Survival analysis of comprehensive treatment in Chinese patients with metastatic melanoma: A retrospective analysis.

BACKGROUND: Most of the current progression of immune checkpoint inhibitors for malignant melanoma is based on data from Caucasians in Western countries, but the benefit of Chinese patients is limited, mainly due to different pathological subtypes. The patients in western countries are mainly skin melanoma (about 90%), while the acral and mucosal types are dominant in China, accounting for 41.8% and 22.6% respectively. Acral and mucosal melanoma have lower response rates to immunotherapy and chemotherapy. OBJECTIVE: Whether immune checkpoint inhibitors can improve the survival of Chinese patients with malignant melanoma, therefore, we conducted a retrospective analysis. METHODS: We analyzed 53 patients with metastatic melanoma treated in our hospital to evaluate the efficacy and safety of PD-1 mAb in Chinese patients with metastatic melanoma, and performed univariate and multivariate analyses of prognostic factors that may affect overall survival (OS). RESULTS: In a study of 125 patients with advanced malignant melanoma, 53 patients participated, with a median follow-up of 16 months. Among these, 69.8% died, and 30.2% remained on treatment. Median progression-free survival (PFS) was 6 months, and median OS was 19 months. Patients treated with immune checkpoint inhibitors had improved outcomes, with a median PFS of 7 months and a median OS of 24 months. Patients with bone metastasis and aberrant Lactate dehydrogenase (LDH) post-treatment had worse prognoses, while immunotherapy was a protective factor. Subgroup analysis showed the benefits of immunotherapy across various patient characteristics. No unexpected toxicities were observed. CONCLUSION: The study highlights the efficacy of immune checkpoint inhibitors, particularly PD-1 mAb, in improving survival outcomes for Chinese patients with metastatic melanoma.

Highly Efficient and Simultaneous Analysis of Three Common Fluorotelomer Alcohols in Vegetables and Soils.

Fluorotelomer alcohols (FTOHs), as precursors of perfluoroalkyl carboxylic acids, are difficult to analyze due to their high volatility and matrix interference. A method based on single-factor experiments and response surface methodology design was developed for simultaneous analysis of three common FTOHs in vegetables and soils, using single extraction, dispersive solid phase extraction cleanup, and gas chromatography-mass spectrometry in negative chemical ionization. The method improved the extraction efficiency up to ∼40 folds and showed a commendable linearity range (1-100 ng/mL, R2 > 0.991), low limit of detection (0.025-0.897 ng/g, dry weight (dw)), and high accuracy and precision (83 ± 7.2-117 ± 6.0% recoveries at 2-20 ng/g fortification levels). It was successfully applied to determine the FTOHs in real vegetables and soils, demonstrating its feasibility for routine analysis. Concentrations of the FTOHs ranged from 3.5 to 37.9 ng/g (dw) and from 6.5 to 141.0 ng/g (dw), respectively, in the vegetables and soils collected nearby fluorochemical factories, which warrants further investigations on FTOH pollution and food safety concerns for which the developed method will be useful.

Development, Evaluation, and Application of Machine Learning Models for Accurate Prediction of Root Uptake of Per- and Polyfluoroalkyl Substances.

Machine learning (ML) models were developed for understanding the root uptake of per- and polyfluoroalkyl substances (PFASs) under complex PFAS-crop-soil interactions. Three hundred root concentration factor (RCF) data points and 26 features associated with PFAS structures, crop properties, soil properties, and cultivation conditions were used for the model development. The optimal ML model, obtained by stratified sampling, Bayesian optimization, and 5-fold cross-validation, was explained by permutation feature importance, individual conditional expectation plot, and 3D interaction plot. The results showed that soil organic carbon contents, pH, chemical logP, soil PFAS concentration, root protein contents, and exposure time greatly affected the root uptake of PFASs with 0.43, 0.25, 0.10, 0.05, 0.05, and 0.05 of relative importance, respectively. Furthermore, these factors presented the key threshold ranges in favor of the PFAS uptake. Carbon-chain length was identified as the critical molecular structure affecting root uptake of PFASs with 0.12 of relative importance, based on the extended connectivity fingerprints. A user-friendly model was established with symbolic regression for accurately predicting RCF values of the PFASs (including branched PFAS isomerides). The present study provides a novel approach for profound insight into the uptake of PFASs by crops under complex PFAS-crop-soil interactions, aiming to ensure food safety and human health.

CircVAPA exerts oncogenic property in non-small cell lung cancer by the miR-876-5p/WNT5A axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most fatal malignant tumors. Emerging studies have clarified the crucial roles of circular RNAs (circRNAs) in the tumorigenesis of cancers. CircVAPA was demonstrated to function in some human cancers. The present study aimed to investigate the role of circVAPA in NSCLC. METHODS: A quantitative real-time polymerase chain reaction was used to measure the expression of genes. Actinomycin D and RNase R were employed to examine the stability of circVAPA. Cell-counting kit-8, 5-ethynyl-2'-deoxyuridine, Transwell and sphere formation assays, and well as western blot analysis, were conducted to examine the changes of NSCLC cells in response to circVAPA knockdown. A luciferase reporter assay was conducted for the molecular mechanism. RESULTS: Our findings demonstrated high expression of circVAPA in tissues and cell lines of NSCLC. Knockdown of circVAPA had a suppressive effect on cell proliferation, migration, invasion and stemness, and also inhibited tumor growth in vivo. Mechanistically, circVAPA acted as a competing endogenous RNA to up-regulate WNT5A by sponging miR-876-5p. Moreover, circVAPA activated Wnt/ß-catenin signaling by up-regulation of WNT5A. Rescue assays showed that silencing of miR-876-5p or overexpression of WNT5A reversed the circVAPA knockdown-mediated inhibition on cellular processes in NSCLC. CONCLUSIONS: CircVAPA promotes aggressive phenotypes of NSCLC cells by the miR-876-5p/WNT5A axis activating Wnt/ß-catenin signaling.

Naturally occurring triterpene Lupane exerts anticancer effects on colorectal cancer cells via induction of apoptosis and autophagy and suppresses cell migration and invasion by targeting MMP-9.

PURPOSE: This study was undertaken with a purpose to examine the anticancer effects of Lupane against human colorectal cancer. METHODS: The SW48 colorectal cell line and CDD18Co normal colon cell line were used in this study. The CCK8 assay was used to determine cell proliferation while acridine orange (AO)/ethidium bromide (EB) and DAPI staining assays were used to detect apoptosis. Wound healing and transwell assays were used to detect the cell migration and invasion. Western blotting was used to determine protein expression. RESULTS: Lupane inhibited the proliferation of colorectal cancer cells and the level of inhibition followed dose-dependent pattern. The antiproliferative role of Lupane was exerted via induction of apoptotic cell death. Western blot showed that the expression of Bcl-2 was decreased and that of Bax was increaced. Lupane also prompted the autophagy of the SW48 colorectal cancer cells and enhanced the expression of LC3-II. However, the expression of p62 was depleted. The treatment of Lupane also resulted to inhibition of the migratory potential of cancer cells as revealed by the wound healing assay. The invasion of SW48 cancer cells was also suppressed and was associated with suppression of metalloproteinase-9 (MMP-9) expression. CONCLUSION: The results indicate the anticancer potential of Lupane against the colorectal cancer growth and propagation. The study envisages the importance of natural compounds for their usage against human cancers.

[Efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen in the treatment of HER2-positive advanced gastric cancer].

OBJECTIVE: To evaluate the safety and efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen (irinotecan plus 5-FU/LV) in the treatment of HER2-positive advanced gastric cancer. METHODS: T Thirty-four patients with pathologically confirmed advanced gastric cancer, all positive for the human epidermal growth factor receptor 2 (HER2) as identified by immunohistochemistry and fluorescence in situ hybridization, were randomized into the test group and control group to for treatment with the combined regimen and the FOLFIRI regimen alone, respectively. FOLFIRI regimen was administered every 2 weeks for 2 to 4 cycles. Trsatuzumab was given intravenously on a weekly basis with an initial dose of 4 mg/kg and a subsequent dose of 2 mg/kg. All the patients were assessed for efficacy and toxicity of the treatments. RESULTS: The overall response rate was 58.8% in the test group and 35.3% in the control group, with disease control rates of 88.2% and 64.7%, respectively, showing significant differences between the two groups (P<0.05). The most frequent grade I/II treatment-related adverse events included diarrhea, nausea/vomiting and neutropenia. CONCLUSION: Trsatuzumab combined with FOLFIRI regimen is effective, safe and well tolerated for treatment of HER2-positive advanced gastric cancer.