Yongan Zhou

The role of microRNA in human lung squamous cell carcinoma

MicroRNAs (miRNAs) are a group of small noncoding RNAs with modulator activity of gene expression. Deregulation of miRNA genes was found in several types of cancers. To explore the role of the miRNAs in Chinese lung squamous cell carcinoma (SCC), the expression profile of 711 miRNAs in SCC was analyzed. Total RNAs were used for hybridization on a commercially available array (miRCURY LNA array v.10.0), which contains 1,200 probes in tetramer, corresponding to 711 human miRNA genes. The results of miRNA microarray analysis were confirmed with quantitative real-time polymerase chain reaction. Seven human miRNAs (miR-126, miR-193a-3p, miR-30d, miR-30a, miR-101, let-7i, and miR-15a) were found to be significantly downregulated in lung SCC (P < 0.05), compared with normal lung tissues. The miRNAs miR-185 * and miR-125a-5p were significantly upregulated in lung SCC (P < 0.05), compared with normal lung tissues. The miRNA let-7i was downregulated in 9 of the 20 SCC samples, and miR-126 was downregulated in 16 of 20. The deregulation of some miRNAs in lung SCC suggests their possible involvement in the development and progression of SCC.

Repair of massive stent-induced tracheoesophageal fistula.

OBJECTIVE The purpose of this report was to discuss a new surgical procedure in treating esophageal stent related large tracheoesophageal fistula without tracheal resection. METHODS Clinical records of 5 patients with esophageal stent-related large tracheoesophageal fistulas treated in this hospital between 1997 and 2006 were reviewed. RESULT All patients had insertion of a covered self-expanding esophageal stent, 1 for benign esophageal stricture and 4 for esophageal perforation resulting from various causes. A double patch technique, in which the esophageal wall was used as a protective patch repairing the defect on the trachea, was performed with an esophagectomy and gastric replacement. No significant complications occurred in the perioperative period. All patients recovered uneventfully. CONCLUSIONS Use of the adjacent esophageal wall as a patch to close a defect on the trachea is a safe procedure with a favorable outcome. It should therefore be recommended as a reliable surgical procedure in treating massive stent-induced tracheoesophageal fistulas and other complicated tracheoesophageal fistulas that tracheal resection could not safely address. However, the esophagus was damaged to a certain degree.

Upregulated fascin1 in non-small cell lung cancer promotes the migration and invasiveness, but not proliferation

Fascin1, an actin-binding protein, is overexpressed in many kinds of tumors. However, its exact role in non-small cell lung cancer (NSCLC) is still unclear. We observed that expression of fascin1 was associated with lymph nodes metastasis and TNM staging but not proliferation in NSCLC by using immunohistochemistry. By generating A549 lung cancer clones stably overexpressing different fascin1 protein, we further confirmed that fascin1 could promote A549 cell migration and invasiveness in vitro and in vivo. Using cell proliferation assay, cell cycle analysis in vitro and tumorigenicity assay in vivo, we showed that fascin1 had little influence on proliferation in A549 cells. These results suggest that fascin1 plays a significant role in NSCLC metastasis and may be a target of intervening to prevent the metastasis of NSCLC.

Intraoperative recurrent laryngeal nerve monitoring: a useful method for patients with esophageal cancer

It is well accepted that recurrent laryngeal nerve paralysis is a severe complication of esophagectomy or lymphadenectomy performed adjacent to the recurrent laryngeal nerves. Herein, determination of the effectiveness of implementing continuous recurrent laryngeal nerve monitoring to reduce the incidence of recurrent laryngeal nerve paralysis after esophagectomy was sought. A total of 115 patients diagnosed with esophageal cancer were enrolled in the thoracic section of the Tangdu Hospital of the Fourth Military Medical University from April 2008 to April 2009. Clinical parameters of patients, the morbidity, and the mortality following esophageal resection were recorded and compared. After the surgery, a 2-year follow up was completed. It was found that recurrent laryngeal nerve paralysis and postoperative pneumonia were more frequently diagnosed in the patients that did not receive continuous recurrent laryngeal nerve monitoring (6/61 vs. 0/54). Furthermore, positive mediastinal lymph nodes (P = 0.015), total mediastinal lymph nodes (P < 0.001), positive total lymph nodes (P = 0.027), and total lymph nodes (P < 0.001) were more often surgically removed in the patients with continuous recurrent laryngeal nerve monitoring. These patients also had a higher 2-year survival rate (P = 0.038) after surgery. It was concluded that continuous intraoperative recurrent laryngeal nerve monitoring is technically safe and effectively identifies the recurrent laryngeal nerves. This may be a helpful method for decreasing the incidence of recurrent laryngeal nerve paralysis and postoperative pneumonia, and for improving the efficiency of lymphadenectomy.

Our experience on management of Boerhaave's syndrome with late presentation

A retrospective review of 18 patients treated for Boerhaaves syndrome in our center from 1954 to 2006 was undertaken. The patients were divided into two groups: group 1, the time delayed before treatment was less than 24 hours; group 2, the time delayed was more than 24 hours. The time interval between perforation and the onset of treatment in group 2 was from 50 hours to 30 days. Roentgenograms of the chest and esophagogram with a water-soluble contrast medium are able to reveal the perforation in most cases, and thoracentesis or thoracic drainage after swallow methylene blue may provide help as well. Surgical intervention was adopted in all three patients in group 1 and 12 in group 2, and conservative intervention in three in group 2. In group 1, two patients recovered uneventfully, the other one developed a postoperative respiratory infection, and he recovered after the infection was controlled. The mortality in group 2 was 33.3% (5/15), and the mortality in patients with conservative intervention was 100% (3/3). Five complications occurred after surgical intervention in group 2, including four fistulae and one incision infection. In conclusion, it may be appropriate to manage patients aggressively with primary repair and adequate mediastinal and pleural drainage when patients present late. Because of the syndromes initial severity and a tendency to postoperative complications, patients should be closely monitored, and correct antibiotic therapy and adequate nutrition are very important in treatment.

The Adenovirus-Mediated Transfer of PTEN Inhibits the Growth of Esophageal Cancer Cells in Vitro and in Vivo

The development and progression of esophageal cancer is associated with multiple alterations in the genome, including loss of the tumor suppressor phosphatase and tensin homolog deleted from the chromosome 10 (PTEN) gene. The purpose of this study was to determine the effects of adenovirus-mediated MMAC/PTEN expression on the growth and survival of human esophageal cancer cells in vitro and in vivo. We found that compared to control cells, overexpression of PTEN significantly suppressed growth and induced apoptosis in esophageal cancer cell lines Eca-109 and TE-1 via downregulation of Bcl-2 expression and changes in cell-cycle progression. Adenovirus PTEN also inhibited the growth of subcutaneous tumor xenografts by significantly reducing tumor size in vivo. Thus our results confirm the proposed functional role of MMAC/PTEN as a regulator of esophageal cancer progression in vivo and in vitro. PTEN might be an important biological marker and potential therapeutic target in the treatment of human esophageal cancer.

Activation of endoplasmic reticulum stress is involved in the activity of icariin against human lung adenocarcinoma cells

In this study, we investigated the anticancer activity of icariin (ICA) against human lung adenocarcinoma cells in vitro and in vivo and explored the role of endoplasmic reticulum (ER) stress (ERS) signaling in this process. ICA treatment resulted in a dose- and time-dependent decrease in the viability of human lung adenocarcinoma A549 cells. Additionally, ICA exhibited potent anticancer activity, as evidenced by reductions in A549 cell adhesion, migration and intracellular glutathione (GSH) levels and increases in the apoptotic index, Caspase 3 activity, and reactive oxygen species. Furthermore, ICA treatment increased the expression of ERS-related molecules (p-PERK, ATF6, GRP78, p-eIF2α, and CHOP), up-regulated the apoptosis-related protein PUMA and down-regulated the anti-apoptosis-related protein Bcl2. The down-regulation of ERS signaling using PERK siRNA desensitized lung adenocarcinoma cells to ICA treatment, whereas the up-regulation of ERS signaling using thapsigargin (THA) sensitized lung adenocarcinoma cells to ICA treatment. Additionally, ICA inhibited the growth of human lung adenocarcinoma A549 cell xenografts by increasing the expression of ERS-related molecules (p-PERK and CHOP), up-regulating PUMA, and down-regulating Bcl2. These data indicate that ICA is a potential inhibitor of lung adenocarcinoma cell growth by targeting ERS signaling and suggest that the activation of ERS signaling may represent a novel therapeutic intervention for lung adenocarcinoma.

Pulmonary Resident Neutrophils Regulate the Production of GM-CSF and Alveolar Macrophages

Alveolar macrophages exist in the lung airspaces, and their differentiation and function are considerably regulated by the microenvironment. In this study, we examine the important role of resident neutrophil/IL‐23/granulocyte/macrophage colony‐stimulating factor (GM‐CSF) axis in the development and preferential phenotype of alveolar macrophages under physiological conditions. Using CD18‐deficient (CD18−/−) mice, we show a correlation between increased granulopoiesis and enhanced alveolar macrophage development in an IL‐23‐ and GM‐CSF‐dependent manner. The apoptotic neutrophils could inhibit the secretion of IL‐23 from alveolar macrophages, which is important for the production of GM‐CSF, and depletion of neutrophils disrupted the regulation of IL‐23 and GM‐CSF. This study reveals a mechanism for the regulation of the local alveolar macrophage population and function by neutrophil apoptosis in the circulatory system.

High ABCG4 Expression Is Associated with Poor Prognosis in Non-Small-Cell Lung Cancer Patients Treated with Cisplatin-Based Chemotherapy

ATP-binding cassette (ABC) transporters are associated with poor response to chemotherapy, and confer a poor prognosis in various malignancies. However, the association between the expression of the ABC sub-family G member 4 (ABCG4) and prognosis in patients with non-small-cell lung cancer (NSCLC) remains unclear. NSCLC tissue samples (n = 140) and normal lung tissue samples (n = 90) were resected from patients with stage II to IV NSCLC between May 2004 and May 2009. ABCG4 mRNA and protein expressions were detected by RT-PCR, western blot, and immunohistochemistry. Patients received four cycles of cisplatin-based post-surgery chemotherapy and were followed up until May 31st, 2014. ABCG4 positivity rate was higher in NSCLC than in normal lung tissues (48.6% vs. 0%, P<0.001) and ABCG4 expression was significantly associated with poor differentiation, higher tumor node metastasis (TNM) stage, and adenocarcinoma histological type (all P<0.001). Univariate (HR = 2.284, 95%CI: 1.570–3.324, P<0.001) and multivariate (HR = 2.236, 95%CI: 1.505–3.321, P<0.001) analyses showed that ABCG4 expression was an independent factor associated with a poor prognosis in NSCLC. Patients with ABCG4-positive NSCLC had shorter median survival than ABCG4-negative NSCLC (20.1 vs. 43.2 months, P<0.001). The prognostic significance of ABCG4 expression was apparent in stages III and IV NSCLC. In conclusion, high ABCG4 expression was associated with a poor prognosis in patients with NSCLC treated with cisplatin-based chemotherapy.