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Glycosylation engineering of therapeutic IgG antibodies： challenges for the safety, functionality and efficacy

Protein & Cell 2018年第1期9卷 47-62页

作者： Yusuke Mimura Toshihiko Katoh Radka Saldova Roisin O'Flaherty Tomonori Izumi Yuka Mimura-Kimura Toshiaki Utsunomiya Yoichi Mizukami Kenji Yamamoto tsuneo matsumoto Pauline M. Rudd Department of Clinical Research NHO Yamaguchi-Ube Medical Center 685 Higashi-Kiwa Ube 755-0241 Japan Laboratory of Molecular Biology and Bioresponse Division of Integrated Life Science Graduate School of Biostudies KyotoUniversity Kitashirakawa Oiwake-Cho Sakyo-Ku Kyoto 606-8502 Japan NIBRT GlycoScience Group National Institute for Bioprocessing Research and Training Mount Merrion Blackrock Dublin 4Ireland Center for Regenerative Medicine Yamaguchi University Graduate School of Medicine 1-1-1 Minami Kogushi Ube 755-8505 Japan Center for Gene Research Yamaguchi University 1-1-1 Minami-Kogushi Ube 755-8505 Japan Research Institute for Bioresources and Biotechnology Ishikawa Prefectural University 1-308 Suematsu Nonoichi Ishikawa 921-8836 Japan

Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary *** oligosaccharide attached to Asn297 of the Fc is essen- tial for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that gen- erate structural heterogeneity （glycoforms） exhibit unique biological activities. Hence, efficient and quan- titative glycan analysis techniques have been increas- ingly important for the development and quality control of therapeutic antibodies, and g｜ycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosy- lation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibili- ties for the design of novel antibody therapeutics. Fur- thermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosyn- thases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next- generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety,functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.

关键词： chemoenzymatic glycoengineering crysta structure endoglycosidase fucose glycosylation,intravenous immunoglobulin sialic acid transglycosylation,ultra performance liquid chromatography

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Clinical relevance of fluorodeoxyglucose positron emission tomography/computed tomography and magnifying endoscopy with narrow band imaging in decision-making regarding the treatment strategy for esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2019年第46期25卷 6767-6780页

作者： Kazuhiro Toriyama Masahiro Tajika Tsutomu Tanaka Makoto Ishihara Yutaka Hirayama Sachiyo Onishi Nobumasa Mizuno Takamichi Kuwahara Nozomi Okuno Shinpei matsumoto Eiichi Sasaki Tetsuya Abe Yasushi Yatabe Kazuo Hara Keitaro Matsuo tsuneo Tamaki Yasumasa Niwa Department of Gastroenterology Aichi Cancer Center HospitalNagoya 464-8681Japan Department of Endoscopy Aichi Cancer Center HospitalNagoya 464-8681Japan Department of Gastroenterology Anjo Kosei HospitalAnjo 446-8602Japan Department of Pathology and Molecular Diagnostics Aichi Cancer Center HospitalNagoya 464-8681Japan Department of Gastroenterological Surgery Aichi Cancer Center HospitalNagoya 464-8681Japan Division of Cancer Epidemiology and Prevention Aichi Cancer Center Research InstituteNagoya 464-8681Japan East Nagoya Imaging Diagnosis Center Nagoya 464-0044Japan

BACKGROUND Recent advances in endoscopic technology,especially magnifying endoscopy with narrow band imaging(ME-NBI)enable us to detect superficial esophageal squamous cell carcinoma(ESCC),but determining the appropriate method of resection,endoscopic resection(ER)vs surgical resection,is often ***,several studies have reported that 18F-fluorodeoxyglucose positron emission tomography(FDG-PET)is a useful indicator for decision-making regarding treatment for superficial ***,there are not enough reports on association between FDG-PET uptake and clinicopathological characteristics of superficial ***,there are not enough reports on evaluating the usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial *** study evaluated clinical relevance of FDG-PET and ME-NBI in decision-making regarding the treatment strategy for *** To investigate the association between FDG uptake and the clinicopathological characteristics of superficial ESCC and its usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial *** A database of all patients with superficial ESCC who had undergone both MENBI and FDG-PET for pre-treatment staging at Aichi Cancer Center Hospital between January 2008 and November 2018 was retrospectively *** uptake was defined positive or negative whether the primary lesion was visualized or could be distinguished from the background,or *** invasion depth of ESCC was classified according to the Japan Esophageal *** endpoint is to evaluate the association between FDG uptake and clinicopathological characteristics of superficial *** endpoint is to investigate the efficacy of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial *** A total of 82 lesions in 82 patients were ***-PET showed positive uptake in 29(35.4%)*** analysis sh

关键词： ^18F-fluorodeoxyglucose positron emission tomography Magnifying endoscopy Narrow band imaging Superficial esophageal cancer Squamous cell carcinoma Treatment strategy

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