Kumamoto University

About: Kumamoto University is a education organization based out in Kumamoto, Kumamoto, Japan. It is known for research contribution in the topics: Cancer & Population. The organization has 19602 authors who have published 35513 publications receiving 901260 citations. The organization is also known as: Kumamoto Daigaku.

Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics

Abstract: Cysteine hydropersulfide (CysSSH) occurs in abundant quantities in various organisms, yet little is known about its biosynthesis and physiological functions. Extensive persulfide formation is apparent in cysteine-containing proteins in Escherichia coli and mammalian cells and is believed to result from post-translational processes involving hydrogen sulfide-related chemistry. Here we demonstrate effective CysSSH synthesis from the substrate L-cysteine, a reaction catalyzed by prokaryotic and mammalian cysteinyl-tRNA synthetases (CARSs). Targeted disruption of the genes encoding mitochondrial CARSs in mice and human cells shows that CARSs have a crucial role in endogenous CysSSH production and suggests that these enzymes serve as the principal cysteine persulfide synthases in vivo. CARSs also catalyze co-translational cysteine polysulfidation and are involved in the regulation of mitochondrial biogenesis and bioenergetics. Investigating CARS-dependent persulfide production may thus clarify aberrant redox signaling in physiological and pathophysiological conditions, and suggest therapeutic targets based on oxidative stress and mitochondrial dysfunction.

Increased Adiponectin Secretion by Highly Purified Eicosapentaenoic Acid in Rodent Models of Obesity and Human Obese Subjects

Abstract: Objectives— Fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) or n-3 PUFAs have been shown to reduce the incidence of coronary heart disease. Here we investigated the effect of highly purifi...

Immunoreactive Hepatocyte Growth Factor Is a Strong and Independent Predictor of Recurrence and Survival in Human Breast Cancer

Abstract: Hepatocyte growth factor (HGF) is a stromally derived modulator of epithelial cell proliferation and motility. In the present study, we have measured immunoreactive (ir)-HGF concentration in tumor extracts of 258 primary human breast cancers using an enzyme-linked immunosorbent assay and have evaluated its association with disease-free and overall survival. The median value of ir-HGF concentration was 11.0 ng/100 mg protein (range, 1.4-566.7 ng/100 mg protein). Correlation analyses between ir-HGF concentration and clinicopathological factors showed that the ir-HGF level was correlated only with tumor size (P = 0.05). No significant associations were found between ir-HGF content and age, menopausal status, nodal status, histological type, histological grade, vessel involvement, estrogen receptor, progesterone receptor, type of surgery, or postoperative adjuvant therapy. Breast cancer patients with high ir-HGF concentration had a significantly shorter relapse-free (P = 0.001) and overall survival (P = 0.001) rate when compared to those with low ir-HGF concentration at the cutoff point of 21.7 ng/100 mg protein, which was determined in another group of 82 patients. In multivariate analysis, ir-HGF level was found to be the most important independent factor in predicting relapse-free and overall survival, of greater import than lymph node involvement. The putative role of HGF in breast cancer growth and metastasis is hereby strengthened.

Pharmaceutical Strategies Utilizing Recombinant Human Serum Albumin

Abstract: Gene manipulation techniques open up the possibility of making recombinant human serum albumin (rHSA) or mutants with desirable therapeutic properties and for protein fusion products. rHSA can serve as a carrier in synthetic heme protein, thus reversibly carrying oxygen. Myristoylation of insulin results in a prolonged half-life because of self aggregation and increased albumin binding. Preferential albumin uptake by tumor cells serves as the basis for albumin-anticancer drug conjugate formulation. Furthermore, drug targeting can be achieved by incorporating drugs into albumin microspheres whereas liver targeting can be achieved by conjugating drug with galactosylated or mannosylated albumin. Microspheres and nanoparticles of different sizes can, with or without drugs and/or radioisotopes, be used for drug delivery or diagnostic purposes. In vivo implantation of albumin fusion protein expressing cells encapsulated in HSA-alginate coated beads showed promising results compared to organoids in rats. Chimeric peptide strategy with cationized albumin as the transport can deliver drugs via receptor mediated transcytosis through the blood brain barrier. Gene bearing, albumin microbubbles containing ultrasound contrast agents can non-invasively deliver gene after destruction by ultrasound. Various site-directed mutants of HSA can be tailor made depending on the application required.