ROCK as a Therapeutic Target of Diabetic Retinopathy

The increasing global prevalence of diabetes is a critical problem for public health. In particular, diabetic retinopathy, a prevalent ocular complication of diabetes mellitus, causes severe vision loss in working population. A better understanding of the pathogenesis and the development of new pharmacologic treatments are needed. This paper describes the relevance between Rho/ROCK pathway and the pathogenesis of diabetic retinopathy from its early to late stages. Moreover, the therapeutic potential of ROCK inhibitor in the total management of diabetic retinopathy is discussed

A Comprehensive and Versatile Multimodal Deep Learning Approach for Predicting Diverse Properties of Advanced Materials

We present a multimodal deep learning (MDL) framework for predicting physical properties of a 10-dimensional acrylic polymer composite material by merging physical attributes and chemical data. Our MDL model comprises four modules, including three generative deep learning models for material structure characterization and a fourth model for property prediction. Our approach handles an 18-dimensional complexity, with 10 compositional inputs and 8 property outputs, successfully predicting 913,680 property data points across 114,210 composition conditions. This level of complexity is unprecedented in computational materials science, particularly for materials with undefined structures. We propose a framework to analyze the high-dimensional information space for inverse material design, demonstrating flexibility and adaptability to various materials and scales, provided sufficient data is available. This study advances future research on different materials and the development of more sophisticated models, drawing us closer to the ultimate goal of predicting all properties of all materials.Comment: 38 pages, 17 figures, 1 tabl

Comprehensive Analysis of Inflammatory Immune Mediators in Vitreoretinal Diseases

Inflammation affects the formation and the progression of various vitreoretinal diseases. We performed a comprehensive analysis of inflammatory immune mediators in the vitreous fluids from total of 345 patients with diabetic macular edema (DME, n = 92), proliferative diabetic retinopathy (PDR, n = 147), branch retinal vein occlusion (BRVO, n = 30), central retinal vein occlusion (CRVO, n = 13) and rhegmatogenous retinal detachment (RRD, n = 63). As a control, we selected a total of 83 patients with either idiopathic macular hole (MH) or idiopathic epiretinal membrane (ERM) that were free of major pathogenic intraocular changes, such as ischemic retina and proliferative membranes. The concentrations of 20 soluble factors (nine cytokines, six chemokines, and five growth factors) were measured simultaneously by multiplex bead analysis system. Out of 20 soluble factors, three factors: interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all groups of vitreoretinal diseases (DME, PDR, BRVO, CRVO, and RRD) compared with control group. According to the correlation analysis in the individual patient's level, these three factors that were simultaneously increased, did not show any independent upregulation in all the examined diseases. Vascular endothelial growth factor (VEGF) was significantly elevated in patients with PDR and CRVO. In PDR patients, the elevation of VEGF was significantly correlated with the three factors: IL-6, IL-8, and MCP-1, while no significant correlation was observed in CRVO patients. In conclusion, multiplex bead system enabled a comprehensive soluble factor analysis in vitreous fluid derived from variety of patients. Major three factors: IL-6, IL-8, and MCP-1 were strongly correlated with each other indicating a common pathway involved in inflammation process in vitreoretinal diseases

Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer

Survivin is a member of the inhibitor of apoptosis protein (IAP) family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL) recognized by CD8+ cytotoxic T lymphocytes (CTLs). We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2), general malaise (grade 1), and fever (grade 1). No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9) decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer

当院における便潜血陽性者に対する大腸CT(CTコロノグラフィー)検査の有用性:大腸がん検診への導入と課題

大腸がん検診におけるスクリーニング検査としての大腸CT(CT colonography: CTC)検査の有用性を検討するために,当院における便潜血陽性者に対するCTCと大腸内視鏡検査の精度比較を行った.2009年7月から2014年1月までに川崎医科大学附属病院で施行されたCTC検査673件中,スクリーニング目的で行われた411件の中で便潜血陽性者に対して行われた183名を対象とした.全例CTC検査と同日に全大腸内視鏡検査も行った.対象とする病変は内視鏡観察あるいは病理組織学的に腺腫,がんと診断されたものとした.CTCの前処置は,経口腸管洗浄剤に水溶性造影剤による標識(タギング)を付けて行った.CT装置は16列Multi-slice CT(MSCT),腸管拡張は自動炭酸ガス注入器を使用した.CTC読影は,まず仮想内視鏡(3D)で行い,後に多断面再構成像(Multi-planar reconstruction: MPR 像(2D))を行う3D primary 法で行った.183名(男性98名,女性85名,年齢40～86歳,平均年齢62.1歳±0.8歳)のうち,病変を認めなかったのは87名(47.5%)であり,病変を認めたのは96名(53%)であった.総病変数は191個であり,うち6mm以上の病変は77個(40%)で,そのうち10mm以上のものは46個(24%)であった.大腸癌は25例(全病変中13%)で,うち腺腫内癌16例(全病変中8%)であった.側方発育型腫瘍は8例(4%)(大きさ平均17mm)であった.病変のうち,内視鏡的切除が行われたものは34病変であり,手術が行われたものは22病変であった.病変形態別による描出率は隆起型病変80%で,平坦型病変65%であった.病変サイズ別の精度は10mm以上の病変(n=46)で感度96%,陽性適中率98%であり,6mm以上の病変(n=77)で感度83%,陽性適中率79%であった.CTCは便潜血陽性者において良好な精度を示し,大腸がんスクリーニング法としての可能性がある.The purpose of this study was to estimate the sensitivity and specificity of CT colonography (CTC) for colorectal cancer screeing following positive fecal occult blood test (FOBT) in Japan. To compare detection rates of colorectal cancer and adenoma between CTC and optical total colonoscopy (TCS). This study included 183 patients with positive result of FOBT in Japanese colorectal cancer screening program. The patients had both CTC and TCS on the same day. 96 patients (53%) had colorectal lesions, on the other hand 87 patients had no lesions. The total number of lesions was 191, including 77 lesions 6 mm in maximum diameter and larger, including 46 lesions 10 mm and larger

Antiangiogenic drugs in the management of ocular diseases: Focus on antivascular endothelial growth factor

Yukio Sassa, Yasuaki HataDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanAbstract: Age-related macular degeneration (AMD) complications are the leading cause of severe vision loss among the aging population in the many western countries. The introduction of molecular inhibitors of vascular endothelial growth factor (VEGF), such as pegaptanib, ranibizumab, and bevacizumab, as treatments for wet AMD has provided new hope for affected patients. Now we have these treatment options, which have the possibility to improve or maintain visual acuity for patients suffering from AMD. The treatment needs to be optimized and this is in progress. Based on emerging evidence, adopting a variable VEGF inhibitor-dosing strategy guided by visual acuity assessment and optical coherence tomography are now being tried to reduce the frequency of injections. VEGF inhibitors in combination with photodynamic therapy are another way to optimize treatment. Physicians are waiting for new guidelines for the management of AMD and the results of current and upcoming trials systematically addressing these issues will be expected to provide it.Keywords: age-related macular degeneration, VEGF inhibitor, verteporfin, pegaptanib, ranibizumab, bevacizuma