Knockdown of miR-1293 attenuates lung adenocarcinoma angiogenesis via Spry4 upregulation-mediated ERK1/2 signaling inhibition.

Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Angiogenesis plays a pivotal role in LUAD progression via supplying oxygen and nutrients for cancer cells. Non-coding miR-1293, a significantly up-regulated miRNA in LUAD tissues, can be potentially used as a novel biomarker for predicting the prognosis of LUAD patients. However, little information is available about the function of miR-1293 in LUAD progression especially cancer-induced angiogenesis. Herein, we found that miR-1293 knockdown could obviously attenuate LUAD-induced angiogenesis in vitro and down-regulate two most important pro-angiogenic cytokines VEGF-A and bFGF expression and secretion. Indeed, miR-1293 abrogation inactivated the angiogenesis-promoting ERK1/2 signaling characterized by decreased ERK1/2 phosphorylation and translocation from nucleus to cytoplasm. Next we found that miR-1293 knockdown reactivated the endogenous ERK1/2 pathway inhibitor Spry4 expression and Spry4 perturbance with specific siRNA transfection abolished the inhibition of ERK1/2 pathway and LUAD-induced angiogenesis by miR-1293 knockdown. Finally, with in vivo assay, we found obvious Spry4 up-regulation and VEGF-A, bFGF, ERK1/2 phosphorylation, micro-vessel density marker CD31 expression down-regulation in vivo, respectively. Collectively, these results indicated that miR-1293 knockdown could significantly attenuate LUAD angiogenesis via Spry4-mediated ERK1/2 signaling inhibition, which might be helpful for uncovering more functions of miR-1293 in LUAD and providing experimental basis for possible LUAD therapeutic strategy targeting miR-1293.

Carbonic Anhydrase 4 Serves as A Novel Prognostic Biomarker and Therapeutic Target for Non-Small Cell Lung Cancer: A Study Based on TCGA Samples.

BACKGROUND: Carbonic anhydrase 4 (CA4) is a member of a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide and was found to have low expression in non-small cell lung cancer (NSCLC). However, the specific role of CA4 in NSCLC and the underlying mechanisms remain unknown. METHODS: The bioinformatic analysis on lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets downloaded from The Cancer Genome Atlas (TCGA) database was performed. We found that CA4 expression was lower in tumors than that in normal tissues, which were verified by Real-time PCR. Lower CA4 levels were significantly associated with higher T stages in LUAD and LUSC cohorts. Multivariate analysis showed that CA4 is an independent prognostic factor for NSCLC. Furthermore, the expression of CA4 also correlated with immune infiltration and drug sensitivity. RESULTS: Ectopic expression of CA4 decreased NSCLC cell proliferation in vitro by CCK-8 assay. CA4 caused G0/G1 cell cycle arrest by cell experiments. Mechanistic studies found that CA affects the cell cycle and inhibits cell proliferation by downregulating the expression of CDK2. CONCLUSION: The present findings highlight the role of CA4 in NSCLC and identify CA4 as a potential novel diagnostic and prognostic biomarker for the treatment of NSCLC.

The Application of Pigtail Catheters in Postoperative Drainage of Lung Cancer.

BACKGROUND: Although minimally invasive surgery has been widely carried out at present, the postoperative pain of patients with lung cancer is still one of the difficult problems to solve in clinical practice. OBJECTIVE: This study explored whether indwelling pigtail catheters after lung cancer surgery can help to reduce postoperative pain and promote the recovery of patients as soon as possible. MATERIALS AND METHODS: From June 2018 to June 2020, patients who underwent thoracoscopic radical resection of lung cancer in our hospital were randomly divided into 2 groups: the pigtail catheter group and the control group. We compared the postoperative time of thoracic catheter removal, postoperative pain score, proportion of postoperative pleural effusion, postoperative hospitalization time, and postoperative complications of the 2 groups. RESULTS: A total of 1375 patients were enrolled, including 677 patients in the pigtail catheter group and 698 patients in the control group. Compared with the control group, the pigtail catheter group had an earlier time of thoracic catheter removal, lower postoperative pain score, lower proportion of pleural effusion diagnosed by postoperative chest radiograph, and shorter postoperative average hospital stay, but there was no significant difference in postoperative complications. CONCLUSION: The application of pigtail catheters after radical resection of lung cancer can reduce postoperative pain, accelerate the recovery of patients and shorten the postoperative hospital stay and is safe and reliable in clinical application.

Diffuse neurofibroma of the chest and abdominal wall invading the diaphragm leads to diaphragmatic eventration: case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant condition with a high rate of new mutation and variable expression. Diffuse neurofibroma of the epidermis invading deeper organs is rare.We report a case of diffuse subcutaneous neurofibroma in the thoracoabdominal wall which had invaded the diaphragm and caused diaphragmatic eventration. CASE PRESENTATION: We describe a patient with diffuse neurofibroma of the chest and abdomen who was admitted to the hospital due to sudden abdominal pain and a possible diaphragmatic hernia. We performed thoracotomy and found that the neurofibroma had invaded the diaphragm and caused diaphragmatic eventration. CONCLUSIONS: This occurrence has not been reported, and it shows that although neurofibromatosis is a benign disease, it still has the biological behavior of a malignant tumor and may cause a serious impact on and damage to other organs.

Genetic profile of non-small cell lung cancer (NSCLC): A hospital-based survey in Jinhua.

BACKGROUND: We describe the clinical features, genetic profile, and their correlation in NSCLC patients. METHODS: A total of 256 Chinese patients with NSCLC were enrolled in this study. NGS-based genomic profiling of major lung cancer-related genes was performed on formalin-fixed paraffin-embedded tumor samples. RESULTS: Of 256 patients with NSCLC, 219 were adenocarcinoma and most of them were in the early stage. Among patients, 63.3% patients have more than two gene mutations. By analyzing variant allele frequency (VAF), we found that the median VAF has significant differences between squamous cell carcinoma and adenocarcinoma, as well as early stage and advanced stage. The frequency of mutations in EGFR, MET, and RET were significantly higher in nonsmokers than in smokers. Besides, Pearson correlation analysis found that ALK, BRAF, and MET mutations had a strong correlation with age. Notably, higher frequencies of ALK and BRAF alterations were associated with younger age, while more frequent MET mutations appear in the patients at age 55 or older. CONCLUSION: More unique features of cancer driver genes in Chinese NSCLC were identified by next-generation sequencing. These findings highlighted that it is necessary to carry out targeted detection according to different clinical features for NSCLC.

Kinetically Controlling the Polymerization of Microgels for Synthesis of Silver Nanoparticles in a Confined Space.

Controllable synthesis of materials is a dream of scientists, which is closing to the reality after the advancement of fundamental studies. It is generally believed that the structure of materials is controlled by thermodynamics and kinetics. When the materials are formed in a condition far away from equilibrium, the kinetic factors play an important role in shaping materials. The aim of this paper is to evaluate whether the diffusion and reaction also influence the structure of organic materials. We take the preparation of poly(N-isopropylamide) microgels as an example. The diffusion of chemicals is regulated by changing the viscosity of solvents while the reaction is regulated by changing the amount of initiators. It is found that slow diffusion and reaction are in favor of propagation reaction, which leads to the formation of long polymer chains. The microgels composed of these long chains have high swelling ratio. On the other hand, the microgels formed in the high diffusion and reaction consists of shorts chains and demonstrates low swelling ratio. In the followings, we used the microgels as reactor to synthesize silver particles. It is found that the size and the density of silver particles are dependent on the swelling ratio of microgels. This study indicates that controlling chemical diffusion and reaction is a general approach to regulate the structure of materials.

Comparative study of directional differentiation of human and mouse embryonic stem cells into cardiomyocytes.

This comparative study investigates the method, efficiency, and anti-hypoxic ability of cardiomyocytes, directionally induced from human (h) and mouse (m) embryonic stem cells (ESCs). hESCs were induced into cardiomyocytes by suspension culture, without inducers, or adherent culture using the inducers activin A and BMP4. mESCs were induced into cardiomyocytes by hanging-drop method, without inducers or induced with vitamin C. All four methods successfully induced ESCs to differentiate into cardiomyocytes. There was a significant difference between groups with and without inducers. A significant difference was found between mESC and hESC groups with inducers. The average beating frequency of cardiomyocytes differentiated from hESC was lower than cardiomyocytes differentiated from mESC, while the average beating frequency of cardiomyocytes differentiated from the same cell line, despite different culture methods, did not differ. Beating cardiomyocytes of each group were positive for cTnT staining. Spontaneous action potentials of beating cardiomyocytes were detected by patch-clamp experiments in each group. Different apoptotic ratios were detected in beating cardiomyocytes in each group and the difference between cardiomyocytes induced from mESCs and hESCs was statistically significant. The differentiation efficiencies in the groups without inducers were significantly higher than those without inducers. The induction of mESCs was more simple and efficient compared with hESCs. Without the presence of other protective factors, the anti-hypoxic ability of cardiomyocytes induced from hESCs was stronger and the beating times were longer in vitro compared with mESCs.