BackgroundThe poor prognosis and minimally successful treatments of malignant glioma indicate a challenge to identify new therapeutic targets which impact glioma progression. Neurotensin (NTS) and its high affinity receptor (NTSR1) overexpression induces neoplastic growth and predicts the poor prognosis in various malignancies. Whether NTS can promote the glioma progression and its prognostic significance for glioma patients remains unclear.MethodsNTS precursor (ProNTS), NTS and NTSR1 expression levels in glioma were detected by immunobloting Elisa and immunohistochemistry assay. The prognostic analysis was conducted from internet by R2 microarray platform. Glioma cell proliferation was evaluated by CCK8 and BrdU incorporation assay. Wound healing model and Matrigel transwell assay were utilized to test cellular migration and invasion. The orthotopic glioma implantations were established to analyze the role of NTS and NTSR1 in glioma progression in vivo.ResultsPositive correlations were shown between the expression levels of NTS and NTSR1 with the pathological grade of gliomas. The high expression levels of NTS and NTSR1 indicate a worse prognosis in glioma patients. The proliferation and invasiveness of glioma cells could be enhanced by NTS stimulation and impaired by the inhibition of NTSR1. NTS stimulated Erk1/2 phosphorylation in glioma cells, which could be reversed by SR48692 or NTSR1-siRNA. In vivo experiments showed that SR48692 significantly prolonged the survival length of glioma-bearing mice and inhibited glioma cell invasiveness.ConclusionNTS promotes the proliferation and invasion of glioma via the activation of NTSR1. High expression levels of NTS and NTSR1 predict a poor prognosis in glioma patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0290-8) contains supplementary material, which is available to authorized users.

Accumulated evidence suggests a major role for the activation of the Sonic Hedgehog (SHH) signaling pathway in the development of neural crest stem cells that give rise to the sympathetic nervous system. We therefore investigated the involvement of SHH signaling in the pathogenesis of neuroblastoma (NB), a common childhood malignant tumor of the sympathetic nervous system. Inhibition of SHH signaling by cyclopamine induced apoptosis and blocked proliferation in all major types of NB cells, and abrogated the tumorigenicity of NB cells. Our study has revealed a molecular mechanism for the persistent activation of the SHH pathway which promotes the development of NB, and suggests a new approach for the treatment of this childhood malignant tumor.

Neuroblastoma is one of the most common solid tumours in children (8-10% of all malignancies). Over 22% of cases have N-myc amplification associated with aggressively growing neuroblastomas. Oncogene-induced sensitization of cells to apoptosis is an important mechanism for suppression of tumorigenesis. Tumour suppressors often play a critical role in linking oncogenes to apoptotic machinery. For example, activated p53 then targets both intrinsic and extrinsic pathways to promote apoptosis through transcription-dependent and -independent mechanisms. Understanding of the involved mechanisms has important clinical implications. We have employed DNA-damaging drug-induced apoptosis sensitized by oncogene N-myc as a model. DNA damaging drugs trigger high levels of p53, leading to caspase-9 activation in neuroblastoma cells. Inactivation of p53 protects cells from drug-triggered apoptosis sensitized by N-myc. These findings thus define a molecular pathway for mediating DNA-damaging drug-induced apoptosis sensitized by oncogene, and suggest that inactivation of p53 or other components of this apoptotic pathway may confer drug resistance in neuroblastoma cells. The data also suggests that inactivation of apoptotic pathways through co-operating oncogenes may be necessary for the pathogenesis of neuroblastoma with N-myc amplification.

OBJECTIVES The feasibility of an Amplatzer septal occluder closure of ventricular septal defects (VSDs) under echocardiographic guidance has already been proven. However, the technique is not used routinely owing to high-rate atrioventricular blocks and the non-absorbability of the occluder. Here, we aimed to evaluate the safety, biocompatibility and effectiveness of a new biodegradable occluder. METHODS A total of 18 adult beagle dogs [mean body weight 8.85 kg (range 8.10–10.40 kg)] were enrolled in our study from March 2015 to July 2018. VSD animal models were prepared by thoracic intervention, and the new bioabsorbable occluder was implanted under the guidance of transthoracic echocardiography. Laboratory examinations, transthoracic echocardiography and electrocardiography were performed after surgery, and pathological samples from dogs were obtained after euthanasia and examined in the 1st, 3rd, 6th, 9th, 12th and 24th months to evaluate the safety, biocompatibility and effectiveness of the biodegradable occluder. RESULTS All the dogs received successful implantations of the biodegradable occluder and survived, showing no follow-up-related complications (such as dislocation, arrhythmia and recanalization). Biochemical tests showed no significant abnormalities or differences, except for an increase in white blood cells and C-reactive proteins on the day after the operation. Histopathological examinations revealed that the bioabsorbable occluders were biocompatible, while immunohistochemical evaluations and electron microscopy showed endothelial cells growing on the occluder surface. CONCLUSIONS The effective occlusion of VSD, good biocompatibility, rapid endothelialization and lack of complications shown by the biodegradable occluder in this study suggest that the device meets acceptable clinical safety and has potential application prospects.