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Objective:To evaluate the effect of surgical resection on the prognosis of patients with China Liver Cancer Staging (CNLC)-Ⅱ hepatocellular carcinoma.Methods:Patients with CNLC-Ⅱ hepatocellular carcinoma between 2004 and 2015 from the SEER database were included. A total of 3 764 patients were enrolled, with the age (64±11)(18-93) years, including 2 935 males and 829 females. Among them, 2 825 patients underwent non-surgery treatment (NST), 510 patients underwent liver resection (LR), and 429 patients underwent local ablation (LA). The effects of different treatment modalities on overall survival (OS) and cancer-specific survival (CSS) were evaluated by using Kaplan-Meier analysis, propensity score matching analysis, and subgroup analysis. Cox regression were used to analyze the prognosis.Results:The 1-, 3- and 5-year overall survival rates of LR group were 76.3%, 51.9% and 34.0% respectively, which were significantly higher than those in LA group (71.7%, 34.8% and 24.9%, χ 2=18.50, P<0.001), and those in NST group (46.8%, 16.1% and 8.4%, χ 2=276.00, P<0.001). Similarly, the 1-, 3-, and 5-year cancer-related survival rates of LR group were 80.2%, 58.9%, and 41.8% respectively, which were significantly higher than those in LA group (75.9%, 42.8%, and 32.6%, χ 2=15.20, P<0.001), and those in NST group (52.3%, 21.5% and 12.7%, χ 2=245.00, P<0.001). Cox regression analysis showed that age, tumor size, chemotherapy, pathological grade, AFP levels, and surgical modalities were independent prognostic factors (all P<0.05). Propensity score matching analysis further showed that the prognosis of LR patients was significantly better than NST group [median OS: 52 months (95% CI: 38-60) vs. 10 months (95% CI: 7-16), P<0.001; median CSS: 59 months (95% CI: 44-77) vs. 11 months (95% CI: 8-18), P<0.001]. However, subgroup analysis showed no clinical benefit from surgical resection when the tumor size exceeded 10.0 cm. Conclusions:It was suggested that surgical resection could improve the OS and CSS of patients with CNLC-Ⅱ hepatocellular carcinoma.
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Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.