Beclin 1 expression is associated with the occurrence and development of esophageal squamous cell carcinoma.

Beclin 1 has a central role in the regulation of autophagy, differentiation, apoptosis resistance, tumorigenesis and cancer progression. The role of Beclin 1 in the development of esophageal squamous cell carcinoma (ESCC) and its subsequent progression is not fully characterized. In the present study, the role of Beclin 1 and autophagy in ESCC was evaluated. The expression of Beclin 1 mRNA and protein levels in human ESCC tumor and adjacent normal esophageal tissue was measured. Beclin 1 mRNA and protein were significantly lower in tumor tissue than in normal esophageal tissue (P<0.05). Cells of the less differentiated esophageal tumors expressed lower Beclin 1 mRNA and protein (P<0.05). Tumors from patients in early clinical stages (I/II) exhibited significantly higher Beclin 1 mRNA and protein expression levels than patients with tumors in mid-to-late stages (III/IV; P<0.05). Tumors from patients with lymph node metastasis exhibited significantly lower Beclin 1 mRNA and protein expression levels compared with tumors from patients without lymph node involvement (P<0.05). Beclin 1 downregulation was demonstrated to significantly upregulate invasion by ESCC EC9706 cells (P<0.01), and downregulate the number of acidic vesicular organelles, a process associated with autophagy. These results suggest that the expression of Beclin 1 is associated with the occurrence and development of ESCC. Measuring the Beclin 1 expression of tumors from patient may improve the understanding of the prognosis of patients with ESCC.

Rituximab effectively reverses Tyrosine kinase inhibitors (TKIs) resistance through inhibiting the accumulation of rictor on mitochondria-associated ER-membrane (MAM).

Tyrosine kinase inhibitors (TKIs), a novel group of target-specific anti lung cancer drugs, have recently been found to resistant to some NSCLC cells which have the T790M EGFR mutation. However, recent investigations on the therapies of resistance to EGFR-TKIs are very limited. Therefore, it is important to develop more effective therapies to reverse EGFR-TKIs resistance. In our present study, erlotinib was used as the TKIs drug and the effects of the erlotinib on cell growth were evaluated. Cell viability and concentration dependent studies were performed using HCI-H1975 and HCI-H1299 cells alone with erlotinib, respectively. Further combined with rituximab, the results showed that erlotinib and rituximab were significantly inhibited the cell growth. Furthermore, the combination of erlotinib and rituximab greatly decreased the expression of p-mTOR and p-EGFR. Additional results from western blotting and immunofluorescence assays demonstrated that the accumulation of rictor was also decreased on MAM. Thus, all these results suggested that EGFR-TKIs combined with CD20 mono-antibody significantly decrease the cell growth of H1975 cells and H1299, with T790M EGFR mutation, and inhibit the localization of the key mTOR pathway proteins to MAM. So, it may be a promising strategy for overcoming EGFR TKI resistance in NSCLC patients.

Primary tracheal schwannoma treated by surgical resection: a case report.

The rarity and non-specific symptoms of benign primary tracheal tumors always leaded to misdiagnosis and delayed treatment, and also undefined the optimal treatment. In this case, a 45-year-old woman had a history of progressive shortness of breath and dry cough for several years, CT scan revealed an intra-luminal tracheal mass invaded the left side of tracheal wall. After being located by bronchoscope preoperatively, the tumor was removed by surgical resection. The tumor was 1.5 cm in diameter with intact capsule. The pathological result confirmed the diagnosis of schwannoma.

Uniportal video-assisted thoracic surgery right upper lobectomy with systemic lymphadenectomy.

This video demonstrated a performance of uniportal video-assisted thoracoscopic surgery (VATS) right upper lobectomy with systemic lymphadenectomy. The patient had a malignant mass in his right upper lobe. The operator took a posterior to anterior approach to dissection the right upper lobe, the adjacent structures were clearly demonstrated after the entire dissection of mediastinal lymph nodes. Postoperative pathological report suggested the stage of the tumor was T1bN0M0 (stage IA).

MiR-25 is up-regulated in non-small cell lung cancer and promotes cell proliferation and motility by targeting FBXW7.

Increasing evidence showed that miR-25 is involved in the carcinogenesis and progression of various human cancers, while its role in non-small cell lung cancer (NSCLC) is still unclear. Here, we found that miR-25 is significantly up-regulated in NSCLC tissue samples and cell lines. Inhibition of miR-25 remarkably suppressed cell proliferation, migration and invasion in NSCLC cells, whereas enforced expression of miR-25 significantly increased NSCLC cells proliferation, migration and invasion. Moreover, we identified F-box and WD repeat domain-containing 7 (FBXW7) as a direct target of miR-25 and overexpression of FBXW7 partially attenuates the oncogenic effect of miR-25 on NSCLC cells. In conclusion, miR-25 is up-regulated in NSCLC and promotes NSCLC cells proliferation and motility partially by targeting FBXW7. Our data suggest that miR-25 might serve as a potential therapeutic target for NSCLC treatment in the future.

Posttranslational modifications of FOXO1 regulate epidermal growth factor receptor tyrosine kinase inhibitor resistance for non-small cell lung cancer cells.

Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are effective clinical therapies for advanced non-small cell lung cancer (NSCLC) patients, while resistance to TKIs remains a serious problem in clinical practice. Recently, it has been proposed that targeting mTOR could overcome TKI resistance in NSCLC cells. Forkhead box class O1 (FOXO1) has emerged as an important rheostat that modulates the activity of Akt and mTOR signaling pathway. However, the role of FOXO1 and related regulatory mechanism in TKI resistance in NSCLC remain largely unknown. Here, we find that mTOR-AKT-FOXO1 signaling cascade is deregulated in TKI-resistant NSCLC cells and that FOXO1 was highly phosphorylated and lowly acetylated upon erlotinib treatment. Combination of mTOR or PI3K inhibitor and erlotinib overcomes TKI resistance to inhibit cell growth and induce apoptosis in TKI-resistant NSCLC cells. Furthermore, the phosphorylation and acetylation of FOXO1 are reversely modulated by mTORC2-AKT signaling pathway. FOXO1 mutation analyses reveal that FOXO1 acetylation inhibits cell proliferation and promotes NSCLC cell apoptosis, while the phosphorylation of FOXO1 plays opposite roles in NSCLC cells. Importantly, increasing FOXO1 acetylation by a HDAC inhibitor, depsipeptide, overcomes TKI resistance to effectively induce TKI-resistant NSCLC cell apoptosis. Together, FOXO1 plays dual roles in TKI resistance through posttranslational modifications in NSCLC and this study provides a possible strategy for treatment of TKI-resistant NSCLC patients.

RAF1-MEK1-ERK/AKT axis may confer NSCLC cell lines resistance to erlotinib.

The fact that advanced NSCLC patients with wild type (wt) EGFR can benefit from erlotinib therapy makes it critical to find out biomarkers for effective selection of patients and improving the therapy effects. In present study, 3 NSCLC cell lines (U1752, Calu-6 and NCI-H292) with wt EGFR and different sensitivities to erlotinib were used for microarray analysis. The differential basal gene expression between 2 NSCLC cell lines was analyzed, about 353 genes were expression-altered with higher than 2-fold changes between Calu-6 and U1752. And Ingenuity Pathway Analysis (IPA) showed that these genes were mainly enriched in regulation of epithelial-mesenchymal transition (EMT) pathway, Wnt-ß catenin signaling, Tec kinase signaling and some types of cancer-related signaling. More interestingly, RAF1 (c-raf), MAP2K1 (MEK1), SNAI and downstream signaling molecules ERK and AKT were predicted to be activated in erlotinib-resistant cell line by IPA. Subsequent immunoblotting experiments showed that the phosphorylation of ERK and AKT were exactly increased stepwise from erlotinib sensitive cell line to erlotinib resistant cell lines. Collectively, activation of RAF1-MEK1-ERK/AKT axis may determine the resistance of NSCLC cell lines bearing wt EGFR to erlotinib. Our work provides potential biomarkers and therapeutic targets for NSCLC patients harboring wt EGFR.