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Sirolimus Decreases Circulating Lymphangioleiomyomatosis Cells in Patients With Lymphangioleiomyomatosis
- Source :
- Chest. 145:108-112
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Background Lymphangioleiomyomatosis (LAM), sporadic or in women with tuberous sclerosis complex (TSC), is characterized by cystic lung destruction, lymphatic involvement (eg, chylous pleural effusions, lymphangioleiomyomas), and renal angiomyolipomas (AMLs). The multisystem manifestations of LAM appear to result from metastatic dissemination of LAM cells bearing inactivating mutations or having loss of heterozygosity (LOH) of the tumor suppressor genes TSC1 or TSC2 , which leads to hyperactivation of the mammalian target of rapamycin. Sirolimus slows the decline of lung function, reduces chylous effusions, and shrinks the size of AMLs. The purpose of this study was to determine the effect of sirolimus on circulating LAM cells. Methods Cells from blood were isolated by a density-gradient fractionation system and from urine and chylous effusions by centrifugation. Blood cells were incubated with anti-CD45-fluorescein isothiocyanate (FITC) and anti-CD235a-R-phycoerythrin (PE) antibodies, and urine and chylous effusion cells were incubated with anti-CD44v6-FITC and anti-CD9-R-PE antibodies. Cells were sorted and analyzed for TSC2 LOH. Results LAM cells with TSC2 LOH were identified in 100% of blood specimens and 75% of urine samples from patients before therapy. Over a mean duration of 2.2 ± 0.4 years of sirolimus therapy, detection rates of LAM cells were significantly decreased to 25% in blood ( P P = .003). Following therapy, a greater loss of circulating LAM cells was seen in postmenopausal patients ( P = .025). Conclusions Patients receiving sirolimus had a progressive loss of circulating LAM cells that depended on time of treatment and menopausal status.
- Subjects :
- Adult
Pulmonary and Respiratory Medicine
Pathology
medicine.medical_specialty
Angiomyolipoma
Loss of Heterozygosity
Critical Care and Intensive Care Medicine
Loss of heterozygosity
Tuberous sclerosis
hemic and lymphatic diseases
Tuberous Sclerosis Complex 2 Protein
medicine
Humans
Lymphangioleiomyomatosis
Original Research
Sirolimus
Antibiotics, Antineoplastic
Lung
biology
business.industry
Tumor Suppressor Proteins
Middle Aged
Neoplastic Cells, Circulating
medicine.disease
Lymphatic system
medicine.anatomical_structure
biology.protein
Female
Antibody
Cardiology and Cardiovascular Medicine
business
Follow-Up Studies
medicine.drug
Subjects
Details
- ISSN :
- 00123692
- Volume :
- 145
- Database :
- OpenAIRE
- Journal :
- Chest
- Accession number :
- edsair.doi.dedup.....8767e46eaa2705152537bab484dd668a