|
Lymphangioleiomyomatosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
LAM and TSC are caused by mutations in the TSC1 or TSC2 tumor suppressor genes leading to elevated mechanistic/mammalian target of rapamycin complex activity.
|
31437431 |
2019 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Human skin <i>TSC2</i><sup>+/-</sup> fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth.
|
29339522 |
2018 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mechanistic target of rapamycin inhibitors reduce loss of lung function in lymphangioleiomyomatosis (LAM), although their benefit varies between individuals.
|
28993539 |
2018 |
|
Lymphangioleiomyomatosis
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Lymphangioleiomyomatosis (LAM) is a rare, almost exclusively female lung disease linked to inactivating mutations in tuberous sclerosis complex 2 (TSC2), a tumor suppressor gene that controls cell metabolic state and growth via regulation of the mechanistic target of rapamycin (mTORC1) signaling. mTORC1 is frequently activated in human cancers and, although the mTORC1 inhibitor rapamycin has a cytostatic effect, it is, in general, unable to elicit a robust curative effect or tumor regression.
|
29758070 |
2018 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
The mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin slows progression of these diseases but is not curative and associated with notable toxicity at clinically effective doses, highlighting the need for better understanding LAM's molecular etiology.
|
28972182 |
2017 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mammalian target of rapamycin (mTOR) inhibitors are the primary treatment for LAM but it is unknown whether these immunosuppressing medications increase the risk for or the severity of respiratory infections in LAM patients.We searched multiple databases for original articles that reported the rate of respiratory infections in LAM patients treated with mTOR inhibitors or placebo.
|
28096282 |
2017 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Sirolimus, an mammalian target of rapamycin inhibitor, has been shown to stabilize lung function, reduce symptoms and resolve chylous effusions in the short term for patients with LAM.
|
29208258 |
2017 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
As a result, the global experience, including the use of mechanistic target of rapamycin (mTOR) inhibitors before and after LT in LAM, is still limited.
|
28823029 |
2017 |
|
Lymphangioleiomyomatosis
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
621-101 cells reduced extracellular pH with acidification dependent on 621-101 mechanistic target of rapamycin activity and net hydrogen ion exporters, particularly sodium bicarbonate co-transporters and carbonic anhydrases, which were also expressed in LAM lung tissue.
|
28623674 |
2017 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
As of today, sirolimus (an mammalian target of rapamycin complex 1 inhibitor) is the only treatment, available for LAM patients that is approved by the Food and Drug Administration; however, this drug and others in its class provide stabilization but not remission of LAM.
|
27409646 |
2016 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Whilst the mTOR inhibitor rapamycin has shown some benefit in patients with LAM, with stabilisation of lung function and improved quality of life, cessation of treatment results in recurrence of the disease progression.
|
26713679 |
2016 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
LAM is caused by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) as a consequence of tuberous sclerosis complex (TSC) 1/2 inactivation.
|
25844891 |
2015 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mutations in TSC1 or TSC2 cause TSC, result in hyperactivation of mammalian target of rapamycin (mTOR), and are also seen in LAM cells in sporadic LAM.
|
25347447 |
2014 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women associated with the metastasis of tuberin-null cells with hyperactive mammalian target of rapamycin complex 1 (mTORC1) activity.
|
23983265 |
2013 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
We conclude that TSC1/TSC2 deficiency leads to MMP-2 overproduction that is rapamycin-insensitive, and that several genes exhibit similar patterns, suggesting that TSC1/TSC2-dependent, but mammalian target of rapamycin-independent, pathways may be involved in the pathogenesis of LAM.
|
19395678 |
2010 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
The involvement of mTOR in LAM pathogenesis is the basis for initiation of therapeutic trials of mTOR inhibitors (e.g., sirolimus).
|
20630348 |
2010 |
|
Lymphangioleiomyomatosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Angiomyolipomas in patients with the tuberous sclerosis complex or sporadic lymphangioleiomyomatosis are associated with mutations in tuberous sclerosis genes resulting in constitutive activation of the mammalian target of rapamycin (mTOR).
|
18184959 |
2008 |
|
Lymphangioleiomyomatosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
However, the re-expression of TSC2 or inhibition of mTOR/S6K1 with rapamycin (sirolimus) augmented antiproliferative effects of IFNbeta in LAM and TSC2-null ELT3 cells.
|
18094073 |
2008 |