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BackgroundIn recent years, an increasing number of thoracic surgeons have attempted to apply no routine chest tube drainage (NT) strategy after thoracoscopic lung resection. However, the safety and feasibility of not routinely placing a chest tube after lung resection remain controversial. This study aimed to investigate the effect of NT strategy after thoracoscopic pulmonary resection on perioperative outcomes.MethodsA comprehensive literature search of PubMed, Embase, and the Cochrane Library databases until 3 January 2022 was performed to identify the studies that implemented NT strategy after thoracoscopic pulmonary resection. Perioperative outcomes were extracted by 2 reviewers independently and then synthesized using a random-effects model. Risk ratio (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. Subgroup analysis and sensitivity analysis were subsequently performed.ResultsA total of 12 studies with 1,381 patients were included. The meta-analysis indicated that patients in the NT group had a significantly reduced postoperative length of stay (LOS) (SMD = -0.91; 95% CI: -1.20 to -0.61; P < 0.001) and pain score on postoperative day (POD) 1 (SMD = -0.95; 95% CI: -1.54 to -0.36; P = 0.002), POD 2 (SMD = -0.37; 95% CI: -0.63 to -0.11; P = 0.005), and POD 3 (SMD = -0.39; 95% CI: -0.71 to -0.06; P = 0.02). Further subgroup analysis showed that the difference of postoperative LOS became statistically insignificant in the lobectomy or segmentectomy subgroup (SMD = -0.30; 95% CI: -0.91 to 0.32; P = 0.34). Although the risk of pneumothorax was significantly higher in the NT group (RR = 1.75; 95% CI: 1.14–2.68; P = 0.01), the reintervention rates were comparable between groups (RR = 1.04; 95% CI: 0.48–2.25; P = 0.92). No significant difference was found in pleural effusion, subcutaneous emphysema, operation time, pain score on POD 7, and wound healing satisfactory (all P > 0.05). The sensitivity analysis suggested that the results of the meta-analysis were stabilized.ConclusionsThis meta-analysis suggested that NT strategy is safe and feasible for selected patients scheduled for video-assisted thoracoscopic pulmonary resection.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-4-0026, identifier INPLASY202240026.

BackgroundThe efficacy of sublobar resection and selective lymph node dissection is gradually being accepted by thoracic surgeons for patients within early-stage non-small cell lung cancer (NSCLC). Nevertheless, there are still some NSCLC patients develop lymphatic metastasis at clinical T1 stage. Lung adenocarcinoma with a micropapillary (MP) component poses a higher risk of lymph node metastasis and recurrence even when the MP component is not predominant. Our study aimed to explore the genetic features and occult lymph node metastasis (OLNM) risk factors in patients with a non-predominant micropapillary component (NP-MPC) in a large of patient’s cohort with surgically resected lung adenocarcinoma.MethodsBetween January 2019 and December 2021, 6418 patients who underwent complete resection for primary lung adenocarcinoma at the Qilu Hospital of Shandong University. In our study, 442 patients diagnosed with lung adenocarcinoma with NP-MPC with a tumor size ≤3 cm were included. Genetic alterations were analyzed using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Abnormal protein expression of gene mutations was validated using immunohistochemistry. A nomogram risk model based on clinicopathological parameters was developed to predict OLNM. This model was invalidated using the calibration plot and concordance index.ResultsIn our retrospective cohort, the incidence rate of the micropapillary component was 11.17%, and OLNM was observed in 20.13% of the patients in our study. ARMS-PCR suggested that EGFR exon 19 del was the most frequent alteration in NP-MCP patients compared with other gene mutations (frequency: 21.2%, PConclusions.Intense expression of EGFR exon 19 del characterizes lung adenocarcinoma in patients with NP-MCP and it’s a potential risk factor for OLNM. We firstly established a nomogram based on age, CYFRA21-1 level, tumor size, micropapillary and solid composition, that was effective in predicting OLNM among NP-MCP of lung adenocarcinoma measuring ≤ 3 cm.

Background: Many evidences proved important roles of microRNAs in the occurrence and development of non-small cell lung cancer (NSCLC). This work aimed to explore the effects and regulating mechanism of microRNA-665 (miR-665) in NSCLC. Methods: Here, quantitative real time PCR was used to evaluate the expression level of miR-665 in NSCLC tissues and several cell lines (H520, H1299, PC9, H358, and A549). Then, MTT, apoptosis assays and wound-healing assays were performed to study miR-665 functions on cell proliferation, apoptosis and migration. Based on bioinformatics analysis, nemo-like kinase (NLK) was predicted as a potential target of miR-665 and then a series of experiments were performed to explore miR-665 mechanism.Results: In NSCLC tissues and several cell lines, miR-665 was up-regulated and cell experiments displayed that it had abilities to promote cell proliferation and migration, and inhibit cell apoptosis. MiR-665 over-expression could reduce NLK mRNA and protein level by binding to 3′-untranslated region of NLK, which suggested that miR-665 could regulate NLK expression. Further analysis found that there was an inverse correlation f between miR-665 and NLK in NSCLC. Moreover, low-level NLK possessed same effects on cells as miR-665 over-expression, and its knockdown could partly recovery the miR-665-mediated cell proliferation, migration and anti-apoptosis, indicating that miR-665 might regulate biological behaviors of NSCLC cells via targeting NLK. Conclusion: MiR-665 probably promoted NSCLC occurrence and progression via targeting NLK, which might be a hopeful biomarker for NSCLC diagnosis or a target for treatment.

Objective. This Work is aimed at exploring the effect of microRNA (MiR)-608 on the function of nonsmall cell lung cancer (NSCLC) A549 cells and related mechanisms. Methods. Blood samples of 106 NSCLC patients (experimental group) as well as 124 normal people (control group) were selected for relevant investigation. Polymerase chain reaction (PCR) as well as DNA sequencing was used to determine the genotyping of the MiR-608 rs4919510 polymorphism. MiR-608 expression in cells was detected by real-time PCR technology. Western blotting was used to detect changes in protein levels. NSCLC tissues as well as adjacent tissues were explored in 33 patients undergoing surgery. Results. MiR-608 rs4919510 does not influence the incidence of NSCLC patients. In addition, MiR-608 expression was downregulated in the tumor tissue of NSCLC patients, while the transcription factor activating enhancer-binding protein 4 (TFAP4) expression was upregulated. MiR-608 promotes DOX- (Doxorubicin-) induced apoptosis by negatively regulating TFAP4 expression in NSCLC tissue. TFAP4 can significantly inhibit the migration of A549 cells. Conclusion. The findings in this investigation can contribute to the effective treatment of NSCLC patients. Also, the investigation can provide some theoretical support for the application of new targets for NSCLC treatment.

OBJECTIVE To investigate the effect of ZHX2 on lung cancer cells proliferation and apoptosis. MATERIALS AND METHODS The mRNA and protein expression of ZHX2 were detected by qRT-PCR and western blot, respectively. The human lung cancer cells were divided into Control, NC, ZHX2, SB, and ZHX2 + Ani groups. The cell proliferation was detected by CCK-8 assay and the cell migration and invasion were detected by Transwell assay. Cell apoptosis was detected by flow cytometry. Apoptosis and p38MAPK signaling pathway related proteins were detected by western blot. The nude mice model of lung cancer xenograft was constructed. The tumor volume and tumor weight were measured. The expression of PCNA protein in tumor tissues was detected by immunohistochemistry. The apoptosis of tumor cells was detected by TUNEL staining. The ZHX2 and p38MAPK signaling pathway related proteins in tumor tissues were detected by western blot. RESULTS The expression of ZHX2 gene and protein in the cancer cell lines were significantly decreased. Compared with control and NC groups, the cells proliferation, migration and invasion were inhibited in ZHX2 and SB groups, while the apoptosis and apoptosis related proteins were increased (p< 0.05). Meanwhile, compared with ZHX2 group, the tumor growth rate, volume, weight, the percentage of PCNA-positive cells, and p-P38 MAPK/P38 MAPK were increased significantly in ZHX2 + Ani group, while the apoptotic index and the expression of MMP-9 protein were significantly decreased (p< 0.05). CONCLUSION ZHX2 could inhibit proliferation and promote apoptosis of lung cancer cells by inhibiting p38MAPK signaling pathway.

MicroRNAs (miRNAs/miRs) are a class of small, highly conserved non-coding RNAs that can serve either oncogenic or tumor-suppressive roles in a wide variety of tumors. miR-200c is a member of the miR-200 family whose specific role in non-small cell lung cancer (NSCLC) has not yet been elucidated. The purpose of the present study was to detect the expression level of miR-200c in NSCLC, and to analyze its association with clinicopathological factors and patient prognosis. The present study determined the expression levels of miR-200c in 110 tumor samples collected from patients diagnosed with NSCLC who underwent complete tumor resection with regional lymph node dissection, as assessed by reverse transcription-quantitative polymerase chain reaction. The association between the expression level of miR-200c and clinicopathological features and patient prognosis was also analyzed. The results showed that miR-200c overexpression was detected in 66 of the 110 cases and was significantly associated with positive lymph node metastasis (P

Background Circular RNA (circRNA) has become a new focus in the field of tumor biology research in recent years. Many circRNAs have been showed to play an important role in the progression of lung adenocarcinoma (LUAD). In this work, we studied the oncological role of hsa-circ-000881 in LUAD and attempted to explore the related mechanism. Methods The relative expressions of hsa-circ-000881, miR-665, and PRICKLE2 were detected by RT-qPCR or western blot. Functional assays were conducted to analyze the role of hsa-circ-000881 in the proliferation, migration, and invasion of LUAD cells. A luciferase reporter assay was performed to verify whether hsa-circ-000881, miR-665, and PRICKLE2 interact with each other. Results Circ-000881 was remarkably downregulated in LUAD. Overexpression of circ-000881 attenuated cell growth, migration, and invasion, whereas its knockdown enhanced the malignancy of LUAD cells. The results of luciferase reporter assay and bioinformatics analysis confirmed that circ-000881 served as a sponge for miR-665, and PRICKLE2 was a direct target of miR-665.Overexpression of miR-665 or silencing of PRICKLE2 abolished circ-000881-mediated inhibition of malignant tumor behavior in LUAD cells. Conclusions Circ-000881 has inhibitory effects on LUAD via a miR-665/PRICKLE2 axis, suggesting that circ-000881 may be an underlying therapeutic target for LUAD.

Lysosome-associated protein transmembrane-4β (LAPTM4B) is a novel cancer-related gene that is upregulated in many tumors, and which plays important roles in carcinogenesis. It has two alleles, LAPTM4B 1 and LAPTM4B 2. LAPTM4B 1 contains only one copy of a 19-bp sequence in the first exon, whereas LAPTM4B 2 contains two tight tandem segments. Previous studies have shown that LAPTM4B 2 is a risk factor for susceptibility and prognosis of many tumors. The present study investigated the relationship between LAPTM4B polymorphism and non-small cell lung cancer (NSCLC) susceptibility and prognosis. We identified LAPTM4B genotypes with polymerase chain reaction (PCR) in peripheral blood samples. In the adjusted multivariate logistic regression analysis, we found that LAPTM4B 1/2, LAPTM4B 2/2 exhibited 1.48-fold [95% confidence interval (CI), 1.076-2.037] and 2.855-fold (95%CI, 1.722-4.734) increases in the risk of developing NSCLC compared with non-LAPTM4B 2 carriers. Furthermore, our results showed that overall survival time and disease-free survival time of patients with LAPTM4B 2 were significantly shorter than in patients carrying LAPTM4B 1 (P=0.001 and P=0.001, respectively). In addition, multivariate Cox regression analysis revealed that LAPTM4B 2 was also an independent prognostic factor for NSCLC. These results suggest that LAPTM4B polymorphisms may be a prospective marker for evaluating the risk and prognosis of NSCLC.

Heparanase is a mammalian endoglycosidase that degrades heparan sulfate at the cell surface and in the extracellular matrix. The expression of heparanase was detected in a wide variety of human malignant tumors and closely associated with tumor invasion, metastasis, and angiogenesis. However, the specific roles of heparanase and its mechanisms of regulating the malignant potential of non-small cell lung cancer (NSCLC) cells still remain unclear. In the present study, the expression of heparanase was down-regulated in NSCLC cell line by antisense oligodeoxynucleotide. Results showed that down-regulation of heparanase led to significant inhibition of invasive and proliferative potentials of A549 cells in vitro and in vivo. Further research demonstrated that down-regulation of heparanase significantly inhibited the angiogenic potential of A549 cells, which might be the mechanism responsible for the inhibition of A549 cell proliferation in BALB/c nude mice in vivo. These findings demonstrate that heparanase plays essential roles in regulating the invasion, proliferation, and angiogenesis of A549 cells.

Lung cancer is the leading cause of cancer-related mortality all over the world. In recent years, pulmonary adenocarcinoma has surpassed squamous cell carcinoma in frequency and is the predominant form of lung cancer in many countries. Epidemiological investigations have shown an inverse relationship between garlic (Allium sativum) consumption and death rate from many cancers. Diallyl trisulfide (DATS) is one of the garlic-derived compounds (also known as: organosulfer compounds, OSC). DATS can induce apoptosis and inhibit the growth of many cancer cell lines. Our study demonstrated that the apoptotic incidents induced by DATS were a mitochondria-dependent caspase cascade through a significant decrease of the anti-apoptotic Bcl-2 that resulted in up-regulation of the ratio of Bax/Bcl-2 and the activity of caspase-3, -8, and -9. Eventually, DATS induced the apoptosis and inhibited the proliferation in a concentration- and time-dependent manner. Furthermore, by establishing an animal model of female BALB/c nude mice with A549 xenografts, we found that oral gavage of DATS significantly retarded growth of A549 xenografts in nude mice without causing weight loss or any other side effects compared with the control group. All the evidence both in vitro and in vivo suggested that DATS could be an ideal anti-cancer drug.

Human mesenchymal stem cells (hMSCs) are mostly studied for their potential clinical use. Recently, much attention in the field of cancer research has been paid to hMSCs. In this study, we investigated the influence of hMSCs on the proliferation of lung cancer cell lines SK-MES-1 and A549 in vitro and in vivo by using a co-culture system and the hMSCs-conditioned medium. Our results demonstrated that hMSCs could inhibit the proliferation of SK-MES-1 and A549 cells, and induce the apoptosis of tumor cells in vitro via some soluble factors. Animal study showed that these soluble factors from hMSCs could suppress tumorigenesis and tumor angiogenesis by treating preliminarily tumor cells with the hMSCs-conditioned medium. The downregulated expression of vascular endothelial growth factor in tumor cells might be the mechanism of interference in tumor angiogenesis, which was verified by western blot analysis and immunohistochemistry assay. Taken together, our results suggested that the hMSCs could inhibit tumor cell growth by secreting some soluble factors.

Based on previous findings regarding the angiogenic activities and prognostic roles of metastasis-associated protein 1 (MTA1) in early-stage non-small cell lung cancer, the clinicopathological and prognostic significance of MTA1 protein expression, and its correlation with angiogenesis in lung invasive adenocarcinoma, were further assessed in the present study, according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. High protein expression levels of MTA1 were commonly observed in patients with lung invasive adenocarcinoma, and were significantly correlated with tumor size (P=0.030), lymph node metastasis (P=0.021) and microvessel density (P=0.015). Survival analysis demonstrated that patients with high protein expression levels of MTA1 exhibited significantly shorter five-year disease-free and overall survival than those patients whose protein expression levels of MTA1 were low (24.5% vs. 48.7%, P=0.001, and 34.7% vs. 59.2%, P=0.005, respectively). In addition, Cox regression multivariate analysis demonstrated that high protein expression levels of MTA1 significantly correlated with unfavorable five-year disease-free survival (P=0.024). These findings indicate that MTA1 protein expression may possess clinical potential as an indicator of progressive phenotype. Therefore, MTA1 is a promising prognostic predictor to identify subgroups of patients with high risk of relapse, and a potentially novel therapeutic target for antiangiogenesis in patients with lung invasive adenocarcinoma.

The nuclear receptor coactivator 5 (NCOA5) was a unique coactivator independent of AF2 that can modulate ERα-mediated transcription. Recent researches have indicated that its downregulation may participate in cancer development and progression. The aims of the present study were to investigate NCOA5 expression in esophageal squamous cell carcinoma (ESCC) and validate its possible influence on patients' prognosis. NCOA5 expression was examined by immunohistochemical staining in 119 ESCC patients' tissues. Ten paired tumor and adjacent normal specimens were examined by Western blot analysis. Statistical analysis was performed to assess its relevance with various clinicopathologic features and its influence on patients' survival. By immunohistochemistry analysis, NCOA5 expression was found to be significantly correlated with differentiation (P = 0.039), T status (P = 0.047) and stage (P = 0.036). Furthermore, we found NCOA5 higher expression in normal tissues than in tumor tissues by Western blot analysis. Univariate analysis showed that poor differentiation (P = 0.035, P = 0.027), lymph node metastasis (P < 0.001, P < 0.001), high T status (P = 0.010, P = 0.012), advanced stage (P < 0.001, P < 0.001) and NCOA5 low expression (P < 0.001, P < 0.001) were significantly correlated with poor prognosis of both disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that NCOA5 low expression (P = 0.019, P = 0.047), high T status (P = 0.015, P = 0.012), lymph node metastasis (P = 0.040, P = 0.021) and advanced stage (P = 0.017, P = 0.046) were independent prognostic factors of poor DFS and OS. Our findings suggest that NCOA5 low expression is associated with ESCC progression and is a potential biomarker in predicting poor prognosis. Further studies of NCOA5 may help develop new therapeutic strategies against ESCC.

Background: Golgi phosphoprotein-3 (GOLPH3) is implicated in cancer development and progression. The aim of this study was to evaluate the prognostic significance of GOLPH3 protein and its association with tumor angiogenesis in patients with early-stage NSCLC. Materials and Methods: Immunohistochemistry was performed to determine GOLPH3 protein expression and allow assessment of intratumoral microvessel density (MVD) by counting CD-34 positive immunostained endothelial cells. Correlations of expression with MVD, clinicopathologic features and clinical prognosis were analyzed. Results: A notably higher level of GOLPH3 expression was found in early-stage NSCC tissues at the protein level. However, we do not find any correlation between GOLPH3 expression and clinicopathologic features (p>0.05), although higher MVD was positively associated with GOLPH3 overexpression (p

Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is a novel oncogene, which has been indicated to be dramatically overexpressed in various malignant tumors. The aims of this study were to detect LAPTM4B protein expression in patients with non-small cell lung cancer (NSCLC) and then analyze the relationships of LAPTM4B protein with clinicopathologic factors, tumor angiogenesis and prognosis with SPSS statistical software. Immunohistochemistry was used to examine the expression of LAPTM4B and CD34 proteins in NSCLC tissues, and its results showed that LAPTM4B protein expression in NSCLC tissues was significantly higher than that in normal lung tissues (P < 0.001). Of the186 NSCLC cases, 129 (69.35 %) had strong expression of LAPTM4B protein, which was associated with histopathologic differentiation (P = 0.017), lymph node metastasis (P = 0.001) and TNM stage (P = 0.046), as well as the microvessel density (MVD) (P = 0.019). Kaplan-Meier survival analysis revealed that patients with strong LAPM4B protein expression and high MVD might have poor overall survival (OS; P = 0.001, P = 0.002, respectively) and disease-free survival (DFS; P = 0.002, P = 0.038, respectively). Multivariate analysis demonstrated that LAPTM4B protein was an independent prognostic marker for OS and DFS of NSCLC patients (P = 0.037, P = 0.046, respectively). These findings illustrated that LAPTM4B protein was closely associated with NSCLC progression, angiogenesis and poor prognosis, suggesting that LAPTM4B protein could be applied not only in predicting patient's outcome, but also in antiangiogenic therapy as a possible novel target molecule.

Background Sirtuin1 (SIRT1) is an NAD+-dependent type III histone deacetylase (HDAC). This research investigated the prevalence of SIRT1 protein expression and its prognostic influence with the aim of validating its potential role in lymphangiogenesis and lymphovascular invasion (LVI) in pN0 esophageal squamous cell carcinoma (ESCC). Methods A total of 206 patients were enrolled in this retrospective study. SIRT1 and VEGF-C protein expression was detected by immunohistochemical staining. Peritumoral lymphatic microvessel density (LVD) and LVI were evaluated by immunostaining for D2-40. Statistical analysis was then preformed to investigate the relevance of SIRT1 expression and various clinicopathologic features and to examine the effect of SIRT1 on tumor-induced lymphangiogenesis, LVI and prognosis. Results SIRT1 positive expression was identified in 95 cases in the nucleus and was significantly correlated with T status (P

The apoptotic ligand TNF-related apoptosis-inducing ligand (TRAIL) is believed to be a promising candidate for cancer gene therapy, yet gene therapy strategies to tackle this disease systemically are often impaired by inefficient delivery of the vector to the tumor tissue. Mesenchymal stem cells (MSCs) have been shown to home to tumor sites and could potentially act as a shield and vehicle for an antitumor gene therapy vector. Here, we used an adenoviral vector expressing TRAIL to transduce MSCs and studied the apoptosis-inducing activity of these TRAIL-carrying MSCs on esophageal cancer cell Eca-109. Our results showed that, in vitro, TRAIL-expressing MSCs were able to inhibit proliferation and induce apoptosis in Eca-109 cells by an MTT assay, co-culture experiments and flow cytometry analysis. In vivo, TRAIL-expressing MSCs also displayed an ability to inhibit tumor growth in an Eca-109 xenograft mouse model. Together, our findings indicated that the gene therapy strategy of MSCs-based TRAIL gene delivery has a wide potential value for improving the treatment of esophageal cancer.

BACKGROUND: The aim of this study was to examine BRF2 expression in patients with non-small cell lung cancer (NSCLC) and explore the relationship of BRF2 protein with clinicopathologic factors, tumor angiogenesis and prognosis. METHODS: Both BRF2 protein and intratumoral microvessels were examined by immunohistochemical staining in 107 non-small cell lung cancer patients. Intratumoral microvessel density (MVD) was measured by counting CD-34 positive immunostained endothelial cells. Western blot and RT-PCR analyses were utilized to investigate the BRF2 expression status in tissues. RESULTS: A notably higher level of BRF2 expression was found in NSCLC tissues at protein levels. In addition, univariate and multivariate analysis demonstrated that BRF2 protein over-expression and high MVD were significantly associated with tumor relapse. Although BRF2 overexpression and high MVD indicated poor 5-year overall survival (p = 0.004 and p = 0.019, respectively), multivariate analysis demonstrated that only BRF2 overexpression was an independent prognostic factor for unfavorable overall survival (P = 0.021). CONCLUSIONS: BRF2 is a promising biomarker to identify individuals with poor prognostic potential and a possible target for anti-angiogenic therapy for patients with early-stage NSCLC.

Studies have shown that genetic activation of TFIIB-related factor 2 (BRF2) represents a unique mechanism of tumorigenesis through the increase in Pol III-mediated transcription. Several studies have shown that BRF2 is overexpressed in several types of cancer and suggest the oncogenic role of BRF2. This study aimed to examine the expression of TFIIB-related factor 2 (BRF2) in patients with esophageal squamous cell cancer (ESCC) and explore the relationship of BRF2 expression with clinicopathologic factors, tumor angiogenesis and prognosis. We found that increased BRF2 protein expression was prevalent in esophageal squamous cell cancer and was significantly associated with deeper tumor invasion (P = 0.039) and microvessel density (P = 0.007). Additionally, expression of BRF2 was found to be an independent prognostic factor in ESCC patients. Furthermore, a significant correlation between high BRF2 expression and shorter overall survival time was found in different subgroups of ESCC patients stratified by the clinical stage, T classification and lymph node metastasis. High expression of BRF2 protein is closely associated with tumor progression and angiogenesis and poor survival of ESCC. BRF2 is a promising biomarker to identify individuals with poor prognostic potential and concludes the possibility of its use as a prognostic marker in patients with ESCC.

Metastasis-associated protein 1 (MTA1) high expression has been detected in a wide variety of human aggressive tumors and plays important roles in the malignant biological behaviors such as invasion, metastasis, and angiogenesis. However, the specific roles and mechanisms of MTA1 protein in regulating the malignant behaviors of non-small-cell lung cancer (NSCLC) cells still remain unclear. To elucidate the detailed functions of MTA1 protein, we down-regulated the MTA1 protein expression in NSCLC cell line by RNA interference (RNAi) in vitro, and found that down-regulation of MTA1 protein significantly inhibited the migration and invasion potentials of 95D cells. Further research revealed that down-regulation of MTA1 protein significantly decreased the activity of matrix metalloproteinase-9, which could be the mechanism responsible for the inhibition of 95D cells migration and invasion. In addition, the tube formation assay demonstrated that the number of complete tubes induced by the conditioned medium of MTA1-siRNA 95D cells was significantly smaller than that of 95D cells. These findings demonstrate that MTA1 protein plays important roles in regulating the migration, invasion, and angiogenesis potentials of 95D cells, suggesting that MTA1 protein down-regulation by RNAi might be a novel therapeutic approach to inhibit the progression of NSCLC.

Introduction Neural stem cell transplantation is a promising tool for the restoration of the enteric nervous system in a variety of motility disorders. However, limited cell viability after transplantation has restricted its regenerative capacity. The aim of this study was to evaluate the effect of transplantation of neuroepithelial stem cell (NESC) overexpressing anti-apoptotic gene Bcl-2 on the survival, differentiation and function of grafted cells in rat aganglionic colon. Methods NESCs were isolated from neural tube of embryonic rat (embryonic day 11.5) and manipulated to overexpress the Bcl-2 gene. After transplantation into the benzalkonium chloride-induced rat aganglionic colon, grafted cells were visualized in colonic sections. Apoptosis and differentiation of the implanted cells were assessed 1, 4 and 8 weeks post transplantation, respectively. Eight weeks post transplantation, neuronal function of the colon was assessed by measuring the response of muscle strips to electrical field stimulation. Results Transplantation with Bcl-2-NESCs reduced apoptosis within the transplant at 1 week compared with the vector-NESC grafted group. Our findings also indicated that overexpression of Bcl-2 in the transplanted NESCs enhanced differentiation into PGP9.5-positive and neuronal nitric oxide synthase-positive neurons at 8-week assessment. Moreover, electrical field stimulation-induced relaxation of colonic strips was also significantly increased in the Bcl-2-NESC grafted group. Conclusion Transplantation of NESCs genetically modified to overexpress Bcl-2 may have value for enhancing survival and neurogenesis of grafted cells in the adult gut environment and for improving the efficacy of stem cell therapy following a broad range of gastrointestinal motility disorders.