Serum-volatile organic compounds in the diagnostics of esophageal cancer.

The early diagnosis of esophageal cancer (EC) is extremely challenging due to a lack of effective diagnostic methods. The study presented herein aims to assess whether serum volatile organic compounds (VOCs) could be utilised as emerging diagnostic biomarkers for EC. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect VOCs in the serum samples of 55 patients with EC, with samples from 84 healthy controls (HCs) patients analysed as a comparison. All machine learning analyses were based on data from serum VOCs obtained by GC-IMS. A total of 33 substance peak heights were detected in all patient serum samples. The ROC analysis revealed that four machine learning models were effective in facilitating the diagnosis of EC. In addition, the random forests model for 5 VOCs had an AUC of 0.951, with sensitivities and specificities of 94.1 and 96.0%, respectively.

Identification of urinary volatile organic compounds as a potential non-invasive biomarker for esophageal cancer.

Early diagnosis of esophageal cancer (EC) is extremely challenging. The study presented herein aimed to assess whether urinary volatile organic compounds (VOCs) may be emerging diagnostic biomarkers for EC. Urine samples were collected from EC patients and healthy controls (HCs). Gas chromatography-ion mobility spectrometry (GC-IMS) was next utilised for volatile organic compound detection and predictive models were constructed using machine learning algorithms. ROC curve analysis indicated that an 8-VOCs based machine learning model could aid the diagnosis of EC, with the Random Forests having a maximum AUC of 0.874 and sensitivities and specificities of 84.2% and 90.6%, respectively. Urine VOC analysis aids in the diagnosis of EC.

Feasibility research of enhanced recovery after surgery implemented in esophageal cancer patients who underwent neoadjuvant chemotherapy.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a perioperative management protocol to accelerate patient recovery. This study aimed to evaluate the feasibility of ERAS protocols implemented in patients who underwent neoadjuvant chemotherapy (NACT) before minimally invasive McKeown esophagectomy. METHODS: This retrospective study compared the short-term clinical outcomes in esophagectomy patients from June 2018 to June 2021. Subjects were divided into two categories: those who underwent NACT (NACT group) and the non-NACT group. RESULTS: There was no significant difference in total postoperative complication morbidity between the NACT and non-NACT groups (21.2% vs. 20.7%, P=0.936). In addition, the hospital length of stay post-surgery (7.90 vs. 7.71 days, P=0.424) was not significantly longer when compared to the non-NACT group. The time to chest tube removal (5.37 vs. 5.13 days, P=0.238) and first bowel movement (2.92 vs. 3.01 days, P=0.560) was also similar between the two groups. CONCLUSIONS: There was no significant difference in postoperative complications rate, postoperative hospital length of stay, and readmission rate between the two group. This study proved that ERAS protocols seemed to be safe and feasible for patients who received NACT before esophagectomy.

Enhanced Recovery After Surgery Improves Short-term Outcomes in Patients Undergoing Esophagectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a perioperative management protocol used to accelerate patient recovery. This study evaluated its benefits in patients with resectable esophageal cancer. METHODS: This retrospective study compared patients before (January 2013 to December 2016) and after (June 2018 to December 2020) ERAS protocol implementation in our hospital. A propensity score-matched analysis was used to compare short-term surgical outcomes between ERAS and non-ERAS groups. After propensity score matching each group included 243 patients. RESULTS: There were significant differences in hospital length of stay after surgery (7.40 vs 11.17 days, P < .001) and hospitalization cost (¥69380 vs ¥78075, P < .001) between the ERAS and non-ERAS groups. The time to chest tube removal (4.91 vs 7.16 days, P < .001) and first bowel movement (2.87 vs 3.97 days, P < .001) was significantly shorter in the ERAS group. However there was no significant difference in total postoperative complication morbidity (20.2% vs 25.1%, P = .193). The complication of postoperative atelectasis or pneumonia was significantly lower in the ERAS group (P = .003), but there was no significant difference in occurrence of at least grade III complications between the 2 groups (12.3% vs 11.5%, P = .889). CONCLUSIONS: We demonstrated that ERAS could reduce hospital stay, numerical pain scores, and hospitalization costs without increasing postoperative complication and readmission. Furthermore subgroup analyses revealed that ERAS was safe for older people (>70 years old).

MiR-522-3p inhibits proliferation and activation by regulating the expression of SLC31A1 in T cells.

We investigated the role of miR-522-3p in thymoma-associated myasthenia gravis (TAMG), and the mechanism of action in T cells. The miR-522-3p expression in normal serum, non-thymoma MG patient serum and TAMG patient serum and tissues was detected by quantitative real-time PCR (qRT-PCR), respectively. We assessed miR-522-3p expression in Jurkat cells and human CD4+ T cells after activation by anti-CD3 and anti-CD28 using qRT-PCR. The viability, proliferation, cycle distribution and the levels of CD25, CD69, interleukin-2 (IL-2) and IL-10 in transfected Jurkat cells were detected by Cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, qRT-PCR, respectively. Targeting relationships of miR-522-3p and SLC31A1 were predicted and validated by bioinformatics analysis and dual-luciferase reporter. The viability, proliferation, cycle distribution and the levels of SLC31A1, CD25, CD69, IL-2 and IL-10 in transfected Jurkat cells were detected by above methods and western blot. The miR-522-3p expression was declined in TAMG and activated T cells. MiR-522-3p inhibitor promoted cell viability, EdU positive cells, cycle progression, and the level of CD25, CD69, IL-2 and IL-10 in Jurkat cells, while the effect of miR-522-3p mimic was the opposite. SLC31A1 was targeted by miR-522-3p, and miR-522-3p inhibited SLC31A1 expression. Overexpressed SLC31A1 reversed the inhibitory effects of miR-522-3p mimic on cell viability, EdU positive cell, cycle progression, and the levels of IL-2 and IL-10 in transfected Jurkat cells. MiR-522-3p expression was down-regulated in TAMG, and miR-522-3p inhibited proliferation and activation by regulating SLC31A1 expression in T cells.

Circular RNA hsa-circ-000881 suppresses the progression of lung adenocarcinoma in vitro via a miR-665/PRICKLE2 axis.

BACKGROUND: Circular RNA (circRNA) has become a new focus in the field of tumor biology research in recent years. Many circRNAs have been showed to play an important role in the progression of lung adenocarcinoma (LUAD). In this work, we studied the oncological role of hsa-circ-000881 in LUAD and attempted to explore the related mechanism. METHODS: The relative expressions of hsa-circ-000881, miR-665, and PRICKLE2 were detected by RT-qPCR or western blot. Functional assays were conducted to analyze the role of hsa-circ-000881 in the proliferation, migration, and invasion of LUAD cells. A luciferase reporter assay was performed to verify whether hsa-circ-000881, miR-665, and PRICKLE2 interact with each other. RESULTS: Circ-000881 was remarkably downregulated in LUAD. Overexpression of circ-000881 attenuated cell growth, migration, and invasion, whereas its knockdown enhanced the malignancy of LUAD cells. The results of luciferase reporter assay and bioinformatics analysis confirmed that circ-000881 served as a sponge for miR-665, and PRICKLE2 was a direct target of miR-665.Overexpression of miR-665 or silencing of PRICKLE2 abolished circ-000881-mediated inhibition of malignant tumor behavior in LUAD cells. CONCLUSIONS: Circ-000881 has inhibitory effects on LUAD via a miR-665/PRICKLE2 axis, suggesting that circ-000881 may be an underlying therapeutic target for LUAD.

Identification of key genes associated with esophageal adenocarcinoma based on bioinformatics analysis.

BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive malignancy and accounts for the majority of cancer-related death worldwide. It is often diagnosed at an advanced stage and entails a poor prognosis for those afflicted. The mechanisms of its pathogenesis and progress remain unclear and require urgent elucidation. This study aimed to identify specific genes and potential pathways associated with the progression and prognosis of EAC using bioinformatics analyses. METHODS: EAC microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were analyzed to identify differentially expressed genes (DEGs) using bioinformatics analysis. The DEGs in TCGA were then analyzed to construct a co-expression network by weighted correlation network analysis (WGCNA), and module-clinical trait relationships were analyzed to explore the genes that associated with clinicopathological parameters of EAC. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were performed for the cancer-related genes, and a DEG-based protein-protein interaction (PPI) network was used to extract hub genes through Cytoscape plugins. The consensus survival analysis for EAC (OSeac) was performed to identify the prognosis-related genes. The immune infiltration was evaluated by tumor immune estimation resource (TIMER) algorithms, and a risk score prognostic model was established using univariate, multivariate Cox proportional hazards regression, and lasso regression analysis. RESULTS: Ultimately, 190 cancer-related DEGs were identified, 6 of which were found to play vital roles in the progression of EAC, including ACTA2, BGN, CALD1, COL1A1, COL4A1, and DCN. The risk score prognostic model consisted of 6 other genes that had an important impact on the prognosis of EAC, including CLDN3, EPB41L4A, ESM1, MT1X, PAQR5, and PLAU. The area under the curve of the prognostic model for predicting the survival of patients at 1, 2, and 3 years was 0.707, 0.702, and 0.726, respectively. CONCLUSIONS: This study identified several genes with the potential to become useful targets for the diagnosis and treatment of EAC. The 6-gene-related risk score prognostic model and nomogram based on these genes may be a reliable tool for predicting the prognosis of patients with EAC.

Evaluation of Serum Exosomal lncRNAs as Diagnostic and Prognostic Biomarkers for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Exosomal long non-coding RNAs (lncRNAs) have been recognised as promising stable biomarkers in cancers. The aim of this study was to identify an exosomal lncRNA panel for diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Exosomes were isolated from serum by ExoQuick Solution. To validate the exosomes, exosomal markers and characterization of nanoparticle were performed. Quantitative real-time PCR was used to measure the levels of lncRNAs in exosomes from ESCC patients and healthy subjects. In the training set, exosomal lncRNA profiles from 404 samples were conducted and established new models by multivariate logistic regression. In the validation set, the diagnostic performance of the panel was further validated in 222 additional individuals with a receiver operating characteristic curve (ROC). Kaplan-Meier and multivariate Cox proportional hazards analysis were applied to assess the correlation between lncRNAs and survival rate of ESCC patients. RESULTS: A 4-lncRNA panel (UCA1, POU3F3, ESCCAL-1 and PEG10) in exosomes for ESCC diagnosis was developed by logistic regression model. The diagnostic accuracy of panel was evaluated with AUC value of 0.844 and 0.853 for training and validation stage, respectively. The corresponding AUCs for patients with TNM stage I-II and III were 0.820 and 0.935, significantly higher than squamous cell carcinoma antigen (P<0.001), which were 0.652 and 0.642, respectively. Kaplan-Meier analysis indicated that patients with higher level of UCA1 and POU3F3 had lower survival rate (P<0.001). Additionally, POU3F3 might be as an independent prognostic factor for ESCC patients (P=0.004). CONCLUSION: These findings suggested that serum exosomal 4-lncRNA panel has considerable value for ESCC diagnosis, and POU3F3 may serve as a novel and independent prognostic predictor in clinical applications.

ZHX2 inhibits proliferation and promotes apoptosis of human lung cancer cells through targeting p38MAPK pathway.

OBJECTIVE: To investigate the effect of ZHX2 on lung cancer cells proliferation and apoptosis. MATERIALS AND METHODS: The mRNA and protein expression of ZHX2 were detected by qRT-PCR and western blot, respectively. The human lung cancer cells were divided into Control, NC, ZHX2, SB, and ZHX2 + Ani groups. The cell proliferation was detected by CCK-8 assay and the cell migration and invasion were detected by Transwell assay. Cell apoptosis was detected by flow cytometry. Apoptosis and p38MAPK signaling pathway related proteins were detected by western blot. The nude mice model of lung cancer xenograft was constructed. The tumor volume and tumor weight were measured. The expression of PCNA protein in tumor tissues was detected by immunohistochemistry. The apoptosis of tumor cells was detected by TUNEL staining. The ZHX2 and p38MAPK signaling pathway related proteins in tumor tissues were detected by western blot. RESULTS: The expression of ZHX2 gene and protein in the cancer cell lines were significantly decreased. Compared with control and NC groups, the cells proliferation, migration and invasion were inhibited in ZHX2 and SB groups, while the apoptosis and apoptosis related proteins were increased (p< 0.05). Meanwhile, compared with ZHX2 group, the tumor growth rate, volume, weight, the percentage of PCNA-positive cells, and p-P38 MAPK/P38 MAPK were increased significantly in ZHX2 + Ani group, while the apoptotic index and the expression of MMP-9 protein were significantly decreased (p< 0.05). CONCLUSION: ZHX2 could inhibit proliferation and promote apoptosis of lung cancer cells by inhibiting p38MAPK signaling pathway.

Comparison of circular stapling, triangulating stapling and T-shape stapling for cervical anastomosis with minimally invasive esophagectomy.

BACKGROUND: The triangulating stapling (TST) and T-shape stapling (TS) methods have been proposed to decrease the incidence of anastomotic leakage after esophagectomy, but few studies have compared them to the circular stapling technique (CS). This retrospective study aimed to compare the efficacy and safety of three cervical anastomosis methods after esophagectomy. METHODS: Squamous cell carcinoma patients who underwent minimally invasive esophagectomy (MIE) with CS, TST or TS anastomosis between April 2010 and June 2012 were recruited. Their clinical characteristics and short-term outcome were analyzed. Kaplan-Meier analyses compared with log-rank test were used to calculate the effect of the three types of cervical anastomosis on overall survival (OS) and disease-free survival (DFS). RESULTS: The incidence of anastomotic leakage was 21.8% in the CS group, 7.7% in the TS group and 11.9% in the TST group (P=0.029). There were significant differences in the incidence of gastroesophageal reflux among the three groups (P<0.001). Rates of anastomotic stenosis, pulmonary infection, chylothorax and hoarseness were not different among the groups. There were significant differences in anastomotic time, operation time and hospitalization time (all P<0.001), but there was no significant difference in albumin content at 1 month after operation (P=0.226). There was no differences in long-term surgical effects of the three types of anastomosis. CONCLUSIONS: Cervical esophagogastric anastomosis by TST or TS can be considered feasible and safe and with improved short-term outcome.

Expression of MiR-608 in Nonsmall Cell Lung Cancer and Molecular Mechanism of Apoptosis and Migration of A549 Cells.

OBJECTIVE: This Work is aimed at exploring the effect of microRNA (MiR)-608 on the function of nonsmall cell lung cancer (NSCLC) A549 cells and related mechanisms. METHODS: Blood samples of 106 NSCLC patients (experimental group) as well as 124 normal people (control group) were selected for relevant investigation. Polymerase chain reaction (PCR) as well as DNA sequencing was used to determine the genotyping of the MiR-608 rs4919510 polymorphism. MiR-608 expression in cells was detected by real-time PCR technology. Western blotting was used to detect changes in protein levels. NSCLC tissues as well as adjacent tissues were explored in 33 patients undergoing surgery. RESULTS: MiR-608 rs4919510 does not influence the incidence of NSCLC patients. In addition, MiR-608 expression was downregulated in the tumor tissue of NSCLC patients, while the transcription factor activating enhancer-binding protein 4 (TFAP4) expression was upregulated. MiR-608 promotes DOX- (Doxorubicin-) induced apoptosis by negatively regulating TFAP4 expression in NSCLC tissue. TFAP4 can significantly inhibit the migration of A549 cells. CONCLUSION: The findings in this investigation can contribute to the effective treatment of NSCLC patients. Also, the investigation can provide some theoretical support for the application of new targets for NSCLC treatment.

Detection of circulating exosomal miR-17-5p serves as a novel non-invasive diagnostic marker for non-small cell lung cancer patients.

Exosome-shuttled bioactive miRNAs act as novel non-invasive biomarkers for cancer diagnosis have received increasing attention. In this study, we aimed to investigate the expression signatures of exosomal miRNAs and develop a serum exosome-derived miRNA panel for diagnosis of non-small cell lung cancer (NSCLC). The miR-17-92 cluster including 6 miRNAs (miR-17-5p, miR-18a-5p, miR-19a-3p, miR-19b-1-5p, miR-20a-5p and miR-92a-1-5p) was selected as potential diagnostic candidate molecule. Then, expression profiles of the candidate miRNAs were firstly analyzed in 43 pairs of serum samples from the training set by quantitative real-time PCR, and the dysregulated miRNA along with three tumor markers (carcinoembryonic antigen, CEA; cytokeratin 19 fragment, CYFRA21-1; squamous cell carcinoma antigen, SCCA) were further validated in two independent cohorts, which consisted of training set (including 100 NSCLC patients and 90 healthy controls) and validation set (including 72 NSCLC patients and 47 healthy controls). The expression of miR-17-5p was significantly up-regulated in NSCLC patients compared with the healthy controls (P < 0.001), suggesting that miR-17-5p might have considerable clinical value in the diagnosis of NSCLC. Based on the data from the training set, we next used a logistic regression model to construct a 4-molecule panel consisting of miR-17-5p and three tumor markers for NSCLC diagnosis. The performance of such 4-molecule panel was verified with an area under the ROC curve of 0.860 (95% CI = 0.802 to 0.906, sensitivity = 63.0% and specificity = 93.3%) and 0.844 (95% CI = 0.766 to 0.904, sensitivity = 76.4% and specificity = 76.6%) in the training set and validation set, respectively. In conclusion, the newly developed diagnostic panel consisting of exosomal miR-17-5p, CEA, CYFRA21-1 and SCCA may have considerable clinical value in the diagnosis of NSCLC.

siRNA of DNA polymerase iota inhibits the migration and invasion in the lung cancer cell A549.

DNA polymerase iota (polɩ) is a member of low-fidelity Y-family of DNA polymerases. Our previous studies have demonstrated that the overexpression of polι is associated with the poorer prognosis in lung cancer patients. Here, we designed the small interfering RNA (siRNA) targeting polɩ gene (POLI) to investigate the effect of polɩ on the proliferation, apoptosis, and invasion of the lung cancer cell line A549 in order to reveal the role of polι in lung cancer progression. Our results showed that siRNA of POLI had no significant effect on the proliferation and apoptosis of the lung cancer cell line A549. However, siRNA of POLI could inhibit the migration and invasion of the lung cancer cell line A549 by upregulating the E-cadherin expression and downregulating the expressions of N-cadherin, MMP2, and MMP9. Together, our findings indicate that polι plays a positive role in lung cancer progression via promoting the migration and invasion of lung cancer cells. Therefore, polι might be a potential target for the clinical treatment of lung cancer in the future.

Circulating long noncoding RNA act as potential novel biomarkers for diagnosis and prognosis of non-small cell lung cancer.

Lung cancer is the first leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Increasing evidence shows that long noncoding RNA (lncRNA) are capable of modulating tumor initiation, proliferation and metastasis. In the present study, we aimed to evaluate whether circulating lncRNA could be used as biomarkers for diagnosis and prognosis of NSCLC. Expression profiles of 14 lncRNA selected from other studies were validated in 20 pairs of tissues by quantitative real-time PCR, and the dysregulated lncRNA thus identified were further validated in serum samples from two independent cohorts along with three tumor makers (CEA, CYFRA21-1, and SCCA). Receiver-operating characteristic analysis was utilized to estimate the diagnostic efficiency of the candidate lncRNA and tumor markers. Importantly, we observed an association between lncRNA expression and overall survival (OS) rate of NSCLC. The expressions of SOX2 overlapping transcript (SOX2OT) and ANRIL were obviously upregulated in NSCLC tissues and serum samples compared with normal controls (P < 0.01). Based on the data from the training set, we next used a logistic regression model to construct an NSCLC diagnostic panel consisting of two lncRNA and three tumor markers. The area under the curve of this panel was 0.853 (95% confidence interval = 0.804-0.894, sensitivity = 77.1%, specificity = 79.2%), and this was distinctly superior to any biomarker alone (all at P < 0.05). Similar results were observed in the validation set. Intriguingly, Kaplan-Meier analysis demonstrated that low expressions of SOX2OT and ANRIL were both associated with higher OS rate (P = 0.008 and 0.017, respectively), and SOX2OT could be used as an independent prognostic factor (P = 0.036). Taken together, our study demonstrated that the newly developed diagnostic panel consisting of SOX2OT, ANRIL, CEA, CYFRA21-1, and SCCA could be valuable in NSCLC diagnosis. LncRNA SOX2OT and ANRIL might be ideal biomarkers for NSCLC prognosis.

Potential use of microRNA-200c as a prognostic marker in non-small cell lung cancer.

MicroRNAs (miRNAs/miRs) are a class of small, highly conserved non-coding RNAs that can serve either oncogenic or tumor-suppressive roles in a wide variety of tumors. miR-200c is a member of the miR-200 family whose specific role in non-small cell lung cancer (NSCLC) has not yet been elucidated. The purpose of the present study was to detect the expression level of miR-200c in NSCLC, and to analyze its association with clinicopathological factors and patient prognosis. The present study determined the expression levels of miR-200c in 110 tumor samples collected from patients diagnosed with NSCLC who underwent complete tumor resection with regional lymph node dissection, as assessed by reverse transcription-quantitative polymerase chain reaction. The association between the expression level of miR-200c and clinicopathological features and patient prognosis was also analyzed. The results showed that miR-200c overexpression was detected in 66 of the 110 cases and was significantly associated with positive lymph node metastasis (P<0.001). Univariate survival analysis demonstrated that high miR-200c expression, positive lymph node metastasis and advanced Tumor-Node-Metastasis (TNM) classification stage significantly predicted decreased 5-year disease-free survival rates (all P<0.05) and poor 5-year overall survival rates (all P<0.01), respectively. The results of multivariate Cox regression analysis showed that TNM stage and miR-200c expression retained its significance as an independent prognostic factor for unfavorable 5-year disease-free survival rates (P<0.05) and poor 5-year overall survival rates (P<0.01). The present findings suggest that miR-200c overexpression is significantly associated with poor survival rates in NSCLC and that miR-200c could play an oncogenic role. miR-200c may have clinical potential as a promising prognostic predictor for patients with NSCLC.

Subxiphoid vs intercostal single-incision video-assisted thoracoscopic surgery for spontaneous pneumothorax: A randomised controlled trial.

INTRODUCTION: The conventional video-assisted thoracoscopic surgery (VATS) is performed through the intercostals incisions. In this study, we reported our current experience of thoracoscopic surgery using a subxiphoid single-incision and compared it with the intercostal uniport VATS in the operation time and postoperative pain for spontaneous pneumothorax. METHODS: From July 2014 to September 2015, 43 consecutive patients with spontaneous pneumothorax underwent the unilateral or bilateral bullectomy vie VATS. Among these, 22 patients were treated by the subxiphoid single-incision VATS, and 21 patients were treated using the conventional intercostals uniport VATS. The duration of operation, hospital stay days and inpatient pain scores were compared between each group. RESULTS: The postoperative pain scores on postoperative days (POD) 0, 1, 2 and 3 were significantly lower for patients who underwent the subxiphoid single-incision VATS than those who underwent the intercostal uniport VATS (p < 0.05). However, the subxiphoid single-incision VATS needed longer surgical time than the intercostal uniport VATS (p < 0.001). DISCUSSION: The subxiphoid uniport VATS could decrease the postoperative pain and was safe and effective for performing the unilateral or bilateral bullectomy, but, demanded longer surgical time comparing with the intercostal uniport VATS. CONCLUSIONS: Subxiphoid single-incision VATS, as a new method for bullectomy, could provide a good choice of the incision position for these young patients with spontaneous pneumothorax.

Rotenone induces apoptosis in human lung cancer cells by regulating autophagic flux.

Reactive oxygen species (ROS) are at the center of many physiological and pathological processes. ROS generated due to oxidative stress can potentiate both cancer initiation and progression. Rotenone, which is an inhibitor of the mitochondrial electron transport chain complex I, results in the activation of NOX2 and release of ROS, and has been shown to display anticancer activity through the induction of apoptosis in various cancer cells. The mechanistic link between rotenone-dependent activation of NOX2 and induction of apoptosis is still elusive. In this study, we used the human lung cancer A549 cells to study the molecular mechanism(s) involved between rotenone-dependent activation of NOX2 and impairment of autophagic machinery. We report that acute exposure to rotenone induced mild NOX2-dependnet oxidative stress, which impaired the autophagic flux, resulting in cytosolic accumulation of LC3 and p62/STSQM1. We further show that this induction occurs through the PI3K/Akt/mTORC1 signaling pathway. We furthermore show that chronic exposure to rotenone lead to excessive NOX2-dependent ROS generation, increases autophagy, and decreases p62 level via increased-autophagic flux. Taken together, this study is the first mechanistic elucidation of how rotenone can be used to potently target cancer cells without overhauling the entire cellular machinery. © 2016 IUBMB Life 68(5):388-393, 2016.

Clinicopathological and prognostic significance of metastasis-associated protein 1 expression and its correlation with angiogenesis in lung invasive adenocarcinomas, based on the 2011 IASLC/ATS/ERS classification.

Based on previous findings regarding the angiogenic activities and prognostic roles of metastasis-associated protein 1 (MTA1) in early-stage non-small cell lung cancer, the clinicopathological and prognostic significance of MTA1 protein expression, and its correlation with angiogenesis in lung invasive adenocarcinoma, were further assessed in the present study, according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. High protein expression levels of MTA1 were commonly observed in patients with lung invasive adenocarcinoma, and were significantly correlated with tumor size (P=0.030), lymph node metastasis (P=0.021) and microvessel density (P=0.015). Survival analysis demonstrated that patients with high protein expression levels of MTA1 exhibited significantly shorter five-year disease-free and overall survival than those patients whose protein expression levels of MTA1 were low (24.5% vs. 48.7%, P=0.001, and 34.7% vs. 59.2%, P=0.005, respectively). In addition, Cox regression multivariate analysis demonstrated that high protein expression levels of MTA1 significantly correlated with unfavorable five-year disease-free survival (P=0.024). These findings indicate that MTA1 protein expression may possess clinical potential as an indicator of progressive phenotype. Therefore, MTA1 is a promising prognostic predictor to identify subgroups of patients with high risk of relapse, and a potentially novel therapeutic target for antiangiogenesis in patients with lung invasive adenocarcinoma.

Regulator of G-protein signaling 4: A novel tumor suppressor with prognostic significance in non-small cell lung cancer.

Regulator of G-protein signaling (RGS) family members are regulatory molecules which act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. Emerging data indicated that RGS members were involved with tumorigenesis and metastasis. In the current study, we identified RGS4 as a novel tumor suppressor with prognostic significance in non-small cell lung cancer (NSCLC). To be specific, we found that RGS4 expression was higher in normal lung tissues than NSCLC specimens (P = 0.003). Further studies demonstrated that RGS4 was generally down-regulated in NSCLC specimens compared with the matched normal lung tissues, both at mRNA and protein levels. In addition, correlational analysis indicated that RGS4 expression levels negatively correlated with lymph node metastasis (P = 0.009) and TNM stage (P = 0.008). Survival analysis demonstrated that patients with lower RGS4 protein expression exhibited a much worse 5-year overall survival and 5-year disease-free survival than those with high expression. More importantly, we proved that over-expression of RGS4 in NSCLC cells decreased invasion and migration due to inhibition of MMP2/9 and reversal of EMT while down-regulation of RGS4 in normal lung cell lines promoted invasion and migration. At last, nude mice metastatic model proved that over-expression of RGS4 suppressed tumor metastasis in vivo. All of these results confirmed the critical role of RGS4 in NSCLC progression.

Laparoscopic repair of Morgagni hernia by artificial pericardium patch in an adult obese patient.

BACKGROUND: Morgagni hernia is a kind of rare congenital diaphragmatic hernia. We reported a case of Morgagni hernia repaired successfully with artificial pericardium patch via the laparoscopic approach. METHODS: The patient was admitted with a 3-month history of postprandial nausea and vomiting, and accompanied by epigastric pain. Computed tomography (CT) scans showed a large anteromedial diaphragmatic hernia. The hernial contents were reduced back into the abdominal cavity and the diaphragmatic defect was repaired with artificial pericardium patch by laparoscopic intracorporeal suture. RESULTS: We achieved satisfactory intracorporeal repair of this large diaphragmatic defect. The patient had excellent recovery and started on oral diet on the first postoperative day, and then was discharged just two days after operation. CONCLUSIONS: The minimally invasive advantage of laparoscopic approach offers a secure, reliable and satisfactory way to confirm the diagnosis and achieve the repair of non-complicated Morgagni hernia.