Association of leptin receptor polymorphisms with susceptibility of non-small cell lung cancer: Evidence from 2249 subjects.

Non-small cell lung cancer (NSCLC) is increasing dramatically. It is believed that energy metabolism-related genes could play an important role in etiology of NSCLC. In this study, we sought to assess the correlation between three LEPR single nucleotide polymorphisms (rs1137101, rs1137100 and rs6588147) with NSCLS susceptibility. In total, 1193 NSCLC cases and 1056 controls were included. SNPscan™ genotyping method was used to analyze the genotypes of LEPR polymorphisms. Compared to rs6588147 GG in LEPR gene, this study identified a protective role of LEPR rs6588147 GA and GA/AA for the occurrence of NSCLC (GA vs. GG [p = 0.021] and GA/AA vs. GG [p = 0.030]). As well, we found that a protective role of LEPR rs6588147 for the occurrence of non-SCC subgroup (p < 0.05). By logistic regression analysis, we found that the rs6588147 A allele related genotypes might play a protective role for the occurrence of NSCLC in drinking, BMI ≥24 kg/m2, smoking and male subgroups. We also found that the rs1137101 A allele related genotypes played a protective role for the occurrence of NSCLC in male, younger participants (under 59 years) and overweight/obesity (BMI ≥24 kg/m2) subgroups. We found that LEPR Ars1037100Ars1037101Ars6588147 haplotype might play a protective role for the occurrence of NSCLC (p = 0.013). In addition, our findings indicated that LEPR rs1137100 G>A SNP might increase the risk of lymph node metastases (p = 0.038). This study highlights that LEPR rs6588147, rs1137101 genotypes and LEPR Ars1037100Ars1037101Ars6588147 haplotype are correlated with the occurrence of NSCLC. LEPR rs1137100 G>A SNP increases the risk of lymph node metastases.

MiR-502 mediates esophageal cancer cell TE1 proliferation by promoting AKT phosphorylation.

Esophageal cancer is one of the most common cancers in the world and esophageal squamous cell carcinoma is one of the two main types in esophageal cancer. MicroRNA is a small non-coding RNA molecule functions in many different cancers including esophageal cancer. We found miR-502 was up-regulated in esophageal tissues, which indicated miRNA-502 may play important roles in esophageal cancer. In this study, we used esophageal cancer cell line TE1 as an in vitro model for investigating the role of miR-502 in promoting the proliferation of the cancer cells. We found that overexpressing miR-502 in TE1 cells promoted the proliferation and inhibited the apoptosis induced by dox. Down-regulating miR-502 made the opposite phenomenon. Furthermore, western blot showed that miR-502 enhanced the phosphorylation levels of AKT pathways, which may be the mechanism of the overgrowth for esophageal cancer cell. Our data provide the evidence of a role for miR-502 in the regulation the proliferation of esophageal cancer cell through promoting the phosphorylation of AKT signaling. Due to its ability to promote the overgrowth of esophageal cancer cell, miR-502 may be a novel target for esophageal cancer therapeutic.

Y-box-binding protein 1 promotes tumor progression and inhibits cisplatin chemosensitivity in esophageal squamous cell carcinoma.

Y-box-binding protein 1 (YB-1) has been identified as a pleotropic oncoprotein in multiple human malignancies and is involved in the regulation of various DNA/RNA-dependent events, including transcription and translation. However, little is known about expression pattern and underlying functions of YB-1 in esophageal squamous cell carcinoma (ESCC). In this study, we report that up-regulated YB-1 is closely correlated with TNM stage and tumor size in ESCC specimens and predicts a poor prognosis in ESCC patients. Genetic silencing of YB-1 inhibits cell proliferation and invasive potential by regulating its targeted genes associated with tumor growth and metastasis. In particular, we also show that silencing of YB-1 enhances chemotherapy-induced cytotoxicity in EC109 and TE-1 cells by targeting multidrug resistance 1 (MDR1). Our findings demonstrate the oncogenic roles of YB-1 in ESCC and support it as a target for ESCC therapy.

Dynamic investigation of alveolar type II cell function in a long-term survival model of rat lung ischemia-reperfusion injury.

BACKGROUND: Alveolar type II (ATII) cells are capable of repairing the alveolar epithelium injury induced by lung ischemia-reperfusion injury (LIRI). In the present study, we aim to dynamically investigate the morphological and functional alternations of ATII cells using a long-term survival model of rat LIRI. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomized into sham and ischemia-reperfusion (IR) groups. Animals of IR group underwent warm ischemia for 60 minutes by left pulmonary hilum occlusion. Injury was assessed by histological examination and myeloperoxidase activity assay. The proliferation profile of ATII cells was evaluated by immunofluorescence double staining. Surfactant protein-C (SP-C) and caspase-3 expression were determined by reverse transcription polymerase chain reaction. Ultrastructure and stereological analysis were used to quantify the alterations of nuclei and lamellar bodies (LBs) of ATII cells. RESULTS: As compared with the sham group, SP-C expression in the IR group significantly decreased at the early phase of LIRI and returned to normal in 7 days after reperfusion. SP-C/PCNA double positive cell number significantly increased at 1d, peaked at 3d and decreased to normal until 7 days after reperfusion. Ultrastructure and stereological analysis of ATII cells also showed that LBs were remarkably impaired at the early phase of LIRI and recovered up to 7 days after reperfusion. CONCLUSIONS: This model is simple, stable and reproducible. ATII cells demonstrated a self-repair capacity in a slow manner following the early phase of LIRI. Enhancing self-repair capacity of ATII cells may be a potential way of alleviating or curing LIRI.

Clinical experience of lobectomy with pulmonary artery reconstruction for central non-small-cell lung cancer.

BACKGROUND: In patients with central lung cancer, lobectomy can be achieved without pneumonectomy by surgical reconstruction of the pulmonary artery (PA). Herein, we report our clinical experience of 34 patients who had lobectomy with PA reconstruction, including perioperative administration, morbidity, mortality, and long-term survival. PATIENTS AND METHODS: The clinical records of 34 patients who received lobectomy with PA reconstruction in our department between August 2003 and September 2005 were reviewed. RESULTS: In our series, PA reconstruction with end-to-end anastomosis was performed in 18 patients (52.9%). Seven patients (20.6%) required partial PA reconstruction with autologous pericardium patch. Five patients (14.7%) with a lower lobe tumor required PA reconstruction with artery flap. The perioperative mortality was 2.9%, and 1 patient died on postoperative day 13 because of severe bronchopleural fistula. Another 2 patients had acute respiratory distress syndrome (ARDS) and required reintubation in our Intensive Care Unit. The overall Kaplan-Meier 3-year and 5-year survival rates were 46% and 37%, respectively. As compared with the stage III patients, stage I patients had significantly greater 5-year survival (80% vs. 11%; P = .005). Patients with pN0 disease also had greater 5-year survival than patients with pN2-3 disease (71% vs. 9%; P = .004). CONCLUSION: In our department, PA reconstruction has been more frequently and actively performed for patients with central lung cancer, especially for some patients with a lower lobe tumor. Although the morbidity and mortality is acceptable, surgeons should be more attentive to lethal postoperative complications such as ARDS induced by lung ischemia-reperfusion injury.

[Selection of Therapy Method for Stage III Non Small Cell Lung Cancer after Induction Chemotherapy.].

BACKGROUND: It is the main choice that neoadjust chemotherapy following surgery and induction chemotherapy following radiation therapy for locally advanced lung cancer. The aim of this study is to explore the selection of operation or synchronous radiotherapy and chemotherapy for stage III non small cell lung cancer (NSCLC) after induction chemotherapy. METHODS: After two cycles of induction chemotherapy, patients with stage III NSCLC were divided at random into synchronous radiotherapy and chemotherapy group or operation therapy group for therapy by the chemotherapy effect PR or CR, or estimated complete excision; and patients accepting complete excision operation continuously accepted two cycles of chemotherapy according to original proposal. RESULTS: Total 71 patients with stage III NSCLC entered therapy group after induction chemotherapy. Where, 37 patients accepted synchronous radiotherapy and chemotherapy, and 34 patients accepted operation. The 1-year, 2-year, and 3-year survival rate of synchronous radiotherapy and chemotherapy group was 78.4%, 40.5% and 23.4% respectively, while that of operation group was 81.1%, 39.5% and 35.1% respectively. The medium survival of the two groups was 18.0+/-2.4 and 23.0+/-1.6 respectively, and there was no statistical difference (P=0.23) in survival rate. The disease-free survival rate of synchronous radiotherapy and chemotherapy group and operation group was 14.0+/-1.7 months and 19.0+/-3.2 months respectively (P=0.044), and obviously, there was statistical difference. CONCLUSIONS: After induction chemotherapy, patients with stage III NSCLC could select operation therapy and synchronous radiotherapy and chemotherapy. Where, synchronous radiotherapy and chemotherapy is relatively safe, but the adverse reaction can't be ignored. Operation therapy has higher risk and difficulty for induction chemotherapy, but has shown its superiority in disease-free survival.

[Surgical treatment for locally advanced lung cancer invading heart and great vessels].

BACKGROUND: To summarize the surgical treatment for locally advanced lung cancer invading heart and great vessels. METHODS: One hundred and eighteen cases of lung cancer accepting cardiovascular plasty operation from 1980 to 2001 were reviewed. RESULTS: The operations included partial resection of left atrium in 38 cases, pulmonary artery resection and restruction in 48 cases, replacement or partial resection of superior vena cava in 25 cases, partial resection of pulmonary conus in 3 cases, and lober replantation in 4 cases respectively. There was no perioperative death, and the 1-, 3-, 5- and 10 year survival rate was 72.68%, 55.20%, 28.62% and 20.36% respectively. CONCLUSIONS: Cardiovascular plasty in the surgical treatment of locally advanced lung cancer invading heart or great vessels can remarkably increase the long-term survival and improve the life quality of the patients.