(Salen)osmium (Ⅵ) nitrides catalyzed glutathione depletion in chemotherapy

Glutathione depletion provides a promising strategy for the design of non-platinum anticancer drugs.Here we report a series of electrophilic (salen)osmium(Ⅵ) nitrides that react with glutathione to generate (salen)osmium(Ⅲ) ammine compounds.In vitro studies indicate that these osmium(VI) nitrides show comparable cytotoxicity to cisplatin against various carcinoma.Mechanistic studies with the representative compound[OsⅥ(N)(LH)(OH_(2))](PF6)(1,LH=N,N’-bis(salicylidene)-o-cyclohexyldiamine dianion) suggest that 1 induces glutathione depletion,reactive oxygen species generation,endoplasmic reticulum stress,and in turn triggers death receptor-mediated apoptosis and autophagy in lung cancer cells.In vivo evaluations show that 1 can inhibit tumor xenograft growth effectively with no body weight drop.

Predictive Model of Oxaliplatin-induced Liver Injury Based on Artificial Neural Network and Logistic Regression

Background and Aims:Identifying potential high-risk groups of oxaliplatin-induced liver injury(OILI)is valuable,but tools are lacking.So artificial neural network(ANN)and logistic regression(LR)models will be developed to predict the risk of OILI.Methods:The medical information of patients treated with oxaliplatin between May and November 2016 at 10 hospitals was collected prospectively.We used the updated Roussel Uclaf causality assessment method(RUCAM)to identify cases of OILI and summarized the patient and medication characteristics.Furthermore,the ANN and LR models for predicting the risk of OILI were developed and evaluated.Results:The incidence of OILI was 3.65%.The median RUCAM score with interquartile range was 6(4,9).The ANN model performed similarly to the LR model in sensitivity,specificity,and accuracy.In discrimination,the area under the curve of the ANN model was larger(0.920>0.833,p=0.019).In calibration,the ANN model was slightly improved.The important predictors of both models overlapped partially,including age,chemotherapy regimens and cycles,single and total dose of OXA,glucocorticoid drugs,and antihistamine drugs.Conclusions:When the discriminative and calibration ability was given priority,the ANN model outperformed the LR model in predicting the risk of OILI.Other chemotherapy drugs in oxaliplatin-based chemotherapy regimens could have different degrees of impact on OILI.We suspected that OILI may be idiosyncratic,and chemotherapy dose factors may be weakly correlated.Decision making on prophylactic medications needs to be carefully considered,and the actual preventive effect needed to be supported by more evidence.