Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation.

Background: Gastric cancer (GC) is an extremely heterogeneous malignancy with a complex tumor microenvironment (TME) that contributes to unsatisfactory prognosis. Methods: The overall activity score for assessing the immune activity of GC patients was developed based on cancer immune cycle activity index in the Tracking Tumor Immunophenotype (TIP). Genes potentially affected by the overall activity score were screened using weighted gene co-expression network analysis (WGCNA). Based on the expression profile data of GC in The Cancer Genome Atlas (TCGA) database, COX analysis was applied to create an immune activity score (IAS). Differences in TME activity in the IAS groups were analyzed. We also evaluated the value of IAS in estimating immunotherapy and chemotherapy response based on immunotherapy cohort. Gene expression in IAS model and cell viability were determined by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and Cell Counting Kit-8 (CCK-8) assay, respectively. Results: WGCAN analysis screened 629 overall activity score-related genes, which were mainly associated with T cell response and B cell response. COX analysis identified AKAP5, CTLA4, LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 as critical genes affecting the prognosis of GC, based on which the IAS was developed. Further RT-qPCR analysis data showed that the expression of AKAP5 and CTLA4 was downregulated, while that of LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 was significantly elevated in GC cell lines. Inhibition of AKAP5 increased cell viability but siAOAH-IT1 promoted viability of GC cells. IAS demonstrated excellent robustness in predicting immunotherapy outcome and GC prognosis, with low-IAS patients having better prognosis and immunotherapy. In addition, resistance to Erlotinib, Rapamycin, MG-132, Cyclopamine, AZ628, and Sorafenib was reduced in patients with low IAS. Conclusion: IAS was a reliable prognostic indicator. For GC patients, IAS showed excellent robustness in predicting GC prognosis, immune activity status, immunotherapy response, and chemotherapeutic drug resistance. Our study provided novel insights into the prognostic assessment in GC.

Circ_0015756 promotes ovarian cancer progression via the miR-145-5p/PSAT1 axis.

Circular RNA (circRNA) have been shown to exert vital functions in the pathological progressions of ovarian cancer (OC). Herein, this study aimed to investigate the role and mechanisms of circ_0015756 in OC progression. Levels of circ_0015756, microRNA (miR)- 145-5p and phosphoserine aminotransferase 1 (PSAT1) were detected using quantitative real-time polymerase chain reaction, Western blot or immunohistochemistry assays. Cell proliferation, apoptosis, migration and invasion were determined using cell counting kit-8, 5-Ethynyl-2'-Deoxyuridine (Edu) incorporation, flow cytometry, transwell and Western blot assays. The binding interaction between miR-145-5p and circ_0015756 or PSAT1 was confirmed by bioinformatics prediction and dual-luciferase reporter assay. Tumor formation assay in nude mice was performed to determine the tumor growth in vivo. Circ_0015756 was highly expressed in OC tissues and cells. Knockdown of circ_0015756 suppressed cancer cell growth, migration and invasion in vitro, as well as impeded tumor growth in vivo. In a mechanical study, circ_0015756 directly bound to miR-145-5p, and inhibition of miR-145-5p reversed the effects of circ_0015756 knockdown on OC cells. Moreover, miR-145-5p directly targeted PSAT1, and miR-145-5p weakened OC cell growth, migration and invasion via targeting PSAT1. Importantly, further studies confirmed that circ_0015756 could indirectly regulate PSAT1 expression via sponging miR-145-5p. In all, circ_0015756 accelerated OC tumorigenesis through regulating miR-145-5p/PSAT1 axis, providing a new therapeutic target for OC.

Nacre-inspired underwater superoleophobic films with high transparency and mechanical robustness.

Underwater superoleophobic materials have attracted increasing attention because of their remarkable potential applications, especially antifouling, self-cleaning and oil-water separation. A limitation of most superoleophobic materials is that they are non-transparent and have limited mechanical stability underwater. Here, we report a protocol for preparing a transparent and robust superoleophobic film that can be used underwater. It is formed by a hydrogel layer prepared by the superspreading of chitosan solution on a superhydrophilic substrate and biomimetic mineralization of this layer. In contrast to conventional hydrogel-based materials, this film exhibits significantly improved mechanical properties because of the combination of high-energy, ordered, inorganic aragonite (one crystalline polymorph of calcium carbonate) and homogeneous external hierarchical micro/nano structures, leading to robust underwater superoleophobicity and ultralow oil adhesion. Moreover, the mineralized film is suitable for neutral and alkaline environments and for containing organic solvent underwater and can be coated on different transparent materials, which has promising applications in underwater optics, miniature reactors and microfluidic devices. In this protocol, the time for the whole biomimetic mineralization process is only ~6 h, which is significantly shorter than that of traditional methods, such as gas diffusion and the Kitano method. The protocol can be completed in ~2 weeks and is suitable for researchers with intermediate expertise in organic chemistry and inorganic chemistry.

The Highly Expressed IFIT1 in Nasopharyngeal Carcinoma Enhances Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma Cells.

In this study, we aimed to identify potential targets modulating the progression of nasopharyngeal carcinoma (NPC) using integrated bioinformatics analysis and functional assays. Differentially expressed genes (DEGs) between NPC and normal tissues samples were obtained from publicly availably microarray datasets (GSE68799, GSE34573, and GSE53819) in the Gene Expression Omnibus (GEO) database. The bioinformatics analysis identified 49 common DEGs from three GEO datasets, which were mainly enriched in cytokine/chemokine pathways and extracellular matrix organization pathway. Further protein-protein interaction network analysis identified 11 hub genes from the 49 DEGs. The 11 hub genes were significantly up-regulated in the NPC tissues when compared to normal tissues by analyzing the Oncomine database. The 8 hub genes including COL5A1, COL7A1, COL22A1, CXCL11, IFI44L, IFIT1, RSAD2, and USP18 were significantly up-regulated in the NPC tissues when compared to normal tissues by using the Oncomine database. Further validation studies showed that IFIT1 was up-regulated in the NPC cells. Knockdown of IFI1T1 suppressed the proliferation, migration, and invasion of NPC cells; while IFIT1 overexpression promoted the proliferation, migration, and invasion of NPC cells. In conclusion, a total of 49 DEGs and 11 hub genes in NPC using the integrated bioinformatics analysis. IFIT1 was up-regulated in the NPC cells lines, and IFIT1 may act as an oncogene by promoting NPC cell proliferation, migration, and invasion.

Knockdown of lncRNA FOXD2-AS1 Inhibits Proliferation, Migration, and Drug Resistance of Breast Cancer Cells.

OBJECTIVE: In order to investigate the effect of lncRNA FOXD2-AS1 on breast cancer cells proliferation, migration, and drug resistance as well as its molecular mechanism. METHODS: Real-time PCR was used to detect the expression of breast cancer tissues and cells from patients admitted to our hospital and the expression of lncRNA FOXD2-AS1 in MCF-7/ADR in adriamycin- (ADR-) resistant breast cancer cells. After interfering with or overexpressing lncRNA FOXD2-AS1 in MCF-7/ADR cells, cell proliferation, apoptosis, invasion, and migration were detected using CCK-8, flow cytometry, Transwell assay, and scratch test, respectively. The protein levels of PI3K, p-PI3K, AKT, and p-AKT in the PI3K/AKT signaling pathway were detected by Western blot. RESULTS: lncRNA FOXD2-AS1 was upregulated in breast cancer tissues and cells and increased cell drug resistance to ADR. Downregulation of lncRNA FOXD2-AS1 inhibited invasion and migration of MCF-7/ADR cells, promoted apoptosis, increased chemosensitivity of MCF-7/ADR cells, and inhibited the activity of PI3K/AKT signaling pathway in MCF-7/ADR cells. CONCLUSIONS: lncRNA FOXD2-AS1 can promote the proliferation, invasion, migration, and drug resistance of breast cancer cells, inhibit apoptosis, and accelerate the development of breast cancer by positively regulating the PI3K/AKT signaling pathway.

Efficacy of Olanzapine-Triple Antiemetic Regimen in Patients with Gastrointestinal Tumor and High Risk of Chemotherapy-Induced Nausea and Vomiting Receiving Moderately Emetogenic Chemotherapy: A Retrospective Study.

PURPOSE: Dexamethasone combined with 5-hydroxytryptamine type 3 receptor antagonists (5-HT3 RA) dual regimen is the standard prophylaxis regimen for patients receiving moderately emetogenic chemotherapy (MEC). However, it has been found in real-world practice that chemotherapy-induced nausea and vomiting (CINV) remains poorly controlled among patients with gastrointestinal tumor, especially in those with high-risk factors for vomiting, such as female, young, and non-alcoholic individuals. Hence, we aimed to evaluate the efficacy of an olanzapine-containing triple regimen in this clinical setting. PATIENTS AND METHODS: We retrospectively reviewed the clinical records of gastrointestinal tumor patients who received mFOLFOX6, XELOX, or FOLFIRI chemotherapy at two institutions. All patients included were female and less than 55 years old, with no history of drinking. The patients were divided into two groups for olanzapine-containing triple therapy (olanzapine, tropisetron, and dexamethasone) and non-olanzapine dual therapy (tropisetron and dexamethasone). The study outcomes were complete response (CR), complete control (CC), nausea control, and quality of life (QoL) by the functional living index-emesis (FLIE) questionnaire. RESULTS: A total of 93 patients were included in the study (olanzapine: 40; control: 53). The CR rate in the olanzapine group was significantly higher than that in the control group in delayed and overall phase (75.0% vs 54.7%, p=0.044; 70.0% vs 47.2%; p=0.028). The CC rate in the overall phase was also better in the olanzapine group (62.5% vs 39.6%, p=0.029). The control of nausea in the overall phase showed a superior trend in the olanzapine group (p=0.059). The olanzapine group exhibited higher FLIE scores, which demonstrated better QoL. More patients in the olanzapine group exhibited somnolence and dizziness. Conversely, the incidence of insomnia and anorexia in the olanzapine group was lower. CONCLUSION: This retrospective study indicates that in gastrointestinal tumor patients with high-risk factors for CINV who were receiving MEC, olanzapine-containing triple antiemetic regimen exhibit better efficacy and QoL as compared to non-olanzapine dual regimen. Further randomized studies are required to confirm these results.

LncRNA NRON promotes the proliferation, metastasis and EMT process in bladder cancer.

Background: Bladder cancer (BC) is one of the most common malignancies world-wide with high morbidity and mortality. Long noncoding RNAs (lncRNAs) are thought to play a critical role in cancer development. LncRNA NRON, a repressor of activated T-cell nuclear factor (NFAT), has been shown to be dysregulated in many cancer types. However, the clinical significance and molecular mechanism of NRON in bladder cancer is still unknown. Methods: The expression levels of NRON in BC tissues and cell lines were tested by RT-qPCR. Survival analysis was performed to detect the correlation between NRON expression and clinical outcomes in patients with BC. The biological role of NRON in BC cells proliferation and metastasis was examined in vitro and in vivo. Results: The expression of NRON was significantly upregulated in BC specimens and cell lines compared with paired adjacent normal tissues and normal cell lines. The upregulation of NRON in bladder cancer patients was significantly associated with the depth of bladder tumor invasion and poor prognosis. Knockdown of NRON inhibited BC cells proliferation, migration, invasion and tumorigenicity. Furthermore, NRON promoted epithelial-mesenchymal transition (EMT) progression, and NRON-induced EZH2 expression contributed to this process. Conclusion: In conclusion, our results suggested that NRON acted as an oncogene and tumor biomarker for BC.

Enumeration And Characterization Of Circulating Tumor Cells And Its Application In Advanced Gastric Cancer.

BACKGROUND: Advanced gastric cancer (aGC) has a high global incidence and a high mortality rate and because of its high malignancy and heterogeneity, the existing methods for prognosis are limited, and a new treatment model is necessary. Circulating tumor cells (CTCs) could be considered as a "liquid biopsy" for tumor diagnosis and for monitoring treatment responses and predicting clinical outcome. Clinical studies support the efficacy of programmed cell death 1 (PD-1) immunotherapy in a subset of aGC. METHODS: Cell capture efficiency, as described by the CanPatrol CTC enrichment technique, was validated using artificial blood samples as well as blood samples from 32 aGC patients. Clinicopathologic data of patients were collected from the hospital information system. We used CanPatrol for CTC isolation, classification, and clinical analysis. RESULTS: A cell capture efficiency of >80% was achieved. Significant correlation was observed between CTC enumeration and clinicopathology parameters, including the Lauren classification (r=0.470, P=0.008), perineural invasion (r=0.393, P=0.029), TNM stage (r=0.740, P<0.001), and Ki-67 level (r=0.510, P=0.005). When compared to the traditional methods, monitoring CTC subtypes exhibits higher sensitivity of evaluating the disease status. Enumeration of epithelial CTC subset and its relative abundance in the total CTC pool are highly correlated with clinical efficacy. CTC programmed cell death ligand-1 (PD-L1) could be successfully detected for immunotherapy in addition to PD-L1 immunohistochemistry and microsatellite instability. CONCLUSION: We provide a new method that allows for the simple and effective detection of CTCs in aGC. It has potential clinical applications in monitoring prognosis and guiding future individualized immunotherapy.