Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met-GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met-GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nano-platform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

Purpose To study the relationshiPbetween CD88 expression and clinicopathologic features and epithelial-mesenchymal transition(EMT)in esophageal squamous cell carcinoma.Methods TCGA and TIMER database were used to analyze the expression level of CD88 in esophageal squamous cell carcinoma and adjaecnt esophageal squamous cell epithelium and its relationship with epithelial-mesenchymal transition.Par-affin specimens were collected from 199 patients with clinically diagnosed esophageal squamous cell carcinoma.Immunohisto-chemical EnVision method was used to detect the expression of CD88 and EMT-related proteins in esophageal squamous cell carcinoma and adjacent tissues,the relationship between CD88 expression and clinicopathological features,prognosis and EMT in ESCC tumors was analyzed.Results There were 86 cases with high CD88 expression and 113 cases with low CD88 expres-sion.The expression level of CD88 in esophageal squamous cell carcinoma was significantly higher than that of paracancerous tis-sue(P＜0.001).The group with high CD88 expression had lower ESCC differentiation level(P＜0.001)and higher T stage(P=0.03).The 5-year survival of patients with high CD88 ex-pression was significantly lower than that of patients with low CD88 expression(P=0.002).Cox univariate and multivariate analysis showed that CD88 expression was an independent prog-nostic factor for overall survival of patients with esophageal squa-mous cell carcinoma(P=0.013).The high expression of CD88 was negatively correlated with E-cadherin(r=-0.146,P=0.039),and positively correlated with vimentin(r=0.387,P=1.61e-08)and N-cadherin(r=0.304,P=1.3e-05).Con-clusion CD88 is highly expressed in esophageal squamous cell carcinoma.CD88 may affect the occurrence,development,in-vasion and metastasis of esophageal squamous cell carcinoma through EMT,and it might be used as a prognostic marker for e-sophageal squamous cell carcinoma patients.