Signaling pathways and inhibitors of cells from patients with kaposiform lymphangiomatosis
Boscolo E., Pastura P., Glaser K., Goines J., Hammill AM., Adams DM.
Retrospective Study, published in Pediatr Blood Cancer (2019) — summary generated from the PubMed abstract.
Early human evidence such as case series or small samples is exploring possible benefits.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Retrospective Study
- Journal
- Pediatr Blood Cancer (2019)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 31045327
- PMCID
- PMC6588438
- DOI
- 10.1002/pbc.27790
- Citations
- 25
Abstract (original English)
Background Kaposiform lymphangiomatosis (KLA) is a rare lymphatic anomaly with significant morbidity and mortality. KLA is characterized by diffuse multifocal lesions comprised of focal areas of "kaposiform" spindled cells accompanying malformed lymphatic channels. The goal of this study was to identify activated signaling pathways in cells isolated from three KLA patients for the purpose of testing new therapies. Procedure Cells were obtained from the lungs of one patient isolated at autopsy and the spleen of two patients removed in surgery due to disease complications. A protein kinase array was performed on the KLA cell lysates and normal lymphatic endothelial cells. Results Higher activation of key signaling pathways in the KLA cells, including PRAS40, AKT1/2/3, and ERK-1/2, was identified by protein kinase array and confirmed by Western blot analysis. This indicated a role for highly activated PI3K-AKT and MAPK-ERK-1/2 signaling pathways in KLA cells. Cell proliferation studies assessed PI3K inhibitors (LY294002; BYL719), AKT inhibitor ARQ092, mTOR inhibitor rapamycin, and MAPK inhibitor U0126. These studies demonstrated that PI3K-AKT-mTOR and MAPK signaling are important mediators of KLA cell proliferation. BYL719 and rapamycin were more effective at inhibiting KLA cell proliferation than U0126. Conclusions Our studies using cells from KLA patient lesions demonstrate that
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • Without an adequate control group, treatment effects cannot be separated from other factors.
Evidence level
Early human evidence such as case series or small samples is exploring possible benefits.
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