Endostatin, a M(r) 20,000 COOH-terminal fragment of collagen XVIII, is currently in preclinical development as a novel antiangiogenic agent. The gene expression of this molecule in 23 normal ovaries with follicle or corpus luteum and in 64 cases of epithelial ovarian cancer (27 serous, 18 mucinous, 13 endometrioid, 4 clear cell, and 2 undifferentiated carcinomas) was analyzed by PCR of RNA afte...

PURPOSE To investigate the role of stimulators and inhibitors of angiogenesis in the pathogenesis of diabetic retinopathy. METHODS Undiluted vitreous samples and simultaneous paired plasma samples were obtained from 30 diabetic patients (35 eyes) undergoing vitreous surgery. The levels of vascular endothelial growth factor (VEGF), endostatin, and platelet factor-4 (PF-4) were measured simulta...

We examined the feasibility of using adeno-associated virus (AAV)-mediated systemic delivery of endostatin in gene therapy to treat metastasis of pancreatic cancer. We established an animal model of orthotopic metastatic pancreatic cancer in which the pancreatic cancer cell line PGHAM-1 was inoculated into the pancreas of Syrian golden hamsters. Transplanted cells proliferated rapidly and metas...

Endostatin is a well-characterized endogenous inhibitor of angiogenesis that affects cell proliferation and migration by inhibiting integrin and Wnt-mediated signalling pathways. Here, we show that endothelial cells treated with native and P125A-endostatin activate autophagy. Because autophagy can either be protective or induce programmed cell death, experiments were carried out to understand t...

OBJECTIVE We have previously shown that transient coronary artery occlusion stimulated coronary collateral growth (CCG) in healthy (Sprague Dawley) but not in metabolic syndrome (JCR:LA-cp [JCR] ) rats. Here, we sought to determine whether matrix metalloproteinases (MMPs) negatively regulate CCG in the metabolic syndrome via release of endostatin and angiostatin. APPROACH AND RESULTS Rats und...

In this study, we evaluated the plasma levels of endostatin (PE) and its prognostic importance in patients with acute myeloblastic (AML) and lypmhoblastic leukemia (ALL). We therefore analyzed plasma levels of endostatin before the chemotherapy and during the complete remission period in adult ALL and AML patients. The PE levels of the control group were significantly lower than both cases with...

PURPOSE Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance. We explored the effects of tamoxifen and aromatase inhibitors on concentrations of VEGF and endostatin in plasma, serum, and platelet releasate (induced by platelet activation). EXPERIMENTAL DESIGN VEGF and endo...

Cathepsin L is a cysteine protease that can generate endogenous endostatin in vascular and epithelial basement membranes and importantly participates in a variety of pathophysiological processes. The present study was designed to determine whether this cathepsin L-derived endogenous endostatin alters endothelium-dependent vasodilator responses in coronary arteries via NAD(P)H oxidase activation...

PURPOSE To investigate the nature and origin of the vitreous membranes in mice with knock-out of the Norrie gene product (ND mice). METHODS Eighty-two eyes of ND mice of different age groups (postnatal day [P]0-13 months) and 95 age-matched wild-type control mice were investigated. In vitreoretinal wholemounts and in sagittal sections, vessels and free cells were visualized by labeling for le...

umor growth is accompanied by angiogenesis, and because surgical removal of certain tumors may lead to rapid growth of remote metastases, endogenous angiogenesis inhibitors may be secreted from the tumor. The endogenous angiogenesis inhibitor, angiostatin, was identified in urine in 1994, and a more potent angiogenesis inhibitor, endostatin, was discovered in 1997 in the conditioned media of cu...