The antidiabetic drug metformin exerts chemopreventive and antineoplastic effects in many types of malignancies. However, the mechanisms responsible for metformin actions appear diverse and may differ in different types of cancer. Understanding the molecular and cellular mechanisms specific for different cancers is important to optimize strategy for metformin treatment in different cancer types. Here, we investigate the in vitro and in vivo effects of metformin on esophageal squamous cell carcinoma (ESCC) cells. Metformin selectively inhibited cell growth in ESCC tumor cells but not immortalized noncancerous esophageal epithelial cells. In addition to apoptosis, metformin triggered autophagy. Pharmacological or genetic inhibition of autophagy sensitized ESCC cells to metformin-induced apoptotic cell death. Mechanistically, signal transducer and activator of transcription 3 (Stat3) and its downstream target Bcl-2 was inactivated by metformin treatment. Accordingly, small interfering RNA (siRNA)-mediated Stat3 knockdown enhanced metformin-induced autophagy and apoptosis, and concomitantly enhanced the inhibitory effect of metformin on cell viability. Similarly, the Bcl-2 proto-oncogene, an inhibitor of both apoptosis and autophagy, was repressed by metformin. Ectopic expression of Bcl-2 protected cells from metformin-mediated autophagy and apoptosis. In vivo, metformin downregulated Stat3 activity and Bcl-2 expression, induced apoptosis and autophagy, and inhibited tumor growth. Together, inactivation of Stat3-Bcl-2 pathway contributes to metformin-induced growth inhibition of ESCC by facilitating crosstalk between apoptosis and autophagy.

We have demonstrated that subclones carrying driver mutations are more prone to release DNA. We have also demonstrated the quantitative ability of capture-based sequencing, paving its way for routine utilization in clinical settings.

Background: Endobronchial ultrasound (EBUS) elastography is a new imaging procedure for describing the elasticity of intrathoracic lesions and providing important additional diagnostic information. Objectives: The aim of this study was to utilize the feasibility of qualitative and quantitative methods to evaluate the ability of EBUS elastography to differentiate between benign and malignant mediastinal and hilar lymph nodes (LNs) during EBUS-guided transbronchial needle aspiration (EBUS-TBNA). Methods: Patients with enlarged intrathoracic LNs required for EBUS-TBNA examination at a clinical center for thoracic medicine from January 2014 to April 2014 were prospectively enrolled. EBUS sonographic characteristics on B-mode, vascular patterns and elastography, EBUS-TBNA procedures, pathological findings, and microbiological results were recorded. Furthermore, elastographic patterns (qualitative method) and the mean gray value inside the region of interest (quantitative method) were analyzed. Both methods were compared with a definitive diagnosis of the involved LNs. Results: Fifty-six patients including 68 LNs (33 benign and 35 malignant nodes) were prospectively enrolled into this study and retrospectively analyzed. Using qualitative and quantitative methods, we were able to differentiate between benign and malignant LNs with high sensitivity, specificity, positive and negative predictive values, and accuracy (85.71, 81.82, 83.33, 84.38, and 83.82% vs. 91.43, 72.73, 78.05, 88.89, and 82.35%, respectively). Conclusions: EBUS elastography is potentially capable of further differentiating between benign and malignant LNs. These proposed qualitative and quantitative methods might be useful tools for describing EBUS elastography during EBUS-TBNA.

Objectives: The most recently discovered cytokine interleukin 37 (IL-37) received growing attention. Its function on tumor is largely unknown. Here, we investigated the biological function of IL-37 on cervical cancer (CC).Materials and methods: HPV+ Hela cells and HPV- C33A cells were used. RT-qPCR was performed to detect the transcription of IL-37, STAT3, TNF-αand IL-1β. Western blotting was used for protein detection. CCK-8 assay and transwell assay were employed for cell proliferation and invasion detection, respectively.Results: Successful gene transfection of IL-37 suppressed the proliferation and invasion of CC. Interestingly, IL-37 showed higher anticancer ability in HPV+ Hela cells than that in HPV- C33A cells. Then, the molecular mechanism of IL-37 anticancer was explored. Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels. IL-37 also down regulated the phosphorylation of STAT3. Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion. Thirdly, STAT3 knockdown reduced markedly the inhibition of IL-37 on the transcription of tumor-derived TNF-α and IL-1β, indicating the contribution of STAT3 for the cancer associated antiinflammation of IL-37. Finally, STAT3 up regulation restored the ability of cell proliferation, cell invasion and the expression of inflammatory cytokines, TNF-α and IL-1β.Conclusions: IL-37 suppressed cell proliferation and invasion of CC and STAT3 is involved in this process. Thus, IL-37 emerges as a new anticancer cytokine for CC. This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment.