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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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Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： toshiaki Tsurui Yuya Hirasawa Yutaro Kubota Kiyoshi Yoshimura Takuya Tsunoda Department of Medical Oncology Showa UniversityTokyo 1428555Japan Department of Clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic ***,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently *** SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe *** tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated *** RAS or BRAF mutations were *** Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was *** drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly ***,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse *** Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

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Tumor size discrepancy between endoscopic and pathological evaluations in colorectal endoscopic submucosal dissection

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World Journal of Gastrointestinal Endoscopy 2024年第3期16卷 136-147页

作者： Takeshi Onda Osamu Goto toshiaki Otsuka Yoshiaki Hayasaka Shun Nakagome Tsugumi Habu Yumiko Ishikawa Kumiko Kirita Eriko Koizumi Hiroto Noda Kazutoshi Higuchi Jun Omori Naohiko Akimoto Katsuhiko Iwakiri Department of Gastroenterology Nippon Medical SchoolGraduate School of MedicineBunkyo-ku 113-8603TokyoJapan Endoscopy Center Nippon Medical School HospitalBunkyo-ku 113-8603TokyoJapan Department of Hygiene and Public Health Nippon Medical SchoolBunkyoku 113-8603TokyoJapan Center for Medical Education Nippon Medical SchoolBunkyo-ku 113-8603TokyoJapan

BACKGROUND Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection(ESD);however,the preoperative evaluation of tumor size is often different from histological *** influential factors on failure to obtain an accurate tumor size evaluation could help prepare optimal conditions for safer and more reliable *** This was a retrospective study conducted at a single institution.A total of 377 lesions removed by colorectal ESD at our hospital between April 2018 and March 2022 were *** first assessed the difference in size with an absolute per-centage of the scaling ***,we compared the clinicopatho-logical characteristics of the correct scaling group(>-33%and33%),which was further subdivided into the underscaling group(-33%or less of the discrepancy)and overscaling group(33%or more of the discrepancy),*** secondary outcome measures,parameters on size estimation were compared between the underscaling and correct scaling groups,as well as between the overscaling and correct scaling ***,multivariate analysis was performed in terms of the following relevant parameters on size estimation:Pathological size,location,and possible influential factors(P<0.1)in the univariate *** The mean of absolute percentage in the scaling discordance was 21%,and 91 lesions were considered to be incorrectly estimated in *** incorrect scaling was significantly remarkable in larger lesions(40 mm vs 28 mm;P<0.001)and less experience(P<0.001),and these two factors were influential on the underscaling(75 lesions;P<0.001).Conversely,compared with the correct scaling group,16 lesions in the overscaling group were significantly small(20 mm vs 28 mm;P<0.001),and the small lesion size was influential on the overscaling(P=0.002).CONCLUSION Lesions indicated for colorectal ESD tended to be underestimate

关键词： Endoscopic submucosal dissection Colorectal tumor Tumor size Size estimation Size discrepancy

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Sodium-glucose cotransporter 2 inhibitors in Asian patients with heart failure

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Chinese Medical Journal 2023年第8期136卷 1004-1005页

作者： Shingo Kato Nobuyuki Horita Daisuke utsunomiya Department of Diagnostic Radiology Yokohama City University Graduate School of MedicineKanagawaJapan Department of Cardiology Kanagawa Cardiovascular and Respiratory CenterKanagawaJapan Chemotherapy Center Yokohama City University HospitalKanagawaJapan

To the Editor:Sodium-glucose cotransporter 2(SGLT-2)inhibitors are recognized as one of the essential drugs for the treatment of heart failure(HF).Recent randomized controlled trials(RCTs)have shown that the SGLT-2 in... 详细信息

关键词： patients drugs mortality

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Goblet cell carcinoid of the appendix:Six case reports

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World Journal of Clinical Cases 2024年第22期12卷 5217-5224页

作者： toshiaki Toshima Ryo Inada Shinya Sakamoto Eri Takeda Takahiro Yoshioka Kento Kumon Naoki Mimura Nobuo Takata Motoyasu Tabuchi Kazuyuki Oishi Takuji Sato Kenta Sui Takehiro Okabayashi Kazuhide Ozaki Toshio Nakamura Yuichi Shibuya Manabu Matsumoto Jun Iwata Department of Gastroenterological Surgery Kochi Health Sciences CenterKochi 781-8555Japan Department of Diagnostic Pathology Kochi Health Sciences CenterKochi 781-8555Japan

BACKGROUND Goblet cell carcinoid(GCC)of the appendix is a rare tumor characterized by neuroendocrine and adenocarcinoma *** preoperative diagnosis is very difficult,with most patients complaining mainly of abdominal *** tomography shows swelling of the appendix,so diagnosis is usually made incidentally after appendectomy based on a preoperative diagnosis of *** if a patient undergoes preoperative colonoscopy,accurate endoscopic diagnosis is very difficult because GCC shows a submucosal growth pattern with invasion of the appendiceal *** SUMMARY Between 2017 and 2022,6 patients with GCC were treated in our *** presenting complaint for 5 of these 6 patients was abdominal *** 5 patients underwent appendectomy,including 4 for a preoperative diagnosis of appendicitis and the other for diagnosis and treatment of an appendiceal *** sixth patient presented with vomiting and underwent ileocecal resection for GCC diagnosed from preoperative *** 2 patients with GCC underwent colonoscopy,no neoplastic changes were *** of the six patients showed lymph node metastasis on pathological *** of the last followup(median:15 mo),all cases remained alive without *** As preoperative diagnosis of GCC is difficult,this possibility must be considered during surgical treatments for presumptive appendicitis.

关键词： Goblet cell carcinoid Appendix Preoperative diagnosis Endoscopic diagnosis Surgical treatment Case report

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Woody plant cell walls:Fundamentals and utilization

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Molecular Plant 2024年第1期17卷 112-140页

作者： Wei Li Ying-Chung Jimmy Lin Ying-Lan Chen Chenguang Zhou Shuang Li Nette De Ridder Dyoni M.Oliveira Lanjun Zhange Baocai Zhang Jack P.Wang Changzheng Xu Xiaokang Fu Keming Luo Ai-Min Wu Taku Demura Meng-Zhu Lu Yihua Zhou Laigeng Li toshiaki Umezawa Wout Boerjan Vincent L.Chiang State Key Laboratory of Tree Genetics and Breeding Northeast Forestry UniversityHarbin 150040China Department of Life Science National Taiwan UniversityTaipeiTaiwanChina Department of Biotechnology and Bioindustry Sciences College of Bioscience and BiotechnologyNational Cheng Kung UniversityTainanTaiwanChina Department of Plant Biotechnology and Bioinformatics Ghent UniversityTechnologiepark 719052 GhentBelgium VIB Center for Plant Systems Biology Technologiepark 719052 GhentBelgium State Key Laboratory of Plant Genomics Insttute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Forest Biotechnology Group Department of Forestry and Environmental ResourcesNorth Carolina State UniversityRaleighNC 27695USA Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation Integrative Science Center of Germplasm CreationSchool of Life SciencesSouthwest UniversityChongqing 400715China Guangdong Key Laboratory for Innovative Developmentand Utilization of Forest Plant Germplasm College of Forestry and Landscape ArchitecturesSouth China Agricultural UniversityGuangzhou510642China Center for Digital Green-innovation Nara Institute of Science and TechnologykomaNara 630-0192Japan State Key Laboratory of Subtropical Siviculture College of Forestry and BiotechnologyZhejang A&F UniversityHangzhou 311300China CAS Center for Excellence in Molecular Plant Sciences Chinese Academy of Sciences300 Fenglin RoadShanghai 200032China Laboratoryof MetabolicScienceofForest Plants and Microorganisms Rsearch Institute for Sustainable HumanosphereKyoto UniversityUjiKyoto 611-0011 Japan

Cell walls in plants,particularly forest trees,are the major carbon sink of the terrestrial *** and biosynthetic features of plant cell walls were revealed early on,focusing mostly on herbaceous model *** developments in genomics,transcriptomics,epigenomics,transgenesis,and associated analytical techniques are enabling novel insights into formation of woody cell ***,we review multilevel regulation of cell wall biosynthesis in forest tree *** highlight current approaches to engineering cell walls as potential feedstock for materials and energy and survey reported field tests of such engineered transgenic *** outline opportunities and challenges in future research to better understand cell type biogenesis for more efficient wood cell wall modification and utilization for biomaterials or for enhanced carbon capture and storage.

关键词： regulation of cell wall formation biosynthesis of cell wall components lignin cellulose hemicellulose cell wall utilization

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Surface manipulation of a triple-conducting cathode for protonic ceramic fuel cells to enhance oxygen reduction activity and CO_(2) tolerance

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Journal of Energy Chemistry 2023年第12期87卷 450-459,I0012页

作者： Wenwen Zhang Hiroki Muroyama Yuichi Mikami toshiaki Matsui Koichi Eguchi Department of Energy and Hydrocarbon Chemistry Graduate School of EngineeringKyoto UniversityNishikyo-kuKyoto 615-8510Japan Technology Division Panasonic Holdings Corporation3-1-1 Yagumo-naka-machiMoriguchi CityOsaka 570-8501Japan

One of the main obstacles limiting the performance of protonic ceramic fuel cells(PCFCs) is the sluggish kinetics of the oxygen reduction reaction(ORR) at reduced ***,the surface manipulation of a triple-conducting cathode BaCe_(0.5)Pr_(0.3)Y_(0.2)O_(3-δ)(BCPY) by an efficient catalyst coating PrNi_(0.5)Co_(0.5)O_(3-δ)(PNC) to enhance the ORR activity and CO_(2) tolerance is *** developed PNC-coated BCPY cathode achieves the polarization resistance of 0.25 and 1.00 Ω cm^(2) at 600 and 500 ℃,respectively,approximately 1/5 of that for the pristine BCPY cathode(0.99 and 4.79 Ω cm^(2)),while maintaining an excellent CO_(2) *** single cell on a BaZr_(0.8)Yb_(0.2)O_(3-δ) electrolyte also exhibits a high peak power density of 0.79 W cm^(-2)at 700 ℃ and a stable operation for 200 h at 600 ℃.Such high ORR activity is mainly attributed to the synergistic effect of BCPY support and PNC ***,BCPY provides a tripleconducting path(mainly protons),and PNC nanoparticles facilitates surface oxygen exchange and steam adsorption/desorption processes due to the enriched surface oxygen *** study will provide a new design strategy for developing high-performance PCFCs cathode.

关键词： Triple-conducting cathode Surface manipulation Oxygen reduction reaction CO_(2)tolerance Protonic ceramicfuel cells

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Assessment of the stiffened panel performance in the OTEC seawater tank design:Parametric study and sensitivity analysis

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Theoretical & Applied Mechanics Letters 2023年第4期13卷 261-271页

作者： Yogie Muhammad Lutfi Ristiyanto Adiputra Aditya Rio Prabowo Tomoaki utsunomiya Erwandi Erwandi Nurul Muhayat Department of Mechanical Engineering Universitas Sebelas MaretSurakarta 57126Indonesia Research Center for Hydrodynamics Technology National Research and Innovation Agency(BRIN)Surabaya 60117Indonesia Department of Marine Systems Engineering Kyushu UniversityFukuoka 819-0395Japan

Ocean thermal energy conversion(OTEC)is a process of generating electricity by exploiting the temperature difference between warm surface seawater and cold deep *** to the high static and dynamic pressures that are caused by seawater circulation,the stiffened panel that constitutes a seawater tank may undergo a reduction in ultimate *** current paper investigates the design of stiffening systems for OTEC seawater tanks by examining the effects of stiffening parameters such as stiffener sizes and span-over-bay ratio for the applied combined loadings of lateral and transverse pressure by fluid motion and axial compression due to global bending *** ultimate strength calculation was conducted by using the non-linear finite element method via the commercial software known as *** stress and deformation distribution due to pressure loads was computed in the first step and then brought to the second step,in which the axial compression was *** effects of pressure on the ultimate strength of the stiffener were investigated for representative stiffened panels,and the significance of the stiffener parameters was assessed by using the sensitivity analysis *** a result,the ultimate strength was reduced by approximately 1.5%for the span-over-bay ratio of 3 and by 7%for the span-over-bay ratio of 6.

关键词： Ocean thermal energy conversion(OTEC) Seawater tank Stiffened panels Numerical analysis Combined loadings

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Anticipation phenomenon in familial adenomatous polyposis:an analysis of its origin

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World Journal of Gastroenterology 2000年第3期6卷 335-338页

作者： Takeo Iwama Joji utsunomiya Department of Surgery Kyoundo HospitalSasaki Institute KandaSurugadai 1-8Chiyoda-KuTokyo 101-0062Japan Institute for Advanced Medical Sciences Hyogo Medical College Mukogawa 1-1NisinomiyaHyogo 663-8131Japan

AIM To analyze the origin of the anticipationphenomenon,which means earlier death insuccessive generation in familial *** The study subjects were 2161patients with familial adenomatous polyposisand their 7465 first-degree relatives who weremembers of 750 families registered at ourPolyposis *** ages at death andcumulative mortality rates in the parent,theproband,and the child generations werecompared for both all subjects and the *** In the patients over 5 years of age,the mean age at death was 50.9 years for theparent,42.3 years for the proband,and 33.3years for the child generations,respectively(P<0.001).The deceased rates in the threegenerations were 90.7%,51.3% and 23.1% ofthe patients,respectively,and this differencewas the main cause of the anticipation measuredby parent-child paring *** cumulativemortality rates for all subjects failed to showanticipation,however the cumulative mortalityrates for the patients showed the *** anticipation phenomenon was shown by anyparent-child pairing methods for the *** important causes of theanticipation were different proportion of causesof death between generations(P<0.001),and alow proportion of detected or deceased patients (P<0.001)in the child *** Anticipation in familialadenomatous polyposis may be caused byparent-child paring methods as well as severalintergenerational biases.

关键词： familial adenomatous apolyposis (FAP) anticipation phenomenon intergenerational bias child generations hereditary disorder mortality

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Extracellular matrix gene expression in human trabecular meshwork cells following mechanical fluid flow stimulation

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International Journal of Ophthalmology(English edition) 2022年第3期15卷 388-393页

作者： Koichi Yoshida Motofumi Kawai Tsugiaki utsunomiya Akihiro Ishibazawa Young-Seok Song Mariana Sayuri BUdo Yoshikazu Tasaki Akitoshi Yoshida Department of Ophthalmology Asahikawa Medical UniversityAsahikawaHokkaido 078-8510Japan Department of Hospital Pharmacy&Pharmacology Asahikawa Medical UniversityAsahikawaHokkaido 078-8510Japan

AIM: To investigate changes in extracellular matrix(ECM) gene expression in human trabecular meshwork(HTM) cells in response to mechanical fluid flow ***: HTM cells were grown on a glass plate coated with 0.02% type Ⅰ collagen(COL) and exposed to shear stress(0, 0.2, 1.0 dyne/cm;) for 12 *** in genes related to the ECM were evaluated by real-time reverse transcriptase-polymerase chain *** of Smad2 protein was investigated by Western ***: After mechanical stimulation, COL type 4 alpha 2, COL type 6 alpha 1, and fibronectin-1 mRNA were significantly higher than the static control(P<0.05, <0.05, and <0.01, respectively).The metalloproteinase-2 and plasminogen activator inhibitor-1 mRNA were significantly higher than the static control(P<0.05 and <0.01, respectively), while the differences in the tissue inhibitors of metalloproteinases-2 mRNA were not *** phosphorylation of Smad2 levels was significantly higher compared to the static control ***: Changes in the expressions of genes associated ECM metabolism result in HTM cells after mechanical *** mechanical stimulation of the aqueous humor to the trabecular meshwork may promote ECM turnover and contribute to intraocular pressure homeostasis.

关键词： trabecular meshwork shear stress aqueous humor extracellular matrix glaucoma intraocular pressure

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