| Jagged-1 Signaling Pathway in Prostate Cancer Cell Growth and Angiogenesis |
Apr-2009 |
16 pages |
| Authors:
Zhiwei Wang; WAYNE STATE UNIV DETROIT MI
|
 | Prostate cancer is the most commonly diagnosed cancer and is the second leading cause of cancer death in the US. Most patients diagnosed with prostate cancer are treatable, but the patients usually die from hormone refractory (HRPC) and metastatic disease. We have previously shown that expression of Notch receptors and their ligands is upregulated in many cancers including prostate cancer. We hypothesize that inactivation of Jagged-1 signaling, which could be ... |
|
| Angiogenesis Research to Improve Therapies for Vascular Leak Syndromes, Intra-Abdominal Adhesions, and Arterial Injuries |
Apr-2009 |
176 pages |
| Authors:
Donald Ingber; CHILDREN'S HOSPITAL CORP 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 made considerable progress in determining the efficacy ... |
|
| Role of Caveolin-1 in Prostate Cancer Angiogenesis |
Dec-2008 |
41 pages |
| Authors:
Timothy C Thompson; M D ANDERSON CANCER CENTER HOUSTON TX
|
| We have made a significant progress toward our stated goals. Notable achievements for the past year of funding include comprehensive documentation that prostate cancer cell derived, secreted caveolin-1 is taken up by cancer cells and tumor associated endothelial cells (Tahir et al, Cancer Res 2008). This autocrine/paracrine activity of secreted caveolin-1 promotes malignant progression by stimulation of specific angiogenic activities. We have shown in cav-1 negative LP-LNCaP cells that adenoviral ... |
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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 Impact of Diabetes Treatment on Survival in a Breast Cancer/Diabetes Model |
09-Oct-2008 |
9 pages |
| Authors:
Sai-Ching J Yeung; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Epidemiological studies have identified that type 2 diabetes mellitus (DM2) is a significant risk factor for carcinogenesis and cancer death. A few recent studies have also shown that different antidiabetic treatments have different impact on cancer. This proposal is to address the impact of antidiabetic treatments on the survival of breast cancer. We participated in the Era of Hope meeting in Chicago and presented our cell culture data in a ... |
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| Characterization of Gene Expression in Human Breast Tumor Endothelium |
01-May-2008 |
15 pages |
| Authors:
Nancy Klauber-DeMore; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| Angiogenesis is the growth of new capillary blood vessels, and is a critical component of solid tumor growth. We characterized molecular changes between human breast tumor vessels and normal vessels to identify genes that may serve as therapeutic targets. We developed a method for rapid immunohistochemistry (IHC) and laser capture microdissection (LCM) of vascular cells from frozen human breast tumors and normal breast tissue for genomic analysis. We found SFRP2 ... |
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| Molecular Imaging of Ovarian Carcinoma Angiogenesis |
Mar-2008 |
16 pages |
| Authors:
Xiaoyuan Chen; STANFORD UNIV CA
|
| This purpose of this proposal is to use high resolution microPET technology to image ovarian cancer integrin expression in vivo. Ovarian cancer is angiogenesis dependent. Integrin av Beta 3, a key player in tumor angiogenesis and metastasis, has been identified as a target for diagnostic and therapeutic interventions for several highly proliferative and metastatic tumor types. Specific Aim 1: To develop and optimize 18F-labeled RGD peptides for ovarian carcinoma targeting. ... |
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| Role of ADAM15 in Tumor/Endothelial Interactions Prostate Cancer Regression |
Mar-2008 |
5 pages |
| Authors:
Mark L Day; MICHIGAN UNIV ANN ARBOR
|
| The primary purpose of this proposal was to demonstrate that the membrane disintegrin, ADAM-15 mediates the interaction (binding) between prostate tumor cells and vascular endothelium and that in this regard ADAM-15 would support the metastatic spread of human prostate cancer. The successful completion of one of the earliest aspects of this proposal has given substance to the hypothesis and confidence as we move ahead with more functional analysis of this ... |
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| Treatment of Prostate Cancer with a DBP-MAF-Vitamin D Complex to Target Angiogenesis and Tumorigenesis |
01-Feb-2008 |
20 pages |
| Authors:
Michael W Fannon; KENTUCKY UNIV LEXINGTON
|
| The purpose of this study has been to determine the efficacy of combined therapy using vitamin D binding protein-macrophage activating factor (DBP-maf) and vitamin D as therapy for human prostate cancer. We had found that in endothelial tube formation vitamin D and DBP-maf inhibited the tube formation. Both molecules were effective on their own however the vitamin D showed evidence of toxicity at higher concentration. We here show that the ... |
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| Role of Dopamine as Antiangiogenic Agent in the Treatment of Prostate Cancer |
FEB 2008 |
7 pages |
| Authors:
Sujit Basu; MAYO CLINIC ROCHESTER MN
|
| Prostate cancer is a major cause of cancer-related mortality for men in the United States. The established treatment protocol for the advanced stage of the disease is by surgical castration and or chemotherapy. Although androgen ablation therapy is initially effective in inhibiting tumor growth in most patients, however with time, the tumors recurs with a more aggressive and metastatic phenotype, ultimately causing death. Thus limitation of treatment underscores the need ... |
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| Anti-Angiogenic Action of Neutral Endopeptidase |
NOV 2007 |
30 pages |
| Authors:
David M. 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 ... |
|
| Nitric Oxide Generating Polymeric Coatings for Subcutaneous Glucose Sensors |
OCT 2007 |
11 pages |
| Authors:
Mark E. Meyerhoff; MICHIGAN UNIV ANN ARBOR
|
| Heretofore efforts to develop implantable sensors for real-time clinical monitoring of glucose subcutaneously (SQ) in diabetic patients have been hindered by the unreliable analytical results owing largely to biocompatibility problems induced by sensor implantation (e.g. inflammatory/foreign body response). The goal of this research program is to explore and optimize the chemistries required to fabricate implantable amperometric glucose sensors with outer polymeric coatings that slowly generate low levels of nitric oxide ... |
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| VEGF-Iron Oxide Conjugate for Dual MR and PET Imaging of Breast Cancer Angiogenesis |
SEP 2007 |
18 pages |
| Authors:
Xiaoyuan Chen; STANFORD UNIV CA SCHOOL OF MEDICINE
|
| The overall hypothesis of this concept award proposal is that a single probe that allows simultaneous acquisition of both positron emission tomography (PET) and molecular magnetic resonance imaging (mMRI) data will maximizes the topographical, anatomical, functional, and molecular information of breast cancer. In this proposal, we choose to image breast cancer tumor vasculature by visualization and quantification of Flt-1 and Flk-1/KDR. Objectives: Aim 1: To develop iron oxide (IO) nanoparticles ... |
|
| Does Skeletal Muscle Mass Influence Breast Cancer? Evaluating Mammary Tumorigenesis and Progression in Genetically Hyper-Muscular Mice |
JUL 2007 |
14 pages |
| Authors:
Teresa Zimmers; MIAMI UNIV FL
|
| Epidemiologic evidence demonstrates that caloric restriction and physical activity independently reduce breast cancer, potentially by decreasing adiposity and insulin resistance. To determine the role of increased skeletal muscle mass on breast cancer, the authors sought to measure rates of chemically induced mammary tumorigenesis and progression in genetically hypermuscular mice, including mice lacking the muscle growth inhibitor myostatin and mice expressing a dominant negative form of the myostatin receptor (MLC-dnActRIIB mice). ... |
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| Angiogenic Signaling in Living Breast Tumor Models |
JUN 2007 |
28 pages |
| Authors:
Edward Brown; ROCHESTER UNIV NY
|
| In this grant we propose to elucidate the signaling pathway that translates VEGFR activation into elevated vessel permeability, in endothelial cells within living breast tumor models. The working hypothesis is that the signaling pathway involved is a constitutively active form of the pathway shown for healthy mesenteric microvessels. Progress to date includes the training of personnel in the laboratory, the completion of instrumentation development for a novel method for the ... |
|
| Targeting Tie2 to Increase Breast Cancer Responsiveness to Antiangiogenic Therapy |
JUN 2007 |
9 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 ... |
|
| Targeting Therapy Resistant Tumor Vessels |
01 MAY 2007 |
35 pages |
| Authors:
Erkki Ruoslahti; BURNHAM INST LA JOLLA CA
|
| Anti-angiogenic therapy appears to eliminate immature blood vessels. This paradoxically leads to improvement of tumor blood supply, as the structure and function of mature tumor blood vessels, not specific for anti-angiogenic effect, is normalized. This is a serious limitation to the anti-angiogenic therapy. The goal of this project is to specifically distinguish these "normalized" therapy resistant vessels in breast cancer from those sensitive to anti-angiogenic treatment. To achieve this, we ... |
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| Prevention of the Angiogenic Switch in Human Breast |
01 MAR 2007 |
22 pages |
| Authors:
Judah Folkman; CHILDREN'S HOSPITAL CORP BOSTON MA
|
| Our overall goal is to determine if human breast cancer can be prevented from becoming angiogenic when it is still at a microscopic size (< ~ 1 mm3). To date we have made the following progress: (1) We have cloned three different human breast cancers that undergo the angiogenic switch at predictable times. (2) We have found that the angiogenic switch time is modified by host stroma: two-fold earlier for ... |
|
| Molecular Imaging of Ovarian Carcinoma Angiogenesis |
MAR 2007 |
69 pages |
| Authors:
Xiaoyuan Chen; STANFORD UNIV CA
|
| This purpose of this proposal is to use high resolution microPET technology to image ovarian cancer integrin expression in vivo. Ovarian cancer is angiogenesis dependent. Integrin , a key player in tumor angiogenesis and metastasis, has been identified as a target for diagnostic and therapeutic interventions for several highly proliferative and metastatic tumor types. The interaction between vitronectin and integrin alphavbeta3 is essential for ovarian cancer cell survival and invasion. ... |
|
| 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 ... |
|
| To Investigate the Therapeutic Effects of the COX-2 Inhibitor NS-398 as a Single Agent, and in Combination with Vitamin D, in Vitro and in Vivo |
JAN 2007 |
25 pages |
| Authors:
Yi-Fen Lee; ROCHESTER UNIV NY
|
| The incidence of prostate cancer has increased and effort is needed towards understanding mechanisms involved in development/progression of prostate cancer and developing new strategies for prevention/treatment. Studies suggested nonsteroidal anti-inflammatory drugs, such as COX-2 inhibitor, act as chemopreventative agents and found COX-2 expression in prostate cancer correlated with cancer progression. Treatment of prostate cancer cells with COX-2 inhibitor, NS-398, induces VDR expression, and might increase vitamin D sensitivity. Treatment of ... |
|
| Design and Development of Peptides from the Anti-Angiogenic Pigment Epithelial-Derived Factor for the Therapy of Prostate Cancer |
01 DEC 2006 |
18 pages |
| Authors:
Yelena Mirochnik; NORTHWESTERN UNIV EVANSTON IL
|
| To create PEDF based therapy for hormone-refractory CaP we have proposed to generate short synthetic peptides corresponding to the 34-mer anti-angiogenic epitope of PEDF. The 3D structure of the 34-mer peptide was analyzed using Protean software in terms of relative hydrophobicity charge distribution and antigenic index. Three synthetic peptides covering the 34-mer fragment were generated and tested for the ability to reproduce anti-angiogenic effect of PEDF. All peptides (14, 18 ... |
|
| 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 ... |
|
| Potentiation of Prostate Cancer Radiotherapy using Combined Antiangiogenic and Antitumor Therapies |
OCT 2006 |
24 pages |
| Authors:
Bruce M. Fenton; ROCHESTER UNIV NY
|
| The focus of this grant period was to delineate the effects of monotherapies or combinations of radiotherapy and AG-013736 (a multiple angiogenic receptor inhibitor) on vascular maturity and function, based on perfusion and hypoxia indices as well as pericyte coverage. In 3 major experiments, 250 tumors were frozen for immunohistochemical staining and image analysis. Almost complete growth inhibition was observed for the combined therapy. Total and perfused vessel counts were ... |
|
| The Clinical Development of Thalidomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer |
OCT 2006 |
18 pages |
| Authors:
Christopher J. Logothetis; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Significant progress has been made in the understanding of key factors that regulate the cell-cell interaction in the context of the microenvironment of prostate cancer. This includes technical advances in getting information from small amounts of tissue to forward understanding of the molecular determinants of progression. We have developed tissue micro arrays (TMAs), and stained them for candidate factors implicated in stromal epithelial interaction and have demonstrated that they are ... |
|
| Engineered Autologous Stromal Cells for the Delivery of Kringle 5, a Potent Endothelial Cell Specific Inhibitor for Anti-Angiogenic Breast Cancer Therapy |
AUG 2006 |
27 pages |
| Authors:
Sabrina R. Perri; SIR MORTIMER B DAVIS JEWISH GENERAL HOSPITAL MONTREAL (QUEBEC)
|
| The plasminogen kringle 5 (K5) domain - which is distinct from angiostatin - possesses potent anti-angiogenic properties on its own which can be exploited in cancer therapy. We have previously shown that K5 suppresses cancer growth in tumor xenograft models, its modulation of inflammation in experimental mice with intact immune systems is unknown. To determine whether K5 possesses immune proinflammatory properties, we investigated the effects of K5 in an immune ... |
|
| Chemokine Blockade in Combination with Cytoreductive Conditioning in Metastatic Breast Cancer |
AUG 2006 |
12 pages |
| Authors:
William J. Murphy; NEVADA UNIV RENO
|
| Chemokines have been shown to provide angiogenic effects. Blocking chemokines can reduce metastatic breast cancer cell growth. We proposed that cytoreductive conditioning will force the tumor to rely on angiogenesis as a survival mechanism and thus make the tumor more susceptible to chemokine blockade. We demonstrate that tumor cells increase production of IL-8 and MCP-1 transcripts in vivo in response to IL-8 neutralization and/or gamma irradiation and cytoxan administration. We ... |
|
| Targeting of an Antimetastatic and Antiangiogenic Compound to Breast Tumors |
JUL 2006 |
10 pages |
| Authors:
David Peters; BURNHAM INST LA JOLLA CA
|
| Anastellin is a fragment of fibronectin which inhibits angiogenesis, tumor growth, and metastasis in vivo, but the mechanisms behind these effects were previously unknown. We have shown that anastellin co-localizes with Annexin V, a marker for anionic phospholipids on the surface of tumor blood vessels in vivo. Anastellin potentially uses the increased levels of phosphatidylserine on the surface of proliferating endothelial cells in angiogenic blood vessels to bind to the ... |
|
| Angiogenesis and Invasiveness in Prostate Cancer Detected with High Spectral and Spatial Resolution MRi |
JUL 2006 |
71 pages |
| Authors:
Greg Karczmar; CHICAGO UNIV IL
|
| We propose to develop new MR methods to improve early and accurate detection of prostate cancer, and guide treatment of the cancer. Although conventional MRI has high sensitivity, its specificity has been disappointing. New more specific and sensitive MRI methods would have a significant impact on clinical management of prostate cancer. Previous work in this laboratory showed that high spectral and spatial resolution (HiSS) MRI improves image quality and detection ... |
|
| A New Transgenic Approach to Target Tumor Vasculature |
JUN 2006 |
21 pages |
| Authors:
Elena B. Pasquale; BURNHAM INST LA JOLLA CA
|
| Breast cancer growth relies on a blood supply. Therefore, anticancer therapies that disrupt tumor angiogenesis to starve tumor cells can be very effective. To examine the importance of candidate proteins in adult angiogenesis, we generated a transgenic mouse model expressing the receptor for an avian retrovirus only in new blood vessels. The avian retrovirus was en-gineered to express ephrin-B2 (a protein whose importance in blood vessel growth we wanted to ... |
|
| Angiogenic Signaling in Living Breast Tumor Models |
JUN 2006 |
23 pages |
| Authors:
Edward Brown; ROCHESTER UNIV NY
|
| In this grant we propose to elucidate the signaling pathway that translates VEGFR activation into elevated vessel permeability, in endothelial cells within living breast tumor models. The working hypothesis is that the signaling pathway involved is a constitutively active form of the pathway shown for healthy mesenteric microvessels. Progress to date includes the recruitment of personnel to the new laboratory, the development and testing of a novel method for the ... |
|
| Manipulation of NF-KappaB Activity in the Macrophage Lineage as a Novel Therapeutic Approach |
MAY 2006 |
79 pages |
| Authors:
Fiona Yull; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| Morphogenesis of the mammary gland is a highly complex process which when misregulated can result in tumorigenesis. It involves the interactions of multiple cell types in a highly regulated manner with complex signal transduction pathways coordinating the physiological processes. Interactions between epithelial and mesenchymal cells are known to be important. However, recent studies are beginning to highlight the importance of other cell types, such as macrophages. One of the signaling ... |
|
| Inhibition of Breast Cancer-Induced Angiogenesis by a Diverged Homeobox Gene |
MAY 2006 |
121 pages |
| Authors:
David H. Gorski; ROBERT WOOD JOHNSON MEDICAL SCHOOL PISCATAWAY NJ
|
| Homeobox genes represent a class of transcription factors important in embryogenesis, organogenesis cell growth and differentiafion and cell migration. However there is little known about their role in regulating endothelial cell (EC) phenotype in response to proangiogenic factors secreted by breast cancer although at least two homeobox genes have been implicated in inducing the angiogenic phenotype in ECs. We are therefore testing the homeobox gene Gax regulates breast cancer-induced angiogenesis ... |
|
| 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 ... |
|
| Angiogenesis and Therapeutic Approaches to NF1 Tumors |
APR 2006 |
61 pages |
| Authors:
David F. Muir; FLORIDA UNIV GAINESVILLE
|
| The main goal of this project is to specify how anti-angiogenic approaches can be effectively applied to NF1 tumors. To this end, we will first determine whether NF1 heterozygosity alters the responsiveness of endothelial cells to angiogenic regulators. We will test if Nf1-/+ endothelial cells are particularly responsive to pro-angiogenic factors produced by NF1 tumor cells and, perhaps even more importantly, which anti-angiogenic factors are most effective in abrogating the ... |
|
| Targeting Microvascular Pericytes in Angiogenic Vessels of Prostate Cancer |
APR 2006 |
49 pages |
| Authors:
Ugur Ozerdem; LA JOLLA INST FOR MOLECULAR MEDICINE SAN DIEGO CA
|
| The walls of neovascular capillaries in prostate cancer are composed of endothelial cells and pericytes. Pericytes of postnatal pathological neovascularization have dual origin: They derive from bone marrow progenitors (vasculogenesis),or by sprouting from pre-existing vessels (angiogenesis). NG2+ nascent pericytes promote neovascularization and increase interstitial fluid pressure in tumors. The aims of this investigation are to determine whether therapeutic interference with pericyte-NG2 proteoglycan decreases prostate cancer neovascularization, and controls tumor growth. ... |
|
| Notch and VEGF Interactions in Breast Cancer |
APR 2006 |
19 pages |
| Authors:
Carrie J. Shawber; COLUMBIA UNIV NEW YORK
|
| The proposal objective is to define Notch and VEGFR-3 in breast cancer. We investigated this relationship in primary endothelial cell cultures, mouse embryos, human breast tumors, and mouse mammary tumor xenografts. We demonstrate that Notch signaling promotes VEGFR-3 messages and protein in both primary endothelial cell cultures and mouse embryos in which Notch4 signaling is activated within the endothelium. In normal breast tissue, Notch1, Notch4 and Dll4 are expressed in ... |
|
| Prevention of the Angiogenic Switch in Human Breast Cancer |
MAR 2006 |
28 pages |
| Authors:
Judah Folkman; CHILDREN'S HOSPITAL MEDICAL CENTER BOSTON MA
|
| The overall goal of this project is to determine if human breast cancer can be prevented from becoming angiogenic when it is still at a microscopic size (i.e., < 1 cubic millimeter). During the past year, from February 2005 to February 2006, the authors cloned three different human breast cancers that undergo the angiogenic switch at predictable times. They found that the angiogenic switch time is modified by host stroma; ... |
|
| Blocking Blood Supply to Breast Carcinoma With a DNA Vaccine Encoding VEGF Receptor-2 |
MAR 2006 |
186 pages |
| Authors:
He Zhou; Yunping Luo; Charles D. Kaplan; Joerg A. Krueger; Sung-Hyung Lee; Rong Xiang; Ralph A. Resifeld; SCRIPPS RESEARCH INST LA JOLLA CA
|
| We proved the major hypothesis driving this project that effective regression of breast cancer growth and metastases can be achieved by suppressing tumor angiogenesis with an orally delivered DNA-based vaccine carried by double attenuated Salmonella typhimurium. For this approach, the murine vascular endothelial growth factor receptor-2 (FLK-1) proved to be an effective target. We also targeted the inhibitor of apoptotic protein, surviving, and endoglin and achieved a similar protection against ... |
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| Vasculature-Specific Adenovirus Vectors for Gene Therapy of Prostate Cancer |
FEB 2006 |
12 pages |
| Authors:
Victor Krasnykh; M D ANDERSON CANCER CENTER HOUSTON TX
|
| In Year 2 of the project we have completed Task 2 (as per approved Statement of Work) by characterizing the binding specificity of the Ad fiber proteins designed to bind IL-11Ralpha. In Task 3 of the project we identified the most promising fiber ligand constructs and designed Ad genomes that incorporate the genes for these proteins in addition to the reporter expressing gene cassettes. |
|
| Lymphatic Regeneration within Porous VEGF-C Hydrogels for Secondary Lymphedema |
JAN 2006 |
16 pages |
| Authors:
Mauricio A. Contreras; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Lymphedema is an abnormal swelling in which lymph production exceeds drainage capabilities. This occurs as a result of lymphatic vessel destruction during the removal of lymph nodes or subsequent radiation therapy in breast cancer treatment. Management of lymphedema remains a clinical problem. In adult lymphangiogenesis, VEGF-C (Vascular Endothelium Growth Factor C) has been shown to be a specific mitogen for lymphatic endothelial cells (LEC) via the VEGF-C receptor. VEGF-C also ... |
|
| Annexin II-Mediated Ca++ Influx Regulates Endothelial Cell (EC) Apoptosis and Tumor Angiogenesis |
OCT 2005 |
17 pages |
| Authors:
Mahesh C. Sharma; DREXEL UNIV PHILADELPHIA PA
|
| Angiostatin (AS) the first four kringle domain (K1-4) of plasminogen (PLG), blocks angiogenesis and breast cancer progression almost 95 % in xenograft model. Despite great therapeutic potential in breast cancer its mechanism of action is unclear. We previously reported that AS ligand binds to endothelial cell surface annexin II and blocks PLG bindings. Emerging role of annexin II in cancer prompted us to investigate its possible mechanism in breast cancer. ... |
|
| Inducible Anti-Angiogenic Gene Therapy |
28 SEP 2005 |
14 pages |
| Authors:
Paul J. Higgins; ALBANY MEDICAL COLL NY
|
| Clinical studies indicate that high breast tumor levels of plasminogen activator inhibitor 1 (PAI-1) are associated with an increased metastatic risk, decreased survival, tumor angiogenesis; and overall poor prognosis. Since PAI-1 is required for tumor angiogenesis and inhibition of capillary regression, a targeted genetic approach was used to ablate PAI-1 synthesis in endothelial cells employing antisense PAI-1 and dominant-negative Constructs. Such targeting provided proof of principle that reduced PAI-1 synthesis ... |
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| Angiogenesis-Independent Neovascularization is a Major Contributor to Tumor Growth |
SEP 2005 |
16 pages |
| Authors:
Alan J. Schroit; Weixin Lu; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Tumors must manipulate the host vasculature to provide a blood supply adequate for their proliferation. Although tumors may arise as avascular masses. there is increasing evidence that some tumors begin to proliferate by coopting the host vasculature. By analyzing cell proliferation kinetics of endothelial cells (EC) and PC3 prostate cancer cells, we provide evidence that EC proliferation could not account for rapid tumor growth. Although PC3mm2 expressing green fluorescent protein ... |
|
| Are Breast Tumor Stem Cells Responsible for Metastasis and Angiogenesis? |
SEP 2005 |
6 pages |
| Authors:
Quintin Pan; MICHIGAN UNIV ANN ARBOR
|
| Despite advances in the early detection and treatment of breast cancer, the mortality rate for 20% of patients with recurrences and/or metastases is nearly 100% (1). Thus, it is critical to understand the mechanism of breast cancer metastasis to allow for better therapies targeted at the cellular culprits of metastasis. The current dogma of metastasis is that most primary tumor cells have low metastatic potential, but rare cells, less than ... |
|
| Analysis of Alk-1 Signaling in Endothelial Cells and its Role in Breast Tumor Angiogenesis. Addendum |
SEP 2005 |
13 pages |
| Authors:
Marcus Kretzschmar; Hans-Willem Snoeck; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| The process of tumor angiogenesis i.e. the vascularization of the tumor mass by formation of new blood vessels is important for tumor growth and metastasis. Inhibition of tumor angiogenesis is therefore an important goal for therapeutic intervention in breast cancer. Understanding the regulation of tumor angiogenesis at the molecular level is a prerequisite for successful manipulation of this process. Angiogenesis is regulated by the coordinated action of various growth factors ... |
|
| Novel Angiogenic Compounds for Targeted Drug Delivery |
13 JUL 2005 |
5 pages |
| Authors:
Kristen A. Wieghaus; Scott M. Capitosti; Milton L. Brown; Edward A. Botchwey; VIRGINIA UNIV CHARLOTTESVILLE DEPT OF CHEMISTRY
|
| Induction of angiogenesis is necessary for the success of engineered implantable tissues in order to meet oxygen and nutrient requirements of cells during tissue repair. Insufficient vascularization in bone graft reconstruction may impede healing and initiate hypoxic cell death at the interior of the implant. As a result, endogenous growth factors have been studied to enhance angiogenesis during wound repair. However, these peptide-based molecules are highly sensitive to processing that ... |
|
| Fibrinolysis in Tumor Associated Angiogenesis |
JUL 2005 |
20 pages |
| Authors:
Sandra W. McLeskey; MARYLAND UNIV BALTIMORE
|
| Endothelial cells from different vascular beds, including tumor vasculature, have been shown to have different behavior and different gene expression. In tumors, abundant fibrin in the extracellular matrix dictates that fibrinolytic capability is required for new vessel formation. We have developed an in vitro breast cancer angiogenesis assay using mammary vessels from mice in a 3-dimensional fibrin matrix. Confocal microscopy of these assays is used to quantitate the number of ... |
|
| Estimation of Tumor Angiogenesis With Contrast Enhanced Subharmonic Ultrasound Imaging |
JUL 2005 |
49 pages |
| Authors:
Flemming Forsberg; THOMAS JEFFERSON UNIV PHILADELPHIA PA
|
| New contrast-specific imaging modalities such as harmonic imaging (HI) may improve the accuracy of breast ultrasound. Unfortunately, HI suffers from reduced blood-to-tissue contrast resulting from second harmonic generation and accumulation in tissue. As an alternative we propose using subharmonic imaging (SHI) by transmitting at the double the resonance frequency (f0/2) and receiving at the subharmonic (f0). Hence, the current project proposes to increase the ability of breast ultrasound to differentiate ... |
|
| Targeted Gene Therapy for Breast Cancer |
JUN 2005 |
24 pages |
| Authors:
Selvarangan Ponnazhagan; ALABAMA UNIV IN BIRMINGHAM
|
| During the last three years of support of the career development award, we sought to develop and evaluate recombinant adeno-associated virus vectors encoding anti- angiogenic factors. We have completed the work with significant outcome, and also initiated new studies that will allow us to test novel possibilities for breast cancer treatment. The outcome of the present studies strongly indicated that sustained expression of anti-angiogenic factors not only provide significant growth ... |
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Reports by Keyword(s)
*ANGIOGENESIS
