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

The aim of this study was to evaluate the safety of the continuous administration of recombinant human endostatin (Endostar) in healthy mice. A total of 16 nude mice were randomly divided into four treatment groups: a continuous administration group injected intraperitoneally (i.p.) with 14 mg/kg Endostar over seven days, an intermittent administration group injected i.p. with 2 mg/kg Endostar daily for seven days, a saline injection group and an untreated control group. All mice were implanted with an intraperitoneal mini-osmotic drug pump filled with Endostar or saline. The serum concentration of Endostar, the cell fraction of CD11b(-)CD146(+)CD105(+) vascular endothelial cells in the peripheral blood, the injury of the myocardial, lung and kidney tissues and the density of microvessels within these organs were observed 24 h after the termination of drug or saline administration. Only trace amounts of Endostar were detected in the serum of the continuous administration and intermittent administration groups. Myocardial, lung and kidney tissues exhibited no detectable signs of injury and no differences in the density of microvessels were found in these organs among the four groups. Yet, the cell fraction (in %) of CD11b(-)CD146(+)CD105(+) vascular endothelial cells in the peripheral blood was higher in the continuous administration group compared with that in the other treatment groups (P=0.011). This suggests that intermittent Endostar delivery did not significantly impact the vascular endothelium, while continuous Endostar administration may promote injury of the endothelium. In conclusion, the continuous administration of Endostar does not appear to be a safe method by which to administer this antiangiogenic agent to healthy nude mice.
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PMID:Continuous administration of recombinant human endostatin (Endostar): A pre-clinical safety study. 2297 10

Endostar, a novel recombinant human endostatin, has been proven to inhibit tumor angiogenesis and is utilized as an anticancer drug. While free drugs can display limited efficacy, nanoscaled anticancer drugs have been fabricated and proven to possess superior therapeutic effects. Poly(lactic acid) (PLA) is a FDA-approved biomaterial displaying excellent biocompatibility and low toxicity. In this study, Endostar-loaded PLA nanoparticles (EPNPs) were first prepared, and a near-infrared (NIR) dye, IRDye 800CW, was conjugated to the surface for detecting nanoparticle biodistribution through fluorescence molecular imaging (FMI) using an orthotopic breast tumor mouse model. The antitumor efficacy of EPNPs was examined using bioluminescence imaging (BLI) and immunohistology. To further improve the antitumor effects, we combined EPNPs with zoledronic acid monohydrate (ZA), which is known to decrease the tumor-associated macrophages (TAM) and inhibit tumor progression. We found that EPNPs decreased human umbilical vein endothelial cell (HUVEC) viability by inhibiting tumor growth gene expression more significantly than free Endostar in vitro. In vivo, EPNPs displayed better tumor growth inhibitory effects compared with free Endostar, and the combination of EPNPs with ZA exhibited more significant antitumor effects. As confirmed by CD31 and CD11b immunohistochemistry, the combination of EPNPs and ZA showed synergistic effects in reducing tumor angiogenesis and TAM accumulation in tumor regions. Taken together, this study presents a novel and effective form of nanoscaled Endostar for the treatment of breast cancer that displays synergistic antitumor effects in combination with ZA.
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PMID:Infra Red Dye and Endostar Loaded Poly Lactic Acid Nano Particles as a Novel Theranostic Nanomedicine for Breast Cancer. 2728 Feb 47

Different subtypes of macrophages have been shown to participate in different stages of inflammation and tissue repair. In the late stage of tissue repair, the macrophages, following their engulfment of apoptotic neutrophils, acquire a new phenotype termed alternatively activated macrophages. These macrophages produce growth factors, such as vascular endothelial growth factor (VEGF), that facilitate the angiogenic response as part of tissue restoration. Then, in the later stages of tissue healing, capillary regression takes place. It is presently unknown whether macrophages play an antiangiogenic role in the final stages of tissue repair. Here, we examined whether soluble mediators secreted by pro-resolving CD11blow macrophages (Mres) inhibit angiogenesis in the context of the resolution of tissue repair. Our findings indicate that soluble mediators produced by ex vivo generated Mres (CM-Mres) attenuate angiogenesis in vitro by inhibiting human umbilical vein endothelial cell (HUVEC) proliferation by lowering their cyclin D1 expression. In addition, CM-Mres lowered HUVEC survival by inducing caspase 3/7 activation, and also inhibited VEGFR2 activation via VEGF. HUVEC migration and differentiation to tubular-like structure was also inhibited by CM-Mres. Similarly, CM-Mres significantly inhibited neovascularization as depicted ex vivo by utilizing the rat aorta ring assay and in vivo by utilizing the chick chorioallantoic membrane assay. Notably endostatin, which was shown previously to exert its antiangiogenic effect by inhibiting proliferation, survival, motility, and morphogenesis of endothelial cells via inhibition of VEGFR2 activation, is produced by Mres. Taken together, our results suggest that a specialized subset of macrophages that appear during the resolution of inflammation can produce antiangiogenic mediators, such as endostatin. These mediators can halt angiogenesis, thereby restoring tissue structure.
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PMID:Soluble Mediators Produced by Pro-Resolving Macrophages Inhibit Angiogenesis. 2992 74