The role of silymarin and MAPK pathway in the regulation of proliferation and invasion of non-small cell lung cancer cells.

We aimed to explore the role of silymarin and mitogen-activated protein kinase (MAPK) pathway in the regulation of proliferation and invasion of non-small cell lung cancer cells. Non-small cell lung cancer cells were cultured and divided into groups and treated with drugs, and A blank control group was set up. The concentration of silymarin in the experimental group was 10 mg/L, 20 mg/L and 40 mg/L, respectively, which were recorded as groups A, B and C, and three repeated experiments were performed in each group. Absorbance (A value), survival rate and number of invasions were measured at 490 nm 24 h and 48 h after treatment, and the protein expression levels of MMP-2, MMP-9, p-p38, p-JNK and p-ERK 1/2 of cells in each group were detected. There were differences in the A value (control group > Group A > Group B > Group C), cell survival rate (control group < group A < group B < group C) and the number of cell invasions (control group > Group A > Group B > group C) at 24h and 48h among all groups (P<0.05). After 24h of administration, the mRNA expression of MMP-2 and MMP-9, P-P38 and P-JNK protein expression were significantly different among groups, and the control group was > group A > Group B > group C (P<0.05). There were no significant differences in protein expression levels of p38, JNK, ERK 1/2 and P-ERK 1/2 among all groups (P>0.05). Silymarin may inhibit the proliferation and invasion of non-small cell lung cancer cells by inhibiting the activity of MAPK pathway, and the higher the concentration, the more obvious the inhibition effect, which provides a basis for further research and treatment of non-small cell lung cancer.

IDO1 facilitates esophageal carcinoma progression by driving the direct binding of NF-κB and CXCL10.

Esophageal carcinoma (EC), one of the most lethal human malignancies, lacks effective targeted therapies. Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in a variety of cancers, but its role and mechanism in EC are still unclear. Immunohistochemistry and qRT-PCR were used to analyze the expression of IDO1 in EC, and the prognostic value of IDO1 in EC was evaluated by Kaplan-Meier test. The in vitro and in vivo function loss/acquisition tests were performed to evaluate the biological effects of IDO1 in EC. The mechanism of action of IDO1-regulation EC was explored through Firefly luciferase & Renilla luciferase activity reporter, chromatin immunoprecipitation (ChIP) and immunofluorescence (IF) assays. Clinically, IDO1 expression was abnormally elevated in EC and positively correlated with overall survival. Functionally, IDO1 was contributed to the proliferation and migration of EC cells. Mechanically, IDO1 regulated the expression of chemokine C-X-C ligand 10 (CXCL10) by promoting the entry of NF-κB into the nucleus to combine with the promoter of CXCL10. Consistently, IDO1 facilitated EC progression may dependent on the presence of CXCL10. Moreover, NF-κB alleviated the inhibitory effect of IDO1 knockdown on EC. IDO1 drove the progression of EC by directly binding NF-κB and CXCL10, the finding that may provide an effective theoretical basis for precise therapies for EC.

Circ_0030411 aggravates cisplatin-resistance in non-small cell lung cancer by serving as a miR-495-3p sponge to enhance CCND1 expression.

Circular RNAsplay important modulators in cisplatin (DDP) resistant non-small cell lung cancer (NSCLC). Herein, the role and mechanism of circ_0030411 in DDP-resistant NSCLC was explored. Circ_0030411, miR-495-3p, CCND1, PCNA, Bax, E-cadherin, and ki-67 expression were examined byqRT-PCR, western blot and IHC. DDP resistance, cell proliferation, apoptosis, and motility were assessed usingCCK, EdU flow cytometry, and transwell. Xenograft tumour model was established to explore the role of circ_0030411 in DDP-resistant NSCLC. Interaction between miR-495-3p and circ_0030411 or CCND1 wasverified via luciferase reporterand RIP. Circ_0030411 and CCND1 were increased in DDP-resistant NSCLC tissues and cells, andmiR-495-3p level was decreased. Circ_0030411 knockdown hindered cell growth, migration, invasion, in DDP-resistant NSCLC cells, and improved DDP sensitivityof NSCLC in vivo. Mechanistically, circ_0030411 acted as a sponge of miR-495-3p to affect CCND1expression. Circ_0030411 facilitated DDP resistance by regulating the miR-495-3p/CCND1 axis, highlighting a promising target for NSCLC patients.

TAF1 promotes NSCLC cell epithelial-mesenchymal transition by transcriptionally activating TGFß1.

Despite tremendous advances in the diagnosis and treatment of NSCLC, the morbidity and mortality of NSCLC still rank high worldwide. Epithelial-mesenchymal transition (EMT) is vital to the invasion, metastasis, and recurrence of NSCLC. Unfortunately, the mechanism behind NSCLC cancer cell EMT remains elusive. Therefore, determining the potential key molecules that induce EMT is important. TATA-binding protein-associated factor-1 (TAF1) is an important component of the preinitiation complex (PIC) that is dysregulated in carcinogenesis. However, the role of TAF1 in NSCLC development is unknown. Therefore, we studied the role of TAF1 in the pathogenesis of NSCLC. First, the expression of TAF1 was determined in human NSCLC tissues and cell lines. TAF1-overexpressing and TAF1 knockdown cell lines were established to evaluate the effect of TAF1 on NSCLC cell proliferation, invasion and migration by colony formation and Transwell assays. The target genes of TAF1 were identified by PCR array and verified by luciferase reporter assay. Our data demonstrated that TAF1 is upregulated in NSCLC. Higher TAF1 expression predicted poor outcomes in NSCLC patients. Mechanistically, TAF1 transcriptionally activated TGFß1, thus promoting NSCLC cell EMT and the development of NSCLC. Targeting TAF1/TGFß1 signalling may be potentially helpful as a therapeutic for NSCLC.

Esophageal magnetic compression anastomosis in dogs.

BACKGROUND: Magnetic compression anastomosis (MCA) is a novel suture-free reconstruction of the digestive tract. It has been used in gastrointestinal anastomosis, jejunal anastomosis, cholangioenteric anastomosis and so on. The traditional operative outcomes of congenital esophageal atresia and benign esophageal stricture are poor, and there are too many complications postoperatively. AIM: To test MCA technology to reconstruct the esophagus in dogs, prior to studying the feasibility and safety of MCA in humans. METHODS: Thirty-six dogs were randomized into either the study or control group (n = 18 per group). The dogs in the study group were subjected to end-to-end esophageal anastomosis with the magnetic compression device, while those in the control group underwent hand-sewn anastomosis with 4-0 absorbable multifilament Vicryl. We used interrupted single-layer inverting sutures. The anastomosis time, gross appearance, weight and pathology of the anastomosis were evaluated at one month, three months and six months postoperatively. RESULTS: The anastomosis time of the MCA group was shorter than that of the hand-sewn group (7.5 ± 1.0 min vs 12.5 ± 1.8 min, P < 0.01). In the MCA group, X-ray examination was performed every day to locate the magnetic device in the esophagus before the magnetic device fell off from the esophagus. In the hand-sewn group, dogs did not undergo X-ray examination. One month after the surgeries, the mean weight of the dogs in the hand-sewn group had decreased more than that of the dogs in the MCA group (11.63 ± 0.71 kg vs 12.73 ± 0.80 kg, P < 0.05). At 3 mo and 6 mo after the operation, the dogs' weights were similar between the two groups (13.75 ± 0.84 kg vs 14.03 ± 0.82 kg, 14.93 ± 0.80 kg vs 15.44 ± 0.47 kg). The number of inflammatory cells in MCA group was lower than that in hand-sewn group on 1 mo after operation. CONCLUSION: MCA is an effective and safe method for esophageal reconstruction. The anastomosis time of the MCA group was less than that of the hand-sewn group. This study shows that MCA technology may be applied to human esophageal reconstruction, provided these favorable results are confirmed by more publications.

Identification of OTUD6B as a new biomarker for prognosis and immunotherapy by pan-cancer analysis.

Background: Ovarian-tumor (OTU) domain-containing protein 6B (OTUD6B), one of newly identified OTU deubiquitylating enzyme families, is proved to be associated with tumor progression. However, whether it plays a key role in pan-cancer still remains unknown. Methods: The profiles of OTUD6B expression in multiple cancers were analyzed using The Cancer Genome Atlas (TCGA) database. Information of protein expression was performed based on the HPA, GeneCards, and String databases. K-M plotter and survival data analysis were used to analyze the prognostic value of OTUD6B expression, including overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). R package "clusterProfiler" was used for enrichment analysis of OTUD6B. Furthermore, we analyzed the correlation between the expression of OTUD6B, immune infiltration, and immune-related genes. Additionally, we preliminarily validated its tumorigenic effect in lung cancer cell lines. Findings: OTUD6B expression was upregulated in most cancers, such as COAD, CHOL, and LUAD, and predicted poor prognosis in most cancers in TCGA. Results showed that OTUD6B expression was positively correlated with memory CD4+ T cells, Th1 CD4+ T cells, and CD8+ T cells. In terms of the immune-related genes, OTUD6B was found to be associated with most types of genes, such as immunostimulatory genes KDR, TGFBR1, and IL-10. Moreover, for most types of tumors, the immune score was found to be negatively correlated with OTUD6B expression. In addition, lung cancer cell lines with OTUD6B knockdown significantly inhibited proliferation and invasion ability of lung cancer cells. Conclusions: The study indicated that OTUD6B is an oncogene and may serve as a new potential biomarker in various tumors. OTUD6B may play a part in TIME, which could be applied as a new target for cancer therapy.

A Pulmonary Nodule Spiculation Recognition Algorithm Based on Generative Adversarial Networks.

Pulmonary nodules have been found as the main pathological change in the lung. Signs of pulmonary nodule lay the major basis for the recognition of the benign and malignant of pulmonary nodules. The spiculation of pulmonary nodules is one of the main signs. Pulmonary nodules are small in volume, so they are difficult to extract accurately. Moreover, the number of spiculation samples is limited, so it is difficult to build a stable network structure. Thus, a novel pulmonary nodule spiculation recognition algorithm is proposed. MCA (morphological component analysis) model is built to segment pulmonary nodules in accordance with the composition of pulmonary CT images. Subsequently, the maximum density projection mechanism is introduced to characterize the boundary features of pulmonary nodules to the maximum extent. Inspired by time series dynamic programming, this paper proposes DTW (dynamic time warping) distance to measure data similarity. Lastly, a semisupervised generative adversarial network is built to solve the problem of insufficient positive samples, and it is capable of recognizing pulmonary nodule spiculation. As revealed by the experimental result, the proposed algorithm exhibited strong robustness.

Circular RNA circ_0002360 regulates the Taxol resistance and malignant behaviors of Taxol-resistant non-small cell lung cancer cells by microRNA-585-3p-dependent modulation of G protein regulated inducer of neurite outgrowth 1.

Drug resistance has become the major obstacle for the treatment of non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) are tightly linked to the development of drug resistance of NSCLC. Herein, we tested the function of circ_0002360 in the Taxol resistance of NSCLC. Circ_0002360, microRNA (miR)-585-3p and G protein regulated inducer of neurite outgrowth 1 (GPRIN1) were quantified by quantitative real-time PCR (qRT-PCR). To identify the circular structure of circ_0002360, RNase R digestion was applied. To detect cell proliferation, colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays were used. For assessment of cell apoptosis, flow cytometry was adopted. For motility and invasion analyses, transwell assay was employed. Our data showed that circ_0002360 was mainly located in the cytoplasm and was highly expressed in the Taxol-resistant NSCLC. Silencing of circ_0002360 inhibited cell Taxol resistance, proliferation, motility, and invasiveness and induced apoptosis in vitro. MiR-585-3p was underexpressed in Taxol-resistant NSCLC and was targeted by circ_0002360. MiR-585-3p knockdown alleviated the influence of circ_0002360 silence on Taxol-resistant cells. GPRIN1 was directly targeted by miR-585-3p. The influence of miR-585-3p on cell Taxol resistance and functional behaviors was reversed by GPRIN1 overexpression. Moreover, circ_0002360 modulated GPRIN1 through miR-585-3p. Additionally, silencing of circ_0002360 weakened the growth of xenografts in vivo. Our study demonstrated that silencing of circ_0002360 enhanced the Taxol sensitivity and suppressed the malignant behaviors of Taxol-resistant NSCLC cells by miR-585-3p/GPRIN1 axis, providing novel targets for improving the anti-tumor efficacy of Taxol in NSCLC.

[Development of Magnetic Anchoring Lung Nodule Positioning Device].

The magnetic anchoring lung nodule positioning device is composed of a target magnet, an anchor magnet, a coaxial puncture needle and a puncture navigation template, through these, a new type of accurate positioning technology for small pulmonary nodules is derived. The device inserts the target magnet into the both sides nearby the lung nodule under the guidance of CT. Helped by the mutual attraction of the two target magnets, they can be fixed in the lung tissue, avoiding the movement in the lung, and accurately positioning the target lung nodule before surgery. In thoracoscopic surgery, the anchor magnet and the target magnet attract each other to achieve the purpose of positioning the target nodule. The device uses the characteristics of non-contact suction of magnetic materials biomedical engineering technology, eliminating the previous procedure of direct interaction with the positioning marks, finally achieves the target of precise positioning of lung nodules and rapid surgical removal.

Nutlin-3-Induced Sensitization of Non-Small Cell Lung Cancer Stem Cells to Axitinib-Induced Apoptosis Through Repression of Akt1/Wnt Signaling.

The aim of this study was to investigate the potential biological activities of nutlin-3 in the regulation of growth and proliferation of non-small cell lung cancer (NSCLC) stem cells (CSCs), which may help in sensitizing to axitinib-induced apoptosis. Nutlin-3 induction of p53 expression was used to test its role in controlling the cell division pattern and apoptosis of NSCLC cells. A549 cells and H460 cells were pretreated with nutlin-3 and then treated with either an Akt1 activator or shRNA-GSK3ß, to investigate the potential role of p53 sensitization in the biological effects of axitinib. We also determined the expression levels of GSK3ß and p-Akt1 in patients with NSCLC and determined their potential association with survival data using Kaplan-Meier plots and CBIOTAL. Increased p53 expression stimulated the induction of apoptosis by axitinib and promoted asymmetric cell division (ACD) of NSCLC CSCs. The repression of Akt phosphorylation induced by nutlin-3 promoted the ACD of lung CSCs, decreasing the proportion of the stem cell population. In addition to the induction of apoptosis by axitinib through inhibition of Wnt signaling, nutlin-3 treatment further enhanced axitinib-induced apoptosis by inhibiting Akt1/GSK3ß/Wnt signaling. The low expression of GSK3ß and increased expression of p-Akt in patients with NSCLC were closely associated with the development of NSCLC. TP53 stimulates the induction of apoptosis in NSCLC by axitinib and the ACD of lung CSCs through its regulatory effects on the p53/Akt/GSK3ß pathways.

Theoretical Analysis and Determination of the Correction Factor for a Waveguide Microcalorimeter.

This paper proposes a new method for determining the correction factor of a newly developed waveguide primary power measurement system (i.e., microcalorimeter), based on the electromagnetic field theory analysis for waveguide thermal isolation section (TIS) in foil short measurement mode. The new method determines the contribution of the power dissipated within the TIS into the correction factor, in term of the physical dimensions of the TIS. Performance comparison and analysis show that the newly proposed method can significantly reduce the measurement uncertainty when evaluating the correction factor of waveguide microcalorimeters.

Prognostic value of FOXQ1 in patients with malignant solid tumors: a meta-analysis.

BACKGROUND: Forkhead box Q1 (FOXQ1, also known as HFH1), a member of the forkhead transcription factor family, has been demonstrated to be overexpressed in multiple tumors and is thought to be an indicator of poor clinical outcomes. METHODS: A meta-analysis using qualified relevant literature was performed to evaluate the prognostic significance of FOXQ1 in various malignant solid tumors. A search of electronic databases was conducted in MEDLINE, Embase, and the Cochrane Library to identify relevant studies published from 1966 to July 30, 2016, and the studies were identified by further evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for analyses were assessed to investigate the association between FOXQ1 expression and overall survival (OS) of patients with malignant solid tumors. RESULTS: A total of 1,520 patients from six studies (seven cohorts) with multiple malignant solid tumors were included. For OS, high FOXQ1 expression could significantly predict worse outcome with the pooled HR of 1.38 (95% CI: 1.17-1.59; P<0.001). The subgroup analysis suggested that the elevated levels of FOXQ1 appear to be associated with worse OS in hepatocellular carcinoma (HR =1.34; 95% CI: 1.11-1.57; P<0.001) and other cancers (HR =1.62; 95% CI: 1.09-2.14; P<0.001). CONCLUSION: This meta-analysis indicated that the high expression of FOXQ1 is associated with an adverse OS in malignant solid tumors, suggesting that FOXQ1 may be a predictor of poor prognosis for the development of malignant solid tumors.

CCL2 expression correlates with Snail expression and affects the prognosis of patients with gastric cancer.

We aim to explore the associations of CCL2 and Snail in gastric cancer to the clinicopathologic features and prognosis of gastric cancer (GC). In our study, the expression of CCL2 and Snail in clinical specimens of 178 GC patients was detected by immunohistochemistry. High expression of CCL2 and Snail were closely related to the clinicopathologic features. The results showed there is a link between CCL2 and Snail expression at protein levels (Pearson Χ2=40.751, P<0.001). The Kaplan-Meier survival analysis showed that CCL2 or Snail expression was correlated with 5-year survival rate (P<0.001, P<0.001, respectively). Univariate analysis showed that CCL2, Snail, pTNM stage, depth of invasion, nodal involvement, metastasis and tumor diameter were significantly associated with 5-year survival rate respectively. Multivariate Cox analysis showed that the CCL2, Snail and nodal involvement were independent prognostic factor for patients with GC. In conclusion, the expression of CCL2 is significantly correlated with Snail expression and may be used as a predictive co-biomarker for patient prognosis and tumor aggressiveness in GC. The exactly mechanism between CCL2 and Snail in the process of EMT in GC need further investigation.

Impact of neoadjuvant and adjuvant radiotherapy on disease-specific survival in patients with stages II-IV rectal cancer.

OBJECTIVES: The purposes of this study were to determine whether neoadjuvant or adjuvant radiotherapy affected disease-specific survival (DSS) in patients with rectal cancer and whether stratification by tumor stage affected the results. RESULTS: 55.5% patients had neoadjuvant-radiotherapy (NRT), and 18.3% patients had adjuvant- radiotherapy (ART). Multivariable models showed that treatment type was independently associated with DSS. Patients with stages III/IV tumors who received ART plus chemotherapy had significantly worse DSS than did those who received NRT plus chemotherapy (NCRT) (P = 0.03). Among patients with stage II tumors, those who received ART plus chemotherapy and those who received NCRT had similar DSS. Further stratification by risk group revealed that patients with stage IIIA tumors who received ART plus chemotherapy had significantly better DSS than did those who received NCRT (P = 0.04). The ART plus chemotherapy and NCRT groups had similar DSS in patients with stage IIA tumors. Among high-risk patients (T3N+/T4), the NCRT group had significantly better DSS than did the ART plus chemotherapy group. Patients who underwent surgery only had the worst DSS of all the treatment groups. MATERIALS AND METHODS: From the Surveillance, Epidemiology, and End Results database, patients diagnosed with stages II-IV rectal cancer from 2004-2014 were identified. Clinicopathologic features, treatments, and DSS in different treatment groups were compared. CONCLUSIONS: NCRT or ART plus chemotherapy can reduce deaths from rectal cancer. Patients with stage IIIA tumors will benefit most from ART plus chemotherapy, whereas NCRT should be recommended to patients with stages II, IIIB, or higher tumors.

Research progress of cardioprotective agents for prevention of anthracycline cardiotoxicity.

Anthracyclines, including doxorubicin, epirubicin, daunorubicin and aclarubicin, are widely used as chemotherapeutic agents in the treatment of hematologic and solid tumor, including acute leukemia, lymphoma, breast cancer, gastric cancer, soft tissue sarcomas and ovarian cancer. In the cancer treatment, anthracyclines also can be combined with other chemotherapies and molecular-targeted drugs. The combination of anthracyclines with other therapies is usually the first-line treatment. Anthracyclines are effective and potent agents with a broad antitumor spectrum, but may cause adverse reactions, including hair loss, myelotoxicity, as well as cardiotoxicity. We used hematopoietic stimulating factors to control the myelotoxicity, such as G-CSF, EPO and TPO. However, the cardiotoxicity is the most serious side effect of anthracyclines. Clinical research and practical observations indicated that the cardiotoxicity of anthracyclines is commonly progressive and irreversible. Especially to those patients who have the first time use of anthracyclines, the damage is common. Therefore, early detection and prevention of anthracyclines induced cardiotoxicity are particularly important and has already aroused more attention in clinic. By literature review, we reviewed the research progress of cardioprotective agents for prevention of anthracycline cardiotoxicity.

FOXQ1 promotes gastric cancer metastasis through upregulation of Snail.

Gastric cancer (GC) is one of the most common cancers, and the second most common cause of cancer deaths worldwide. Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family and its upregulation is closely correlated with tumor progression and prognosis of multiple cancer types, including GC. FOXQ1 has been shown to regulate EMT and function in human cancers. However, the role of FOXQ1 in regulating EMT in GC and the exactly mechanism has not been clarified. The purpose of this study was to investigate the effects of FOXQ1 on EMT in human GC. FOXQ1 protein was detected by immunohistochemistry in human GC specimens and their clinical significance evaluated. We examined the cell biology and molecular biology changes after overexpression and knockdown of FOXQ1 in gastric cancer cells in vitro. To further understand the underlying mechanisms of EMT promoted by FOXQ1, we examined the changes of target genes of FOXQ1 after overexpression and knockdown of FOXQ1 in gastric cancer cells. In the present study, we demonstrate that FOXQ1 is overexpressed in GC tissues and its expression level is closely correlated with histologic differentiation, pTNM stage, and lymphatic metastasis of GC. Kaplan-Meier survival analysis showed that a high expression level of FOXQ1 resulted in a significantly poor prognosis of GC patients. FOXQ1 modulated GC cell invasion in vitro, and induced E-cadherin repression. FOXQ1 also upregulated the expression of vimentin in vitro. The Snail signaling pathway was likely involved in the induction of EMT by FOXQ1 in GC. Our results demonstrate that FOXQ1 is a prognostic marker for patients with GC, FOXQ1 over-expression is involved in acquisition of the mesenchymal phenotype of gastric cancer cells, and that subsequent Snail expression is essential for induction of EMT. The results suggest that FOXQ1 is a potential therapeutic target for the development of therapies for GC.

FoxM1: a novel tumor biomarker of lung cancer.

FoxM1 is a member of the Forkhead box (Fox) family of transcription factors, which is expressed in actively dividing cells and is critical for cell cycle progression. Increased expression of FoxM1 was found in many tumors including non-small cell lung cancer (NSCLC). A more recent study showed FoxM1 is associated with poor prognosis of NSCLC patients through promoting tumor metastasis; elucidated FoxM1 could exert a direct effect on the prognosis of NSCLCs patients. In this review, we summarize the role FoxM1 in lung cancer in the hope of providing insights into the utility of FoxM1 as a novel biomarker of lung cancer.

A sutureless method for digestive tract reconstruction during pancreaticoduodenectomy in a dog model.

UNLABELLED: Development of pancreatic fistulas as a result of anastomotic gaps is still a major complication after pancreaticoduodenectomy, and can cause post-operative death. Therefore, safer and more effective methods of anastomosis are needed to avoid leakage and decrease mortality. MATERIALS AND METHODS: Twenty domestic dogs with body weights ranging from 15 to 25 kg were used, regardless of gender. A model of common bile duct and pancreatic duct dilatation was surgically prepared in these dogs. Pancreaticobiliary stents combined with magnetic anastomoses (PB-MA), and controls were treated with fibrin glue were studied in terms of and efficacy by measurement of serum amylase, incidence of complications, and survival times. RESULTS: The mean time required to create the fibrin glue pancreaticoenterostomy was 9 ± 2.05 min, while the mean time required to create the magnet cholangioenterostomy was 5 ± 0.9 min. The total operative time was 2.7 ± 0.6 h. Eighty percent of the dogs that underwent the operations were still alive for 15 days after the operations and none developed pancreatic fistulas. Examination by macroscopic observation, and hematoxylin and eosin staining of the pathological specimens showed that the anastomoses were completed healed. CONCLUSIONS: The use of a PB-MA in sutureless digestive tract reconstruction for pancreatoduodenectomy resulted in an elimination of pancreatic fistulas, and shortening of the stent removed time. In addition, the procedure is simple to perform, fast, and appears to be safe in this dog model.

Impact of NPR-A expression in gastric cancer cells.

BACKGROUND: The receptors for the cardiac hormone atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPR-A), have been reported to be expressed in lung cancer, prostate cancer, ovarian cancer. NPR-A expression and signaling is important for tumor growth, its deficiency protect C57BL/6 mice from lung, skin, and ovarian cancers, and these result suggest that NPR-A is a new target for cancer therapy. Recently, NPR-A has been demonstrated to be expressed in pre-implantation embryos and in ES cells, it has a novel role in the maintenance of self-renewal and pluripotency of ES cells. However, the direct role of NPR-A signaling in gastric cancer remains unclear. METHOD: NPR-A expression was downregulated by transfection of shRNA. The proliferation of gastric cancer cells was measured by Hoechst 33342 stain. Cell proliferation and invasion were determined via BrdU and transwell assays, respectively. RESULTS: Down-regulation of NPR-A expression by shNPR-A induced apoptosis, inhibited proliferation and invasion in AGS cells. The mechanism of shNPR-A-induced anti-AGS effects was linked to NPR-A-induced expression of KCNQ1, a gene to be overexpressed in AGS and significantly reduced by shNPR-A. CONCLUSION: Collectively, these results suggest that NPR-A promotes gastric cancer development in part by regulating KCNQ1. Our findings also suggest that NPR-A is a target for gastric cancer therapy.

Prevention of late postpneumonectomy complications using a 3D printed lung in dog models.

OBJECTIVES: Repositioning of the mediastinum with implantation of a prosthesis seems the favoured approach to treat late complications of pneumonectomy caused by mediastinal shift. However, the traditional prostheses are not designed specifically for use in the thoracic cavity, sometimes resulting in failure of treatment for many reasons. The aim of our study was to develop a novel prosthesis to promote prevention or treatment of late postpneumonectomy complications. METHODS: Using 3D printing technology, we created a novel mimetic lung model replicating the native one and then transplanted it into the thoracic cavity of postpneumonectomy dogs to maintain the original position of the mediastinum. Postoperative morbidity and mortality of late complications were compared between transplanted and non-transplanted groups. The safety and feasibility of implanting a 3D printed prosthesis were also evaluated by chest computed tomography (CT) scan and pathological examination. RESULTS: At the 1-year follow-up, pneumonectomy dogs with 3D printed lungs showed less morbidity and mortality of late complications. CT images indicated dynamic mediastinal shift in pneumonectomy-only dogs with enlarged contralateral lungs. Nevertheless, there was no obvious change in the position of the mediastinum in 3D printed lung transplanted individuals. Moreover, the 3D printed lungs did not cause any additional side effects and revealed good histocompatibility and tolerance of recipients. CONCLUSIONS: Our experiences indicated the safety, feasibility and efficacy of transplantation with 3D printed lungs for prevention of late postpneumonectomy complications and provided a practical and possibly unique clinical application of 3D printing technology for surgical therapy.