Jianxin Shi

MicroRNA-181 functions as a tumor suppressor in non-small cell lung cancer (NSCLC) by targeting Bcl-2.

MicroRNAs (miRNAs) are small non-coding RNAs frequently dysregulated in human malignancies. In this study, we analyzed the global expression profile of miR-181 in non-small cell lung cancer (NSCLC), as its participation in some other types of cancer has been suggested by previous reports. We found that miR-181 was downregulated both in NSCLC tissues and cell lines. Overexpression of miR-181evidently inhibited A549 cell proliferation, migration, and invasion and promotes cell apoptosis. Moreover, we also found miR-181 reduction was associated with increased Bcl-2 levels and miR-181 was further suggested to exert its pro-apoptotic function mainly through targeting Bcl-2 expression. Taken together, our study implicates important roles of miR-181 in lung cancer pathogenesis and implicates its potential application in cancer therapy.

Hydrogen saline is protective for acute lung ischaemia/reperfusion injuries in rats

BACKGROUND Protective effects of saturated hydrogen (H(2)) saline on cardiac ischaemia-reperfusion (I/R) injury have been demonstrated previously. This study was designed to show that hydrogen-rich saline is protective in preventing lung I/R injury in rats. METHODS Adult male Sprague-Dawley rats underwent 45 min occlusion of the right lung roots and 120 min reperfusion. Rats were divided randomly into three groups: sham-operated control group, I/R plus saline treatment, and I/R plus hydrogen-rich saline treatment (0.6 mmol/L, 0.5 ml/kg/d). Three days of intraperitoneal injection of hydrogen-rich saline before the reperfusion combined with immediate administration of hydrogen-rich saline after the reperfusion were performed. Following reperfusion, the lung tissue and the pulmonary artery was immediately obtained and the W/D ratio, pulmonary artery contraction and relaxation ability, H-E staining, TUNEL staining, caspase-3, MDA, 8-OHdG content and measurement of such biomarkers as WBC, CRP were measured or carried out. RESULTS Hydrogen saline significantly protected vasoactivity of the pulmonary artery, reduced pulmonary oedema, decreased lung malondialdehyde (MDA), 8-OHdG concentration, alleviated lung epithelial cell apoptosis and lowered the level of such biomarkers as WBC, CRP, ALT and TBiL. CONCLUSIONS It is concluded that hydrogen-rich saline is a novel, simple, safe and effective method to attenuate pulmonary I/R injury.

HMGCR is necessary for the tumorigenecity of esophageal squamous cell carcinoma and is regulated by Myc

Hydroxymethylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme of mevalonate pathway, has been involved in the tumorigenesis of several tumor types. Our previous study has showed that statin, the inhibitor of HMGCR, inhibited the tumorigenecity of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. However, the function of HMGCR in the carcinogenesis of ESCC cells remains unknown. In this study, we have observed the up-regulation of HMGCR in ESCC tissues compared with the paired normal tissues. Over-expression of HMGCR in ESCC cells promoted cell growth and migration, while knockdown of the expression of HMGCR inhibited the growth, migration and colony formation of ESCC cells in vitro and in vivo. Furthermore, we found that oncogene Myc positively regulated the expression of HMGCR. Taken together, our study revealed the pivotal function of HMGCR and mevalonate pathway in the progression of ESCC and supported the clinical application of statin.

Mevalonate pathway is a therapeutic target in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors in the world. Thus, it is very urgent to develop new therapeutic targets against this disease. The mevalonate (MVA) pathway, paced by its rate-limiting enzyme, hydroxymethylglutaryl coenzyme A reductase, is required for the generation of several fundamental end products including cholesterol and isoprenoids. The function of the MVA pathway in ESCC has not been investigated. In this study, it was found that the MVA pathway was upregulated in ESCC clinical samples. Statin, the inhibitor of the MVA pathway, exerted potent cytotoxicity against human ESCC cells by inhibiting cell growth and proliferation, while it exerted lesser effects on non-tumorigenic SHEE cells. Further study revealed that statin could potently induce cell apoptosis and cell cycle arrest and also dose-dependently inhibit the growth of xenograft tumors in nude mice. With regard to the molecular mechanism, statin treatment was related to decreased extracellular signal-regulated kinase activation and proliferating cell nuclear antigen, cyclin D1 expression, and increased cleavage of poly(ADP-ribose) polymerase. Taken together, our findings suggest that the MVA pathway plays an important role in the progression of ESCC by modulating cell growth and statin might be a potential therapeutic agent in ESCC.

Genetic Polymorphisms and Plasma Levels of Interleukin-22 Contribute to the Development of Nonsmall Cell Lung Cancer

Interleukin (IL)-22, a relatively new member of the IL-10 family, has been implicated in inflammation and tumorigenesis. The aim of this study was to identify genetic polymorphisms in IL-22 and to measure plasma levels of IL-22 in patients with nonsmall cell lung cancer (NSCLC). Patients with NSCLC had a significantly higher frequency of IL-22 rs2227484 CT genotype (odds ratio [OR]=1.917, 95% confidence interval [CI] 1.001-3.670, p=0.038) and T allele (OR=1.878, 95% CI 1.010-3.491, p=0.049) as compared with controls. The rs2227484 genotype was associated with a 2.263-fold increased risk for advanced NSCLC (p=0.041). Among different subtypes of NSCLC, these associations were more obvious in the adenocarcinoma. Moreover, patients with high frequencies of genotypic polymorphisms had high plasma levels of IL-22. IL-22 polymorphisms and corresponding high levels of IL-22 in plasma may contribute to the development of NSCLC, especially adenocarcinoma.

Surgical treatment of thymoma: an 11-year experience with 761 patients.

OBJECTIVES Thymomas are rare, and information regarding their surgical outcomes and possible prognostic factors is limited. In this study, we aimed to determine the clinicopathological characteristics of thymoma and estimate independent predictors of both overall and disease-free survival in thymoma patients. METHODS We carried out a retrospective review of the clinicopathological characteristics and prognostic factors in 761 consecutive patients with pathologically confirmed thymoma treated in Shanghai Chest Hospital between January 2001 and December 2011. Survival was calculated using the Kaplan-Meier method and evaluated with log-rank tests. Multivariable analysis was performed using the Cox regression model. RESULTS Complete follow-up information was available for 544 patients. The overall survival rate was 92.8% at 5 years and 90.5% at 10 years. The 5- and 10-year disease-free survival was 87.9 and 82.1%, respectively. On multiple Cox regression analysis, the Masaoka-Koga clinical stage [odds ratio (OR), 2.057; 95% confidence interval (CI), 1.454-2.911; P < 0.01] and sex (OR, 2.244; 95% CI, 1.115-4.519; P = 0.02) were found to be independent predictors of overall survival. The Masaoka-Koga clinical stage (OR, 2.127; 95% CI, 1.487-3.042; P < 0.01) and completeness of resection (OR, 2.935; 95% CI, 1.410-6.109; P < 0.01) predicted disease-free survival. CONCLUSIONS The four-tiered Masaoka-Koga clinical stage is the most important prognostic factor, predicting not only overall survival but also disease-free survival after thymoma resection. Completeness of resection predicts disease-free survival, and the World Health Organization histological classification may not have significant prognostic implications.

Evaluation of the proposed International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancies Interest Group (ITMIG) staging revisions in thymic well-differentiated neuroendocrine carcinoma patients.

OBJECTIVES In 2014, the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancies Interest Group (ITMIG) launched a worldwide Tumor Node Metastasis (TNM) staging proposal for the next edition of thymic tumours. The objective of the current study was to evaluate the proposed new staging system specific to the thymic well-differentiated neuroendocrine carcinoma (TWDNC). METHODS From November 2003 to July 2014, 61 consecutive patients were enrolled in this study with pathologically confirmed TWDNC in Shanghai Chest Hospital. Clinical and pathological data were retrospectively reviewed. Survival analysis was performed using the Kaplan-Meier and log-rank tests. Validity evaluation was addressed by Cox proportional hazards regression model, after adjusting for potential confounders and visually assessing the distinction of curves generated based on the staging system of Masaoka-Koga and the proposed TNM ones. RESULTS Thymic carcinoids made up 4% of total thymic tumours in our institution. The 5-year overall survival (OS) rate and the disease-free survival (DFS) rate were 72 and 41%, respectively. Neither Masaoka-Koga staging system nor the proposed TNM system showed ordered appropriateness visually in survival curves and the prognostic demarcation between stages was poor on both OS and DFS. CONCLUSIONS The IASLC/ITMIG suggested that the TNM and Masaoka-Koga staging systems fail to predict the clinical course of TWDNC patients. Collaborative effort is needed in the future staging validation as ITMIG recommended.

Downregulation of MED23 promoted the tumorigenecity of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors in the world. It is very urgent to develop new therapeutic strategies. MED23, a component of the mediator complex, is known as a hub to integrate various signaling pathways. However, the function of MED23 in ESCC remains unknown. Here, we found that the expression of MED23 was downregulated in the clinical ESCC samples and the expression of MED23 reversely correlated with tumor size and clinical stage. Moreover, overexpression of MED23 in ESCC cells inhibited cell growth dramatically, while downregulation of MED23 promoted the tumorigenecity of ESCC cells in vitro and in vivo. Mechanistically, knockdown the expression of MED23 inhibited cell apoptosis by downregulation of Bax, activated Caspase 3, activated Caspase 9 and upregulation of cyclinD1 and Bcl2. Taken together, our study revealed the suppressive role of MED23 in ESCC and MED23 might be an important therapeutic target in ESCC.

Initial Experience of Robotic Sleeve Resection for Lung Cancer Patients

BACKGROUND The purpose of this study was to identify the technical aspects and short-term results of robotic sleeve resection for lung cancer patients. METHODS Twenty-one consecutive cases of robotic sleeve resection from September 2014 to September 2015 were reviewed. RESULTS There were 17 single sleeve resection (bronchial) and 4 double sleeve resection (bronchial and vascular) cases. Nineteen of 21 cases (90.5%) achieved R0 resection. The mean console time was 120.4 ± 37.3 minutes. The mean operation time was 158.4 ± 42.0 minutes. There was no massive bleeding (800 mL or more) during operation. The mean intraoperative blood loss was 157.1 ± 97.8 mL. One case (4.8%) was converted to thoracotomy owing to severe calcification of lymph node. There was no intraoperative death. The overall complication rate was 19.0%. The major complications were subcutaneous emphysema (14.4%), cardiac arrhythmia (9.6%), pneumonia (9.6%), pyothorax (9.6%), bronchial anastomosis bleeding (4.8%), bronchial anastomosis leakage (4.8%), and multiple organ failure (4.8%). The 30-day mortality rate was 4.8%. The mean postoperative length of stay was 10.7 ± 7.6 days. CONCLUSIONS Robotic sleeve resection is technically feasible and can be carried out with acceptable short-term results.

Robotic Assisted Extended Sleeve Lobectomy After Neoadjuvant Chemotherapy.

A 61-year-old man had experienced an irritating cough for 1 month. He received a diagnosis of lung adenocarcinoma by bronchoscopy. Computed tomography showed a mass in the left hilum and mediastinal lymph node enlargement. After two cycles of neoadjuvant chemotherapy, the patient underwent a robotic assisted atypical sleeve lobectomy (left lower lobe + S4+5). The patients postoperative course was uneventful, and he was discharged on the tenth postoperative day. This is the first description of the feasibility of robotic extended sleeve lobectomy for a lung cancer patient receiving neoadjuvant chemotherapy.