Fumarate hydratase functions as a tumor suppressor in endometrial cancer by inactivating EGFR signaling.

Fumarase hydratase (FH) is an enzyme that catalyzes the reversible hydration and dehydration of fumarate to malate in the tricarboxylic acid cycle. The present study addressed the role of FH in endometrial cancer and clinically observed that the expression of FH was significantly lower in endometrial cancer tissues compared with normal endometrial tissues and, furthermore, that the decreased FH expression in endometrial cancer tissues was significantly associated with increased tumor size and lymph node metastasis. Further analysis in in vitro study showed that cell proliferation, migration and invasion abilities were increased when the expression of FH in the endometrial cancer cells was knocked down, but, by contrast, overexpression of FH in endometrial cancer cells decreased cell proliferative, migratory and invasive abilities. Mechanistic studies showed that the expression of vimentin and twist, being two well-studied mesenchymal markers in endometrial cancer cells, were upregulated in fumarate hydratase-knockdowned cells. In addition, phosphokinase array analysis demonstrated that the expression of phospho-EGFR (Y1086), which promotes carcinogenesis in cancers, was increased in endometrial cancer cells when FH was knocked down. In conclusion, the present study suggested that FH is a tumor suppressor and inhibits endometrial cancer cell proliferation and metastasis by inactivation of EGFR. Further studies are required to clarify its role as a prognostic biomarker and therapeutic target for endometrial cancer.

Enhanced Raman sensitivity and magnetic separation for urolithiasis detection using phosphonic acid-terminated Fe3O4 nanoclusters.

Surface-functionalized Fe3O4 nanoparticles are emerging as promising agents for the selective and magnetic separation of various biological molecules. In principle, by engineering the surface of Fe3O4 nanoparticles, they can be applied as tracers to seek and recognize metabolites and secretions of specific diseases. In this report, we developed Fe3O4 nanoclusters with high magnetization and an amino-functionalized surface via the reaction between FeCl2, a hydrazine reductant, and a gelatin polymer to demonstrate magnetically separated prevalent urinary crystals. The surface of the gelatin-coated Fe3O4 nanoclusters was modified by using aminopropylphosphonic acid by amine coupling using EDC and NHS, which led to the exposure of their phosphonic acid groups and improved their affinity for fine Ca-based urinary crystals in the patient's urine. By subjecting the Fe3O4 nanoclusters that were bound to urinary crystals to Raman spectroscopy analysis, the crystalline types of the pre-concentrated urinary components were easily identified. The assignment of the vibration peaks of the crystals is promising for eliminating the false positives that occur when using a microscopic analysis method for urine crystal diagnosis. Sample preparation and identification required less than 10 min. Finally, we demonstrated that this non-invasive analytic platform exhibits a rapid and efficient detection rate of single- and multi-component urinary crystals from urine metabolites. A good correlation (86%) was observed between this non-invasive analytic platform and the diagnostic reports from 35 urolithiasis patients. We expect that this Fe3O4 nanocluster integrated Raman spectrum method will provide crystal information that could help early management for urolithiasis patients.