ヒト神経膠腫組織における細胞膜貫通型マトリックスメタロプロテアーゼ1,2,3の発現と組織内局在

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1370号，学位授与年月日：平成11年3月31日,学位授与年：199

新規細胞外マトリックス分解酵素阻害分子による神経膠芽腫浸潤抑制の試み

金沢大学附属病院【目的】我々は近年,gliomaの浸潤に関与する細胞外マトリックス分解酵素MT1-MMP (membrane type 1-matrix metalloproteinase)に対する抑制分子を脳細胞外マトリックスTestican family(TF)内に見出した(Cancer Res 61:8896-902,2001)。本研究ではTF間の相互作用およびヒトglioma組織におけるTFの発現および局在を検討した。【方法】MT1-MMP, MMP-2とともにTFの発現ベクターおよびdeletion mutantを293T細胞に遺伝子導入し,Zymographyと免疫沈降を行った。またWound assayによりglioma細胞株に対する浸潤抑制効果を検討した。Glioma 51例につき,ABI PRISM 7700を用いmRNA発現量を計測した。またin situ hybridizationを行った。【結果】MT1-MMP阻害効果を有しないT-2は同効果を有するT-1,T-3,N-Tesと結合することによりその働きを阻害することが分かった。その結合サイトはT-1,T-3,N-Tesのextracellular calcium binding (EC) domainとT-2のunique domainであった。N-TesのEC domainを欠失した変異体(Δ122)はMT1-MMPを抑制し,かつT-2との結合を逃れた。Wound assayの結果もこれと矛盾しない所見であった。またTFの発現量はいずれもglioblastomaで有意に低く,その局在はneuronで強く,腫瘍細胞では弱かった。発現量はTFのうちT-2で最も高かった。【結論】脳組織内に比較的多量に存在するT-2はT-1,T-3,N-TesのMT1-MMP阻害能を解除することによって浸潤を促進させる。Δ122は抗浸潤治療の候補分子になり得ることが示唆された。研究課題/領域番号:14770707, 研究期間(年度):2002-2003出典：「新規細胞外マトリックス分解酵素阻害分子による神経膠芽腫浸潤抑制の試み」研究成果報告書　課題番号14770707（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-14770707/)を加工して作

Timber industries and licensing system in Malaysia

This paper discusses the licensing system of Malaysia's sawmilling and plywood industries which has grown in tandem with the massive land development program begun in the 1960s. Since then, the industry has contributed a significant amount of government revenue, employment opportunities and foreign exchange. Progressive development of the sector has been underpinned by various governmental policies and regulations to nurture legal timber supplies for down-stream processing as well as developing secondary and tertiary processing industries. Policies provide various incentives to modernize the industries in order to upgrade processing efficiency, diversification into value-added and quality products and reduction of processing residues. This includes wider use of the under-utilized timber species as part of an effort to attain a rational balance between national processing capacity and resource availability. Various strategies have been targeted to enhance efficient utilization of all forms of forest products from legal sources. In addition, timber production and licensing are now closely monitored and regulated throughout the supply chain management

Incompressible Liquid Based Force Sensible Silicone Retractor Attachable to Surgical Suction Instruments

This paper presents a silicone retractor, which is a continuation and extension of a previously developed system that had the same three functions as the old version: 1) retracting, 2) suction, and 3) force sensing. These features make the retractor a safe choice for use in neurosurgery. Suction is achieved by attaching the retractor to a suction pipe. The retractor has a deformation area filled with an incompressible liquid that is displaced in proportion to the extent of deformation; fiberscopes or human eyes detecting the displacement get a visual representation of the force. The new design improves on the old one in three ways—miniaturization, made possible by the incompressible-liquid-based mechanism, and measurement of force distribution by distribution of the areas deformed by force. The system was validated by conducting experiments

Haptic threshold for pulling force feedback on surgeon\u27s fingertip in medical robotic systems

The human fingertip has very high density of the receptor to accept sense of touch stimulation. The corresponding somatic sensory area in a brain is very large, and considered to be a specialized part for palpation. A lot of haptic display system then have been developed with the investigation of human haptic perception. However, the researches about the human perception for pulling force at grasping, namely static frictional force are limited. This paper investigated it, aiming at a future development of pulling and grasping force feedback system for neurosurgical robotic systems. For the purpose, this paper explored the possibility of displaying pulling force to an index finger during grasping. The absolute and difference thresholds for pulling sense were the targets. The results showed that grasping disturbs the pulling sense, and the sides of index fingertip can be used to display pulling sense, relatively large force, namely scaled force feedback is required for the perception. The results provide an important insight at a hardware and controller design of force feedback systems. © 2016 IEEE.42nd Conference of the Industrial Electronics Society, IECON 2016; Palazzo dei CongressiFlorence; Italy; 24 October 2016 through 27 October 2016; Category numberCFP16IEC-ART; Code 12554

Drug Repositioning for the Treatment of Glioma: Current State and Future Perspective

Gliomas are the most common primary brain tumors. Among them, glioblastoma (GBM) possesses the most malignant phenotype. Despite the current standard therapy using an alkylating anticancer agent, temozolomide, most patients with GBM die within 2 years. Novel chemotherapeutic agents are urgently needed to improve the prognosis of GBM. One of the solutions, drug repositioning, which broadens the indications of existing drugs, has gained attention. Herein, we categorize candidate agents, which are newly identified as therapeutic drugs for malignant glioma into 10 classifications based on these original identifications. Some drugs are in clinical trials with hope. Additionally, the obstacles, which should be overcome in order to accomplish drug repositioning as an application for GBM and the future perspectives, have been discussed

Fluorescence intensity and bright spot analyses using a confocal microscope for photodynamic diagnosis of brain tumors

Background In photodynamic diagnosis using 5-aminolevulinic acid (5-ALA), discrimination between the tumor and normal tissue is very important for a precise resection. However, it is difficult to distinguish between infiltrating tumor and normal regions in the boundary area. In this study, fluorescent intensity and bright spot analyses using a confocal microscope is proposed for the precise discrimination between infiltrating tumor and normal regions. Methods From the 5-ALA-resected brain tumor tissue, the red fluorescent and marginal regions were sliced for observation under a confocal microscope. Hematoxylin and eosin (H&E) staining were performed on serial slices of the same tissue. According to the pathological inspection of the H&E slides, the tumor and infiltrating and normal regions on confocal microscopy images were investigated. From the fluorescent intensity of the image pixels, a histogram of pixel number with the same fluorescent intensity was obtained. The fluorescent bright spot sizes and total number were compared between the marginal and normal regions. Results The fluorescence intensity distribution and average intensity in the tumor were different from those in the normal region. The probability of a difference from the dark enhanced the difference between the tumor and the normal region. The bright spot size and number in the infiltrating tumor were different from those in the normal region. Conclusions Fluorescence intensity analysis is useful to distinguish a tumor region, and a bright spot analysis is useful to distinguish between infiltrating tumor and normal regions. These methods will be important for the precise resection or photodynamic therapy of brain tumors. © 2016 Elsevier B.V.Embargo Period 12 month