Towards improving lymphangioleiomyomatosis care : a study of biomarkers and therapies
LAM is a rare metastasizing and destructive disorder of the lung. The disease is caused by cells carrying mutations in the TSC1/2 genes, but the tissue of origin of diseased cells remains unknown. The standard of care for LAM is the inhibition of mTOR with sirolimus. The standard of care for LAM is...
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| Format: | doctoral thesis |
| Status: | Published version |
| Publication Date: | 2019 |
| Country: | España |
| Institution: | CBUC, CESCA |
| Repository: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/668273 |
| Online Access: | http://hdl.handle.net/10803/668273 |
| Access Level: | Open access |
| Keyword: | Lymphangioleiomyomatosi Biomarkers Therapies Monoaminoxidases Histamine Linfangioleiomiomatosis Biomarcadores Terapias Monoaminoxidasas Histamina 616.2 |
| Summary: | LAM is a rare metastasizing and destructive disorder of the lung. The disease is caused by cells carrying mutations in the TSC1/2 genes, but the tissue of origin of diseased cells remains unknown. The standard of care for LAM is the inhibition of mTOR with sirolimus. The standard of care for LAM is the inhibition of mTOR with sirolimus. However, the therapy has variable tolerability. LAM diagnosis and monitoring can be challenging due to the heterogeneity of symptoms. In this thesis, we aimed to provide evidence for improving LAM care through the identification of useful biomarkers and exploration of novel therapeutic approaches. In parallel, we also studied disease origin. At the level of biomarkers, the major histamine-derived metabolite MIAA has been found to be more abundant in LAM plasmas. Combined studies of LAM lung tissues and cell models showed enhanced monoamine metabolism and histamine-mediated signaling. In addition, the inhibition of these two pathways decreased LAM tumorigenesis in mouse models. The results of this thesis may help improve the diagnostic process, clinical monitoring and therapeutic management of LAM patients. |
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