelerated neuron death due to increased oxidative stress resulting from mitochondrial dysfunction can be compensated or corrected by neurotrophin stimulation. The experiments will be carried out in two models of mitochondrial dysfunction. 1)hippocampal neurons from the trisomy 16 mouse, which undergo increased apoptosis and have a mitochondrial defect, that has now been identified as a decrease in Complex I-mediated respiration and altered mitochondrial protein ... |
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| Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer |
SEP 2006 |
8 pages |
| Authors:
Christopher P. Evans; CALIFORNIA STATE UNIV SACRAMENTO
|
| In the past twelve months we have demonstrated that bombesin stimulates the androgen receptor preferentially to a proximal androgen response element in the promoter region rather than in the enhancer region, which is primarily stimulated by androgens. We have shown that gastrin-releasing peptide prostate cancer cells have their growth in soft agar inhibited by the specific Src inhibitor AZD0530. This is a dose-dependent response. AZD0530 abolishes the nuclear translocation of ... |
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| Early Host Responses to Prion Infection and Development of an In Vitro Bioassay |
SEP 2006 |
13 pages |
| Authors:
George A. Carison; MCLAUGHLIN RESEARCH INST GREAT FALLS MT
|
| The goal of this project is to identify pathways and networks of genes and proteins perturbed by prion replication. The unusual nature of prion disease prompted a systems approach to identify networks specifically perturbed by prion infections and to determine which perturbations are essential for various aspects of the disease. We previously tracked changes in gene expression ninbrain and spleen for two different prion strains and five different lines of ... |
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| Speed-Accuracy Tradeoff in Olfaction |
02 AUG 2006 |
13 pages |
| Authors:
Dmitry Rinberg; ALexel Koulakov; Alan Gelperin; MONELL CHEMICAL SENSES CENTER PHILADELPHIA PA
|
| The basic psychophysical principle of speed-accuracy tradeoff (SAT) has been used to understand key aspects of neuronal information processing in vision and audition, but the principle of SAT is still debated in olfaction. In this study we present the direct observation of SAT in olfaction. We developed a behavioral paradigm for mice in which both the duration of odorant sampling and the difficulty of the odor discrimination task were controlled ... |
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| Tumor-Secreted Autocrine Motility Factor (AMF): Causal Role in an Animal |
AUG 2006 |
6 pages |
| Authors:
John M. Chirgwin; VIRGINIA UNIV CHARLOTTESVILLE
|
| Cancer cachexia has three clinical features: I) loss of appetite (anorexia), 2) nutritional mal-absorption, and 3) muscle and fat wasting caused by tumor-stimulated factors. This project focused on muscle wasting. A number of factors have been proposed to cause cancer cachexia. Lack of progress in the area is unfortunate, given the tremendous benefit patients with advanced cancer would receive from effective treatment of cachexia to improve quality of life and ... |
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| In Vivo Molecular Imaging of Mammary Tumorigenesis in Murine Model Systems |
AUG 2006 |
23 pages |
| Authors:
Margaret S. Saha; COLLEGE OF WILLIAM AND MARY WILLIAMSBURG VA
|
| The development of accurate diagnostic tools and effective breast cancer treatments requires the ability to detect the presence of pre-cancerous, cancerous, and metastatic tissue and to identify the particular subtype or class of tumor. It is equally imperative to develop the capability of performing a molecular diagnosis non-invasively, employing in vivo imaging technologies in order to follow the tumor progression over time. This project entails an interdisciplinary approach which employs ... |
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| A Tissue Engineering Approach to Study the Progression of Breast Tumor Metastasis in Bone |
AUG 2006 |
7 pages |
| Authors:
Mingxin Che; Daotai Nie; WAYNE STATE UNIV DETROIT MI
|
| Most patients dying of breast cancer suffer painful bone metastasis. It is our hypothesis that the invasive growth and progression of breast metastatic lesions in bone requires the participation of various constituents from "soil". A reconstitution of such "soil" for the growth of breast metastatic cells will provide tremendous insights into factors critical for breast cancer growth in bone. We will firstly use our basic calcium minerals to reconstitute the ... |
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| Role of the Stem Cell Niche in Hormone-induced Tumorigenesis in Fetal Mouse Mammary Epithelium |
AUG 2006 |
15 pages |
| Authors:
Gloria Chepko; Leena Hilakivi-Clarke; GEORGETOWN UNIV WASHINGTON DC
|
| Develop an immunohistochemical method for identifying stem cells and stem cell niches, and to use this to determine if in utero estrogenic overstimulation causes changes in the number of stem cells or their niches. To extend the power of ex vivo stem cell isolation and enumeration by providing a way to identify functional cell types in situ. This identification method should ultimately provide a diagnostic refinement for mammary cancers. We ... |
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| Does Combination Immunotherapy With Human Monoclonal Antibodies Against HER2 and CXCR4 Augment Breast Cancer Killing in Vitro and Vivo? |
AUG 2006 |
8 pages |
| Authors:
Wayne A. Marasco; DANA-FARBER CANCER INST BOSTON MA
|
| The chemokine receptor CXCR4 and its ligand CXCL12 (SDF1 ) have been proposed to regulate the directional migration and invasion of breast cancer cells to sites of metastasizes. The CXCR4 molecule could be a potential target to control breast cancer. Human epidermal growth factor receptor-2 (HER2) overexpression contributes to tumor progression and metastasis. A humanized monoclonal antibody Herceptin (Trastuzumab) is currently in clinical use. Thus, both of CXCR4 and HER2 ... |
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| Are Anti-Inflammatory Lymphocytes Able to Induce Remission of Breast Cancer |
AUG 2006 |
|
| Authors:
Susan E. Erdman; MASSACHUSETTS INST OF TECH CAMBRIDGE
|
 | Recent studies suggest that inflammation is a key contributor to development of breast cancer in women. Increasing scientific and medical data point to immune cells, in particular pro-inflammatory CD4+ effector (TE) cells and anti-inflammatory CD4+regulatory (TR) cells, as pivotal mediators in human health and disease. We have previously demonstrated that antiinflammatory TR cells prevent colorectal cancer (CRC) in mice by suppressing inflammatory growth factors. We show here that transfer of ... |
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| The Role of C-SRC Activation in Prostate Tumor Progression |
JUL 2006 |
27 pages |
| Authors:
Gary E. Gallick; M D ANDERSON CANCER CENTER HOUSTON TX
|
| DOD Award number DAMD17-03-1-0484, The Role of c-Src Activation in Prostate Tumor Progression", had as its goal an understanding of how activation of the protein tyrosine kinase, Src, contributes to prostate tumor progression. During the award period, we demonstrated that Src activation directly contributes to the development of lymph node metastases by increasing the expression of vascular endothelial growth factor (VEGF). We demonstrated that Src must be activated (i.e. increased ... |
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| The Role of a Novel Topological Form of the Prion Protein in Prion Disease |
JUL 2006 |
7 pages |
| Authors:
Richard S. Stewart; WASHINGTON UNIV ST LOUIS MO
|
| Most(but not all) cases of prion disease are associated with a conformationally altered form of the prion protein (PrP) known as PrPSc. Several lines of evidence indicate that while PrpSc is the infectious molecule, it may not be the proximate cause of toxicity in prion disease. Several other candidates for such a toxic species have been proposed, including an altered topological form of PrP known as CtmPrP. Lines of transgenic ... |
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| The Role of DN-GSK3beta in Mammary Tumorigenesis |
JUL 2006 |
22 pages |
| Authors:
Marganit D. Farago; BOSTON MEDICAL CENTER CORP MA
|
| Recent studies have implicated ectopic activation of the Wnt pathway in many human cancers, including breast cancer. b-catenin is a critical co-activator in this signaling pathway, and is regulated in a complex fashion by phosphorylation, degradation, and nuclear translocation. Glycogen synthase kinase-3b (GSK3b) phosphorylation of the N-terminal domain of bcatenin targets it for ubiquitination and proteosomal degradation. We hypothesized that expression of dominant negative (DN) GSK3b in mammary glands would ... |
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| Posttranscriptional Regulation of the Neurofibromatosis 2 Gene |
JUL 2006 |
122 pages |
| Authors:
Long-Sheng Chang; CHILDREN'S HOSPITAL COLUMBUS OH
|
| Neurofibromatosis type 2 (NF2) is associated with a homozygous inactivation of the neurofibromatosis 2 (NF2) gene. Despite intense study of the NF2 gene, the mechanism by which the NF2 tumor suppressor acts to prevent tumor formation is not well understood. The goal of this research is to examine the role of posttranscriptional regulation of the NF2 gene. With this grant support, we have confirmed that vestibular schwannomas express a distinct ... |
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| Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens |
JUL 2006 |
7 pages |
| Authors:
R. T. Reilly; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
|
| HER-2/neu (neu) transgenic mice (neu-N mice) overexpress the neu proto-oncogene in a mammary specific fashion and develop spontaneous neuexpressing mammary neoplasia. The neu-N mouse model is among the most informative pre-clinical models available for the development of vaccine strategies for the treatment and prevention of breast cancer. The goal of this proposal was to test the hypothesis that reproductive hormones can modulate immunity to breast cancer antigens in neu-N mice. ... |
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| Integrated Cancer Research in Five Thematic Areas of Interest |
JUL 2006 |
10 pages |
| Authors:
Wadie F. Bahou; STATE UNIV OF NEW YORK AT STONY BROOK
|
| During the last FY of the award, the Cancer Institute of Long Island benefited from CDMRP funding in a manner consistent with the proposed activities of the award. In the area of core instrumentation acquisition, an Olympus upright microscope has been added and integrated in to the previously funded two-photon system. The new instrument is essential for in vivo imaging for mice and rats. The previously funded Zeiss TIRF Microscope ... |
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| High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals |
JUL 2006 |
36 pages |
| Authors:
Byron Caughey; NATIONAL INSTITUTES OF HEALTH HAMILTON MT ROCKY MOUNTAIN LABS
|
| Transmissible spongiform encephalopathies are fatal untreatable neurodegenerative diseases associated with the accumulation of a disease-specific form of priori protein (PrPSc) in the brain. One therapeutic approach is the inhibitors of PrPSc accumulation indeed many inhibitors of PrPSc accumulation in scrapie-infected cells also have anti-scrapie activity in rodents During This year. cell line derived from deer has been chronically infected with CWD to more effectively search for agents to combat that ... |
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| New Structural Approaches to Understanding the Disease Related Forms of the Prion Protein |
JUL 2006 |
19 pages |
| Authors:
David E. Wemmer; CALIFORNIA UNIV REGENTS BERKELEY
|
| The mouse pron protein peptide (residues 89-143 with the substitution of Leu for Pro atresidue 101) induces prion disease in sensitized mice. Samples of this peptide, isotope labeled with 15N, have been prepared by expression of a fusion in E.coli, cleaved to yield anunmodified peptide, and then fibrillized. Hydrogen exchange was allowed to occur in the fibrils for periods from 1 hour to 6 weeks. The extent of exchange was ... |
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| Does Skeletal Muscle Mass Influence Breast Cancer? Evaluating Mammary Tumorigenesis and Progression Genetically Hyper-Muscular Mice |
JUL 2006 |
9 pages |
| Authors:
Teresa Zimmers; MIAMI UNIV FL
|
| Epidemiologic evidence demonstrates that caloric restriction and physical activity independently reduce breast cancer. Conversely, obesity and insulin resistance are associated with increased breast cancer incidence, metastasis and mortality. To date, no studies have addressed the role of skeletal muscle in breast cancer. To determine the effect of skeletal muscle mass on breast cancer, we are measuring rates of chemically induced mammary tumorigenesis and progression in genetically hypermuscular mice. Mice lacking ... |
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| Functional Analysis of the Beclin-1 Tumor Suppressor Interaction With hVps34 (Type-III P13-Kinase) in Breast Cancer Cells |
JUN 2006 |
39 pages |
| Authors:
William A. Maltese; MEDICAL COLL OF OHIO AT TOLEDO
|
| 14. ABSTRACT: Macroautophagy plays a pivotal role in type II programmed cell death. Beclin 1 regulates macroautophagy. Overexpression of Beclin promotes autophagy and inhibits tumorigenesis in breast carcinoma cells, and conversely, heterozygous disruption of the Beclin gene can promote tumorigenesis in mice. In Year-1 we established that Beclin associates with the human type-III phosphatidylinositol 3-kinase (PI3K), hVps34, but not with another putative partner, Bcl-2. The lipid product of Vps34, PI(3)P, ... |
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| Chemoprevention of Breast Cancer by Mimicking the Protective Effect of Early First Birth |
JUN 2006 |
31 pages |
| Authors:
Malcolm C. Pike; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| We have successfully identified a set of breast tissue gene expression changes that distinguish parous from nulliparous rats and mice. This is a critical step in our development of a chemoprevention approach to mimic the protective effect of pregnancy in women. These differences are now being studied in women. We have also shown that breast epithelium is overwhelmingly concentrated in mammographically dense areas. This provides a deep insight into the ... |
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| A Novel Mouse Model for Genetic Validation of Therapeutic Targets in Breast Cancer |
JUN 2006 |
10 pages |
| Authors:
Gerardi Evans; CALIFORNIA UNIV SAN FRANCISCO
|
| Identifying the optimal molecular targets for effective and specific treatment of breast carcinoma is limited by our ignorance of which molecular pathways or network nodes are critical for the initiation, evolution and, above all, maintenance of breast cancers. Our overarching hypothesis is that although tumors appear genetically complex, they most probably are dependent upon a very much more limited repertoire of mutations for their maintenance. To test this hypothesis, we ... |
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| Mullerian Inhibiting Substances (MIS) Augments IFN-gamma Mediated Inhibition of Breast Cancer Cell Growth |
JUN 2006 |
30 pages |
| Authors:
Vandana Gupta; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| MIS is a member of the TGF family. The purpose of this study is to test the hypothesis that MIS and IFN-gamma might be more effective in the inhibition of breast cancer cell growth than either agent alone. We observed MIS and IFN-gamma costimulate IRF1 expression through NFkB and STAT pathways, respectively with a synergistic induction of CEACAM1 and MHCII mRNA expression, benisons of IRF1. In concordance with this observation, ... |
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| Targeting Tie2 to Increase Breast Cancer Responsiveness to Antiangiogenic Therapy |
JUN 2006 |
8 pages |
| Authors:
William Lee; PENNSYLVANIA UNIV PHILADELPHIA
|
| Antiangiogenic therapy of cancers targets tumor blood vessels to deprive malignant cells of oxygen and nutrients. Therapy of human cancers has produced poorer results than therapy of mouse tumors, a disparity that may be explained by more extensive coverage of human tumor vessels (e.g. in breast cancers) by pericytes, which may be rendering vessels more therapy-resistant. Mouse mammary tumor virus (MMTV)-induced mammary carcinomas reproduce the extensive pericyte coverage of tumor ... |
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| 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 ... |
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| A Novel Therapy System for the Treatment of Occult Prostate Cancer |
MAY 2006 |
10 pages |
| Authors:
Zhongyun Dong; CINCINNATI UNIV OH
|
| The goal of this research was to investigate efficacy and mechanisms of H5BVIFN- , a novel immunotherapeutic agent, against prostate cancer in animal models. The objectives in year 2 were to determine efficacy of a mixture of irradiated TRAMP-L5 mouse prostate cancer cells and lyophilized H5BVIFN- in regressing orthotopic tumors of TRAMP-L5 cells and to study effects of intratumoral injection of H5BVIFN- on expression of immune stimulatory cytokine in tumors. ... |
|
| Identification of Potential Therapeutic Mechanisms for HIP1 Inhibition in Breast Cancer |
MAY 2006 |
43 pages |
| Authors:
Theodora S. Ross; MICHIGAN UNIV ANN ARBOR
|
| The first hypothesis we are testing is that HIP1 expression is necessary for breast tumorigenesis. We have successfully generated a cohort of breast cancer prone mice (MMTV-Myc) that are deficient (n=20) or replete for HIP1 (n=20). The ongoing experiments show that HIP1 deficiency inhibits the formation of breast tumors. This result is similar to our work that demonstrated that HIP1 is necessary for prostate tumorigenesis (Bradley et al. 2005 Ca ... |
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| Antibody-Based Drug Carriers for Targeted Prostate Cancer Chemotherapy |
MAY 2006 |
8 pages |
| Authors:
Gennady Gololobov; TEXAS UNIV HEALTH SCIENCE CENTER AT HOUSTON
|
| The goal of this project was to create a universal, antibody-based drug delivery system for targeted delivery of small chemotherapeutic drugs to the site of prostate cancer. The authors wanted to explore the ability of the antibodies to reversibly hold small organic molecules (haptens or antigens) via non-covalent interactions with six flexible polypeptide loops (CDRs). Binding of this class of molecules, including chemotherapeutic drugs, usually does not require the participation ... |
|
| 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 ... |
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| Systemic Oncolytic Cytokine HSV Therapy of Prostate Cancer |
MAY 2006 |
11 pages |
| Authors:
Susan Varghese; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| We have made substantial progress toward the goals outlined in our grant application. In particular, we demonstrate the efficacy of systemically administered oncolytic viruses for the treatment prostate cancer in the transgenic TRAMP mouse model. We show that while intravenous administration of the NV1023 parental virus at 12 weeks of age (presence of prostate adenocarinoma) resulted in reduced tumor burden, the effects by the IL-12 expressing NV1042 virus were substantially ... |
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| Role of Notch/VEGF-Receptor 3 in Breast Tumor Angiogenesis and Lymphangiogenesis |
MAY 2006 |
11 pages |
| Authors:
Jan K. Kitajewski; COLUMBIA UNIV NEW YORK
|
| The overall objective is to define the interaction between Notch and VEGFR-3 signaling in breast cancer. We are examining a role for Notch in breast tumor vessels and attempting to block Notch and VEGFR-3 activity in breast tumors grown in mice. We proposed two aims: 1) studies of Notch/Dll4 function in murine mammary tumorigenesis and 2) studies of the inhibitory effects of a Notch antagonist (Notch decoy) in a murine ... |
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| Amplification of Anti-Tumor Immunity Without Autoimmune Complications |
MAY 2006 |
17 pages |
| Authors:
Wei-Zen Wei; WAYNE STATE UNIV DETROIT MI
|
| The goal is to combine Treg inactivation with Nau DNA vaccination to inhibit tumor growth in BALB NeuT mice without inducing excessive autoimmunity such as experimental autoimmune thyroiditis (EAT). We established a test system to access in the same animal the effect of tumor regression and mouse thyroglobulin immunization and observed a synergy between anti-neu and anti-mTg immunity. We tested the vaccination efficacy of pE2TM (encoding human Her-2 ECO and ... |
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Reports by Keyword(s)
MICE
