Bifidobacterium infantis Induces Protective Colonic PD-L1 and Foxp3 Regulatory T Cells in an Acute Murine Experimental Model of Inflammatory Bowel Disease

BACKGROUND/AIMS: The current study aims to investigate the protective effects of Bifidobacterium infantis on the abnormal immune response to inflammatory bowel disease (IBD) in dextran sodium sulfate (DSS)-induced colitis. METHODS: Eight-week-old BALB/c mice were separated into five groups at random (control, DSS, DSS+B9 [B. infantis 1×10⁹ CFU], DSS+B8 [B. infantis 1×10⁸ CFU], and DSS+B7 [B. infantis 1×10⁷ CFU]). Colitis was induced by 5% DSS ad libitum for 7 days, at which time we assessed weight, the disease activity index (DAI) score, and the histological damage score. The nuclear transcription factor Foxp3 (a marker of Treg cells), cytokines interleukin-10 (IL-10) and transforming growth factor β1 (TGF-β1), and related proteins (programmed cell death ligand 1 [PD-L1] and programmed cell death 1 [PD-1]) were detected by an immunohistochemical method and Western blot. RESULTS: B. infantis increased weight, decreased DAI scores and histological damage scores, increased the protein expression of Foxp3 (p<0.05) and cytokines IL-10 and TGF-β1 in mouse colon tissue (p<0.05), and increased the expression of PD-L1 in the treatment groups relative to that in the DSS group (p<0.05). The effect of B. infantis on Foxp3 and PD-L1 was dose dependent in the treatment groups (p<0.05). PD-L1 was positively correlated with Foxp3, IL-10, and TGF-β1. CONCLUSIONS: In a mouse model of IBD, B. infantis can alleviate intestinal epithelial injury and maintain intestinal immune tolerance and thus may have potential therapeutic value for the treatment of immune damage in IBD.

Analysis on the relationship of epidermal growth factor receptor gene mutation with gene copy number in lung adenocarcinoma / 肿瘤研究与临床

Objective To detect epidermal growth factor receptor (EGFR) 19, 21 exon gene mutation and gene copy number in lung adenocarcinoma tissue, and to analyze the relationship of EGFR 19, 21 mutation with copies number. MethodsEGFR mutations and gene copy number in the tissue samples embedded by paraffin and fixed by for marlin from 58 cases of lung adenocarcinoma were detected by RT-PCR and FISH. The statistical data were analyzed by chi-square test.ResultsOf 58 cases, the overall single mutation rate of EGFR exon 19, 21 was 43.1% (25/58), and 2 cases contained both types of the mutation.The overall FISH positive rate of EGFR was 51.7 % (30/58), including 8 positive amplification and 22 highly ploidy amplification. The testing results showed that there had no statistically differences in FISH positive rates of EGFR mutation among different differentiation lung adenocarcinoma tissues(P ＞0.05), and the FISH positive rates of EGFR mutation in poorly differentiated cancer were lower than those in moderatedly differentiated and well-differentiated cancer (P ＜0.05). EGFR mutation was closely related to EGFR gene copies (P ＜0.01). ConclusionThere are high EGFR mutation frequencies and FISH positive rates in lung adenocarcinoma tissue; Combined detection of EGFR mutation and gene copy number may provide a better approach in selecting patients who may benefit from anti-EGFR target therapy.

Effect of radiotherapy on cell apoptosis and FHIT gene expression of cervical squamous carcinoma cells / 肿瘤

Objective:To explore the effect of radiotherapy on the FHIT protein expression and cell apoptosis of cervical squamous carcinoma and discuss the relationship between FHIT protein expression and cell apoptosis. Methods:Expression of FHIT protein was measured by immunohistochemical method and cell apoptosis was detected by TdT-mediated dUTP terminal nick end labeling (TUNEL) staining in 50 cases of squamous cell cervical carcinoma at ⅡB-ⅢB stages before, during (Dt 10 Gy and Dt 30 Gy), and after radiotherapy. Results:Of the 50 patients, the positive rates of the expression of FHIT protein was 56% at Dt 10 Gy, 68% at Dt 30 Gy, and 84% after radiotherapy, which were significantly increased compared with that before radiotherapy (36%, P<0.05). The positive rates of cell apoptosis was 52% at Dt 10 Gy, 64% at Dt 30 Gy and 78% after radiotherapy, which were significantly elevated compared with that before radiotherapy (28%, P<0.05). In the process of radiotherapy, cell apoptosis was positively related to the expression of FHIT protein (P<0.05). Conclusion:Radiotherapy reinforces the expression of FHIT protein and induces apoptosis cocurrently. FHIT protein has regulatory effects in cell apoptosis induced by radiotherapy.

Research on DNA methylation in 5′CpG island of P16 gene and P16 expression in primary breast cancer and benign breast lesions / 重庆医科大学学报

Objective: To examine the involvement of methylation of p16 gene on the p16 status and tumor progression in primary breast cancer and the role of p16 protein in primary breast cancer.Methods: DNA was extracted from 45 cases of primary breast carcinomas and 15 cases of benign breast lesions.Polymerase chain reaction(PCR),using the extracted DNA and methylation-sensitive restriction enzymes(HpaⅡ?SacⅡ),was performed to detect the methylation of 5′CpG island in the p16 gene.The results were compared with the P16 expression by immunostaining.Results:(1) p16 was overexpressed in breast cancer.With the increase of histological grade of breast carcinomas,p16 expression decreased.In addition,the low expression of p16 in primary breast cancer was associated with tumor size and lymph node involvement.(2) Methylation of the CpG island of the p16 gene was inversely correlated with p16 expression in a subset of the primary breast carcinomas.With the increase of histological grade of breast carcinomas,DNA methylation was enhanced.Conclusion:Methylation of p16 gene may be the cause of loss of p16 expression.