Artesunate enhances radiosensitivity of esophageal cancer cells by inhibiting the repair of DNA damage.

Radiotherapy plays an important therapeutic role in esophageal cancer (EC). However, acquired radioresistance impairs the efficacy of radiotherapy, often leading to treatment failure. Therefore, it is important to develop novel radiosensitizers to enhance the clinical treatment of EC. The purpose of this study was to investigate the role of artesunate (ART) on radiosensitivity of human EC cell line TE-1. We found that ART inhibited the proliferation of EC cells and enhanced the radiosensitivity of TE-1 cells (SER = 1.24). In vivo tumor growth of xenografts was inhibited markedly by irradiation (IR) combined with ART, with a tumor inhibition rate of 53.76% in IR + ART group vs. 41.13% in IR-alone group. Pretreatment with ART significantly prompted cell apoptosis and reversed the IR-induced G2/M arrest. ART treatment could aggravate DNA damage of EC cells and prolong the formation of γ-H2AX foci induced by IR. ART up-regulated P21 and down-regulated the expression of cyclin D1, RAD51, RAD54, Ku70 and Ku86 protein of irradiated TE-1 cells. These findings support that ART induce radiosensitivity of TE-1 cells in vitro and in vivo, and may prove to be a promising radiosensitizer for EC treatment.

Characteristics of clinical trials for non-small cell lung cancer therapeutic vaccines registered on ClinicalTrials.gov.

Background: Even after complete surgical treatment or chemotherapy, Non-Small Cell Lung Cancer (NSCLC) patients are also at substantial risk for recurrence and spread trend. Therapeutic cancer vaccination could increase the anti-tumor immune response and prevent tumor relapse. This study aimed to assess the characteristics of NSCLC therapeutic vaccines registered on ClinicalTrials.gov. Methods: We conducted a cross-sectional, descriptive study of clinical trials for Non-Small Cell Lung Cancer Therapeutic Vaccines Registered on ClinicalTrials.gov (https://clinicaltrials.gov/) through March 17, 2022. Results: This study encompassed 117 registered trials included for data analysis. The number of trials was significantly correlated with a beginning year (r = 0.504, P < 0.010). Of these trials, 45.30% were completed, 12.82% were terminated, and 8.55% were withdrawn. More than half of trials (52.99%) were funded by industry, and more than half of trials (52.14%) were located in economically developed North America. Regarding study designs of these trials, 27.35% were randomized, 52.14% were single group assignment, 83.76% were without masking, 35.90% were phase 1, and more than half of the trials (56.41%) recruited less than 50 participants. The highest proportion of vaccine types was protein/peptide vaccines (41.88%). Regarding TNM staging, the highest proportion of the trials is stage III-IV (26.50%). Conclusion: The number of clinical trials about the cancer therapeutic vaccines was sustained an increase in recent years. The main characteristic of clinical trials for NSCLC therapeutic vaccines is lack of randomized control, lack of mask, and recruiting less than 50 participants. In recent years, the protein/peptide vaccines for NSCLC active immunotherapy have been well studied.

MC2 (M = Y, Zr, Nb, and Mo) monolayers containing C2 dimers: prediction of anode materials for high-performance sodium ion batteries.

Seeking novel high performance anode materials for sodium ion batteries (SIBs) is an attractive theme in developing energy storage devices. In this work, by means of density functional theory computations, we predicted a family of MC2 (M = Y, Zr, Nb, and Mo) monolayers containing C2 dimers to be promising anode materials for SIBs. The stability, electronic structure, and adsorption/diffusion/storage behavior of sodium atoms in MC2 (M = Y, Zr, Nb, and Mo) monolayers were explored. Our computations revealed that Na adsorbed MC2 (M = Y, Zr, Nb, and Mo) monolayers show metallic characteristics that give rise to excellent electrical conductivity and Na mobility with low activation energies for diffusion (0.21, 0.04, 0.20, and 0.22 eV, respectively) in these materials, indicative of a high charge/discharge rate. In addition, the theoretical capacities of Na-adsorbed on YC2, ZrC2, NbC2, and MoC2 monolayers are 478, 697, 687, and 675 mA h g-1, respectively, higher than that of commercial graphite (284 mA h g-1), and the open-circuit voltages are moderate (0.11-0.25 V). Our results suggest that MC2 (M = Y, Zr, Nb, and Mo) monolayers have great potential to serve as anode materials for SIBs.

Luteolin-Loading Her-2 Nanospheres Enhances Targeting and Therapeutic Effects of Breast Cancer.

Despite the broad anticancer activity, whereas the clinical application of luteolin is hindered by unsatisfactory water solubility and non-targeting. Herein, targeted inhibitory effects of luteolin-loading HER2 nanospheres (Her-2-NPs) were successfully prepared by thin film ultrasonic method. In comparison with the non-targeted nanospheres, Her-2 nanospheres could significantly boost the intake of luteolin in SK-BR-3 cells. The proliferation and apoptosis of breast cancer cells were detected by MTT testing and flow cytometry examination, respectively. Consequently, the expressions of FOXO1 mRNA level was detected using qPCR assay and protein level was detected using Westernblot. We discovered that Luteolin-loading Her-2 nanospheres could significantly hinder the proliferation of breast cancer cells, down-regulation their migration, and up-regulation FOXO1 expression at mRNA and protein levels, reveal a mechanism whereby luteolin interferes with breast cancer. Collectively, these results suggest Her-2-modified nanospheres increases the efficiency of luteolin uptake and thus improves the treatment benefit of breast cancer.

Role of CXCR4 as a Prognostic Biomarker Associated With the Tumor Immune Microenvironment in Gastric Cancer.

Background: Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, accounting for high rates of morbidity and mortality in the population. The tumor microenvironment (TME), which plays a crucial role in GC progression, may serve as an optimal prognostic predictor of GC. In this study, we identified CXC motif chemokine receptor 4 (CXCR4) as a TME-related gene among thousands of differentially expressed genes (DEGs). We showed that CXCR4 can be used to predict the effect of immunotherapy in patients with GC. Methods: GC samples obtained from The Cancer Genome Atlas (TCGA) were analyzed for the presence of stroma (stromal score), the infiltration of immune cells (immune score) in tumor tissues, and the tumor purity (estimate score) using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm. DEGs were sorted based on differences in the values of the three scores. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological processes and pathways enriched in these DEGs. The correlations of scores with clinicopathological features and overall survival (OS) of patients with GC were assessed by the Kaplan-Meier survival and Cox regression analyses. Through subsequent protein-protein interaction (PPI) network and univariate Cox regression analyses, CXCR4 was identified as a TME-related gene. Gene Set Enrichment Analysis (GSEA) was performed to assess the role of CXCR4 in the TME of GC. The CIBERSORT algorithm was used to further explore the correlation between tumor-infiltrating immune cells (TIICs) and CXCR4. Finally, the TISIDB database was used to predict the efficacy of immunotherapy in patients with GC. Results: We extracted 1231 TME-related DEGs and by an overlapping screening of PPI network and univariate Cox regression, CXCR4 was identified as a biomarker of TME, which deeply engaged in immune-related biological processes of gastric cancer and have close association with several immunocompetent cells. Conclusion: CXCR4 may be a useful biomarker of prognosis and an indicator of the TME in GC.

Automatic Time-Resolved Fluorescence Immunoassay of Serum Alpha Fetoprotein-L3 Variant via LCA Magnetic Cationic Polymeric Liposomes Improves the Diagnostic Accuracy of Liver Cancer.

PURPOSE: The aim of this study was to develop an avidin-modified macromolecular lipid magnetic sphere and its application in differential diagnosis of liver disease and liver cancer. MATERIALS AND METHODS: Lectin-modified macromolecular lipid magnetic spheres were prepared by thin-film hydration method using lentil lectin derivatives (LCA-HQ) and cholesterol as raw materials. Alpha-fetoprotein variants (AFP-L3) in serum from healthy people, liver disease and liver cancer patients were isolated using the prepared lectin-modified macromolecular lipid magnetic spheres, and alpha-fetoprotein (AFP) and AFP-L3 were detected by fully automatic time-resolved fluorescence immunoassay. RESULTS: The lectin polymer lipid magnetic sphere prepared in this study was superparamagnetic and encapsulated by a lectin derivative. There was no significant difference in the recovery rate of AFP-L3 between avidin magnetic ball-automatic time-resolved fluorescence immunoassay and manual micro-affinity column method (p>0.05). We found that AFP-L3 can be used as a differential indicator between liver cancer and liver disease. The positive rate of AFP and AFP-L3 in liver cancer patients was higher than that in healthy people and liver disease patients (p<0.001). The AUC (95% CI) of AFP and AFP-L3 were 0.743 ± 0.031 and 0.850 ± 0.024, respectively. AFP-L3 AUC value is greater than AFP; therefore, AFP-L3 distinguishes liver cancer more accurately, and the difference is statistically different, p<0.05. CONCLUSION: We proposed a novel method for integration of the lectin polymer lipid magnetic spheres and time-resolved fluorescence immunoassay that enables simple, accurate and rapid determination of AFP-L3 in clinical samples. To be noted, fully automatic time-resolved fluorescence immunoassay compared with the commonly used techniques in clinical practice, the measurement procedure is simple and is expected to be used for the detection and accurate diagnosis of liver cancer.

High Mean Corpuscular Volume as a Predictor of Poor Overall Survival in Patients with Esophageal Cancer Receiving Concurrent Chemoradiotherapy.

BACKGROUND: Increasing numbers of recent studies have demonstrated that high mean corpuscular volume (MCV) is a predictor of poor overall survival (OS) and therapeutic response in patients with solid tumors. The aim of the present study was to explore the association between high MCV and OS in patients with advanced esophageal cancer (EC) undergoing concurrent chemoradiotherapy. PATIENTS AND METHODS: Enrolled in this study were 249 patients with advanced EC who underwent concurrent chemoradiotherapy. Pre-treatment MCV values were collected in all patients and their correlations with OS and pathophysiological characteristics were analyzed. The chi-square test was used to explore the correlation between MCV and various clinical pathophysiological characteristics, and the prognostic significance of high MCV using Kaplan-Meier curves and the Cox proportional hazards model. All P-values were two-tailed and a P-value <0.05 was considered statistically significant. RESULTS: According to ROC curve analysis, the optimal cut-off value of MCV was 93.6 fL. The mean OS was 14.7 months in all 249 EC patients, 10.9 months in patients with MCV >93.6 fL, and 18.8 months in patients with MCV <93.6 fL; the difference is statistically significant (P<0.05). Chi-square test showed that the MCV value was correlated with the N stage of the tumor and the therapeutic effect, indicating that the higher the MCV was, the higher the T stage of the tumor and the worse the therapeutic effect would be (p=0.012 and p <0.01). Multivariate analysis showed that MCV (OR = 1.864, 95% CI: 1.439-2.415) was an independent prognostic factor for OS in EC patients. CONCLUSION: High MCV is a poor predictor of OS in patients with advanced EC receiving concurrent chemoradiotherapy.

NEAT1 mediates paclitaxel-resistance of non-small cell of lung cancer through activation of Akt/mTOR signalling pathway.

Development of paclitaxel-resistance is a main problem during non-small cell lung cancer (NSCLC) chemotherapy. Nuclear paraspeckle assembly transcript 1 (NEAT1) is an oncogenic long non-coding RNA (lncRNA) which has been proved to be aberrantly upregulated in many human malignancies. In this study, we investigated the mechanism by which NEAT1 contributed to paclitaxel-resistance in NSCLC. NEAT1 was upregulated significantly in paclitaxel-resistant NSCLC cell line, compared with other NSCLC cell lines and normal bronchial epithelial (BE) cell line. Knockdown of NEAT1 could reverse the paclitaxel-resistance through induction of apoptosis by increasing cleaved PARP and cleaved caspase-3 expression. Moreover, NEAT1 was associated with Akt/mTOR signalling pathway activation by increasing expression of p-Akt, p-mTOR, Bcl-2 and decreasing expression of Bax. In conclusion, these results demonstrated that NEAT1 underlay paclitaxel-resistance in NSCLC.

Anticancer activity of polyphyllin I in nasopharyngeal carcinoma by modulation of lncRNA ROR and P53 signalling.

Nasopharyngeal carcinoma (NPC) is the most common aggressive squamous cell carcinoma in head and neck cancers. Although advanced radiochemotherapy has been applied, the prognosis of NPC patients still remains poor due to the regional relapse and distant metastasis. Polyphyllin I (PP I) is extracted from natural herb Paris polyphylla that has been widely used in cancer treatment and long non-coding RNA (lncRNA) has been reported to play a key role in the anti-tumour activity of PP I. In this study, it has been found that PP I inhibited the proliferation and induced apoptosis of NPC cells in a dose-dependent manner. A higher level of lncRNA regulator of reprogramming (ROR) expression was detected in NPC cell lines compared with normal nasopharyngeal cell line and PP I must significantly down-regulate the expression level of lncRNA ROR. LncRNA ROR/P53 signalling was essential for PP I-suppressed NPC progression. These data indicated that PP I suppressed tumour growth and induced apoptosis of NPC in vitro and in vivo through down-regulation of lncRNA-ROR, subsequently upregulating of P53 signalling. LncRNA ROR may be a potential therapeutic target and PP I would be a promising candidate for NPC treatment.

Genomic and molecular characterization of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized mutated genes such as FAT1, FAT2, ZNF750 and KMT2D, in addition to those already known (TP53, PIK3CA and NOTCH1). Further SCNV evaluation, immunohistochemistry and biological analysis suggested their functional relevance in ESCC. Notably, RTK-MAPK-PI3K pathways, cell cycle and epigenetic regulation are frequently dysregulated by multiple molecular mechanisms in this cancer. Our approaches also uncovered many druggable candidates, and XPO1 was further explored as a therapeutic target because it showed both gene mutation and protein overexpression. Our integrated study unmasks a number of novel genetic lesions in ESCC and provides an important molecular foundation for understanding esophageal tumors and developing therapeutic targets.