Circ-CUL2/microRNA-888-5p/RB1CC1 axis participates in cisplatin resistance in NSCLC via repressing cell advancement.

Elevated evidences manifest that circular RNAs (circRNAs) are vital in human tumor advancement and chemotherapy resistance. The study was to explore the character of Circ-CUL2 in non-small cell lung cancer (NSCLC). Firstly, the expression of circ-CUL2, microRNA (miR)-888-5p and RB1CC1 was detected in human NSCLC tissues and cell lines by reverse transcription quantitative polymerase chain reaction or Western blot. Then, cell counting kit (CCK)-8, plate clone, Transwell assays, and flow cytometry were applied to separately detect the impacts of circ-CUL2 on proliferation, migration, invasion, apoptosis and cisplatin (DDP) resistance of A549/DDP cells. In this study, exploration of the biological function of Circ-CUL2 was via the Circ-CUL2/miR-888-5p/RB1CC1 axis. The results manifested circ-CUL2 and RB1CC1 were down-regulated in NSCLC tissues and cell lines, while miR-888-5p was up-regulated. Elevated Circ-CUL2 or refrained miR-888-5p repressed A549/DDP cell progression with depressive DDP resistance. Circ-CUL2 curbed miR-888-5p, which targeted RB1CC1. Restrained RB1CC1 turned around the impacts of Circ-CUL2 on the cells. All in all, Circ-CUL2 is anti-NSCLC via miR-888-5p/RB1CC1 axis, enhancing the sensitivity of A549/DDP cells to DDP. Hence, Circ-CUL2 is supposed to be a novel biomarker offering a brand-new strategy for NSCLC therapy.

Osimertinib for the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer patients with leptomeningeal metastases and different T790M status.

BACKGROUND: Leptomeningeal metastasis (LM) is a catastrophic complication for patients with non-small cell lung cancer (NSCLC) and carries an extremely poor prognosis. The efficacy of osimertinib 80 mg once daily for epidermal growth factor receptor-mutated (EGFRm) NSCLC with LM has yet to be fully assessed. This study aimed to investigate the efficacy of osimertinib in such patients and their genetic profiles at the time of LM diagnosis. METHODS: From January 2016 to April 2020, pretreated EGFRm NSCLC patients who had progressed with cytologically confirmed symptomatic LM and received osimertinib 80 mg once daily were enrolled retrospectively. The objective response rate (ORR) and disease control rate (DCR) were evaluated, along with progression-free survival (PFS) and overall survival (OS). Next-generation sequencing of paired samples of cerebrospinal fluid and plasma collected at LM diagnosis was performed simultaneously. RESULTS: Forty cases of EGFRm lung adenocarcinoma with LM were analyzed. Females accounted for 75.0% of enrollees. Of the patients, 37.5% had a poor Eastern Cooperative Oncology Group score (≥2). Twelve patients had received at least 2 prior lines of treatment. All patients received osimertinib treatment regardless of their T790M status. According to the Response Assessment in Neuro-Oncology (RANO)-LM criteria, the ORR and DCR were 20.0% and 95.0%, respectively. The median PFS and OS were 10.0 (95% CI: 7.7-12.3) and 15.1 months (95% CI: 11.0-19.4), respectively. No significant difference was observed between T790M-negative patients (n=24) and T790M-positive patients (n=16) with respect to PFS [median, 10.8 (95% CI: 7.7-13.8) vs. 8.8 months (95% CI: 7.3-10.3), HR=0.595, P=0.158] or OS [median, 17.2 (95% CI: 8.7-25.7) vs. 11.4 months (95% CI: 3.9-19.0), HR=0.913, P=0.822]. The detection rate of EGFR sensitizing mutations in cerebrospinal fluid was higher than that in plasma (97.5% vs. 50%, P=0.311), whereas the incidence of T790M detection in cerebrospinal fluid was significantly lower than that in plasma (20.0% vs. 32.5%, P=0.043). CONCLUSIONS: Osimertinib 80 mg once daily shows good efficacy in pretreated EGFRm NSCLC patients with LM regardless of their T790M status. Combining cerebrospinal fluid and plasma testing can aid in revealing more genetic information.

Long noncoding RNA HEIH depletion depresses esophageal carcinoma cell progression by upregulating microRNA-185 and downregulating KLK5.

Numerous studies have reported the association of long non-coding RNAs (lncRNAs) in cancers, yet the function of lncRNA high expressed in hepatocellular carcinoma (HEIH) in esophageal carcinoma (EC) has seldom been explored. Here, we aimed to explore the mechanism of HEIH on EC via microRNA-185 (miR-185)/kallikrein-related peptidase 5 (KLK5) modulation. Cancer and non-tumoral tissues were collected, in which HEIH, miR-185 and KLK5 expression were detected, as well as their correlations. Also, the relation between the prognosis of EC patients and HEIH/miR-185/KLK5 expression was clarified. EC cells (KYSE-30 and TE-1) were screened for subsequent gain- and loss-of-function assays and their biological functions were further monitored. Tumor volume and weight in EC mice were also measured. Results from this study indicated that HEIH and KLK5 were elevated and miR-185 was declined in EC. The positive correlation was seen in HEIH and KLK5 expression, while the negative correlation was observed in HEIH or KLK5 and miR-185 expression. High HEIH and KLK5 indicated worse prognosis and high miR-185 suggested better prognosis of EC patients. Depleting HEIH or restoring miR-185 suppressed the malignant phenotypes of EC cells, and delayed tumor growth in EC mice. HEIH was found to bind with miR-185 to regulate KLK5 expression. Overexpressing KLK5 alone promoted EC cell progression while up-regulating miR-185 reversed such effects on EC cells. Collectively, we reveal that HEIH depletion dampens EC progression by upregulating miR-185 and downregulating KLK5, which provides novel treatments for EC.

Computer-Guided Discovery of a pH-Responsive Organic Photocatalyst and Application for pH and Light Dual-Gated Polymerization.

In this work, we adopted a fully computer-guided strategy in discovering an efficient pH-switchable organic photocatalyst (OPC), unprecedentedly turning colorless at pH 5 and recovering strong visible-light absorption and photoactivity at pH 7. This is the first example of an OPC design fully guided by comprehensive density functional theory (DFT) studies covering electrostatic, electrochemical, and photophysical predictions. Characterization of the designed OPC after synthesis confirmed the computational predictions. We applied this OPC to mediate an aqueous photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization under green LED light (nominal emission wavelength: 530 nm, 5 mW/cm2). We demonstrated that the polymerization can be reversibly ceased by a slight change of pH (pH ≤ 5.0) or in the absence of light. Furthermore, we demonstrated that the polymerization rate could be significantly retarded by bubbling carbon dioxide into the reaction solution under visible light. Conversely, the rate could be fully recovered via exposure to nitrogen gas. This is the first example of a pH and light dual-gated polymerization system with complete and reversible inhibition.

[Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after radical resection of esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the prognostic significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with esophageal squamous cell carcinoma (ESCC) who received radical resection. METHODS: A retrospective review was performed on 475 patients who underwent radical resection for ESCC in our hospital between January 2007 and December 2008, all patients were diagnosed with ESCC by pathological examination. None accepted neoadjuvant therapy. RESULTS: The median value of NLR was 1.77 (range, 0.53-11). Based on this cut-off value of 2.5, all the patients were divided into 2 groups: a low NLR (<2.5, n = 389) group and a high NLR ( ≥ 2.5, n = 86) group. The 5-year overall survival rate was 48.6% in patients of the low NLR group and 36.0% in those of the high NLR group (P = 0.009). The ratio of women was higher in the low NLR group (P = 0.04). Univariate analysis showed NLR, age, history of smoking, T stage, N stage, and postoperative adjuvant therapy were associated with survival (P < 0.05 for all). We also found that NLR could be used to divide patients with or without lymph node metastasis into a high and low risk groups. Multivariate analysis revealed that NLR, age, N stage, and postoperative adjuvant therapy were independent risk factors of prognosis. CONCLUSION: Our results show that preoperative NLR ≥ 2.5 may be a convenient biomarker to predict patients with a poor prognosis after radical resection for ESCC.

Serological thymidine kinase 1 is a prognostic factor in oesophageal, cardial and lung carcinomas.

In this study we examine the use of the concentration of thymidine kinase 1 in serum (STK1) as a prognostic factor in routine clinical settings. For this purpose we used sera from patients with oesophageal (n=101) and cardial (n=39) carcinomas and nonsmall-cell lung carcinoma (NSCLC) (n=157). Sera from healthy individuals (n=95) were used as controls. STK1 was analysed by a chemiluminiscence dot blot assay. The mean STK1 concentrations and the STK1 positive rates of the patients with oesophageal and cardial carcinomas and with NSCLC were significantly higher as compared with healthy controls (P=0.01). The mean STK1 value of oesophageal carcinoma patients correlated with T-values (P=0.021) and with stage (P<0.005), but not with grade. The mean STK1 value of cardial carcinoma patients did not correlate with grade. No data on stage and T-values were available for these patients, due to advanced disease. The mean STK1 value of NSCLC patients with squamous cell carcinoma was significantly higher as compared with adenocarcinoma type (P=0.024). The mean STK1 value of the NSCLC patients correlated with clinical grade (P=0.006), T-values (P=0.001), stage (P=0.035) and to size of the tumour (P=0.030). The mean STK1 value and the number of STK1 positive patients were also higher in recurrent NSCLC patients. There was a tendency that stage I-II NSCLC patients with an STK1 level above 2 pmol/l showed a higher frequency of recurrence/death than patients below 1 pmol/l. Our results show that STK1 is a useful marker for prognosis in patients with oesophageal, cardial and lung carcinomas.