1.Effects of galectin-3 on growth, migration and inflammation of endothe-lial cells
Lin ZHONG ; Pingping LIANG ; Lei GONG ; Jiahui WANG ; Yujie ZHU ; Zerun LIN ; Jun YANG
Chinese Journal of Pathophysiology 2017;33(6):1065-1072
AIM:To explore the effects of galectin-3 (GAL-3) on the viability, migration and inflammation of human umbilical vein endothelial cells (HUVECs) and the mechanisms.METHODS:The HUVECs were cultured in vitro and treated with GAL-3 recombinant protein at 2 mg/L or GAL-3 short hairpin RNA (shRNA).The HUVECs were divided into normal group, recombinant GAL-3 group, shControl group and GAL-3-shRNA group.The mRNA expression of GAL-3, monocyte chemotactic protein (MCP)-1, IL-6, matrix metalloproteinase (MMP)-9 and cyclin D1 was detected by real-time quantitative PCR,and the protein expression of GAL-3, IL-6 and MCP-1 was detected by Western blot.The secretion levels of MCP-1 and IL-6 in the culture medium were measured by ELISA.The viability and the ability of migration of the HUVECs were examined by CCK-8 assay and wound healing assay.The protein levels of heat shock protein 90 (HSP90), ERK1/2, p-ERK1/2, JNK and p-JNK were determined by Western blot.RESULTS:The expression of GAL-3, MCP-1 and IL-6 at mRNA and protein levels, the mRNA expression of MMP-9 and cyclin D1, and the secretion levels of MCP-1 and IL-6 in the culture medium were significantly higher than those in normal group (P<0.05) after the HUVECs were treated with GAL-3 recombinant protein.However, these molecules mentioned above in GAL-3-shRNA group were significantly lower than those in normal group and negative control group (P<0.05).Compared with normal group, the viability and migration ability of the HUVECs in recombinant GAL-3 group were significantly increased, but the viability and migration ability of the HUVECs in GAL-3-shRNA group were lower than those in normal group and shControl group (P<0.05).In addition, the protein levels of p-ERK1/2 and HSP90 in recombinant GAL-3 group were higher than those in normal group (P<0.05), but those in GAL-3-shRNA group were lower than those in normal group and shControl group (P<0.05).The protein level of p-JNK was not oviously changed among the 4 groups.CONCLUSION:GAL-3 is involved in regulating the cell growth, migration and the release of inflammatory cytokines in vascular endothelial cells, which may be mediated by HSP90-ERK1/2 signaling pathway.
2.Application of tumor burden score in predicting recurrence after radical resection of HCC
Jianda YU ; Zhijian CHEN ; Zerun LIN ; Hanyin HONG ; Xiaobin CHI ; Jianwei CHEN ; Yongbiao CHEN
Chinese Journal of Hepatobiliary Surgery 2024;30(10):727-732
Objective:To study the predictive role of tumor burden score (TBS) for tumor recurrence after radical resection in patients with hepatocellular carcinoma (HCC).Methods:Clinical data of 202 patients with HCC undergoing radical surgery at the 900th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army, between January 2015 and December 2017 were retrospectively analyzed, including 128 males and 74 females, aged (53.66±11.93) years old. The receiver operating characteristic (ROC) curve was used to assess the accuracy of TBS in predicting postoperative tumor recurrence. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors influencing postoperative tumor recurrence. A nomogram was established and validated using calibration curves and the C-index. Kaplan-Meier survival analysis was utilized to compare survival differences between the two patient groups.Results:The area under the ROC curve for TBS in predicting postoperative tumor recurrence in HCC patients was 0.779 (95% CI: 0.717-0.842), with an optimal cutoff value of 6.2. Univariate analysis revealed that factors such as hepatitis B virus DNA level >500 IU/ml, larger maximum tumor dia-meter, and TBS>6.2 were significant risk factors for postoperative tumor recurrence (all P<0.05). Multivariate analysis further indicated that TBS>6.2 ( OR=3.60, 95% CI: 1.081-12.012, P=0.037) and maximum tumor diameter ( OR=1.240, 95% CI: 1.034-1.487, P=0.020) were independent risk factors for postoperative recurrence. Based on these risk factors, a nomogram model was established, achieving a C-index of 0.788. Kaplan-Meier survival analysis showed a better postoperative overall survival and recurrence-free survival of the low TBS group compared to those of the high TBS group (all P<0.05). Conclusion:TBS can serve as a predictive indicator for the recurrence after radical resection in patients with HCC. Both TBS and tumor size are independent risk factors for postoperative recurrence. The nomogram model can be used for predicting recurrence following radical resection in HCC patients.