Kagawa University

About: Kagawa University is a education organization based out in Takamatsu, Japan. It is known for research contribution in the topics: Cancer & Population. The organization has 6028 authors who have published 11918 publications receiving 224111 citations. The organization is also known as: Kagawa Daigaku.

Bevacizumab for malignant gliomas: current indications, mechanisms of action and resistance, and markers of response.

Abstract: Vascular endothelial growth factor (VEGF) is an attractive target of antiangiogenic therapy in glioblastomas. Bevacizumab (Bev), a humanized anti-VEGF antibody, is associated with the improvement of progression-free survival and performance status in patients with glioblastoma. However, randomized trials uniformly suggest that these favorable clinical effects of Bev do not translate into an overall survival benefit. The mechanisms of action of Bev appear to include the inhibition of tumor angiogenesis, as well as indirect effects such as the depletion of niches for glioma stem cells and stimulation of antitumor immunity. Although several molecules/pathways have been reported to mediate adaptation and resistance to Bev, including the activation of alternative pro-angiogenic pathways, the resistance mechanisms have not been fully elucidated; for example, the mechanism that reinduces tumor hypoxia remains unclarified. The identification of imaging characteristics or biomarkers predicting the response to Bev, as well as the better understanding of the mechanisms of action and resistance, is crucial to improve the overall clinical outcome and optimize individual therapy. In this article, the authors review the results of important clinical trials/studies, the current understanding of the mechanisms of action and resistance, and the knowledge of imaging characteristics and biomarkers predicting the response to Bev.

Fusarium toxins in wheat from an area in Henan Province, PR China, with a previous human red mould intoxication episode.

Abstract: Wheat samples of the 1998 and 1999 crops from Puyang, an area in Henan Province, PR China with a previous human red mould intoxication episode, were analysed for trichothecenes and zearalenone (ZEA). For the 1998 Puyang crop, deoxynivalenol (DON) was the predominant toxin detected abundantly and frequently at a level of up to 14000 μgkg-1 (mean 2850 μgkg-1) in 30 of 31 (97%) wheat samples. Among these were 21 (70%) with a DON level that exceeded the Chinese regulation of 1000 μgkg-1. Nivalenol (NIV) and 15-acetyl-DON (15-ADON) were also found at 578 μgkg-1 (one sample) and 59–1800 μgkg-1 (mean 365 μgkg-1, 20 samples), respectively. ZEA co-occurred in 21 samples at 9–1400 μgkg-1 (mean 209 μgkg-1). Twenty-five (89%) wheat samples from Zhumadian, a region without a history of human red mould intoxication in the same province, contained low levels of DON (53–1240, mean 223 μgkg-1) with seven (25%) co-contaminated with ZEA (10–217, mean 108 μgkg-1). All were free from 15-ADON and NIV. Significant differences i...

Megalin-Mediated Tubuloglomerular Alterations in High-Fat Diet–Induced Kidney Disease

Abstract: Obesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)-induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control littermates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion. These were ameliorated in HFD-fed megalin KO mice, even though these mice had the same levels of obesity, dyslipidemia, and hyperglycemia as HFD-fed control mice. Intravital renal imaging of HFD-fed wild-type mice also demonstrated the accumulation of autofluorescent lipofuscin-like substances in PTECs of the S2 segment, accompanied by focal narrowing of tubular lumens and peritubular capillaries. In cultured PTECs, fatty acid-rich albumin induced the increased expression of genes encoding PDGF-B and monocyte chemoattractant protein-1 via megalin, with large (auto)lysosome formation, compared with fatty acid-depleted albumin. Collectively, the megalin-mediated endocytic handling of glomerular-filtered (lipo)toxic substances appears to be involved primarily in hypertrophic and senescent PTEC injury with autophagy impairment, causing peritubular capillary damage and retrograde glomerular alterations in HFD-induced kidney disease. Megalin could be a therapeutic target for obesity/MetS-related CKD, independently of weight, dyslipidemia, and hyperglycemia modification.

Dual-Site Recognition of Different Extracellular Matrix Components by Anti-Angiogenic/Neurotrophic Serpin, PEDF

Abstract: Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor (serpin) superfamily, possesses anti-angiogenic and neurotrophic activities. PEDF has been reported to bind to extracellular matrix (ECM) components such as collagens and glycosaminoglycans (GAGs). In this study, to determine the binding sites for collagens and GAGs, we analyzed the interaction of recombinant mouse PEDF (rPEDF) with collagen I and heparin. By utilizing residue-specific chemical modification and site-directed mutagenesis techniques, we revealed that the acidic amino acid residues on PEDF (Asp255, Asp257, and Asp299) are critical to collagen binding, and three clustered basic amino acid residues (Arg145, Lys146, and Arg148) are necessary for heparin binding. Mapping of these residues on the crystal structure of human PEDF (Simonovic, M., Gettins, P. G. W., and Volz, K. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 11131−11135) demonstrated that the collagen-binding site is oriented toward the opposite side of the...