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Bioorthogonal approach for functional peptides and proteins
( Yoshihiro Ito ) 한국공업화학회 2016 한국공업화학회 연구논문 초록집 Vol.2016 No.1
A wide variety of different biomaterials are currently employed in medical applications throughout the world. Research towards the development of new biomaterials has traditionally focused on the preparation of functional materials capable of the simple adhesion of cells or the connection of tissues to metals and ceramics. There is a growing interest in the development of biomaterials involving the immobilization of growth factors, which would allow these artificial materials to regulate specific cellular functions, including the gene expression processes associated with cell growth and differentiation. In order to design growth factor proteins which can adhere these artificial materials, bioorthogonal approaches inspired by underwater adhesive proteins have recently been employed.
Current Status of the Diagnosis and Management of Pancreatic Neuroendocrine Tumors in Japan
Tetsuhide Ito,Masami Miki,Keijiro Ueda,Lingaku Lee,Ken Kawabe,Hisato Igarashi,Nao Fujimori,Kazuhiko Nakamura,Kohei Yasunaga,Robert T. Jensen,Takao Ohtsuka,Yoshihiro Ogawa Korean Society of Gastrointestinal Cancer 2016 Journal of digestive cancer reports Vol.4 No.2
The epidemiology of pancreatic neuroendocrine neoplasms (PNENs) in Asia has been clarified through epidemiological studies, including one conducted in Japan, and subsequently another in South Korea. As endoscopic ultrasonography (EUS) has become more widely accessible, endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been performed in pancreatic tumors for which the clinical course was only monitored previously. This has enabled accurate diagnosis of pancreatic tumors based on the 2010 WHO classification; as a result, the number of patients with an accurate diagnosis has increased. Although surgery has been the standard therapy for PNENs, new treatment options have become available in Japan for the treatment of advanced or inoperable PNENs; of particular note is the recent introduction of molecular target drugs (such as everolimus and sunitinib) and streptozocin. Treatment for progressive PNENs needs to be selected for each patient with consideration of the performance status, degree of tumor differentiation, tumor mass, and proliferation rate. Somatostatin receptor (SSTR)-2 is expressed in many patients with neuroendocrine tumor. Somatostatin receptor scintigraphy (SRS), which can visualize SSTR-2 expression, has been approved in Japan. The SRS will be a useful diagnostic tool for locating neuroendocrine neoplasms, detecting distant metastasis, and evaluating therapy outcomes. In this manuscript, we review the latest diagnostic methods and treatments for PNENs.
Photoreactive natural polymer for medical application
Hana Na,Yoshihiro Ito,Hyoungjae Lee,Shinhye Park,Siwoong Seo,Kwangil Kim,Taeil Son 한국당과학회 2011 한국당과학회 학술대회 Vol.2011 No.1
Mainly, chemical and physical methods have been used for immobilization of bioactive materials. However, there are some of drawbacks with those methods. For example, chemical method may produce potential toxic by-product and, in case of physical method, low efficiency of immobilized bioactive material is observed. To solve these problems, recently, the immobilization by photoreaction has been researched widely. The advantages of photo-immobilization are 1) high selectivity of chemical reactions or processes under mild conditions (ambient temperature of also much below), 2) typically no need for added catalysts or special solvents, 3) spatially addressable effects (2D and 3D structuring possible) and 4) applicable to very small and (relatively) large scales. To use for photo-immobilization, various natural polymers reacted by irradiation to ultra violet and visible light can be synthesized. It is considered that these photoreactive natural polymers can be applied for medical area to increase biocompatibility and functionality, for example, coating agent for bioinnert devices like stent and implant, anti-adhesive agent, wound dressing and bio-adhesive.
Takashi Yagi,Yoshihiro Fujikawa,Tomoko Sawai,Takeji Takamura-Enya,Sayoko Ito-Harashima,Masanobu Kawanishi 한국독성학회 2017 Toxicological Research Vol.33 No.4
Aryl hydrocarbons such as 3-nitrobenzanthrone (NBA), 4-aminobiphenyl (ABP), acetylaminofluorene (AAF), benzo(a)pyrene (BaP), and 1-nitropyrene (NP) form bulky DNA adducts when absorbed by mammalian cells. These chemicals are metabolically activated to reactive forms in mammalian cells and preferentially get attached covalently to the N² or C8 positions of guanine or the N6 position of adenine. The proportion of N² and C8 guanine adducts in DNA differs among chemicals. Although these adducts block DNA replication, cells have a mechanism allowing to continue replication by bypassing these adducts: translesion DNA synthesis (TLS). TLS is performed by translesion DNA polymerases—Pol η, κ, ι, and ζ and Rev1—in an error-free or error-prone manner. Regarding the NBA adducts, namely, 2-(2"-deoxyguanosin-N²-yl)-3-aminobenzanthrone (dG-N²-ABA) and N-(2"-deoxyguanosin-8-yl)-3-aminobenzanthrone (dG-C8-ABA), dG-N²-ABA is produced more often than dG-C8-ABA, whereas dG-C8-ABA blocks DNA replication more strongly than dG-N²-ABA. dG-N2-ABA allows for a less error-prone bypass than dG-C8-ABA does. Pol η and κ are stronger contributors to TLS over dG-C8-ABA, and Pol κ bypasses dG-C8-ABA in an error-prone manner. TLS efficiency and error-proneness are affected by the sequences surrounding the adduct, as demonstrated in our previous study on an ABP adduct, N-(2"-deoxyguanosine-8-yl)-4-aminobiphenyl (dG-C8-ABP). Elucidation of the general mechanisms determining efficiency, errorproneness, and the polymerases involved in TLS over various adducts is the next step in the research on TLS. These TLS studies will clarify the mechanisms underlying aryl hydrocarbon mutagenesis and carcinogenesis in more detail.
Synthesis of Visible Light-induced Cross-linkable Chitosan as an Anti-adhesive Agent
김광일,나하나,Yoshihiro Ito,손태일 한국고분자학회 2011 Macromolecular Research Vol.19 No.3
Visible light-induced cross-linkable chitosan was synthesized by the incorporation of furfuryl isocyanate. The synthesized chitosan derivative was analyzed by ^1H NMR and GPC. The synthesized chitosan derivative showed no significant toxicity. The synthesized chitosan derivative was mixed with Rose Bengal in distilled water and irradiated with visible light for 5 min in the presence of a photomask. A micropattern that matched the micropattern of photomask was formed and the photoreactivity of the synthesized chitosan derivative was confirmed. Solidification of the synthesized chitosan is believed to have occurred by a photo-oxidation-induced cross-linking mechanism. Contact angle measurements and cell culture on the surface of solidified chitosan derivative were also carried out. Cell adhesion on the surface of solidified chitosan was not shown. Considering these results, the synthesized chitosan derivative is non-cytotoxic, solidifies rapidly by visible light not chemicals, and has fewer cell interactions. The synthesized chitosan derivative is a novel candidate for anti-adhesive agent.
Preparation of injectable forms of immobilized protein drugs using UV-curable gelatin derivatives
이태훈,김신웅,Yoshihiro Ito,손태일 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.80 No.-
Photo-immobilization is an effective technique for loading protein-based drugs in a natural polymer,which can help maintain the drugs’ effects constantly. An ideal drug immobilization material is a naturalpolymer with biocompatibility, biodegradability, and low toxicity, which can be applied as a medicalmaterial. However, current formulations have limitations such as rapid degradation of loaded proteindrugs by the enzymes in the body, thus reducing the drugs’ therapeutic efficiency. In the present study,we aimed to develop an injectable formulation as a drug delivery system using gelatin, a natural polymerthat is safe for use in humans and meets the criteria for injectable derivatives. Gelatin was functionalizedwith UV-irradiated azidophenyl to prepare particles for the immobilization of a protein. We confirmedthe immobilization offluorescent-conjugated bovine serum albumin byfluorescent microscopy. Azidophenyl gelatin (Az-gelatin) showed no cytotoxicity, and the epidermal growth factor immobilizedin the particle maintained its function of promoting cell proliferation for up to 48 h. Based on thesecharacteristics, UV-curable Az-gelatin is expected to have widespread applications in the medicalfield.