Role of STING in the treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a prevalent form of lung cancer. Patients with advanced NSCLC are currently being treated with various therapies, including traditional radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. However, a considerable proportion of advance patients who cannot benefit from them. Consequently, it is essential to identify a novel research target that offers an encouraging perspective. The stimulator of interferon genes (STING) has emerged as such a target. At present, it is confirmed that activating STING in NSCLC tumor cells can impede the proliferation and metastasis of dormant tumor cells. This review focuses on the role of STING in NSCLC treatment and the factors influencing its activation. Additionally, it explores the correlation between STING activation and diverse therapy modalities for NSCLC, such as radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. Furthermore, it proposes the prospect of innovative therapy methods involving nanoparticles, with the aim of using the features of STING to develop more strategies for NSCLC therapy.

Cuprotosis clusters predict prognosis and immunotherapy response in low-grade glioma.

Cuprotosis, an emerging mode of cell death, has recently caught the attention of researchers worldwide. However, its impact on low-grade glioma (LGG) patients has not been fully explored. To gain a deeper insight into the relationship between cuprotosis and LGG patients' prognosis, we conducted this study in which LGG patients were divided into two clusters based on the expression of 18 cuprotosis-related genes. We found that LGG patients in cluster A had better prognosis than those in cluster B. The two clusters also differed in terms of immune cell infiltration and biological functions. Moreover, we identified differentially expressed genes (DEGs) between the two clusters and developed a cuprotosis-related prognostic signature through the least absolute shrinkage and selection operator (LASSO) analysis in the TCGA training cohort. This signature divided LGG patients into high- and low-risk groups, with the high-risk group having significantly shorter overall survival (OS) time than the low-risk group. Its predictive reliability for prognosis in LGG patients was confirmed by the TCGA internal validation cohort, CGGA325 cohort and CGGA693 cohort. Additionally, a nomogram was used to predict the 1-, 3-, and 5-year OS rates of each patient. The analysis of immune checkpoints and tumor mutation burden (TMB) has revealed that individuals belonging to high-risk groups have a greater chance of benefiting from immunotherapy. Functional experiments confirmed that interfering with the signature gene TNFRSF11B inhibited LGG cell proliferation and migration. Overall, this study shed light on the importance of cuprotosis in LGG patient prognosis. The cuprotosis-related prognostic signature is a reliable predictor for patient outcomes and immunotherapeutic response and can help to develop new therapies for LGG.

Investigation of actual exposure to facial sheet mask preceding its risk assessment.

The present study aimed to reveal the amount per application of facial sheet masks and its influencing factors in Chinese population to form the base for an accurate exposure assessment. A total of 175 healthy subjects aged 18 years or older were recruited and divided into two subgroups: one group of 35 subjects were asked to apply same mask for 5, 10, 15, 20, 25, and 30 min respectively, and the other 140 subjects were instructed to apply one of four types of facial sheet masks presented in the market for 15 min. Furthermore, phenoxyethanol and methylparaben were measured to reflect actual exposure to chemicals. The sharp increase in the relative exposure to phenoxyethanol (CAS NO.122-99-6) and methylparaben at 25 min and longer suggests applying facial sheet masks for longer than 20 min may drive the exposure to hazardous chemicals to increase significantly. The 90th percentile of amount per application for plant-cellulose, bamboo charcoal fiber, bio-cellulose, and binchotan charcoal fiber-based masks was 5.753, 5.371, 5.017, and 4.821 g respectively. In addition, men and subjects with sebaceous skin demonstrated lower amount per application compared to women and subjects with dry skin, respectively. Finally, our data showed that the larger the contacting area between face and mask, the more amount per application. We concluded that the appropriate time of application should be less than 20 min. And mask fabrics, gender, sebum content, and contacting area could significantly impact the risk assessment of facial sheet masks. Our data for the first time provides insights into a realistic risk assessment of facial sheet masks in Chinese population.

Concurrent cisplatin or cetuximab with radiotherapy in patients with locally advanced head and neck squamous cell carcinoma: A meta-analysis.

BACKGROUND: Concurrent cisplatin with radiotherapy (CRT) or concurrent cetuximab with radiotherapy (BRT) improves outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) compared with radiotherapy alone. Nevertheless, a detailed comparison between CRT and BRT in locally advanced HNSCC is required due to inconclusive results. METHODS: A comprehensive literature search was conducted on PubMed, Web of Science, Cochrane databases, and EMBASE. Studies that evaluated CRT vs BRT in locally advanced HNSCC were included. The primary outcome that was overall survival (OS), whereas the secondary outcomes were progression-free survival (PFS), locoregional control (LRC), and distant metastasis-free survival (DMFS). Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to evaluate prognosis. All the analyses were performed using Stata Statistical Software 12.0. RESULTS: Twenty-three studies, with a total of 8701 patients, were considered eligible and included in this meta-analysis. Our results revealed that patients treated with CRT had longer OS (HR = 0.51, 95%CI, 0.41-0.64, P < .001), PFS (HR = 0.37, 95%CI, 0.23-0.60, P < .001), LRC (HR = 0.46, 95%CI, 0.37-0.57, P < .001), and DMFS (HR = 0.56, 95%CI, 0.40-0.77, P < .001) than those treated with BRT. Furthermore, the results of the subgroup analyses were consistent with the primary analysis. CONCLUSIONS: CRT has a better OS, PFS, LRC, and DMFS than BRT in locally advanced HNSCC, and should be the preferred treatment for patients with the disease.

Identification of BTG1 Status in Solid Cancer for Future Researches Using a System Review and Meta-analysis.

Abundant studies have been conducted to identify how B-cell translocation gene 1 protein (BTG1) gene affects the differentiation, proliferation, metastasis of cancer cells, and how it further regulates the generation or development of diseases to influence the prognosis of patients. However, the data from single research were not powerful enough. The correlations between BTG1 expression and mechanisms of tumorigenesis or prognosis of patients are still in controversial. Our system review and meta-analysis provided a complete explanation about the association between BTG1 expression and clinicopathological features or prognosis of patients, which further laid a foundation for future research on BTG1. Fifteen eligible studies consisting of 1992 participants were included. We uncovered that BTG1 expression in solid tumors was associated with lymph node status (RR=0.66, 95% CI: 0.58-0.75, P=0.142), TMN stage status (RR=2.13, 95% CI: 1.71-2.65, P=0.001), T category (RR=1.90, 95% CI: 1.20-3.00, P=0.000), histological differentiation (RR=1.91, 95% CI: 1.55-2.37, P=0.012), vascular invasion (RR=0.90, 95% CI: 0.57-1.41, P=0.001). BTG1 low expression was significantly associated with overall survival (OS) (HR=0.47, 95% CI: 0.38-0.67, P=0.000). It concluded that BTG1 possessed the potential value for future research and could be recommended as a significant biomarker in solid tumor.

Supramolecular Copolymerization Strategy for Realizing the Broadband White Light Luminescence Based on N-Deficient Porous Graphitic Carbon Nitride (g-C3N4).

The N-deficient porous g-C3N4 with broadband white light emission was constructed by supramolecular copolymerization design, which combined organic copolymers cyanuric acid and 2,4,6-triaminopyrimidine with melamine upon the mixture gas environment of (95%)N2/(5%)H2. Herein, we achieved great breakthrough in narrowing the band gap of g-C3N4 from 2.64 to 1.39 eV. Furthermore, in contrast to pristine g-C3N4, we demonstrated that the emission wavelengths of N-deficient porous g-C3N4 can be tuned from narrow blue to broadband white range, where the optimal white light coordinate position is (0.297, 0.345). The prepared N-deficient porous g-C3N4 overcomes the limitation of the narrow adjusting range of optical properties while using conventional g-C3N4 and makes it more promising for applications in solid-state displays.

Pre-treatment Serum Lactate Dehydrogenase Predicts Distant Metastasis and Poor Survival in Nasopharyngeal Carcinoma.

Background: Pre-treatment serum lactate dehydrogenase (LDH) has emerged as prognostic factor for many cancers. In this study, we evaluated the value of LDH in predicting distant metastasis and poor survival for patients with nasopharyngeal carcinoma (NPC). Methods: Clinical data from 172 non-metastatic NPC patients were retrospectively collected and serum LDH levels were routinely measured before treatment. The independent-samples t test was used to calculate differences between serum LDH levels from the various patient groups. Receiver-operating characteristic (ROC) curve analysis was performed to select the optimal cutoff points. The Kaplan-Meier method and log-rank test were adopted to calculate and compare the distant metastasis free survival (DMFS) and overall survival (OS) rates. The Cox proportional hazards model was used to carry out univariate and multivariate analyses. Results: NPC patients progressed with distant metastasis often have higher pre-treatment serum LDH levels than those did not develop distant metastasis (mean LDH level was 237.1U/L and 108.8U/L, respectively, p=0.001). Elevated LDH level was identified as an independent prognostic factor for poor DMFS (hazard ratio (HR), 8.31; 95% confidence interval (CI), 2.44-28.32; p=0.001) and OS (HR, 4.45; 95% CI, 1.77-11.21; p=0.002). Moreover, subgroup analyses revealed significant associations between serum LDH level and worse survival in advanced stage patients. Conclusions: Pre-treatment serum LDH level can predict distant metastasis and associate with the poor survival in patients with NPC.

Correction: Core-shell like glass containing lanthanide doped nanocrystals for efficient luminescence.

Correction for 'Core-shell like glass containing lanthanide doped nanocrystals for efficient luminescence' by Qunhuo Liu et al., Chem. Commun., 2018, 54, 13092-13095.

Identification of Potential Biomarkers in Glioblastoma through Bioinformatic Analysis and Evaluating Their Prognostic Value.

Glioblastoma is a common malignant tumor in the central nervous system with an extremely poor outcome; understanding the mechanisms of glioblastoma at the molecular level is essential for clinical treatment. In the present study, we used bioinformatics analysis to identify potential biomarkers associated with prognosis in glioblastoma and elucidate the underlying mechanisms. The result revealed that 552 common genes were differentially expressed between glioblastoma and normal tissues based on TCGA, GSE4290, and GSE 50161 datasets. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction (PPI) network were carried out to gain insight into the actions of differentially expressed genes (DEGs). As a result, 20 genes (CALB1, CDC20, CDCA8, CDK1, CEP55, DLGAP5, KIF20A, KIF4A, NDC80, PBK, RRM2, SYN1, SYP, SYT1, TPX2, TTK, VEGFA, BDNF, GNG3, and TOP2A) were found as hub genes via CytoHubba in Cytoscape and functioned mainly by participating in cell cycle and p53 signaling pathway; among them, RRM2 and CEP55 were considered to have relationship with the prognosis of glioblastoma, especially RRM2. High expression of RRM2 was consistent with shorter overall survival time. In conclusion, our study displayed the bioinformatic analysis methods in screening potential oncogenes in glioblastoma and underlying mechanisms. What is more is that we successfully identified RRM2 as a novel biomarker linked with prognosis, which might be expected to be a promising target for the therapy of glioblastoma.

Fe3+-selective and sensitive "on-off" fluorescence probe based on the graphitic carbon nitride nanosheets.

An effective and facile "on-off" fluorescence sensing approach for the determination of Fe3+ ion using a large area and relatively uniform size graphitic carbon nitride nanosheets (GCNS) was developed. The prepared GCNS have blue and stable emission, as well as excellent water dispersion, and were applied as an effective fluorescent probe that based on the quenched fluorescence for selective and sensitive detection of Fe3+ ion. Herein, we explain the ambiguous fluorescence quenching mechanism between the GCNS and Fe3+, which mainly springs from the redox potential and empty d orbital of Fe3+. The redox potential and unfilled d orbit of Fe3+ endow it excellent binding force with GCNS, which generates most obvious fluorescence quenching effect with respect to other metal ions. The limit of detection (LOD) for Fe3+ was found to be about 2.06 µM. Therefore, the prepared GCNS has the potential to be used as a fluorescent probe for detection.

Core-shell like glass containing lanthanide doped nanocrystals for efficient luminescence.

We constructed a core-shell like nanoarchitecture in Yb/Er ion and Yb/Ho SrTiO3 nanocrystal-codoped tellurite-borate glass. We demonstrated that the adverse energy transfer between Er3+ ions in the glass region and Ho3+ ions in the crystal region was effectively prohibited, which permits independent and highly efficient emission from Er3+ and Ho3+ ions.

Effects of Dexamethasone in the Treatment of Recurrent Chronic Subdural Hematoma.

OBJECTIVE: Recurrent chronic subdural hematoma (CSDH) is not rare. Some studies have demonstrated the role of dexamethasone in the medical management of chronic subdural hematoma. However, no systematic study in the treatment of recurrent CSDH has been published. The aim of our study is to evaluate the efficacy and safety of dexamethasone in patients with recurrent CSDH. METHODS: We retrospectively reviewed medical records of consecutive patients from July 2010 to September 2014. A total of 27 patients with symptomatic recurrent CSDH were included in the analysis. Follow-up for each patient consisted of computed tomography or magnetic resonance imaging every 28 days from admission to the resolution of hematoma. Data were collected on hematoma volume, complications, and outcome. RESULTS: Among the 27 patients, 3 patients with recurrent CSDH were only treated by burr hole surgery. Of the other 24 patients who primarily underwent dexamethasone treatment, 17 (70.8%) patients were treated successfully with medical treatment, whereas 7 patients required reoperation. Complications were noted in 3 (12.5%) patients (1 hyperglycemia, 1 urinary tract infection, and 1 pneumonia). There was 1 mortality (4.2%) for massive brain infarction. Twenty-one of the 24 patients (87.5%) recovered to their previous functional levels. There was no statistical significance in Fisher text between surgery and dexamethasone regarding success, complication, and functional recovery rate. CONCLUSIONS: Patients with recurrent CSDH can be treated successfully and safely with the nonsurgical medical treatment of dexamethasone. By use of this method, reoperation may be avoided.

Overcoming chemo/radio-resistance of pancreatic cancer by inhibiting STAT3 signaling.

Chemo/radio-therapy resistance to the deadly pancreatic cancer is mainly due to the failure to kill pancreatic cancer stem cells (CSCs). Signal transducer and activator of transcription 3 (STAT3) is activated in pancreatic CSCs and, therefore, may be a valid target for overcoming therapeutic resistance. Here we investigated the potential of STAT3 inhibition in sensitizing pancreatic cancer to chemo/radio-therapy. We found that the levels of nuclear pSTAT3 in pancreatic cancer correlated with advanced tumor grade and poor patient outcome. Liposomal delivery of a STAT3 inhibitor FLLL32 (Lip-FLLL32) inhibited STAT3 phosphorylation and STAT3 target genes in pancreatic cancer cells and tumors. Consequently, Lip-FLLL32 suppressed pancreatic cancer cell growth, and exhibited synergetic effects with gemcitabine and radiation treatment in vitro and in vivo. Furthermore, Lip-FLLL32 reduced ALDH1-positive CSC population and modulated several potential stem cell markers. These results demonstrate that Lip-FLLL32 suppresses pancreatic tumor growth and sensitizes pancreatic cancer cells to radiotherapy through inhibition of CSCs in a STAT3-dependent manner. By targeting pancreatic CSCs, Lip-FLLL32 provides a novel strategy for pancreatic cancer therapy via overcoming radioresistance.

ATDC/TRIM29 phosphorylation by ATM/MAPKAP kinase 2 mediates radioresistance in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by therapeutic resistance for which the basis is poorly understood. Here, we report that the DNA and p53-binding protein ATDC/TRIM29, which is highly expressed in PDAC, plays a critical role in DNA damage signaling and radioresistance in pancreatic cancer cells. Ataxia-telangiectasia group D-associated gene (ATDC) mediated resistance to ionizing radiation in vitro and in vivo in mouse xenograft assays. ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC. Our results identify a DNA repair pathway leading from MK2 and ATM to ATDC, suggesting its candidacy as a therapeutic target to radiosensitize PDAC and improve the efficacy of DNA-damaging treatment.

Antibody against CD44s inhibits pancreatic tumor initiation and postradiation recurrence in mice.

BACKGROUND & AIMS: CD44s is a surface marker of tumor-initiating cells (TICs); high tumor levels correlate with metastasis and recurrence, as well as poor outcomes for patients. Monoclonal antibodies against CD44s might eliminate TICs with minimal toxicity. This strategy is unclear for treatment of pancreatic cancer, and little is known about how anti-CD44s affect pancreatic cancer initiation or recurrence after radiotherapy. METHODS: One hundred ninety-two pairs of human pancreatic adenocarcinoma and adjacent nontumor pancreatic tissues were collected from patients undergoing surgery. We measured CD44s levels in tissue samples and pancreatic cancer cell lines by immunohistochemistry, real-time polymerase chain reaction, and immunoblot; levels were correlated with patient survival times. We studied the effects of anti-CD44s in mice with human pancreatic tumor xenografts and used flow cytometry to determine the effects on TICs. Changes in CD44s signaling were examined by real-time polymerase chain reaction, immunoblot, reporter assay, and in vitro tumorsphere formation assays. RESULTS: Levels of CD44s were significantly higher in pancreatic cancer than adjacent nontumor tissues. Patients whose tumors expressed high levels of CD44s had a median survival of 10 months compared with >43 months for those with low levels. Anti-CD44s reduced growth, metastasis, and postradiation recurrence of pancreatic xenograft tumors in mice. The antibody reduced the number of TICs in cultured pancreatic cancer cells and xenograft tumors, as well as their tumorigenicity. In cultured pancreatic cancer cell lines, anti-CD44s down-regulated the stem cell self-renewal genes Nanog, Sox-2, and Rex-1 and inhibited signal transducer and activator of transcription 3-mediated cell proliferation and survival signaling. CONCLUSIONS: The TIC marker CD44s is up-regulated in human pancreatic tumors and associated with patient survival time. CD44s is required for initiation, growth, metastasis, and postradiation recurrence of xenograft tumors in mice. Anti-CD44s eliminated bulk tumor cells as well as TICs from the tumors. Strategies to target CD44s cab be developed to block pancreatic tumor formation and post-radiotherapy recurrence in patients.

HAb18G/CD147 promotes pSTAT3-mediated pancreatic cancer development via CD44s.

PURPOSE: Signal transducer and activator of transcription 3 (STAT3) plays a critical role in initiation and progression of pancreatic cancer. However, therapeutically targeting STAT3 has failed clinically. We previously identified HAb18G/CD147 as an effective target for cancer treatment. In this study, we aimed to investigate the potential role of HAb18G/CD147 in STAT3-involved pancreatic tumorigenesis in vitro and in vivo. EXPERIMENTAL DESIGN: The expression of HAb18G/CD147, pSTAT3, and CD44s was determined in tissue microarrays. The tumorigenic function and molecular signaling mechanism of HAb18G/CD147 were assessed by in vitro cellular and clonogenic growth, reporter assay, immunoblot assay, immunofluorescence staining, immunoprecipitation, and in vivo tumor formation using loss or gain-of-function strategies. RESULTS: Highly expressed HAb18G/CD147 promoted cellular and clonogenic growth in vitro and tumorigenicity in vivo. Cyclophilin A (CyPA), a ligand of CD147, stimulated STAT3 phosphorylation and its downstream genes cyclin D1/survivin through HAb18G/CD147-dependent mechanisms. HAb18G/CD147 was associated and colocalized with cancer stem cell marker CD44s in lipid rafts. The inhibitors of STAT3 and survivin, as well as CD44s neutralizing antibodies suppressed the HAb18G/CD147-induced cell growth. High HAb18G/CD147 expression in pancreatic cancer was significantly correlated with the poor tumor differentiation, and the high coexpression of HAb18G/CD147-CD44s-STAT3 associated with poor survival of patients with pancreatic cancer. CONCLUSIONS: We identified HAb18G/CD147 as a novel upstream activator of STAT3, which interacts with CD44s and plays a critical role in the development of pancreatic cancer. The data suggest that HAb18G/CD147 could be a promising therapeutic target for highly aggressive pancreatic cancer and a surrogate marker in the STAT3-targeted molecular therapies.

[Determination of selenium in plant samples by hydride generation atomic fluorescence spectrometry].

A method was developed by hydride generation atomic fluorescence spectrometry (HG-AFS)for the determination of selenium in plant samples. Effects of reagent and pre-reduction method on the fluorescence intensity of selenium were studied. The influence of coexisting foreign ions on the determination of selenium was also investigated. Under the optimized digestive and experimental conditions, the linear regression equation was I = 139.98c + 27.71 for Se. The linear range, the correlation coefficient,and the detection limit of Se was 0-10 ng x mL(-1), 1.0000, and 1.45 ng x g(-1) respectively. The recovery of Se (98.9%-101%, mean=100%) was determined through the use of standard reference material. The relative standard deviation for nine replicate analyses was 0.73% for Se content in shrub leaves. This method was verified by analyzing the national reference material (GSV-1)and the found value was in good agreement with the certified value. The proposed method that was successfully used for the determination of Se in plant samples has the advantages of simple operation, low cost, and high efficiency.