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Background and objective Compared with tissue biopsy, liquid biopsy is the most preferable non-invasive promising method in personalized medicine, although it has many limitations in isolating circulating tumor cells (CTC). Lung cancer associated mortality is drastically increased due to a shortfall of early-stage detection, which remains a challenge. Herein, we aimed to detect lung cancer at an early-stage using CellCollector device. Methods 39,627 volunteers underwent low-dose computed tomography; 2508 cases with pulmonary nodules and 7080 with no pulmonary nodules were chosen. After follow-up, 24 patients were diagnosed with early-stage non-small cell lung cancer (NSCLC), and subjected to CTC detection using CellCollector, along with 72 healthy volunteers. Immunofluorescence staining for EpCAM/CKs and CD45 were performed for CTC validation. Results Fifteen out of twenty-four (stage I, n = 18; stage II, n = 6) early-stage lung cancer patients were found to be CTC-positive, whereas no CTC was found in the control group. Genetic mutation of TP53, ERBB2, PDGFRA, CFS1R and FGFR1 in the CTC revealed 71.6% of the mutation sites similar to the tumor tissues of 13 patients. Molecular characterization revealed higher expression of protein PD-LI in CTC (40%) as compared to tumor tissue (26.7%). Moreover, CTC clusters were detected in 40% of patients. Conclusion CTC detection using the CellCollector in early-stage NSCLC had a relative high capture rate. Moreover, CTC analysis is a prospective setting for molecular diagnostic in cases when tumor tissue biopsy is not desirable.

A pulse-coupled neural network (PCNN) is a promising image segmentation approach that requires no training. However, it is challenging to successfully apply a PCNN to medical image segmentation due to common but difficult scenarios such as irregular object shapes, blurred boundaries, and intensity inhomogeneity. To improve this situation, a novel framework incorporating fuzzy connectedness ( FC ) is proposed. First, a comparative study of the traditional PCNN models is carried out to analyze the framework and firing mechanism. Then, the characteristic matrix of fuzzy connectedness ( CMFC ) is presented for the first time. The CMFC can provide more intensity information and spatial relationships at the pixel level, which is helpful for producing a more reasonable firing mechanism in the PCNN models. Third, by integrating the CMFC into the PCNN framework models, a construction scheme of FC-PCNN models is designed. To illustrate this concept, a general solution that can be applied to different PCNN models is developed. Next, the segmentation performances of the proposed FC-PCNN models are evaluated by comparison with the traditional PCNN models, the traditional segmentation methods, and deep learning methods. The test images include synthetic and real medical images from the Internet and three public medical image datasets. The quantitative and visual comparative analysis demonstrates that the proposed FC-PCNN models outperform the traditional PCNN models and the traditional segmentation methods and achieve competitive performance to the deep learning methods. In addition, the proposed FC-PCNN models have favorable capability to eliminate inference from surrounding artifacts.

The 9-bp deletion of CCCCCTCTA at position 8272 in region V of mitochondrial DNA is one of the mitochondrial DNA microsatellite instability (mtMSI) sites that associated with cancers. In the present study, we investigated the association of 8272 deletion with the cancer risk and outcome for colorectal cancer (CRC). By the log-rank analysis, the 8272 CCCCCTCTA/del was identified as a prognostic marker for outcome of colorectal cancer patients with the deleted ones associated with shorter postoperative survival. After adjusted with Cox Hazard model, this MSI was associated independently with CRC outcome (relative risk, 2.038; 95%CI, 1.20-3.707; p = 0.020). The analysis of mtMSI can help to identify patient subgroups that are at high risk for poor disease outcomes.

At present, most of the classic Discriminative Correlation Filter (DCF) use rectangle to track targets. Although this method of selecting targets by rectangle is convenient, the shortcomings are also particularly obvious. For example, DCF may mistake some background information as target. Moreover, the DCF simply uses the linear method to update the target template, which will introduce interference into the model. In order to solve the above problems, we propose a mask and multi-peaks re-prediction correlation filter algorithm. First, the segmentation algorithm is used to extract the edge information in the target region, and the target mask is made according to the edge information. In this way more accurate target information is obtained. Secondly, when the target is interfered, the filtered response graph will fluctuate drastically. We compare the similarity between the target of the first frame and the alternative region that made through multiple peaks to select the most accurate and effective target, and use this target to update the model. We evaluated the proposed algorithm on the OTB-2013 dataset and UAV123 dataset, experiments show that our algorithm can better deal with background interference and has better performance than other advanced algorithms.

Whether smokers respond to anti-cancer drugs differently than non-smokers remains controversial. The objective of this study is to explore whether the better response of the smokers is specific to therapy of anti-PD-1/PD-L1, anti-checkpoint inhibitor, individual drugs on the cell surface, or lung cancer. Our results showed that among all non-small cell lung cancer (NSCLC) patients, when the data from anti-PD-1/PD-L1, anti-CTLA-4, and anti-MUC1 drugs are combined, the mean hazard ratios (HR) of smokers and non-smokers were 0.751 and 1.016, respectively. A meta-analysis with a fixed effect (FE) model indicated that the smokers have an HR value of 0.023 lower than that of the non-smokers. A stratified subgroup meta-analysis indicated that when treated with anti-CTLA-4 drugs, smokers had reduced HR values of 0.152 and 0.165 on average and FE model meta-analysis, respectively. When treated with an anti-MUC1 drug, smokers had reduced HR values of 1.563 and 0.645, on average and FE model meta-analysis, respectively. When treated with a combination of nivolumab and ipilimumab drugs, smokers had, on average, reduced HR and FE model meta-analysis values (0.257 and 0.141), respectively. Smoking is a clinical response predictor for anti-PD/PD-L1 monotherapy or first-line treatment in lung, urothelial carcinoma, and head and neck cancer. Smokers treated with other drugs have shown worse responses in comparison to non-smokers. These data suggest that, along with the progress in the development of new drugs for cancer, drugs acting on specific genotypes of smokers likely will arise.

BackgroundLung cancer is a malignant tumor that has the highest morbidity and mortality rate among all cancers. Early diagnosis of lung cancer is a key factor in reducing mortality and improving prognosis.MethodsIn this study, we performed CTC next-generation sequencing (NGS) in early-stage lung cancer patients to identify lung cancer-related gene mutations. Meanwhile, a serum liquid chromatography-tandem mass spectrometry (LC-MS) untargeted metabolomics analysis was performed in the CTC-positive patients. To screen potential diagnostic markers for early lung cancer.Results62.5% (30/48) of lung cancer patients had ≥1 CTC. By CTC NGS, we found that > 50% of patients had 4 commonly mutated genes, namely, NOTCH1, IGF2, EGFR, and PTCH1. 47.37% (9/19) patients had ARIDH1 mutations. Additionally, 30 CTC-positive patients and 30 healthy volunteers were subjected to LC-MS untargeted metabolomics analysis. We found 100 different metabolites, and 10 different metabolites were identified through analysis, which may have potential clinical application value in the diagnosis of CTC-positive early-stage lung cancer (AUC >0.9).ConclusionsOur results indicate that NGS of CTC and metabolomics may provide new tumor markers for the early diagnosis of lung cancer.

Background: Synchronous multiple ground-glass nodules (SMGGNs) in synchronous multiple lung cancers (SMLCs) are associated with specific imaging findings. It is difficult to distinguish whether multiple nodules are primary tumors or metastatic lesions in the lungs. The need for positron-emission tomography/computed tomography (PET/CT) and contrast-enhanced brain magnetic resonance imaging (MRI) for these patients remains unclear. This study investigated the necessity of these two imaging examinations for SMGGN patients by means of retrospective analysis. Methods: SMGGN patients who were diagnosed and treated in the Department of Thoracic Surgery in our hospital from October 2017 to May 2020 and underwent whole-body PET/CT and/or contrast-enhanced brain MRI examinations were enrolled in this study. We analyzed the imaging and clinical characteristics of these patients to evaluate SMGGN patients’ need to undergo whole-body PET/CT and brain MRI examination. Results: A total of 87 SMGGN patients (26 men and 61 women, with a median age of 58 years at onset) were enrolled. Fifty-one patients underwent whole-body PET/CT examinations and did not show signs of primary tumors in other organs, metastatic foci in other organs, or metastasis to surrounding lymph nodes. Eighty-seven patients underwent whole-brain MRI, which did not reveal brain metastases but did detect an old cerebral infarction in 23 patients and a new cerebral infarction in one patient. Eighty-seven patients underwent surgical treatment in which 219 nodules were removed. All nodules were diagnosed as adenocarcinoma or atypical adenomatous hyperplasia. No lymph node metastasis was noted. Conclusion: For SMGGN patients, it is not necessary to perform a whole-body PET/CT examination before surgery. Contrast-enhanced brain MRI can assess the patient’s cerebrovascular function before surgery and reduce the risk of perioperative cerebrovascular accidents. Thus, it is a necessary examination.

Purpose The major concern technologies during the processing through three-dimensional printing (3DP) are the mechanical and boundary properties of sand models. The parameters such as activator content, resolution X, layer thickness and re-coater speed play a vital role in 3DP sand components. The purpose of this paper is to recommend the optimal process parameters for the best sand mold properties. Design/methodology/approach In this paper, taking the parameters of the activator content, resolution X, layer thickness and re-coater speed as the influence factors, an orthogonal test of L16(44) was designed to discuss the influences of those parameters on the mechanical and boundary properties. Three-point bending (3PB) test was used to characterize the actual bending strength, and the boundary accuracy was assessed by the deviation of the three-point bending samples compared with its design scale. Findings The experimental results showed that the resolution X and layer thickness are the main parameters affecting sand mold properties. The strength will attain its maximum when the resolution X and layer thickness are the minimum. The optimal parameters were screened and verified by the confirmation test. The optimal process parameters for best strength and less gas evolution are the activator of 0.19%, resolution X of 0.1 mm, layer thickness of 0.28 mm and re-coater speed of 210 mm/s. Originality/value The novelty of this paper is the select of significant parameters on 3D-printed sand model properties. A mathematical model was built to analyze the effect of these parameters. The optimal process parameters for the best properties were got.

Background: It remains controversial whether patients with EGFR-mutant lung adenocarcinoma should stop using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after progression during treatment. Case report: We report a 35-year-old man with poorly differentiated adenocarcinoma of the left upper lobe and an exon 19 deletion (Ex19Del) mutation found by large-panel next-generation sequencing. The patient underwent video-assisted thoracoscopic surgery 12 months after oral administration of icotinib 125 mg tid, and the left upper lobe and surrounding lymph nodes were removed. Postoperative pathology supported a diagnosis of left upper lobe adenocarcinoma and subcarinal (1/2), main pulmonary artery window (1/2), and left hilar (1/2) lymph node metastases. The EGFR mutations in the residual lesions had disappeared, and Ex19Del mutations were still visible in the mediastinal lymph node metastasis. Conclusion: Spatial heterogeneity of the resistance mechanism may explain why patients who continue to receive EGFR-TKIs in combination with local therapies (e.g., radiotherapy) for progressing lesions may benefit even after progression during EGFR-TKI therapy. The loss of the EGFR mutation allele as a putative resistance mechanism requires additional preclinical and clinical confirmation.

Supplemental Digital Content is available in the text, Introduction: Smoking is well-known to increase cancer risk, particularly risk of lung cancer, and negatively affects efficacy of cancer treatment. However, recent evidence suggests that among cancer patients, paradoxically, smokers respond to treatment better than non-smokers. We propose to conduct a focused review and meta-analysis to compare response to drug treatment between smoking and non-smoking cancer patients. Methods and design: We will collect data from large clinical trials of therapies for cancer patients which have included smokers and non-smokers. We will search PubMed, PMC/ MEDLINE, SCOPUS, Embase, and the registries for clinical trials and four major clinical journals up to June 30, 2019. Search terms will be “Drug name” phase-3” or “Drug name” phase-III.” Data collection will be focused on randomized clinical trials of cancer drugs that enrolled at least 100 participants and reporting treatment results from smoking and nonsmoking patients. Initial selection criteria will be clinical trial studies of drug treatment of 100 or more cancer patients, and reporting hazard ratios (HR) for smokers and non-smokers. Two persons will be searching such publications independently, or data will be provided, double checked, or confirmed by authors. Multiple sub-group analyses will be conducted by at least two persons to avoid bias or experimental errors. Discussion: The results will clarify whether smoking and response to treatment of cancer are linked not. Our results may possibly identify drug/s that work better among cancer patients who are smokers. Trial registration: PROSPERO registration number: CRD42019146402.

The treatment regimen for the eradication of Helicobacter pylori may be best when therapy is susceptibility guided. However, it is unrealistic to use a strategy based on susceptibility testing to prioritize therapy for every patient in China. Empirical therapy of H. pylori is still widely used. The study was designed to discuss the best first‐line treatment regimen depending on empirical therapy. The focal point of the study was the optimal length of the therapy. Also, the selection of antibiotics was discussed in the article. This was a prospective, randomized, non‐inferiority trial. H. pylori‐infected patients who have no previous eradication therapy were randomly assigned to the following: 20 mg of rabeprazole, 1000 mg of amoxicillin, 500 mg of clarithromycin, and 220 mg of bismuth potassium citrate (BACPPI), administered twice a day for 10 or 14 days. The efficacy, side effects, and remission rate of clinical symptoms were determined. A total of 240 subjects were included in the study. The eradication rate with 14 and 10 days was essentially identical in both intention‐to‐treat (90.83% [95% CI, 86%–96%] vs. 87.50% [95% CI, 82%–93%]) and per‐protocol (94.78% [95% CI, 91%–99%] vs. 92.11% [95% CI, 87%–97%]) analyses. Loss of appetite and belching symptoms were significantly better in the BACPPI‐10 group than those in the control group after treatment. Side effects were generally mild and similar between groups. Our results showed that a 10‐day amoxicillin–clarithromycin‐containing bismuth quadruple therapy may be recommended for the primary empirical treatment of H. pylori infection in Beijing, China., 10‐day amoxicillin–clarithromycin‐containing bismuth quadruple therapy may be recommended for the primary empirical treatment of Helicobacter pylori infection in China. The 14‐day therapy is expensive, uncomfortable for the patients, and has an increased risk of side effects. The 10‐day therapy was not inferior to the 14‐day therapy in terms of efficacy.

Background: There are potential benefits for cancer patients with programmed death-1 (PD-1) positive status to have a smoking status when treated with programmed death-1 (PD-1) and programmed death-ligand 1 (PD-1/PD-L1) inhibitors. This study is to compare the advantage of smokers with PD-L1 positive status over that of non-smokers in all types of cancer when treated by Anti-PD-1 and PD-L1 drugs. Methods: This study is a prospectively planned meta-analysis of Hazard ratios (HR) of both progression-free survival (PFS) and overall survival (OS) from the randomized clinical trials enrolling at least 100 participants treated with cancer drugs in different smoking status. HR of both PFS and OS were independently screened, extracted and compared among patients with different smoking behavior status from: 1) ten clinical trials of PD-1/PD-L1 inhibitors for non-small cell lung cancer (NSCLC), 2) Thirty-nine large clinical trials of all known other cancer drugs for NSCLC, 3) six trials of patients with on other types of cancer treated with PD-1/PD-L1 inhibitors, and 4) four trials of patients with other types of cancer treated with other drugs. HR values from smokers and non-smokers were used as the criteria of response to drug treatment and were compared with T-tests and Meta-analysis. Findings: The primary outcome was smokers who were treated with PD-1/PD-L1 inhibitors had better outcomes than non-smokers when the drug was used as monotherapy in the treatment of NSCLC as well as other types of cancer. A total of 59 clinical trials with more than 40,000 total patients were included in this systematic review and 27,600 in meta-analysis. Among NSCLC patients, treated with PD-1/PD-L1 inhibitors, smokers had a better outcome with a mean HR value of 0.070 lower than non-smokers when the drugs were used as monotherapy. Among patients having other types of cancer, response to PD-1/PD-L1 inhibitor treatment was better in smokers than non-smokers, with a mean HR value of 0.028-0.038 in smokers less than the non-smokers . Response in smokers was worse than non-smokers among cancer patients treated with all other known drugs. Interpretation: For all types of cancer patients with PD-L1 positive status, smoking appears to confer some benefit to patients treated with PD-1/PD-L1 inhibitors. Funding Statement: This work was partially supported by funding from merit grant I01 BX000671 to WG from the Department of Veterans Affairs and the Veterans Administration Medical Center in Memphis, TN, USA and University of Tennessee Health Science Center, TN, USA. Declaration of Interests: Authors have no interest of conflict.

Chronic psychological stress is associated with an increased risk for relapse of inflammatory bowel diseases (IBD) and impedes the treatment of this condition. However, the impact of stress on the risk of IBD onset remains unclear. The goal of the present study was to examine whether chronic unpredictable mild stress (CUMS) could initiate or aggravate the onset of colon inflammation in rats which, in turn, would be capable of triggering bowel disease. We found that CUMS exposure increased infiltration of CD-45 positive cells and MPO activity, as well as augmented the expression of the inflammatory cytokines, IFN-γ and IL-6 within the colon of these rats. In addition, CUMS treatment changed the composition and diversity of gut microbiota and enhanced intestinal epithelial permeability, indicating the presence of a defect in the intestinal barrier. This CUMS-induced disruption of mucosal barrier integrity was associated with a reduction in expression of the tight junction protein, occludin 1, and an inhibition in mucosal layer functioning via reductions in goblet cells. Results from bacterial cultures revealed an increased presence of bacterial invasion after CUMS treatment as compared with that observed in controls. Thus, our data indicate that CUMS treatment induces alterations of the fecal microbiome and intestinal barrier defects, which facilitates bacterial invasion into colonic mucosa and further exacerbates inflammatory reactions within the colon. Accordingly, chronic stress may predispose patients to gastrointestinal infection and increase the risk of inflammation-related gut diseases.

Aim. Analyze the gender difference of esophageal cancer patients in response to drug treatment. Methods. All publications on clinical trials were collected from PubMed, Scopus, and PMC. Each publication was examined to determine whether the publication is a clinical trial and whether data on gender difference were reported. Results. Selected from a total of 191 publications, data from 7 trials with a total of 2041 patients were evaluated for gender differences. These clinical trials involve different drugs and disease phenotype. A significant difference was obtained between male and female groups from Student’s t-test. There is no conclusive result on age, ethnicity, tumor size, and drug influence. Conclusions. Gender difference in response to treatment potentially most likely exists in esophageal cancer patients, regardless of age, race, and drugs.

Hepatic vessel segmentation of CT image is of great importance in the computer aided diagnosis. This paper proposes an automatic segmentation method of 3D vessel CT images to obtain better segmentation results. First, the single Gaussian kernel of Hessian matrix in the Jerman’s algorithm is replaced by bi-Gaussian kernel. Then, a histogram-based method is adopted to adaptively estimate the threshold value of the region growing. Finally, a new scheme is proposed forautomatically searching seed points of the region growing. The experimental results show that the proposed method achieves a significant enhancement of hepatic vessels segmentation with an average accuracy 98.1%.

In this paper, a level set model without the need of generating initial contour and setting controlling parameters manually is proposed for medical image segmentation. The contribution of this paper is mainly manifested in three points. First, we propose a novel adaptive mean shift clustering method based on global image information to guide the evolution of level set. By simple threshold processing, the results of mean shift clustering can automatically and speedily generate an initial contour of level set evolution. Second, we devise several new functions to estimate the controlling parameters of the level set evolution based on the clustering results and image characteristics. Third, the reaction diffusion method is adopted to supersede the distance regularization term of RSF-level set model, which can improve the accuracy and speed of segmentation effectively with less manual intervention. Experimental results demonstrate the performance and efficiency of the proposed model for medical image segmentation.

Because of genetic complex and variations of auto antibodies of rheumatoid arthritis (RA) in different populations, the data on the association of HLA-DRB1 alleles in anti-citrullinated protein antibody of (ACPA) RA were inconsistent. The purpose of the study is to systematically summarize results of published data through performing a meta-analysis using data in which HLA-DRB1 alleles are associated with ACPApositive RA and ACPA-negative RA. In this study, we collected data from 12 studies with 13,861 cases and 12,896 controls. Information in these studies included HLADRB1 typing and ACPA status from different countries. Odds ratios (ORs) and corresponding 95% confidence intervals (CI) were used to analyze the association of different HLA-DRB1 alleles with ACPA-positive RA or ACPA-negative RA. To correct skewing data, the analysis of ACPA-status was stratified by patient distribution. Our analyses indicate that in ACPA-positive RA, all patients with RA had significantly higher frequencies of HLA-DRB1*01, *04, *0401, *0405, *07, *11, *13 and *14 than controls. One of the HLA-DRB1*07, *11, *13 and *14 showed protective association with RA. In addition, HLA-DRB1*03, *10 and *12 had more influence than control to RA in European populations; the HLA-DRB1*03 and *12 alleles were associated with the protection. In ACPA-negative RA, only DRB1*07 was associated with the protection (OR 0.53 [95% CI 0.36 - 0.76]) among all HLA-DRB1 alleles in European populations. In ACPA-positive RA, currently available results indicate that *01, *04, *0401 and *0405 are susceptible, while HLA-DRB1*07, *11, *13 and *14 are protective in all populations. While the HLA-DRB1*10 is susceptible, HLA-DRB1*03 and *12 show protective association with RA in European populations. Additionally, regardless of the positive or negative ACPA, the DRB1*07 is always associated with protection in European populations.

Circulating tumor cells (CTCs) are promising biomarkers for clinical application. Cancer screening with Low-Dose Computed Tomography (LDCT) and CTC detections in pulmonary nodule patients has never been reported. The aim of this study was to explore the effectiveness of the combined methods to screen lung cancer. Out of 8313 volunteers screened by LDCT, 32 ground-glass nodules (GGNs) patients and 19 healthy volunteers were randomly selected. Meanwhile, 15 lung cancer patients also enrolled. CellCollector, a new CTC capturing device, was applied for CTCs detection. In GGNs group, five CTC positive patients with six CTCs were identified, 15.6% were positive (range, 1–2). In lung cancer group, 73.3% of the analyzed CellCollector cells were positive (range, 1–7) and no “CTC-like” events were detected in healthy group. All CTCs detected from GGNs group were isolated from the CellCollector functional domain and determined by whole genomic amplification for next-generation sequencing(NGS) analysis. NGS data showed that three cancer-related genes contained mutations in five CTC positive patients, including KIT, SMARCB1 and TP53 genes. In four patients, 16 mutation genes existed. Therefore, LDCT combined with CTC analysis by an in vivo device in high-risk pulmonary nodule patients was a promising way to screen early stage lung cancer.

The electromigration (EM) of a solder ball under high-current stressing causes it damage and reduces its service life. Previous studies suggest that the EM life of solder can be improved by properly selecting the solder stress property (compressive or tensile) at the corners where the electron current enters and exits, but complete and relevant research on this proposition is absent. In this paper, we investigated this proposition systematically with experiments and finite element simulations. The experimental results show that the mean time to failure of solder under EM is slightly greater if the stresses at the electron current entrance and exit are compressive instead of tensile. The simulation results show that the increasing rate of the vacancy density at the cathode corner will be the lowest if the stress at the cathode is compressive and the stress at the anode is tensile. The reverse case produced the highest rate of increasing vacancy density, while the other two cases of identical cathode/anode stress types were intermediate, as verified in the experiments. However, the differences in the increasing rate of vacancy density under different stress types were not obvious, and the influence of stress on the EM life of a 0.3-mm-diameter solder ball is negligible. Further investigation found that pre-existing stresses at any two corners of solder may have an effect on the EM life of the solder only when its size is under $10~\mu \text{m}$ . In summary, our investigation provides guidance to improve the reliability of solder under EM.

Leptin, an adipocyte-derived cytokine associated with obesity, has been reported to participate in carcinogenesis. Epithelial‐mesenchymal transition (EMT) is also considered as a key event in tumor metastasis. The aim of this study is to investigate the mechanism of leptin in the promotion of EMT leading to metastasis in A549 lung cancer cells. We investigated the effect of leptin on migration of A549 cells using wound healing and transwell assays. The incidence of EMT in A549 cells was examined by real-time PCR and immunofluorescence staining. The expression of TGF-β in A549 cells was detected by real-time PCR, and blocking of TGF-β in A549 cells was achieved by siRNA techniques. Additional work was performed using 100 patient samples, which included samples from 50 patients diagnosed with lung cancer and an additional 50 patients diagnosed with lung cancer with metastatic bone lesions. Leptin expression was measured using immunohistochemistry techniques. We demonstrated that leptin can effectively enhance the metastasis of human lung cancer A549 cell line using both wound healing and transwell assays. We also found the incidence of EMT in A549 cells after leptin exposure. Furthermore, we detected the expression of TGF-β in A549 cells, which had been reported to play an important role in inducing EMT. We showed that leptin can significantly upregulate TGF-β at both the mRNA and protein levels in A549 cells. Using siRNA to block the expression of TGF-β in A549 cells, we confirmed the role of TGF-β in the promotion of metastasis and induction of EMT. Furthermore, we found that in patient samples leptin was present at higher levels in samples associated with diagnosis of lung cancer bone metastases tissue than lung cancer tissue. Our results indicated that leptin promoted the metastasis of A549 human lung cancer cell lines by inducing EMT in a TGF-β-dependent manner.