Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma.

BACKGROUNDPatients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI.RESULTSThe MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately.CONCLUSIONMuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.

Vitamin B6 prevents excessive inflammation by reducing accumulation of sphingosine-1-phosphate in a sphingosine-1-phosphate lyase-dependent manner.

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti-inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti-inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine-1-phosphate (S1P) in a S1P lyase (SPL)-dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro-inflammatory cytokines by suppressing nuclear factor-κB and mitogen-activated protein kinases signalling pathways. Furthermore, vitamin B6-reduced accumulation of S1P by promoting SPL activity. The anti-inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti-inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.

Evaluation of the efficacy and safety of elemene in treating malignant pleural effusion caused by tumors: A PRISMA guided meta-analysis.

OBJECTIVE: Elemene is widely used to treat malignant pleural effusion in China. This meta-analysis aimed to evaluate the efficacy and safety of elemene in treating malignant pleural effusion. METHODS: Electronic databases including Pubmed, the Cochrane Library, Embase and Chinese biomedical literature database were searched until March 2017. Clinical controlled trials (CCTs) assessing the efficacy and safety of elemene in the treatment of malignant pleural effusion were included. The quality of the included studies was evaluated using the quality evaluation criteria of the Cochrane Handbook version 5.1.0. RESULTS: A total of 46 CCTs were included, with 2992 patients. Results of meta-analysis showed that elemene significantly improved the overall response rate (ORR) in controlling malignant pleural effusion (risk ratio [RR] = 1.16; 95% CI: 1.08-1.23; P < .05). Subgroup results showed that the ORR of elemene in the treatment of lung cancer patients with malignant pleural effusion (RR = 1.20, 95% CI: 1.07-1.34; P < .05) was higher than that of other cancers (RR = 1.14, 95% CI: 1.05-1.23; P < .05). Meanwhile, elemene did not significantly increase the incidences of chest pain and fever (P > .05). CONCLUSION: Elemene is suggested to have the ability of improving the treatment outcome of malignant pleural effusion with acceptable safety.

Antioxidant and anti-inflammatory activities of Radix Isatidis polysaccharide in murine alveolar macrophages.

Radix Isatidis is an official herbal medicine for treatment of infection and inflammation in China. In this study, a novel heteropolysaccharide (RIWP) was isolated from R. Isatidis through DEAE Sepharose Fast Flow column and Sepharose CL-6B column. RIWP had a molecular weight of 57 kDa and was mainly composed of glucose, galactose and arabinose with a relative molar ratio of 2.0:1.1:1.0. The cytoprotective, antioxidant and anti-inflammatory properties of RIWP in lipopolysaccharide (LPS) stimulated murine alveolar macrophages were first reported here. Pretreatment with RIWP was found to potently prolong cell survival and repress the generation of reactive oxygen species (ROS) and lipid peroxidation after LPS-stimulation in murine alveolar macrophages. Furthermore antioxidant status was significantly deteriorated in the LPS-treated alveolar macrophages, such as low superoxide dismutase (SOD) activity and G-SH content, which was effectively restored by RIWP supplementation. More importantly, RIWP significantly suppressed LPS-induced increase in nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production in murine alveolar macrophages. Additionally RIWP recovered mitochondrial membrane potential to normal conditions. All above response to LPS stimulation behaved in a concentration-dependent manner. This study provided evidences that RIWP appears to have the potential to prevent inflammatory disease in lung.