A5017938441- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Protease and Inhibitor Mechanisms
- Brake Systems and Friction Analysis
- Cellular Mechanics and Interactions
- Vehicle Dynamics and Control Systems
- Mechanical Engineering and Vibrations Research
- Hippo pathway signaling and YAP/TAZ
- Blood Coagulation and Thrombosis Mechanisms
- Cancer Cells and Metastasis
- Platelet Disorders and Treatments
- Tribology and Lubrication Engineering
- Mechanical stress and fatigue analysis
- Cancer, Stress, Anesthesia, and Immune Response
- Hydraulic and Pneumatic Systems
- Peptidase Inhibition and Analysis
- Tribology and Wear Analysis
- Gear and Bearing Dynamics Analysis
- Adhesion, Friction, and Surface Interactions
- Monoclonal and Polyclonal Antibodies Research
- Inflammatory mediators and NSAID effects
- Nicotinic Acetylcholine Receptors Study
- TGF-β signaling in diseases
- Structural Health Monitoring Techniques
- Cancer, Hypoxia, and Metabolism
University of Leeds
2012-2023
MaineHealth
2022-2023
University of Maine
2011-2022
Maine Medical Center Research Institute
2011-2021
Maine Medical Center
2009-2020
Center for Molecular Medicine and Immunology
2014
Tufts University
2014
Northwestern University
2011
New York University
2001-2010
Cornell University
2007-2009
Angiogenesis depends on the adhesive interactions of vascular cells. The adhesion receptor integrin α v β 3 was identified as a marker angiogenic tissue. Integrin expressed blood vessels in human wound granulation tissue but not normal skin, and it showed fourfold increase expression during angiogenesis chick chorioallantoic membrane. In latter assay, monoclonal antibody to blocked induced by basic fibroblast growth factor, tumor necrosis factor-α, melanoma fragments had no effect...
Angiogenesis depends on cytokines and vascular cell adhesion events. Two cytokine-dependent pathways of angiogenesis were shown to exist defined by their dependency distinct integrins. In vivo in corneal or chorioallantoic membrane models induced basic fibroblast growth factor tumor necrosis factor-α depended α v β 3 , whereas initiated endothelial factor, transforming factor-α, phorbol ester 5 . Antibody each integrin selectively blocked one these pathways, a cyclic peptide antagonist both...
Angiogenesis plays a fundamental role in human breast tu- mor progression.In fact, recent findings indicate that vascu- lar density is prognostic indicator of cancer disease status.Evidence presented the integrin avfi3 not only marker tumor-associated blood vessels, but it significant angiogenesis and tumor growth.To assess avvp3dependent progression cancer, we examined SCID mouse/human chimeric model with transplanted full thickness skin containing avfi3-negative cells.This in- duced...
Inhibitors of VEGF signaling can block angiogenesis and reduce tumor vascularity, but little is known about the reversibility these changes after treatment ends. In present study, regrowth blood vessels in spontaneous RIP-Tag2 tumors implanted Lewis lung carcinomas mice was assessed inhibition receptor by AG-013736 or AG-028262 for 7 days. Both agents caused loss 50%–60% vasculature. Empty sleeves basement membrane were left behind. Pericytes also survived had less α–SMA immunoreactivity....
Abstract. Carcinoma cells selected for their ability to migrate in vitro showed enhanced invasive properties vivo. Associated with this induction of migration was the anchorage-dependent phosphorylation p130CAS (Crk-associated substrate), leading its coupling adaptor protein c-CrkII (Crk). In fact, expression CAS or partner Crk sufficient promote cell migration, and depended on tyrosine facilitating an SH2-mediated complex Crk. Cytokine-stimulated blocked by lacking binding site containing a...
Modulation of Tie2 receptor activity by its angiopoietin ligands is crucial for angiogenesis, blood vessel maturation, and vascular endothelium integrity. It has been proposed that angiopoietins 1 (Ang1) 2 (Ang2) are pro- anti-angiogenic owing to their respective agonist antagonist signaling action through the receptor. The function Ang2 remained controversial, however, with recent reports suggesting in some circumstances, it may be pro-angiogenic. We have examined this issue using transient...
Evidence is provided that proteolytic cleavage of collagen type IV results in the exposure a functionally important cryptic site hidden within its triple helical structure. Exposure this was associated with angiogenic, but not quiescent, blood vessels and required for angiogenesis vivo. HUIV26 epitope loss alpha1beta1 integrin binding gain alphavbeta3 binding. A monoclonal antibody (HUIV26) directed to disrupts integrin-dependent endothelial cell interactions potently inhibits tumor growth....
Induction of p53 activity in cells undergoing DNA synthesis represents a molecular conflict that can lead to apoptosis. During angiogenesis, proliferative endothelial become apoptotic response antagonists integrin alphavbeta3 and this leads the regression angiogenic blood vessels, thereby blocking growth various human tumors. Evidence is presented administration during angiogenesis vivo selectively caused activation cell increased expression p53-inducible cycle inhibitor p21WAF1/CIP1. In...
Collagen type IV is a major component of the basal lamina blood vessels. Six genetically distinct collagen chains have been identified and are distributed in tissue-specific manner. Here we define novel function for soluble non-collagenous (NC1) domains α2(IV), α3(IV), α6(IV) human regulation angiogenesis tumor growth. These NC1 were shown to regulate endothelial cell adhesion migration by α<sub>v</sub> β<sub>1</sub>integrin-dependent mechanisms. Systemic administration recombinant potently...
Elevated expression of plasminogen activator inhibitor-1 (PAI-1) in tumors is associated with a poor prognosis many cancers. Reduced tumor growth and angiogenesis have also been reported mice deficient PAI-1. These results suggest that PAI-1 may be required for efficient growth. In the present study, we demonstrate can both enhance inhibit M21 human melanoma nude this appears to due regulation angiogenesis. Quantitative analysis Matrigel implant assay indicated null was reduced ∼60% compared...
The NPXY sequence is highly conserved among integrin beta subunit cytoplasmic tails, suggesting that it plays a fundamental role in regulating integrin-mediated function. Evidence provided the structural motif within 3 subunit, comprising residues 744-747, essential for cell morphological and migratory responses mediated by alpha v vitro vivo. Transfection of CS-1 melanoma cells with cDNA encoding wild-type results de novo expression attachment, spreading, migration on vitronectin....
The process of angiogenesis is important in both normal and pathologic physiology. However, the mechanisms whereby factors such as basic fibroblast growth factor promote formation new blood vessels are not known. In present study, we demonstrate that exogenously added plasminogen activator inhibitor-1 (PAI-1) at therapeutic concentrations a potent inhibitor factor-induced chicken chorioallantoic membrane. By using specific PAI-1 mutants with either their vitronectin binding or proteinase...
Tumor cell interactions with adhesion proteins and growth factors likely contribute to the metastatic cascade. Evidence is provided that insulin or insulin-like factor-mediated signals cooperate commonly expressed integrin alpha v beta 5 promote spontaneous pulmonary metastasis of multiple tumor types in both chick embryo severe combined immune deficiency mouse/human chimeric models. Expression cells promoted their vitronectin vitro. However, motility required cytokine stimulation, which...