A Low Advanced Lung Cancer Inflammation Index Predicts a Poor Prognosis in Patients With Metastatic Non–Small Cell Lung Cancer

Introduction: Inflammation plays a crucial role in cancers, and the advanced lung cancer inflammation index (ALI) is considered to be a potential factor reflecting systemic inflammation.Objectives: This work aimed to explore the prognostic value of the ALI in metastatic non–small cell lung cancer (NSCLC) and classify patients according to risk and prognosis.Methods: We screened 318 patients who were diagnosed with stage IV NSCLC in Hubei Cancer Hospital from July 2012 to December 2013. The formula for ALI is body mass index (BMI, kg/m2) × serum albumin (Alb, g/dl)/neutrophil–lymphocyte ratio (NLR). Categorical variables were analyzed by the chi-square test or Fisher’s exact test. The overall survival (OS) rates were analyzed by the Kaplan–Meier method and plotted with the R language. A multivariate Cox proportional hazard model was used to analyze the relationship between ALI and OS.Results: According to the optimal cut-off value determined by X-tile software, patients were divided into two groups (the ALI <32.6 and ALI ≥32.6 groups), and the median OS times were 19.23 and 39.97 months, respectively (p < 0.01). A multivariable Cox regression model confirmed that ALI and chemotherapy were independent prognostic factors for OS in patients with NSCLC. OS in the high ALI group was better than that in the low ALI group (HR: 1.39; 95% CI: 1.03–1.89; p = 0.03).Conclusions: Patients with a low ALI tend to have lower OS among those with metastatic NSCLC, and the ALI can serve as an effective prognostic factor for NSCLC patients.

The advanced lung cancer inflammation index predicts outcomes of patients with non-small cell lung cancer following video-assisted thoracic surgery

Objective The advanced lung cancer inflammation index (ALI) predicts overall survival (OS) in patients with advanced lung cancer. However, few studies have tested ALI’s prognostic effect in patients with non-small cell lung cancer (NSCLC) following video-assisted thoracic surgery (VATS), especially patients at stage III. This study investigated the relationship between ALI and outcomes of patients with NSCLC following VATS. Methods We retrospectively examined 339 patients with NSCLC who underwent VATS at Hebei General Hospital, China. Preoperative clinical and laboratory parameters were collected and analyzed. Optimal cutoff values of potential prognostic factors, including ALI, were determined. Kaplan–Meier and Cox regression analyses were used to determine each factor’s prognostic value. Results The median OS was 31 months. The optimal cutoff value for ALI was 41.20. Patients with high ALI (≥41.20) displayed increased OS (33.87 vs. 30.24 months), higher survival rates, and milder clinical characteristics. Univariate and multivariate analyses showed a significant correlation between ALI and the prognosis of patients with NSCLC, including those at stage IIIA, who underwent VATS. Conclusions Low ALI correlated with poor outcomes in patients with NSCLC following VATS. Preoperative ALI might be a potential prognostic biomarker for patients with NSCLC following VATS, including patients at stage IIIA.

Fluorinated rhamnosides inhibit cellular fucosylation

The sugar fucose is expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis via competitive GMDS inhibition. We demonstrate that cell permeable fluorinated rhamnose 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.

Advanced Lung Cancer Inflammation Index Predicts Survival Outcomes of Patients With Oral Cavity Cancer Following Curative Surgery

AimThe aim of our study was to investigate the prognostic value of preoperative advanced lung cancer inflammation index (ALI) and to establish prognostic nomograms for the prediction of survival outcomes in patients with oral cavity squamous cell carcinoma (OSCC).Materials and MethodsA total of 372 patients who received primary curative surgery for OSCC during 2008–2017 at a tertiary referral center were enrolled. We used the receiver operating characteristic curve to determine the optimal cutoff point of ALI. Through a Cox proportional hazards model and Kaplan–Meier analysis, we elucidated the ALI–overall survival (OS) and ALI–disease-free survival (DFS) associations. Prognostic nomograms based on ALI and the results of multivariate analysis were created to predict the OS and DFS. We used the concordance indices (C-indices) and calibration plots to assess the discriminatory and predictive ability.ResultsThe results revealed that the ALI cutoff was 33.6, and 105 and 267 patients had ALI values of <33.6 and ≥33.6, respectively. ALI < 33.6 significantly indicated lower OS (44.0% vs. 80.1%, p < 0.001) and DFS (33.6% vs. 62.8%; p < 0.001). In multivariate analysis, ALI < 33.6 was independently associated with poor OS and DFS (both p < 0.001). The C-indices of established nomograms were 0.773 and 0.674 for OS and DFS, respectively; moreover, the calibration plots revealed good consistency between nomogram-predicted and actual observed OS and DFS.ConclusionALI is a promising prognostic biomarker in patients undergoing primary surgery for OSCC; moreover, ALI-based nomograms may be a useful prognostic tool for individualized OS and DFS estimations.

Alpha-Ketoglutarate: A Potential Inner Mitochondrial and Cytosolic Protector against Peroxynitrite and Peroxynitrite-Induced Nitration?

The generation of peroxynitrite (ONOO−) is associated with several diseases, including atherosclerosis, hypertension, neurodegeneration, cancer, inflammation, and sepsis. Alpha-ketoglutarate (αKG) is a known potential highly antioxidative agent for radical oxidative species such as peroxides. The question arises as to whether αKG is also a potential scavenger of ONOO− and a potential protector against ONOO−-mediated nitration of proteins. NMR studies of 1 mM αKG in 100 mM phosphate-buffered saline at pH 7.4 and pH 6.0 were carried out in the presence or absence of a final concentration of 2 mM ONOO−. An ONOO−–luminol-induced chemiluminescence reaction was used to measure the scavenging function of several concentrations of αKG; quantification of αKG was performed via spectrophotometric enzymatic assay of αKG in the absence or presence of 0, 1, or 2 mM ONOO−. The nitration of tyrosine residues on proteins was measured on ONOO−-treated bovine serum albumin (BSA) in the presence or absence of 0–24 mM αKG by an ELISA technique using a specific anti-IgG against nitro-tyrosine. The addition of ONOO− to αKG led to the formation of succinic acid and nitrite at pH 7.0, but not at pH 6.0, as αKG was stable against ONOO−. The absorbance of enzymatically estimated αKG at the time point of 30 min was significantly lower in favour of ONOO− (1 mM: 0.21 ± 0.03, 2 mM: 0.12 ± 0.05 vs. 0 mM: 0.32 ± 0.02; p < 0.001). The luminol technique showed an inverse logarithmic correlation of the ONOO− and αKG concentrations (y = −2 × 105 ln(x) + 1 × 106; r2 = 0.99). The usage of 4 mM αKG showed a significant reduction by nearly half in the chemiluminescence signal (284,456 ± 29,293 cps, p < 0.001) compared to the control (474,401 ± 18,259); for 20 and 200 mM αKG, there were further reductions to 163,546 ± 26,196 cps (p < 0.001) and 12,658 ± 1928 cps (p < 0.001). Nitrated tyrosine residues were estimated using the ELISA technique. A negative linear correlation was obtained by estimating nitrated tyrosine residues in the presence of αKG (r2 = 0.94): a reduction by half of nitrated tyrosine was estimated using 12 mM αKG compared to the control (326.1 ± 39.6 nmol vs. 844.5 ± 128.4 nmol; p < 0.001).