RESUMEN
The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and im-mune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.
RESUMEN
An analytical method was developed for the determination of unsymmetrical dimethylhydrazine ( UDMH ) in soil samples by gas chromatography-mass spectrometry with the pretreatment of alkaline distillation and ultrasonic derivatization. After pretreated by the alkaline distillation, the quantitative analysis of UDMH was conducted in selected ion monitoring ( SIM ) mode by using salicylaldehyde as derivatization reagent and ultrasonic to accelerate the derivative reaction. The characteristic ion of the derivative product named salicylaldehyde dimethylhydrazone was m/z 164 . Impact factors including types of the alkaline distillation and the derivative conditions with ultrasonic were investigated. The conditions of derivatization were optimized. Under the optimal conditions, linear range of the method was 0. 4-30 mg/L. The limit of detection (LOD, S/N=3) was 0. 0078 mg/kg. The method was used to detect total UDMH in real soil samples with known concentration. The recoveries ranged from 76% to 108% with relative standard deviations ( RSD) of 12%-19% at different spiked concentration levels from 10 mg/kg to 100 mg/kg. In comparison with the methods of spectrophotometry and Soxhlet extraction-ultrasonic derivatization, this method had lower detection limit, and could be used to detect total UDMH in soil samples.