Daping Yu

Pulmonary Lobectomy Combined with Pulmonary Arterioplasty by Complete Video-assisted Thoracic Surgery in Patients with Lung Cancer

OBJECTIVE To explore the feasibility of pulmonary lobectomy combined with pulmonary arterioplasty by complete video-assisted thoracic surgery (VATS) in patients with lung cancer, and summarize its surgical methods. MATERIALS AND METHODS Twenty-one patients with lung cancer in Beijing Chest Hospital Affiliated to Capital Medical University from Feb., 2010 to Jun., 2013 were selected, males and females accounting for 15 and 6 cases, respectively. Ten underwent right upper lobectomy, 5 right lower lobectomy, 4 left upper lobectomy (in which left upper sleeve lobectomy was conducted for 2) and 2 left lower lobectomy. At the same time, local resection of pulmonary arterioplasty was performed for 12 patients, and sleeve resection of pulmonary arterioplasty for 9. RESULTS Twenty-one patients recovered well after surgery. Thoracic drainage tube was maintained for 3-8 days, with an average of 4.9 days, and hospital stays were 8-15 days, with an average of 11 days. There were no deaths in the perioperative period, and the complications like pulmonary embolism, bronchopleural fistula, chest infection and pulmonary atelectasis did not occur after surgery. CONCLUSIONS Performance of pulmonary lobectomy and pulmonary arterioplasty together by complete VATS is a safe and effective surgical method, which can expand the indications of patients with lung cancer undergoing thoracoscopic pulmonary lobectomy, and make more patients profit from such minimally invasive treatment.

CD3+ CD4+ and CD3+ CD8+ lymphocyte subgroups and their surface receptors NKG2D and NKG2A in patients with non-small cell lung cancer.

BACKGROUND To explore the prevalence of lymphocyte subgroups CD3+ CD4+ and CD3+ CD8+ and their surface receptors NKG2D and NKG2A in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS A total of 40 patients with NSCLC were divided into different groups according to different clinical factors (TNM staging, pathological patterns and genders) for assessment of relations with CD3+ CD4+ and CD3+ CD8+ and the surface receptors NKG2D and NKG2A of T lymphocytes in peripheral blood by flow cytometry. RESULTS Patients in the advanced group had evidently lower levels of CD3+ CD4+ but markedly higher levels of CD3+ CD8+ in peripheral blood than those with early lesions (p<0.05). In addition, NSCLC patients in the advanced group had obviously higher CD3+ CD4+ NKG2D and CD3+ CD8+ NKG2A expression rates but lower CD3+ CD4+ NKG2A and CD3+ CD8+ NKG2D expression rates (p<0.05). However, there were no significant differences between NSCLC patients with different genders and pathological patterns in expression levels of lymphocyte subgroups CD3+ CD4+ and CD3+ CD8+ and their surface receptors NKG2D and NKG2A. CONCLUSIONS Unbalanced expression of surface receptors NKG2D and NKG2A in CD3+ CD4+ and CD3+ CD8+ lymphocytes may be associated with a poor prognosis, greater malignancy and immunological evasion by advanced cancers, related to progression of lung cancer.

Sleeve lobectomy by video-assisted thoracic surgery versus thoracotomy for non-small cell lung cancer

BackgroundBoth video-assisted thoracic surgery (VATS) and thoracotomy are used for sleeve lobectomy for patients with non-small cell lung cancer (NSCLC). This retrospective study aimed to assess the safety and efficacy of VATS sleeve lobectomy for NSCLC patients.MethodsBetween May 2009 and May 2013, 51 sleeve lobectomies (10 by VATS and 41 by thoracotomy) were performed for patients with NSCLC. Operative characteristics and postoperative course were compared between two groups.ResultsPatient demographics were similar between the two groups. Thoracotomy patients had larger tumors compared with VATS patients (p = 0.02). VATS patients had a longer operating time (p < 0.001) but a shorter length of postoperative hospital stay (p = 0.009). The two groups did not differ in pathologic stage, histologic results, blood loss, ICU stay, amount of chest drainage, duration of chest drainage, numbers and distributions of dissected lymph nodes and the occurrence of complications. There were no perioperative deaths in the VATS group, whereas there was one death (2.4 %) in the thoracotomy group. There were no conversions to thoracotomy in the VATS group. The overall median survival between the two groups was similar (3.2 years VATS versus 3.2 years thoracotomy, log-rank p = 0.58).ConclusionsVATS sleeve lobectomy for the treatment of NSCLC is technically feasible and safe and is associated with comparable complication rates and survival compared with thoracotomy approach, but it deserves further investigation in large series.

CiRS‐7 targeting miR‐7 modulates the progression of non‐small cell lung cancer in a manner dependent on NF‐κB signalling

The purpose of this study was to figure out the effect of ciRS‐7/miR‐7/NF‐κB axis on the development of non‐small cell lung cancer (NSCLC). In response, the expressions of ciRS‐7, miR‐7 and NF‐κB subunit (ie RELA) within NSCLC tissues and cell lines were determined with real‐time polymerase chain reaction (RT‐PCR) and Western blot. Moreover, the NSCLC cells were transfected with pcDNA3‐ciRS‐7‐ir, pcDNA3‐ciRS‐7, miR‐NC and miR‐7 mimic. Furthermore, the targeted relationships between ciRS‐7 and miR‐7, as well as between miR‐7 and RELA, were confirmed by luciferase reporter assay. The proliferation, migration and apoptosis of NSCLC cells were, successively, measured using CCK‐8 assay, wound‐healing assay and flow cytometry test. Consequently, ciRS‐7, miR‐7, histopathological grade, lymph node metastasis and histopathological stage could independently predict the prognosis of patients with NSCLC (all P < .05). Moreover, remarkably up‐regulated ciRS‐7 and RELA expressions, as along with down‐regulated miR‐7 expressions, were found within NSCLC tissues and cells in comparison with normal ones (P < .05). Besides, overexpressed ciRS‐7 and underexpressed miR‐7 were correlated with increased proliferation, migration and invasion, yet reduced apoptosis rate of NSCLC cells (P < .05). More than that, ciRS‐7 specifically targeted miR‐7 to reduce its expressions (P < .05). Ultimately, the NSCLC cells within miR‐7 + RELA group were observed with superior proliferative, migratory and invasive capabilities than those within miR‐7 group (P < .05), and RELA expression was also significantly modified by both ciRS‐7 and miR‐7 (P < .05). In conclusion, the ciRS‐7/miR‐7/NF‐kB axis could exert pronounced impacts on the proliferation, migration, invasion and apoptosis of NSCLC cells.

The clinicopathological significance of hMLH1 hypermethylation in non-small-cell lung cancer: a meta-analysis and literature review

The hMLH1 gene plays an essential role in DNA repair. Methylation of the hMLH1 gene is common in many types of cancer and can lead to the loss of hMLH1 expression. However, the association and clinicopathological significance between hMLH1 promoter hypermethylation and non-small-cell lung cancer (NSCLC) is elusive. Here, we investigated the correlation of hMLH1 promoter hypermethylation and NSCLC using 13 studies by comprising 1,056 lung cancer patients via a meta-analysis. We observed that 1) loss of hMLH1 protein expression was significantly associated with its promoter hypermethylation, 2) hMLH1 gene inactivation through hypermethylation contributed to the tumorigenesis of NSCLC, which could be a decisive factor for the pathogenesis of NSCLC due to its high occurrence in NSCLC tissues compared to normal lung tissues, 3) a correlation exists between histologic subtypes/disease stages (TNM I+II vs III+IV) and hypermethylation status of hMLH1 gene, and 4) NSCLC patients with hMLH1 hypermethylation and subsequent low expression levels of hMLH1 have a short overall survival period than those patients with normal expression of hMLH1 gene. hMLH1 mRNA predicts patient survival in lung cancer, and this was confirmed by using a public database. We then discussed the tumor suppressor function of hMLH1 and the clinicopathological significance of hMLH1 in NSCLC. We concluded that hMLH1 hypermethylation should be an early diagnostic marker for NSCLC and also a prognostic index for NSCLC. hMLH1 is an interesting therapeutic target in human lung cancers.

Clinicopathological significance and a potential drug target of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic review

Lung cancer is the leading cause of cancer-related mortality in men worldwide. Aberrant RARβ promoter methylation has been frequently investigated in non-small-cell lung carcinoma (NSCLC), the most common form of lung cancer. The aim of present study was to carry out a meta-analysis and a systematic review to evaluate clinicopathological significance of RARβ promoter hypermethylation in NSCLC. A systematic literature search was carried out. The data were extracted and assessed by two reviewers independently. The Cochrane software Review Manager 5.2 was used to conduct the review. Odds ratios (ORs) with 95% corresponding confidence intervals (CIs) were calculated. A total of 18 relevant articles were available for meta-analysis which included 1,871 participants. The frequency of RARβ hypermethylation was significantly increased in NSCLC than in nonmalignant lung tissue, and the pooled OR was 5.69 (P<0.00001). RARβ hypermethylation was significantly more frequently observed in adenocarcinoma (AC) than in squamous cell carcinoma (SCC), and the pooled OR was 1.47 (P=0.005). Hypermethylation of RARβ gene in NSCLC was 2.46 times higher in smoking than in nonsmoking individuals, and the pooled OR was 2.46 (P=0.0002). RARβ hypermethylation rate was not significantly correlated with stage of the disease and sex. RARβ gene methylation status was not associated with prognosis of patients with NSCLC. In conclusion, RARβ promoter hypermethylation significantly increased in NSCLC than in non-neoplastic lung tissue and is predominant in AC, suggesting that RARβ methylation contributes to the development of NSCLC, especially AC. RARβ gene is a potential novel target for development of personalized therapy in patients with NSCLC, and is promising in restoration of retinoic acid-target gene induction via demethylation of RARβ1′ promoter.

Surgical treatment for pulmonary tuberculosis: is video-assisted thoracic surgery "better" than thoracotomy?

OBJECTIVE To compare video-assisted thoracoscopic surgery (VATS) lobectomy and conventional open lobectomy in patients with pulmonary tuberculosis (TB) who require surgery. METHODS Forty patients with pulmonary TB who required lobectomy were randomized to receive either VATS or open lobectomy. Patient demographic, pulmonary function, operative, and postoperative data were compared between the groups. RESULTS There were 20 patients who received VATS lobectomy (median age 31.5 years, range 19-67 years) and 20 that received open lobectomy (median age 33.5 years, range 16-60 years). The two groups were similar with respect to gender, age and pulmonary function (all, P>0.05). Lobectomy was completed by VATS in 19 of 20 patients (95%), and by thoracoscope-assisted mini-incision lobectomy in 1 patient. The median intraoperative blood loss was 345 mL (range, 100-800 mL), and the median duration of pleural cavity closed drainage was 5 days (range, 3-7 days). All open lobectomies were completed successfully, and the median intraoperative blood loss was 445 mL (range, 150-950 mL) and the median duration of pleural cavity closed drainage was 5 days (range, 3-9 days). No statistically significant differences were found between the groups with respect to operation completion rates, type of lung resection, intraoperative blood loss, closed pleural drainage duration and volume of postoperative chest drainage. The operation time, number of postoperative complications, postoperative pain index at 24 hours after surgery and postoperative hospital stay were all significantly less in the VATS group. With a median follow-up duration of 14 months (range, 8-18 months) no positive sputum examination results were found in either group. CONCLUSIONS VATS lobectomy is an effective and minimally invasive method for treating patients with pulmonary TB.

Exploratory study on the correlation between 14 lung cancer-related gene expression and specific clinical characteristics of NSCLC patients

Personalized medicine has become essential in the treatment of lung cancer. However, the lung cancer-related gene expression profiles in non-small cell lung cancer (NSCLC) patients have not been elucidated. In this study, the correlation between gene expression profiles and clinicopathological characteristics was investigated in NSCLC patients. A total of 95 patients were enrolled in this study. The mRNA expression levels of 14 genes were assessed by multiplex branched DNA liquidchip (MBL) technology and data on 9 clinicopathological characteristics of patients were collected simultaneously. The correlation between gene expression and clinicopathological characteristics was investigated. Out of the 9 clinicopathological parameters, 6 were associated with several of the 14 genes analyzed. Patient gender was associated with TYMS and TOP2A. Clinical stage was associated with VEGFR2, KIT and HER2. There was weak correlation between primary tumor size of ≤3 cm and the expression level of KIT. The mRNA expression levels of VEGFR2 and HER2 correlated with distant metastasis. BRCA1, TYMS, TOP2A and HER2 were associated with histological type. Smoking correlated with higher expression levels of BRCA1, TYMS and TOP2A and lower expression levels of PDGFRβ. The results were suggestive of correlation between the clinicopathological parameters of the NSCLC patients and the mRNA expression levels of certain lung cancer-related genes, including BRCA1, TYMS, TOP2A, PDGFRβ, VEGFR2, KIT and HER2.

Transdermal delivery of isoniazid and rifampin in guinea pigs by electro-phonophoresis

Abstract Electro-phonophoresis (EP) has been used as a drug delivery approach in clinical fields. The objective of the present study is to evaluate the skin permeability of isoniazid and rifampin in guinea pigs by EP to provide reference basis for clinical applications of such transdermal delivery system in the treatment of patients with superficial tuberculosis. Isoniazid and rifampin solutions were delivered transdermally with or without EP in health guinea pigs for 0.5 h. Local skin and blood samples were collected serially at 0, 1/2, 1, 2, 4, 6 and 24 h after dosing. Drug concentrations in local skin and blood were evaluated by high-performance liquid chromatography. Isoniazid concentrations in local skin of guinea pigs receiving isoniazid through EP transdermal delivery were significantly higher than in animals receiving only isoniazid with transdermal patch. However, for rifampin, patches alone group presented almost uniform concentration versus time curve with that of EP group, and both groups had concentrations much higher than the therapeutic concentration of the drug over sustainable time. After EP transdermal delivery, the mean peak concentrations of isoniazid and rifampin in skin were 771.0 ± 163.4 μg/mL and 81.2 ± 17.3 μg/mL respectively. Neither isoniazid nor rifampin concentration in blood could be detected (below the lower detection limit of 1 μg/mL) at any time point. The present study showed that application of EP significantly enhanced INH penetration through skin in guinea pigs, while RIF patch alone obtained therapeutic concentration in local skin. Our work suggests several possible medication approaches for efficient treatment of superficial tuberculosis.

Long Noncoding RNA LINC00472 Inhibits Proliferation and Promotes Apoptosis of Lung Adenocarcinoma Cells via Regulating miR-24-3p/DEDD

Objective: We aimed to detect the role of LINC00472 via regulating miR-24-3p and death effector domain-containing DNA-binding protein in lung adenocarcinoma. Methods: Long noncoding RNA, microRNA, and messenger RNA levels were determined using reverse transcription quantitative polymerase chain reaction. The expression of death effector domain-containing DNA-binding protein was determined using Western blot assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay were conducted to explore the proliferation of cells. The cell apoptosis was tested by flow cytometry assay. Target relationships between miR-24-3p, death effector domain-containing DNA-binding protein, and LINC00472 were validated by dual-luciferase reporter gene assay. Results: LINC00472 and death effector domain-containing DNA-binding protein were found to be underexpressed, whereas miR-24-3p was found overexpressed in lung adenocarcinoma cell lines and tissues. Both LINC00472 and death effector domain-containing DNA-binding protein can bind to miR-24-3p. Overexpression of LINC00472 led to higher death effector domain-containing DNA-binding protein level, demoting cell proliferation while promoting apoptosis. Overexpression of miR-24-3p reduced death effector domain-containing DNA-binding protein level, which facilitated cell proliferation and inhibited cell apoptosis, as well as to some extent restrained the effects of LINC00472. The high expression of miR-24-3p in tumor cells was negatively related to LINC00472 and death effector domain-containing DNA-binding protein, whereas the expression of LINC00472 and that of death effector domain-containing DNA-binding protein were positively correlated. Conclusion: Our findings suggested that LINC00472 contributed to the increase in lung adenocarcinoma cell apoptosis and the inhibition of proliferation via regulating miR-24-3p/DEDD, which might provide a novel insight into potential therapeutic approach for lung adenocarcinoma.