Lijia Gu

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.

HiF-1α siRNA and Cisplatin in Combination SuppressTumor Growth in a Nude Mice Model of Esophageal Squamous Cell Carcinoma

INTRODUCTION The esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances, and a current challenge is the development of effective therapeutic agents. Our present work addressed the effect of HIF-1α siRNA alone or in combination with cisplatin on the growth of ESCC in nude mice. MATERIALS AND METHODS Xenografts were established by inoculating ESCC TE-1 cells in nude mice, and transplanted tumors were treated with HIF-1α siRNA, cisplatin alone or together. Growth was assessed by measuring tumor volume. HIF-1α mRNA and protein expression were detected using RT-PCR and immunohistochemistry, respectively. Apoptosis of ESCC TE-1 cells was analyzed by flow cytometry. RESULTS In our nude mice model, HIF-1α siRNA effectively inhibited the growth of transplanted ESCC, downregulating HIF-1α mRNA and protein expression, and inducing ESCC TE-1 cell apoptosis. Notably when combinated with cisplatin, HIF-1α siRNA showed synergistic interaction in suppressing tumor growth. Furthermore, the proportion of apoptotic cells in HIF- 1α siRNA plus cisplatin group was significantly higher than that in cisplatin or HIF-1α siRNA-treated groups (P<0.05). CONCLUSIONS Down-regulated HIF-1α expression induced by siRNA could effectively suppress the growth of transplanted ESCC in vivo. HIF-1α siRNA could enhance the cytotoxicity of cisplatin, which suggests that a combination of these two agents may have potential for therapy of advanced ESCC.

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.

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.

Predictive value of preoperative peripheral lymphocyte count on recurrence of resectable non-small cell lung cancer.

81 Background: Recently, the prognostic value of cancer-related inflammatory response has been revealed. Previous studies showed that peripheral neutrophils and lymphocytes had significant impact on the prognosis of advanced and early node-negative non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic value of preoperative lymphocyte and neutrophil counts in patients with NSCLC who underwent radical surgery and adjuvant chemotherapy. METHODS Retrospective analyses were performed to examine the impact of preoperative peripheral lymphocyte and neutrophil counts on disease-free survival (DFS) and overall survival (OS) and to analyze the relationships of these factors to clinicopathological factors. RESULTS 142 patients with NSCLC were evaluated totally. 57 (40.1%) patients had local recurrence or metastasis. Multivariate analysesrevealed that peripheral lymphocyte count was an independent favorable prognostic factor of DFS (hazard ratio: 0.548; 95% confidence interval: 0.351-0.857; p=0.008) but not OS (p=0.164). The maximum log-rank statistical value was 9.504 (p=0.002) when the cutoff value of lymphocyte was 1800mm-3. The median DFS were 318.0 days (95% confidence interval: 226.0-410.0) for lymphocyte≤1800mm-3 group and 669.0 days (95% confidence interval: 0.0-1431.0) for lymphocyte>1800mm-3 group. Low lymphocyte count was related with lymphatic invasion (p=0.012) and recurrence of NSCLC (p=0.022). Peripheral neutrophil count had no impact on DFS or OS when analysis included all the 142 patients. In addition, T stage (p=0.001), N stage (p=0.001) and vascular invasion (p=0.021) were also independent unfavorable prognostic factors of DFS. Pathological stage (p=0.001), vascular invasion (p=0.011), and ECOG score (p=0.009) were independent unfavorable prognostic factor of OS. CONCLUSIONS Preoperative peripheral lymphocyte count, which is related with lymphatic invasion, is an independent favorable prognostic factor of DFS in patients with NSCLC who underwent radical surgery and adjuvant chemotherapy.