Autor segons l'article: Herranz, Carmen; Mateo, Francesca; Baiges, Alexandra; de Garibay, Gorka Ruiz; Junza, Alexandra; Johnson, Simon R.; Miller, Suzanne; Garcia, Nadia; Capellades, Jordi; Gomez, Antonio; Vidal, August; Palomero, Luis; Espin, Roderic; Extremera, Ana, I; Blommaert, Eline; Revilla-Lopez, Eva; Saez, Berta; Gomez-Olles, Susana; Ancochea, Julio; Valenzuela, Claudia; Alonso, Tamara; Ussetti, Piedad; Laporta, Rosalia; Xaubet, Antoni; Rodriguez-Portal, Jose A.; Montes-Worboys, Ana; Machahua, Carlos; Bordas, Jaume; Menendez, Javier A.; Cruzado, Josep M.; Guiteras, Roser; Bontoux, Christophe; La Motta, Concettina; Noguera-Castells, Aleix; Mancino, Mario; Lastra, Enrique; Rigo-Bonnin, Raul; Perales, Jose C.; Vinals, Francesc; Lahiguera, Alvaro; Zhang, Xiaohu; Cuadras, Daniel; van Moorsel, Coline H. M.; van der Vis, Joanne J.; Quanjel, Marian J. R.; Filippakis, Harilaos; Hakem, Razq; Gorrini, Chiara; Ferrer, Marc; Ugun-Klusek, Aslihan; Billett, Ellen; Radzikowska, Elzbieta; Casanova, Alvaro; Molina-Molina, Maria; Roman, Antonio; Yanes, Oscar; Pujana, Miquel A.;
Departament: Enginyeria Electrònica, Elèctrica i Automàtica
Autor/s de la URV: Junza Martínez, Alexandra / Yanes Torrado, Óscar
Paraules clau: Vasculotropin d Unclassified drug Tumor xenograft Tsc2 Therapy Sirolimus Signal transduction Rasagiline Rapamycin Protein expression level Protein expression Protein depletion Promotes P70 s6 kinase Nonhuman Mtor Mouse Monotherapy Molecular dynamics Methylimidazoleacetic acid Metastatic breast cancer Metastasis Metabolic fingerprinting Major clinical study Lymphangioleiomyomatosis Lung tumor Lung neoplasms Lung function Loratadine Imidazoleacetic acid Humans Human tissue Human Histopathology Histidine derivative Histamine metabolism Histamine h1 receptor Histamine Gene Female Enzyme activity Embryo Drug targeting Drug potentiation Disease burden Disease association Diet restriction Controlled study Cohort analysis Clorgyline Clinical feature Cells Carcinogenesis Cancer inhibition Breast-cancer Biomarkers Biomarker Biological marker Article Antitumorigenic activity Animal tissue Animal model Animal experiment Animal cell Amine oxidase (flavin containing) isoenzyme b Amine oxidase (flavin containing) isoenzyme a Adult Activation
Resum: Inhibition 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.
Àrees temàtiques: Molecular medicine Medicine, research & experimental Medicina veterinaria Medicina ii Medicina i Farmacia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
Adreça de correu electrònic de l'autor: oscar.yanes@urv.cat alexandra.junza@urv.cat
Identificador de l'autor: 0000-0003-3695-7157 0000-0001-7205-0419
Data d'alta del registre: 2023-12-16
Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
Enllaç font original: https://www.embopress.org/doi/full/10.15252/emmm.202113929
URL Document de llicència: http://repositori.urv.cat/ca/proteccio-de-dades/
Referència a l'article segons font original: Embo Molecular Medicine. 13 (9):
Referència de l'ítem segons les normes APA: Herranz, Carmen; Mateo, Francesca; Baiges, Alexandra; de Garibay, Gorka Ruiz; Junza, Alexandra; Johnson, Simon R.; Miller, Suzanne; Garcia, Nadia; Cap (2021). Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis. Embo Molecular Medicine, 13(9), -. DOI: 10.15252/emmm.202113929
DOI de l'article: 10.15252/emmm.202113929
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2021
Tipus de publicació: Journal Publications
Repositori URV