The expression of squalene epoxidase in human gastric cancer and its clinical significance.

Context: Squalene epoxidase (SQLE) is overexpressed in a variety of tumors, which may play an important role in their tumorigenesis, development, and prognosis. Aims: The aim of this study is to investigate the expression of SQLE and explore its clinicopathological significance in gastric cancer. Settings and Design: The correlation between its positive expression and the pathological characteristics of patients (such as sex, age, tumor size, survival, tumor differentiation, TNM staging, and lymph node metastasis) was analyzed. Materials and Methods: Immunohistochemical method was used to detect its expression in 107 cases of gastric carcinoma and 34 cases of tumor-adjacent tissues. Statistical Analysis Used: Counting data were analyzed by Chi-square test. Its overall survival was analyzed by Kaplan-Meier method and log-rank test. Its hazard factors were analyzed by Cox multivariate analysis. Results: The positive rate of SQLE in gastric cancer is 67.3%, which is higher than that in tumor-adjacent tissues (17.6%), <0.001. Expression of SQLE is closely related to tumor differentiation, TNM staging and lymph node metastasis (P = 0.030, P = 0.009, and P = 0.011, respectively). Furthermore, compared with those low expression of SQLE, the patients of overexpression had worse overall survival by Kaplan-Meier analysis (P = 0.025). Cox multivariate analysis shows that lymph node metastasis, tumor differentiation, SQLE, and TNM staging are independent factors for prognosis of gastric cancer (P = 0.003, 0.020, 0.018, and P = 0.001 respectively). Conclusions: SQLE is overexpressed in gastric cancer. It could be used for the diagnosis and prognosis of the gastric cancer patients.

Genomic signatures define three subtypes of EGFR-mutant stage II-III non-small-cell lung cancer with distinct adjuvant therapy outcomes.

The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.

Muscleblind-like 1 antisense RNA 1 inhibits cell proliferation, invasion, and migration of prostate cancer by sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR signaling.

The present study aimed to investigate the role and underlying mechanisms of long non-coding RNA (lncRNA) muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) in the progression of Prostate cancer (PCa). MBNL1-AS1 and microRNA (miR)-181a-5p expression in PCa tissues and several human PCa cell lines were analyzed, respectively, using StarBasev3.0 project and RT-qPCR assay. After MBNL1-AS1 overexpression, cell proliferation, invasion and migration were, respectively, evaluated using CCK-8, colony formation, transwell and wound healing assays. Dual luciferase assay were used for analysis of the interactions among MBNL1-AS1, miR-181a-5p, and phosphatase and tensin homolog (PTEN). Subsequently, the expression of PTEN and proteins in PI3K/AKT/mTOR signaling was examined using western blot analysis after transfection with miR-181a-5p mimic. The rescue assays were performed to investigate the effects of MBNL1-AS1 and miR-181a-5p on the functions of PCa cells and the expression of PTEN/PI3K/AKT/mTOR signaling by co-transfection with MBNL1-AS1 plasmid and miR-181a-5p mimic. Results indicated that MBNL1-AS1 was conspicuously downregulated while miR-181a-5p upregulating in PCa tissues and cell lines. MBNL1-AS1 overexpression decreased the abilities of cell proliferation, invasion, and migration. Further study revealed that MBNL1-AS1 acted as a sponge for miR-181a-5p and positively regulated PTEN by a sponge effect. Additionally, rescue assays proved that the effect of MBNL1-AS1-upregulation on the proliferation, invasion, and migration of PCa cells was dependent on miR-181a-5p. Furthermore, miR-181a-5p overexpression counteracted the expression of PTEN and proteins in PI3K/AKT/mTOR signaling exerted by MBNL1-AS1-upregulation in PCa cells. This study suggests that MBNL1-AS1 inhibits the progression of PCa via sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR pathway.

Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial.

PURPOSE: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results. METHODS: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data. RESULTS: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% (P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP (P = .316) and 5y DFS rates were 22. 6% and 23.2% (P = .928), respectively. CONCLUSION: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

Quality of life with adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant non-small-cell lung cancer: Results from the ADJUVANT (CTONG1104) study.

OBJECTIVES: Health-related quality of life (HRQoL) data complement conventional clinical endpoints when comparing adjuvant gefitinib with chemotherapy in patients with early-stage non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. This study aimed to assess changes in HRQoL with adjuvant gefitinib vs chemotherapy in this patient group. MATERIALS AND METHODS: In the phase III ADJUVANT trial, patients with completely resected, stage II-IIIA (N1-N2), EGFR-mutant NSCLC were randomized (1:1) to receive either gefitinib for 24 months or vinorelbine plus cisplatin (VP) every 3 weeks for four cycles. HRQoL was assessed as a secondary endpoint using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L), Lung Cancer Symptom Scale (LCSS) questionnaires, and Trial Outcome Index (TOI) composite score. HRQoL dynamics, improvements, and time to deterioration were compared between groups. RESULTS: At baseline, 104 of 106, and 80 of 87 patients receiving gefitinib and VP, respectively, completed two questionnaires (FACT-L and LCSS). Baseline scores were balanced between groups. Although HRQoL fluctuated and gradually improved in both groups, longitudinally higher scores were reported with gefitinib than VP (FACT-L, odds ratio 418.16, 95 % confidence interval [CI] 2.75-63509.05, p =  0.019; LCSS, 1.13, 1.04-1.22, p =  0.003; TOI, 88.39, 4.40-1775.05, p =  0.003). Time to deterioration in HRQoL was delayed with gefitinib compared with VP (FACT-L, median 69 vs 6 weeks, hazard ratio 0.62, 95 % CI 0.42-0.90, p =  0.013; LCSS, median 45 vs 6 weeks, 0.63, 0.43-0.93, p =  0.020; TOI, median 164 vs 9 weeks, 0.51, 0.33-0.77, p =  0.001). CONCLUSION: Adjuvant gefitinib is associated with improved HRQoL over VP, supporting its use in patients with stage II-IIIA (N1-N2), EGFR-mutant NSCLC.

Kank1 and Ki67 expression are associated with poor prognosis in human pulmonary adenocarcinoma.

KN motif and ankyrin repeat domains 1 (Kank1) and ki67 are associated with tumorigenesis and progression. This paper researched the expression of Kank1 and Ki67 and their clinicopathologic significance in pulmonary adenocarcinoma (PA). We monitored the expression of KanK1 and ki67 in 94 cases of human PA and 31 cases of paracancerous tissue by the immunohistochemical method. The results showed that Kank1 protein was detected in 74.2% (41/94) of PA tissues, and they were associated with differentiation (P = 0.025) and lymphatic metastasis (P = 0.002). Kaplan-Meier analysis suggested that patients with low Kank1 expression had shorter overall survival in PA (P = 0.020). Ki67 protein was detected in 79.8% (75/94) of PA tissues, and they were associated with differentiation (P < 0.001), TNM classification (P = 0.007), and lymphatic metastasis (P = 0.044). Furthermore, Kaplan-Meier analysis showed that patients with overexpression of Ki67 had shorter overall survival (P = 0.014). Cox multivariate analysis showed that tumor differentiation, TNM classification, lymphatic metastasis, Kank1, and ki67 expression were independent factors for prognosis of PA (P = 0.012, 0.016, 0.007, 0.021 and P = 0.003 respectively). In conclusion, compared with paracancerous tissues, Kank1 had low expression, while Ki67 was overexpressed in PA. They are closely related to its occurrence and development, and the prognosis of patients with low expression of Kank1 or overexpression of ki67 was poor in PA. Kank1 and Ki67 can be helpful for diagnosing and detecting the prognosis of patients with PA.

Prognostic and clinicopathologic significance of PAQR3 and VEGF-A expression in pulmonary adenocarcinoma.

Progesterone and adipoQ receptor family member 3 (PAQR3) and vascular endothelial growth factor (VEGF)-A are associated with tumorigenesis and progression. The aim of this study is to investigate the expression of PAQR3 and VEGF-A in pulmonary adenocarcinoma (PA) and explore their clinical and pathologic significance. The expressions of PAQR3 and VEGF-A protein were detected in 86 cases of human PA and 26 cases of tumor-adjacent tissue by immunohistochemistry. The positive rate of PAQR3 was 39.5% in PA, which was lower than that in tumor-adjacent tissues (80.8%), P=0.001. Negative expression of PAQR3 was obviously linked to tumor TNM stage, differentiation, and lymphatic metastasis; and P values were 0.013, 0.025, and 0.034, respectively. The positive expression rate of VEGF-A was 68.6% in human PA whichwas higher than that of tumor-adjacent tissues (11.5%), P<0.001. The positive expression of VEGF-A was correlated with tumor TNM stage, differentiation, and lymphatic metastasis, and P values were 0.026, 0.001 and P=0.001, respectively. The expression of PAQR3 was negatively correlated with the expression of VEGF-A (r=-0.698, P<0.001). Log-rank test statistical analysis suggested that patients with negative expression of PAQR3 or positive expression of VEGF-A had shorter overall survival. Cox multivariate analysis indicated that tumor TNM stage, differentiation, and lymphatic metastasis, and PAQR3 and VEGF-A expression were independent factors for prognosis of PA, and P values were 0.021, 0.017, 0.006, 0.018 and P=0.007 respectively. In conclusion, negative expression of PAQR3 and positive expression of VEGF-A are markedly correlated with tumor TNM classification, histologic grade, and lymphatic metastasis. Tumor TNM stage, differentiation, and lymphatic metastasis, negative expression of PAQR3, and positive expression of VEGF-A are risk factors for prognosis of patients with PA. Detection of PAQR3 and VEGF-A may be helpful to evaluate prognosis and infiltrative capability of PA.

Allicin enhances the radiosensitivity of colorectal cancer cells via inhibition of NF-κB signaling pathway.

Radioresistance is an important factor affecting the radiotherapy effect of colorectal cancer (CRC). Allicin is a versatile sulfur-containing organic compound extracted from garlic (Allium sativum L.), which has many pharmacological effects. However, the effect of allicin on the sensitivity of CRC radiotherapy has not been confirmed. The present study is to observe the radiosensitivity effects of allicin and to explore its mechanism in CRC radiotherapy. The proliferation inhibition effects of allicin combined with X-ray radiotherapy in HCT116 cells were measured by growth curve of cell and colony formation assays. The cell apoptosis was detected by Hoechst 33258 nucleus staining assay. The migration ability of cells was detected by Transwell chamber migration assay. The animal model of CRC was established in BALB/c mice via transplantation of CT26 cell, and the radiosensitization effect of allicin on CRC was detected in vivo. The mRNA expressions of NF-κB, IKKß, and IκBα were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of NF-κB, p-NF-κB, IKKß, p-IKKß, IκBα, and p-IκBα were detected by western blotting. Our results showed that allicin improves the sensitivity of X-ray radiotherapy in CRC, and its mechanism may be associated with inhibition of NF-κB signaling pathway. These findings suggest that allicin may be used as a potential sensitizer for tumor radiotherapy in the clinic.

Development and validation of nomogram estimating post-surgery hospital stay of lung cancer patients: relevance for predictive, preventive, and personalized healthcare strategies.

OBJECTIVE: In the era of fast track surgery, early and accurately estimating whether postoperative length of stay (p-LOS) will be prolonged after lung cancer surgery is very important, both for patient's discharge planning and hospital bed management. Pulmonary function tests (PFTs) are very valuable routine examinations which should not be underutilized before lung cancer surgery. Thus, this study aimed to establish an accurate but simple prediction tool, based on PFTs, for achieving a personalized prediction of prolonged p-LOS in patients following lung resection. METHODS: The medical information of 1257 patients undergoing lung cancer surgery were retrospectively reviewed and served as the training set. p-LOS exceeding the third quartile value was considered prolonged. Using logistic regression analyses, potential predictors of prolonged p-LOS were identified among various preoperative factors containing PFTs and intraoperative factors. A nomogram was constructed and subjected to internal and external validation. RESULTS: Five independent risk factors for prolonged p-LOS were identified, including older age, being male, and ratio of residual volume to total lung capacity (RV/TLC) ≥ 45.0% which is the only modifiable risk factor, more invasive surgical approach, and surgical type. The nomogram comprised of these five predictors exhibited sufficient predictive accuracy, with the area under the receiver operating characteristic curve (AUC) of 0.76 [95% confidence interval (CI) 0.73-0.79] in the internal validation. Also its predictive performance remained fine in the external validation, with the AUC of 0.70 (95% CI 0.60-0.79). The calibration curves showed satisfactory agreements between the model predicted probability and the actually observed probability. CONCLUSIONS: Preoperative amelioration of RV/TLC may prevent lung cancer patients from unnecessary prolonged p-LOS. The integrated nomogram we developed could provide personalized risk prediction of prolonged p-LOS. This prediction tool may help patients perceive expected hospital stays and enable clinicians to achieve better bed management after lung cancer surgery.

The overexpression of uPA promotes the proliferation and fibrinolytic activity of human umbilical vein endothelial cells.

The purpose of this article is to study whether the overexpression of urokinase-type plasminogen activator (uPA) can promote the proliferation and fibrinolytic activity of human umbilical vein endothelial cells (HUVECs). The recombinant adenovirus vectors containing the human uPA gene were constructed and transfected into HUVECs. In this study, the mRNA of uPA was detected by qPCR, and the uPA protein was measured by Western blot. The cell proliferation was measured using MTT. The fibrinolytic activity of uPA was quantified using a colorimetric assay. We also measured MMP2 (metalloproteinase-2), MMP9 (metalloproteinase-9), and VEGF (vascular endothelial growth factor) proteins using ELISA. The results showed that the levels of the uPA mRNA and the protein in the overexpression group were significantly higher compared to the other groups, (P < 0.05). The cell proliferation and uPA activity were increased significantly in the overexpression group, compared to the other groups, (P < 0.05). The secretions of MMP2, MMP9, and VEGF in the overexpression group were significantly higher than they were in the other two groups (P < 0.05). In conclusion, we successfully transfected a recombined adenovirus vector carrying uPA into a HUVEC. The exogenous uPA gene could transcribe and secrete the uPA protein in the HUVECs. The overexpression of uPA can increase cell proliferation and uPA activity. It can improve the invasion and angiogenesis ability in HUVECs by promoting their secretions of MMP2, MMP9, and VEGF.

The Unique Spatial-Temporal Treatment Failure Patterns of Adjuvant Gefitinib Therapy: A Post Hoc Analysis of the ADJUVANT Trial (CTONG 1104).

INTRODUCTION: Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized. METHODS: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted. RESULTS: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib. CONCLUSIONS: Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored.

Prevalence of and risk factors for presenting initial respiratory symptoms in patients undergoing surgery for lung cancer.

Background: Patients with early stage lung cancer seldom present initial respiratory symptoms, causing a delayed diagnosis and missed opportunity to receive operation. This study aimed to investigate the prevalence of initial respiratory symptoms and identity what factors would predispose lung cancer patients to present initial respiratory symptoms in patients undergoing lung cancer surgery. Methods: A retrospective chart review was conducted on 3,203 patients undergoing surgery for primary lung cancer. The prevalence of initial respiratory symptoms was investigated and the comparisons of clinicopathological parameters were performed between patients with and without initial respiratory symptoms or between patients with single and multiple initial respiratory symptoms. Independent risk factors for presenting initial respiratory symptoms or multiple initial respiratory symptoms were identified using a logistic regression. Results: A total of 1,474 (46.0%) patients with lung cancer were admitted to hospital due to present initial respiratory symptoms. Symptom clusters of cough or sputum (33.1%) and bloody sputum or hemoptysis (16.7%) presented as the two major chief complaints for medical consultation while chest pain (6.9%) and chest distress or dyspnea (5.6%) remained relatively unusual. Multiple analyses found that coexisting chronic obstructive pulmonary disease (OR=1.70, 95% CI=1.41-2.05), tumor size >3 cm (OR=2.27, 95% CI=1.93-2.67), squamous cell carcinoma (OR=2.22, 95% CI=1.86-2.65), tumor located in left lower lung (OR=1.39, 95% CI=1.10-1.74) and advanced tumor stage (OR=1.27, 95% CI=1.06-1.52) were independent risk factors for presenting initial respiratory symptoms. Furthermore, current smoking (OR=1.36, 95% CI=1.07-1.73), tumor size >3 cm (OR=1.53, 95% CI=1.21-1.93) and squamous cell carcinoma (OR=1.68, 95% CI=1.32-2.15) were demonstrated to be independent risk factors for presenting multiple initial respiratory symptoms. Conclusions: Presenting initial respiratory symptoms was the common cause for medical consultation in patients undergoing lung cancer surgery. Patients with lung cancer in larger tumor size or squamous cell carcinoma more likely presented initial and even multiple initial respiratory symptoms.

Status of coexisting chronic obstructive pulmonary disease and its clinicopathological features in patients undergoing lung cancer surgery: a cross-sectional study of 3,006 cases.

BACKGROUND: Lung cancer is often complicated with chronic obstructive pulmonary disease (COPD). Coexistence of COPD has significant impacts on the decision-making process for lung cancer surgery as well as the postoperative effects. This study aimed to investigate the status of coexisting COPD and analyze its clinicopathological characteristics in lung cancer patients undergoing surgical resection. METHODS: Clinical data of 3,006 patients with resected primary lung cancer from January 2008 to April 2014 were analyzed. Status of coexisting COPD was evaluated according to patient's lung function. Differences of clinicopathological characteristics between the COPD group and the non-COPD group were compared. RESULTS: A total of 643 patients (21.4%) were complicated with COPD. The average age of patients with COPD (64.9±8.5 years) was significantly older than those without COPD (59.4±9.9 years). The percentage of males (85.7% vs. 54.0%) and current smokers (43.4% vs. 22.5%) were both higher in the COPD group than the non-COPD group (P<0.05). The percentage of patients with initial symptoms was higher in the COPD group than the non-COPD group (63.9% vs. 44.5%, P<0.05). The average white blood cell count was higher in the COPD group than the non-COPD group [(6.72±2.28 vs. 6.28±2.24) ×109/L, P<0.05]. The percentage of tumor size more than 3 cm was higher in the COPD group than the non-COPD group (53.2% vs. 38.0%, P<0.05). Squamous cell carcinoma accounted for 47.6% in the COPD group while adenocarcinoma accounted for 72.4% in the non-COPD group (P<0.05). A higher percentage of lung cancer with poor differentiation was found in the COPD group than the non-COPD group (53.2% vs. 43.6%, P<0.05). The median total and postoperative length of hospital stay were significantly longer in the COPD group than the non-COPD group (13 vs. 11 days, 8 vs. 7 days, respectively, P<0.05). CONCLUSIONS: COPD is a common comorbidity of early stage lung cancer. Lung cancer patients with coexistence of COPD have obviously different clinicopathological features compared to patients without COPD, which requires special attention and management during the perioperative period of lung cancer.

Prognostic and clinicopathologic significance of AEG-1/MTDH and E-cadherin expression in human gallbladder carcinoma.

Astrocyte elevated gene-1 (AEG-1) and E-cadherin are associated with tumorigenesis and progression. The aim of this study is to investigate the expression of AEG-1 and E-cadherin in human gallbladder cancer (GBC) and explore their clinical and pathological significance. The expression of AEG-1 and E-cadherin protein were detected in 71 cases of human GBC and 22 cases of tumor-adjacent tissue by the immunohistochemical method. Our results demonstrate that the positive expression (high expression) rate of AEG-1 was 62.0% in human GBC which was higher than that in tumor-adjacent tissues (13.6%), P<0.001. The positive expression of AEG-1 protein was correlated with tumor TNM classification, histologic grade, and lymph node metastasis (P=0.037, P=0.033 and P=0.020, respectively). The positive expression rate of E-cadherin was 40.8% in GBC, which was lower than that in tumor-adjacent tissues (77.3%), P=0.003. Negative expression (Low expression) of E-Cadherin was significantly related with tumor TNM classification, histologic grade and lymphatic metastasis (P=0.028, P=0.003 and P=0.040, respectively). The expression of AEG-1 was negatively correlated with the expression of E-Cadherin (r=0.530, P<0.001). The log-rank test statistical analysis suggested that patients with positive expression of AEG-1 or negative expression of E-Cadherin protein had shorter overall survival time. Cox multivariate analysis showed that tumor TNM classification, histologic grade and lymphatic metastasis, AEG-1 and E-cadherin expression were independent factors for prognosis of GBC (P=0.013, P=0.019, P=0.001, P=0.011 and P=0.025 respectively). In conclusion, positive expression of AEG-1 and negative expression of E-Cadherin are markedly correlated with tumor TNM classification, histologic grade and lymphatic metastasis. The expression of AEG-1 was negatively correlated with the expression of E-Cadherin. Cox multivariate analysis showed that tumor TNM classification, histologic grade and lymphatic metastasis, positive expression of AEG-1 and negative expression of E-Cadherin were risk factors for prognosis of GBC. Detection of AEG-1 and E-Cadherin may be helpful to evaluate prognosis and infiltrative capability of gallbladder carcinoma.

Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study.

BACKGROUND: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC. METHODS: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079. FINDINGS: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related. INTERPRETATION: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature. FUNDING: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.

Video-Assisted Thoracoscopic Surgery for Intralobar Pulmonary Sequestration: Wedge Resection Is Feasible in Limited Peripheral Lesions.

Objectives Pulmonary sequestration is a rare developmental abnormality of the lower respiratory system. This study aimed to evaluate the effectiveness of wedge resection compared with lobectomy for the treatment of intralobar pulmonary sequestration. Methods Video-assisted thoracic surgery (VATS) for intralobar pulmonary sequestration was performed in 26 patients in our institute between December 2006 and January 2015. Data regarding patient demographics, major complaints, diagnostic procedures, operative treatment, and treatment outcome were retrospectively analyzed. Results VATS was performed successfully in all patients. Wedge resection was performed in 7 patients and lobectomy in 19 patients. Conversion to thoracotomy was not required in any case. Statistical analysis revealed that operation duration and blood loss with wedge resection were significantly less than with lobectomy (p = 0.032 and 0.014, respectively). No significant differences were found in the mean drainage time, postoperative length of hospital stay, or complications. During our long-term follow-up, no patients had chronic cough, bloody sputum, or pneumonia. Conclusion VATS for intralobar pulmonary sequestration is feasible and safe. Lobectomy is the generally accepted operative method. However, wedge resection is a feasible alternative to lobectomy in select cases.

Management of symptomatic caliceal diverticular calculi: Minimally invasive percutaneous nephrolithotomy versus flexible ureterorenoscopy.

OBJECTIVE: To retrospectively evaluate appropriate treatment for patients with symptomatic caliceal diverticular calculi, by comparing the therapeutic outcomes for those undergoing minimally invasive percutaneous nephrolithotomy (MPCNL) and flexible ureterorenoscopy (F-URS). METHODS: From March 2009 to May 2014, 36 consecutive patients with caliceal diverticular calculi were divided into 2 groups: 21 patients underwent MPCNL, and 15 were treated by F-URS. All procedures were performed by one surgical group, which ensured relatively constant parameters. Patient characteristics, operative time, hospital stay after surgery, stone-free rate, symptomatic improvement rate, complications, diverticular obliteration, and stone composition were analyzed retrospectively in the 2 groups. RESULTS: Patient preoperative variables were comparable between the two groups, with no significant difference (P > 0.05). Mean operative time was 136.9 ± 22.8 min in the MPCNL group and 117.3 ± 24.3 min in the F-URS group (P = 0.019). Hospital stay was significantly longer in the MPCNL group than in the F-URS group (9.4 ± 3.1 vs. 6.9 ± 2.1 days, P = 0.010). The stone-free rates after MPCNL and F-URS were 90.5% (19/21) and 60.0% (9/15), respectively (P = 0.046). Additionally, 71.4% (15/21) of patients in the MPCNL group and 46.7% (7/15) of patients in the F-URS group had symptomatic improvement at the 6-month follow-up (P = 0.175); the rates of complications in the 2 groups were 19.0% (4/21) and 13.3% (2/15), respectively (P = 0.650). Complete diverticular obliteration was achieved in 16 (76.2%) cases in the MPCNL group and 5 (33.3%) cases in the F-URS group (P = 0.017). The distributions of calcium oxalate and hydroxyapatite in the stones were 66.7% (14/21) and 33.3% (7/21), respectively, in the MPCNL group; however, the distributions in the F-URS group were 46.7% (7/15) and 53.3% (8/15), respectively (P = 0.310). CONCLUSION: MPCNL is an effective method for the treatment of caliceal diverticular calculi. However, F-URS is an alternative technique in selected patients with a patent infundibulum, despite lower stone-free rates than with MPCNL. Fulguration of the diverticular lining with a high-power holmium laser and permitting the cavity to collapse are useful to increase the chance of diverticular obliteration.

Targeting MACC1 by RNA interference inhibits proliferation and invasion of bladder urothelial carcinoma in T24 cells.

The purpose of this article is to research on whether MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma (BUC). In this study, the expression of MACC1 gene was knocked down by RNA interference (RNAi) in the T24 cell (human BUC cell). The transcription level of MACC1 was detected by RT-PCR. Activities of MACC1, caspase-3, caspase-8, Bax and Met (mesenchymal-epithelial transition factor) protein were measured by Western blot. The cell proliferation and apoptosis were detected by MTT and flow cytometry. The cell's invasion ability was performed on Matrigel transwell assay. We also detect MMP2 (metalloproteinase-2) proteins by ELISA. The results showed that the level of MACC1 mRNA and protein was significantly reduced after RNAi. MTT assay showed that the proliferation of T24 cell was decreased due to RNA interference. Apoptosis studies also showed that MACC1 gene interference in T24 loses its anti-apoptotic effects. The expression of apoptosis proteins (Caspase-3, Caspase-8 and Bax) increased significantly due to the MACC1 RNAi. The level of Met protein was down-regulated obviously due to RNAi. Transwell assay showed that invasion abilities of T24 cells were reduced obviously due to MACC1 RNAi. Further studies showed that the secretion of MMP-2 was reduced by RNAi. It can conclude that the ability of proliferation and invasion in T24 cells can be inhibited by RNAi-targeting MACC1. As a result, MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma.

The downregulation of OPN inhibits proliferation and migration and regulate activation of Erk1/2 in ECA-109 cells.

Osteopontin (OPN) involves in tumor formation, and strongly correlated with the tumor progression. It was overexpressed in human esophageal squamous cell carcinoma (ESCC). To study the molecular mechanisms of OPN in ESCC, we examined its roles in inhibiting proliferation and invasion of ECA-109 (esophageal squamous cell carcinoma) cells. The expression of OPN gene was knockdown by RNA interference (RNAi) in the Eca-109 cell. The transcription level of OPN was to detect by reverse transcription-quantitative PCR (RT-qPCR). Western blot assay was performed to detect the expression of OPN, Caspase-3,Caspase-8, Caspase-9, ERK1/2, phospho-ERK1/2 and MMP2 after RNAi. The cell proliferation and apoptosis were detected by MTT and Hoechst33342 assay. Transwell inserts was used for detecting ECA-109 cell's migration ability. The results shown that the level of OPN mRNA and protein was significantly reduced after RNAi. Proliferation and migration of cell line (ECA-109) was significantly inhibited in vitro. The protein phosphorylation and activation of ERK1/2 in the OPN RNAi group reduced significantly than the negative control groups. In Conclusion, the proliferation and migration of human ESCC can be inhibited by RNAi-targeting OPN. OPN can promote the expression of MMP2 through the ERK signaling pathways. OPN could serve as a potential therapeutic target for human ESCC.