エイコサペンタエン酸はラットにおいて脳動脈瘤の増大を抑制する

京都大学0048新制・課程博士博士(医学)甲第22827号医博第4666号新制||医||1047(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 井上 治久, 教授 髙橋 良輔, 教授 Shohab YOUSSEFIAN学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells

Aerobic glycolysis is an emerging hallmark of many human cancers, as cancer cells are defined as a “metabolically abnormal system”. Carbohydrates are metabolically reprogrammed by its metabolizing and catabolizing enzymes in such abnormal cancer cells. Normal cells acquire their energy from oxidative phosphorylation, while cancer cells acquire their energy from oxidative glycolysis, known as the “Warburg effect”. Energy–metabolic differences are easily found in the growth, invasion, immune escape and anti-tumor drug resistance of cancer cells. The glycolysis pathway is carried out in multiple enzymatic steps and yields two pyruvate molecules from one glucose (Glc) molecule by orchestral reaction of enzymes. Uncontrolled glycolysis or abnormally activated glycolysis is easily observed in the metabolism of cancer cells with enhanced levels of glycolytic proteins and enzymatic activities. In the “Warburg effect”, tumor cells utilize energy supplied from lactic acid-based fermentative glycolysis operated by glycolysis-specific enzymes of hexokinase (HK), keto-HK-A, Glc-6-phosphate isomerase, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase, phosphofructokinase (PFK), phosphor-Glc isomerase (PGI), fructose-bisphosphate aldolase, phosphoglycerate (PG) kinase (PGK)1, triose phosphate isomerase, PG mutase (PGAM), glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase isozyme type M2 (PKM2), pyruvate dehydrogenase (PDH), PDH kinase and lactate dehydrogenase. They are related to glycolytic flux. The key enzymes involved in glycolysis are directly linked to oncogenesis and drug resistance. Among the metabolic enzymes, PKM2, PGK1, HK, keto-HK-A and nucleoside diphosphate kinase also have protein kinase activities. Because glycolysis-generated energy is not enough, the cancer cell-favored glycolysis to produce low ATP level seems to be non-efficient for cancer growth and self-protection. Thus, the Warburg effect is still an attractive phenomenon to understand the metabolic glycolysis favored in cancer. If the basic properties of the Warburg effect, including genetic mutations and signaling shifts are considered, anti-cancer therapeutic targets can be raised. Specific therapeutics targeting metabolic enzymes in aerobic glycolysis and hypoxic microenvironments have been developed to kill tumor cells. The present review deals with the tumor-specific Warburg effect with the revisited viewpoint of recent progress

Tribological characterization of dental restorative materials

Human teeth are exposed to a considerable amount of wear on a daily basis due to chemical and mechanical actions. To overcome the damage seen on natural teeth, the dental restorations have been widely used. Like teeth, the restorations are also submitted to shear stresses and, therefore, the evaluation of their tribological behaviour is essential. The aim of this study was to compare the wear behaviour of the main types of dental restorative materials used (polymers, composites and ceramics) under the same conditions. Among them was included a polychromatic feldspathic porcelain material which was selected to find out if the opacity or translucency influences the tribological behaviour of the material. The wear tests were performed in a reciprocating ball-on-plate tribometer under 37 °C using artificial saliva to mimic oral conditions as well as alumina balls as antagonists. Friction coefficient (COF) and specific wear rate values were determined, and SEM/EDS examinations were made to identify the dominant wear mechanisms. Results showed that zirconia exhibited the highest wear resistance, with an average value of specific wear rate of k = 1.63E-07 mm3N−1m−1, and this result was significantly different from that of other materials. Composite material presented the lowest wear resistance (k = 1.24E-05 mm3N−1m−1). The results indicated that the wear behaviour of ceramics can be affected by their optical properties, possibly associated with the crystal structure modifications. Specific wear rate and hardness have a statistically significant linear relationship. Zirconia revealed to be a potential material for constructing high wear-resistant dental restorations.This work was supported by Fundação para a Ciência e Tecnologia (FCT, Portugal) through the grant SFRH/BD/145421/2019 and the projects NORTE-01-0145-FEDER-000018-HAMaBICo, UID/EEA/ 04436/2019 and FunImp, POCI-01-0145-FEDER-030498