| Genetic Manipulation of Mammary Stem Cells to Reconcile Tumor Stem Cell Theory with Breast Cancer Heterogeneity |
Jul-2009 |
10 pages |
| Authors:
Justine Hutchinson; DARTMOUTH COLL HANOVER NH
|
 | This report serves as a progress report on the first year of my training grant. I have just completed my fourth year as a graduate student in Dartmouth Medical School's Department of Pharmacology and Toxicology, part of the Program in Experimental Molecular Medicine (PEMM). Dr. James DiRenzo serves as my mentor and chair of my thesis committee, and also directs the lab where I work, hereafter referred to as the ... |
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| Oxygen and Cell Fate Decisions |
27-May-2009 |
10 pages |
| Authors:
Qun Lin; Yuri Kim; Rodolfo M Alarcon; Zhong Yun; YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE
|
 | Molecular oxygen has been known to play a critical role in a wide range of biological processes including glycolysis, mitochondrial respiration, angiogenesis, pulmonary functions, and cardiovascular activities. An emerging theme has developed in recent years that oxygen has significant impact on embryonic development, maintenance of stem cells, and cellular differentiation or cell fate decisions. Among the notable observations, early embryonic development takes place in a hypoxic microenvironment. Hematopoietic stem cells ... |
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| Development of Medical Technology for Contingency Response to Marrow Toxic Agents Held January 1, 2009 Through March 31, 2009 |
11-May-2009 |
30 pages |
| Authors:
Michelle Setterholm; NATIONAL MARROW DONOR PROGRAM MINNEAPOLIS MN
|
 | 1. Contingency Prepardness: Collect information from transplant centers, build awareness of the Transplant Center Contingency Planning Committee and educate the transplant community about the critical importance of establishing a nationwide contingency response plan. 2. Rapid Identification of Matched Donors : Increase operational efficiencies that accelerate the search process and increase tient access are key to preparedness in a contingency event. 3. Immunogenetic Studies: Increase understanding of the immunologic factors important ... |
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| Development of Medical Technology for Contingency Response to Marrow Toxic Agents Held January 1, 2009 Through March 31, 2009 |
11-May-2009 |
19 pages |
| Authors:
Michelle Setterholm; NATIONAL MARROW DONOR PROGRAM MINNEAPOLIS MN
|
 | Contingency Preparedness: Collect information from transplant centers, build awareness of the Transplant Center Contingency Planning Committee and educate the transplant community about the critical importance of establishing a nationwide contingency response plan. Rapid Identification of Matched Donors : Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency event. Immunogenetic Studies: Increase understanding of the immunologic factors important in HSC transplantation. ... |
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| 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 ... |
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| Systemic and Gene Modified Mesenchymal Stem Cell Therapy for Metastatic Prostate Cancer |
May-2009 |
70 pages |
| Authors:
Selvarangan Ponnazhagan; ALABAMA UNIV IN BIRMINGHAM
|
 | Bone is the frequent metastatic site for human prostate cancer resulting in significant morbidity and mortality in patients with advanced disease. The type of bone defect encountered in prostate cancer bone metastasis is osteoblast lesions resulting in excess bone. However, initiation of osteoclastogenesis is first aided by osteolysis, mediated by osteoclasts. The areas provided as source for osteoblast accumulation later leads to thickening of the bone. In this proposal, we ... |
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| Inhibition of Rac GTPases in the Therapy of Chronic Myelogenous Leukemia |
Apr-2009 |
56 pages |
| Authors:
Jose Cancelas; CHILDREN'S HOSPITAL MEDICAL CENTER CINCINNATI OH
|
 | Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) characterized by the expression of the p210-BCR/ABL fusion gene [1]. This gene is produced by the reciprocal translocation (9; 22) (q34; q11) that juxtaposes the 3end of Abelson leukemia virus (ABL) gene with the 5' end of the breakpoint cluster region (Bcr) gene on chromosome 22. The transcript formed as a result encodes for the BCR/ABL fusion protein with constitutively ... |
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| Modulation of Stem Cells Differentiation and Myostatin as an Approach to Counteract Fibrosis in Muscle Dystrophy and Regeneration After Injury |
Mar-2009 |
64 pages |
| Authors:
Nestor F Gonzalez-Cadavid; CHARLES DREW UNIV LOS ANGELES CA
|
 | During Year 2 we have confirmed that muscle derived stem cells (MDSC) obtained from the wild type (wt) mouse skeletal muscle have in vitro a long-term myogenic capacity, but restricted to passages 10 to about 40-45 or earlier. The in vitro yield of myotubes from wt MDSC expressing myosin heavy chain II was not modified even at the optimal myotube forming capacity at early passages, by any of the several ... |
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| Using Human Stem Cells to Study the Role of the Stroma in the Initiation of Prostate Cancer |
Mar-2009 |
6 pages |
| Authors:
Gail Risbridger; MONASH UNIV CLAYTON (AUSTRALIA)
|
 | This project aims to determine the role of tumor stroma in prostate cancer biology. To do this, we are using a model of human embryonic stem cell (hESC) differentiation that was established in our laboratory. Using hESC-derived prostatic epithelial cells, we will test whether or not tumor stroma derived from human prostate cancer specimens will induce and initiate carcinogenesis. Our first task has been to optimize our current protocols of ... |
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| Characterization of Neurofibromas of the Skin and Spinal Roots in a Mouse Model |
Feb-2009 |
87 pages |
| Authors:
Yuan Zhu; PENNSYLVANIA UNIV PHILADELPHIA
|
 | Benign neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) contribute to the majority of morbidity and mortality associated with NF1. The proposed studies are attempting to provide insights into one of the fundamental questions in neurofibroma biology: whether bi-allelic NF1 inactivation is necessary for neurofibroma formation. The objectives of this proposal are to use a newly established mouse model to (1) identify and characterize neurofibromas that are exclusively or predominantly ... |
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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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| Enhanced Angiogenesis for Tissue Regeneration using Human Stem Cells and Biodegradable Nanoparticulate Polymeric Vectors |
Dec-2008 |
4 pages |
| Authors:
Fan Yang; Robert Langer; Seungwoo Cho; Said Botatyrev; Deepika Singh; Jordan J Green; Daniel G Anderson; MASSACHUSETTS INST OF TECH CAMBRIDGE DEPT OF CHEMICAL ENGINEERING
|
 | Mesenchymal stem cells (MSC) are progenitor cells which can differentiate down multiple lineages including bone. Ideally, scaffold for bone tissue engineering should exhibit biofunctionality of natural materials. In this regards, a novel polymeric biocomposite hydrogel was synthesized by covalently binding of polyethylene glycol (PEG). The most common injuries in battle fields are amputated limbs and massive loss of craniofacial tissues. Current therapies for traumatic tissue injury utilize non-biological and non-degradable ... |
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| The Bone Marrow Stem Cell Origin of Human Breast Cancer Using Transgenic Mouse Models |
Oct-2008 |
13 pages |
| Authors:
Sanford H Barsky; OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS
|
 | There is emerging evidence that transformed stem cells may be the source of human cancers. We felt that transgenic mouse models were ideally suited to examine this question and proposed to conduct marrow transplant experiments to test whether marrow stem cells are the cells of breast cancer origin. Our most significant findings included: 1) the demonstration that stromal cells within the transgenic breast cancers contain significant percentages of tissue macrophages, ... |
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| Characterization of Human Mammary Epithelial Stem Cells |
Oct-2008 |
17 pages |
| Authors:
Peter D Eirew; BRITISH COLUMBIA CANCER AGENCY VANCOUVER
|
 | The mammary epithelium of normal adult female mice contains stem cells with extensive in vivo regenerative and self-renewal potential. Analogous cells presumably exist in the mammary glands of adult women, and are candidate targets for the first transforming mutations that lead to the evolution of breast cancer stem cells. The objective of this grant is to develop a robust, quantitative and specific assay for these hypothesized normal human mammary stem ... |
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| Role of Myelofibrosis in Hematotoxicity of Munition RDX Environmental Degradation Product MNX |
Sep-2008 |
11 pages |
| Authors:
Sharon A Meyer; LOUISIANA UNIV AT MONROE
|
 | The purpose of this research is to determine mechanisms through which hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) environmental degradation product of high energetic munition hexahydro-1,3,5-trinitro-1,3,5-triazine(RDX) causes persistent anemia in the rat. We have hypothesized MNX targets hematopoeitic stem cells and like other myelosuppressive chemicals will be fibrogenic to the bone marrow. Findings of this period are: 1) detection of extramedullary hematopoiesis in support of the hypothesis that RDX is toxic to hematopoietic bone marrow ... |
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| Identify in Breast Cancer Stem Cell-Like Cells the Proteins Involved in Non- Homologous End Joining DNA Repair |
Sep-2008 |
32 pages |
| Authors:
Hong Yin; LOUISIANA STATE UNIV IN SHREVEPORT HEALTH SCIENCE CENTER
|
 | Breast cancer stem cells exist in several breast cancer cell lines based on recognized surface marker CD44+/CD24 or low or Hoechst efflux/ABCG2. The increased radiation resistance of breast cancer stem-like cells (CD44+/CD24 or low) was found in MCF-7, HCC1937, and MDA-MB-231 cells lines. The differential radiation resistance among the subpopulation might not rely on the NHEJ activity. Differential activation of ATM pathway could contribute to differential radiation resistance among the ... |
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| Novel Transgenic Mouse Model for Testing the Effect of Circulating IGF-I on Mammary Stem/Progenitor Cell Number and Tumorigenesis |
Aug-2008 |
7 pages |
| Authors:
Adrian V Lee; BAYLOR COLL OF MEDICINE HOUSTON TX
|
 | Epidemiological evidence indicates that high levels of circulating IGF-I (within the normal range) predict risk of breast cancer. To examine this experimentally, investigators have previously injected mice with IGF-I and shown that this increases mammary cancer incidence and progression. However, injection of IGF-I may create non-physiological peaks of IGF-I in the circulation. In this proposal we tested whether transgenic mice (TTR-IGF-I) that had a 30% increase in circulating levels of ... |
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| Mesenchymal Stem Cell as Targeted-Delivery Vehicle in Breast Cancer |
01-Jun-2008 |
17 pages |
| Authors:
Xiaoyuan Chen; STANFORD UNIV CA
|
 | Mesenchymal stem cells (MSCs) have been proposed to be cellular vehicles for the targeted delivery and local production of biological agents in tumors. In this proposal we will stably transfect mesenchymal stem cells with a lentiviral vector containing a therapeutic gene and dual reporter gene mrfp-ttk. Specific Aims: 1) We will monitor breast cancer tropism of mesenchymal stem cells by multimodality imaging techniques; 2) We will demonstrate the ability of ... |
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| Characterization of the Hematopoietic Stem Cell in the Peripheral Blood of Patients with Idiopathic Myelofirosis |
Jun-2008 |
6 pages |
| Authors:
Ronald Hoffman; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
 | The clinical course of patients with Philadelphia chromosome negative myeloproliferative disorder (MPD) is frequently complicated by thrombotic events. Post-natal vasculogenesis has been proposed to play a critical role in angiogenesis by acting through a hierarchy of endothelial progenitor cells (EPC). Some EPC have been shown to share a number of features associated with monocytes while other more primitive progenitor cells produce EC in vitro exclusively. The cells which share features ... |
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| Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical, Hematompoietic Progenitor-Cell Transplant |
01-May-2008 |
33 pages |
| Authors:
Laurence Cooper; Rita Young; M D ANDERSON CANCER CENTER HOUSTON TX
|
 | To develop T-cell therapies for B-cell malignancies we have developed a chimeric antigen receptor (CAR) which when expressed on the cell surface redirects T-cell specificity for CD19, a B-lineage cell-surface antigen. We have undertaken a series of systematic experiments to improve the ability of these CAR+ T cells to persist after adoptive transfer based on conditional expression of interleukin-2 (IL-2) which is a potent cytokine that can prolong T-cell persistence. ... |
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| Isolation and Growth of Prostate Stem Cells and Establishing Cancer Cell Lines from Human Prostate Tumors |
May-2008 |
31 pages |
| Authors:
Vander; Donald J Griend; JOHNS HOPKINS HOSPITAL 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 ... |
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| Quarterly Performance/Technical Report of the National Marrow Donor Program (Trademark) |
30 APR 2008 |
21 pages |
| Authors:
Michelle Setterholm; NATIONAL MARROW DONOR PROGRAM MINNEAPOLIS MN
|
 | 1. Contingency Prepardness: Collect information from transplant centers, build awareness of the Transplant Center Contingency Planning Committee and educate the transplant community about the critical importance of establishing a nationwide contingency response plan. 2. Rapid Identification of Matched Donors : Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency event. 3. Immunogenetic Studies: Increase understanding of the immunologic factors important ... |
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| Targeted Eradication of Prostate Cancer Mediated by Engineered Mesenchymal Stem Cell |
01-Apr-2008 |
11 pages |
| Authors:
Yan Cui; LOUISIANA STATE UNIV NEW ORLEANS
|
 | Prostate cancer is the second leading cause of cancer death among men in North America. Our long-range goal is to develop an innovative non-invasive approach to reach those metastatic prostate cancer cells via tumor interacting stroma cells and eliminate them on-site through cytotoxic gene delivery. This is achieved by using engineered mesenchymal stem cells (MSC) as a gene delivery vehicle to reach tumor cells as they tend to serve as ... |
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| Identification of Human Prostate Cancer Stem Cells by Creation and Characterization of Prostaspheres |
01-Apr-2008 |
39 pages |
| Authors:
Isla Garraway; CALIFORNIA UNIV LOS ANGELES
|
 | Stem cells (SCs) are present in specialized niches within tissues and enable long-term organ function by replacing dying cells over time. SCs have the unique capability for self-renewal and can be stimulated to transform into different cell types within the organ. Since SCs are genetically coded to live longer than other cells and resist mechanisms that would normally induce cell death, they may be especially susceptible to carcinogenic changes. Recent ... |
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| Modulation of Stem Cells Differentiation and Myostatin as an Approach to Counteract Fibrosis in Muscle Dystrophy and Regeneration after Injury |
01-Mar-2008 |
102 pages |
| Authors:
Nestor F Gonzalez; CHARLES R DREW UNIV OF MEDICINE AND SCIENCE LOS ANGELES CA
|
 | Muscle derived stem cells (MDSC) were isolated from the myostatin wild type mouse (Wt) the myostatin knock out mouse (Mst ko) and a DMD mouse model (mdx) and shown that: 1) Implants of Wt MDSC regenerate in vivo smooth muscle tissue and other cell types in injured or impaired tissue and correct the functional dysfunction created by the loss of these cells and myofibroblast generation and also convert into myofibers ... |
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| Function of PTP1B in Neuroendocrine Differentiation of Prostate Cancer |
JAN 2008 |
33 pages |
| Authors:
Jiaoti Huang; ROCHESTER UNIV NY
|
 | The goal of the project is to identify the molecular mechanisms responsible for therapeutic failure in prostate cancer patients receiving hormonal therapy Scope: The scope of the project is to use prostate cancer cell lines in in-vitro cell culture systems to study the complex signal transduction pathways that may be responsible for the neuroendocrine differentiation of prostate cancer cells, particularly the relationship of PTP1B to IL-8 signaling through its receptors ... |
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| Cells with Unique Properties in Prostate Cancer-Associated Stroma are Mesenchvmal Stem Cells |
DEC 2007 |
11 pages |
| Authors:
Donna M. Peehl; STANFORD UNIV CA
|
 | The importance of tumor stroma in prostate cancer development and progression has been recognized through its stimulating effects on cancer cell growth, migration and angiogenesis. Our hypothesis was that the prostate cancer stroma is derived, at least in part, from mesenchymal stem cells (MSCs) that are proliferative, multipotent and self-renewing. Our objective was to demonstrate that cancer-derived stromal cells have characteristics of mesenchymal stem cells. Comparing primary cultures of stromal ... |
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| Properties of Leukemia Stem Cells in a Novel Model of Cml Progression to Lymphoid Blast Crisis |
01-Oct-2007 |
9 pages |
| Authors:
Craig T Jordan; ROCHESTER UNIV NY
|
 | The objective of the study was to employ a novel mouse model of CML blast crisis to characterize various forms of leukemia stem cells (LSC) and their relative properties. In particular, distinguishing how differing normal target cells contribute to disease pathogenesis was regarded as an important priority in establishing relative heterogeneity of LSC. |
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| Identify in Breast Cancer Stem Cell-Like Cells the Proteins Involved in Non-Homologous End Joining DNA Repair |
SEP 2007 |
24 pages |
| Authors:
Hong Yin; LOUISIANA STATE UNIV IN SHREVEPORT HEALTH SCIENCE CENTER
|
 | In breast cancer stem-like cells could contribute not only to the initiation of the cancer but also to recurrence because of the resistance of stem cells to chemo/radiation therapy. From several breast cancer cell lines we have demonstrated the existence of breast cancer stem-like cell subpopulations based on the recognized cell surface markers CD44+/CD24 and ABCG2-mediated Hoechst effiux. After radiation we found that a CD44+/CD24-or low subpopulation showed increased clonogenic ... |
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| Novel Transgenic Mouse Model for Testing the Effect of Circulating IGF-I on Mammary Stem/Progenitor Cell Number and Tumorigenesis |
AUG 2007 |
7 pages |
| Authors:
Adrian V. Lee; BAYLOR COLL OF MEDICINE HOUSTON TX
|
 | Epidemiological evidence indicates that high levels of circulating IGF-I (within the normal range) predict risk of breast cancer. To examine this experimentally investigators have previously injected mice with IGF-I and shown that this increases mammary cancer incidence and progression. However injection of IGF-I may create non-physiological peaks of IGF-I in the circulation. In this proposal we tested whether transgenic mice (TTR-IGF-I) that had a 30% increase in circulating levels of ... |
|
| Unmasking Stem/Progenitor Cell Properties in Differentiated Epithelial Cells Using Short-term Transplantation |
AUG 2007 |
12 pages |
| Authors:
Michael T. Lewis; BAYLOR COLL OF MEDICINE HOUSTON TX
|
 | Background: Prevailing models maintain that stem cells comprise a minority of epithelial cells. However, some data suggest the percentage of mammary stem cells may be underestimated using common assays. Rationale: Short term transplantation using fragments of mammary duct offer an opportunity to test the prevailing stem cell model. If division-competent stem cells represent a small percentage of all epithelial cells, the initial rate of cell division in transplanted fragments should ... |
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| Development of Micro-Scale Assays of Mammary Stem and Progenitor Cells |
JUL 2007 |
29 pages |
| Authors:
Amy L. Paguirigan; WISCONSIN UNIV-MADISON
|
 | The main focus of this work is to study the effects of population demographics in the mammary gland on cancer risk using mathematical means and employ microtechnology for in vitro studies of primary cell characteristics. Specific attention has been paid to developing more quantitative methods for analyzing microfluidic cell cultures using In Channel Westerns. Also understanding how the microfluidic culture platform differs from traditional macro-scale techniques is critical. By thoroughly ... |
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| A Novel Strategy for Isolation, Molecular and Functional Characterization of Embryonic Mammary Stem Cells Using Molecular Genetics and Microfluidic Sorting |
JUN 2007 |
9 pages |
| Authors:
Geoffrey Wahl; SALK INST FOR BIOLOGICAL STUDIES LA JOLLA CA
|
 | We are developing a genetic system to identify isolate and characterize mammary stem cells. Our system consists of both activator and reporter components. The activator component is dependent both on Wnt signaling which is essential for mammary gland development and on doxycycline to toggle the system on and off. The reporter component labels cells for direct visualization. We used a modular design to enable the system to be applied to ... |
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| Implications of Stem Cell Growth Regulation for Breast Cancer |
JUN 2007 |
9 pages |
| Authors:
Caroline M. Alexander; WISCONSIN UNIV-MADISON
|
 | We propose that mammary stem cells could be involved in tumor development in either of two ways. The first is that altered function could change the course of development, and affect the susceptibility to transformation in adult life. We have found and characterized a model to test this hypothesis, and have preliminary array data to describe these cell populations. The second way that mammary stem cells could affect tumor development ... |
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| Chemo Resistance of Breast Cancer Stem Cells |
01 MAY 2007 |
79 pages |
| Authors:
Max S. Wicha; MICHIGAN UNIV ANN ARBOR
|
 | There is increasing evidence that breast cancers are driven by a small subcomponent that displays stem cell properties. We hypothesize that these breast cancer stem cells are resistant to chemotherapy and may contribute to tumor relapse. In order to provide evidence for this, we determined the effect of chemotherapeutic agents on breast cancer stem cell populations in primary mouse xenografts. Tumor regression induced by these chemotherapeutic agents is accompanied by ... |
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| Cord Blood Stem Cell Procurement in Minority Donors |
MAR 2007 |
10 pages |
| Authors:
Voravit Ratanatharathorn; WAYNE STATE UNIV DETROIT MI
|
 | This progress report summarizes the clinical activity of cord blood procurement and the preliminary analysis of the yield of cord blood cells for the purpose of clinical transplantation. The purpose of collection and procurement of cord blood is for public use and will be accessible to all stem cell transplantation centers worldwide. Cord blood is a readily available source of hematopoietic stem cells. It is more accessible than other sources ... |
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| A BCR-ABL Kinase Activity-Independent Signaling Pathway in Chronic Myelogenous Leukemia |
FEB 2007 |
14 pages |
| Authors:
Shaoguang Li; JACKSON LAB BAR HARBOR ME
|
 | The BCR-ABL tyrosine kinase inhibitor imatinib mesylate (Gleevec) is the preferred treatment for human chronic myeloid leukemia (CML), but does not cure mice with BCR-ABL-induced acute lymphoblastic leukemia (ALL), similar to CML lymphoid blast crisis. The inability of imatinib to cure CML in mice leads us to hypothesize that a BCR-ABL kinase activity-independent pathway also plays a critical role in the development of this disease. We identified Src kinases as ... |
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| Origin and Properties of Prostatic Stem Cells |
FEB 2007 |
32 pages |
| Authors:
E. L. Wilson; Rashmi Gupta; NEW YORK UNIV NY SCHOOL OF MEDICINE
|
 | The aims of this proposal were to isolate and characterize prostatic epithelial stem cells and also to determine if bone marrow (BM) cells can differentiate into prostatic tissue. We show that the murine prostate contains a small population of cells ( |
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| Angiogenesis Research to Improve Therapies for Vascular Leak Syndromes, Intra-Abdominal Adhesions, and Arterial Injuries |
FEB 2007 |
78 pages |
| Authors:
Judah Folkman; Mark Puder; Joyce Bischoff; CHILDREN'S HOSPITAL MEDICAL CENTER BOSTON MA
|
 | The three goals of this project are: (i) to discover and develop novel drugs which could prevent or reverse the vascular leak syndrome; (ii) to develop angiogenesis inhibitors which would inhibit post-operative abdominal adhesions; and, (iii) to isolate endothelial progenitor cells from blood, capable of being expanded in vitro and applied to vascular grafts. Progress has been made in each category: we have demonstrated suppression of vascular leak by Caplostatin ... |
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| Mechanism of Action of Prostate Stem Cell Antigen Targeted Antibody Therapy and Its Relevance to Clinical Application in Prostate Cancer |
JAN 2007 |
7 pages |
| Authors:
Robert Reiter; Chau Tran; CALIFORNIA UNIV LOS ANGELES
|
 | We have recently demonstrated that a monoclonal antibody against prostate stem cell antigen (PSCA) can exert anti-tumor activity in a xenograft animal model, suggesting oncogenic activity of PSCA in prostate cancer. Therefore the our goal is to elucidate the role of PSCA in the development of prostate cancer. A better understanding of PSCA function and its antibody activity will enable rational patient selection and trial design, all of which are ... |
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| Autologous Marrow-Derived Stem Cell-Seeded Gene-Supplemented Collagen Scaffolds for Spinal Cord Regeneration as a Treatment for Paralysis |
JAN 2007 |
29 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 tubes and porous collagen scaffolds. Moreover we will be investigating the effects of incorporating genes from nerve growth factors into the collagen scaffolds and seeding the scaffolds with marrow-derived mesenchymal stem cells. The standardized defect site is a 5-mm gap ... |
|
| Quarterly Performance/Technical Report |
DEC 2006 |
20 pages |
| Authors:
Patricia A. Coppo; NATIONAL MARROW DONOR PROGRAM MINNEAPOLIS MN
|
 | 1. Contingency Preparedness: Collect information from transplant centers, build awareness of the Transplant Center Contingency Planning Committee and educate the transplant community about the critical importance of establishing a nationwide contingency response plan. 2. Rapid Identification of Matched Donors : Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency event. 3. Immunogenetic Studies: Increase understanding of the immunologic factors important ... |
|
| Bioengineered Skin From Stem Cells for Treatment of Cutaneous Vesicant Injury |
01-Nov-2006 |
8 pages |
| Authors:
Myriane Isidore; Richard K Gordon; Madhusoodana P Nambiar; Michael P Castagna; Kenneth C Rogers; Ruthie H Ratcliffe; Bhupendra P Doctor; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
|
 | Severe exposure to HD induces blistering skin reactions and significant loss of stem cell keratinocytes that are required for a continuous renewal of the epidermal cell layer. Therefore, HD injuries require long healing periods leaving significant cosmetic and/or functional deficits. We are developing bioengineered skin from embryonic stem cells for improved therapy for HD-induced skin damage. Since stem cell keratinocytes lack major histocompatibility class II antigens, they exhibit little immunogenicity ... |
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| Properties of Leukemia Stem Cells in a Novel Model of CML Progression to Lymphoid Blast Crisis |
OCT 2006 |
9 pages |
| Authors:
Craig T. Jordan; ROCHESTER UNIV NY
|
 | Progression of CML from chronic phase to lymphoid blast crisis is a poorly characterized event. However, at least some of the molecular events that accompany evolution of the disease have been described. One such event, mutation of the p16Ink4a/p19Arf locus, is known to occur in approximately 50% of patients developing acute lymphoid disease. Based on this observation, we generated a novel mouse model in which combination of the well-known BCR/ABL ... |
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| Identification of Stem Cells in a Novel Human Mammary Epithelial Culture (HMEC) System that Reproducibly Demonstrates Ductal Organotypic Architecture in 3 Weeks |
OCT 2006 |
55 pages |
| Authors:
Jean J. Latimer; MAGEE WOMENS HEALTH CORP PITTSBURGH PA
|
 | Our laboratory has published a novel culture system for Human Mammary Epithelial Cells (HMEC), both normal and malignant. This system allows for unusually long-term (3 months or longer) establishment of normal primary cultures that begin as three-dimensional "mammospheres," which are structures made up of 40-100 epithelial cells. These mammospheres subsequently differentiate into complex organotypic branching ducts and lobules that demonstrate Epithelial Specific Antibody (ESA) staining, lumen, polarized nuclei, desmosomes along ... |
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| A New Paradigm for African American Breast Cancer Involving Stem Cell Differentiation in a Novel Cell Culture System |
OCT 2006 |
32 pages |
| Authors:
Jean J. Latimer; PITTSBURGH UNIV MEDICAL CENTER PA
|
 | Our laboratory has published a novel culture system for Human Mammary Epithelial Cells (HMEC), both normal and malignant. This system allows for unusually long-term establishment of normal primary cultures that begin as three-dimensional "mammospheres," which subsequently differentiate into complex organotypic branching ducts and lobules that demonstrate Epithelial Specific Antibody (ESA) staining, lumen, polarized nuclei, desmosomes along the lateral surfaces of the cells, and microvilli on the apical surfaces. We hypothesize ... |
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| Signaling from a Novel Receptor Tyrosine Kinase and the Control of Multipotent Mammary Progenitor Cells |
Sep-2006 |
28 pages |
| Authors:
Cindy A Wilson; CALIFORNIA UNIV LOS ANGELES
|
 | Our objective was to determine if signaling through the ROR1 receptor tyrosine kinase controls the proliferation, self-renewal and/or differentiation of mammary epithelial cells. We silenced ROR1 by stable expression of siRNA ROR1 sequences using a retroviral expression system in human cell lines with progenitor properties. We also overexpressed the ROR1 cDNA in immortalized human mammary epithelial cell lines (184A1, 184B5). The effects of depleted and overexpressed ROR1 were assayed using ... |
|
| Proteinated Subnano Particles of Elemental Selenium for the Treatment of Breast Cancer |
SEP 2006 |
9 pages |
| Authors:
Fritz Sieber; MEDICAL COLL OF WISCONSIN MILWAUKEE
|
 | The purpose of this award is to test in preclinical models the hypothesis that cytotoxic conjugates of elemental selenium and proteins are safe and effective for the systemic therapy of invasive breast cancer. The grant has three specific aims, 1) to evaluate the safety and efficacy of systemically administered Se(0)- protein conjugates in athymic nude mice bearing xenografts of human breast cancer cells, 2) to assess the functional integrity of ... |
|
| 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 ... |
|
| Unmasking Stem/Progenitor Cell Properties in Differentiated Epithelial Cells Using Short-term Transplantation |
AUG 2006 |
47 pages |
| Authors:
Michael T. Lewis; BAYLOR COLL OF MEDICINE HOUSTON TX
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 | Background: Prevailing models maintain that stem cells comprise a minority of epithelial cells. However, some data suggest the percentage of mammary stem cells may be underestimated using common assays. Rationale: Short term transplantation using fragments of mammary duct offer an opportunity to test the prevailing stem cell model. If division-competent stem cells represent a small percentage of all epithelial cells, the initial rate of cell division in transplanted fragments should ... |
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