Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An angiogenic response originating from peritumoral sinusoids and portal tracts that leads to the formation of metastases with sinusoidal- and portal-type angiogenic patterns, respectively, occurs during the course of liver colonization by murine 51b colon carcinoma (51b-CC) cells. We found a 5-fold increase in endogenous endostatin levels from hepatic blood over baseline (25 +/- 6 ng/mL) when micrometastatic foci had a detectable size and a 14-fold increase when macrometastases were developed. Despite this endogenous endostatin production, subcutaneous administration of recombinant human endostatin (rh-E; 50 mg/kg) decreased metastasis number by 60% when dosed from days 1 to 20 after 51b-CC cell injection, by 40% when given from days 10 to 20, and by 30% when administered as a single dose 30 minutes before 51b-CC cell injection compared with controls. In addition, administration of rh-E from days 10 to 20 decreased overall metastasis volume by 90% compared with controls. rh-E increased the number of necrotic sinusoidal-type metastases by 7-fold and decreased their intrametastatic CD31(+)-microvessel density by 80% without affecting portal-type metastases. Flow cytometry showed rh-E binding to mouse liver sinusoidal cells but not to CD45(+) cells (leukocytes and Kupffer cells) or 51b-CC cells. Furthermore, rh-E induced sinusoidal endothelium cell apoptosis. In conclusion, despite the direct correlation between metastasis development and endogenous endostatin generation in the liver, administration of rh-E inhibited micrometastasis generation and macrometastasis growth very efficiently. The antiangiogenic mechanism was selective for sinusoidal-type metastases, in which the neovasculature originating from sinusoidal endothelium cells was targeted by rh-E.
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PMID:Endostatin inhibits murine colon carcinoma sinusoidal-type metastases by preferential targeting of hepatic sinusoidal endothelium. 1198 60

Tumor escape from immunity, as well as the failure of several anti-cancer vaccination and cellular immunotherapy approaches, is suggested to be due to the angiogenesis-mediated suppression of endothelial cell (EC) adhesion molecules involved in leukocyte-vessel wall interactions. We hypothesized that inhibition of angiogenesis would overcome this escape from immunity. We investigated this in vivo by means of intravital microscopy and ex vivo by immunohistochemistry in two mouse tumor models. Angiogenesis inhibitors anginex, endostatin, and angiostatin, and the chemotherapeutic agent paclitaxel were found to significantly stimulate leukocyte-vessel wall interactions by circumvention of EC anergy in vivo, i.e., by the up-regulation of endothelial adhesion molecules in tumor vessels. This was confirmed by in vitro studies of cultured EC at the protein and mRNA levels. The new angiostatic designer peptide anginex was most potent at overcoming EC anergy; the enhanced leukocyte-vessel interactions led to an increase in the numbers of tumor infiltrating leukocytes. While anginex inhibited tumor growth and microvessel density significantly, the amount of infiltrated leukocytes (CD45), as well as the number of CD8+ cytotoxic T lymphocytes, was enhanced markedly. The current results suggest that immunotherapy strategies can be improved by combination with anti-angiogenesis.
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PMID:Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors. 1658 70

Tissue regeneration is impaired in aged individuals. Adipose-derived mesenchymal stromal cells (ADSCs), a promising source for cell therapy, were shown to secrete various angiogenic factors and improve vascularization of ischemic tissues. We analyzed how patient age affected the angiogenic properties of ADSCs. ADSCs were isolated from subcutaneous fat tissue of patients with coronary artery disease (CAD; n = 64, 43-77 years old) and without CAD (n = 31, 2-82 years old). ADSC phenotype characterized by flow cytometry was CD90(+)/CD73(+)/CD105(+)/CD45(-)/CD31(-) for all samples, and these cells were capable of adipogenic and osteogenic differentiation. ADSCs from aged patients had shorter telomeres (quantitative reverse transcription polymerase chain reaction) and a tendency to attenuated telomerase activity. ADSC-conditioned media (ADSC-CM) stimulated capillary-like tube formation by endothelial cells (EA.hy926), and this effect significantly decreased with the age of patients both with and without CAD. Angiogenic factors (vascular endothelial growth factor, placental growth factor, hepatocyte growth factor, angiopoetin-1, and angiogenin) in ADSC-CM measured by enzyme-linked immunosorbent assay significantly decreased with patient age, whereas levels of antiangiogenic factors thrombospondin-1 and endostatin did not. Expression of angiogenic factors in ADSCs did not change with patient age (real-time polymerase chain reaction); however, gene expression of factors related to extracellular proteolysis (urokinase and its receptor, plasminogen activator inhibitor-1) and urokinase-type plasminogen activator receptor surface expression increased in ADSCs from aged patients with CAD. ADSCs from aged patients both with and without CAD acquire aging characteristics, and their angiogenic potential declines because of decreasing proangiogenic factor secretion. This could restrict the effectiveness of autologous cell therapy with ADSCs in aged patients.
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PMID:Adipose-derived mesenchymal stromal cells from aged patients with coronary artery disease keep mesenchymal stromal cell properties but exhibit characteristics of aging and have impaired angiogenic potential. 2435 75