Echinocystic acid induces the apoptosis, and inhibits the migration and invasion of non-small cell lung cancer cells.

An increasing amount of evidence has demonstrated the anticancer activity of triterpenes extracted from traditional medicines. Echinocystic acid (EA), a natural triterpene isolated from Eclipta prostrata (L.) L., has previously been shown to exhibit anticancer activity in HepG2 and HL-60 cells. The aim of the present study was to investigate the anticancer activity of EA in non-small cell lung cancer (NSCLC) cells. For this purpose, the viability and proliferation of A549 cells were determined using a Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine staining. The migratory and invasive ability of the A549 cells were measured using wound healing and Transwell assays. Hoechst staining was also performed to detect the apoptosis of A549 cells. The proliferation of A549 cells and the distributions of different growth phases were determined using a flow cytometer. Western blot analysis was used to detect the expression levels of cyclin D, partitioning defective 3 homolog (Par3), PI3K, Akt, mTOR, Bax, Bcl-2 and caspase-3. EA inhibited the proliferation, and the migratory and invasive abilities of cultured lung carcinoma cells (A549 cells), and induced cell cycle arrest in the G1 phase of the cell cycle. Treatment with EA upregulated Par3 expression and inhibited the PI3K/Akt/mTOR pathway in vitro. In addition, EA treatment inhibited tumor growth, suppressed proliferation and induced the apoptosis of tumor cells in NSCLC tumor xenografts in mice. On the whole, these results suggest that EA may represent a potential therapeutic agent for NSCLC.

Neoadjuvant sintilimab plus chemotherapy for locally advanced resectable esophageal squamous cell carcinoma: a prospective, single-arm, phase II clinical trial (CY-NICE).

Background: Adding immune checkpoint inhibitors (ICIs) to the chemotherapy has shown significant clinical benefits in neoadjuvant treatment of locally advanced esophageal squamous cell carcinoma (ESCC). Sintilimab is one such ICI used for treatment. Herein, we designed a trial to evaluate the safety and efficacy of sintilimab combined with paclitaxel and platinum for locally advanced resectable ESCC. Methods: Patients with locally advanced resectable (stage II-III) ESCC were enrolled and received at least two cycles of neoadjuvant therapy with sintilimab (200 mg on day 1) plus platinum-based chemotherapy in each 3-week cycle followed by esophagectomy. The primary endpoint of the trial was the pathological complete response (pCR) rate. The secondary endpoints were the major pathological response (MPR) rate, the objective response rate (ORR), the treatment-related adverse events (TRAEs), the immune-related adverse events (irAEs) and quality of life (QOL). Besides, relapse-free survival (RFS), overall survival (OS) were exploratory endpoints. Forty-three cases were needed to be enrolled in this trial. It was assumed the regimen of the neoadjuvant sintilimab plus chemotherapy would achieve a pCR rate of 30.5%. Results: Between March 2021 and January 2023, a total of 43 patients (41 men and 2 women) were enrolled, including 11 cases (25.6%) of clinical stage II and 32 cases (74.4%) of clinical stage III at baseline. All the 43 patients completed two cycles of neoadjuvant therapy, and 32 patients received McKeown radical resection for esophageal cancer. The pCR rate was 28.1% (9/32), which was below the 30.5% reference cutoff value, and the MPR rate was 37.5% (12/32). According to RECIST 1.1, four patients (4/43, 9.3%) had a complete response (CR), 21 patients (21/43, 48.8%) had a partial response (PR), ORR was 58.1% (25/43). The incidence of ≥ grade 3 TRAEs was 23.3% (10/43) and there were no ≥ grade 4 TRAEs. Conclusions: Sintilimab plus platinum-based chemotherapy as neoadjuvant therapy is safe, feasible and effective in locally advanced resectable ESCC, suggesting a supportive rationale for its further evaluation in randomized clinical trials. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2200056558.

Effects of ALOX5, IL6R and SFTPD gene polymorphisms on the risk of lung cancer: A case-control study in China.

BACKGROUND: ALOX5, IL6R and SFTPD are all immune related genes that may be involved in the development of lung cancer. We sought to explore the effect of polymorphisms of these genes on the risk of lung cancer. METHODS: Six single nucleotide polymorphisms (SNPs) were genotyped using a MassARRAY platform in a case-control cohort including 550 patients with lung cancer and 550 healthy controls. RESULTS: The rs4845626-T and rs4329505-C alleles were associated with a decreased risk of lung cancer (p < 0.001), while the rs745986-G and rs2245121-A alleles were correlated with an increased risk of lung cancer (p < 0.01). The rs4845626-GT/GG and rs4329505-TC genotypes were protective against lung cancer (p < 0.001). However, the rs745986-AG and rs2245121-AG/AA genotypes were associated with an increased risk of lung cancer (p < 0.01). Stratification analysis showed that the rs4845626 and rs4329505 polymorphisms of IL6R were associated with a reduced risk of lung cancer in both smokers and nonsmokers (p < 0.05). However, rs892690, rs745986 and rs2115819 of ALOX5 were associated with an increased risk of disease in nonsmokers, while rs2245121 of SFTPD was correlated with a higher risk of disease in smokers (p < 0.05). CONCLUSION: Our results provide candidate SNPs for early screening for lung cancer and new clues for further study of the pathogenesis of the disease.

Screening for differential genes of the esophageal squamous cell carcinoma after DDX46 knockdown and bioinformatics analysis of their interaction / 中国胸心血管外科临床杂志

@#Objective    To explore the mechanism of DDX46 regulation of esophageal squamous cell carcinoma. Methods    Picture signals of fluorescence in gene array were scanned and differential expression of gene in two groups (a DDX46-shRNA-LV group and a control-LV group) were compared by GCOSvL.4 software. These differential expressed genes were analyzed by bioinformatics methods finally, and validated by quantitative real time polymerase chain reaction (qRT-PCR) analysis. Results    According to the screening criteria of fold change ≥2 and P<0.05, 1 006 genes were differentially expressed after DDX46 knockdown, including 362 up-regulated and 644 down-regulated genes. Bioinformatics analysis and gene co-expression network building identified that these differentially expressed genes were mainly involved in cell cycle, proliferation, apoptosis, adhesion, energy metabolism, immune response, etc. Phosphatidylinositol 3-kinase (PI3K) was the key molecule in the network. The results of RT-qPCR were completely consistent with the results of gene microarra. Conclusion    Bioinformatics can effectively exploit the microarray data of esophageal squamous cell carcinoma after DDX46 knockdown, which provides a valuable clue for further exploration of DDX46 tumorigenesis mechanism and helps to find potential drug therapy.

MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma.

The long-term prognosis of patients with lung cancer remains poor and thus it is imminent to further elucidate the molecular mechanism for the oncogenesis of lung cancer. In this study, we observed that surfactant protein C (SFTPC) expression was downregulated in human lung adenocarcinoma tissues and cell lines, and low SFTPC expression correlated with poor overall survival of lung adenocarcinoma patients. Moreover, we found that overexpression of SFTPC could inhibit lung cancer cell proliferation in vitro and in vivo, but downregulation of SFTPC showed the opposite results. Besides, it was observed that miR-629-3p expression was upregulated in human lung adenocarcinoma tissues and cell lines. More importantly, we found that miR-629-3p could downregulate SFTPC expression by directly binding to the SFTPC 3'-UTR and inhibit the regulatory effect of SFTPC on lung adenocarcinoma cell proliferation. In conclusion, these data suggested that miR-629-3p-meditated downregulation of SFTPC may promote lung adenocarcinoma progression.

Effect of DDX46 gene on the growth of xenografted tumor of esophageal squamous cell carcinoma in nude mice / 中国胸心血管外科临床杂志

@#Objective To observe the growth of xenografted tumor in nude mice after DDX46 expression decreased, and to further study the role of DDX46 in the development and progression of esophageal squamous cell carcinoma. Methods DDX46-shRNA mediated RNAi was applied to silencing DDX46 in Eca-109 cells. Twenty-five female BALB/c nude mice were divided into 3 groups: an experiment group (DDX46-shRNA-LV, n=10), a control group (Control-LV, n=10) and a blank control group (Het-1A, n=5). The prepared Eca-109 cells of DDX46-shRNA-LV and Control-LV were subcutaneously injected into the right armpit of mice (4×106 cells per mouse), while Het-1A cells were subcutaneously injected into the bilateral armpits of mice (4×106 cells per side). Tumor growth was monitored twice a week on the 14th day after injection. Tumor volume was measured with calipers, in vivo imager to observe the fluorescence of each group. Further, western blotting analysis was used to detect the changes of apoptosis signaling molecules in xenografted tumor after DDX46 silence. Results The growth of xenografted tumor in nude mice was significantly slower in the DDX46-shRNA-LV group than that in the Control-LV group throughout the study period (P<0.001). Western blotting analysis showed that silencing DDX46 effectively suppressed the expression of DDX46, and upregulated the expression of cleaved Caspase-3 and cleaved PARP-1 in xenografted tumor (P<0.01). Conclusion DDX46 is involved in the development and progression of esophageal squamous cell carcinoma, and the silence of DDX46 expression can inhibit the growth of esophageal squamous cell carcinoma, which probably by positive regulation of apoptosis signaling pathway.

Impact of high body mass index on surgical outcomes and long-term survival among patients undergoing esophagectomy: A meta-analysis.

BACKGROUND: The impact of high body mass index (BMI, >23/25 kg/m) on surgical outcomes and prognosis in patients with esophageal carcinoma (EC) after undergoing esophagectomy remains controversial. We herein conducted a systematic review and meta-analysis to determine the relationship between high BMI and surgical outcomes and prognosis in patients undergoing esophagectomy for EC. METHODS: The study search was conducted by retrieving publications from the PubMed, Embase, Web of Science, and CNKI (up to September 8, 2017). Nineteen studies with 13,756 patients were included in this meta-analysis. RESULTS: We found that high BMI was closely associated with a higher incidence of wound infection (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.02-1.97, P = .04), cardiovascular complications (OR: 2.51, 95% CI, 1.65-3.81, P < .0001), and anastomotic leakage (OR: 1.50, 95% CI, 1.21-1.84, P = .0002), but a lower incidence of chylous leakage (OR: 0.59, 95% CI, 0.40-0.88, P = .01) when compared with normal BMI. The high BMI group was not associated with better or worse overall survival (OS) (hazard ratio [HR]: 0.95, 95% CI, 0.85-1.07, P = .4) and disease-free survival (HR: 0.95, 95% CI, 0.72-1.25, P = .72) than the normal BMI group. However, in the subgroup analysis, the pooled result of HRs generated from multivariate analyses suggested that high BMI could improve OS in EC patients (HR: 0.84, 95% CI, 0.76-0.93, P < .01). CONCLUSIONS: Overweight patients with EC should not be denied surgical treatment, but intraoperative prevention and careful postoperative monitoring for several surgical complications must be stressed for this population. Besides, high BMI might be a prognostic predictor in EC patients; further studies are warranted.

Clinical efficacy of stapler technique for repair of cervical tracheoesophageal fistula / 中国胸心血管外科临床杂志

@#Objective    To evaluate the clinical efficacy of fistula repair by stapler technique in patients with cervical tracheoesophageal fistula. Methods    Retrospective analysis of 8 patients with cervical tracheoesophageal fistula who accepted operative treatment in the Department of Thoracic Surgery, Lanzhou University Second Hospital from October 2014 to October 2016 was conducted. There were 5 males and 3 females at a mean age of 46.4±13.9 years ranging from 23 to 67 years. The fistula was induced by tracheal intubation in 4 patients, by esophageal foreign bodies in 2, by tracheal stent in 1 and by esophageal diverticulum in 1. The fistula was closed by stapler technique. The surgical effects were evaluated through Karnofsky performance score (KPS), image assessment, patient satisfaction score and assessment of improvement in feeding-induced bucking. Results    The operations were performed successfully with time of 117.5±6.6 min and intraoperative blood loss of 60.0±7.0 ml. After the operations, the patients did not suffer incision bleeding and infection, hoarseness, dyspnea, drinking-induced bucking, fistula relapse, tracheoesophageal stenosis or any other complications, and no death occurred during the perioperative period. The chest X-ray test was performed 1 week later showed that the pulmonary infection disappeared, and only 1 patient suffered from esophageal stenosis 1 year later. The postoperative KPS score was 90.0±7.0 points, which significantly improved in contrast to preoperation (P<0.01).   Postoperative pulmonary infection area reduced significantly (P<0.05), tracheoesophageal fistula disappeared, postoperative patients satisfaction rate was 90%, and assessment of feeding-induced bucking was excellent. Conclusion    Using stapler technique to repair cervical tracheoesophageal fistula is safe, easy and useful, with less operation time and postoperative complications.

MicroRNA-146a regulates cisplatin-resistance of non-small cell lung cancer cells by targeting NF-κB pathway.

The aim of this study is to explore the influence of miR-146a on cisplatin resistance in non-small cell lung cancer (NSCLC) cells and the related molecular mechanism. The expression of miR-146a in NSCLC tumor samples and cell lines was measured by qRT-PCR. The DDP (cisplatin) cytotoxicity was detected by CCK-8 assay. The protein expressions of TRAF6, IRAK1, p50, p-p65, p65 in normal DDP-resistant cells were determined by western blot analysis. Luciferase reporter assay was used to investigate the relationship between miR-146a and NF-κB pathway activity. The expression of miR-146a in DDP-resistant NSCLC tumor samples was significantly lower than that in DDP-sensitive ones. Its expression in DDP-resistant cell lines was much lower as well. The protein levels of TRAF6, IRAK1 and p50 were up-regulated in A549/DDP and Calu-1/DDP cells compared to parental cells, and phosphorylation of p65 was also increased, indicating the activation of NF-κB signaling pathway. Furthermore, NF-κB activity was conversely related with miR-146a level in NSCLC. It was revealed that miR-146a expression in NSCLC was negatively correlated with activation of of NF-κB pathway. In conclusion, the study indicates that miR-146a regulates the DDP sensitivity by inhibiting NF-κB signaling pathway in NSCLC cells.

Misdiagnosis of a small cell lung cancer resulting from inaccurate pathology.

Currently, a biopsy provides the most reliable evidence for diagnosing a disease, and the majority of doctors do not question the diagnosis made by a pathologist. However, an inaccurate diagnosis may lead to serious consequences; for example, a benign tumor may be misdiagnosed as a malignancy, or a malignancy may be deemed to be benign. How to avoid these types of mistakes is a continuing issue of concern to all doctors. Here, we report a case of small cell lung cancer misdiagnosed as an inflammatory myofibroblastic tumor. Fortunately, we performed a mediastinoscopy on the patient and discovered the actual pathologic condition. This case is presented to caution against the possibility of the misdiagnosis of uncommon diseases in clinical practice.