کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3943394 1254103 2008 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Expression, mutational analysis and in vitro response of imatinib mesylate and nilotinib target genes in ovarian granulosa cell tumors
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی زنان، زایمان و بهداشت زنان
پیش نمایش صفحه اول مقاله
Expression, mutational analysis and in vitro response of imatinib mesylate and nilotinib target genes in ovarian granulosa cell tumors
چکیده انگلیسی

Objectives.Granulosa cell tumors of the ovary (GCT) represent ∼ 5% of malignant ovarian tumors. Surgery remains the primary modality of therapy and treatment options for advanced disease are limited. The molecular pathogenesis of GCT is not known but is likely to involve activation of tyrosine kinase-mediated cell signaling pathways. A recent case report of a patient with advanced recurrent GCT responding to the tyrosine kinase inhibitor, imatinib mesylate prompted us to explore a role for these therapies in GCT.Methods.The expression of the imatinib-sensitive tyrosine kinases, c-kit, c-Abl, PDGFR-α and PDGFR-β, was determined using RT–PCR in a panel of GCT. Activating mutations of c-kit and PDGFR-α were also sought. The functional response was examined in two human-derived GCT cell lines.Results.All four kinases were expressed but at levels lower than those observed in pre-menopausal ovarian samples. Mutations in c-kit and PDGFR-α were not found. Both cell lines responded to imatinib and to the second generation, tyrosine kinase inhibitor, nilotinib, with dose-dependent decreases in cell proliferation and viability. These responses paralleled the imatinib-sensitive, K562 cell line but at ∼ 240- and ∼ 1000-fold higher concentrations of imatinib and nilotinib, respectively.Conclusions.Our study suggests that human GCT, in general, are unlikely to respond to imatinib or nilotinib therapy. The response of the cell lines at high concentrations implies an “off-target” effect, which suggests that a tyrosine kinase inhibitor, of appropriate specificity, may represent a therapeutic option in GCT.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gynecologic Oncology - Volume 108, Issue 1, January 2008, Pages 182–190
نویسندگان
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