The Overall Efficacy and Outcomes of Metronomic Tegafur-Uracil Chemotherapy on Locally Advanced Head and Neck Squamous Cell Carcinoma: A Real-World Cohort Experience.

Metronomic chemotherapy inhibits tumor growth by continuous administration of lower-dose chemotherapy. Our study aimed to demonstrate the outcomes of metronomic chemotherapy with tegafur-uracil in locally advanced head and neck squamous cell carcinoma (LA HNSCC). This was a retrospective study including 240 patients with LA HNSCC. After standard treatment, 96 patients were further treated with metronomic tegafur-uracil, and 144 patients were not. No statistical differences were found between both groups with regard to sex, clinical stage, or primary treatment choice. There were more hypopharyngeal cancers and more patients with poor clinicopathological features, including lymphovascular invasion, extranodal extension, and positive margins in the tegafur-uracil group. The median follow-up duration was 31.16 months. Overall survival (OS) was not reached in the tegafur-uracil group and was 54.1 months in the control group (p = 0.008). The median disease-free survival (DFS) was 54.5 months in the tegafur-uracil group and 34.4 months in the control group (p = 0.03). Neither group reached distant metastasis-free survival (DMFS, p = 0.02). In patients with LA HNSCC, adding tegafur-uracil as metronomic chemotherapy after either curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved the OS, DFS, and DMFS with tolerable adverse events.

Investigation of the mechanism of beta-amyloid fibril formation by kinetic and thermodynamic analyses.

Extracellular beta-amyloid (A beta) deposit is considered as one of the primary factors that induce Alzheimer's disease (AD). The effects of various environmental factors, including temperature, ionic strength, and pH, on A beta (1-40) aggregation mechanisms were investigated in this study by spectrometry, isothermal titration calorimetry (ITC), and hydrophobic fluorescence assay. In the aggregation process, the secondary structure of A beta (1-40) transforms to the beta-sheet conformation, which could be described as a two-state model. As the temperature and ionic strength increase, the conformation of A beta converts to the beta-sheet structure with an increased rate. Results of circular dichroism monitoring demonstrate that the rate constant of nucleation is smaller than that of elongation, and the nucleation is the rate-determining step during the overall A beta aggregation. The beta-sheet structure was stabilized by hydrophobic forces, as revealed by the ITC measurements. The different structural aggregates and forming pathways could be identified and discriminated at high and low ionic strengths, resulting in distinctive fibril conformations. Furthermore, the thermodynamic analysis shows that hydrophobic interaction is the major driving force in the nucleation step. Our study provides an insight into the discriminative mechanisms of beta-amyloid aggregation via kinetics and thermodynamics, especially the first reported thermodynamics information obtained by ITC.

Kinetics and enthalpy measurements of interaction between beta-amyloid and liposomes by surface plasmon resonance and isothermal titration microcalorimetry.

The objective of this research is to understand the interaction mechanism of beta-amyloid (Abeta) with cell and were basically divided into two parts. The first part focused on the time-dependent structural changes of Abeta (1-40) by circular dichroism (CD) spectroscopy, thioflavin T (ThT) fluorescence assay, and atomic force microscopy (AFM). The second part emphasized the kinetics and enthalpy of interaction between Abeta (1-40) and liposome by surface plasmon resonance (SPR) and isothermal titration microcalorimetry (ITC). Results obtained from CD, ThT and AFM confirmed the formation of 1 microm fibril after single day incubation. The driving force of kinetic interaction between Abeta and liposomes was revealed by SPR to be electrostatics. Further studies indicated that fresh Abeta has high GM1 affinity. Besides, addition of cholesterol to the liposome could alter membrane fluidity and affect the interactions of fresh Abeta with liposomes especially in the amount of Abeta absorbed and preserving the structure of liposome after adsorbing. Hydrophobicity was found to be the driving force leading to the interaction between Abeta fibrils and liposomes. These reactions are endothermic as supported by ITC measurements. When the composition of liposomes is zwitterionic lipids, the interaction of Abeta with liposomes is predominantly hydrophobic force. In contrast, the driving force of interaction of charged lipids with Abeta is electrostatic.