ライフサイエンスコーパス: HHT

1 HHT [corrected] shows considerable variation in clinical

2 HHT and the transcription inhibitor SNS-032 induced syne

3 HHT at pH 6.6 resulted in denaturation of approximately

4 HHT has also shown activity in KIT-mutant mastocytosis m

5 HHT inhibited protein synthesis and reduced the Bcr-Abl

6 HHT is a very effective treatment of early chronic phase

7 HHT is caused by inheritance of a loss of function mutat

8 HHT is caused by loss-of-function (LoF) mutations in one

9 HHT is caused by loss-of-function mutations in the BMP9-

10 HHT is characterized by development of fragile, direct c

11 HHT manifests highly variable incidence and severity of

12 HHT patients presented a significantly lower rate of hea

13 HHT prevalence is estimated at 1 in 5000 and is accordin

14 HHT treatment resulted in a rapid and complete abolishme

15 HHT type 2 is caused by loss of function mutations in ac

16 HHT types 1 and 2 are caused by loss of function mutatio

17 HHT-associated bleeding results in substantial psychosoc

18 HHT-associated missense mutations in the ALK-1 extracell

19 HHT/MDA synthase activity was present in purified P450s

20 11-hydroxy-7,9,13-hexadecatrienoic acid (11-HHT) and 13-hydroxy-9,11,15-octadecatrienoic acid (13-HO

21 hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT), and synthetic CAY10583 (CAY) have been recently de

22 and 12(S)-hydroxyheptadecatrienoic acid (12-HHT), protects mice from lung injury caused by a pneumoc

23 hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT), thus effectively reducing levels of effector PGs (

24 hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT), which has been proposed as a promising therapeutic

25 hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT).

26 ent here the NMR structure of the agonist 12-HHT in its BLT2-bound state and a model of interaction o

27 or loxoprofen inhibited the production of 12-HHT and increased the sensitivity toward PLY, which was

28 or HHT, developed from a pilot study using 3 HHT patients and 6 lesions over the course of multiple i

29 led randomized clinical trial performed at 6 HHT centers of excellence.

30 Five of the aforementioned HHT patients underwent LT at Mayo Clinic, 4 with high ou

31 2C12 cells expressing BMP9-unresponsive ALK1 HHT mutants and in HHT patient blood outgrowth ECs.

32 Although HHT is associated with increased morbidity, the appropri

33 We calculated an HHT prevalence of between 2.1 in 5000 and 11.9 in 5000,

34 Here, we established an HHT mouse model with exclusive liver involvement and ade

35 ion in Acvrl1 were carefully examined for an HHT-like phenotype.

36 argue that bi-allelic loss of function in an HHT gene is a required event in the pathogenesis of HHT-

37 evelop by a two-hit mutation mechanism in an HHT gene.

38 thway can shift vascular responses toward an HHT-like state, potentially altering disease susceptibil

39 te that accelerated recovery of HHT-5371 and HHT-5411 decreased accumulation of these channels in ina

40 For mutants HHT-5411 and HHT-5371, the residual current appeared associated with

41 The combinations of flavopiridol and HHT and flavopiridol and imatinib synergistically decrea

42 were not cross-resistant to flavopiridol and HHT.

43 eriogenesis, and vascular disorders, such as HHT and pulmonary hypertension.

44 Because HHT is caused by loss-of-function mutations in bone morp

45 Furthermore, both HHT-5371 and -5411 recovered from inactivation significa

46 fludarabine, this induction was reversed by HHT, which overcame stromal cell-mediated protection.

47 ized that inhibition of protein synthesis by HHT would decrease Mcl-1 expression and induce apoptosis

48 ifferent genes, endoglin or ALK-1, can cause HHT.

49 n one of the additional genes that may cause HHT.

50 cular mechanism by which ENG mutations cause HHT is haploinsufficiency.

51 guingly, the constitutional mutation causing HHT is present throughout the body, yet the multiple VMs

52 In primary CLL cells, HHT induced significant apoptosis independent of the pro

53 line loss-of-function alleles cause combined HHT and colonic polyposis (MIM: 175050).

54 ts were 18 to 70 years old and had confirmed HHT, severe liver involvement, and a high cardiac index

55 Eighty consecutive HHT patients were randomized and treated in the phase 2

56 image and quantitatively characterize dermal HHT lesion behavior over time or throughout the course o

57 ing detailed morphological changes of dermal HHT lesions to understand the underlying dynamic process

58 utation predisposes an individual to develop HHT-associated vascular lesions.

59 linical criteria for HHT and had experienced HHT-related epistaxis with an Epistaxis Severity Score o

60 t patients who met the clinical criteria for HHT and had experienced HHT-related epistaxis with an Ep

61 Care delivery for HHT patients is impeded by the need for laborious, repea

62 has allowed the repurposing of new drugs for HHT treatment.

63 re undiscovered mutations in other genes for HHT and possibly vascular disorders with overlapping phe

64 LT listing for HHT has increased in substantially in more recent eras.

65 ients prospectively followed up after LT for HHT in the Lyon Liver Transplant Unit from 1993 to 2010,

66 Outcomes after LT for HHT patients are excellent with 86% survival after a med

67 term evaluation of graft status after LT for HHT, with a focus on the risk of recurrence.

68 study were (1) to determine trends in LT for HHT-related liver involvement in the United States using

69 ng pathways, the pathogenetic mechanisms for HHT remain elusive.

70 iber, and support a novel two-step model for HHT-associated AVM development in which pathological art

71 AD4 and GDF2 less frequently responsible for HHT.

72 f experience in the use of sclerotherapy for HHT-associated epistaxis and cutaneous telangiectasias,

73 We present refined metrics tailored for HHT, developed from a pilot study using 3 HHT patients a

74 no regulatory agency-approved therapies for HHT, multiple large studies, including randomized contro

75 Optimal treatment for HHT-related epistaxis is uncertain.

76 t local somatic mutations seed the formation HHT-related telangiectasia in a genetic two-hit mechanis

77 al with national recruitment from the French HHT Network.

78 In adults, the most frequent HHT manifestations relate to iron deficiency and anaemia

79 Data from HHT patients treated between July 2019 and November 2022

80 We found that human liver microsomes have HHT/MDA synthase activity that is concentration-dependen

81 ted individuals clinically suspected to have HHT was investigated with the use of exome and Sanger se

82 Homoharringtonine (HHT) is a first-in-class inhibitor of protein biosynthes

83 Homoharringtonine (HHT) is a novel plant alkaloid that produced a complete

84 Homoharringtonine (HHT) is a plant alkaloid that inhibits the elongation ph

85 Using this approach, homoharringtonine (HHT) shows high affinity to the PPI and strongly disrupt

86 clinical agents, such as homoharringtonine (HHT, 1), used to treat chronic myeloid leukemia (CML), i

87 The ribosome inhibitor, homoharringtonine (HHT), is used for the clinical treatment of leukemia, ye

88 a combination regimen of homoharringtonine (HHT) and low-dose cytarabine (ara-C) in patients with Ph

89 hibitor of transcription, homoharringtonine (HHT), a protein synthesis inhibitor, and imatinib were u

90 However, HHT is suspected to be underdiagnosed.

91 we studied the 12-hydroxyheptadecatrienoate (HHT)/malondialdehyde (MDA) synthase activity of human li

92 rentially expressed to Bonferroni P < .05 in HHT+/PTC BOECs clustered significantly only to generic p

93 ng BMP9-unresponsive ALK1 HHT mutants and in HHT patient blood outgrowth ECs.

94 tive to CT for detection of pulmonary AVM in HHT, while avoiding repeated exposure to radiation, neph

95 ent of arteriovenous malformations (AVMs) in HHT is not known.

96 ic medical therapeutics to treat bleeding in HHT.

97 e cobalamin deficiency is not more common in HHT than in the general population, though low-normal le

98 The North American Study of Epistaxis in HHT was a double-blind, placebo-controlled randomized cl

99 mutation is a necessary (required) event in HHT pathogenesis.

100 /5/8 signaling in primary ECs - including in HHT patient blood outgrowth ECs - and partially rescued

101 ristics, indications, and outcomes for LT in HHT.

102 he pathogenesis of vascular malformations in HHT.

103 leeding rate at presentation was observed in HHT (p = 0.069) and an increased rate of giant venous po

104 nvironmental factors that cause pathology in HHT type 2 patients.

105 osing has therefore therapeutic potential in HHT.

106 tinely tested in chronic anemia, its role in HHT has not been studied until now.

107 everity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse

108 spleen and brain), similar to those seen in HHT patients.

109 ls similar to vascular malformations seen in HHT patients.

110 histological similarities to lesions seen in HHT patients.

111 inducing endothelial cell cycle G1 state in HHT to prevent AVMs by repurposing the Food and Drug Adm

112 mined its prevalence and related symptoms in HHT patients.

113 role of imaging and image-guided therapy in HHT.

114 that rather than haploinsufficiency, VMs in HHT are caused by a Knudsonian two-hit mechanism.

115 ivin A receptor like type 1 (Alk1) to induce HHT in Fucci (fluorescent ubiquitination-based cell cycl

116 in the cytoplasmic connecting link to IVS5 (HHT-5371) and in IVS5 transmembrane segment (HHT-5411) w

117 lude that parallel sequencing of the 4 known HHT genes, multidisciplinary team review of variant call

118 t a unique case of a young female with known HHT and a series of retinal fundus images including opti

119 The long-term surviving Alk1HEC-KO HHT model offers opportunities to develop targeted thera

120 slation inhibitor omacetaxine mepesuccinate (HHT).

121 Testing several GIST cell line models, HHT led to a significant reduction in nascent protein sy

122 For mutants HHT-5411 and HHT-5371, the residual current appeared ass

123 Thirty-nine HHT patients were listed for LT in the SRTR database fro

124 The antitumor activity of HHT was confirmed in a GIST xenograft model.

125 stigating the simultaneous administration of HHT and IFN-alpha, as well as that of HHT and low-dose c

126 Importantly, a combination of HHT with the inhibition of the JNK-USP36-Snail1 axis syn

127 nts treated by LT for liver complications of HHT.

128 In this study, six courses of HHT were administered to 90 patients with early chronic

129 vide a rationale for clinical development of HHT in CLL as single agent or in combinations.

130 s aged 18 years or older with a diagnosis of HHT were recruited from 5 French centers from April 2014

131 CVRL1 (4.3 +/- 6%) leading to a diagnosis of HHT, and 14 in RASA1 (60.9 +/- 14.4%) leading to a diagn

132 s the precipitating event in the etiology of HHT.

133 15% of individuals with clinical features of HHT do not have mutations in these genes, suggesting tha

134 mations mimicking all pathologic features of HHT.

135 k to chromosome 12q13 or in which linkage of HHT to chromosome 9q33 had been excluded.

136 The great majority of HHT cases are caused by heterozygous loss-of-function mu

137 Diagnosis and management of HHT is guided in large part by imaging studies, making i

138 insights into the pathogenetic mechanisms of HHT and potential therapeutic approaches.

139 nodepleted postnatal retina-a mouse model of HHT vascular pathology-tacrolimus activated endothelial

140 , noninvasive, reliable, and robust model of HHT vascular pathology.

141 oblocked (BMP9/10ib) neonatal mouse model of HHT, we report here that the mTOR inhibitor, sirolimus,

142 AVMs, the source of much of the morbidity of HHT.

143 1 signaling pertinent to the pathogenesis of HHT and suggest that HHT might not be a TGF-beta subfami

144 e 2 receptors play a role in pathogenesis of HHT is unknown.

145 that may be relevant to the pathogenesis of HHT vascular lesions.

146 e is a required event in the pathogenesis of HHT-associated vascular malformations.

147 mportant questions about the pathogenesis of HHT.

148 s driving the organ-specific pathogenesis of HHT.

149 understanding of the molecular pathology of HHT [corrected] in particular and to angiogenesis in gen

150 common and most challenging presentations of HHT-associated bleeding that hematologists are likely to

151 To estimate the true prevalence of HHT, we summed allele frequencies of predicted pathogeni

152 ata demonstrate that accelerated recovery of HHT-5371 and HHT-5411 decreased accumulation of these ch

153 The combination regimen of HHT and ara-C is effective and safe in patients with CML

154 TGFBM2 locus influence clinical severity of HHT, [corrected] as assessed by development of pulmonary

155 ting that they may appear in later stages of HHT development.

156 ion of HHT and IFN-alpha, as well as that of HHT and low-dose cytosine arabinoside in patients failin

157 uidelines for the Diagnosis and Treatment of HHT, in which systemic therapies including antiangiogeni

158 improve the prognostication and treatment of HHT.

159 fficacy of pomalidomide for the treatment of HHT.

160 we hypothesize that phenotypic variation of HHT is not related to a particular ENG mutation.

161 Contrary to the current view of HHT as venous disease, our findings suggest that the art

162 There is limited data on HHT patients undergoing liver transplantation (LT) in th

163 Smad1/5/8, mTOR, and VEGFR2 pathways opposes HHT pathogenesis.

164 VFs, and show the predominance of RASA1 over HHT mutations.

165 A recent increase in potential HHT treatments have created a demand for quantitative me

166 Patients received HHT 2.5 mg/m(2) by continuous infusion daily for 5 days

167 ere seen in 66% of the patients who received HHT and IFN-alpha compared with 61% of the historical co

168 After receiving HHT, patients required lower doses of IFN-alpha to maint

169 In addition, we find that 12-S-HHT, but not 16:4(n-3), functions via leukotriene B4 rec

170 or chemical inhibition of BLT2 prevents 12-S-HHT-mediated resistance.

171 HHT-5371) and in IVS5 transmembrane segment (HHT-5411) with both diltiazem and verapamil.

172 r to pathogenic allele frequency and similar HHT prevalence across genetic ancestries.

173 uncharacterized, unrelated HHT and suspected HHT cases using the ThromboGenomics high-throughput sequ

174 Hereditary haemorrhagic telangiectasia (HHT) [corrected] is a vascular dysplasia syndrome caused

175 Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia inherited as an autosomal d

176 d in hereditary haemorrhagic telangiectasia (HHT), atherosclerosis, tumorigenesis and immunomodulatio

177 sia, hereditary haemorrhagic telangiectasia (HHT), wherein arterial and venous beds fail to remain di

178 with hereditary hemorrhagic telangiectasia (HHT) and cardiac failure is liver transplant.

179 ling: hereditary hemorrhagic telangiectasia (HHT) and cerebral cavernous malformation (CCM).

180 ed in hereditary hemorrhagic telangiectasia (HHT) and vascular remodeling, acting via the HHT target

181 ) and hereditary hemorrhagic telangiectasia (HHT) are two distinct vascular diseases linked to impair

182 Hereditary hemorrhagic telangiectasia (HHT) can cause recurrent, severe epistaxis, as well as a

183 M) in hereditary hemorrhagic telangiectasia (HHT) can necessitate liver transplantation.

184 Hereditary hemorrhagic telangiectasia (HHT) is a highly debilitating and life-threatening genet

185 Hereditary hemorrhagic telangiectasia (HHT) is a Mendelian disease characterized by vascular ma

186 Hereditary hemorrhagic telangiectasia (HHT) is a near-fully penetrant autosomal dominant disord

187 Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening genetic vascular

188 Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by the inappr

189 Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that manifests as

190 Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascu

191 Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characte

192 Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia.

193 Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant disorder characterized by

194 Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal dominant vascular dysplas

195 Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of vascular malformations

196 Hereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and a

197 Hereditary hemorrhagic telangiectasia (HHT) leads to fragile blood vessels, causing frequent bl

198 Hereditary hemorrhagic telangiectasia (HHT) management is evolving because of the emergence and

199 olved hereditary hemorrhagic telangiectasia (HHT) recruits to the 100,000 Genomes Project, GROFFFY-ba

200 with hereditary hemorrhagic telangiectasia (HHT) who smoke tobacco are more prone to PAVM persistenc

201 nt in hereditary hemorrhagic telangiectasia (HHT) with severe hepatic involvement.

202 ic of hereditary hemorrhagic telangiectasia (HHT), a disease caused by mutations in activin-like kina

203 Hereditary hemorrhagic telangiectasia (HHT), a genetic bleeding disorder leading to systemic ar

204 Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome is a blee

205 cause hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disorder of localized angiod

206 uding hereditary hemorrhagic telangiectasia (HHT), cancer, atherosclerosis and immunomodulation.

207 ds to hereditary hemorrhagic telangiectasia (HHT), characterized by fragile and leaky arterial-venous

208 with hereditary hemorrhagic telangiectasia (HHT), is regularly attending retinal screening since she

209 Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is an autosomal domi

210 In hereditary hemorrhagic telangiectasia (HHT), severe liver vascular malformations are associated

211 In hereditary hemorrhagic telangiectasia (HHT), the hallmark vascular lesion is termed an arteriov

212 Hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, is ca

213 ty in hereditary hemorrhagic telangiectasia (HHT), we subcategorized pathogenic DNA variants in ENG/e

214 gated hereditary hemorrhagic telangiectasia (HHT), which is caused by mutations in TGFbeta/bone morph

215 ermed hereditary hemorrhagic telangiectasia (HHT), which is characterized by recurrent nosebleeds, mu

216 sease hereditary hemorrhagic telangiectasia (HHT).

217 with hereditary hemorrhagic telangiectasia (HHT).

218 rk of hereditary hemorrhagic telangiectasia (HHT).

219 auses hereditary hemorrhagic telangiectasia (HHT).

220 on of hereditary hemorrhagic telangiectasia (HHT).

221 with hereditary hemorrhagic telangiectasia (HHT).

222 cause hereditary hemorrhagic telangiectasia (HHT, or Rendu-Osler-Weber syndrome), clinical evaluation

223 with hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu disease).

224 Hereditary hemorrhagic telangiectasia (HHT; Osler-Weber-Rendu disease) affects 1 in 5000 person

225 Hereditary hemorrhagic telangiectsia (HHT) is an inherited vascular disorder with highly varia

226 e notion that HHT is underdiagnosed and that HHT prevalence may be above the threshold of a rare dise

227 Further, we demonstrate that HHT induces autophagic degradation of the CDK2 protein v

228 Genetic studies have demonstrated that HHT can be caused by loss-of-function mutations in the g

229 We hypothesized that HHT could be effective in GIST through downregulation of

230 Our results support the notion that HHT is underdiagnosed and that HHT prevalence may be abo

231 Furthermore, we show that HHT activates the JNK-USP36-Snail1 axis in solid tumor c

232 We previously showed that HHT-associated skin telangiectases develop by a two-hit

233 to the pathogenesis of HHT and suggest that HHT might not be a TGF-beta subfamily disease.

234 These data suggest that HHT pathogenesis involves disruption of a complex networ

235 Evidence suggests that HHT pathogenesis strongly relies on overactivated PI3K/A

236 iron deficiency anemia management across the HHT disease severity spectrum.

237 MP9-regulated proteins that could affect the HHT phenotype.

238 The mean difference in the changes in the HHT-specific quality-of-life score between the groups wa

239 HHT) and vascular remodeling, acting via the HHT target genes, endoglin and ALK1.

240 A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with

241 exposed to ara-C and 11% had been exposed to HHT.

242 tes with BMP9/10 blocking antibodies lead to HHT-like vascular defects in the postnatal retinal angio

243 nsights into molecular mechanisms leading to HHT by defining how endothelial cell cycle is dysregulat

244 Two genes are linked to HHT: endoglin (ENG) in HHT1 and activin receptor-like ki

245 ed as the most likely ALK1 ligand related to HHT, yet the identity of the physiologic ALK1 ligand rem

246 lvement, and a high cardiac index related to HHT.

247 rmalities have been described in relation to HHT, but the pathogenesis of retinal involvement is stil

248 resulting in solid tumor cell resistance to HHT.

249 The response to HHT involved induction of apoptosis as well as cell cycl

250 Similar to HHT patients, the mice also exhibited gastrointestinal b

251 East Asia using the Hilbert-Huang transform (HHT).

252 adjusted from 6.6 to 7.5, high heat treated (HHT, 95 degrees Cx2min) or held unheated for 1h, re-adju

253 w objective method to analyse and understand HHT lesions using a minimally invasive, accessible, cost

254 edicted the mutational site for an unrelated HHT/polyposis-affected individual, where a complex inser

255 and OCTA analysis of the retina of unrelated HHT patients, we found a high rate of temporal and nasal

256 om 183 previously uncharacterized, unrelated HHT and suspected HHT cases using the ThromboGenomics hi

257 es were identical with HHT plus ara-C versus HHT alone, but the survival was significantly longer wit

258 Greater synergy was observed when HHT and imatinib were given sequentially compared with s

259 tched cancer-associated fibroblasts, whereas HHT was equally toxic to both.

260 ty-two percent of patients achieved CHR with HHT; CG responses were observed in 60% and were major in

261 pillaris atrophy in a patient diagnosed with HHT in such a young age.

262 tions were found in six of six families with HHT either shown to link to chromosome 12q13 or in which

263 Response rates were identical with HHT plus ara-C versus HHT alone, but the survival was si

264 Although individuals with HHT are haploinsufficient for one of these genes through

265 dy, yet the multiple VMs in individuals with HHT occur focally, rather than manifesting as a systemic

266 ly syndrome that has phenotypic overlap with HHT.

267 experts indicates that stable patients with HHT are eligible for sclerotherapy, with individualized

268 In this preliminary study of patients with HHT associated with severe hepatic vascular malformation

269 Materials and Methods Patients with HHT treated for PAVMs between January 2000 and August 20

270 In patients with HHT, a bevacizumab nasal spray treatment of 3 administra

271 Among patients with HHT, pomalidomide treatment resulted in a significant, c

272 Among patients with HHT, there were no significant between-group differences

273 provide therapeutic benefit in patients with HHT.

274 c, selective AKT inhibitor, in patients with HHT.

275 mice and in liver specimens of patients with HHT.

276 ved morbidity and mortality in patients with HHT.

277 anticoagulation, and anemia in patients with HHT.

278 l may be used to treat AVMs in patients with HHT.

279 ious study group of 73 patients treated with HHT alone.