Clinical analysis of immunotherapy rechallenge in advanced gastric cancer / 中华肿瘤杂志

Objective: To evaluate the efficacy and influencing factors of programmed death protein 1 (PD-1) monoclonal antibody rechallenge therapy in advanced gastric cancer (GC). Methods: The clinical data of patients with advanced GC who were treated with anti-PD-1 rechallenge in Henan Cancer Hospital from January 2020 to December 2021 were collected retrospectively. The progression-free survival (PFS) was defined as the time from the first or second used of anti-PD-1 treatment to the date of disease progression or the last follow-up, named PFS(1) and PFS(2), respectively. Kaplan-Meier method and Log rank test were used for survival analysis, Cox proportional hazard model was used to analyze the influencing factors. Results: A total of 60 patients with anti-PD-1 rechallenge therapy were collected, the median follow-up time was 12.2 months. The median progression-free survival (PFS(2)) of anti-PD-1 rechallenge therapy was 2.9 months, the objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.0%. The median PFS(2) of the first and second anti-PD-1 identical and different rechallenge treatment was 3.5 months and 1.9 months (P=0.007) respectively. The median PFS(2) of positive PD-L1 expression in rechallenge therapy was 3.4 months, ORR was 22.7%, and DCR was 63.6%; the median PFS(2) was 4.5 months, ORR was 27.3%, and DCR was 54.5% in patients with median PFS(1)≥6 months. Multivariate analysis showed that peritoneal metastasis was independently associated with anti-PD-1 rechallenge therapy with PFS(2) (HR=2.327, 95% CI, 1.066-5.082, P=0.034). The incidence of adverse reactions in grade 1-2 and grade 3-4 of anti-PD-1 rechallenge therapy was 83.3%, and 35.0%, respectively, and the safety was controllable. Conclusion: Rechallenge therapy with anti-PD-1 is a feasible treatment in advanced GC, but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.

Reversal of drug resistance in A549/DDP cells by silencing MT1H gene with MT1H siRNA / 肿瘤

Objective: To explore the feasibility of using siRNA targeting metallothionein 1H (MT1H) gene to reverse the drug resistance of A549/ DDP cells to cisplatin (DDP). Methods: The expressions of MT1H mRNA in A549 and A549/DDP cells were detected by reverse transcriptase polymerase chain reaction (RT-PCR). MT1H siRNA was transfected into A549/DDP cells with high expression of MT1H. The mRNA and protein levels of MT1H were detected by RT-PCR and Dot blotting, respectively. The chemosensitivity of A549/DDP cells to cisplatin was assessed by MMT assay. The apoptotic ratio induced by DDP was determined by TUNEL and flow cytometry analysis (FCM). The apoptosis-related protein levels of Bcl-2 and Bax were determined by immunohistochemistry. Results: MT1H mRNA was highly expressed in A549/DDP cells but not in A549 cells. The mRNA and protein levels of MT1H were significantly down-regulated at 48 h after transfection in MT1H siRNA group compared with the control group. The chemosensitivity of A549/DDP cells to DDP was significantly elevated. The apoptotic ratio induced by DDP was significantly increased. Expression of Bcl-2 was greatly down-regulated but the expression of Bax had little change. Conclusion: Silencing MT1H gene with MT1H siRNA reduces the expression of Bcl-2, enhanced the apoptosis-inducing effect of DDP on A549/DDP cells, and effectively reverses the drug resistance of A549/DDP cells.