ライフサイエンスコーパス: endostatin

1 migration, and proliferation in response to endostatin.

2 This activity is inhibited by monomeric endostatin.

3 determinant of the bioactivity of oligomeric endostatin.

4 e unable to inhibit the action of oligomeric endostatin.

5 necessary for OS patients harboring p.104NN endostatin.

6 tatin) showed sustained expression of mutant endostatin.

7 malities seen in mice lacking collagen XVIII/endostatin.

8 ptides corresponding to different regions of endostatin.

9 ced the amount of the antiangiogenic protein endostatin.

10 corresponding to the NH2-terminal domain of endostatin.

11 e structures with potency similar to that of endostatin.

12 f metastasis than OS patients with wild type endostatin.

13 ne transfer resulted in high serum levels of endostatin.

14 nd suggest that beta-catenin is a target for endostatin.

15 tilized to inhibit the motogenic activity of endostatin.

16 ere found in association with high levels of endostatin.

17 er as essential for the inhibitory effect of endostatin.

18 inase-9, and up to 3-fold more activin A and endostatin.

19 f LC3beta expression and ablated response to endostatin.

20 exclusively present in RAC exosomes, such as endostatin.

21 and vessel cooption was blocked only by the endostatin.

22 o the target for the angiogenesis inhibitor, endostatin.

23 up-regulation of the angiogenesis inhibitor endostatin.

24 up-regulation of the angiogenesis inhibitor endostatin.

25 ed toward the mature endothelial response to endostatin.

26 vasostatin and collagen 18a1, a precursor of endostatin.

27 atin (4.4+/-0.9-fold increase, P<0.001), and endostatin (2.9+/-0.4-fold increase, P=0.03) were signif

28 sed expression of the antiangiogenic protein endostatin (210+/-48%; P=0.004 versus NORM).

29 Endostatin, a 20-kd fragment of collagen XVIII, is a pot

30 Endostatin, a 20-kDa fragment of collagen XVIII, is a po

31 Endostatin, a C-terminal fragment of collagen XVIII (col

32 Endostatin, a fragment of the basement membrane componen

33 sm in a phase I dose-escalating protocol for endostatin, a novel antiangiogenic agent.

34 Endostatin, a proteolytic fragment of basement membrane-

35 Endostatin, a proteolytic fragment of collagen XVIII, is

36 Endostatin, a type XVIII collagen fragment, is a potent

37 mechanism for the perturbation of oligomeric endostatin action by its monomeric counterpart via compe

38 iption through the LEF1 site as critical for endostatin action in vitro and suggest that beta-catenin

39 this apparent requirement for E-selectin in endostatin action, we manipulated E-selectin expression

40 ting that cyclin D1 is a critical target for endostatin action.

41 Endostatin activated autophagic gene expression through

42 replication-defective adenovirus expressing endostatin (Ad-mEndo) administered during the preinvasiv

43 In corneal micropocket assays, recombinant endostatin administered i.p. by osmotic pump inhibited b

44 In addition to increased generation of endostatin, AdMMP-9 promoted an antitumor immune respons

45 half-life as compared with that of G129R or endostatin alone, and exhibited greater tumor inhibitory

46 of the mice compared with the treatments of endostatin alone, cytosine deaminase alone, or endostati

47 Coexpression of endostatin along with VEGF reversed the tumorigenic phen

48 ctor (VEGF) (an angiogenesis stimulator) and endostatin (an angiogenesis inhibitor), or for thrombosp

49 Endostatin, an angiogenesis inhibitor tested in multiple

50 at can be proteolytically cleaved to release Endostatin, an antiangiogenesis signaling factor.

51 of AD patients also show an accumulation of endostatin and Abeta peptides which have been shown to b

52 These studies indicate that stable endostatin and angiostatin gene therapy may be more effe

53 o significant protection, the combination of endostatin and angiostatin gene transfer from a single v

54 at AAV-mediated long-term expression of both endostatin and angiostatin may have clinical utility aga

55 Finally, endostatin and angiostatin, which have been sources of c

56 udy was to examine the immunolocalization of endostatin and coll XVIII in the retina and choroid of h

57 In the choroid, endostatin and coll XVIII were localized to blood vessel

58 for endorepellin and that endorepellin binds endostatin and counteracts its anti-angiogenic effects.

59 , parstatin increased the gingival levels of endostatin and decreased vascular endothelial growth fac

60 stigated the functional relationship between endostatin and E-selectin.

61 arcinoma cells treated with a combination of endostatin and either DI-TSPa or TNP-470, at doses that

62 effects of two known antiangiogenic agents (endostatin and fumagillin) on the gene expression profil

63 e induced CNV in mice lacking collagen XVIII/endostatin and in control mice.

64 ntibody that blocks the interactions between endostatin and laminin was utilized to inhibit the motog

65 The responses of matrix metalloproteinases, endostatin and nucleolin poorly correlated with detraini

66 vascular endothelial growth factor-A (VEGF), endostatin and nucleolin were increased at 2-4 h (P < 0.

67 lial progenitor cells are a novel target for endostatin and suggest that the relative numbers of CECs

68 uppress tumor growth, whereas the absence of endostatin and tumstatin did not alter the effect of LDC

69 pression of anti-angiogenic factors, such as endostatin, and decreased pro-angiogenic factors, includ

70 ion and VEGF production, increased TSP-1 and endostatin, and inhibited corneal neovascularization.

71 strate the dual therapeutic effects of G129R-endostatin, and suggests that this fusion protein has gr

72 e cells also showed increased sensitivity to endostatin, and this effect required the E-selectin cyto

73 The tumor-suppressive action of TSP-1, endostatin, and tumstatin correlates with expression of

74 ed with goat anti-human and mouse anti-human endostatin antibodies and rabbit anti-mouse coll XVIII.

75 Endostatin, antithrombin, and anastellin are members of

76 The two binding domains on endostatin appear to be separate with the possibility of

77 ndings demonstrate that high serum levels of endostatin are capable of inhibiting endothelial regener

78 itumor activities of the soluble recombinant endostatin are equally as potent as those of the previou

79 igration, and antipermeability activities of endostatin are mimicked by a 27-amino-acid peptide corre

80 Although both angiostatin and endostatin are potent inhibitors of tumor angiogenesis,

81 ere, we demonstrate that these properties of endostatin are primarily mediated by laminin in the base

82 Tumstatin and endostatin are two inhibitors of angiogenesis derived fr

83 identified clusterin and collagen 18 alpha1/endostatin as GOM components.

84 f the antiangiogenic factors angiostatin and endostatin as secretory proteins by recombinant adeno-as

85 genic peptides (thrombospondin-1, TSP-1; and endostatin) as well as pro-angiogenic factors (vascular

86 It is not known whether endogenous endostatin at physiological levels has a protective role

87 tial of stable expression of angiostatin and endostatin before the onset of neoplasia and during the

88 lined retinal blood vessels, which suggested endostatin binding to a component of vessel walls.

89 itol 3-kinase/Akt/mTOR/4E-BP1 pathway, human endostatin binding to alpha 5 beta 1 integrin leads to t

90 mmunodeficiency lentiviral vector coding for endostatin (BIV-vectored endostatin, or BIVendostatin).

91 whereas, thromboxane A(2) (TXA(2)) released endostatin but not VEGF.

92 Pericardial fluid levels of endostatin, but not VEGF, are associated with the presen

93 ulin-like growth factor binding proteins, or endostatin by >/=30%.

94 s of G129R and the antiangiogenic effects of endostatin by creating a novel fusion protein (G129R-end

95 of surgery and were assayed for the VEGF and endostatin by enzyme-linked immunosorbent assay comparin

96 we demonstrate that the effect of oligomeric endostatin can also be inhibited by exogenous glycosamin

97 Together, our data suggest that endostatin can be recognized as an endogenous AR inhibit

98 es show a paraendothelial mechanism by which endostatin can inhibit peritoneal dissemination of ovari

99 Finally, we showed that endostatin can repress cyclin D1 promoter activity in ce

100 We have investigated the mechanism by which endostatin causes G(1) arrest in endothelial cells.

101 In control mice treated with recombinant endostatin, CNV lesions were almost undetectable.

102 stigated ocular structures in collagen XVIII/endostatin (Col18a1(-/-))-deficient mice to elucidate th

103 s associated with Notch3 activity, including endostatin/collagen 18alpha1 and Notch3 extracellular do

104 ic peptide independent manner, whereas human endostatin competes with fibronectin/RGD cyclic peptide

105 Purified heparin-monomeric endostatin constructs generated by zero-length cross-lin

106 gonist (AYPGKF-NH(2)) resulted in release of endostatin-containing granules, but not VEGF-containing

107 gonist (TFLLR-NH(2)) liberated VEGF, but not endostatin-containing granules.

108 This property of monomeric endostatin contrasts with that of the trimeric endostati

109 This endostatin-cytosine deaminase fusion approach opens an a

110 When we used the endostatin-cytosine deaminase fusion protein to treat s.

111 The endostatin-cytosine deaminase protein significantly inhi

112 l metastasis tumors, our results showed that endostatin-cytosine deaminase treatment provided stronge

113 ly expressed genes included COL7A1, COL18A1 (endostatin), DAF, COMP, and VEGFB.

114 Endostatin decreased the hyperphosphorylated retinoblast

115 fer, the allografts eventually rejected, and endostatin decreased.

116 Increased myocardial expression of endostatin, decreased expression of vascular endothelial

117 ndostatin was administered to collagen XVIII/endostatin-deficient mice, CNV lesions were similar to t

118 Endostatin deposits were also absent in the injured arte

119 ents revealed that overexpression of p.104NN endostatin did not significantly inhibit OS lung metasta

120 to provide tamoxifen-inducible expression of endostatin, diffuse endostatin immunoreactivity was indu

121 Here, we show that endostatin directly induces apoptosis and inhibits the W

122 Finally, we show that endostatin directly induces cell death on primary FAP-re

123 We have shown previously that the oligomeric endostatin domain of collagen XVIII (NC1) functioned as

124 olecular studies demonstrated binding of the endostatin domain to heparan sulfate and to BM component

125 que functional domains, including Kunitz and endostatin domains, suggesting direct involvement in pro

126 activity in endothelial cells and found that endostatin down-regulated the cyclin D1 promoter.

127 Interestingly, administration of endostatin dramatically inhibited OS lung metastasis in

128 0.1 microg/ml) of recombinant mouse or human endostatin during the culture period.

129 n may be a useful predictor and modulator of endostatin efficacy in antiangiogenic therapy.

130 virus (AAV)-mediated expression of a mutant endostatin either alone or in combination with carboplat

131 e, adenovirus-mediated in situ expression of endostatin either inside the peritoneum or by the ovaria

132 uents (decorin, collagen VI, laminin alpha2, endostatin, endorepellin, and kringle V), can modulate a

133 , such that in the absence of collagen XVIII/endostatin, endothelial cells are more adhesive to fibro

134 Endostatin (ES) is a fragment of collagen XVIII that pos

135 ere, we report for the first time that human endostatin (ES) prevents androgen-independent growth phe

136 on may be prevented by coadministration with endostatin (ES), an endogenous angiogenesis inhibitor wi

137 Endostatin (ES), the C-terminal fragment of collagen XVI

138 relationship of a potent angiostatic factor, endostatin (ES), with disease severity and mortality in

139 t recipients with the angiogenesis inhibitor endostatin failed to inhibit leukocyte infiltration of t

140 lagen XVIII and its proteolytically released endostatin fragment are abundant proteoglycans in vascul

141 Of these, those who first heard about endostatin from the media were five times more likely to

142 Those who first heard about endostatin from the media were no more motivated by hope

143 vating mutations in the human collagen XVIII/endostatin gene (COL18A1) in patients with Knobloch synd

144 ning a fusion transgene comprising the human endostatin gene and the kringle-5 domain of the human pl

145 ent against desmoid tumors, we advocate that endostatin gene therapy represents an attractive new the

146 f carboplatin treatment combined with mutant endostatin gene therapy resulted in 60% of the animals r

147 In patients with diabetic retinopathy, endostatin gene transfer may provide a way to decrease t

148 Endostatin gene transfer resulted in high serum levels o

149 Endostatin given daily as a 1-hour intravenous infusion

150 Endostatin given on this schedule was essentially free o

151 developed based on the observation that the endostatin-green fluorescence protein gene and endostati

152 and TNP-470 (TNP) were very similar, whereas endostatin had a dramatically different profile.

153 In addition, OS patients with p.104NN endostatin had a shorter survival time and a higher rate

154 In contrast, mice that received VEGF and endostatin had significantly lower numbers of CECs and r

155 G129R-endostatin has a significantly prolonged serum half-life

156 Remarkably, Endostatin has a specific activity, independent of basel

157 That collagen XVIII/endostatin has an essential role in ocular development a

158 Endostatin has attracted considerable attention because

159 The D104N polymorphism (p.D104N) in endostatin has been previously identified in many types

160 up, suggesting that individuals with p.104NN endostatin have a significantly increased risk for OS.

161 Laboratory investigations with endostatin have indicated broad antitumor activity coupl

162 e basement membrane component collagen XVIII/endostatin have massive accumulation of sub-RPE deposits

163 the physiological function of collagen XVIII/endostatin have recently been obtained through the ident

164 tory effect was 10-50 times more potent than endostatin, IFN-gamma, and IFN-inducible protein 10 in v

165 -inducible expression of endostatin, diffuse endostatin immunoreactivity was induced thoroughout the

166 Endostatin immunoreactivity was significantly higher in

167 ame markedly more sensitive to inhibition by endostatin in a vascular endothelial growth factor-induc

168 trastructural organization of collagen XVIII/endostatin in basement membranes, including Bruch's memb

169 mulation of clusterin and collagen 18 alpha1/endostatin in brain vessel pathology.

170 nstrate an important role for collagen XVIII/endostatin in cell-matrix interactions in certain tissue

171 gest that AAV-mediated gene therapy of P125A-endostatin in combination with carboplatin is a useful m

172 Induction of endostatin in double transgenic mice with doxycycline-in

173 r16K hPRL was 100 times more potent than endostatin in inducing apoptosis in HRECs.

174 E. coli (r16K hPRL) was compared to that of endostatin in inducing apoptosis of cultured human retin

175 in more discrete, less intense staining for endostatin in the retina than that seen with the inducib

176 required for the antiangiogenic activity of endostatin in vivo and ex vivo and confers endostatin se

177 Mean serum levels of endostatin increased about 8-fold above that of controls

178 ater tumor inhibitory effects than G129R and endostatin individually or in combination.

179 Endostatin-induced apoptosis was probably responsible fo

180 of XBP1 or IRE1alpha by shRNA in ECs ablated endostatin-induced autophagosome formation.

181 At the same time, G129R-endostatin inhibited human umbilical vein endothelial ce

182 Similarly, endostatin inhibited vascular endothelial growth factor-

183 Endostatin inhibits androgen-independent prostate cancer

184 Endostatin is a 20-kd proteolytic fragment of collagen X

185 Endostatin is a specific inhibitor of endothelial cell g

186 Endostatin is a well-known antiangiogenic protein that h

187 Endostatin is an antiangiogenic factor that maintains co

188 These findings demonstrate that endogenous endostatin is an inhibitor of induced angiogenesis and t

189 ether, these results suggest that p.104NN of endostatin is associated with the risk of OS and demonst

190 This suggests that collagen XVIII/endostatin is critical for normal blood vessel formation

191 Our data demonstrate that collagen XVIII/endostatin is essential for RPE function, and suggest an

192 ta 3 integrin, whereas the activity of human endostatin is mediated by alpha 5 beta 1 integrin.

193 Endostatin is the first endogenous angiogenesis inhibito

194 s transduced with a lentivirus containing an endostatin::kringle-5 fusion gene demonstrated an inhibi

195 Overexpression of endostatin led to decreased reendothelialization and inc

196 growth factor-beta1, and the anti-angiogenic endostatin levels in either serum or carcinoma tissue ex

197 data suggest that the angiogenesis inhibitor endostatin levels may locally modulate coronary collater

198 However, pericardial fluid endostatin levels were nearly 40% lower in patients with

199 ose observations and report that leptospiral endostatin-like protein A (LenA) binds human plasminogen

200 dostatin-green fluorescence protein gene and endostatin-luciferase gene selectively target to endothe

201 ese regions include those for collagen XVIII/endostatin, matrix metalloproteinase 11, integrin beta2,

202 These data suggest that endostatin may be an endogenous inhibitor of vasopermeab

203 Endostatin may have a regulatory role in the pathogenesi

204 o fibronectin suggesting that collagen XVIII/endostatin may regulate interactions between endothelial

205 a(1) in ovarian cancer cells interfered with endostatin-mediated inhibition of peritoneal seeding.

206 mass spectroscopy were employed to evaluate endostatin metabolism.

207 dostatin contrasts with that of the trimeric endostatin moiety generated from the intact C-terminal d

208 mbinant adenovirus, expressing either murine endostatin (n=19) or control adenoviral vector (n=12), b

209 lture of aortic explants from collagen XVIII/endostatin-null mice (ko) to wild-type (wt) littermates.

210 The inhibitory effect of endostatin occurred during or after the progression to i

211 Here, we report a profound effect of endostatin on prostate cancer cells by efficient intrace

212 The action of oligomeric endostatin on these cells was shown to be dependent on c

213 y, although overall, no consistent effect of endostatin on tumor vasculature was seen.

214 fects of increased intraocular expression of endostatin on vascular endothelial growth factor (VEGF)-

215 hereas treatment with rAAV containing either endostatin or angiostatin alone resulted in moderate to

216 mice with an absence of type XVIII collagen (endostatin) or type IV collagen alpha3 chain (tumstatin)

217 l vector coding for endostatin (BIV-vectored endostatin, or BIVendostatin).

218 endent lines of mice deficient in tumstatin, endostatin, or thrombospondin-1 (TSP-1), to address the

219 We examined the effect of endostatin overexpression on reendothelialization and ne

220 In addition, endostatin overexpression resulted in increased neointim

221 hanced endothelial apoptosis, in response to endostatin overexpression, were associated with increase

222 However, it is unknown whether endostatin p.D104N affects the risk and progression of o

223 the angiogenesis inhibitors caplostatin and endostatin peptide mP-1 delayed and suppressed the onset

224 Endostatin pharmacokinetics were linear with dose, and s

225 Our results suggest that endostatin plays an important role in corneal allograft

226 nant adeno-associated virus-6 encoding mouse endostatin plus angiostatin (E+A) by i.m. injection.

227 dostatin alone, cytosine deaminase alone, or endostatin plus cytosine deaminase.

228 hese data suggest that reduced levels of the endostatin portion of coll XVIII in Bruch's membrane, RP

229 control eyes, coll XVIII and endostatin (the endostatin portion of coll XVIII) immunoreactivity was o

230 uced angiogenesis and that administration of endostatin potently inhibits CNV growth and vascular lea

231 vidence suggests that lack of collagen XVIII/endostatin predisposes to hydrocephalus formation.

232 Thus far, however, recombinant endostatin prepared from Escherichia coli is insoluble a

233 s with no effect on migration, whereas human endostatin prevents endothelial cell migration with no e

234 ells into the grafts promotes destruction of endostatin-producing cells, resulting in corneal neovasc

235 l, specifically the potential correlation of endostatin production and T cell recruitment.

236 of an increase in CXCL1 along with decreased endostatin production in SMCs.

237 rafts around POD10 correlated with decreased endostatin production.

238 Addition of recombinant endostatin protein or blockade of CXCL1 with a neutraliz

239 Deposits of endostatin protein were detected along the denuded arter

240 inct properties of human tumstatin and human endostatin provide the first insight into their diverse

241 nfirmed in a Tie2/LacZ mouse model, in which endostatin reduced the number of beta-galactosidase-expr

242 factor, VEGF) or an anti-angiogenic factor (endostatin) related to the presence of coronary collater

243 Human endostatin released from the microcapsules brought about

244 eneic and syngeneic corneal grafts survived; endostatin remained high throughout.

245 We evaluated recombinant human endostatin (rh-Endo) in a phase I trial designed to asse

246 -finding clinical trial of recombinant human endostatin (rh-Endo) that examined potential surrogates

247 d human phase I studies of recombinant human endostatin (rhEndostatin) suggested activity in neuroend

248 f endostatin in vivo and ex vivo and confers endostatin sensitivity to nonresponsive human endothelia

249 ere was a strong inverse correlation between endostatin serum level and area of CNV.

250 ndothelialization correlated negatively with endostatin serum levels (P<0.05).

251 nd neointima area correlated positively with endostatin serum levels, whereas the degree of reendothe

252 VIII and its proteolytically derived product endostatin show delayed regression of blood vessels in t

253 an endostatin with P125A substitution (P125A-endostatin) showed sustained expression of mutant endost

254 port a model in which proteolytic release of Endostatin signals trans-synaptically, acting in concert

255 iral induction of high levels of circulating endostatin significantly inhibits mammary tumor growth d

256 umor growth in transgenic mice overproducing endostatin specifically in the endothelial cells (a 1.6-

257 in by creating a novel fusion protein (G129R-endostatin) specifically for breast cancer therapy.

258 Endostatin staining outlined retinal blood vessels, whic

259 Endostatin tended to decrease in D14 and D28 compared to

260 The first recombinant endostatin that elicited strong antitumor activity was e

261 In aged control eyes, coll XVIII and endostatin (the endostatin portion of coll XVIII) immuno

262 eoblasts with inhibitors of the Wnt pathway (endostatin), the BMP pathway (Noggin), or the ER pathway

263 In addition, endostatin therapy may be necessary for OS patients harb

264 levels of antiangiogenic factors, including endostatin, thrombospondin-1 (TSP-1), and pigment epithe

265 tic neuroendocrine cancer, administration of endostatin, thrombospondin-1, and tumstatin peptides, as

266 Endostatin, thrombospondin-1, fumagillin, and its synthe

267 Therefore, the ability of endostatin to competitively inhibit tumor cell seeding o

268 possibility of intraperitoneal expression of endostatin to reduce recurrence.

269 The ability of endostatin to reduce VEGF-induced retinal vascular perme

270 I but was not suppressed by increasing serum endostatin to wild-type levels.

271 ty in response to the angiogenesis inhibitor endostatin, to determine if HemEPCs share this abnormal

272 Endostatin treatment also prevented primary ovarian canc

273 Furthermore, exogenous endostatin treatment delayed allograft rejection and pro

274 as balanced by the inducible coexpression of endostatin under the control of Tet-activated promoter.

275 es in the cleavage of collagen XVIII to form endostatin using FN-439 reverses RAC exosome-mediated re

276 Here, we analyzed the p.D104N endostatin variant in 236 patients with OS and 418 healt

277 Endostatin was administered as a 1-hour intravenous infu

278 When recombinant endostatin was administered to collagen XVIII/endostatin

279 Oligomeric endostatin was also found to induce morphological change

280 els and allowed visualization of sites where endostatin was concentrated.

281 portantly, the therapeutic efficacy of G129R-endostatin was confirmed using a mouse breast cancer cel

282 This angiogenic response to endostatin was consistently expressed by HemEPCs over se

283 A phase I trial of recombinant human endostatin was designed to evaluate toxicity and explore

284 Using this method, endostatin was found to bind ovarian cancer cells throug

285 The activity of endostatin was impaired in both fibronectin- and vitrone

286 In vitro, endostatin was synergistically antiangiogenic with eithe

287 Importantly, endostatin was unable to arrest cyclin D1 overexpressing

288 To enhance the therapeutic efficacy of endostatin, we fused endostatin with cytosine deaminase,

289 and systemic levels of both angiostatin and endostatin were confirmed by in situ hybridization of th

290 encies of wild type and heterozygous p.104DN endostatin were observed in controls and OS patients.

291 ADP) stimulated the release of VEGF, but not endostatin whereas, thromboxane A(2) (TXA(2)) released e

292 the best-studied angiogenesis inhibitors is endostatin, which acts through the inhibition of endothe

293 n its C-terminal domain releases a fragment, endostatin, which has been reported to have anti-angioge

294 This correlates with endogenous endostatin, which increased and remained high in syngene

295 aled that phenylalanine-rich alpha1-helix in endostatin-which shares structural similarity with nonca

296 These findings provide new insights into endostatin whose antitumor effect is not limited to inhi

297 therapeutic efficacy of endostatin, we fused endostatin with cytosine deaminase, which converts a pro

298 ction of recombinant AAV (rAAV)-mutant human endostatin with P125A substitution (P125A-endostatin) sh

299 Our data are consistent with a model of endostatin with two binding sites: one mainly to laminin

300 inhibited OS lung metastasis in the p.104NN endostatin xenograft model.