Clinical application of bronchoalveolar lavage fluid metagenomics next-generation sequencing in cancer patients with severe pneumonia.

OBJECTIVE: Metagenomic next-generation sequencing (mNGS), as an emerging technique for pathogen detection, has been widely used in clinic. However, reports on the application of mNGS in cancer patients with severe pneumonia remain limited. This study aims to evaluate the diagnostic performance of bronchoalveolar lavage fluid (BALF) mNGS in cancer patients complicated with severe pneumonia. METHODS: A total of 62 cancer patients with severe pneumonia simultaneously received culture and mNGS of BALF were enrolled in this study. We systematically analyzed the diagnostic significance of BALF mNGS. Subsequently, optimization of anti-infective therapy based on the distribution of pathogens obtained from BALF mNGS was also assessed. RESULTS: For bacteria and fungi, the positive detection rate of mNGS was significantly higher than culture method (91.94% versus 51.61%, P < 0.001), especially for poly-microbial infections (70.97% versus 12.90%, P < 0.001). Compared with the culture method, mNGS exhibited a diagnostic sensitivity of 100% and a specificity of 16.67%, with the positive predictive value (PPV) and negative predictive value (NPV) being 56.14% and 100%, respectively. The agreement rate between these two methods was 59.68%, whereas kappa consensus analysis indicated a poor concordance (kappa = 0.171). After receipt of BALF mNGS results, anti-infective treatment strategies in 39 out of 62 cases (62.90%) were optimized. Moreover, anti-tumor therapy was a high-risk factor for mixed infections (87.18% versus 65.22%, P = 0.04). CONCLUSIONS: The present study showed that cancer patients with severe pneumonia, especially those received anti-tumor therapy, were more likely to have poly-microbial infections. BALF mNGS can provide a rapid and comprehensive pathogen distribution of pulmonary infection, making it a promising technique in clinical practice, especially for optimizing therapeutic strategies for cancer patients.

Efficacy of adalimumab combined with Tripterygium wilfordii Hook F in the treatment of patient with rheumatoid arthritis: A multicenter, open-label, randomized-controlled trial.

OBJECTIVES: To evaluate the efficacy and safety of adalimumab (ADA) combined with Tripterygium wilfordii Hook F (TwHF) in the treatment of methotrexate (MTX)-inadequate response patients with rheumatoid arthritis (RA). METHODS: In this multicenter, open-label, randomized controlled clinical trial, 64 RA patients with inadequate response to MTX were 1:1 randomly assigned into treatment or control groups. The treatment group was treated with ADA in combination with TwHF, and the control group was treated with ADA in combination with MTX for 24 weeks. The primary endpoint was the percentage of patients having low disease activity (2.6 ≤ DAS28-ESR < 3.2) and remission rates (DAS28-ESR < 2.6) at week 24. RESULTS: In total, 53 of the 64 patients (82.8%) completed this 24-week clinical trial. By intent-to-treat (ITT) analysis, a comparable outcome was observed between the two groups. The percentage of patients achieving low disease activity in the treatment group and control group were 43.8% and 46.9% (95% CI, 21.28 to 27.48, p = .802). Percentage of patients achieving low disease activity rates were respectively 28.1% and 31.3% in the treatment group and control group (95% CI, 19.18 to 25.58, p = .784). In per-protocol (PP) analysis, the results were consistent with the ITT model. The incidence of adverse events was comparable between the two groups. CONCLUSIONS: There were no significant differences in efficacy and safety between ADA combined with TwHF versus ADA combined with MTX in the treatment of RA. TwHF might be an alternative treatment for RA patients who are intolerant to MTX.

LUCAT1 inhibits ferroptosis in bladder cancer by regulating the mRNA stability of STAT3.

OBJECT: In this study, we aimed to elucidate the role of LUCAT1, a recently identified lncRNA, in ferroptosis within the context of bladder cancer (BC). METHODS: Through a comprehensive array of experimental techniques, including transmission electron microscopy (TEM), RNA pull-down assays, and fluorescence in situ hybridization (FISH), we investigated the molecular interactions and functional consequences associated with LUCAT1 in BC cells. RESULTS: Our findings indicate that LUCAT1 acts as a pivotal regulator in BC, fostering cell proliferation, migration, and invasion, while concurrently impeding ferroptosis. Mechanistically, we unveiled a direct binding between LUCAT1 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which governs the mRNA stability of signal transducer and activator of transcription 3 (STAT3). Intriguingly, ectopic expression of STAT3 counteracted the suppressive effect of LUCAT1 on ferroptosis induction in BC cells. Notably, in an in vivo setting, LUCAT1 emerged as a crucial modulator of ferroptosis inhibition in BC by regulating STAT3 mRNA stability. CONCLUSION: Collectively, our study identifies LUCAT1 as a novel oncogenic player, repressing ferroptosis in BC. These findings shed light on the intricate interplay between lncRNAs and ferroptosis in cancer, implicating LUCAT1 as a promising therapeutic target for patients afflicted with BC. Further investigations into the underlying mechanisms governing LUCAT1-mediated ferroptosis resistance are warranted, with the potential to uncover novel strategies for combating BC progression and improving patient outcomes.

Evaluation of cell surface vimentin positive circulating tumor cells as a prognostic biomarker for stage III/IV colorectal cancer.

Currently, little is known about the phenotypes of circulating tumor cells (CTCs), particularly epithelial and mesenchymal phenotypes, and their impact on the prognosis of colorectal cancer (CRC) patients. This study aims to investigate the CTC phenotypes and their prognostic implications in stage III/IV CRC. Patients who were diagnosed with CRC and underwent CTC detection at two hospitals were included. CTCs were detected using a mesenchymal CTC kit, and the clinical and pathological characteristics of CTCs were compared with those of cell surface vimentin-positive CTCs (CSV-CTCs). Disease-free survival (DFS) was assessed and used as an indicator of CTC phenotype-related prognosis. Univariate and multivariate Cox regression analyses were made to identify risk factors, and nomogram models were employed for prognostic prediction. A total of 82 patients were enrolled, with a CTC detection rate of 86.6%. Among the detected CTCs, 60% were CSV-CTCs. The CSV-CTC count showed a positive correlation with the T-stage, the M-stage, and the location of the primary tumor (P = 0.01, P = 0.014, and P = 0.01, respectively). Kaplan-Meier survival analysis revealed that CSV-CTCs were associated with worse DFS in patients receiving first-line oxaliplatin chemotherapy (hazard ratio (HR) = 3.78, 95% CI 1.55-9.26, p = 0.04). When the cut-off value of the CSV-CTC count was 3, the optimal prognostic prediction was achieved. Compound models considering CSV-CTCs, TNM staging, the site of the primary tumor and the Ras gene status yielded the best results in both the receiver operating characteristic (ROC) analysis and the decision curve analysis (DCA). This study indicates that CSV-CTCs predominate in CTCs of CRC patients, and a count of CSV-CTCs ≥ 3 is an independent risk factor for worse prognosis.

Immune checkpoint blockade therapy for BRAF mutant metastatic colorectal cancer: the efficacy, new strategies, and potential biomarkers.

BRAF mutant metastatic colorectal cancer has long been considered a tumor with a poor prognosis and a poor response to chemotherapy. Despite the efficacy of targeted therapy with multi-targeted blockade of the mitogen-activated protein kinase (MAPK) signaling pathway has brought a glimmer of hope to this group of patients, the need to improve treatment efficacy remains unmet, especially for the microsatellite stability/DNA proficient mismatch repair (MSS/pMMR) subtype. BRAF mutant colorectal cancer patients with high microsatellite instability/DNA deficient mismatch repair (MSI-H/dMMR) have high tumor mutation burden and abundant neoantigen, who are deemed as ones that could receive expected efficacy from immunotherapy. Generally, it is believed that MSS/pMMR colorectal cancer is an immunologically "cold" tumor that is insensitive to immunotherapy. However, targeted therapy combined with immune checkpoint blockade therapy seems to bring light to BRAF mutant colorectal cancer patients. In this review, we provide an overview of clinical efficacy and evolving new strategies concerning immune checkpoint blockade therapy for both MSI-H/dMMR and MSS/pMMR BRAF mutant metastatic colorectal cancer and discuss the potential biomarkers in the tumor immune microenvironment for predicting immunotherapeutic response in BRAF mutant colorectal cancer.

Impact of endoscopic metallic stent placement and emergency surgery on detection of viable circulating tumor cells for acute malignant left-sided colonic obstruction.

BACKGROUND: Self-expanding metal stents (SEMS) served as a bridge to surgery (BTS). However, this method may be associated with worse long-term prognosis and relapse of CRC patients. Therefore, we attempted to clarify this in the angle of circulating tumor cells (CTCs). METHODS: A multicenter study was performed from March 2018 to January 2021. Thirty-two colorectal cancer patients with obstruction were selected, of which 21 patients were performed SEMS as a BTS while 11 patients were performed emergency surgery. Bloods samples were collected in two groups of patients for further detecting CTCs. In the SEMS group, the samples were collected before and after stent insert and after radical surgery performed. In the ES group, the samples were collected before stent insert and after emergency surgery performed. RESULTS: The number of CTCs did not show statistically significant differences before and after stent placement (34.90 vs 38.33, p=0.90), neither between the SEMS group and ES group in initial CTC levels (34.90 vs 58.09, p=0.394). No significant differences (38.33 vs 58.09, p=0.632) were observed after stent insert in the SMES group and the initial CTC levels in the ES group. Moreover, no major differences (24.17 vs 42.27, p=0.225) were observed after radical operation performed in both groups. CONCLUSION: The treatment of SEMS does not cause an increase in the number of CTC after stent insertion. Furthermore, there are may be other factors besides CTC to cause these poorer oncologic outcomes after SEMS placement.

Anethole ameliorates inflammation induced by monosodium urate in an acute gouty arthritis model via inhibiting TLRs/MyD88 pathway.

OBJECTIVE: To assess the effects of anethole on monosodium urate (MSU)-induced inflammatory response, investigate its role in acute gouty arthritis (AGA), and verify its molecular mechanism. METHODS: Hematoxylin and eosin staining assay and time-dependent detection of degree of ankle swelling were performed to assess the effects of anethole on joint injury in MSU-induced AGA mice. Enzyme-linked-immunosorbent serologic assay was performed to demonstrate the production levels of inflammatory factors (interleukin 1ß [IL-1ß], interleukin 6 [IL-6], interleukin 8 [IL-8], tumor necrosis factor α [TNF-α], and monocyte chemo-attractant protein-1 [MCP-1]) in MSU-induced AGA mice. Western blot assays were used to confirm the effects of anethole on oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activity and the activation of toll-like receptors (TLRs)-myeloid differentiation factor 88 (MyD88) pathway in MSU-induced AGA mice. RESULTS: We observed that a significant joint injury occurred in MSU-induced AGA mice. Anethole could alleviate the pathological injury of the synovium in MSU-induced AGA mice and suppressed ankle swelling. In addition, we observed that anethole could inhibit MSU-induced inflammatory response and inflammasome activation in MSU-induced AGA mice. Moreover, we discovered that anethole enabled to inhibit the activation of TLRs/MyD88 pathway in MSU-induced AGA mice. Our findings further confirmed that anethole contributed to the inhibitory effects on progression in MSU-induced AGA mice. CONCLUSION: It confirmed that anethole ameliorated the MSU-induced inflammatory response in AGA mice in vivo via inhibiting TLRs-MyD88 pathway.

Emerging Role of ERBB2 in Targeted Therapy for Metastatic Colorectal Cancer: Signaling Pathways to Therapeutic Strategies.

Despite recent improvements in the comprehensive therapy of malignancy, metastatic colorectal cancer (mCRC) continues to have a poor prognosis. Notably, 5% of mCRC cases harbor Erb-B2 receptor tyrosine kinase 2 (ERBB2) alterations. ERBB2, commonly referred to as human epidermal growth factor receptor 2, is a member of the human epidermal growth factor receptor family of protein tyrosine kinases. In addition to being a recognized therapeutic target in the treatment of gastric and breast malignancies, it is considered crucial in the management of CRC. In this review, we describe the molecular biology of ERBB2 from the perspective of biomarkers for mCRC-targeted therapy, including receptor structures, signaling pathways, gene alterations, and their detection methods. We also discuss the relationship between ERBB2 aberrations and the underlying mechanisms of resistance to anti-EGFR therapy and immunotherapy tolerance in these patients with a focus on novel targeted therapeutics and ongoing clinical trials. This may aid the development of a new standard of care in patients with ERBB2-positive mCRC.

A comprehensive analysis of the microbiota composition and host driver gene mutations in colorectal cancer.

Studies of both, microbiota and target therapy associated with gene mutations in colorectal cancer, (CRC) have attracted increasing attention. However, only a few of them analyzed the combined effects on CRC. we analyzed differences in intestinal microbiota of 44 colorectal cancer patients and 20 healthy controls (HC) using 16S rRNA gene sequencing of fecal samples. For 39 of the CRC patients, targeted Next Generation Sequencing (NGS) was carried out at formalin fixed paraffin embedded (FFPE) samples to identify somatic mutation profiles. Compared to the HC group, the microbial diversity of CRC patients was significantly lower. In the CRC group, we found a microbiome that was significantly enriched for strains of Bifidobacterium, Bacteroides, and Megasphaera whereas in the HC group the abundance of Collinsella, Faecalibacterium, and Agathobacter strains was higher. Among the mutations detected in the CRC group, the APC gene had the highest mutation rate (77%, 30/39). We found that the KRAS mutant type was closely associated with Faecalibacterium, Roseburia, Megamonas, Lachnoclostridium, and Harryflintia. Notably, Spearman correlation analysis showed that KRAS mutations were negatively correlated with the existence of Bifidobacterium and positively correlated with Faecalibacterium. By employing 16S rRNA gene sequencing, we identified more unique features of microbiota profiles in CRC patients. For the first time, our study showed that gene mutations could directly be linked to the microbiota composition of CRC patients. We hypothesize that the effect of a targeted colorectal cancer therapy is also closely related to the colorectal flora, however, this requires further investigation.

Development of anoikis-related genes signature to predict the prognosis in gastric cancer patients.

Background: It is well known that the prognosis of Gastric cancer (GC) patient is affected by many factors. However, the latent impact of anoikis on the prognosis of GC patients is insufficient understood. Methods: According to the Cancer Genome Atlas (TCGA) database, we elected discrepantly expressed anoikis-related genes (ARGs). Univariate cox and the least absolute shrinkage and selection operator (lasso) analysis were applied to build the ARGs signature. The prognostic effect of the ARGs signature was also evaluated. A series of algorithms were performed to evaluate the discrepancies in the immune microenvironment. Moreover, the correlation between drug sensitivity and ARGs signature was analyzed. We also performed Real-Time Polymerase Chain Reaction (RT-PCR) to probe the signature. Results: The ARGs signature of 9 genes was constructed, which was apparently interrelated with the prognosis. The nomogram was established by combining the ARGs signature with clinicopathological characteristics. We found that the predictive power was noteworthily superior to other individual predictors. The immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, StromalScores, tumor immune dysfunction and exclusion (TIDE) score were lower in the low-risk group, while immunophenoscore (IPS) was on the contrary. The infiltrated immune cells and immune checkpoint (ICP) expression levels were significantly different between the two groups. Furthermore, nine drugs were positively associated with the ARGs signature score. The results of RT-PCR analysis were consistent with our previous differential expression analysis. Conclusion: The developed ARGs signature could act as the biomarker and provide a momentous reference for Individual therapy of GC patients.

The mechanism study of Miao medicine Tongfengting decoction in the treatment of gout based on network pharmacology and molecular docking.

AIM: This study sought to clarify the mechanism of action of Miao medicine Tongfengting decoction in the treatment of gout through network pharmacology and molecular docking by searching for its key targets and related pathways. METHODS: The active ingredients of Miao medicine Tongfengting Decoction were obtained from the TCMSP data platform, searched the relevant databases for gout-related targets,using String and Cytoscape 3.9 to build a "compound-cross-target-disease" network diagram,performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis in the DAVID database, and performed the docking analysis using PyMoL 2.3.0 and AutoDock. RESULTS: After screening, 298 main targets of the Miao medicine Tongfengting decoction for gout were identified. The target network is established, and the topology of protein-protein interaction (PPI) network is analyzed. The enrichment analysis of KEGG pathway showed that these targets were related to Pathways in cancer, PI3K Akt signaling pathway, MAPK signaling pathway and other pathways. Molecular docking showed that the target protein had good binding power with the main active components of the compound of Miao medicine Tongfengting Decoction. CONCLUSION: Miao medicine Tongfengting decoction probably regulates immune mechanism using a multi-component, multi-target, and multi-pathway strategy to reduce inflammatory response and exert its therapeutic effect on gout.

LncRNA HOTTIP from synovial fibroblast-derived exosomes: A novel molecular target for rheumatoid arthritis through the miR-1908-5p/STAT3 axis.

Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. HOTTIP, a long noncoding RNA (lncRNA), participates in cell proliferation and invasion. However, the correlation between HOTTIP and RA remains unclear. Therefore, this study aimed to clarify how HOTTIP works in RA and to investigate its role in the development of RA. Flow cytometry was used to analyze cell cycle progression. Binding between HOTTIP, signal transducer and activator of transcription 3 (STAT3) and miR-1908-5p was demonstrated by dual-luciferase assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T cell differentiation-related proteins. We found that HOTTIP was upregulated in rheumatoid arthritis synovial fibroblasts (RASFs). HOTTIP directly bound to miR-1908-5p and negatively modulated miR-1908-5p expression while positively regulating STAT3. The effects of HOTTIP overexpression on regulating the balance of the Th17/Treg cell ratio were partly reversed by miR-1908-5p overexpression. In addition, in vivo experiments demonstrated that overexpression of HOTTIP aggravated inflammation in RA mice, which was demonstrated by hematoxylin and eosin (HE) staining and the increased expression levels of CD4+ interleukin (IL)-17+, forkhead Box P3 (FOXP3) and retinoid-related orphan receptor gamma-t (RORγt). In summary, our study suggests that HOTTIP plays a damaging role in RA by promoting inflammation, which may be related to the regulation of miR-1908-5p expression and the STAT3 signaling pathway. These results suggest that the regulation of HOTTIP may be a promising therapeutic strategy for RA.

OPCML Methylation and the Risk of Ovarian Cancer: A Meta and Bioinformatics Analysis.

Background: The association of opioid binding protein cell adhesion molecule-like (OPCML) gene methylation with ovarian cancer risk remains unclear. Methods: We identified eligible studies by searching the PubMed, Web of Science, ScienceDirect, and Wanfang databases. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to determine the association of OPCML methylation with ovarian cancer risk. Meta-regression and subgroup analysis were used to assess the sources of heterogeneity. Additionally, we analyzed the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets to validate our findings. Results: Our study included 476 ovarian cancer patients and 385 controls from eight eligible studies. The pooled OR was 33.47 (95% CI = 12.43-90.16) in the cancer group vs. the control group under the random-effects model. The association was still significant in subgroups according to sample type, control type, methods, and sample sizes (all P < 0.05). Sensitivity analysis showed that the finding was robust. No publication bias was observed in Begg's (P = 0.458) and Egger's tests (P = 0.261). We further found that OPCML methylation was related to III/IV (OR = 4.20, 95% CI = 1.59-11.14) and poorly differentiated grade (OR = 4.37; 95% CI = 1.14-16.78). Based on GSE146552 and GSE155760, we validated that three CpG sites (cg16639665, cg23236270, cg15964611) in OPCML promoter region were significantly higher in cancer tissues compared to normal tissues. However, we did not observe the associations of OPCML methylation with clinicopathological parameters and overall survival based on TCGA ovarian cancer data. Conclusion: Our findings support that OPCML methylation is associated with an increased risk of ovarian cancer.

PRMT5 functionally associates with EZH2 to promote colorectal cancer progression through epigenetically repressing CDKN2B expression.

Background: Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that symmetrically di-methylates arginine residues on both histone and non-histone protein substrates. Accumulating evidence suggests that PRMT5 exerts its oncogenic properties in a wide spectrum of human malignancies. However, the underlying mechanisms by which PRMT5 contributes to the progression of colorectal cancer (CRC) remain to be defined. Methods: Western blot and real-time PCR were used to analyze the expression of CDKN2B. Co-immunoprecipitation (Co-IP), immunofluorescence and GST pulldown assays were employed to investigate the interaction between PRMT5 and EZH2. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to validate CDKN2B as a direct target of PRMT5/EZH2. DNA methylation status at the CpG islands of promoter region of CDKN2B gene was analyzed by bisulfite sequencing. The effect of PRMT5/EZH2 on malignant phenotypes was examined through in vitro and in vivo assays. PRMT5 and EZH2 protein expression levels in CRC tissues were analyzed by immunohistochemistry (IHC) staining. Results: We observed that PRMT5-deficient CRC cells exhibit proliferation defects in vitro. PRMT5 was identified as a major transcriptional repressor of CDKN2B (p15INK4b) for determining CRC progression. Mechanistically, PRMT5-mediated histone marks H4R3me2s and H3R8me2s were predominantly deposited at the promoter region of CDKN2B gene in CRC cells. Knockdown of PRMT5 in CRC cells decreased the accumulation of H4R3me2s and H3R8me2s marks and reduced the CpG methylation level of CDKN2B promoter, then re-activated CDKN2B expression. Strikingly, silencing of CDKN2B partially abrogated the proliferation defects caused by PRMT5 depletion in vitro and in vivo. Furthermore, we proved that PRMT5 interacted with Enhancer of zeste homolog 2 (EZH2), leading to enhanced EZH2 binding and H3K27me3 deposition together with decreased transcriptional output of CDKN2B gene. Importantly, we found that the combined interventions exerted a synergistic inhibitory effect of combined treatment with PRMT5i (GSK591) and EZH2i (GSK126) on the growth of CRC cells/xenografts in vitro and in vivo. Moreover, PRMT5 and EZH2 were found to be significantly elevated and associated with poor prognosis in CRC patients. Conclusion: PRMT5 functionally associates with EZH2 to promote CRC progression through epigenetically repressing CDKN2B expression. Thus, our findings raise the possibility that combinational intervention of PRMT5 and EZH2 may be a promising strategy for CRC therapy.

Propensity score-matched comparison of stenting as a bridge to surgery and emergency surgery for acute malignant left-sided colonic obstruction.

BACKGROUND: Bridge to elective surgery (BTS) using self-expanding metal stents (SEMSs) is a common alternative to emergency surgery (ES) for acute malignant left-sided colonic obstruction (AMLCO). However, studies regarding the long-term impact of BTS are limited and have reported unclear results. METHODS: A multicenter observational study was performed at three hospitals from April 2012 to December 2019. Propensity score matching (PSM) was introduced to minimize selection bias. The primary endpoint was overall survival. The secondary endpoints included surgical approaches, primary resection types, total stent-related adverse effects (AEs), surgical AEs, length of hospital stay, 30-day mortality and tumor recurrence. RESULTS: Forty-nine patients in both the BTS and ES groups were matched. Patients in the BTS group more often underwent laparoscopic resection [31 (63.3%) vs. 8 (16.3%), p < 0.001], were less likely to have a primary stoma [13 (26.5%) vs. 26 (53.1%), p = 0.007] and more often had perineural invasion [25 (51.0 %) vs. 13 (26.5 %), p = 0.013]. The median overall survival was significantly lower in patients with stent insertion (41 vs. 65 months, p = 0.041). The 3-year overall survival (53.0 vs. 77.2%, p = 0.039) and 5-year overall survival (30.6 vs. 55.0%, p = 0.025) were significantly less favorable in the BTS group. In multivariate Cox regression analysis, stenting (hazard ratio(HR) = 2.309(1.052-5.066), p = 0.037), surgical AEs (HR = 1.394 (1.053-1.845), p = 0.020) and pTNM stage (HR = 1.706 (1.116-2.607), p = 0.014) were positively correlated with overall survival in matched patients. CONCLUSIONS: Self-expanding metal stents as "a bridge to surgery" are associated with more perineural invasion, a higher recurrence rate and worse overall survival in patients with acute malignant left-sided colonic obstruction compared with emergency surgery.

The Cancer-Testis Long Non-coding RNA PCAT6 Facilitates the Malignant Phenotype of Ovarian Cancer by Sponging miR-143-3p.

Background: It has been reported that long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis. However, their roles in ovarian cancer (OC) remain to be elucidated. The aim of this study was to uncover the function and underlying mechanisms of PCAT6 in OC. Methods: The expression pattern of PCAT6 in OC was analyzed in the GSE137238, GSE143897 and Gene Expression Profile Interactive Analysis (GEPIA) datasets. Kaplan-Meier Plotter online software was used for survival analysis. Loss-of-function assays and gain-of-function assays were used to assess the function of PCAT6 in OC development. Moreover, small-RNA sequencing, bioinformatic analysis, luciferase assays and rescue experiments were carried out to clarify the potential mechanism of PCAT6 in OC. Results: PCAT6 expression was significantly increased in OC tissues and positively correlated with advanced stages and with poor overall survival, progression-free survival and post-progression survival. Knockdown of PCAT6 in A2780 and SKOV3 cells inhibited OC cell proliferation, migration and invasion. In contrast, Overexpression of PCAT6 exerted the opposite effects on OC cells. Notably, PCAT6 bound to miR-143-3p and affected the expression of transforming growth factor (TGF)-ß-activated kinase 1 (TAK1). Subsequent rescue assays confirmed that upregulation of miR-143-3p decreased the PCAT6 overexpression-induced promotion of proliferation, migration and invasion. Moreover, downregulation of miR-143-3p reversed the PCAT6 knockdown-induced inhibition of proliferation, migration, and invasion. Conclusions: Our findings demonstrate that PCAT6 plays an oncogenic role in OC and may be useful as a therapeutic target for OC.

Profiling Analysis Reveals the Crucial Role of the Endogenous Peptides in Bladder Cancer Progression.

BACKGROUND: Peptide drugs provide promising regimes in bladder cancer. In order to identify potential bioactive peptides involved in bladder cancer, we performed the present study. METHODS: Liquid chromatography/mass spectrometry assay was used to compare the endogenous peptides between bladder cancer and normal control. The potential biological functions of these dysregulated peptides are assessed by GO analysis and KEGG pathway analysis of their precursors. The SMART and UniProt databases are used to identify the sequences of the dysregulated peptides located in the functional domains. The Open Targets Platform database was used to investigate the precursors related to metabolic diseases. RESULTS: A total of 9 up-regulated peptides and 110 down-regulated peptides in bladder cancer compared with normal control were identified (fold change > 1.2, P < 0.05). The MW of these dysregulated peptides ranged from 500 Da to 2500 Da and the MW of all identified peptides was below 3500 Da. The GO and KEGG pathway analysis indicated that these dysregulated peptides could play an important role in bladder cancer. Our further analysis revealed that 45HFNPRFNAHGDAN 57 derived from LGALS1 and those peptides derived from P4HB and SERPINA1 might be the promising diagnostic biomarkers and therapeutic targets of bladder cancer. CONCLUSION: In the present study, we have identified the profile of the peptides significantly dysregulated in bladder cancer. Moreover, using bioinformatic analysis, we found the peptides derived from LGALS1, P4HB and SERPINA1 could be the promising diagnostic biomarkers and therapeutic targets of bladder cancer.

Long non-coding RNA in bladder cancer.

Bladder cancer (BC) is the ninth most common malignant disease and ranks fourteenth in cancer mortality worldwide. Moreover, among cancers, the incidence and mortality of BC in males increased to the 6th and 9th place, respectively. The overall survival (OS) declines dramatically as the cancer progresses, especially when urothelial cells transition from noninvasive to invasive. It is well known that epithelial cells can acquire invasive properties and a propensity to metastasize through the epithelial-to-mesenchymal transition (EMT) process in tumourigenesis and progression. However, the potential molecular mechanisms and key pathways are still unclear. As the sequencing technology advances, long non-coding RNAs (lncRNAs) have been proven to play an important role in regulating biological processes and cellular pathways. Here, we reviewed important lncRNAs, such as H19, UCA1 and MALAT1, that participate in the malignant phenotype of BC and regulate EMT signalling networks in the invasion-metastasis cascade during BC development. We further discuss MALAT1, PCAT-1 and SPRY4-IT1, and also urine and blood exosomal H19 and PTENP as potential noninvasive biomarkers. Moreover, antisense oligonucleotides (ASOs) and a double-stranded DNA plasmid (BC-819) have been designed for use in preclinical cancer models and clinical trials in patients. Therefore, the results of investigations have gradually prompted the utility of lncRNAs.

Regioselective O/C phosphorylation of α-chloroketones: a general method for the synthesis of enol phosphates and ß-ketophosphonates via Perkow/Arbuzov reaction.

A regioselective O/C phosphorylation of α-chloroketones with trialkyl phosphites was performed for the first time, which employed solvent-free Perkow reaction and NaI-assisted Arbuzov reaction under mild conditions respectively. Versatile enol phosphates were prepared in good to excellent yields as well as ß-ketophosphinates.