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dc.contributor.authorHerranz, C
dc.contributor.authorMateo, F
dc.contributor.authorBaiges, A
dc.contributor.authorRuiz de Garibay, G
dc.contributor.authorJunza, A
dc.contributor.authorJohnson, SR
dc.contributor.authorMiller, S
dc.contributor.authorGarcía, N
dc.contributor.authorCapellades, J
dc.contributor.authorGómez, A
dc.contributor.authorVidal, A
dc.contributor.authorPalomero, L
dc.contributor.authorEspín, R
dc.contributor.authorExtremera, AI
dc.contributor.authorBlommaert, E
dc.contributor.authorRevilla-López, E
dc.contributor.authorSaez, B
dc.contributor.authorGómez-Ollés, S
dc.contributor.authorAncochea, J
dc.contributor.authorValenzuela, C
dc.contributor.authorAlonso, T
dc.contributor.authorUssetti, P
dc.contributor.authorLaporta, R
dc.contributor.authorXaubet, A
dc.contributor.authorRodríguez-Portal, JA
dc.contributor.authorMontes-Worboys, A
dc.contributor.authorMachahua, C
dc.contributor.authorBordas, J
dc.contributor.authorMenendez, JA
dc.contributor.authorCruzado, JM
dc.contributor.authorGuiteras, R
dc.contributor.authorBontoux, C
dc.contributor.authorLa Motta, C
dc.contributor.authorNoguera-Castells, A
dc.contributor.authorMancino, M
dc.contributor.authorLastra, E
dc.contributor.authorRigo-Bonnin, R
dc.contributor.authorPerales, JC
dc.contributor.authorViñals, F
dc.contributor.authorLahiguera, A
dc.contributor.authorZhang, X
dc.contributor.authorCuadras, D
dc.contributor.authorvan Moorsel, CHM
dc.contributor.authorvan der Vis, JJ
dc.contributor.authorQuanjel, MJR
dc.contributor.authorFilippakis, H
dc.contributor.authorHakem, R
dc.contributor.authorGorrini, C
dc.contributor.authorFerrer, M
dc.contributor.authorUgun-Klusek, A
dc.contributor.authorBillett, E
dc.contributor.authorRadzikowska, E
dc.contributor.authorCasanova, Á
dc.contributor.authorMolina-Molina, M
dc.contributor.authorRoman, A
dc.contributor.authorYanes, O
dc.contributor.authorPujana, MA
dc.date.accessioned2021-09-02T08:26:27Z
dc.date.available2021-09-02T08:26:27Z
dc.date.issued2021-08-11
dc.identifier.citationEMBO molecular medicine, 2021, pp. e13929 - ?
dc.identifier.issn1757-4676
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4786
dc.identifier.eissn1757-4684
dc.identifier.doi10.15252/emmm.202113929
dc.description.abstractInhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.
dc.formatPrint-Electronic
dc.format.extente13929 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleHistamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.
dc.typeJournal Article
dcterms.dateAccepted2021-07-21
rioxxterms.versionVoR
rioxxterms.versionofrecord10.15252/emmm.202113929
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2021-08-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEMBO molecular medicine
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.publication-statusPublished
pubs.embargo.termsNo embargo
icr.researchteamPaediatric Solid Tumour Biology and Therapeutics
icr.researchteamPaediatric Solid Tumour Biology and Therapeuticsen_US
dc.contributor.icrauthorGorrini, Chiaraen


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