O caminho à frente da linfangioleiomiomatose: um ensaio para cada paciente, cada paciente em um ensaio

McCormack, Francis X.

doi:10.1590/s1806-37132011000400002

J. bras. pneumol.

2011

DOI: 10.1590/s1806-37132011000400002

|View full text |Cite

O caminho à frente da linfangioleiomiomatose: um ensaio para cada paciente, cada paciente em um ensaio

Francis X. McCormack¹

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2013

2020

Publication Types

Select...

Article3

Relationship

Self Cite1

Independent2

Authors

Journals

Cited by 3 publications

(1 citation statement)

References 13 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…( 29 ) This latter study was discussed in an editorial by Professor Francis McCormack, who works in the American city of Cincinnati. ( 30 ) Thanks to the efforts of research groups across Brazil who study interstitial lung diseases, the Brazilian Thoracic Association finally issued guidelines for the diagnosis and management of this important family of diseases. ( 31 ) …”

mentioning

confidence: 99%

Publicações do Jornal Brasileiro de Pneumologia

Carvalho

2013

J. bras. pneumol.

View full text Add to dashboard Cite

mentioning

confidence: 99%

Publicações do Jornal Brasileiro de Pneumologia

Carvalho

2013

J. bras. pneumol.

View full text Add to dashboard Cite

Therapeutic Targeting of the Secreted Lysophospholipase D Autotaxin Suppresses Tuberous Sclerosis Complex-Associated Tumorigenesis

et al. 2020

View full text Add to dashboard Cite

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by multiorgan hamartomas, including renal angiomyolipomas and pulmonary lymphangioleiomyomatosis (LAM). TSC2 deficiency leads to hyperactivation of mTOR Complex 1 (mTORC1), a master regulator of cell growth and metabolism. Phospholipid metabolism is dysregulated upon TSC2 loss, causing enhanced production of lysophosphatidylcholine (LPC) species by TSC2-deficient tumor cells. LPC is the major substrate of the secreted lysophospholipase D autotaxin (ATX), which generates two bioactive lipids, lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). We report here that ATX expression is upregulated in human renal angiomyolipoma-derived TSC2-deficient cells compared with TSC2 addback cells. Inhibition of ATX via the clinically developed compound GLPG1690 suppressed TSC2-loss associated oncogenicity in vitro and in vivo and induced apoptosis in TSC2-deficient cells. GLPG1690 suppressed AKT and ERK1/2 signaling and pro-foundly impacted the transcriptome of these cells while inducing minor gene expression changes in TSC2 add-back cells. RNAsequencing studies revealed transcriptomic signatures of LPA and S1P, suggesting an LPA/S1P-mediated reprogramming of the TSC lipidome. In addition, supplementation of LPA or S1P rescued proliferation and viability, neutral lipid content, and AKT or ERK1/2 signaling in human TSC2-deficient cells treated with GLPG1690. Importantly, TSC-associated renal angiomyolipomas have higher expression of LPA receptor 1 and S1P receptor 3 compared with normal kidney. These studies increase our understanding of TSC2-deficient cell metabolism, leading to novel potential therapeutic opportunities for TSC and LAM.Significance: This study identifies activation of the ATX-LPA/ S1P pathway as a novel mode of metabolic dysregulation upon TSC2 loss, highlighting critical roles for ATX in TSC2-deficient cell fitness and in TSC tumorigenesis.

show abstract

Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management

McCormack¹,

Gupta²,

Finlay³

et al. 2016

Am J Respir Crit Care Med

Self Cite

255

289

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

O caminho à frente da linfangioleiomiomatose: um ensaio para cada paciente, cada paciente em um ensaio

Cited by 3 publications

References 13 publications

Publicações do Jornal Brasileiro de Pneumologia

Publicações do Jornal Brasileiro de Pneumologia

Therapeutic Targeting of the Secreted Lysophospholipase D Autotaxin Suppresses Tuberous Sclerosis Complex-Associated Tumorigenesis

Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management

Contact Info

Product

Resources

About