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The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells
Oleh:
Grudzien, Meagan M.
;
Low, Philip Steven
;
Manning, Peter C.
Jenis:
Article from Journal - ilmiah internasional
Dalam koleksi:
Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 93 no. 04 (Mar. 2010)
,
page 1290-1298.
Topik:
halofuginone
;
leiomyoma
;
myometrium
;
collagen
;
antifibrotic
Ketersediaan
Perpustakaan FK
Nomor Panggil:
F02.K.2010.02
Non-tandon:
1 (dapat dipinjam: 0)
Tandon:
tidak ada
Lihat Detail Induk
Isi artikel
Objective To investigate the effects of the antifibrotic drug halofuginone on extracellular matrix production, cell proliferation, and apoptosis of cultured myometrial and leiomyoma smooth muscle cells. Design Comparative and controlled experimental research study. Setting University research laboratory. Patient(s) Leiomyoma and myometrial tissues were obtained from eight different patients at the time of elective hysterectomy. Main Outcome Measure(s) The effects of halofuginone on cell proliferation were assessed by tritiated thymidine uptake assays and cell count assays. Effects on TGFß1, collagen type I, and collagen type III mRNA levels were assessed by quantitative real-time polymerase chain reaction. Effects on apoptosis were assayed using a chemiluminescent assay to measure changes in caspase 3 and 7. Result(s) Halofuginone inhibited cell proliferation of both leiomyoma and autologous myometrial cells in a dose-dependent manner by inhibiting DNA synthesis within 24 hours and later inducing apoptosis (as measured by increased caspase 3/7) by 48–72 hours. Halofuginone also significantly reduced collagen type I (a1) and collagen type III (a1) mRNA levels, as well as the profibrotic factor TGFß1 mRNA levels in both cell types. Conclusion(s) These results provide evidence to support the use of the antifibrotic drug halofuginone as a novel drug treatment for uterine leiomyomas.
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