Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects
Venous malformations (VMs) are composed of ectatic veins with scarce smooth muscle cell coverage. Activating mutations in the endothelial cell tyrosine kinase receptor TIE2 are a common cause of these lesions. VMs cause deformity, pain, and local intravascular coagulopathy, and they expand with time...
Uloženo v:
| Vydáno v: | The Journal of clinical investigation Ročník 125; číslo 9; s. 3491 - 3504 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
American Society for Clinical Investigation
01.09.2015
|
| Témata: | |
| ISSN: | 0021-9738, 1558-8238 |
| On-line přístup: | Získat plný text |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | Venous malformations (VMs) are composed of ectatic veins with scarce smooth muscle cell coverage. Activating mutations in the endothelial cell tyrosine kinase receptor TIE2 are a common cause of these lesions. VMs cause deformity, pain, and local intravascular coagulopathy, and they expand with time. Targeted pharmacological therapies are not available for this condition. Here, we generated a model of VMs by injecting HUVECs expressing the most frequent VM-causing TIE2 mutation, TIE2-L914F, into immune-deficient mice. TIE2-L914F-expressing HUVECs formed VMs with ectatic blood-filled channels that enlarged over time. We tested both rapamycin and a TIE2 tyrosine kinase inhibitor (TIE2-TKI) for their effects on murine VM expansion and for their ability to inhibit mutant TIE2 signaling. Rapamycin prevented VM growth, while TIE2-TKI had no effect. In cultured TIE2-L914F-expressing HUVECs, rapamycin effectively reduced mutant TIE2-induced AKT signaling and, though TIE2-TKI did target the WT receptor, it only weakly suppressed mutant-induced AKT signaling. In a prospective clinical pilot study, we analyzed the effects of rapamycin in 6 patients with difficult-to-treat venous anomalies. Rapamycin reduced pain, bleeding, lesion size, functional and esthetic impairment, and intravascular coagulopathy. This study provides a VM model that allows evaluation of potential therapeutic strategies and demonstrates that rapamycin provides clinical improvement in patients with venous malformation. |
|---|---|
| AbstractList | Venous malformations (VMs) are composed of ectatic veins with scarce smooth muscle cell coverage. Activating mutations in the endothelial cell tyrosine kinase receptor TIE2 are a common cause of these lesions. VMs cause deformity, pain, and local intravascular coagulopathy, and they expand with time. Targeted pharmacological therapies are not available for this condition. Here, we generated a model of VMs by injecting HUVECs expressing the most frequent VM-causing TIE2 mutation, TIE2-L914F, into immune-deficient mice. TIE2-L914F-expressing HUVECs formed VMs with ectatic blood-filled channels that enlarged over time. We tested both rapamycin and a TIE2 tyrosine kinase inhibitor (TIE2-TKI) for their effects on murine VM expansion and for their ability to inhibit mutant TIE2 signaling. Rapamycin prevented VM growth, while TIE2-TKI had no effect. In cultured TIE2-L914F-expressing HUVECs, rapamycin effectively reduced mutant TIE2-induced AKT signaling and, though TIE2-TKI did target the WT receptor, it only weakly suppressed mutant-induced AKT signaling. In a prospective clinical pilot study, we analyzed the effects of rapamycin in 6 patients with difficult-to-treat venous anomalies. Rapamycin reduced pain, bleeding, lesion size, functional and esthetic impairment, and intravascular coagulopathy. This study provides a VM model that allows evaluation of potential therapeutic strategies and demonstrates that rapamycin provides clinical improvement in patients with venous malformation. |
| Audience | Academic |
| Author | Hammer, Jennifer Legrand, Catherine Boon, Laurence M. Uebelhoer, Melanie Seront, Emmanuel Boscolo, Elisa Vikkula, Miikka Bischoff, Joyce Limaye, Nisha Kang, Kyu-Tae Huang, Lan Dupont, Sophie Mendola, Antonella Eklund, Lauri Soblet, Julie Natynki, Marjut Brugnara, Carlo |
| AuthorAffiliation | 2 Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium 5 Center for Vascular Anomalies, Division of Plastic Surgery, Cliniques Universitaires Saint Luc, Université catholique de Louvain, Brussels, Belgium 6 Institute of Statistics, Biostatistics, and Actuarial Sciences, Université catholique de Louvain, Louvain-la-Neuve, Belgium 4 Centre du Cancer, Department of Pediatric Oncology, and 3 Oulu Center for Cell-Matrix Research, Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland 1 Vascular Biology Program and Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA 7 Department of Laboratory Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA |
| AuthorAffiliation_xml | – name: 4 Centre du Cancer, Department of Pediatric Oncology, and – name: 7 Department of Laboratory Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA – name: 2 Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium – name: 6 Institute of Statistics, Biostatistics, and Actuarial Sciences, Université catholique de Louvain, Louvain-la-Neuve, Belgium – name: 5 Center for Vascular Anomalies, Division of Plastic Surgery, Cliniques Universitaires Saint Luc, Université catholique de Louvain, Brussels, Belgium – name: 1 Vascular Biology Program and Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA – name: 3 Oulu Center for Cell-Matrix Research, Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland |
| Author_xml | – sequence: 1 givenname: Elisa surname: Boscolo fullname: Boscolo, Elisa – sequence: 2 givenname: Nisha surname: Limaye fullname: Limaye, Nisha – sequence: 3 givenname: Lan surname: Huang fullname: Huang, Lan – sequence: 4 givenname: Kyu-Tae surname: Kang fullname: Kang, Kyu-Tae – sequence: 5 givenname: Julie surname: Soblet fullname: Soblet, Julie – sequence: 6 givenname: Melanie surname: Uebelhoer fullname: Uebelhoer, Melanie – sequence: 7 givenname: Antonella surname: Mendola fullname: Mendola, Antonella – sequence: 8 givenname: Marjut surname: Natynki fullname: Natynki, Marjut – sequence: 9 givenname: Emmanuel surname: Seront fullname: Seront, Emmanuel – sequence: 10 givenname: Sophie surname: Dupont fullname: Dupont, Sophie – sequence: 11 givenname: Jennifer surname: Hammer fullname: Hammer, Jennifer – sequence: 12 givenname: Catherine surname: Legrand fullname: Legrand, Catherine – sequence: 13 givenname: Carlo surname: Brugnara fullname: Brugnara, Carlo – sequence: 14 givenname: Lauri surname: Eklund fullname: Eklund, Lauri – sequence: 15 givenname: Miikka surname: Vikkula fullname: Vikkula, Miikka – sequence: 16 givenname: Joyce surname: Bischoff fullname: Bischoff, Joyce – sequence: 17 givenname: Laurence M. surname: Boon fullname: Boon, Laurence M. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26258417$$D View this record in MEDLINE/PubMed |
| BookMark | eNqNk11rFDEUhoNU7LYK_gIZEEQvpiaZmSRzI5Sl6kqhUGtvQzYfu1kmyTrJLPbfm9Vuu6N7UUISSJ7zknPekxNw5IPXALxG8Awhij9-m84ogbB-BiaoaVjJcMWOwARCjMqWVuwYnMS4ghDVdVO_AMeY4IbViE7A7bVYC3cnrS-sW_dho2NxM7vApRuSSFoVG-3DEAsnOhN6J5INmfSFG3rrdeGC0l0hvCqWgxO-iMN8pWWKL8FzI7qoX93vp-DH54ub6dfy8urLbHp-WUpS0VQaCBmljCFCKlFhpBir5q2stGK1ZLQxtFXKKAKJIYYZqlCNqcZYkAZLlMFT8Omv7nqYO62k9qkXHV_31on-jgdh-fjG2yVfhA2vG5aLRLPA-3uBPvwcdEzc2Sh11wmvc948Vxfn2TTtE1DYVi2pCMro23_QVRh6nyuRKYRIXuAetRCd5tabkJ8ot6L8vMYMZeNYnanyALXQXud8chsYm49H_NkBPg-lnZUHAz6MAjKT9K-0EEOMfPb9-uns1e2YfbfHLrXo0jKGbti2UByDb_ZNfHBv16WPKck-xNhrw6VNf1oxp2Y7jiDffgO--waPVj0E7DT_Q38DMGoBJw |
| CitedBy_id | crossref_primary_10_1126_scitranslmed_aad9982 crossref_primary_10_1172_JCI84923 crossref_primary_10_23736_S0392_9590_19_04154_3 crossref_primary_10_1016_j_otc_2017_09_006 crossref_primary_10_1097_PRS_0000000000007909 crossref_primary_10_1016_j_lpm_2025_104297 crossref_primary_10_1111_cge_14636 crossref_primary_10_3389_fsurg_2020_610758 crossref_primary_10_1177_02683555251361663 crossref_primary_10_3389_fmed_2023_1155476 crossref_primary_10_1016_j_lpm_2019_03_010 crossref_primary_10_23736_S0021_9509_21_11911_1 crossref_primary_10_1016_j_arcped_2017_04_001 crossref_primary_10_1016_j_diii_2024_07_004 crossref_primary_10_1016_j_pediatrneurol_2015_11_009 crossref_primary_10_1111_jop_13318 crossref_primary_10_1016_j_coms_2023_09_013 crossref_primary_10_1097_GOX_0000000000003391 crossref_primary_10_1002_path_4802 crossref_primary_10_1016_j_jvsv_2024_101997 crossref_primary_10_1172_JCI84871 crossref_primary_10_1177_17085381241241853 crossref_primary_10_1186_s13023_021_01898_y crossref_primary_10_1016_j_radcr_2025_03_016 crossref_primary_10_1016_j_anplas_2016_06_015 crossref_primary_10_1007_s40257_020_00528_w crossref_primary_10_1136_jmedgenet_2021_108179 crossref_primary_10_1016_j_humpath_2024_02_004 crossref_primary_10_1016_j_jpedsurg_2023_03_002 crossref_primary_10_1016_j_banm_2024_12_016 crossref_primary_10_3892_etm_2018_6782 crossref_primary_10_1161_ATVBAHA_118_310921 crossref_primary_10_12688_f1000research_16160_1 crossref_primary_10_1016_j_ajhg_2024_05_020 crossref_primary_10_1007_s10456_024_09925_9 crossref_primary_10_1016_j_ajhg_2019_09_002 crossref_primary_10_3389_fneur_2023_1099328 crossref_primary_10_1038_s44161_022_00081_1 crossref_primary_10_1016_j_phrs_2022_106331 crossref_primary_10_1097_JOVA_0000000000000092 crossref_primary_10_1097_MD_0000000000022596 crossref_primary_10_1161_CIRCRESAHA_119_316500 crossref_primary_10_1002_mgg3_1931 crossref_primary_10_3389_fmed_2017_00162 crossref_primary_10_1016_j_jvsv_2017_05_001 crossref_primary_10_1093_bjd_ljae492 crossref_primary_10_1186_s13023_021_01929_8 crossref_primary_10_1186_s42155_018_0028_y crossref_primary_10_1002_pbc_27896 crossref_primary_10_1016_S1761_2896_24_50025_5 crossref_primary_10_1016_j_jid_2016_07_034 crossref_primary_10_1161_ATVBAHA_118_312315 crossref_primary_10_1161_ATVBAHA_121_316651 crossref_primary_10_1111_bcpt_13027 crossref_primary_10_1055_s_0042_1757940 crossref_primary_10_1177_2050313X221097755 crossref_primary_10_1016_j_anpede_2024_09_009 crossref_primary_10_1111_1346_8138_15297 crossref_primary_10_1002_gcc_22739 crossref_primary_10_1016_j_jaad_2017_03_045 crossref_primary_10_1097_MOH_0000000000000498 crossref_primary_10_3389_fped_2022_734286 crossref_primary_10_1001_jamadermatol_2021_3459 crossref_primary_10_1249_JSR_0000000000000989 crossref_primary_10_1016_j_yjmcc_2020_07_010 crossref_primary_10_1111_jop_13324 crossref_primary_10_1016_j_jvsv_2017_05_016 crossref_primary_10_1111_jpc_13461 crossref_primary_10_1007_s10456_018_9595_8 crossref_primary_10_1177_0268355520972918 crossref_primary_10_1111_dth_15074 crossref_primary_10_1055_s_0040_1716727 crossref_primary_10_1111_ped_70002 crossref_primary_10_1016_j_jid_2019_10_001 crossref_primary_10_1093_hmg_ddac169 crossref_primary_10_1097_JOVA_0000000000000072 crossref_primary_10_1111_pde_13260 crossref_primary_10_1111_ajd_13856 crossref_primary_10_1002_pbc_30915 crossref_primary_10_1053_j_ro_2019_06_004 crossref_primary_10_1016_j_rpth_2024_102400 crossref_primary_10_1016_j_anpedi_2024_07_009 crossref_primary_10_1007_s40746_018_0130_3 crossref_primary_10_1007_s10456_018_9624_7 crossref_primary_10_1016_j_thromres_2018_06_013 crossref_primary_10_1097_JOVA_0000000000000103 crossref_primary_10_1038_s41467_020_16496_y crossref_primary_10_1097_SCS_0000000000007310 crossref_primary_10_1007_s00112_020_01096_3 crossref_primary_10_1542_peds_2019_0319 crossref_primary_10_1016_j_ejmg_2022_104637 crossref_primary_10_1161_ATVBAHA_121_316798 crossref_primary_10_1038_s41598_019_48854_2 crossref_primary_10_1097_JOVA_0000000000000069 crossref_primary_10_1007_s10143_022_01883_4 crossref_primary_10_1016_j_anndiagpath_2019_151434 crossref_primary_10_1016_j_sempedsurg_2020_150976 crossref_primary_10_1007_s00381_022_05608_2 crossref_primary_10_1016_j_biopha_2024_117740 crossref_primary_10_1111_dth_14238 crossref_primary_10_7554_eLife_21032 crossref_primary_10_7554_eLife_82543 crossref_primary_10_1038_nrd_2016_278 crossref_primary_10_1038_s44161_025_00655_9 crossref_primary_10_1007_s10456_018_9613_x crossref_primary_10_1146_annurev_genom_121222_114518 crossref_primary_10_1186_s41065_025_00486_5 crossref_primary_10_1007_s00247_023_05670_1 crossref_primary_10_3389_fcell_2023_1178045 crossref_primary_10_1002_pbc_28277 crossref_primary_10_1016_j_ajhg_2015_11_011 crossref_primary_10_1016_j_jtha_2024_07_013 crossref_primary_10_1016_j_jvs_2018_12_033 crossref_primary_10_1161_CIRCRESAHA_124_323181 crossref_primary_10_1172_JCI172842 crossref_primary_10_1038_s41467_020_20774_0 crossref_primary_10_1161_CIRCRESAHA_121_318145 crossref_primary_10_1007_s00441_022_03672_3 crossref_primary_10_1016_j_sempedsurg_2020_150967 crossref_primary_10_1186_s12964_020_00606_w crossref_primary_10_1016_j_bulcan_2018_01_016 crossref_primary_10_1161_CIRCRESAHA_121_318142 crossref_primary_10_1177_0268355519885216 crossref_primary_10_1016_j_jvsv_2021_03_001 crossref_primary_10_1177_1591019920943752 crossref_primary_10_1016_j_clindermatol_2022_02_006 crossref_primary_10_1002_pbc_31032 crossref_primary_10_1007_s12325_021_01758_y crossref_primary_10_1111_jpc_14345 crossref_primary_10_1038_s44321_025_00235_1 crossref_primary_10_1016_j_jvsv_2021_08_020 crossref_primary_10_1093_brain_awad104 crossref_primary_10_1016_j_ajpath_2023_08_017 crossref_primary_10_1089_lrb_2015_29044_fb crossref_primary_10_1016_j_stem_2024_10_015 crossref_primary_10_3389_fped_2021_697960 crossref_primary_10_1093_hmg_ddv349 crossref_primary_10_1016_j_heliyon_2024_e32690 crossref_primary_10_1186_s13023_018_0934_z crossref_primary_10_1016_j_hoc_2019_01_011 crossref_primary_10_3389_fcell_2025_1622961 crossref_primary_10_1007_s10456_021_09785_7 crossref_primary_10_1111_odi_14608 crossref_primary_10_1016_j_jid_2016_08_011 crossref_primary_10_1016_j_jid_2024_01_033 crossref_primary_10_1126_scitranslmed_aaf1164 crossref_primary_10_1371_journal_pone_0252342 crossref_primary_10_1016_j_otc_2017_09_003 crossref_primary_10_1038_s41467_025_58686_6 crossref_primary_10_1007_s00018_020_03664_y crossref_primary_10_1002_ame2_12343 |
| Cites_doi | 10.1097/00005650-199401000-00004 10.1001/archderm.140.8.971 10.1159/000348327 10.1161/01.RES.86.1.24 10.1038/ng.272 10.1038/nrm2639 10.1128/MCB.18.7.4131 10.1093/hmg/ddm211 :10.1007/s00431-015-2572 10.1258/phleb.2009.009041 10.1016/j.yexcr.2013.03.011 10.1002/pbc.23124 10.1007/s10456-012-9313-x 10.1016/S0092-8674(00)81814-0 10.1038/jid.2008.89 10.1101/cshperspect.a006460 10.1016/j.bjps.2007.12.062 10.1016/j.ccr.2005.08.002 10.1038/sj.onc.1202288 10.1542/peds.2010-3611 10.1097/00006534-200212000-00001 10.1016/j.cell.2012.03.017 10.1016/j.bmcl.2007.06.068 10.1101/gad.8.16.1897 10.1139/y77-007 10.1126/science.1715094 10.1172/JCI33493 10.1074/jbc.M203995200 10.1016/S1051-0443(07)61482-1 10.1016/S0092-8674(00)81812-7 10.1016/j.ccr.2006.07.003 10.1001/archderm.144.7.861 10.1172/JCI46322 10.1001/archdermatol.2009.296 10.1097/01.RVI.0000124949.24134.CF 10.1016/j.cell.2004.07.004 10.2214/ajr.177.6.1771359 10.1016/S0092-8674(00)81813-9 10.1073/pnas.90.20.9355 10.1007/s00109-004-0601-9 10.1016/S0969-2126(00)00516-5 10.1001/archderm.144.7.873 10.1016/j.molcel.2006.03.029 10.1038/ejhg.2009.193 10.1093/hmg/8.7.1279 10.1093/hmg/ddt198 |
| ContentType | Journal Article |
| Copyright | COPYRIGHT 2015 American Society for Clinical Investigation Copyright American Society for Clinical Investigation Sep 2015 Copyright © 2015, American Society for Clinical Investigation 2015 American Society for Clinical Investigation |
| Copyright_xml | – notice: COPYRIGHT 2015 American Society for Clinical Investigation – notice: Copyright American Society for Clinical Investigation Sep 2015 – notice: Copyright © 2015, American Society for Clinical Investigation 2015 American Society for Clinical Investigation |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM IOV ISR 3V. 7RV 7X7 7XB 88A 88E 8AO 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BEC BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ HCIFZ K9. KB0 LK8 M0S M1P M7P NAPCQ PHGZM PHGZT PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS S0X 7X8 7T5 H94 5PM |
| DOI | 10.1172/JCI76004 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Gale In Context: Opposing Viewpoints Science (Gale in Context) ProQuest Central (Corporate) Nursing & Allied Health Database Health & Medical Collection ProQuest Central (purchase pre-March 2016) Biology Database (Alumni Edition) Medical Database (Alumni Edition) ProQuest Pharma Collection ProQuest SciTech Collection ProQuest Natural Science Collection ProQuest Hospital Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central UK/Ireland ProQuest Central Essentials Biological Science Collection eLibrary ProQuest Central Natural Science Collection ProQuest One Community College ProQuest Central Korea Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Database (Alumni Edition) Biological Sciences ProQuest Health & Medical Collection PML(ProQuest Medical Library) Biological Science Database Nursing & Allied Health Premium ProQuest Central Premium ProQuest One Academic ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic (retired) ProQuest One Academic UKI Edition ProQuest Central China SIRS Editorial MEDLINE - Academic Immunology Abstracts AIDS and Cancer Research Abstracts PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) ProQuest Central Student ProQuest One Academic Middle East (New) ProQuest Central Essentials SIRS Editorial elibrary ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest One Health & Nursing ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Central China ProQuest Biology Journals (Alumni Edition) ProQuest Central ProQuest One Applied & Life Sciences ProQuest Health & Medical Research Collection Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Health & Medical Research Collection Biological Science Collection ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest Biological Science Collection ProQuest One Academic Eastern Edition ProQuest Nursing & Allied Health Source ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection ProQuest Hospital Collection (Alumni) Nursing & Allied Health Premium ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest Nursing & Allied Health Source (Alumni) ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic AIDS and Cancer Research Abstracts Immunology Abstracts |
| DatabaseTitleList | AIDS and Cancer Research Abstracts ProQuest Central Student MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7RV name: Nursing & Allied Health Database url: https://search.proquest.com/nahs sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1558-8238 |
| EndPage | 3504 |
| ExternalDocumentID | PMC4588237 3805971331 A428173884 26258417 10_1172_JCI76004 |
| Genre | Clinical Trial Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural Feature |
| GeographicLocations | Belgium |
| GeographicLocations_xml | – name: Belgium |
| GrantInformation_xml | – fundername: NIAMS NIH HHS grantid: P01 AR048564 – fundername: NHLBI NIH HHS grantid: R01 HL117952 |
| GroupedDBID | --- -~X .55 .XZ 08G 08P 29K 354 36B 5GY 5RE 5RS 7RV 7X7 88E 8AO 8F7 8FE 8FH 8FI 8FJ 8R4 8R5 AAWTL AAYXX ABOCM ABPMR ABUWG ACGFO ACIHN ACNCT ACPRK ADBBV ADPDF AEAQA AENEX AFCHL AFFHD AFKRA AHMBA ALMA_UNASSIGNED_HOLDINGS AOIJS ASPBG AVWKF AZFZN BAWUL BBNVY BCU BEC BENPR BHPHI BKEYQ BLC BPHCQ BVXVI CCPQU CITATION CS3 D-I DIK DU5 E3Z EBD EBS EJD EMB EMOBN EX3 F5P FRP FYUFA GROUPED_DOAJ GX1 HCIFZ HMCUK HYE IAO IEA IHR IHW INH IOF IOV IPO ISR ITC KQ8 L7B LK8 M1P M5~ M7P NAPCQ OBH OCB ODZKP OFXIZ OGEVE OHH OK1 OVD OVIDX OVT P2P P6G PHGZM PHGZT PJZUB PPXIY PQGLB PQQKQ PROAC PSQYO Q2X RPM S0X SJFOW SV3 TEORI TR2 TVE UKHRP VVN W2D WH7 WOQ WOW X7M XSB YFH YHG YKV YOC ZY1 ~H1 .GJ 2WC 3O- 53G AAKAS AAYOK ADZCM AFFNX AI. ALIPV BCR CGR CUY CVF ECM EIF FEDTE HVGLF H~9 J5H MVM N4W NPM OHT UHU VH1 ZGI ZXP 3V. 7XB 88A 8FK AZQEC DWQXO GNUQQ K9. PKEHL PQEST PQUKI PRINS 7X8 PUEGO 7T5 H94 5PM |
| ID | FETCH-LOGICAL-c637t-f00877881663a321d883b9c3ed84c875f79ddfd606f6f8f7d1427e22a652c19c3 |
| IEDL.DBID | 7RV |
| ISICitedReferencesCount | 173 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000362303600025&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0021-9738 |
| IngestDate | Tue Nov 04 01:49:48 EST 2025 Wed Oct 01 14:20:22 EDT 2025 Wed Oct 01 17:06:17 EDT 2025 Mon Oct 06 18:15:24 EDT 2025 Mon Nov 24 16:07:21 EST 2025 Mon Nov 24 15:53:42 EST 2025 Mon Nov 24 15:41:27 EST 2025 Wed Nov 26 09:20:03 EST 2025 Wed Nov 26 10:07:52 EST 2025 Thu May 22 21:22:41 EDT 2025 Thu Apr 03 07:07:00 EDT 2025 Tue Nov 18 21:27:28 EST 2025 Sat Nov 29 01:34:26 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 9 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c637t-f00877881663a321d883b9c3ed84c875f79ddfd606f6f8f7d1427e22a652c19c3 |
| Notes | SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-2 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Authorship note: Miikka Vikkula, Joyce Bischoff, and Laurence M. Boon contributed equally to this work. |
| OpenAccessLink | http://www.jci.org/articles/view/76004/files/pdf |
| PMID | 26258417 |
| PQID | 1711617101 |
| PQPubID | 42166 |
| PageCount | 14 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_4588237 proquest_miscellaneous_1722172559 proquest_miscellaneous_1709396361 proquest_journals_1711617101 gale_infotracmisc_A428173884 gale_infotracgeneralonefile_A428173884 gale_infotracacademiconefile_A428173884 gale_incontextgauss_ISR_A428173884 gale_incontextgauss_IOV_A428173884 gale_healthsolutions_A428173884 pubmed_primary_26258417 crossref_citationtrail_10_1172_JCI76004 crossref_primary_10_1172_JCI76004 |
| PublicationCentury | 2000 |
| PublicationDate | 2015-09-01 |
| PublicationDateYYYYMMDD | 2015-09-01 |
| PublicationDate_xml | – month: 09 year: 2015 text: 2015-09-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Ann Arbor |
| PublicationTitle | The Journal of clinical investigation |
| PublicationTitleAlternate | J Clin Invest |
| PublicationYear | 2015 |
| Publisher | American Society for Clinical Investigation |
| Publisher_xml | – name: American Society for Clinical Investigation |
| References | B20 B42 B21 B43 B22 B44 B24 B46 B25 Kontos (B37) 1998; 18 B47 Brouillard (B2) 2007; 16 Spec No. 2 B26 B48 B27 Dumont (B23) 1992; 7 B28 B29 Dompmartin (B6) 2009; 145 Boon (B1) 2004; 140 Yuksekkaya (B45) 2012; 129 Soblet (B15) 2013; 4 B30 B31 B10 B32 B33 B12 Mazoyer (B7) 2008; 144 B13 Greenberger (B34) 2011; 1 B35 B14 B36 Marrocco-Trischitta (B11) 2002; 28 B16 B38 B17 B39 B19 Augustin (B18) 2009; 10 B3 B4 Dompmartin (B5) 2008; 144 B8 B9 B40 B41 21445948 - Pediatr Blood Cancer. 2011 Dec 1;57(6):1018-24 12082108 - J Biol Chem. 2002 Aug 30;277(35):31768-73 19917952 - Arch Dermatol. 2009 Nov;145(11):1239-44 22229118 - Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006460 11860427 - Dermatol Surg. 2002 Feb;28(2):153-5 16904613 - Cancer Cell. 2006 Aug;10(2):159-70 23801934 - Mol Syndromol. 2013 Apr;4(4):179-83 843990 - Can J Physiol Pharmacol. 1977 Feb;55(1):48-51 8277801 - Med Care. 1994 Jan;32(1):40-66 23500414 - Exp Cell Res. 2013 May 15;319(9):1271-80 22392180 - Pediatrics. 2012 Apr;129(4):e1080-4 18571489 - J Plast Reconstr Aesthet Surg. 2009 May;62(5):684-9; discussion 689 10625301 - Circ Res. 2000 Jan 7-21;86(1):24-9 18645137 - Arch Dermatol. 2008 Jul;144(7):861-7 8980224 - Cell. 1996 Dec 27;87(7):1171-80 16603397 - Mol Cell. 2006 Apr 21;22(2):159-68 8980225 - Cell. 1996 Dec 27;87(7):1181-90 17670762 - Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R140-9 23086340 - Angiogenesis. 2013 Jan;16(1):207-22 9926914 - Oncogene. 1999 Jan 7;18(1):1-8 11080633 - Structure. 2000 Nov 15;8(11):1105-13 26040705 - Eur J Pediatr. 2015 Dec;174(12):1579-84 16169466 - Cancer Cell. 2005 Sep;8(3):211-26 11340138 - J Vasc Interv Radiol. 2001 May;12(5):595-600 1630810 - Oncogene. 1992 Aug;7(8):1471-80 7958865 - Genes Dev. 1994 Aug 15;8(16):1897-909 15126652 - J Vasc Interv Radiol. 2004 May;15(5):431-45 23633549 - Hum Mol Genet. 2013 Sep 1;22(17):3438-48 15526080 - J Mol Med (Berl). 2005 Jan;83(1):58-63 18401423 - J Invest Dermatol. 2008 Sep;128(9):2325-33 19888299 - Eur J Hum Genet. 2010 Apr;18(4):414-20 15313813 - Arch Dermatol. 2004 Aug;140(8):971-6 12447041 - Plast Reconstr Surg. 2002 Dec;110(7):1625-35 21606590 - J Clin Invest. 2011 Jun;121(6):2278-89 22500797 - Cell. 2012 Apr 13;149(2):274-93 11717083 - AJR Am J Roentgenol. 2001 Dec;177(6):1359-63 19079259 - Nat Genet. 2009 Jan;41(1):118-24 15260986 - Cell. 2004 Jul 23;118(2):149-61 8980223 - Cell. 1996 Dec 27;87(7):1161-9 17618114 - Bioorg Med Chem Lett. 2007 Sep 1;17(17):4756-60 18645138 - Arch Dermatol. 2008 Jul;144(7):873-7 8415706 - Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9355-8 20870869 - Phlebology. 2010 Oct;25(5):224-35 10369874 - Hum Mol Genet. 1999 Jul;8(7):1279-89 1715094 - Science. 1991 Aug 23;253(5022):905-9 19234476 - Nat Rev Mol Cell Biol. 2009 Mar;10(3):165-77 9632797 - Mol Cell Biol. 1998 Jul;18(7):4131-40 18535669 - J Clin Invest. 2008 Jul;118(7):2592-9 |
| References_xml | – ident: B48 doi: 10.1097/00005650-199401000-00004 – volume: 140 start-page: 971 issue: 8 year: 2004 ident: B1 article-title: Glomuvenous malformation (glomangioma) and venous malformation: distinct clinicopathologic and genetic entities publication-title: Arch Dermatol doi: 10.1001/archderm.140.8.971 – volume: 4 start-page: 179 issue: 4 year: 2013 ident: B15 article-title: Variable somatic TIE2 mutations in half of sporadic venous malformations publication-title: Mol Syndromol doi: 10.1159/000348327 – ident: B36 doi: 10.1161/01.RES.86.1.24 – ident: B14 doi: 10.1038/ng.272 – volume: 10 start-page: 165 issue: 3 year: 2009 ident: B18 article-title: Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system publication-title: Nat Rev Mol Cell Biol doi: 10.1038/nrm2639 – volume: 18 start-page: 4131 issue: 7 year: 1998 ident: B37 article-title: Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt publication-title: Mol Cell Biol doi: 10.1128/MCB.18.7.4131 – volume: 16 Spec No. 2 start-page: R140 year: 2007 ident: B2 article-title: Genetic causes of vascular malformations publication-title: Hum Mol Genet doi: 10.1093/hmg/ddm211 – ident: B46 doi: :10.1007/s00431-015-2572 – ident: B4 doi: 10.1258/phleb.2009.009041 – ident: B19 doi: 10.1016/j.yexcr.2013.03.011 – ident: B44 doi: 10.1002/pbc.23124 – ident: B28 doi: 10.1007/s10456-012-9313-x – ident: B13 doi: 10.1016/S0092-8674(00)81814-0 – ident: B31 doi: 10.1038/jid.2008.89 – volume: 1 start-page: a006460 issue: 1 year: 2011 ident: B34 article-title: Infantile hemangioma-mechanism(s) of drug action on a vascular tumor publication-title: Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a006460 – ident: B8 doi: 10.1016/j.bjps.2007.12.062 – ident: B21 doi: 10.1016/j.ccr.2005.08.002 – ident: B32 doi: 10.1038/sj.onc.1202288 – volume: 129 start-page: 4 issue: 4 year: 2012 ident: B45 article-title: Blue rubber bleb nevus syndrome: successful treatment with sirolimus publication-title: Pediatrics doi: 10.1542/peds.2010-3611 – ident: B10 doi: 10.1097/00006534-200212000-00001 – ident: B43 doi: 10.1016/j.cell.2012.03.017 – ident: B33 doi: 10.1016/j.bmcl.2007.06.068 – ident: B26 doi: 10.1101/gad.8.16.1897 – ident: B42 doi: 10.1139/y77-007 – volume: 28 start-page: 153 issue: 2 year: 2002 ident: B11 article-title: Reversible cardiac arrest after polidocanol sclerotherapy of peripheral venous malformation publication-title: Dermatol Surg – ident: B41 doi: 10.1126/science.1715094 – ident: B47 doi: 10.1172/JCI33493 – ident: B39 doi: 10.1074/jbc.M203995200 – ident: B9 doi: 10.1016/S1051-0443(07)61482-1 – ident: B22 doi: 10.1016/S0092-8674(00)81812-7 – ident: B35 doi: 10.1016/j.ccr.2006.07.003 – volume: 144 start-page: 861 issue: 7 year: 2008 ident: B7 article-title: Coagulation disorders in patients with venous malformation of the limbs and trunk: a case series of 118 patients publication-title: Arch Dermatol doi: 10.1001/archderm.144.7.861 – ident: B27 doi: 10.1172/JCI46322 – volume: 145 start-page: 1239 issue: 11 year: 2009 ident: B6 article-title: Elevated D-dimer level in the differential diagnosis of venous malformations publication-title: Arch Dermatol doi: 10.1001/archdermatol.2009.296 – ident: B3 doi: 10.1097/01.RVI.0000124949.24134.CF – ident: B20 doi: 10.1016/j.cell.2004.07.004 – ident: B12 doi: 10.2214/ajr.177.6.1771359 – ident: B25 doi: 10.1016/S0092-8674(00)81813-9 – ident: B24 doi: 10.1073/pnas.90.20.9355 – ident: B29 doi: 10.1007/s00109-004-0601-9 – ident: B40 doi: 10.1016/S0969-2126(00)00516-5 – volume: 144 start-page: 873 issue: 7 year: 2008 ident: B5 article-title: Association of localized intravascular coagulopathy with venous malformations publication-title: Arch Dermatol doi: 10.1001/archderm.144.7.873 – ident: B38 doi: 10.1016/j.molcel.2006.03.029 – volume: 7 start-page: 1471 issue: 8 year: 1992 ident: B23 article-title: tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors publication-title: Oncogene – ident: B16 doi: 10.1038/ejhg.2009.193 – ident: B17 doi: 10.1093/hmg/8.7.1279 – ident: B30 doi: 10.1093/hmg/ddt198 – reference: 18535669 - J Clin Invest. 2008 Jul;118(7):2592-9 – reference: 15313813 - Arch Dermatol. 2004 Aug;140(8):971-6 – reference: 23086340 - Angiogenesis. 2013 Jan;16(1):207-22 – reference: 16603397 - Mol Cell. 2006 Apr 21;22(2):159-68 – reference: 11340138 - J Vasc Interv Radiol. 2001 May;12(5):595-600 – reference: 11860427 - Dermatol Surg. 2002 Feb;28(2):153-5 – reference: 15526080 - J Mol Med (Berl). 2005 Jan;83(1):58-63 – reference: 23633549 - Hum Mol Genet. 2013 Sep 1;22(17):3438-48 – reference: 22500797 - Cell. 2012 Apr 13;149(2):274-93 – reference: 10369874 - Hum Mol Genet. 1999 Jul;8(7):1279-89 – reference: 23500414 - Exp Cell Res. 2013 May 15;319(9):1271-80 – reference: 21445948 - Pediatr Blood Cancer. 2011 Dec 1;57(6):1018-24 – reference: 11080633 - Structure. 2000 Nov 15;8(11):1105-13 – reference: 12082108 - J Biol Chem. 2002 Aug 30;277(35):31768-73 – reference: 19234476 - Nat Rev Mol Cell Biol. 2009 Mar;10(3):165-77 – reference: 1630810 - Oncogene. 1992 Aug;7(8):1471-80 – reference: 8980223 - Cell. 1996 Dec 27;87(7):1161-9 – reference: 19888299 - Eur J Hum Genet. 2010 Apr;18(4):414-20 – reference: 8980225 - Cell. 1996 Dec 27;87(7):1181-90 – reference: 23801934 - Mol Syndromol. 2013 Apr;4(4):179-83 – reference: 17670762 - Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R140-9 – reference: 18571489 - J Plast Reconstr Aesthet Surg. 2009 May;62(5):684-9; discussion 689 – reference: 15260986 - Cell. 2004 Jul 23;118(2):149-61 – reference: 19917952 - Arch Dermatol. 2009 Nov;145(11):1239-44 – reference: 8415706 - Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9355-8 – reference: 22229118 - Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006460 – reference: 16169466 - Cancer Cell. 2005 Sep;8(3):211-26 – reference: 9926914 - Oncogene. 1999 Jan 7;18(1):1-8 – reference: 8277801 - Med Care. 1994 Jan;32(1):40-66 – reference: 16904613 - Cancer Cell. 2006 Aug;10(2):159-70 – reference: 21606590 - J Clin Invest. 2011 Jun;121(6):2278-89 – reference: 26040705 - Eur J Pediatr. 2015 Dec;174(12):1579-84 – reference: 10625301 - Circ Res. 2000 Jan 7-21;86(1):24-9 – reference: 18401423 - J Invest Dermatol. 2008 Sep;128(9):2325-33 – reference: 15126652 - J Vasc Interv Radiol. 2004 May;15(5):431-45 – reference: 17618114 - Bioorg Med Chem Lett. 2007 Sep 1;17(17):4756-60 – reference: 7958865 - Genes Dev. 1994 Aug 15;8(16):1897-909 – reference: 18645138 - Arch Dermatol. 2008 Jul;144(7):873-7 – reference: 8980224 - Cell. 1996 Dec 27;87(7):1171-80 – reference: 1715094 - Science. 1991 Aug 23;253(5022):905-9 – reference: 9632797 - Mol Cell Biol. 1998 Jul;18(7):4131-40 – reference: 11717083 - AJR Am J Roentgenol. 2001 Dec;177(6):1359-63 – reference: 22392180 - Pediatrics. 2012 Apr;129(4):e1080-4 – reference: 20870869 - Phlebology. 2010 Oct;25(5):224-35 – reference: 18645137 - Arch Dermatol. 2008 Jul;144(7):861-7 – reference: 12447041 - Plast Reconstr Surg. 2002 Dec;110(7):1625-35 – reference: 843990 - Can J Physiol Pharmacol. 1977 Feb;55(1):48-51 – reference: 19079259 - Nat Genet. 2009 Jan;41(1):118-24 |
| SSID | ssj0014454 |
| Score | 2.5779006 |
| Snippet | Venous malformations (VMs) are composed of ectatic veins with scarce smooth muscle cell coverage. Activating mutations in the endothelial cell tyrosine kinase... Venous malformations (VMs) are composed of ectatic veins with scarce smooth muscle cell coverage. Activating mutations In the endothelial cell tyrosine kinase... |
| SourceID | pubmedcentral proquest gale pubmed crossref |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source |
| StartPage | 3491 |
| SubjectTerms | Adolescent Adult Analysis Animal models in research Animals Biomedical research Disease Models, Animal Drug therapy Female Genetic aspects Health aspects Human Umbilical Vein Endothelial Cells - metabolism Human Umbilical Vein Endothelial Cells - pathology Humans Immunosuppressive Agents - administration & dosage Male Mice Mice, Nude Middle Aged Mutation Mutation, Missense Patients Phosphorylation Pilot Projects Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Rapamycin Receptor, TIE-2 - genetics Receptor, TIE-2 - metabolism Risk factors Signal Transduction - drug effects Signal Transduction - genetics Sirolimus - administration & dosage Vascular Malformations - drug therapy Vascular Malformations - genetics Vascular Malformations - metabolism Vascular Malformations - pathology Veins Venous insufficiency |
| Title | Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/26258417 https://www.proquest.com/docview/1711617101 https://www.proquest.com/docview/1709396361 https://www.proquest.com/docview/1722172559 https://pubmed.ncbi.nlm.nih.gov/PMC4588237 |
| Volume | 125 |
| WOSCitedRecordID | wos000362303600025&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVPQU databaseName: Biological Science Database customDbUrl: eissn: 1558-8238 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014454 issn: 0021-9738 databaseCode: M7P dateStart: 20020701 isFulltext: true titleUrlDefault: http://search.proquest.com/biologicalscijournals providerName: ProQuest – providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 1558-8238 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014454 issn: 0021-9738 databaseCode: 7X7 dateStart: 20020701 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: Nursing & Allied Health Database customDbUrl: eissn: 1558-8238 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014454 issn: 0021-9738 databaseCode: 7RV dateStart: 20020701 isFulltext: true titleUrlDefault: https://search.proquest.com/nahs providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: eissn: 1558-8238 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014454 issn: 0021-9738 databaseCode: BENPR dateStart: 20020701 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1bb9MwFLZgQ4gX7rDCKAYh9mStdi52ntCYOlEEpSqj6lvk2vGotKbb0k7i33OO44YFTRMSL5Faf5Vc51zt4-8Q8i6LNLZE4ixShWExeAA2M84wm7ik5_C2rm_nM_kih0M1nWajsOFWhbLKjU30htouDe6R73PJMRQHCfpwds6waxSeroYWGrfJNsfYGORZjifNKUIcJ4GFmbNMRiqQz4LP3v98OMAjqbjljv42yle8Urti8ooLOnrwv5N_SO6H4JMe1NLyiNwqysfk7tdwvP6ETMbgOhe_4AOd-82GoqLHg75gizXGpJZeekZXutCnzaVHCuAFbtkX1HfVobq01Hf-o9V6hrs81VPy46h_fPiJhcYLzKSRXDGHRHXIMw_hiI4Et0pFs8xEhVWxgQTHycxaZyH3calTTloeC1kIodNEGA7AZ2SrXJbFDqFSJZmOUhNLYWKT9maJthq-7AmdSSt5h-xt1j83gZUcm2Oc5j47kSLfvKkOedMgz2omjmswr_EV5vUd0kZ58wNIsjgIgALEW49A6osSa2tO9Lqq8sG3yT-Avo9boL0AckuYsdHhPgP8b6TUaiHft5AnNaH4dcDdFhA03bSHN9KVB0tT5X9ECxaoGcZfYvVcWYBUAKaXRWBp0xsxAnuVgRJ1yPNa2JtlFpAkq5jLDpEtNWgAyFHeHinnPz1XOV6EFpF8cfPUX5J7EIgmde3eLtlaXayLV-SOuVzNq4uuV2p8TqV_qi7Z_tgfjsZdrNQd_Qbl-1e2 |
| linkProvider | ProQuest |
| linkToHtml | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9NAEB6VgoAL70eg0AUBPVmNd22vfUCoKq1qmgZU0ig3s9m1S6TGKXVS1D_Fb2Rm_aBGVcWlB47OfrHs9ew8dme-AXgTCUUtkVxHhKl2PLQAzlhn2jF-5nczqta17XyGPdnvh6NR9GUJftW1MJRWWetEq6jNTNMe-borXXLFUYI-HP9wqGsUna7WLTRKsdhNz35iyFa8jz_i933L-fbWYHPHqboKODoQcu5kxMJGJOpoa5XgrglDMY60SE3oafTeMxkZkxl07LMgCzNpXI_LlHMV-Fy7CMT7XoPrqMclBXty1AR4GJv4Feuz60RShBXZLfoI6582YzoC81rm728jcM4KtjM0z5m87bv_22TdgzuVc802ytVwH5bS_AHc3KvSBx7CcB9dg-kZXrCJ3UxJCzaIt7gzXZDPbdipZaxlU3XUFHUyBE_pSCJltmsQU7lhtrMhKxZj2sUqHsHBlbzVY1jOZ3n6FJgM_UiJQHuSa08H3bGvjMIfu1xF0ki3A2v19050xbpOzT-OEht9SZ7UktGBVw3yuGQauQCzSiKTlDWyjXJKNjCIdFHgQkS8tgii9sgpd-hQLYoiiT8P_wH0db8FWqtA2QyfWKuqXgPfmyjDWsh3LeRhSZh-EXClBURNptvDtTQnlSYtkj-ijBPUDNM_KTswT1EqENONBFqS4FIMp15sGEB34Em5uJpp5gFHP9yVHZCtZdcAiIO9PZJPvlsudir05kI-u_zRV-HWzmCvl_Ti_u5zuI1Ot1_mKa7A8vxkkb6AG_p0PilOXlqFwuDbVS_K30vzrpQ |
| linkToPdf | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1bb9MwFLZGhyZeuF8KgxkE7Mlq41ycPCA0tlaEjVKVrdpbcO14VFrTsbRD-2v8Os5JnLCgaeJlDzym_holzrnZPuc7hLyOXIktkRzmhqliHngANlFGMe0bv2uwWrdo5zPeE4NBeHgYDVfIr6oWBtMqK5tYGGo9V7hH3nGEg6E4SFDH2LSI4U7__ckPhh2k8KS1aqdRishuev4Tlm_5u3gHvvUbzvu9_e2PzHYYYCpwxYIZZGRDQnXwu9Lljg5DdxIpN9WhpyCSNyLS2mgI8k1gQiO043GRci4DnysHgHDfG2RVQJDhtcjqh95gOKrPMDzPtxzQDouEG1rqW4gYOp-2YzwQ8xrO8G-XcMEnNvM1LzjA_p3_eerukts27KZbpZ7cIytpdp-sfbaJBQ_IeARBw-wcLui02GZJc7of9zibLTEa1_Ss4LKlM3lcl3tSAM_wsCKlRT8hKjNNi56HNF9OcH8rf0gOruWtHpFWNs_SJ4SK0I-kGyhPcOWpoDvxpZbwY5fLSGjhtMlm9e0TZfnYsS3IcVKsywRPKilpk5c18qTkILkEs4Hik5TVs7XZSrZgeemA8IWAeFUgkPQjQxk4kss8T-Iv438AfR01QJsWZObwxEraSg54byQTayDfNpBHJZX6ZcD1BhBsnGoOV5KdWBubJ3_EGiaoHsZ_Yt5gloJUAKYbueBjgisxHLu0wdK6TR6XilZPMw84ROiOaBPRUMEagOzszZFs-r1gaccScO6Kp1c_-gZZA11M9uLB7jNyC6Jxv0xgXCetxekyfU5uqrPFND99Ya0LJd-uWyt_A1UJuLQ |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Rapamycin+improves+TIE2-mutated+venous+malformation+in+murine+model+and+human+subjects&rft.jtitle=The+Journal+of+clinical+investigation&rft.au=Boscolo%2C+Elisa&rft.au=Limaye%2C+Nisha&rft.au=Huang%2C+Lan&rft.au=Kang%2C+Kyu-Tae&rft.date=2015-09-01&rft.eissn=1558-8238&rft.volume=125&rft.issue=9&rft.spage=3491&rft_id=info:doi/10.1172%2FJCI76004&rft_id=info%3Apmid%2F26258417&rft.externalDocID=26258417 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0021-9738&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0021-9738&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0021-9738&client=summon |