Progress in Application of TNF-α Inhibitors in Immune Checkpoint Therapy / 肿瘤防治研究

Immune checkpoint inhibitors significantly improves the prognosis of patients with advanced malignancy, but it is also associated with off-target toxicity caused by activation of the immune system, known as immune-related adverse events (irAEs). Severe irAEs will lead to temporary or permanent termination of immunotherapy, which greatly affects its clinical application. At present, glucocorticoids are mainly used to treat irAEs clinically. On one hand, severe adverse reactions will cause serious damage to patients' health; on the other hand, the extensive application of glucocorticoids will affect the efficacy of immune checkpoint inhibitors. In recent years, TNF-α inhibitors have shown significant effect in reducing toxic and side effects. This paper reviews the progress of TNF-α in preventing and treating irAEs.

Relationship between expression of glucose transporter 1 and clinicopathological features and prognosis of patients with gastric cancer: a Meta-analysis / 肿瘤研究与临床

Objective To investigate the expression of glucose transporters 1 (GLUT-1) in gastric cancer and its relation with clinicopathological characteristics and prognosis. Methods PubMed, Web of Science,EMbase,Cochrane Library,WanFang Databases and China National Knowledge Internet(CNKI)were used to search literatures about GLUT-1 and gastric cancer. From the day of establishment to May 15, 2017, according to the inclusion and exclusion criteria, 2 researchers independently screened studies, extracted data and assessed quality of the included studies. Effect value and 95 % CI was calculated respectively. Then Meta-analysis was conducted by using RevMan5.3 software. Results A total of 11 articles were enrolled, including 1 714 cases in the gastric cancer group and 431 cases in the normal gastric mucosa group. The results of Meta-analysis showed that GLUT-1 expression was higher in the gastric cancer group than that in the normal group, and there was a significant difference (OR= 24.23, 95 % CI 11.86-49.51, P< 0.000 01). The expression of GLUT-1 was not related with age, gender, tumor size and invasion depth (all P> 0.05), but related with differentiated degree (OR= 0.41, 95 % CI 0.25-0.67, P= 0.000 4), lymphatic metastasis (OR=5.11, 95 % CI 2.73-9.56, P<0.000 1), and TNM staging (OR= 0.32, 95 % CI 0.20-0.51, P< 0.000 01). Moreover, GLUT-1 had a correlation with the overall survival rate of gastric cancer (HR= 1.61, 95 % CI 1.30-1.99, P < 0.000 1). Conclusions GLUT-1 protein expression is higher in gastric cancer tissues than that in normal gastric mucosa, and it is related to tumor differentiation degree, lymph node metastasis, TNM staging.Besides,GLUT-1 may be correlated with poor prognosis of patients with gastric cancer.

Role and mechanism of FOXG1 in invasion and metastasis of colorectal cancer / 生物工程学报

This study was aimed to investigate the effect of Forkhead Box G1 (FOXG1) on the epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells and the underlying mechanism. For this purpose, FOXG1 lentiviral interference (shRNA) plasmid and expression plasmid were constructed. Western blotting was used to analyze the expression of FOXG1 protein in five CRC cells, namely RKO, SW480, SW620, LoVo and DLD-1. The shRNA fragment of FOXG1 (shFOXG1) was designed and synthesized. Recombinant plasmids were obtained with the aid of DNA recombination technique. Double digestion and sequencing were used to identify the recombinant plasmids, and then lentivirus packaging, purification and stable transfection were carried out. Additionally, stable CRC cell lines were screened out. The changes of FOXG1 knockdown and overexpression efficiency, E-cadherin, Vimentin, Fibronectin, Snail, Twist mRNA and protein were investigated respectively by Western blotting and qRT-PCR analysis. Furthermore, the changes of cell morphology after knockdown and cell migration ability were evaluated respectively with optical microscopy, scratch test and Transwell assay. FOXG1 had the highest protein expression in RKO and the lowest in DLD-1 among the five CRC cells. Compared with those of the control group, the cell morphology in FOXG1 knockdown RKO group was changed from spindle into round or polygonal shape, cell polarization was enhanced and tight junction assembly was acclerated while cell migration distance was noticeably decreased. Moreover, the number of cells invaded and migrated through chambers was significantly reduced. Among these key factors of EMT, the expression of E-cadherin was increased while the expressions of Vimentin, Fibronectin, Snail and Twist were decreased. The opposite was the case in the overexpressed FOXG1 group. The overexpression of FOXG1 in CRC promoted the invasion and metastasis of CRC cells and played a crucial role in regulating the EMT. Thus, FOXG1 might be a novel therapeutic target in CRC treatment.

A bioinformatics analysis of differentially expressed genes associated with liver cancer / 中华肝脏病杂志

Objective@#To investigate differentially expressed genes associated with liver cancer using bioinformatics methods, and to screen out molecular markers for early diagnosis of liver cancer and potential molecular targets for immunotherapy.@*Methods@#The microarray data associated with liver cancer were downloaded from Gene Expression Omnibus. JMP software was used for correlation analysis of GSE datasets, Limma program in R language was used to screen out differentially expressed genes, and the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were performed for differentially expressed genes. A protein-protein interaction (PPI) network was also established for analysis. An analysis of specific expression associated with liver cancer was performed with reference to RNA-seq transcriptome data for other tumors obtained from TCGA to further identify specific differentially expressed genes in liver cancer, and a survival curve analysis was performed for patients with liver cancer.@*Results@#A total of 92 differentially expressed genes were identified, with 21 upregulated genes and 71 downregulated genes. Through the GO, KEGG, and PPI analyses, RNA-seq data verified that only glypican 3 (GPC3) was upregulated in liver cancer, and MBL2, SDS, SLCO1B3, TDO2, SAA4, and SPP2 were downregulated.@*Conclusions@#GPC3 might act as a target for immunotherapy, and other molecular markers may become molecular markers for early detection of liver cancer and potential targets for immunotherapy.

Impacts of Gli1 silencing on cisplatin resistance of lung cancer cell A549/DDP / 中国免疫学杂志

To investigate the role of Gli1 in DDP-resistance in lung cancer.Methods:A DDP-resistant human lung adenocarcinoma cell line A 549/DDP was cultured and transfected with Gli 1 siRNA.The mRNA and protein expression levels of Gli 1 were evaluated by qPT-PCR,Western blot analysis and immunofluorescence microscopy.The expression of Bcl-2、caspases-3、cyclinD1 was evaluated by Western blot analysis.Hoechst 33258 staining and flow cytometry were used to detect spontaneous cell apoptosis and cell cycle.The cell inhibition rate and DDP-induced cell death were examined by MTT and Annexin V-FITC/propidium iodide staining.Results:Gli1-knockdown by using Gli 1-specific siRNA led to a markedly decrease in Gli 1 mRNA and protein expression levels,when compared to negative siRNA transfected cells and untreated control cells (P=0.001).The downstream effectors of Gli1, Bcl-2 and cyclinD1 proteins were also inhibited (P=0.003),the expression of caspase-3 was increased (P=0.001).Hoechst 33258 staining showed that Gli1 depletion by Gli1 siRNA in A549/DDP cells could induce spontaneous apoptosis.The result of cell cycle showed Gli1 siRNA could lead more cells arrest in G1 phase.The IC50 of A549/DDP cells on DDP was (12.63 ±1.11 )μg/ml /(13.81±1.14)μg/ml,which decreased to (2.65±0.85)μg/ml after being transfected with Gli1 siRNA (P=0.000).Annexin V-FITC/propidium iodide staining showed that DDP-induced apoptosis rate in Gli 1-silencing cells was higher than that in negative siRNA or untreated control cells ( 35.19%±3.92% vs 6.43%±0.11%/5.01%±0.77%, P=0.000 ).Conclusion: Application of RNA interference can restrain the expression of Gli 1 mRNA and protein observably in A549/DDP cells,and increase the sensitivity of A549/DDP cells to cisplatin.Maybe Gli1 will become a new target to reverse the cisplatin resistance for lung cancer.