Citations

Abstract Xanthogranuloma (XG) of the sellar region is uncommon and is difficult to diagnose based on intraoperative frozen sections. This study is a case presentation and review of the literature, highlighting the need to explore underlying diseases in order to guarantee an accurate patient diagnosis. Herein, we presented the case of a 43-year-old woman who was afflicted with xanthogranuloma of the sellar region; the patient had a history of headache and lengthened menstrual cycles over the 6 months prior to presentation. Endocrinology tests revealed that the patient’s levels of prolactin were high and the MRI of the patient showed a clearly defined sellar mass. As a result, the patient was considered to have prolactinoma prior to undergoing surgery. The tumor was completely removed using a transsphenoidal approach, and intraoperative frozen section revealed histology similar to xanthogranuloma. When the tumor was removed by surgical operation, the patient’s visual field defects and headache were relieved. Although intraoperative frozen section should provide some guidance with regard to the diagnosis, a pathological study is conducted to confirm the actual diagnosis.

Abstract The emergence of tumor cells with certain stem-like characteristics, such as high aldehyde dehydrogenase (ALDH) activity due to ALDH1A1 expression, contributes to chemotherapy resistance and tumor relapse. However, clinically applicable inhibitors of ALDH activity have not been reported. There is evidence to suggest that epigenetic regulation of stem-related genes contributes to chemotherapy efficacy. Here, we show that bromodomain and extraterminal (BET) inhibitors suppress ALDH activity by abrogating BRD4-mediated ALDH1A1 expression through a super-enhancer element and its associated enhancer RNA. The clinically applicable small-molecule BET inhibitor JQ1 suppressed the outgrowth of cisplatin-treated ovarian cancer cells both in vitro and in vivo. Combination of JQ1 and cisplatin improved the survival of ovarian cancer–bearing mice in an orthotopic model. These phenotypes correlate with inhibition of ALDH1A1 expression through a super-enhancer element and other stem-related genes in promoter regions bound by BRD4. Thus, targeting the BET protein BRD4 using clinically applicable small-molecule inhibitors, such as JQ1, is a promising strategy for targeting ALDH activity in epithelial ovarian cancer. Cancer Res; 76(21); 6320–30. ©2016 AACR.

Key Points The type III TGF-β receptor is a marker that distinguishes “early” and “late” BFU-Es. TGF-β inhibitors increase early BFU-E cell self-renewal and total erythroblast production.