Serum Vascular Endothelial Growth Factor-D Levels in Patients With Lymphangioleiomyomatosis Reflect Lymphatic Involvement

Glasgow, Connie G.; Avila, Nilo A.; Lin, Jing‐Ping; Stylianou, Mario; Moss, Joel

doi:10.1378/chest.08-1160

Cited by 108 publications

(135 citation statements)

References 23 publications

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“…In a recent report, Glasgow et al 15 concluded in a subanalysis that serum VEGF-D was only a "fair predictor" of LAM in patients without lymphadenopathy as defi ned by Einstein et al 16 However, in the Glasgow et al study, 15 the patients with LAM were compared only to healthy volunteers and not to patients with HRCT scan evidence of cystic lung disease, which is the clinically relevant comparison. In addition, the mean VEGF-D in their normal with TSC.…”

Section: Determination Of Overall Test Performancementioning

confidence: 99%

Serum Vascular Endothelial Growth Factor-D Prospectively Distinguishes Lymphangioleiomyomatosis From Other Diseases

Young

VanDyke

Gulleman

et al. 2010

Chest

189

167

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Section: Determination Of Overall Test Performancementioning

confidence: 99%

Serum Vascular Endothelial Growth Factor-D Prospectively Distinguishes Lymphangioleiomyomatosis From Other Diseases

Young

VanDyke

Gulleman

et al. 2010

Chest

189

167

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“…20 Th e disease phenotype is associated with lung nodules infi ltrated with lymphatics, lymphatic vessels showing LAM cells penetrating through the walls, and chylous eff usions. [19][20][21][22][23][24][25] Th ese forms of LAM are characterized by the presence of vascular abnormalities and evidence of arteriolar and venular channels as well as lymphatic channel infi ltration by LAM cells, resulting in both vascular obstruction and vascular wall disruption. 6,18 In the lungs, the consequences of these abnormalities are twofold.…”

Section: Discussionmentioning

confidence: 99%

“…21 LAM cells also exhibit positive immunoreactivity for VEGF-D, and serum levels of VEGF-D are increased in patients with LAM, especially those with lymphatic involvement. 22,23 High VEGF-D levels are associated with severity of lung disease as measured by the degree of airfl ow obstruction, impairment of lung diff usion capacity, and cysts on CT scans. 22,23 Measurement of serum VEGF-D has been shown to be useful as a diagnostic tool and in grading the severity of the disease and the potential response to therapy.…”

mentioning

confidence: 99%

“…22,23 High VEGF-D levels are associated with severity of lung disease as measured by the degree of airfl ow obstruction, impairment of lung diff usion capacity, and cysts on CT scans. 22,23 Measurement of serum VEGF-D has been shown to be useful as a diagnostic tool and in grading the severity of the disease and the potential response to therapy. 24,25 Lymphangioleiomyomas have a distinctive radiologic appearance, and diurnal variation in size of these tumors has been reported.…”

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confidence: 99%

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Effect of Fasting on the Size of Lymphangioleiomyomas in Patients With Lymphangioleiomyomatosis

Taveira-DaSilva¹,

Jones²,

Julien-Williams³

et al. 2015

Chest

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BACKGROUND: Lymphangioleiomyomas occur in 38% of patients with sporadic lymphangioleiomyomatosis (LAM) and may cause pain and increased abdominal girth, mimicking the presence of a malignancy. Lymphatic involvement in LAM is closely associated with elevated serum levels of vascular endothelium growth factor-D (VEGF-D). Because lymphangioleiomyomas undergo diurnal variation in volume, we hypothesized that daytime ingestion of food, by increasing chyle formation and lymphatic fl ow, is the cause of an increase in lymphangioleiomyoma volume.

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“…All LAM cells from 44 pulmonary LAM specimens exhibited immunoreactivity for VEGF-D, suggesting that LAM cells are secreting VEGF-D. 41 Glasgow et al 42 and Young et al 43 also found that VEGF-D levels are higher in LAM patients than healthy volunteers. In addition to its potential role in LAM pathogenesis and as a target for LAM therapy, VEGF-D may be useful diagnostically and=or as a biomarker of disease in LAM patients with lymphatic involvement.…”

Section: Figmentioning

confidence: 94%

mTOR Activation, Lymphangiogenesis, and Estrogen-Mediated Cell Survival: The “Perfect Storm” of Pro-Metastatic Factors in LAM Pathogenesis

Henske

2010

Lymphatic Research and Biology

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Research interest in lymphangioleiomyomatosis (LAM) has grown dramatically in the past decade, particularly among cancer biologists. There are at least two reasons for this: first, the discovery in the year 2000 that LAM cells carry TSC2 gene mutations, linking LAM with cellular pathways including the PI3K=Akt=mTOR axis, and allowing the Tuberous Sclerosis Complex (TSC)-regulated pathways that are believed to underlie LAM pathogenesis to be studied in cells, yeast, Drosophila, and mice. A second reason for the rising interest in LAM is the discovery that LAM cells can travel to the lung, including repopulating a donor lung after lung transplantation, despite the fact that LAM cells are histologically benign. This ''benign metastasis'' underpinning suggests that elucidating LAM pathogenesis will unlock a set of fundamental mechanisms that underlie metastatic potential in the context of a cell that has not yet undergone malignant transformation. Here, we will outline the data supporting the metastatic model of LAM, consider the biochemical and cellular mechanisms that may enable LAM cells to metastasize, including both cell autonomous and non-cell autonomous factors, and highlight a mouse model in which estrogen promotes the metastasis and survival of TSC2-deficient cells in a MEKdependent manner. We propose a multistep model of LAM cell metastasis that highlights multiple opportunities for therapeutic intervention. Taken together, the metastatic behavior of LAM cells and the involvement of tumorrelated signaling pathways lead to optimism that cancer-related paradigms for diagnosis, staging, and therapy will lead to therapeutic breakthroughs for women living with LAM.

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Serum Vascular Endothelial Growth Factor-D Levels in Patients With Lymphangioleiomyomatosis Reflect Lymphatic Involvement

Cited by 108 publications

References 23 publications

Serum Vascular Endothelial Growth Factor-D Prospectively Distinguishes Lymphangioleiomyomatosis From Other Diseases

Serum Vascular Endothelial Growth Factor-D Prospectively Distinguishes Lymphangioleiomyomatosis From Other Diseases

Effect of Fasting on the Size of Lymphangioleiomyomas in Patients With Lymphangioleiomyomatosis

mTOR Activation, Lymphangiogenesis, and Estrogen-Mediated Cell Survival: The “Perfect Storm” of Pro-Metastatic Factors in LAM Pathogenesis

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