|
Lymphangioleiomyomatosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis.
|
10823953 |
2000 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
No patients with S-LAM with TSC1 LOH were identified, suggesting that TSC2 abnormalities are responsible for the vast majority of S-LAM cases and that TSC1-disease may be subclinical.
|
20639436 |
2010 |
|
Lymphangioleiomyomatosis
|
0.700 |
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
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
A TSC2 loss or mutation leads to disruption of the tuberin-hamartin heteromer and dysregulation of S6K1 activation leading to aberrant cell proliferation seen in LAM disease.
|
18408969 |
2008 |
|
Lymphangioleiomyomatosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Failure in the regulation of mTOR (mammalian target of rapamycin) appears to be critical to the pathogenesis of the inherited disorder tuberous sclerosis and the related lung disease LAM (lymphangioleiomyomatosis).
|
19143643 |
2009 |
|
Lymphangioleiomyomatosis
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
These data demonstrate that TSC2 controls cell migration through its N-terminus by associating with TSC1 and regulating RhoA activity, suggesting that TSC2 may play a critical role in modulating cell migration and invasiveness, which contributes to the pathobiology of LAM.
|
16388022 |
2006 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
LAM is caused by inactivating mutations in the tuberous sclerosis complex (TSC) genes, resulting in hyperactivation of mechanistic/mammalian target of rapamycin complex 1 (mTORC1).
|
29171770 |
2018 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
LAM occurs sporadically or in patients with tuberous sclerosis complex (TSC) and is etiologically linked to mutations in the TSC1 and TSC2 genes.
|
24570392 |
2014 |
|
Lymphangioleiomyomatosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Moreover, rapamycin-enhanced migration of TSC2-null cells was inhibited by the uPA inhibitor UK122, dexamethasone, and a FOXO inhibitor. uPA-knock-out mice developed fewer and smaller TSC2-null lung tumors, and introduction of uPA shRNA in tumor cells or amiloride-induced uPA inhibition reduced tumorigenesis <i>in vivo</i> These findings suggest that interference with the uPA-dependent pathway, when used along with rapamycin, might attenuate LAM progression and potentially other TSC-related disorders.
|
28972182 |
2017 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
In this review we describe the evolution of our understanding of the molecular and cellular basis of LAM and TSC, beginning with the discovery of the TSC1 and TSC2 genes and the demonstration of their involvement in sporadic (non-TSC) LAM.
|
17099139 |
2007 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Recent studies, however, revealed that both forms of LAM are genetically related but that sporadic LAM is a distinct clinical entity caused by somatic mutations of TSC2 (not TSC1) rather than a forme fruste of TSC carrying either of the TSC1 or TSC2 germline mutations.
|
15257730 |
2004 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
In HBV-D treated patients the dominant resistance mutation was rtL80V (31.4%) and rtM204I (60%) in LAM+ADV group while LAM-treated patients showed a preference of rtM204V (51.9%).
|
23026293 |
2012 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Mutations in tuberous sclerosis (TSC) genes cause the genetic disorder TSC, as well as other neoplasms, including lymphangioleiomyomatosis (LAM) and angiomyolipomas (AMLs).
|
25476905 |
2014 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
In addition, recent data confirm the potential of next-generation sequencing to detect low-prevalence mutations in tuberous sclerosis (TSC) genes in sporadic LAM.
|
29927757 |
2018 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM) are caused by inactivating mutations in TSC1 or TSC2, leading to mTORC1 hyperactivation.
|
30816188 |
2019 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The detection of a homozygous deletion of TSC1 driving a predicted case of sporadic lymphangioleiomyomatosis, consistent with the common two-hit TSC2 mutation model, has never been reported for sporadic lymphangioleiomyomatosis.
|
28643793 |
2017 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
AML and LAM are etiologically linked to mutations in the tsc2 and tsc1 genes in the case of LAM.
|
27289491 |
2016 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
TSC1/2 mutations also occur in other neoplastic disorders, including lymphangioleiomyomatosis (LAM) and bladder cancer.
|
29669930 |
2018 |
|
Lymphangioleiomyomatosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
These findings suggest a higher rate of LAM in TSC1 than previously recognised, as well as a fundamental difference in CT presentation between TSC1 and TSC2.
|
19419980 |
2009 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Our results indicate that TSC2 and less commonly TSC1 alterations are the primary essential driver event in angiomyolipoma/LAM, whereas other somatic mutations are rare and likely do not contribute to tumor development.
|
27494029 |
2016 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway is hyperactivated in a variety of cancers and disorders, including lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC), which are characterized by mutations in tumor suppressors TSC1 or TSC2.
|
24304514 |
2014 |
|
Lymphangioleiomyomatosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes <i>TSC1</i> and/or <i>TSC2</i> The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM.
|
29339522 |
2018 |
|
Lymphangioleiomyomatosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Immunohistochemical stains of both LAM and renal angiomyolipoma showed positive immunoreactivity for hamartin (TSC1) and loss of immunoreactivity for tuberin (TSC2).
|
10934115 |
2000 |
|
Lymphangioleiomyomatosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Our results illuminate the basis for lymphangioleiomyomatosis growth and demonstrate the therapeutic potential of targeting Syk in this and other settings driven by TSC genetic mutation.<i></i>.
|
28202529 |
2017 |
|
Lymphangioleiomyomatosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Loss of Tsc1 in fibroblasts in mice does not lead to a model of angiomyolipoma or lymphangioleiomyomatosis.
|
27907099 |
2016 |