Circular RNA hsa_circ_0002483 promotes growth and invasion of lung adenocarcinoma by sponging miR-125a-3p.

BACKGROUND: Increasing evidence indicates that the aberrant expression of circular RNAs (circRNAs) is involved in the pathogenesis and progression of lung adenocarcinoma (LUAC). However, the function and molecular mechanisms of hsa_circ_0002483 (circ_0002483) in LUAC remain unclear. METHODS: The association between circ_0002483 expression and clinicopathological characteristics and prognosis in patients with LUAC was analyzed by fluorescence in situ hybridization. The functional experiments such as CCK-8, colony formation and Transwell assays and a subcutaneous tumor model were conducted to determine the role of circ_0002483 in LUAC cells. The specific binding between circ_0002483 and miR-125a-3p was validated by RNA immunoprecipitation, luciferase gene report and qRT-PCR assays. The effects of circ_0002483 on miR-125a-3p-mediated C-C motif chemokine ligand 4 (CCL4)-CCR5 axis were assessed by Western blot analysis. RESULTS: We found that circ_0002483 was upregulated in LUAC tissue samples and associated with Tumor Node Metastasis (TNM) stage and poor survival in patients with LUAC. Knockdown of circ_0002483 inhibited proliferation, colony formation and invasion of A549 and PC9 cells in vitro, whereas overexpression of circ_0002483 harbored the opposite effects. Furthermore, circ_0002483 sponged miR-125a-3p and negatively regulated its expression. CCL4 was identified as a direct target of miR-125a-3p. The rescue experiments showed that miR-125a-3p mimics reversed the tumor-promoting effects of circ_0002483 by targeting CCL4-CCR5 axis in A549 and PC9 cells. In addition, the in vivo experiment further validated that knockdown of circ_0002483 repressed tumor growth. CONCLUSIONS: Our findings demonstrated that circ_0002483 could act as a sponge of miR-125a-3p to upregulate CCL4-CCR5 axis, contributing to the tumorigenesis of LUAC, and represent a potential therapeutic target for LUAC.

Changes in Expressions of HSP27, HSP70, and Soluble Glycoprotein in Heart Failure Rats Complicated with Pulmonary Edema and Correlations with Cardiopulmonary Functions.

The study is aimed at investigating the changes in expressions of heat shock protein 27 (HSP27), HSP70, and soluble glycoprotein (SGP) in heart failure (HF) rats complicated with pulmonary edema and exploring their potential correlations with cardiopulmonary functions. The rat model of HF was established, and the rats were divided into HF model group (model group, n = 15) and normal group (n = 15). After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function indexes were determined, the injury of myocardial tissues was observed via hematoxylin and eosin (HE) staining, and the content of myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-alpha (TNF-α) in the blood was measured. The partial pressure of oxygen (PaO2) and oxygenation index (OI) were observed, and the airway resistance and lung compliance were examined. Moreover, quantitative polymerase chain reaction (qPCR) and Western blotting assay were performed to detect the gene and protein expression levels of HSP27, HSP70, and SGP130. The levels of serum creatine kinase (CK), creatine (Cr), and blood urea nitrogen (BUN) were increased markedly in model group (p < 0.05). Model group had notably decreased fractional shortening (FS) and ejection fraction (EF) compared with normal group (p < 0.05), while the opposite results of left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were detected. In model group, the content of serum MPO, MMP-9, and TNF-α was raised remarkably (p < 0.05), OI and PaO2 were reduced notably (p < 0.05), the airway resistance was increased (p < 0.05), and the lung compliance was decreased (p < 0.05). Obviously elevated gene and protein expression levels of HSP27, HSP70, and SGP130 were detected in model group (p < 0.05). The expressions of HSP27, HSP70, and SGP130 are increased in HF rats complicated with pulmonary edema, seriously affecting the cardiopulmonary functions of the rats.

A cell membrane vehicle co-delivering sorafenib and doxorubicin remodel the tumor microenvironment and enhance immunotherapy by inducing immunogenic cell death in lung cancer cells.

Cancer immunotherapy is a promising approach for cancer therapy but is usually hindered by the inhibition of the tumor microenvironment (TME). Herein, we developed a cell membrane vehicle (CV) to co-deliver doxorubicin (Dox) and sorafenib (Sfn) as a drug delivery system (CV/D-S) to regulate the TME and sensitize the immunogenic cell death (ICD)-induced immune response against tumors. The CV/D-S showed high stability, acid-responsive drug release, high biocompatibility with tumor-specific cellular uptake, and target-ability that preferably resulted in the in vitro and in vivo anticancer performance. Most importantly, the Dox in the DDS can induce significant ICD while Sfn was able to remodel the TME, downregulate Treg, activate effector T cells and relieve programmed cell death protein 1 (PD-1) expression. As a result, the synergistic effect of Dox and Sfn achieved strong immune response in CV/D-S treated mice, which is believed to open a new window for the design and development of future platforms for the more effective immunotherapy of cancer.

Independent prognostic value of HIF-1α expression in radiofrequency ablation of lung cancer.

Radiofrequency ablation (RFA) is widely used in the treatment of lung cancer. Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor regulating oxygen homeostasis that is involved in tumor cell metastasis. The present study investigated the impact of HIF-1α expression and other factors, such as postoperative blood CD4+/CD8+ ratio, on the prognosis of patients with lung cancer who had received RFA treatment. A total of 80 patients with lung cancer were recruited between January 2011 and October 2016 at The Shenzhen People's Hospital. Lung cancer was confirmed following pathological or histological examination. All patients underwent RFA treatment. Patients were followed up for 6-66 months. HIF-1α expression in lung cancer tissues was assessed by immunohistochemistry. Multivariate survival analysis was performed using Cox proportional hazards model. The results demonstrated that HIF-1α level was low in 36 patients and overexpressed in 44 patients with lung cancer. Kaplan-Meier (KM) curve analysis demonstrated that the overall survival time of patients with high HIF-1α expression was significantly shorter compared with patients with low HIF-1α expression (P<0.05). Furthermore, the results from the KM model and log-rank test revealed that age, Union for International Cancer Control stage, primary or metastatic cancer, chemotherapy, postoperative blood CD4+/CD8+ ratio, Eastern Cooperative Oncology Group performance status and HIF-1α expression had significant effects on overall survival of patients with lung cancer. The results from Cox analysis demonstrated that high HIF-1α expression, advanced age, clinical staging and chemotherapy were independent risk factors for the prognosis of lung cancer following RFA treatment, and that high HIF-1α expression was associated with the increased risk (5.91-fold) of mortality. In conclusion, the present study demonstrated that HIF-1α expression was increased in lung cancer tissues and was associated with the prognosis of patients with lung cancer who were treated with RFA. These findings suggest that HIF-1α expression may be considered as a marker for evaluating the prognosis of these patients.

In vitro study on the role of SOX9 in trastuzumab resistance of adenocarcinoma of the esophagogastric junction.

Trastuzumab is recommended for the treatment of human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagogastric junction (AEG) in combination with chemotherapy; however, drug resistance has severely affected its clinical application. The present study aimed to investigate the effect of sex determining region Y-box 9 (SOX9), a prognostic marker in adjuvant oncological settings, on AEG cell proliferation and apoptosis in the presence or absence of trastuzumab. Furthermore, the molecular mechanism underlying the role of SOX9 in trastuzumab resistance was explored. ESO26 cells were treated with various concentrations of trastuzumab, and trastuzumab induced SOX9 expression in a concentration-dependent manner, as determined by reverse transcription-quantitative polymerase chain reaction and western blotting analyses. Transfection of ESO26 cells with SOX9 small interfering RNA was conducted to knock down SOX9 expression, and the results of MTT and flow cytometry assays demonstrated that SOX9 knockdown sensitized ESO26 cells to trastuzumab by inhibiting cell proliferation and enhancing cell apoptosis. In addition, it was observed that the trastuzumab-induced phosphorylation of AKT was suppressed by SOX9 knockdown. In conclusion, the present study demonstrated that SOX9 participated in trastuzumab resistance by affecting cell proliferation and apoptosis, and indicated that SOX9 may exert its effect on trastuzumab resistance via activation of the phosphatidylinositol-3-kinase/AKT signaling pathway. This study identified a novel mechanism underlying trastuzumab resistance in vitro and may be useful in improving the efficacy of trastuzumab treatment.

Uniportal complete video-assisted thoracoscopic surgery lobectomy with partial pulmonary arterioplasty for lung cancer with calcified lymph node.

Now, more and more complete video-assisted thoracoscopic surgery (cVATS) surgeons are capable of performing lobectomy by uniportal approach. However, concerns regarding the safety of uniportal procedures for complex cases such as neoadjuvant chemotherapy, bronchial sleeves or vascular reconstructions still remains. As experience with uniportal VATS has increased, its application toward more technically demanding operations has also expanded. This article describes a uniportal cVATS left upper lobectomy with partial pulmonary arterioplasty for lung cancer with calcified lymph nodes. In order to reduce the risk of bleeding, we looped the left main pulmonary artery and applied two-stage maneuvering for left upper lobe (LUL) bronchus, cut the bronchus at the distal end and close the stump using a stapler at the end, which are conducive to maximal safety.

Uniportal complete video-assisted thoracoscopic lobectomy with systematic lymphadenectomy.

Video-assisted thoracoscopic surgery (VATS) has permeated our thoracic surgical practice and now will develop in depth towards a next level of minimally invasive surgery (MIS). Irrespective of generation gaps and diversified perception within thoracic community, more and more surgical teams are adapting to the uniportal lobectomy. This video demonstrates a case undergoing uniportal VATS lobectomy with systematic lymphadenectomy for lung cancer. We here describe our technique for uniportal approach by using a combination of double-jointed and endoscopic instruments to combat the four major obstacles: (I) interference of the thoracoscope, stapler and the instrumentation in and out of the thoracic cavity? (II) whether the field of vision is enough or not without the other 1-3 ports to improve the exposure? (III) the optimal stapler introduction angle especially for upper and middle lobes resection? (IV) more importantly, the oncologic validity of uniportal procedures as well as the reduction of postoperative morbidity? We believe, uniportal VATS lobectomy with systematic lymphadenectomy is technically safe and feasible and alternative approach to conventional thoracoscopic lobectomy in lung cancer treatment. The issues of patient acceptability, the cosmetic and oncologic results, and cost-effectiveness remain to be determined in the future through multi-institution randomized controlled trials and long-term follow-up.

Biportal complete video-assisted thoracoscopic lobectomy and systematic lymphadenectomy.

The video-assisted thoracoscopic approach (VATS) for lobectomy of non-small-cell lung cancer (NSCLC) has not been standardized. Although three to four incisions are usually made, with the right surgical technique, the operation can be successfully carried out via only two incisions. This video demonstrates a case undergoing biportal complete VATS (biportal cVATS) right upper lobectomy and systematic lymphadenectomy. Here we describe our technique of biportal approach by using a combination of conventional and endoscopic instruments. As our experience gained, we consider the knacks of biportal cVATS lobectomy imply two radical changes of perspectives from the traditional triportal technique. One fundamental step is how to achieve satisfactory exposure in the case of single utility incision for multiple instruments to insert. Another technical tip that should be taken into account is how to introduce staplers conveniently without the third posterior port. Optimization of the whole procedures is critical for accomplishing anatomic hilar vascular, bronchial, and lymphatic dissection via two ports. In conclusion, biportal cVATS lobectomy for lung cancer is a safe and reliable procedure that can achieves good postoperative results without oncological compromise.