ライフサイエンスコーパス: GRPR

1 GRPR activation also induces Akt phosphorylation, a prox

2 GRPR appears to mediate all effects of GRP, but only par

3 GRPR mutant mice showed comparable thermal, mechanical,

4 GRPR overexpression was found in 75.8% of the 1,432 tumo

5 GRPR specificity was confirmed by significantly reduced

6 GRPR-binding specificity was demonstrated by reduced tum

7 GRPR-binding specificity was studied by coinjection of a

8 GRPR-deficient mice showed decreased inhibition of princ

9 ct spinal cerebrospinal fluid injection of a GRPR antagonist significantly inhibited scratching behav

10 tion, we first studied four loss-of-affinity GRPR chimeric receptors formed by exchanging the four ex

11 Interestingly, pancreatic uptake, albeit GRPR-specific, declined rapidly with time.

12 gated for tumor integrin alpha(v)beta(3) and GRPR imaging, respectively.

13 Dual integrin alpha(v)beta(3) and GRPR recognition showed significantly improved tumor-tar

14 omparable dual integrin alpha(v)beta(3)- and GRPR-binding affinities in vitro, both of which were sli

15 used for dual integrin alpha(v)beta(3)- and GRPR-targeted imaging.

16 (177)Lu-NeoBOMB1) showed comparably high and GRPR-specific uptake in the PC-3 xenografts (e.g., 30.6

17 a disruption of crosstalk between 5-HT1A and GRPR may be a useful antipruritic strategy.

18 biophysical studies suggest that 5-HT1A and GRPR may function as receptor heteromeric complexes.

19 egrin or GRPR or that coexpress integrin and GRPR for imaging and therapeutic applications.

20 a promising PET tracer for dual integrin and GRPR positive tumor imaging.

21 fact that many tumors are both integrin and GRPR positive, we designed and synthesized a heterodimer

22 4 amino acids that differed between NMBR and GRPR in the uTM5 region were exchanged, but only the sub

23 In contrast, VIPR, SPR, and GRPR expression was detected in 31%, 27%, and 8% of panc

24 In contrast, VIPR, SPR, and GRPR expression was detected in fewer of the pancreatic

25 Because GRPR is overexpressed in a high percentage of ER-positiv

26 The association between GRPR expression and distant metastasis-free interval was

27 We studied associations between GRPR expression and clinical, pathologic, and biologic p

28 d a significant positive correlation between GRPR and SSTR2 expression analyzed by in vitro autoradio

29 tory concentration of 50% values for binding GRPR of JMV4168, JMV5132, (nat)Ga-JMV4168, and (nat)Ga-J

30 ed a chimeric receptor approach to make both GRPR loss of affinity and NMBR gain of affinity chimeras

31 C cells that express elevated levels of both GRPR and EGFR, we found that GRP induced rapid phosphory

32 at morphine triggers internalization of both GRPR and MOR1D, whereas GRP specifically triggers GRPR i

33 esize that a peptide ligand recognizing both GRPR and integrin will be advantageous because of its du

34 inding affinity with c(RGDyK) and comparable GRPR-binding affinity with BBN(7-14).

35 PEG(3)-Glu-RGD-BBN possesses the comparable GRPR and integrin alpha(v)beta(3) receptor-binding affin

36 domain (uTM5) of the NMBR by the comparable GRPR domains decreased the affinity 16-fold.

37 r subtypes of breast cancer were considered, GRPR was overexpressed in 86.2% of luminal A-like tumors

38 NeoBOMB1 is a novel DOTA-coupled GRPR antagonist with high affinity for GRPR and excellen

39 These analogs have demonstrated GRPR-specific small-animal PET of tumors but have variou

40 of (64)Cu-DOTA-[Lys(3)]BBN is able to detect GRPR-positive prostate cancer.

41 [Lys3]BBN and PET are suitable for detecting GRPR-positive prostate cancer in vivo.

42 PR are the critical residues for determining GRPR selectivity and suggest that both receptor-ligand c

43 atching, an effect largely reduced by either GRPR antagonists or PI3Kgamma inhibitor.

44 nd behavioral approaches to further evaluate GRPR downstream signaling pathways.

45 est a mechanism whereby aberrantly expressed GRPR might alter the outcome of patients with colorectal

46 ectively ablated lamina I neurons expressing GRPR in the spinal cord of mice.

47 upled GRPR antagonist with high affinity for GRPR and excellent in vivo stability.

48 GRP has high affinity for GRPR and lower affinity for NMBR.

49 an RGD for integrin binding and bombesin for GRPR binding.

50 ich patients can be potential candidates for GRPR-based imaging or targeted therapy, we screened inva

51 ults demonstrate that selectivity of GRP for GRPR over NMBR is primarily determined by two amino acid

52 tory concentration of 50% values (in nM) for GRPR binding of JMV5132, JMV4168, (nat)Ga-JMV5132, (nat)

53 for the GRPR and >3,000-fold selectivity for GRPR over the closely related neuromedin B receptor (NMB

54 able three amino acids in NMBR by those from GRPR caused a gain in affinity for each antagonist.

55 t the descending 5-HT system facilitates GRP-GRPR signaling via 5-HT1A to augment itch-specific outpu

56 These data demonstrate that GRP-GRPR signaling is necessary and sufficient for transmitt

57 s article we demonstrate that abrogating GRP/GRPR signaling specifically down-regulates HP1(Hsbeta) e

58 ined the mechanism of EGFR activation by GRP/GRPR in HNSCC proliferation.

59 In contrast, GRP/GRPR can be aberrantly expressed in colon cancer where t

60 tide/gastrin-releasing peptide receptor (GRP/GRPR) autocrine growth pathway is activated early in HNS

61 tide/gastrin-releasing peptide receptor (GRP/GRPR) autocrine growth pathway is activated early in HNS

62 Activation of SCN GRP/GRPR neurons evoked scratching behavior.

63 It triggered GRPR internalization in HEK-GRPR cells and Ca(2+) release in PC-3 cells (EC(50) = 1.

64 Furthermore, high GRPR and SSTR2 mRNA levels were observed more frequently

65 when breast tumors overexpressed GRPR, high GRPR expression was also found in metastatic lymph nodes

66 Primary tumors with high GRPR expression were associated with lower risk of dista

67 attractive biological features--e.g. higher GRPR-selectivity--vs their frog-homologues.

68 Analog affinities for the human GRPR determined against [(125)I-Tyr(4)]BBN were at the n

69 The substitutions of Thr(297) in GRPR by Pro from the comparable position in NMBR, Phe(30

70 ement of Thr(297), Phe(302), and Ser(305) in GRPR by the three comparable NMBR amino acids caused a 5

71 All effects of GRP were abrogated in GRPR-null mice.

72 comparable high and specific accumulation in GRPR-positive PC-3 tumors.

73 Significant accumulation of the activity in GRPR-positive pancreas was also observed (10.4 +/- 0.15

74 , in ex vivo naive mouse spinal cords and in GRPR transiently expressing HEK293 cells.

75 ng experiments against [(125)I-Tyr(4)]BBN in GRPR-positive PC-3 cell membranes.

76 inical evaluation of [(99m)Tc]Demomedin C in GRPR-expressing models are reported.

77 against [(125)I-Tyr(4)]BBN were conducted in GRPR-positive PC-3 cell membranes.

78 In radioligands specifically internalized in GRPR-expressing PC-3 cells.

79 Cs efficiently and specifically localized in GRPR-positive PC-3 xenografts in mice (4.4 percentage in

80 EC3 amino acids that differed in the NMBR in GRPR showed that two separate NMBR substitutions in the

81 tide chain, and compare their performance in GRPR-positive in vitro and in vivo models.

82 11)In-, and (177)Lu-NeoBOMB1 radioligands in GRPR-expressing cells and mouse models.

83 ching behaviour was significantly reduced in GRPR mutant mice in response to pruritogenic stimuli, wh

84 and its intracellular delivery was tested in GRPR expressing PC3 cells stably transfected with a luci

85 odels, in favor of future theranostic use in GRPR-positive cancer patients.

86 motif on key biologic parameters, including GRPR affinity, internalization efficiency, and in vivo s

87 s HP1(Hsbeta) expression and that inhibiting GRPR signaling, or ablating HP1(Hsbeta) expression, incr

88 In addition, blocking MOR1D-GRPR association attenuates MIS but not MIA.

89 Next, GRPR, SSTR2, and CXCR4 mRNA levels were measured by quan

90 raphy on human cancer samples (IC(50) in nM: GRPR, 1.4 +/- 0.2; NMBR, 106 +/- 18; and BB(3)R, >1000).

91 presses integrin on tumor vasculature but no GRPR in tumor tissue, which had no uptake of (64)Cu-NOTA

92 e report on the direct comparison of 3 novel GRPR-targeted radiolabeled tracers: Al(18)F-JMV5132, (68

93 ide of SB3 by Sta(13)-Leu(14)-NH2, the novel GRPR antagonist NeoBOMB1 was generated and labeled with

94 cid with an aromatic ring in position 185 of GRPR and the size of the backbone substitution in positi

95 the backbone substitution in position 198 of GRPR were important for GRP selectivity.

96 g via the unidirectional cross-activation of GRPR signaling by MOR1D heterodimerization.

97 Upstream, but not downstream, aspects of GRPR signaling have been investigated extensively.

98 02), and Ser(305) of the fourth EC domain of GRPR are the critical residues for determining GRPR sele

99 nging the four extracellular (EC) domains of GRPR with the corresponding NMBR EC domains.

100 substitution of the third EC domain (EC3) of GRPR markedly decreased GRP affinity.

101 PLCbeta3 and IP3R3, downstream effectors of GRPR, specifically block MIS but not MIA.

102 correlate messenger RNA (mRNA) expression of GRPR, SSTR2, and CXCR4 with clinicopathologic and biolog

103 ) transients, and action potential firing of GRPR(+) neurons.

104 -radiolabeled GRP analogs for PET imaging of GRPR expression in prostate cancer xenografted mice.

105 Hence, the prognostic impact of GRPR was lost when examined within specific molecular su

106 ochemistry for the presence and intensity of GRPR expression.

107 0.90], P=0.001), whereas high mRNA levels of GRPR were associated with a prolonged progression-free s

108 elop 18F-labeled bombesin analogs for PET of GRPR expression in prostate cancer xenograft models.

109 d that these peptides can be used for PET of GRPR-expressing prostate cancer.

110 lockade diminished serine phosphorylation of GRPR with ozone or OVA.

111 tide conjugate enters cells via a process of GRPR mediated endocytosis followed by trafficking to dee

112 RP sequences in the detection and therapy of GRPR-expressing tumors in humans.

113 pharmacokinetics for imaging and therapy of GRPR-expressing tumors.

114 gnificant impact on staging and treatment of GRPR-expressing tumors.

115 als for potential diagnosis and treatment of GRPR-positive tumors.

116 ause pharmacological blockade of the CGRP or GRPR pathway, or genetic ablation of Grpr, led to a dras

117 gastrin-releasing peptide receptor (GRPR) or GRPR neurons in the SCN abolished contagious scratching

118 or targeting tumors that express integrin or GRPR or that coexpress integrin and GRPR for imaging and

119 r high selectivity of PD168368 for NMBR over GRPR.

120 mportantly, when breast tumors overexpressed GRPR, high GRPR expression was also found in metastatic

121 ated receptor for gastrin-releasing peptide (GRPR), we used a chimeric receptor approach and a site-d

122 ated with estrogen receptor (ER) positivity (GRPR was high in 83.2% of ER-positive and 12% of ER-nega

123 ancer, using recently developed radiolabeled GRPR ligands.

124 neurons, whereas expression of its receptor GRPR is restricted to lamina I of the dorsal spinal cord

125 e mediated by the heptahelical GRP receptor (GRPR) and NMB receptor (NMBR).

126 Moreover, we found that GRP receptor (GRPR) is expressed in GABAergic interneurons of the late

127 littermates, bombesin-treated GRP receptor (GRPR)-null mice had increased interstitial fibrosis but

128 cells, and neutrophils express GRP receptor (GRPR).

129 ), but that none coexpress the GRP receptor (GRPR).

130 of gastrin-releasing peptide (GRP) receptor (GRPR) in both androgen-dependent (AD) and androgen-indep

131 in-releasing peptide (GRP) and its receptor (GRPR) are important components of itch transmission.

132 rin-releasing peptide (GRP) or its receptor (GRPR).

133 ssion of gastrin-releasing peptide receptor (GRPR) and integrin alpha(v)beta(3) as well as unfavorabl

134 e potent gastrin-releasing peptide receptor (GRPR) antagonist (68)Ga-SB3 ((68)Ga-DOTA-p-aminomethylan

135 for the gastrin releasing peptide receptor (GRPR) as determined against [(125)I-Tyr(4)]BBN was high

136 n of the gastrin-releasing peptide receptor (GRPR) gene and that on chromosome 8 occurred approximate

137 n of the gastrin-releasing peptide receptor (GRPR) has been reported on various cancer types, for exa

138 zes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, relaying itch information.

139 ssion of gastrin-releasing peptide receptor (GRPR) in various tumor types suggests that GRPR is an at

140 ted that gastrin-releasing peptide receptor (GRPR) is an itch-specific gene in the spinal cord, a lon

141 The gastrin-releasing peptide receptor (GRPR) is found to be overexpressed in a variety of human

142 Gastrin-releasing peptide receptor (GRPR) is overexpressed in human prostate cancer and is b

143 The gastrin-releasing peptide receptor (GRPR) is overexpressed in human prostate cancer.

144 sts that gastrin-releasing peptide receptor (GRPR) might be a valuable target in breast cancer.

145 ation of gastrin-releasing peptide receptor (GRPR) or GRPR neurons in the SCN abolished contagious sc

146 that the gastrin-releasing peptide receptor (GRPR) plays an important part in mediating itch sensatio

147 CGRP and gastrin-releasing peptide receptor (GRPR) transmission because pharmacological blockade of t

148 eceptor (gastrin-releasing peptide receptor (GRPR)).

149 Gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor superf

150 peptide, gastrin-releasing peptide receptor (GRPR), is an exception, because numerous classes of pept

151 eceptor, gastrin-releasing peptide receptor (GRPR), is expressed by various cell types, and it is ove

152 n of the gastrin-releasing peptide receptor (GRPR), somatostatin receptor 2 (SSTR2), and chemokine C-

153 y to the gastrin-releasing peptide receptor (GRPR), which is overexpressed on a variety of solid tumo

154 erapy of gastrin releasing peptide receptor (GRPR)-expressing tumors.

155 PR), and gastrin-releasing peptide receptor (GRPR).

156 Coactivation of 5-HT1A and GRP receptors (GRPR) greatly potentiates subthreshold, GRP-induced Ca(2

157 Gastrin-releasing peptide receptors (GRPRs) expressed on human tumors can serve as molecular

158 RC-3095 is a selective GRPR antagonist, recently found to have antiinflammatory

159 First, we studied GRPR and SSTR2 expression in 13 clinical breast cancer s

160 rons that express GRP and that likely target GRPR-expressing interneurons.

161 (99m)Tc]Demomedin C, can successfully target GRPR-expressing human tumors in vivo while displaying at

162 y of human GRP-based radiopeptides to target GRPR-positive lesions in vivo and has revealed the impac

163 These data demonstrate that GRPR is required for mediating the itch sensation rather

164 We hypothesize that GRPR signals in part through the PI3Kgamma/Akt pathway.

165 Our results thus indicate that GRPR may represent the first molecule that is dedicated

166 We propose that GRPR is an alternative chemotactic receptor that may pla

167 In a dry skin model of itch, we show that GRPR blockade or PI3Kgamma inhibition reversed the scrat

168 Our data also suggest that GRPR+ neurons are different from the spinothalamic tract

169 electrophysiological studies suggested that GRPR neurons receive glutamatergic input from NMBR neuro

170 r, these findings are highly suggestive that GRPR is expressed by the central terminals of DRG nocice

171 (GRPR) in various tumor types suggests that GRPR is an attractive target for cancer imaging and ther

172 Together, the present study suggests that GRPR+ neurons constitute a long-sought labeled line for

173 The GRPR antagonist JMV594 (H-D-Phe-Gln-Trp-Ala-Val-Gly-His-

174 The GRPR antagonist radioligands (67)Ga-, (111)In-, and (177

175 The GRPR gene was shown to escape X-inactivation.

176 of the 11 amino acid differences between the GRPR and NMBR in this domain were exchanged.

177 Each had high affinity for the GRPR and >3,000-fold selectivity for GRPR over the close

178 showed high affinity and selectivity for the GRPR during receptor autoradiography on human cancer sam

179 ecular basis for their high affinity for the GRPR, two classes of peptide antagonists, a statine anal

180 that two separate NMBR substitutions in the GRPR, Ile for Phe(185) or Ile for Ala(198), markedly dec

181 mpt to demonstrate a gain of affinity in the GRPR, the substitution of Tyr(219) for Phe caused an inc

182 N(7-14)NH(2) specifically accumulated in the GRPR-expressing PC-3 tumors and should be evaluated clin

183 tuting the fourth EC domain of NMBR into the GRPR resulted in a 300-fold gain in affinity for JMV594

184 ed by substituting the uTM5 of NMBR into the GRPR, a 9-fold increase in affinity occurred.

185 A dosage effect of the GRPR and a position effect of the SDC2 gene may, however

186 the fourth extracellular (EC) domain of the GRPR by the comparable NMBR domain markedly decreased th

187 between the aromatic ring of Phe(185) of the GRPR with GRP is the most important for GRP selectivity.

188 In this study, the GRPR-targeting potential of (18)F-labeled NOTA-8-Aoc-BBN

189 n vivo interaction of radiopeptides with the GRPR.

190 G-bombesin(7-14) bound with high affinity to GRPR with an inhibitory concentration of 50% of 3.5 and

191 G-bombesin(7-14) bound with high affinity to GRPR-expressing cells and that these peptides can be use

192 BBS binding to GRPR stimulated Gli through its downstream Galphaq and G

193 Ga-, (nat)In-, and (nat)Lu-NeoBOMB1 bound to GRPR with high affinity (half maximal inhibitory concent

194 SARNCs bound to GRPR with high affinity (range of 50% inhibitory concent

195 s with selectivity and with high affinity to GRPRs.

196 It triggered GRPR internalization in HEK-GRPR cells and Ca(2+) releas

197 and MOR1D, whereas GRP specifically triggers GRPR internalization and morphine-independent scratching

198 in a high percentage of ER-positive tumors, GRPR targeting offers wide perspectives for imaging and

199 ermined in a competition-binding assay using GRPR-overexpressing PC-3 tumors.

200 data indicate that imaging and therapy using GRPR or SSTR2 radioligands might especially be beneficia

201 f peptide +/- 40 nmol of Tyr(4)-BBN: in vivo GRPR blockade) in severe combined immune deficient mice

202 peptide +/- 40 nmol Tyr(4)-BBN: for in vivo GRPR blockade) in severe combined immunodeficiency mice