Huiguo Chen

Clostridium butyricum in combination with specific immunotherapy converts antigen-specific B cells to regulatory B cells in asthmatic patients.

The effect of antigen specific immunotherapy (SIT) on asthma is supposed to be improved. Published data indicate that administration of probiotics alleviates allergic diseases. B cells play important roles in the pathogenesis of allergic diseases. This study aims to modulate antigen specific B cell property by the administration of Clostridium butyrate (CB) in combination with SIT. The results showed that after a 3-month treatment, the total asthma clinical score and serum specific IgE were improved in the patients treated with SIT, which was further improved in those treated with both SIT and CB, but not in those treated with CB alone. Treatment with SIT and CB increased p300 and STAT3 activation, up regulated the IL-10 gene transcription and increased the frequency of peripheral antigen specific B cells. In conclusion, administration with SIT in combination with CB converts Der p 1 specific B cells to regulatory B cells in asthma patients allergic to Der p 1. The data suggest a potential therapeutic remedy in the treatment of allergic diseases.

miR-101 represses lung cancer by inhibiting interaction of fibroblasts and cancer cells by down-regulating CXCL12

Cancer-associated fibroblasts (CAFs) are the main component of tumor stroma which support tumor progression. Here, we set out to determine the factors that may be involved in dramatic alteration of microRNAs (miRNAs) expression pattern in CAFs. miRNAs analyses identified differential expression of 15 microRNAs, with miR-101 being the most downregulated miRNA in CAFs which were different from the normal fibroblasts. We examined several putative miR-101 target genes identified by microarray analysis and demonstrated that miR-101 directly targets CXCL12, which play important roles in CAFs. Overexpression of miR-101 significantly impaired the ability of CAFs to stimulate tumor cell proliferation, sphere formation migration and invasion, and enhanced apoptosis. Further research showed that the cellular biological behavior was regulated by miR-101 targeting CXCL12. These findings provide new insights miR-101 down-regulation in CAFs could inhibit lung cancer proliferation and metastasis via targeting CXCL12.

Activation of proteinase-activated receptor 2 prevents apoptosis of lung cancer cells.

The therapeutics of lung cancer (LC) is unsatisfactory. The pathogenesis of LC remains unclear. Protease-activated receptors (PAR) are involved in the immunoregulation. The present study aims to investigate the activation of PAR2 in regulation of the expression of EGFR and apoptosis of LC cells. The results showed that exposure to tryptase increased EGFR expression in A549 cells and suppressed the cell apoptosis. Tryptase also decreased the expression of Bax and increased Bcl-xL levels in A549 cells. We conclude that activation of PAR2 by tryptase can decrease the ratio of Bax/Bcl-xL and reduce the LC cell line, A549 cells, and apoptosis.

Relapsing suppurative neck abscess after chemocauterization of pyriform sinus fistula

We report a case of relapsing suppurative neck abscess due to a pyriform sinus fistula ever treated by chemocauterization. Pyriform sinus fistula is rare, and chemocauterization is an alternative microinvasive procedure. This case indicates that the possibility of recurrence following management of chemocauterization exists even after a long time and that clinical radiological assessments are necessary.

Maintenance erlotinib improves clinical outcomes of unresectable advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials.

The aim of this study was to evaluate the efficacy and safety of erlotinib as maintenance therapy in patients with unresectable non-small cell lung cancer (NSCLC) by evidence-based methodology. Six eligible studies including 4,372 patients were analyzed. Erlotinib was administered to 2,191 patients as maintenance treatment, while the remaining patients received a placebo or observation only. The meta-analysis was performed using Reviewer Manager Version 5.12 software. Compared with the control group, maintenance erlotinib improved progression-free survival (PFS) and overall survival (OS) with moderate heterogeneity. Results from the random effects model analysis for OS were not in concordance with the difference observed in the fixed effects model analysis. Administration of erlotinib only after chemotherapy obtained a higher objective response rate (ORR). Safety analyses indicated a slight increase in side-effects. The most common adverse events (AEs) were diarrhea and rash, which were usually manageable. There was no significant difference in treatment-related deaths. Erlotinib produced significant clinical benefits with acceptable toxicity as a maintenance strategy in patients with unresectable NSCLC, particularly when sequentially administered with chemotherapy. However, more well-designed randomized control trials (RCTs) are required to identify patients that may derive greater benefits from maintenance with erlotinib, and whether the use of erlotinib as maintenance therapy is more efficient than second-line treatment should also be investigated.

The impact of histological types on the efficacy of angiogenesis inhibitors in the treatment of advanced NSCLC: a meta-analysis of randomized controlled trials.

Purpose We aimed at assessing the overall efficacy of angiogenesis inhibitor (AI)-containing regimens in the treatment of advanced non-small-cell lung cancer (NSCLC) according to histological types. Methods Studies from PubMed and Web of Science, and abstracts presented at American Society of Clinical Oncology (ASCO) meeting up to October 31, 2014 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials (RCTs) evaluating AIs in advanced NSCLC with survival data according to patients’ histologies. The endpoints were overall survival (OS) and progression-free survival (PFS). Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. Results A total of 10,035 patients with advanced NSCLC from 13 RCTs were identified for analysis. The pooled results demonstrated that AI-containing regimens significantly improved the PFS (HR, 0.84, 95% confidence interval (CI): 0.78–0.91, P<0.001) and OS (HR, 0.92, 95% CI: 0.85–0.99, P=0.017) in lung adenocarcinoma when compared to non-AI-containing regimens. Additionally, there was a significantly improved PFS (HR, 0.87, 95% CI: 0.77–0.98, P=0.027) for AI-containing regimens in squamous cell lung carcinoma, but it did not translated into OS benefit (HR, 1.02, 95% CI: 0.92–1.15, P=0.68). For NSCLC patients with other histological types, the use of AIs did not significantly improve PFS (HR, 0.90, 95% CI: 0.75–1.09, P=0.27) and OS (HR, 0.90, 95% CI: 0.76–1.08, P=0.19). Conclusion The findings of this study suggest that the addition of AIs to the treatment therapies for patients with lung adenocarcinoma offers improved survival benefits. Prospective clinical trials investigating the role of AIs in this setting are recommended.

Airway epithelial cell-derived insulin-like growth factor-1 triggers skewed CD8+ T cell polarization

Skewed CD8+ T cell responses are important in airway inflammation. This study investigates the role of the airway epithelial cell‐derived insulin‐like growth factor 1 (IGF1) in contributing to CD8+ T cell polarization. Expression of IGF1 in the airway epithelial cell line, RPMI2650 cells, was assessed by quantitative real time RT‐PCR and Western blotting. The role of IGF1 in regulating CD8+ T cell activation was observed by coculture of mite allergen‐primed RPMI2650 cells and naïve CD8+ T cells. CD8+ T cell polarization was assessed by the carboxyfluorescein succinimidyl ester‐dilution assay and the determination of cytotoxic cytokine levels in the culture medium. Exposure to mite allergen, Der p1, increased the expression of IGF1 by RPMI2650 cells. The epithelial cell‐derived IGF1 prevented the activation‐induced cell death by inducing the p53 gene hypermethylation. Mite allergen‐primed RPMI2650 cells induced an antigen‐specific CD8+ T cell polarization. We conclude that mite allergens induce airway epithelial cell line, RPMI2650 cells, to produce IGF1; the latter contributes to antigen‐specific CD8+ T cell polarization.

Micro RNA-98 interferes with expression interleukin-10 in peripheral B cells of patients with lung cancer

Interleukin (IL)-10-producing B cells (B10 cells) plays an important role in the tumor tolerance. High frequency of peripheral B10 cell was reported in patients with lung cancer recently. Micro RNA (miR) regulates some gene expression. This study test a hypothesis that miR-98 suppresses the expression of IL-10 in B cells of subjects with lung cancer. The results showed that the levels of miR-98 were significantly less in peripheral B cells of patients with lung cancer than that in healthy subjects. IL-10 mRNA levels in peripheral B cells were significantly higher in lung cancer patients as compared with healthy controls. A negative correlation was identified between miR-98 and IL-10 in peripheral B cells. Serum IL-13 was higher in lung cancer patients than that in healthy controls. The levels of IL-13 were also negatively correlated with IL-10 in B cells. Exposure B10 cells to IL-13 in the culture or over expression of miR-98 reduced the expression of IL-10 in B cells. Administration with miR-98-laden liposomes inhibited the lung cancer growth in a mouse model. In conclusion, up regulation of miR-98 inhibits the expression of IL-10 in B cells, which may contribute to inhibit the lung cancer tolerance in the body.

Specific immunotherapy generates CD8+ CD196+ T cells to suppress lung cancer growth in mice

That specific immunotherapy can inhibit cancer growth has been recognized; its efficiency is to be improved. This study aimed to inhibit lung cancer (LC) growth in a mouse model by using an LC-specific vaccination. In this study, a LC mouse model was created by adoptive transplantation with LC cells. The tumor-bearing mice were vaccinated with LC cell extracts plus adjuvant TNBS or adoptive transplantation with specific CD8+ CD196+ T cells. The results showed that the vaccination with LC extracts (LCE)/TNBS markedly inhibited the LC growth and induced CD8+ CD196+ T cells in LC tissue and the spleen. These CD8+ CD196+ T cells proliferated and produce high levels of perforin upon exposure to LCE and specifically induced LC cell apoptosis. Exposure to TNBS induced RAW264.7 cells to produce macrophage inflammatory protein-3α; the latter activated signal transducer and activator of transcription 3 and further induced perforin expression in the CD8+ CD196+ T cells. Adoptive transfer with specific CD8+ CD196+ T cells suppressed LC growth in mice. In conclusion, immunization with LC extracts and TNBS can induce LC-specific CD8+ CD196+ T cells in LC-bearing mice and inhibit LC growth.