ライフサイエンスコーパス: VHL

1 VHL intrinsically orchestrated such conversion under bot

2 VHL is a complex, multiorgan disease that spans the brea

3 VHL is a potential target for treating anemia and ischem

4 VHL is expressed as two variants, VHL30 and VHL19.

5 VHL knockdown activated beta-catenin and elevated AURKA

6 VHL loss activates the HIF-2 transcription factor, and c

7 VHL manifestations can be visualized with (89)Zr-bevaciz

8 VHL mutation and hypoxia-inducible factor 1alpha express

9 VHL patients with at least 1 measurable hemangioblastoma

10 VHL proteostasis is regulated by multiple mechanisms inc

11 VHL-deficient clear cell renal cell carcinomas (ccRCC),

12 VHL-deficient Treg cells failed to prevent colitis induc

13 VHL-mutant cells exhibit metabolic abnormalities that ca

14 VHL-R167Q binds elongin C and elongin B with considerabl

15 In 5 VHL patients, we resected quiescent hemangioblastomas (Q

16 (89)Zr-bevacizumab PET visualized 59 VHL manifestations, 0-17 per patient.

17 is targeting chimeras (PROTACs) containing a VHL ligand can hijack the E3 ligase activity to induce d

18 but retains residual capacity to generate a VHL-elongin C-elongin B complex, downregulate HIF2alpha,

19 ifferentially modulated RCC progression in a VHL-dependent manner.

20 contrast to its hypoxia-regulated activity, VHL mono-, rather than poly-ubiquitinates AURKA, in a PH

21 more effective for the treatment of advanced VHL-associated RCH.

22 Three patients with advanced VHL-associated juxtapapillary RCH were treated with syst

23 Three patients with advanced VHL-related juxtapapillary RCH treated with systemic sun

24 stress as an underlying vulnerability of all VHL mutated renal cancers that could be therapeutically

25 We analyzed VHL-R167Q proteostasis and function at normoxia, at hypo

26 r gene is mutated as frequently in ccRCC and VHL mutations are truncal, VHL inactivation is regarded

27 ied an inverse correlation between Daam2 and VHL expression across a host of cancers, including gliom

28 We report that VHL-deficient and VHL-positive renal cancer cells possess significantly de

29 thetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation.

30 Chromosome 3p loss and VHL aberrations were the only ubiquitous events.

31 Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients.

32 ucing HuR interaction with targets SIRT1 and VHL mRNAs, and accelerating target mRNA decay.

33 s display strong tissue specificity (such as VHL in kidney cancer samples and GATA3 in breast cancer

34 Casein kinase 2-mediated phosphorylation at VHL N-terminus was required for the cleavage.

35 d VHL, is a promising approach to augmenting VHL levels and function.

36 ker analyses revealed a relationship between VHL mutation status and outcome with everolimus but not

37 as a selective inhibitor for ccRCC with both VHL and SETD2 mutations.

38 out could reverse the increased IFN-gamma by VHL-deficient Treg cells and restore their suppressive f

39 that the two major species are generated by VHL protein cleavage, and the cleavage regulates VHL pro

40 ws how loss of heterozygosity, hallmarked by VHL deletion in ccRCC, may uniquely shape tumor metaboli

41 ate that regulation of HIF-1alpha pathway by VHL is crucial to maintain the stability and suppressive

42 LF4 by PRMT5 inhibits KLF4 ubiquitylation by VHL and thereby reduces KLF4 turnover, resulting in the

43 X - caspase-3 pathway unrelated to canonical VHL pathway.

44 her VHL-related disease in patients carrying VHL-R167Q or similar missense mutations.

45 We characterized VHL species using genetical and pharmacological approach

46 mutations, with R167Q being the most common VHL point mutation in hereditary VHL disease.

47 VHL E3 ubiquitin ligase, ECV (Elongins/Cul2/VHL).

48 Conversely, in checkpoint-deficient VHL-negative renal carcinoma cells, inhibition of miR-28

49 The most active compound, CM11, dimerizes VHL with high avidity in vitro and induces potent, rapid

50 Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors.

51 ) associated with von Hippel-Lindau disease (VHL) is challenging because of the malignant potential a

52 Von Hippel-Lindau disease (VHL) is one of the most common inherited neoplasia syndr

53 von Hippel-Lindau disease (VHL) patients develop highly vascular tumors, including

54 the VHL ubiquitin ligase complex, displaces VHL-associated Cullin 2, and impairs HIF2alpha ubiquityl

55 l for high-risk cohorts such as the familial VHL disease patients.

56 umber of tumor suppressors, including FBXW7, VHL, and STK11, also showed such clustering.

57 re are no effective treatments available for VHL disease.

58 Here we identified a novel mechanism for VHL suppression in tumors that do not have inactivating

59 emangioblast as the tumor cell of origin for VHL-associated hemangioblastomas and indicate that it is

60 ) is a novel, hypoxia-independent target for VHL ubiquitination.

61 Furthermore, genetic testing for VHL is indicated in some individuals with seemingly spor

62 Genetic testing for VHL is widely available and will detect a disease-causin

63 ibitors represent potential therapeutics for VHL-deficient CC-RCC.

64 of TNFalpha associated with VHL loss forced VHL-deficient cells to rely on intact RIPK1 to inhibit a

65 African American patients have less frequent VHL inactivation, are enriched in the ccB molecular subt

66 Five patients with VHL died (3 from VHL-related tumors including 1 from PNET), whereas only

67 n slowing progression of ocular disease from VHL-associated RCH.

68 nalyzed the vascular elements in tumors from VHL patients.

69 6-0 renal carcinoma cells lacking functional VHL, with concomitant high S1P levels that appear to be

70 ough the loss of the Von Hippel-Lindau gene (VHL).

71 the von Hippel-Lindau tumor suppressor gene (VHL) predisposes renal epithelial cells to loss of the p

72 he von Hippel-Lindau tumour suppressor gene (VHL).

73 aused by a loss or mutation in a single gene,VHL, but it exhibits a wide phenotypic variability that

74 40% of CNS hemangioblastoma harbor germline VHL mutations without a family history or additional fea

75 ntly less likely than white patients to have VHL mutations (2 of 12 [17%] vs 175 of 351 [50%], respec

76 l-Lindau (VHL)-associated hemangioblastomas (VHL-HB) arise in the central nervous system (CNS), and a

77 most common VHL point mutation in hereditary VHL disease.

78 revealed detailed information describing how VHL-R167Q contributes to tumorigenesis and identified a

79 Our results illustrate how VHL and PBRM1 co-operate to drive renal transformation a

80 rylation of Thr27 of ID2 by DYRK1 blocks ID2-VHL interaction and preserves HIF2alpha ubiquitylation.

81 Together, these data identify VHL as an E3 ligase with important cellular functions un

82 all-molecule targeting of HIF2alpha improves VHL-related phenotypes in a vertebrate animal model and

83 In VHL-positive cancer cells, enhanced expression of miR-28

84 tologic expression of SSTR1, 2a, 4, and 5 in VHL-HBs.

85 tin analogue octreotide induces apoptosis in VHL-HB stromal cells in a dose-dependent fashion by BAX

86 markedly enhanced induction of apoptosis in VHL-null 786-O cells but not in VHL wild-type Caki-2 cel

87 The risk of ccRCC in VHL disease is linked to the degree of destabilization r

88 he complex genotype-phenotype correlation in VHL disease.

89 eutic approaches targeting VHL deficiency in VHL diseases.

90 findings reveal that cystine deprivation in VHL-deficient RCCs presents an attractive therapeutic op

91 ternate mechanism for AURKA dysregulation in VHL-null cells.

92 d somatostatin receptor (SSTR) expression in VHL-HBs, offering an alternative therapeutic strategy.

93 lpha) mediates increased AURKA expression in VHL-null cells.

94 icant increase in primary cilia formation in VHL-deficient cells.

95 ts suggest that higher SK1 and S1P levels in VHL-defective ccRCC could induce invasion in an autocrin

96 leading cause of morbidity and mortality in VHL disease.

97 pathways that drive cancer, but mutations in VHL are restricted to limited subsets of malignancies.

98 We also show that analysis of mutations in VHL using our workflow provides valuable insights into t

99 ation triggered rapid programmed necrosis in VHL-deficient cell lines and primary ccRCC tumor cells,

100 apoptosis in VHL-null 786-O cells but not in VHL wild-type Caki-2 cells.

101 and increased ROS in VHL-/- cells but not in VHL+/+ cells, which utilized glucose oxidation for gluta

102 es and primary ccRCC tumor cells, but not in VHL-restored counterparts.

103 attern of disease manifestations observed in VHL syndrome is perfectly correlated with a gradient of

104 d EGFR, whereas frameshifts are prevalent in VHL, GATA3, TP53, ARID1A, PTEN and ATRX.

105 rs depleted pyrimidines and increased ROS in VHL-/- cells but not in VHL+/+ cells, which utilized glu

106 n is driven by beta-catenin transcription in VHL-null cells.

107 ive HIF-2 activity restores tumorigenesis in VHL-reconstituted ccRCC cells.

108 determine the origin of tumor vasculature in VHL-associated hemangioblastomas, we analyzed the vascul

109 ment of cellular ascorbate levels, increased VHL binding, and decreased HIF-1alpha stability.

110 4 cells and RCC4VHL cells with re-introduced VHL.

111 Von Hippel-Landau (VHL) protein is a potent tumor suppressor regulating num

112 Here, we report that the E3 ubiquitin ligase VHL is essential for Treg cell function.

113 Von Hippel Lindau (VHL) is a tumour suppressor that is lost in the majority

114 Loss of von Hippel Lindau (VHL) protein function is a key driver of VHL diseases, i

115 s of the tumor suppressor von Hippel Lindau (VHL).

116 ociated with mutations in von Hippel-Lindau (VHL) and subsequent normoxic stabilization of hypoxia-in

117 the tumor-suppressor gene von Hippel-Lindau (VHL) are associated with a complex spectrum of condition

118 the tumor suppressor gene von Hippel-Lindau (VHL) are major causes of clear-cell renal cell carcinoma

119 the tumor suppressor gene von Hippel-Lindau (VHL) can lead to benign and malignant tumors, including

120 th a germline mutation in von Hippel-Lindau (VHL) develop renal cell cancers and hypervascular tumors

121 von Hippel-Lindau (VHL) disease is a rare familial cancer predisposition sy

122 mas (RCH) associated with von Hippel-Lindau (VHL) disease treated with systemic sunitinib malate, an

123 ances of a ligand for the von Hippel-Lindau (VHL) E3 ligase.

124 ntragenic mutation in the von Hippel-Lindau (VHL) gene and loss of 3p (where VHL is located).

125 y display inactivation of von Hippel-Lindau (VHL) gene leading to increased level of hypoxia-inducibl

126 von Hippel-Lindau (VHL) gene mutations are associated with clear cell renal

127 he functional loss of the von Hippel-Lindau (VHL) gene occurs in 90% of CC-RCC, driving cancer progre

128 egulated tumor-suppressor von Hippel-Lindau (VHL) is an E3 ligase that recognizes its substrates as p

129 ctors (HIFs) secondary to von Hippel-Lindau (VHL) mutations that occur in over 90% of ccRCC tumours.

130 von Hippel-Lindau (VHL) patients develop multiple central nervous system he

131 von Hippel-Lindau (VHL) protein is known to destabilize myogenin via the ub

132 eting cereblon (CRBN) and Von Hippel-Lindau (VHL) proteins.

133 ease independent of their von Hippel-Lindau (VHL) status.

134 mTORC1 in the absence of von Hippel-Lindau (VHL) tumor suppressor expression.

135 The von Hippel-Lindau (VHL) tumor suppressor gene is inactivated in the majorit

136 The von Hippel-Lindau (VHL) tumor suppressor gene is mutated as an early event

137 ), cells deficient in the von Hippel-Lindau (VHL) tumor suppressor gene use glutamine to generate cit

138 The von Hippel-Lindau (VHL) tumor suppressor protein pVHL is commonly mutated i

139 genesis through targeting von Hippel-Lindau (VHL) tumour suppressor in breast cancer.

140 Von Hippel-Lindau (VHL)-associated hemangioblastomas (VHL-HB) arise in the

141 regulated by hypoxia in a von Hippel-Lindau (VHL)-dependent manner both in RCC cell culture and clini

142 Von Hippel-Lindau (VHL)-null 786-O, RCC4 and A498 Renal Cell Carcinoma (RCC

143 succinate dehydrogenase); von Hippel-Lindau (VHL; n = 2); RET (n = 12); neurofibromin 1 (NF1; n = 2);

144 effect against Y-27632 treatment, mimicking VHL reintroduction.

145 ico approaches and identified other missense VHL mutants in addition to VHL-R167Q that might be rescu

146 Moreover, VHL-deficient cells that expressed activating mTOR mutan

147 is of VHL, especially missense point-mutated VHL, is a promising approach to augmenting VHL levels an

148 Multiple somatic mutations (VHL, PBRM1, SETD2, KDM5C, TP53, BAP1, PTEN, MTOR) were a

149 tools to probe the VHL-HIF pathways and new VHL ligands for next-generation PROTACs.

150 ing the use of systemic sunitinib for ocular VHL lesions during a period of 9 months.

151 tively reduced the colony-forming ability of VHL-deficient CC-RCC, thus mimicking the effect of Y-276

152 has been studied extensively, the ability of VHL-R167Q to downregulate hypoxia-inducible factor 2alph

153 Codeletion of VHL together with HIF2A but not with HIF1A led to appare

154 Deficiency of VHL in limb bud mesenchyme does not alter the timely dif

155 and proteasome-dependent self-degradation of VHL in different cell lines, in a highly isoform-selecti

156 CH1 in mice with tubule-specific deletion of VHL led to dysplastic hyperproliferation of tubular epit

157 Development of VHL-deficient renal cell carcinoma (RCC) relies upon act

158 individuals who have a clinical diagnosis of VHL, making it the standard of care for diagnosis of VHL

159 be aware of when to consider a diagnosis of VHL, when to refer a patient to a genetics specialist fo

160 ing it the standard of care for diagnosis of VHL.

161 s required for binding to the beta domain of VHL and polyubiquitylation via ECV, leading to increased

162 au (VHL) protein function is a key driver of VHL diseases, including sporadic and inherited clear cel

163 pubescin as a novel agent for elimination of VHL-null RCC cells via apoptosis is warranted for furthe

164 nt to explain the observed distinct fates of VHL-deficient and restored cells.

165 t a family history or additional features of VHL disease.

166 he-art information regarding the genetics of VHL and will serve as a key reference for nongenetics pr

167 e is perfectly correlated with a gradient of VHL protein (pVHL) dysfunction in hypoxia signaling path

168 th GLS1 inhibitors to suppress the growth of VHL-/- cells in vitro and in vivo.

169 ase checkpoint, and suppressed the growth of VHL-/- RCC cells.

170 el of VHL, we report a marked improvement of VHL-associated phenotypes following treatment with HIF2a

171 nesis, which could be rescued by increase of VHL-R167Q levels.

172 ression in renal cancer cells independent of VHL status.

173 Here, we show that loss of VHL alone results in DNA replication stress and damage a

174 key organelle in ccRCC is caused by loss of VHL and associated with increased Aurora kinase A (AURKA

175 ession of ARC in RCC can explain how loss of VHL can promote survival early in tumor formation.

176 Our findings indicate that loss of VHL could be driving tumour cell dissemination through s

177 The majority of VHL mutations are private, but there are also well-chara

178 Here, using an animal model of VHL, we report a marked improvement of VHL-associated ph

179 Mutation of VHL results in HIF up-regulation and contributes to proc

180 in multicystic clear cell RCC, mutations of VHL (P = .016) and PBRM1 (P = .017) were significantly m

181 wed that a CRISPR/Cas9-mediated knock out of VHL in the RENCA model leads to morphologic and molecula

182 tively inhibited the down stream products of VHL, SETD2, and PTEN in ccRCC cells with VHL and SETD2 m

183 Modulation of the proteostasis of VHL, especially missense point-mutated VHL, is a promisi

184 ered similar metabolic changes regardless of VHL status, suggesting that metabolic responses alone ar

185 , many details underlying the regulations of VHL proteostasis are unknown.

186 Restoration of VHL in RCC4 cells attenuated the growth inhibitory effec

187 However, the role of VHL loss of function in the development of ccRCC via inf

188 and group-based optimization of a series of VHL inhibitors with low nanomolar potencies and improved

189 formation of primary cilia in the setting of VHL deficiency, opening new avenues for treatment with b

190 However, how these multiple species of VHL are generated and whether the process regulates VHL

191 ona fidehydroxylation-dependent substrate of VHL that potentially influences oxygen homeostasis and c

192 e factor alpha, a well established target of VHL E3 ubiquitin ligase, ECV (Elongins/Cul2/VHL).

193 ied and validated for selective targeting of VHL-deficient CC-RCC in multiple genetic backgrounds by

194 About one third of VHL mutations are missense point mutations, with R167Q b

195 Furthermore, the long-form variant of VHL was often detected as multiple bands by western blot

196 Tumor-associated variants of VHL differentiate between these two functions, as a path

197 mpounds (LOPAC), was screened in parallel on VHL-deficient RCC4 cells and RCC4VHL cells with re-intro

198 Our experience and previous reports on VHL-HB avidity to somatostatin analogues suggested somat

199 eration, including cancers harboring IDH1 or VHL mutations, suggesting multiple mechanisms for pathwa

200 tential targeted therapy for ccRCC and other VHL-related disease in patients carrying VHL-R167Q or si

201 hat it is also the progenitor cell for other VHL-associated tumors.

202 -regulated genes that are upregulated in our VHL knockout cells and whose overexpression signifies an

203 between these two functions, as a pathogenic VHL mutant that retains intrinsic ability to ubiquitinat

204 se effects did not involve the classical PHD/VHL pathway for HIF upregulation, but instead involved t

205 edictions for risk of ccRCC for all possible VHL missense mutations and present these predictions, in

206 Here we disclose VH298, a potent VHL inhibitor that stabilizes HIF-alpha and elicits a hy

207 4.1R may influence myogenesis by preventing VHL-mediated myogenin degradation.

208 nificantly increased in cultured and primary VHL loss-of-function kidney cells.

209 f HIFalpha to the von Hippel-Lindau protein (VHL)-elongin B/C complex, thus signalling for proteosoma

210 are mutations in genes including TP53, PTEN, VHL, EGFR, and FBXW7 and 99 medium-recurrence mutations

211 protein cleavage, and the cleavage regulates VHL proteostasis and subsequent function.

212 generated and whether the process regulates VHL proteostasis and function are unknown.

213 r study reveals a novel mechanism regulating VHL proteostasis and function, which is significant for

214 t to define an upstream mechanism regulating VHL suppression in cancer and describe the role of Daam2

215 ng elevation in TNFalpha expression rendered VHL-deficient cells susceptible to necrosis triggered by

216 ctor PBRM1 (mutated in 40% of ccRCC) rescues VHL-induced replication stress, maintaining cellular fit

217 Compare the long-term outcome of resected VHL-PNET and sporadic PNET.

218 The long-term outcome of resected VHL-PNET is better than that of sporadic PNET.

219 Mice with Foxp3-restricted VHL deletion displayed massive inflammation associated w

220 higher than for hereditary cluster 1 (SDHx, VHL) PPGLs (P = 0.011 and 0.006, respectively).

221 bevacizumab PET might offer a tool to select VHL patients for anti-VEGF therapy.

222 t transcription and tumor growth in selected VHL-deficient clear-cell renal cell carcinoma (ccRCC) mo

223 offers a novel chemical probe for selective VHL knockdown, and demonstrates the potential for a new

224 Unexpectedly, some VHL-mutant ccRCCs were resistant to PT2399.

225 However, kidney-specific VHL deletion in mice fails to elicit ccRCC-specific meta

226 In addition, several type-specific VHL disease-causing mutants, including those that have r

227 in some individuals with seemingly sporadic VHL-related tumor types, as </= 10% of pheochromocytoma

228 rthermore, inhibition of cleavage stabilized VHL protein and thereby promoted HIF downregulation.

229 Daam2 promotes tumorigenesis by suppressing VHL expression.

230 redictions obtained for the tumor suppressor VHL.

231 ed typically by loss of the tumor-suppressor VHL, driving constitutive activation of hypoxia-inducibl

232 loss of von Hippel-Lindau tumor suppressor (VHL) and a potential activation of signal transducer and

233 n of the von Hippel-Lindau tumor suppressor (VHL) protein in the forkhead box FOXD1 cell lineage, fro

234 ncluding von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD

235 of the von Hippel-Lindau tumour suppressor (VHL) and unrestrained activation of hypoxia-inducible tr

236 the most effective way to manage symptomatic VHL-HBs.

237 KI 1447 and GSK 429286, selectively targeted VHL-deficient CC-RCC.

238 eloping new therapeutic approaches targeting VHL deficiency in VHL diseases.

239 ment of therapeutic strategies for targeting VHL-deficient RCC.

240 apoptosis and growth inhibitory effect than VHL wild-type Caki-2 and ACHN RCC cell lines.

241 We conclude that VHL-HBs harbor multiple SSTR subtypes that offer actiona

242 Recent work has demonstrated that VHL knock down induces an epithelial-mesenchymal transit

243 Here we report that VHL has an equally important function distinct from its

244 We report that VHL-deficient and VHL-positive renal cancer cells posses

245 d pharmacological approaches and showed that VHL was first cleaved at the N-terminus by chymotrypsin

246 Here we have shown that VHL-/- RCC cells rely on RC-derived aspartate to maintai

247 The VHL gene product, pVHL, is the substrate recognition uni

248 (interquartile range, 58-131 months) in the VHL and control groups, respectively.

249 Median Ki-67 index was 3% and 4% in the VHL and sporadic groups (P = 0.95), respectively, and ly

250 urvival could not have been estimated in the VHL group due to the low number of events (hazard ratio,

251 Alterations in the VHL tumor suppressor stabilizing the hypoxia-inducible f

252 f hypoxia-inducible factor (HIF) beta in the VHL-deficient CC-RCC had a protective effect against Y-2

253 ppress hypoxic cell cycle progression in the VHL-mutant RCC cells while derepress it in the VHL-resto

254 L-mutant RCC cells while derepress it in the VHL-restored RCC cells.

255 ppressor genes have been identified near the VHL gene, within a region that is frequently deleted in

256 Inactivation of the VHL (Von Hippel Lindau) tumour suppressor has long been

257 is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1alpha for degradation.

258 tein is the substrate binding subunit of the VHL E3 ubiquitin ligase, which targets hydroxylated alph

259 haracterized by frequent inactivation of the VHL gene (infrequently mutated in other tumor types), re

260 Since the discovery of the VHL gene in 1993, more than 900 families with VHL have b

261 In ccRCC the biallelic inactivation of the VHL gene leads to stabilization of hypoxia-inducible fac

262 are initiated by somatic inactivation of the VHL tumor suppressor gene.

263 -dependent and -independent functions of the VHL tumor suppressor protein (pVHL) can contribute to tu

264 the oncogenic transcriptional output of the VHL-HIF axis and provide a functional explanation for th

265 The elucidation of the VHL-HIF-1alpha (hypoxia inducible factor-1alpha)-VEGF (v

266 erent mechanism, that is the blockade of the VHL:HIF-alpha protein-protein interaction downstream of

267 ivating the development of inhibitors of the VHL:HIF-alpha protein-protein interaction.

268 udy provides new chemical tools to probe the VHL-HIF pathways and new VHL ligands for next-generation

269 MiR-155 directly targets the VHL tumor suppressor and, by doing so, promotes the acti

270 ID2 binds to the VHL ubiquitin ligase complex, displaces VHL-associated C

271 ed other missense VHL mutants in addition to VHL-R167Q that might be rescued by similar strategies.

272 ing different polyethylene glycol linkers to VHL ligand VH032.

273 ceptibility genes (including 2 each in TP53, VHL, and BRCA1), 1 recessive liver disorder with hepatoc

274 er exploration of this strategy for treating VHL disease.

275 ntly in ccRCC and VHL mutations are truncal, VHL inactivation is regarded as the governing event.

276 ith considerably less avidity than wild-type VHL does but retains residual capacity to generate a VHL

277 Surgically unresectable VHL-HBs or those in frail patients are challenging probl

278 IF-1alpha failed to undergo EMT changes upon VHL knockout.

279 ppel-Lindau (VHL) gene and loss of 3p (where VHL is located).

280 observed in clear cell kidney cancer, where VHL loss and HIF activation is pathognomonic.

281 We aimed to assess whether VHL manifestations can be visualized with (89)Zr-bevaciz

282 However, the underlying mechanism by which VHL loss increases AURKA levels has not been clearly elu

283 increased levels of TNFalpha associated with VHL loss forced VHL-deficient cells to rely on intact RI

284 an predict the risk of ccRCC associated with VHL missense mutations with high sensitivity and specifi

285 lyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation.

286 We show that 4.1R associates with VHL and, when overexpressed, reverses myogenin ubiquitin

287 hibitor with high selectivity for ccRCC with VHL and SETD2 mutations.

288 mpounds with high selectivity for ccRCC with VHL and/or SETD2 mutations.

289 of VHL, SETD2, and PTEN in ccRCC cells with VHL and SETD2 mutations.

290 ility and tumourigenesis of ccRCC cells with VHL and SETD2 mutations.

291 HL gene in 1993, more than 900 families with VHL have been identified and examined.

292 F/+) mice resembled kidneys from humans with VHL syndrome, containing multiple lesions spanning from

293 compounds that are synthetically lethal with VHL deficiency in CC-RCC.

294 Data of all patients with VHL (n = 23) operated on for nonmetastatic PNET were rev

295 Five patients with VHL died (3 from VHL-related tumors including 1 from PNE

296 Sixteen (70%) patients with VHL had multiple PNET; lesions less than 15 mm were left

297 c characteristics, except that patients with VHL were younger (36 vs 56 years, P < 0.0001).

298 strategy seems appropriate in patients with VHL-PNET, who may develop more life-threatening tumors o

299 cs professionals who encounter patients with VHL.

300 ages with high affinity and specificity with VHL as its only major cellular target, leading to select

301 renal cancer cells (ccRCC), with or without VHL, upon the deprivation of individual amino acids.