Shanqing Li

Expression of miR-148/152 family as potential biomarkers in non-small-cell lung cancer.

Background Altered miR-148/152 family expression contributes to human carcinogenesis. This study was designed to detect the potential for using miR-148/152 family as biomarkers for NSCLC patients. Material/Methods The relative expression levels of miR-148/152 family (miR-148a, miR-148b, and miR-152) in serum of 36 non-small-cell lung carcinoma (NSCLC) patients, 20 patients with benign pulmonary diseases (BPD), and 10 healthy individuals were assessed by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results The expression of all three miRNAs were significantly lower in the serum of NSCLC than that of BPD and healthy controls (all p<0.01), and their expression levels were strongly correlated with each other (r=0.781, 0.720, and 0.645, respectively). Downregulation of miR-148/152 family was found to be corrected with more aggressive tumors. The area under the receiver operating characteristic curves (AUCs) for miR-148a, miR-148b, and miR-152 discriminating NSCLC from BPD were 0.775, 0.725, and 0.774, respectively, all higher than that of CEA (0.506). Combining the three miRNAs increased the discrimination performance, yielding an AUC of 0.789 (95% confidence interval, 0.643 to 0.895), with a sensitivity of 72.2% and a specificity of 90.0%. Conclusions The results of present study suggest that the expression levels of circulating miR-148/152 family may serve as biomarkers for NSCLC.

Clinical features and treatment of bronchogenic cyst in adults.

OBJECTIVE To investigate the clinical features and management of bronchogenic cyst in the adults. METHODS We retrospectively reviewed 50 patients admitted to our hospital with histopathologically proved bronchogenic cyst from January 1983 to December 2007. Of all the patients, 28 were male and 22 were female, with an average age of 36.9 (range, 18 to 64) years. The symptoms, location of the cysts, imaging evaluation, surgical treatment manner, and outcome of these patients were analyzed. RESULTS Symptoms were present in 33 of the 50 patients, and cough was the most common symptom. Thirteen patients presented with complications: hemoptysis, infected cyst, dysphagia, paralysis, and hoarseness. The locations of the cysts included the mediastinum (28 cases), pulmonary parenchyma (12 cases), hilar area (3 cases), visceral pleura (1 case), and some rare locations including the intestinal mesentery (1 case), retroperitoneum (1 case), adrenal gland (1 case), neck (2 cases), and dura matter of the cervical vertebrae (1 case). Chest X-ray was performed in 36 patients and computed tomography (CT) was performed in 41 patients. The bronchogenic cyst in CT was characterized as a round, well circumscribed, unilocular mass, with density ranging from that of water to high density (0-50 Hu). As for treatment, complete resection of the bronchogenic cyst was performed in 47 (94%) patients, subtotal resection was performed in 3 (6%) patients. Open surgery was performed in 45 (90%) patients, and thoracoscopy (video-assisted thoracic surgery) was performed in 5 (10%) paitients. Of the 12 patients with intrapulmonary cyst, 11 patients underwent lobectomy and 1 patient underwent wedge resection. Postoperative sequelae occurred in 2 patients, 1 with persistent air leakage and 1 with hoarseness. All patients were proved with bronchogenic cyst pathologically. The average follow-up period was 6.5 years (range, 4 months to 10 years), and no late sequelae or recurrence of the cyst occurred. CONCLUSIONS The clinical and imaging presentations of bronchogenic cyst in adults are variable. Surgical resection is the best way for diagnosis and treatment. Both open surgery and thoracoscopy are appropriate for the selected candidates.

Long noncoding RNA MALAT-1 is a novel inflammatory regulator in human systemic lupus erythematosus

Despite growing evidence that Long noncoding RNAs (lncRNAs) can regulate gene expression and widely take part in autoimmune and inflammatory diseases, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. In this study, we aimed to explore the contribution of the lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) to the pathogenesis of SLE. PBMCs were obtained from SLE patients and healthy donors. The expression levels of MALAT-1 were measured by quantitative PCR. Small interfering RNA (siRNA) was then used to knock down the expression of MALAT1 in order to determine the role of MALAT1 in the expression levels of IL-21 and SIRT1 signaling pathway in primary monocytes of SLE patients. Here, we found MALAT-1 expression was abnormally increased in SLE patients and predominantly expressed in human monocytes. Additionally, silencing MALAT-1 significantly reduced the expression of IL-21 in primary monocytes of SLE patients. Furthermore, MALAT-1 exerts its detrimental effects by regulating SIRT1 signaling. Our results demonstrate that MALAT-1 is the key regulatory factor in the pathogenesis of SLE and provides potentially novel target for therapeutic intervention.

Surgical Treatment of Intralobar Pulmonary Sequestration

OBJECTIVE To evaluate the clinical features, diagnosis, treatment, and outcome of intralobar pulmonary sequestration (ILS). METHODS Patients who were diagnosed with ILS in our hospital between January 1988 and January 2009 were retrospectively reviewed. We recorded the clinical symptoms, imaging findings, operative technique, complications, and outcome of these patients. RESULTS Forty-seven patients (25 men and 22 women) with an average age of 32.3 years were enrolled. Forty-two patients had symptoms including cough and hemoptysis. Chest X-ray, computed tomography (CT), magnetic resonance imaging (MRI), and angiography were performed. Thoracotomy was performed in 45 patients, while thoracoscopy was performed in 2 patients. Lobectomy was the most common treatment procedure. Massive bleeding developed in 2 patients due to injury of aberrant supplying artery intraoperatively, 1 patient had atrial fibrillation, 1 patient had thrombosis of upper extremity postoperatively. All patients were confirmed the diagnosis pathologically, 4 accompanied with bronchogenic cyst, 15 with bronchiectasis, 8 with infection, 2 with aspergilloma, and 1 with carcinoid. No late complications occurred. CONCLUSIONS ILS is rare, surgery is recommended because some patients may have potential severe complications. Contrast enhanced CT and three-dimensional reconstruction is the best diagnostic method. Both thoracotomy and thoracoscopy are appropriate for the selected candidates.

Determining EGFR-TKI sensitivity of G719X and other uncommon EGFR mutations in non-small cell lung cancer: Perplexity and solution (Review)

Mutations in epidermal growth factor receptor (EGFR) play critical roles in the pathogenesis of non-small cell lung cancer (NSCLC), and they are highly associated with sensitivity to tyrosine kinase inhibitors (TKIs). While the pathogenic and pharmacological characteristics of common mutations in EGFR have been thoroughly investigated, those of uncommon mutations remain to be elucidated. Traditional approaches to study common mutations by randomized controlled trials are not feasible for uncommon mutations owing to their rarity. Therefore, by systematically reviewing laboratory and clinical studies of the G719X mutation, one of the uncommon mutations, we concluded that the G719X mutation was intermediately sensitive to TKIs, with an average response rate of 35.1% (47/134). Moreover, accordingly, we proposed a comprehensive model to investigate uncommon mutations in EGFR. The model involves both basic and clinical components, composed of structural analyses, functional alterations, cell viabilities and animal models with various types of clinical studies. In this review, we systematically reviewed studies of the G719X mutation and put forward a research model that could be generalized to explore uncommon mutations in diseases associated with gene mutations.

Inhibition of miR-23a increases the sensitivity of lung cancer stem cells to erlotinib through PTEN/PI3K/Akt pathway

Epidermal growth factor receptor-targeted tyrosine kinase inhibitors (EGFR-TKIs) have become first-line drugs used for non-small cell lung cancer (NSCLC) treatment. However, drug resistance to EGFR-TKIs will be developed inevitably due to the repeated use of these drugs. In the present study, we isolated cancer stem cells (CSCs) from the PC9 NSCLC cell line. We then observed that the PC9 CSCs showed significant resistance to erlotinib compared with the PC9 non-CSCs. Erlotinib failed to suppress the phosphorylation of PI3K and AKT in PC9 CSCs, although the EGFR was inhibited sufficiently. Mechanically, we observed aberrant upregulation of microRNA-23a (miR-23a) and downregulation of PTEN in PC9 CSCs compared to PC9 non-CSCs. Luciferase reporter assays proved that PTEN was the target of miR-23a in PC9 CSCs. Furthermore, knockdown of miR-23a enhanced the antitumor effect of erlotinib by increasing the expression of PTEN. In addition, transfection with miR-23a inhibitors promoted the erlotinib-dependent inhibition of PI3K/AKT pathway, thus, suppressing the proliferation and inducing apoptosis in PC9 CSCs. These results propose that upregulation of miR-23a is a potential mechanism associated with resistance to EGFR-TKIs in lung cancer stem cells. Inhibition of miR-23a serves as a novel therapeutic strategy to eliminate the EGFR-TKIs resistance of lung cancer stem cells.

Visfatin mediates doxorubicin resistance in human non-small-cell lung cancer via Akt-mediated up-regulation of ABCC1

Non–small‐cell lung cancer (NSCLC) is one of the leading causes of cancer deaths worldwide. Increasing levels of visfatin are correlated with worse clinical prognosis of NSCLC. However, the effects of visfatin on drug resistant are still not well illustrated.

Surgical Resection of Sternal Tumors and Reconstruction with Titanium Mesh

OBJECTIVE To evaluate the use of titanium mesh reconstruction after sternal tumor resection. METHODS From January 2007 to January 2011, 14 patients with sternal tumors were admitted into Peking Union Medical Hospital. The clinical characteristics, surgical resection, and technique of reconstruction were reviewed. RESULTS Of the 14 patients, 3 had a metastatic sternal tumor, the primary sites of which were as follows: hepatic carcinoma in one case (metastasis 19 years after operation), breast carcinoma in another case (metastasis 5 years after operation), and renal carcinoma in the other case (found simultaneously). Two patients showed local involvement of the sternum: 1 had thymic carcinoma, and the other had myofibrosarcoma. The remaining 9 patients had primary tumors: 4 were osteochondroma, 3 chondrosarcoma, 1 eosinophilic granuloma, 1 non-Hodgekins lymphoma. En bloc resection of the sternal tumor was performed in all the 14 patients. The defect was repaired with the titanium mesh adjusted to the shape of the defect and fixed with the stainless steel wire. Eleven patients were followed up for a period from 2 months to 4 years, during which no translocation or broken of the titanium mesh was observed. CONCLUSIONS Radical en bloc excision remains the treatment of choice for sternal tumors. Sternum defect reconstruction using titanium mesh as a rigid replacement proves appropriate and effective.

Paclitaxel increases the sensitivity of lung cancer cells to lobaplatin via PI3K/Akt pathway

The effect of paclitaxel combined with lobaplatin on the sensitivity of lung cancer cell line NCI-H446 through influencing the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was investigated. The sensitivity of lobaplatin to NCI-H446 and the effect of paclitaxel and PI3K inhibitor LY294002 combined with lobaplatin on the sensitivity to NCI-H446 were detected via methyl thiazolyltetrazolium (MTT) assay. The effect of paclitaxel combined with lobaplatin on cell apoptosis was detected using flow cytometry, the effect of paclitaxel combined with lobaplatin on the cell migration was detected via cell wound scratch assay, and the effect of paclitaxel combined with lobaplatin on the cell invasion was detected via Transwell assay. Finally, the effect of paclitaxel on PI3K/Akt pathway was detected via western blotting. MTT assay showed that 30 µg/ml lobaplatin could significantly inhibit the growth of NCI-H446 (p<0.01). Lobaplatin group (group L), 2 µg/ml paclitaxel combined with lobaplatin group (group LP) and lobaplatin combined with 10 µmol/ml LY294002 group (group LL) were set up. The cell survival rates in group LP and group LL were significantly lower than that in group L (p<0.01), and the cell survival rate in group LP was similar to that in group LL (p>0.05). Flow cytometry revealed that the cell apoptotic levels in group LP and group LL were obviously higher than that in group L (p<0.01), and there was no statistically significant difference in the cell apoptotic level between group LP and group LL (p>0.05). Cell wound scratch assay showed that the cell migration capacity in group LP was significantly lower than those in group L and group LL (p<0.01, p<0.05), and the cell migration capacity in group LL was lower than that in group L (p<0.05). Besides, Transwell assay revealed that the cell invasion capacity in group LP was obviously lower than those in group L and group LL (p<0.01, p<0.05), and the cell invasion capacity in group LL was lower than that in group L (p<0.01). Finally, western blotting showed that the levels of PI3K, phosphorylated-Akt (p-Akt) and phosphorylated-glycogen synthase kinase 3β (p-GSK3β) in group LP and group LL were significantly lower than those in group L, and the differences were statistically significant (p<0.01). Paclitaxel can significantly increase the sensitivity of lobaplatin to lung cancer cell line NCI-H446. Moreover, paclitaxel can enhance the effect of lobaplatin on lung cancer cells and reduce the drug resistance through inhibiting PI3K/Akt pathway.

Primary lung carcinoma combined with pulmonary amyloidosis secondary to syphilis infection

A 55-year-old female patient was found to have a pulmonary nodule combined with multiple lung cysts detected on CT scan. Video-assisted thoracoscopic surgery (VATS) lobectomy was performed and the nodule showed adenocarcinoma while the whole left upper lobe showed a heavy deposition of amyloid. Syphilis infection was detected and was suspected contributing to secondary pulmonary amyloidosis. Although very rare, pulmonary amyloidosis should be added to the differential diagnosis for solid pulmonary nodules. Furthermore, widespread lung cysts located apart from pulmonary nodules is especially rare in pulmonary amyloidosis secondary to syphilis infection.