Rac3 regulates cell proliferation through cell cycle pathway and predicts prognosis in lung adenocarcinoma.

Lung cancer is still the leading cause of malignant deaths in the world. It is of great importance to find novel functional genes for the tumorigenesis of lung cancer. We demonstrated that Rac3 could promote cell proliferation and inhibit apoptosis in lung adenocarcinoma cell line A549 previously. The aim of this study was to investigate the function and mechanism of Rac3 in lung adenocarcinoma cell lines. Immunohistochemistry staining was performed in 107 lung adenocarcinoma tissues and matched non-tumor tissues. Multivariate analysis and Kaplan-Meier analysis were used to investigate the correlation between Rac3 expression and the clinical outcomes. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and flow cytometry analysis were employed to determine the proliferative ability, cell cycle distribution, and apoptosis in H1299 and H1975 cell lines. Gene expression microarray and pathway analysis between the Rac3-siRNA group and the control group in A549 cells were performed to investigate the pathways and mechanism of Rac3 regulation. Rac3 was shown to be positively expressed in lung adenocarcinoma tissues, and the expression of Rac3 associates with longer survival in lung adenocarcinoma patients. Silencing of Rac3 significantly induced cell growth inhibition, colony formation decrease, cell cycle arrest, and apoptosis of lung adenocarcinoma cell lines, which accompanied by obvious downregulation of CCND1, MYC, and TFDP1 of cell cycle pathway involving in the tumorigenesis of lung adenocarcinoma based on the gene expression microarray. In conclusion, these findings suggest that Rac3 has the potential of being a therapeutic target for lung adenocarcinoma.

Survival of M1a Non-Small Cell Lung Cancer Treated Surgically: A Retrospective Single-Center Study.

BACKGROUND: Stage IV non-small cell lung cancer (NSCLC) is always associated with a poor outcome and is rarely treated with surgical resection. The aim of this study was to retrospectively analyze the effectiveness of surgical treatments. METHODS: We have retrospectively analyzed the records of NSCLC patients with local thoracic metastatic disease (M1a) who had been treated with surgical resection. The impact on survival of eight variables (age, gender, smoking status, current drinking status, site of metastasis, pathology classifications, resection status, and presence of adjuvant treatment) were further assessed. RESULTS: Eighty patients (49 males, 61%) with a median age of 58 (range, 38-80) were included. Metastatic sites included: pleural nodules with or without effusion metastasis (51, 63.8%), pleural effusion without nodules (7, 8.8%), contralateral lung (9, 11.3%), diaphragm nodules metastasis (5, 6.3%), and pericardium nodules metastasis (8, 10%). Histology was adenocarcinoma in 55, squamous-cell carcinoma in 16, large cell in 5 and other in 4 patients. Types of lung resection performed for primary tumors were complete resection in 43 and limited resection in 37 patients. Survival at 5 years for the overall population reached 31% (95% confidence interval, 19.4-43%). The median overall survival time was 34.3 months. Ten (12.5%) patients survived for more than 5 years. Smoking status and postoperative adjuvant treatment were independent prognostic factors (p = 0.006 and 0.013). There was no impact on survival for the other six variables. CONCLUSION: Surgical treatments in M1a NSCLC seem to be associated with improved survival than published results and might be considered in the management of selected cases. Selected patients, including good performance status and nonsmoking histology, may predict for improved survival in these patients.

Early lung cancer in the elderly: sublobar resection provides equivalent long-term survival in comparison with lobectomy.

AIM OF THE STUDY: The worldwide population shift towards older ages will inevitably lead to more elderly patients being diagnosed with non-small cell lung cancer (NSCLC). It still remains controversial whether sublobar resection is effective in such cases at an early stage. To answer this question, we need to understand the clinical characteristics of these tumors. MATERIAL AND METHODS: From 2004 to 2010, a total of 167 patients with stage I non-small cell lung cancer (NSCLC) of age ≥ 70 years underwent complete resection in our institution. The clinical data were retrospectively analyzed as regards gender, stage of disease, histology, smoking status, smoking amount, drinking status, surgical approaches and overall survival. Survival was analyzed by the Kaplan-Meier method and log-rank test. RESULTS: The overall 5-year survival rate was 62.4%. There were 122 (73.1%) patients who underwent standard lobectomy resection and 45 (26.9%) patients underwent sublobar resection. Patients with different surgical approaches (lobectomy and sublobar resection) had nearly the same 5-year survival rate (60.9% vs. 63.4%, p = 0.558). Gender (p = 0.023), smoking status (p = 0.045) and smoking amount (p = 0.007) significantly influenced the prognosis. CONCLUSIONS: In elderly stage I NSCLC patients, sublobar resection is considered to be an appropriate treatment in comparison with lobectomy, as this procedure provides equivalent long-term survival.

Benign esophageal schwannoma compressing the trachea requiring esophagectomy: a case report.

We report a case of esophageal schwannoma in a 62-year-old woman with a 10-month history of dysphagia and dyspnea. Chest computed tomography showed a giant mediastinal mass with a maximum diameter of 9 cm, extrinsically compressing the trachea and esophagus. With a large esophageal mucosal defect and poor blood supply after removal of the tumor, we had to perform partial esophagectomy and esophagogastrostomy in the right thorax (Ivor-Lewis procedure). Pathologic and immunohistochemical examinations revealed a benign esophageal schwannoma.

Rac3 Regulates Cell Invasion, Migration and EMT in Lung Adenocarcinoma through p38 MAPK Pathway.

Background: The role of Rac3 in cell proliferation in lung adenocarcinoma has been tackled in our previous study. However, the role of Rac3 in cell invasion and migration of lung adenocarcinoma is still not clear. Methods: The expression of Rac3 in lung adenocarcinoma specimens and paired noncancerous normal tissues were evaluated by immunohistochemistry. Lentivirus-mediated RNA interference (RNAi) was employed to silence Rac3 in lung adenocarcinoma cell lines A549 and H1299. A p38 MAPK inhibitor (LY2228820) was employed to inhibit activity of p38 MAPK pathway. Cell invasion and migration in vitro were examined by invasion and migration assays, respectively. PathScan® intracellular signaling array kit and western blot were employed in mechanism investigation. Results: Rac3 expression was frequently higher in lung adenocarcinoma than paired noncancerous normal tissues. Rac3 expression was an independent risk factor for lymphonode metastasis, and was associated with worse survival outcome. Silencing of Rac3 inhibited cell invasion and cell migration in lung adenocarcinoma cell lines. Knockdown of Rac3 decreased activity of p38 MAPK pathway. LY2228820, which was an important p38 MAPK inhibitor, inhibited Rac3-induced cell invasion and migration of lung adenocarcinoma. E-cadherin expression was increased and vimentin expression was decreased after silencing of Rac3 or following the treatment of LY2228820. Conclusions: Our findings suggest that Rac3 regulates cell invasion, migration and EMT via p38 MAPK pathway. Rac3 may be a potential biomarker of invasion and metastasis for lung adenocarcinoma, and knockdown of Rac3 may potentially serve as a promising therapeutic target for lung adenocarcinoma.

Systematic lymph node dissection is necessary for T1a non-small cell lung cancer.

AIM: With the development of computed tomography, the number of surgical interventions for small-sized lung cancer has increased. It still remains controversial whether a systematic lymph node dissection is necessary in such cases. METHODS: From 2004 to 2010, a total of 138 patients with non-small cell lung cancer (NSCLC) of 2 cm or less in diameter were operated on in our institution. The clinical data were retrospectively analyzed using the Kaplan-Meier method and compared using the log-rank test in surgical approaches, lymph node involvement, histology and survival rates. RESULTS: Lymph node metastasis was found in 24 of 138 (17%) patients. The 5-year survival rate for patients without lymph node metastasis was 83%, whereas it was 75 and 48% for those with pN1 and pN2 disease (P=0.001). Patients receiving lobectomy had a significantly better survival rate than patients receiving limited resection (P=0.02). The 5-year survival rates for patients with stage I, stage II and stage III were 90, 78 and 43%, respectively (P<0.001). Lymph node metastasis was found in 1 of 11 (9%) patients with tumors sized less than 1 cm, 7 of 39 (18%) patients with tumors sized from 1.1 to 1.5 cm, and 16 of 64 (25%) patients with a tumor larger than 1.5 cm (statistically not significant). CONCLUSION: The survival of patients with small-sized lung cancer is closely related to the nodal involvement, stage of disease and surgical approaches. Our study supports that systematic lymph node dissection should be performed in patients with T1a NSCLC.

Lentivirus-mediated silencing of SCIN inhibits proliferation of human lung carcinoma cells.

SCIN (scinderin) is a calcium-dependent actin severing and capping protein. Homologue in zebrafish has been found to be related with cell death. In the present study, we found that SCIN is highly expressed in human lung cancer specimens. However, the role of SCIN in lung cancer has not yet been determined. To investigate the function of SCIN in lung carcinoma cells, we took advantage of lentivirus-mediated RNA interference (RNAi) to knockdown SCIN expression in two lung carcinoma cell lines A549 and H1299. Silencing of SCIN significantly inhibited the proliferation and colony formation ability of both cell lines in vitro. Moreover, flow cytometry analysis showed that knockdown of SCIN led to G0/G1 phase cell cycle arrest as well as an excess accumulation of cells in the sub-G1 phase. Furthermore, depletion of SCIN resulted in a significant increase in Cyclin B1, p21 and PARP expression, and a little decrease in Cyclin D1 expression. These results suggest that SCIN plays an important role in lung carcinoma cell proliferation, and lentivirus-mediated silencing of SCIN might be a potential therapeutic approach for the treatment of lung cancer.

MicroRNA-570 promotes lung carcinoma proliferation through targeting tumor suppressor KLF9.

Increasing studies have shown that MicroRNAs (miRNAs) play critical roles in the progression of lung carcinoma. In the present study, the expression and functions of miR-570 were investigated. We found that miR-570 was significantly up-regulated in lung cancer tissues, compared with adjacent non-cancerous tissues. In vitro studies further showed that miR-570 mimics could promote, while its antisense oligos inhibit cell proliferation and invasion. At the molecular level, krüppel-like factor 9 (KLF9), a tumor suppressor gene, was identified as a potential target of miR-570 in lung cancer cells. Indeed, miR-570 could negatively regulate protein levels of KLF9 through targeting its 3'-untranslated region. Taken together, our results suggest a previously unknown miR-570/KLF9 molecular network controlling lung carcinoma progression.

Silencing of Rac3 inhibits proliferation and induces apoptosis of human lung cancer cells.

BACKGROUND: Rac3, a member of the Rac family of small guanosine triphosphatases (GTPases), regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac3 has been reported in several human cancers. However, the role of Rac3 in lung cancer (LC) has not been determined in detail. The purpose of this study was to investigate the effect of silencing of Rac3 expression in human LC cells and the consequences for cell survival. MATERIALS AND METHODS: Lentivirus small hairpin RNA (shRNA) interference techniques were utilized to knock down the Rac3 gene. Gene and protein expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. LC cell apoptosis was examined by annexin V-APC /propidium iodide staining. RESULTS: Efficient silencing of Rac3 strongly inhibited A549 cell proliferation and colony formation ability, and significantly decreased tumor growth. Moreover, flow cytometry analysis showed that knockdown of Rac3 led to G2/M phase cell cycle arrest as well as an excess accumulation of cells in the G1 and S phase. CONCLUSIONS: Thus, functional analysis using shRNAs revealed a critical role for Rac3 in the tumor growth of LC cells. shRNA silencing of Rac3 could provide an effective strategy to treat LC.

Comparison of the Nuss and sternal turnover procedures for primary repair of pectus excavatum.

BACKGROUND: Pectus excavatum (PE) is a common chest wall deformity. There are several surgical alternatives for the repair of PE. In our practice, the sternal turnover (STO) procedure had been performed for decades. In 2008, we started treating PE patients with the Nuss procedure. Our objective of this study is to compare these two procedures. METHODS: A retrospective chart review was conducted on 50 patients undergoing pectus excavatum repairs from March 2005 to January 2013, including 20 patients with the STO procedure and 30 patients with the Nuss procedure. Patients were evaluated for type of repair performed, operating time, drainage after operation, length of postoperative stay, complications, and cosmetic results. RESULTS: The mean age of the STO group was 11.0 years and that of the Nuss group was 15.0 years (p = 0.353). The Nuss procedure had a much shorter mean operating time, a less mean drainage after operation, and a shorter mean time to drainage tube removal than those of the STO procedure. The rate of complication was 40.0% (8/20) in the STO group and 33.3% (10/30) in the Nuss group. Follow-up data indicated that 90% (18/20) of patients in the STO group and 96.7% (29/30) of patients in the Nuss group regarded the results as good or excellent (p = 0.965). CONCLUSION: Our data suggests that both the STO and Nuss procedures are equally safe and effective correction methods. However, less trauma, faster recovery, and better cosmetic results are the benefits of the Nuss procedure.

Brachial plexus palsy, a rare delayed complication of the Nuss procedure for pectus excavatum: a case report.

We report a rare complication after the Nuss procedure for the correction of pectus excavatum in a 15-year-old adolescent boy. He began to have delayed right brachial plexus injury on the 15th postoperative day. Careful physical check-up revealed a painful and enlarged subaxillary lymph node. He was successfully treated using anti-inflammatory medications and physical therapy.