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Background The outcomes of video-assisted thoracic bronchial sleeve lobectomy (VABSL), a minimally invasive video-assisted thoracoscopic (VATS) lobectomy, are mostly unknown in Chinese patients. Objectives To investigate operative and postoperative outcomes of VABSL in a cases series of Chinese patients with lung cancer. Methods Retrospective study of 9 patients (male:female 8:1; mean age 59.4 ± 17.6 years, ranging 21–79 years) diagnosed with lung cancer of a single lobe, treated with VABSL between March 2009 and November 2011, and followed up for at least 2 months (mean follow-up: 14.17 ± 12.91 months). Operative outcomes (tumor size, operation time, estimated blood loss and blood transfusion), postoperative outcomes (intensive care unit [ICU] stay, hospitalization length and pathological tumor stage), death, tumor recurrence and safety were assessed. Results Patients were diagnosed with carcinoid cancer (11.1%), squamous carcinoma (66.7%) or small cell carcinoma (22.2%), affecting the right (77.8%) or left (22.2%) lung lobes in the upper (55.6%), middle (11.1%) or lower (33.3%) regions. TNM stages were T2 (88.9%) or T3 (11.1%); N0 (66.7%), N1 (11.1%) or N2 (22.2%); and M0 (100%). No patient required conversion to thoracotomy. Mean tumor size, operation time and blood loss were 2.50 ± 0.75 cm, 203 ± 20 min and 390 ± 206 ml, respectively. Patients were treated in the ICU for 18.7 ± 0.7 hours, and overall hospitalization duration was 20.8 ± 2.0 days. No deaths, recurrences or severe complications were reported. Conclusions VABSL surgery is safe and effective for treatment of lung cancer by experienced physicians, warranting wider implementation of VABSL and VATS training in China.

Breast cancer is the most common female malignancy and it frequently metastasizes to bone. Metastatic breast cancer continues to be the primary cause of death for women in East and Southeast Asia. Psoralen is a furocoumarin that can be isolated from the seeds of Psoralea corylifolia L. Psoralen exhibits a wide range of biological properties and has been demonstrated as an antioxidant, antidepressant, anticancer, antibacterial, and antiviral agent. Additionally, it is involved in the formation and regulation of bone. This study investigated whether psoralen can inhibit metastasis of breast cancer to bone in vivo. Histological, molecular biological, and imaging analyses revealed that psoralen inhibits bone metastases in mice. Psoralen may function to inhibit breast cancer cell growth in the bone microenvironment and regulate the function of osteoblasts and osteoclasts in tumor-bearing mice. The results of this study suggest that psoralen is a bone-modifying agent and a potential therapeutic to treat patients with bone metastases.

The human epidermal growth factor receptor (EGFR) has been established as an attractive target for lung cancer therapy. However, an acquired EGFR T790M gatekeeper mutation is frequently observed in patients treated with first-line anticancer agents such as gefitinib and erlotinib to cause drug resistance, largely limiting the application of small-molecule kinase inhibitors in EGFR-targeted chemotherapy. Previously, the reversible pan-kinase inhibitor staurosporine and its several analogs such as Go6976 and K252a have been reported to selectively inhibit the EGFR T790M mutant (EGFRT790M ) over wild-type kinase (EGFRWT ), suggesting that the staurosporine scaffold is potentially to develop the wild-type sparing reversible inhibitors of EGFRT790M . Here, we systematically evaluated the inhibitor response of 28 staurosporine scaffold-based compounds to EGFR T790M mutation at structural, energetic, and molecular levels by using an integrated in silico-in vitro analog-sensitive (AS) kinase technology. With the strategy, we were able to identify 4 novel wild-type sparing inhibitors UCN-01, UCN-02, AFN941, and SB-218078 with high or moderate selectivity of 30-, 45-, 5-, and 8-fold for EGFRT790M over EGFRWT , respectively, which are comparable with or even better than that of the parent compound staurosporine (24-fold). Molecular modeling and structural analysis revealed that van der Waals contacts and hydrophobic forces can form between the side chain of mutated residue Met790 and the pyrrolidinone moiety of inhibitor ligand UCN-02, which may simultaneously improve the favorable interaction energy between the kinase and inhibitor, and reduce the unfavorable desolvation penalty upon the kinase-inhibitor binding. A hydroxyl group of UCN-02 additional to staurosporine locates at the pyrrolidinone moiety, which can largely alter the electronic distribution of pyrrolidinone moiety and thus promote the intermolecular interaction with Met790 residue. This can well explain the measured higher selectivity of UCN-02 than staurosporine for mutant over wild-type kinase.

Xiaoyun Song,* Kang Shi,* Shi-Jie Zhou, Da-Ping Yu, Zhidong Liu, Yi Han Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, People’sRepublic of China *These authors contributed equally tothis work Abstract: 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

Hepatoma-derived growth factor (HDGF), a novel growth factor, has a widely expression in many normal cells and tumor cells. It plays an important role in cell proliferation, differentiation and angiogenesis. It is considered as a promising marker for predicting the invasion, matastasis and prognosis of carcinomas in clinical researches. The aim of this study is to evaluate the expression of HDGF and its clinical implication in patients who undergone complete resection for stage I non-small cell lung cancer (NSCLC).Immunohistochemical technology was applied to detect the expression of HDGF in 118 lung cancer tissues and 30 normal lung tissues as control.HDGF staining was observed in nuclear as well as in cytoplasm. HDGF positively staining was seen in all patients, and remarkably higher than that in normal lung tissues (52.23±10.35 vs 156.73±70.95, P0.01). Expresson of HDGF was closely related to histological classification, but not to other clinicopathological factors, and the expression of HDGF in adenocarcinoma was much stronger than that in squamous cancers (P=0.001). Univariate analysis and multivariate Cox regression analysis showed that the patients with high HDGF expression had a shorter overall survival and HDGF was a significantly independent predictive factor for patients with stage I NSCLC (RR=1.011, P=0.002).HDGF may be a promising predictive factor for stage I NSCLC, and the assessment of HDGF may provide new insight on carcinogenesis and development of stage I NSCLC .

The latest studies have demonstrated that postoperative adjuvant chemotherapy may improve survival in patients with stage I non-small cell lung cancer (NSCLC), so it was a challenge for clinician to choose the patients who might benefit from adjuvant chemotherapy. The aim of this study is to evaluate the prognostic implications of angiogenesis and tumor blood vessel invasion (BVI) in stage I NSCLC patients who underwent complete resection.One hundred and eighteen stage I NSCLC patients undergoing complete resection from 1994-2002 were retrospectively reviewed. Angiogenesis was assessed by vascular endothelial growth factor (VEGF) and microvessel density (MVD), BVI was assessed by examining the direct invasion of tumor cells marked by CD34 within vessel lumen.Low VEGF expression was seen in 44 patients (37.3%), high VEGF expression was in 74 patients (62.7%). The MVD of high VEGF expression cases was much higher than that of low VEGF expression ones (33.4±17.8 vs 24.7±14.8, P=0.010). There was a positive correlation between VEGF and MVD (r=0.216, P=0.019). The 5-year survival rate in patients with high VEGF expression was much lower than in those with low VEGF expression (36.48% vs 72.20%, P=0.003). The BVI was present in 32 patients (27.1%) and absent in 86 patients (72.9%). The 5-year survival rate in patients with presence of BVI was much lower than those with absence of BVI (34.38% vs 60.47%, P=0.018). Multivariate COX regression analysis showed that high VEGF expression and BVI were significantly independent predictive factors for overall survival. Finally, the presence of both risk factors, BVI and high VEGF expression was highly predictive of poor outcome (P= 0.001 ).Tumor vessel invasion and high VEGF expression are independent prognostic factors for overall survival of postoperative stage I NSCLC. The assessment of these factors may improve prognostic stratification for adjuvant therapy or a targeted and specific treatment in stage I NSCLC.

Progress has been made in research of lung cancer tumor markers in recent years,and these tumor markers have been used in clinical application. This study is to evaluate the regimens of six serum tumor markers in lung cancer diagnosis.The serum levels of the six tumor markers(NSE, pro-GRP, CYFRA21-1, SCC, p53 antibody and CA199) were detected in 80 healthy adults,170 patients with lung cancer and 80 patients with respiratory infection by ELISA.The levels of the six tumor markers in patients with lung cancer were remarkably higher than those in healthy adults and patients with respiratory infection(P0.01).The levels of the NSE,pro-GRP in patients with small cell lung cancer were significantly higher than those in other subtypes of the lung cancer(P0.01);The levels of the CYFRA21-1,SCC in patients with squamous carcinoma was remarkably higher than that in other subtypes of the lung cancer(P0.01).The sensitivity of the NSE,pro-GRP in diagnosing small cell lung cancer was remarkably higher than that in other subtypes of the lung cancer(P0.01); The sensitivity of the CYFRA21-1, SCC in diagnosing squamous carcinoma was remarkably higher than that in other subtypes of the lung cancer(P0.01).The sensitivity of the tumor markers combinations in diagnosing lung cancer was remarkably higher than that of the single marker (P0.01).Detection of the six tumor markers is helpful for diagnosis lung cancer. Combination of NSE and pro-GRP is more economic than other combinations in diagnosing small cell lung cancer; Combined CYFRA21-1,SCC is more economic than other combinations in diagnosing squamous carcinoma.