- Angiogenesis and VEGF in Cancer
- Signaling Pathways in Disease
- Biochemical and Molecular Research
- Enzyme function and inhibition
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- melanin and skin pigmentation
- Skin Protection and Aging
- Biochemical Analysis and Sensing Techniques
- Estrogen and related hormone effects
- PI3K/AKT/mTOR signaling in cancer
- Oral Health Pathology and Treatment
- Retinoids in leukemia and cellular processes
- Antioxidant Activity and Oxidative Stress
- Connective tissue disorders research
- Platelet Disorders and Treatments
- Vascular Malformations and Hemangiomas
- Cancer, Lipids, and Metabolism
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Surgical Sutures and Adhesives
- Protease and Inhibitor Mechanisms
- Retinal Development and Disorders
- Cancer Treatment and Pharmacology
- Ocular Oncology and Treatments
Boston Children's Hospital
2011-2024
Harvard University
2007-2023
Brigham and Women's Hospital
1999-2023
Moscow Research and Clinical Center for Neuropsychiatry
2018
Boston University
1983-2014
Trinity College Dublin
2013
Albert Ellis Institute
2006
University of Bergen
2006
Dana-Farber Cancer Institute
1997-2004
University of Toronto
2001
Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide an inhibitor of angiogenesis induced by basic fibroblast growth factor rabbit cornea micropocket assay. Experiments including the analysis analogs revealed antiangiogenic activity correlated with teratogenicity but not sedative or mild immunosuppressive properties thalidomide. Electron microscopic examination corneal neovascularization...
Background —Neovascularization within the intima of human atherosclerotic lesions is well described, but its role in progression atherosclerosis unknown. In this report, we first demonstrate that intimal vessels occur advanced apolipoprotein E–deficient (apoE −/−) mice. To test hypothesis promote atherosclerosis, investigated effect angiogenesis inhibitors on plaque growth apoE −/− Methods and Results —ApoE mice were fed a 0.15% cholesterol diet. At age 20 weeks, divided into 3 groups...
The switch from a quiescent tumor to an invasive is accompanied by the acquisition of angiogenic properties. This phenotypic change likely requires in balance stimulators and inhibitors. nature not known. Here, we show that introduction activated H-ras into immortalized endothelial cells capable activating switch. Angiogenic switching up-regulation vascular growth factor matrix metalloproteinase (MMP) bioactivity down-regulation tissue inhibitor MMP. Furthermore, inhibition...
Background: Microscopic human cancers can remain dormant for life. Tumor progression depends on sequential events, including a switch to the angiogenic phenotype, i.e., initial recruitment of new vessels. We previously demonstrated that tumors contain tumor cell populations are heterogeneous in activity. Here, we separated from nonangiogenic and compared their growth. Methods: Severe combined immunodeficient (SCID) mice were inoculated with MDA-MB-436 breast adenocarcinoma, KHOS-24OS...
A metabolite of estradiol, 2-methoxyestradiol (2ME), inhibits angiogenesis in the chicken embryo chorioallantoic membrane assay. Since 2ME causes mitotic perturbations, we examined its interactions with tubulin. In our standard 1.0 M glutamate system (plus mM MgCl2 at 37 degrees C), superstoichiometric concentrations (relative to tubulin) inhibited nucleation and propagation phases tubulin assembly but did not affect reaction extent. Although polymer formed presence was more cold-stable than...
Although the systemic administration of a number different gene products has been shown to result in inhibition angiogenesis and tumor growth animal models, relative potency those not studied rigorously. To address this issue, recombinant adenoviruses encoding angiostatin, endostatin, ligand-binding ectodomains vascular endothelial factor receptors Flk1, Flt1, neuropilin were generated used systemically deliver several preexisting murine models. Single i.v. injections viruses soluble forms...
Tumor growth and metastasis are angiogenesis dependent. Previously, we reported that angiostatin, a potent inhibitor, produced by primary Lewis lung carcinoma suppressed its of metastases (O'Reilly, M.S., L. Holmgren, Y. Shing, C. Chen, R.A. Rosenthal, M. Moses, W.S. Lane, Cao, E.H. Sage, J. Folkman. 1994. Cell. 79:315-328). Now show shift balance tumor gene transfer cDNA coding for mouse angiostatin into murine T241 fibrosarcoma cells suppresses metastatic in vivo. Implantation stable...
Cartilage is an avascular and relatively tumor-resistant tissue. Work from a number of laboratories, including our own, has demonstrated that cartilage enriched source endogenous inhibitors angiogenesis. In the course study designed to identify novel cartilage-derived new capillary growth, we have purified inhibitory protein was identified by peptide microsequencing database analysis as troponin I (TnI). TnI subunit complex (troponin-C troponin-T being other two), which, along with...
No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Feb 2001VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION AND TUMOR ANGIOGENESIS ARE REGULATED BY ANDROGENS IN HORMONE RESPONSIVE HUMAN PROSTATE CARCINOMA: : EVIDENCE FOR ANDROGEN DEPENDENT DESTABILIZATION OF VASCULAR TRANSCRIPTS ROBERT J. STEWART, DIPAK PANIGRAHY, EVELYN FLYNN, and JUDAH FOLKMAN STEWARTROBERT STEWART , PANIGRAHYDIPAK PANIGRAHY FLYNNEVELYN FLYNN FOLKMANJUDAH View All Author...
We have isolated a selectively deglycosylated form of vitamin D binding protein (DBP-maf) generated from systemically available DBP by human pancreatic cancer cell line. DBP-maf is anti proliferative for endothelial cells and antiangiogenic in the chorioallantoic membrane assay. administered daily was able to potently inhibit growth immune compromised mice (T/C=0.09). At higher doses, caused tumor regression. Histological examination revealed that treated tumors had number infiltrating...
In Brief Objective: To determine the effects of COX-2 specific inhibitors on postoperative adhesion formation. Summary and Background Data: Intra-abdominal adhesions are major cause intestinal obstruction secondary infertility after surgical procedures. Because synthesis requires angiogenesis, cyclooxygenase-2 enzyme (COX-2) have antiendothelial activity, we tested in a murine model intra-abdominal Methods: A silicone patch was secured to lateral abdominal wall groups C57BL/6 mice, followed...
Abstract Any imbalance between reactive oxygen species (ROS) generation and the anti-oxidant capacity lead to cellular oxidative stress. Many chemotherapeutic agents mediate their cytotoxic functions through of ROS. c-Met, a receptor tyrosine kinase, is over-expressed in renal cancer plays very crucial role(s) its growth survival. Here, we show that c-Met activation protected cells from ROS, stress cytotoxicity induced by anti-cancer agent sorafenib (used for treatment); it markedly...
Arthrofibrosis is a prevalent condition affecting greater than 5% of the general population and leads to painful decrease in joint range motion (ROM) loss independence due pathologic accumulation periarticular scar tissue. Current treatment options are limited effectiveness do not address underlying cause condition: fibrotic collagenous Herein, naturally occurring peptide hormone relaxin-2 administered for adhesive capsulitis (frozen shoulder) restore glenohumeral ROM shoulder...
Background: Tumor cells are known to be heterogeneous with respect their metastatic activity, proliferation rate, and activity of several enzymes. However, little is about the heterogeneity tumor angiogenic activity. We investigated whether could responsible for well-known observation "no take" human tumors transplanted into immunodeficient mice. Methods: Severe combined (SCID) mice were xenotransplanted subcutaneously tissue (n = 55) or cell suspension a liposarcoma line (SW-872) subclones...
2-Methoxyestradiol (2ME) is an endogenous mammalian catabolite of estradiol with antimitotic activity. Although it a competitive inhibitor the binding colchicine to tubulin, has unusual effects on glutamate-induced tubulin polymerization. Polymer that was little changed in morphology assembled at reduced rate and relatively cold stable. We have now examined interactions [4-3H]2ME unpolymerized polymer. The [3H]2ME binds avidly even ice, readily displaced by other site drugs. An association...
<h3>Background</h3> Clinically undetectable or dormant metastases (mircrometastases) probably account for disease recurrence, ie, clinically evident metastases, in patients after disease-free intervals of variable length. Recently developed animal models have shown that dormancy may potentially be explained by the fact these micrometastases are not vascularized and comparable rates cellular proliferation programmed cell death (apoptosis), enabling them to remain viable indefinitely but show...