Sensitivity improved Cerenkov luminescence endoscopy using optimal system parameters.

BACKGROUND: The challenges of clinical translation of optical imaging, including the limited availability of clinically used imaging probes and the restricted penetration depth of light propagation in tissues can be avoided using Cerenkov luminescence endoscopy (CLE). However, the clinical applications of CLE are limited due to the low signal level of Cerenkov luminescence and the large transmission loss caused by the endoscope, which results in a relatively low detection sensitivity of current CLE. The aim of this study was to enhance the detection sensitivity of the CLE system and thus improve the system for clinical application in the detection of gastrointestinal diseases. METHODS: Four optical fiber endoscopes were customized with different system parameters, including monofilament (MF) diameter of imaging fiber bundles, fiber material, probe coating, etc. The endoscopes were connected to the detector via a specifically designed straight connection device to form the CLE system. The ß-2-[18F]-Fluoro-2-deoxy-D-glucose (18F-FDG) solution and the radionuclide of Gallium-68 (68Ga) were used to evaluate the performance of the CLE system. The images of the 18F-FDG solution acquired by the CLE were used to optimize imaging parameters of the system. By using the endoscope with optimized parameters, including the MF diameter of imaging fiber bundles, fiber materials, etc., the resolution and sensitivity of the assembled CLE system were measured by imaging the radionuclide of 68Ga. RESULTS: The results of 18F-FDG experiments showed that larger MF diameter led to higher collection efficiency. The fiber material and probe coating with high transmission ratios in the range of 400-900 nm also increased signal collection and transmission efficiency. The results of 68Ga evaluations showed that a minimum radioactive activity of radionuclides as low as 0.03 µCi was detected in vitro within 5 minutes, while that of 0.68 µCi can be detected within 1 minute. In vivo experiments also demonstrated that the developed CLE system achieved a high sensitivity at a submicrocurie level; that is, 0.44 µCi within 5 minutes, and 0.83 µCi within 1 minute. The weaker in vivo sensitivity was due to the attenuation of the signal by the mouse tissue skin and the autofluorescence interference produced by biological tissues. CONCLUSIONS: By optimizing the structural parameters of fiber endoscope and imaging parameters for data acquisition, we developed a CLE system with a sensitivity at submicrocurie level. These results support the possibility that this technology can clinically detect early tumors within 1 minute.

SPHK1 contributes to cisplatin resistance in bladder cancer cells via the NONO/STAT3 axis.

Sphingosine­1­phosphate (S1P) serves an important role in various physiological and pathophysiological processes, including the regulation of cell apoptosis, proliferation and survival. Sphingosine kinase 1 (SPHK1) is a lipid kinase that phosphorylates sphingosine to generate S1P. S1P has been proven to be positively correlated with chemotherapy resistance in breast cancer, colorectal carcinoma and non­small cell lung cancer. However, whether SPHK1 is involved in the development of cisplatin resistance remains to be elucidated. The present study aimed to identify the association between SPHK1 and chemoresistance in bladder cancer cells and to explore the therapeutic implications in patients with bladder cancer. Bladder cancer cell proliferation and apoptosis were determined using Cell Counting Kit­8 assays and flow cytometry, respectively. Apoptosis­related proteins were detected via western blotting. The results revealed that SPHK1 was positively correlated with cisplatin resistance in bladder cancer cells, exhibiting an antiapoptotic effect that was reflected by the downregulation of apoptosis­related proteins (Bax and cleaved caspase­3) and the upregulation of an antiapoptotic protein (Bcl­2) in SPHK1­overexpression cell lines. Suppression of SPHK1 by small interfering RNA or FTY­720 significantly reversed the antiapoptotic effect. A potential mechanism underlying SPHK1­induced cisplatin resistance and apoptosis inhibition may be activation of STAT3 via binding non­POU domain containing octamer binding. In conclusion, the present study suggested that SPHK1 displayed significant antiapoptotic effects in cisplatin­based treatment, thus may serve as a potential novel therapeutic target for the treatment for bladder cancer.

A Glycolysis-Based Long Non-coding RNA Signature Accurately Predicts Prognosis in Renal Carcinoma Patients.

BACKGROUND: The prognosis of renal cell carcinoma (RCC) varies greatly among different risk groups, and the traditional indicators have limited effect in the identification of risk grade in patients with RCC. The purpose of our study is to explore a glycolysis-based long non-coding RNAs (lncRNAs) signature and verify its potential clinical significance in prognostic prediction of RCC patients. METHODS: In this study, RNA data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate cox regression displayed six significantly related lncRNAs (AC124854.1, AC078778.1, EMX2OS, DLGAP1-AS2, AC084876.1, and AC026401.3) which were utilized in construction of risk score by a formula. The accuracy of risk score was verified by a series of statistical methods such as receiver operating characteristic (ROC) curves, nomogram and Kaplan-Meier curves. Its potential clinical significance was excavated by gene enrichment analysis. RESULTS: Kaplan-Meier curves and ROC curves showed reliability of the risk score to predict the prognosis of RCC patients. Stratification analysis indicated that the risk score was independent predictor compare to other traditional clinical parameters. The clinical nomogram showed highly rigorous with index of 0.73 and precisely predicted 1-, 3-, and 5-year survival time of RCC patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene set enrichment analysis (GSEA) depicted the top ten correlated pathways in both high-risk group and low-risk group. There are 6 lncRNAs and 25 related mRNAs including 36 lncRNA-mRNA links in lncRNA-mRNA co-expression network. CONCLUSION: This research demonstrated that glycolysis-based lncRNAs possessed an important value in survival prediction of RCC patients, which would be a potential target for future treatment.

An epithelial-mesenchymal transition-related long noncoding RNA signature correlates with the prognosis and progression in patients with bladder cancer.

Bladder cancer is a common malignant tumour worldwide. Epithelial-mesenchymal transition (EMT)-related biomarkers can be used for early diagnosis and prognosis of cancer patients. To explore, accurate prediction models are essential to the diagnosis and treatment for bladder cancer. In the present study, an EMT-related long noncoding RNA (lncRNA) model was developed to predict the prognosis of patients with bladder cancer. Firstly, the EMT-related lncRNAs were identified by Pearson correlation analysis, and a prognostic EMT-related lncRNA signature was constructed through univariate and multivariate Cox regression analyses. Then, the diagnostic efficacy and the clinically predictive capacity of the signature were assessed. Finally, Gene set enrichment analysis (GSEA) and functional enrichment analysis were carried out with bioinformatics. An EMT-related lncRNA signature consisting of TTC28-AS1, LINC02446, AL662844.4, AC105942.1, AL049840.3, SNHG26, USP30-AS1, PSMB8-AS1, AL031775.1, AC073534.1, U62317.2, C5orf56, AJ271736.1, and AL139385.1 was constructed. The diagnostic efficacy of the signature was evaluated by the time-dependent receiver-operating characteristic (ROC) curves, in which all the values of the area under the ROC (AUC) were more than 0.73. A nomogram established by integrating clinical variables and the risk score confirmed that the signature had a good clinically predict capacity. GSEA analysis revealed that some cancer-related and EMT-related pathways were enriched in high-risk groups, while immune-related pathways were enriched in low-risk groups. Functional enrichment analysis showed that EMT was associated with abundant GO terms or signaling pathways. In short, our research showed that the 14 EMT-related lncRNA signature may predict the prognosis and progression of patients with bladder cancer.

Harnessing the Power of Optical Microscopic and Macroscopic Imaging for Natural Products as Cancer Therapeutics.

Natural products (NPs) are an important source for new drug discovery over the past decades, which have been demonstrated to be effectively used in cancer prevention, treatment, and adjuvant therapy. Many methods, such as the genomic and metabolomic approaches, immunochemistry, mass spectrometry, and chromatography, have been used to study the effects of NPs on cancer as well as themselves. Because of the advantages in specificity, sensitivity, high throughput, and cost-effectiveness, optical imaging (OI) approaches, including optical microscopic imaging and macroscopic imaging techniques have also been applied in the studies of NPs. Optical microscopic imaging can observe NPs as cancer therapeutics at the cellular level and analyze its cytotoxicity and mechanism of action. Optical macroscopic imaging observes the distribution, metabolic pathway, and target lesions of NPs in vivo, and evaluates NPs as cancer therapeutics at the whole-body level in small living animals. This review focuses on the recent advances in NPs as cancer therapeutics, with particular emphasis on the powerful use of optical microscopic and macroscopic imaging techniques, including the studies of observation of ingestion by cells, anticancer mechanism, and in vivo delivery. Finally, we prospect the wider application and future potential of OI approaches in NPs as cancer therapeutics.