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Hypoxia, a common feature of solid tumors, can promote chemoresistance in cancer cells. PRMT5 mediates various cellular processes involved in cancer development and progression. However, the role of PRMT5 in hypoxia‐induced chemoresistance is unclear. In this study, hypoxia upregulated PRMT5 expression in lung cancer cells. Additionally, PRMT5 overexpression promoted cancer cell resistance to carboplatin. In carboplatin‐resistant cancer cells, PRMT5 overexpression promoted the methylation of ULK1, a critical regulator of autophagy. ULK1 hypermethylation leads to the upregulation of autophagy, which can improve the survival of cancer cells under hypoxic conditions. Furthermore, this study demonstrated that the PRMT5 inhibitor C9 significantly enhanced the sensitivity of lung cancer cells to carboplatin. These findings suggest that targeting PRMT5‐mediated autophagy with C9 can overcome hypoxia‐induced carboplatin resistance and improve the efficacy of chemotherapy in patients with cancer. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to evaluate the efficacy and safety of non-thoracoscopic extrapleural approach of the Nuss procedure for the correction of pectus excavatum in children. Methods: From October 2007 and January 2009, 42 patients with pectus excavatum were treated in the Tangdu Hospital, Xi’an, China, with surgical correction through the Nuss procedure. Among them, 20 underwent a Nuss procedure with thoracoscopic guidance, and the other 22 patients were treated with non-thoracoscopic extrapleural approach, in which a bilateral extrapleural tunnel to the edge of sternum was created using a blunt dissection through bilateral thoracic skin incisions. Without introducing the thoracoscopy into the thoracic cavity, a steel bar was inserted in the entirely extrapleural tunnel and turned as in the standard Nuss procedure. Results: The operations were completed successfully in all patients treated. The operation time and postoperative hospitalisation time of the non-thoracoscopic extrapleural Nuss group were significantly less than those of the thoracoscopic group (P <0.05). There was no pneumothorax or hydrothorax in our series and no tube thoracostomy was further needed. All patients were followed up for more than 2 months, and the surgical outcomes were excellent. Conclusions: The non-thoracoscopic extrapleural approach of the Nuss procedure is a safe and less traumatic procedure for the correction of pectus excavatum. [Copyright &y& Elsevier]

Background: NOK (Novel Oncogene with Kinase-domain) is a newly identified receptor protein-tyrosine kinases (RPTKs) subfamily, which possesses strong oncogenic potential including enhancing cell transformation, tumorigenesis, invasion and metastasis. However, NOK protein lacks extracellular domain, and how the NOK is activated by the membrane receptor and the expression of NOK in non small cell lung cancer (NSCLC) are not clear. Our aim of this study was to investigate the expressions of NOK, EGFR proteins in NSCLC., Methods: The expression rates of NOK, EGFR proteins in 155 cases with NSCLC was deteced by immunohistochemical stain; The clinical correlations between two proteins were analyzed by statistics., Results: The NOK positive expression was mainly located in cytoplasm and EGFR was mainly located in the plasma membrane and cytoplasm. NOK, EGFR proteins were high expressed in NSCLC and there were extremely differences comparing the expression of NOK, EGFR proteins in squamous cell lung cancer, lung adenocarcinoma with those in corresponding normal tissue respectively (P<0.001); and there were no significant differences between the two kinds of the cancers for their comparison of NOK, EGFR expression (P=0.099; P=0.23); however, there were significant differences for NOK and EGFR expression among histological grades and TNM stages in squamous cell lung cancers, lung adenocarcinoma (P<0.01). There were correlation between positive and intensity of NOK and EGFR expression in whatever total NSCLC or squamous cell lung cancer or lung adenocarcinoma (P<0.001), while the correlation coefficients(rs) were 0742, 0.722, 0.756 respectively., Conclusions: The NOK proteins are highly expressed in the NSCLC, and the expression rates of NOK proteins are correlated with the cancers' histological grades and TNM stages, which may be concern with tumorgenesis and progression; the positive expression rate and intensity of NOK protein correlate well with the expression of EGFR protein in NSCLC, which the activation of NOK probably owe to EGFR activation, all that would provide evidence for further study on the effective mechanism of NOK in the tumorigenesis or tumor progression.

Background: To investigate the biological effects of anti VEGF₁₆₅ ribozyme on human lung adenocarcinoma cell., Methods: Hammerhead ribozyme (VRz) against VEGF₁₆₅ gene transcripts (site 212) and its paired mutant ribozyme (mVRz) were designed and synthesized, and the cleavage activity of the ribozymes on target RNA in a cell-free system was observed. The replication-incompetent adenovirus-mediated eukaryotic expression vectors (rpAdVRz) containing VRz and mVRz gene were constructed and identified. Then the human lung adenocarcinoma cells (A549) were infected with recombinant adenovirus. The biological characteristics of A549 cell before and after infection in vitro were inspected by Northern blot, laser confocal imaging system analysis, flow cytometry and transmission electron microscopy., Results: VRz specifically and efficiently cleaved the VEGF₁₆₅ mRNA. The rpAdVRz was successfully constructed and infected A549 cell. The level of VEGF₁₆₅ expression decreased 87% in rpAdVRz infected cells compared with the other groups, but their biological characteristics were not influenced by the expression of the exogenous gene., Conclusions: The adenovirus mediated hammerhead ribozyme against VEGF₁₆₅ can significantly decrease the expression of VEGF₁₆₅. This provides an experimental basis for human lung cancer gene therapy with antiangiogenesis method.

Background: To observe the suppressive effects of exogenous p27 gene on human lung cancer cell line A549., Methods: An adenovirus expression vector (pAd CMV-p27) containing 570 bp human full-length p27 cDNA was transfected into human lung cancer cell line A549. Expression of exogenous p27 gene was detected by dot-blot hybridization and laser co-focal system. MTT was adopted to measure the effects of exogenous p27 gene on cell cycle progression and cell features of the infected A549., Results: The mRNA and protein expression level of p27 was remarkably increased after transfecting with exogenous p27 gene. The apoptosis of infected A549 occurred and the progression of cell cycle was arrested in G1 phase., Conclusions: p27(kipl) gene transfer may play a therapeutic role in the treatment of lung cancer.