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Structure and function of ALG-2,a penta-EF-hand calcium-dependent adaptor protein

Science China(Life Sciences) 2011年第8期54卷 770-779页

作者： Masatoshi MAKI hironori suzuki Hideki SHIBATA Department of Applied Molecular Biosciences Graduate School of Bioagricultural SciencesNagoya University Structural Biology Research Center Photon FactoryInstitute of Materials Structure ScienceHigh Energy Accelerator Research Organization

ALG-2(a gene product of PDCD6) is a 22-kD protein containing five serially repetitive EF-hand structures and belongs to the penta-EF-hand(PEF) family,including the subunits of typical ***-2 is the most conserved protein among the PEF family members and its homologs are widely found in eukaryotes.X-ray crystal structures of various PEF proteins including ALG-2 have common features:presence of eightα-helices and dimer formation via paired EF5s that are positioned in anti-parallel ***-2 forms a homodimer and a heterodimer with its closest paralog *** calmodulin,a well-known four-EF-hand protein,ALG-2 interacts with various proteins in a Ca2+-dependent fashion,but the binding motifs are completely *** some exceptions,ALG-2-interacting proteins commonly contain Pro-rich regions,and ALG-2 recognizes at least two distinct Pro-containing motifs:PPYP(X) nYP(X,variable;n=4 in ALIX and PLSCR3) and PXPGF(represented by Sec31A) .A shorter alternatively spliced isoform,lacking two residues and designated ALG-2 GF122,does not bind ALIX but maintains binding capacity to Sec31A.X-ray crystal structural analyses have revealed that binding of calcium ions induces the configuration of the side chain of R125 so that it opens Pocket 1,which accepts PPYP,but Pocket 1 remains closed in the case of ALG-2 ***-2 dimer has two ligand-binding sites,each in a monomer molecule,and appears to function as a Ca2+-dependent adaptor protein to either stabilize a preformed complex or to bridge two proteins on scaffolds in systems of the endosomal sorting complex required for transport(ESCRT) and ER-to-Golgi transport.

关键词： ALG-2 calcium penta-EF-hand X-ray crystal structure protein-protein interaction membrane trafficking

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Performance with Respect to Flue Gas Composition of a Combined Desulfurization/Denitration Process Using Powder-Particle Fluidized Bed

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Chinese Journal of Chemical Engineering 1999年第4期7卷 295-306页

作者：许光文王兵 hironori suzuki Kunio Kato Department of Biological and Chemical Engineering Gunma UniversityKiryu 376-8515Japan

A new combined desulfurization/denitration (DeSOx/DeNOx,) process was tested in this study. The process uses the so-called powder-particle fluidized bed (PPFB) as the major reactor in which a coarse DeNOx catalyst, several hundred micrometers in size, is fluidized by flue gas as the fluidization medium particles, while a continuously supplied fine DeSOx sorbent, several to tens of micrometers in diameter, is entrained with the flue gas. Ammonia for NOx reduction is fed to the bottom of the bed, thus, SOX and NOX are simultaneously removed in the single reactor. By adopting a model gas, SO2-NO-H2O-N2-air, to simulate actual flue gas in a laboratory-scale PPFB, simultaneous SO2 and NO removals were explored with respect to various gas components of flue gas. It was found that the variations of SO2 removal with concentrations (fractions) of oxygen, water vapor, SO2 and NO in flue gas are little affected by the simultaneous NOx reduction. However, the dependencies of NO removal upon such gas components are closely related to the inter-actions between DeSOx sorbent and DeNOx catalyst.

关键词： environment combustion combined SOx/NOx removal fluidized bed powder-particle technology

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Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

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World Journal of Gastroenterology 2012年第16期18卷 1933-1939页

作者： Hiroyuki Kirikoshi Masato Yoneda hironori Mawatari Koji Fujita Kento Imajo Shingo Kato Kaori suzuki Noritoshi Kobayashi Kensuke Kubota Shin Maeda Atsushi Nakajima Satoru Saito Gastroenterology Division Yokohama City University Graduate School of Medicine3-9 Fuku-uraKanazawakuYokohama 236-0004Japan

AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy(HAIC) for advanced hepatocellular carcinoma(HCC) resistant to transarterial chemoembolization(TACE).METHODS:This study was conducted on 42 patients who received HAIC for advanced HCC between 2001and 2010 at our hospital.5-fluorouracil(5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection ***-arterial cisplatin or subcutaneous interferon was administered in combination with the *** patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010(written in Japanese);one group of patients who did not fulfill the criteria for TACE resistance(group A,n = 23),and another group who fulfilled the criteria for TACE resistance(group B,n = 19).We compared the outcomes in terms of the response and survival rates between the two ***:Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B(response rate:48% vs 16%,P = 0.028,tumor suppression rate:87% vs 53%,P = 0.014).Furthermore,both the progression-free survival rate and survival time were significantly superior in group A than in group B(3-,6-,12-,and 24-mo = 83%,70%,29% and 20% vs 63%,42%,16% and 0%,respectively,P = 0.040,and 9.8 mo vs 6.2 mo,P = 0.040).A multivariate analysis(Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival(P = 0.007).CONCLUSION:HAIC administrating 5-FU was not effective against advanced HCC resistant to *** tools for treatment,i.e.,molecular-targeting agents may be considered for these cases.

关键词： Hepatocellular carcinoma Hepatic arterial infusion chemotherapy 5-fluorouracil Transarterial chemoembolization

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MicroRNA-31 expression in colorectal serrated pathway progression

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World Journal of Gastroenterology 2014年第34期20卷 12346-12349页

作者： hironori Aoki Katsuhiko Nosho Hisayoshi Igarashi Miki Ito Kei Mitsuhashi Takafumi Naito Eiichiro Yamamoto Tokuma Tanuma Masafumi Nomura Hiroyuki Maguchi Toshiya Shinohara Hiromu suzuki Hiroyuki Yamamoto Yasuhisa Shinomura Center for Gastroenterology Teine-Keijinkai HospitalSapporo 006-0811Japan Department of Gastroenterology Rheumatology and Clinical ImmunologySapporo Medical University School of MedicineSapporo 060-8543Japan Department of Gastroenterology Rheumatology andClinical ImmunologySapporo Medical University School of MedicineSapporo 060-8543Japan Department of Pathology Teine-KeijinkaiHospitalSapporo 006-0811Japan Department of Molecular Biology SapporoMedical University School of MedicineSapporo 060-8543Japan Division of Gastroenterology and Hepatology Department of Internal MedicineSt. Marianna University School of MedicineKawasaki 216-8511Japan

MicroRNAs have been increasingly recognized as useful biomarkers for colorectal cancers(CRC).We have recently observed that microRNA-31(miR-31)expression is associated with BRAF mutation and prognosis in ***,high miR-31 expression is frequently detected in sessile serrated adenomas compared with hyperplastic polyps(HPs).These results suggest that miR-31 may contribute to the progression of serrated *** a follow-up colonoscopy,we observed the case of a 75-year-old man with a 7-mm flat-elevated lesion in the cecum and diagnosed the lesion as an early invasive carcinoma with serrated *** specimens were obtained from the representative areas to compare the molecular alterations in the carcinoma component with those in the HP *** miR-31 expression was observed in the carcinoma component(57-fold increase)and the HP component(8-fold increase)compared with the paired normal mucosa,suggesting that miR-31 may be one of the key molecules in serrated pathway progression.

关键词： BRAF Colorectal carcinoma MicroRNA-31 MLH1 microsatellite instability Serrated pathway

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Mineral and Sea-Salt Aerosol Fluxes over the Last 340 kyr Reconstructed from the Total Concentration of Al and Na in the Dome Fuji Ice Core

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Atmospheric and Climate Sciences 2013年第2期3卷 186-192页

作者： hironori Sato Toshitaka suzuki Motohiro Hirabayashi Yoshinori Iizuka Hideaki Motoyama Yoshiyuki Fujii Department of Earth and Environmental Sciences Faculty of Science Yamagata University Yamagata Japan Institute of Low Temperature Science Hokkaido University Sapporo Japan National Institute of Polar Research Tokyo Japan

A quantitative analysis of the total concentrations of Al and Na in the Antarctic ice sheet during the past 340 kyr was performed by applying the acid digestion method to the Dome Fuji ice core. Atmospheric fluxes of mineral and sea-salt aerosol to Dome Fuji were calculated from the total concentration. The average fluxes of mineral aerosol to Dome Fuji in the periods of glacial maximum, 18.6 ± 10.1 mg·m–2·yr–1, were larger than the value in the interglacial periods, 3.77 ± 2.20 mg·m–2·yr–1. Conversely, the fluxes of sea-salt have no significant difference between the average value of glacial maximum, 130 ± 55 mg·m–2·yr–1, and that of interglacial, 111 ± 54 mg·m–2·yr–1. The results obtained in this study suggest that the variation of mineral aerosol flux in Dome Fuji, together with climate change, was much larger than that of sea-salt aerosol flux. This result may have occurred because the variety in the intensity of the source and transport during the glacial-interglacial cycle is more significant for mineral aerosol than that for sea-salt aerosol.

关键词： Ice Core Antarctica Dome Fuji Climate Change Aerosol Flux Full Digestion

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IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions

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World Journal of Gastroenterology 2014年第29期20卷 10050-10061页

作者： Takafumi Naito Katsuhiko Nosho Miki Ito Hisayoshi Igarashi Kei Mitsuhashi Shinji Yoshii hironori Aoki Masafumi Nomura Yasutaka Sukawa Eiichiro Yamamoto Yasushi Adachi Hiroaki Takahashi Masao Hosokawa Masahiro Fujita Toshinao Takenouchi Reo Maruyama Hiromu suzuki Yoshifumi Baba Kohzoh Imai Hiroyuki Yamamoto Shuji Ogino Yasuhisa Shinomura Department of Gastroenterology Rheumatology and Clinical ImmunologySapporo Medical University School of Medicine Department of Gastroenterology Keiyukai Sapporo Hospital Center for Gastroenterology Teine-Keijinkai Hospital Department of Medical Oncolo-gy Dana-Farber Cancer InstituteBostonMA 02115United States Department of Surgery Keiyukai SapporoHospital Department of Pathology Keiyukai Sapporo Hospital Department of Molecular Biology Sapporo Medical University School of Medicine Department of Gastroenterological Surgery Graduate School of Medical ScienceKumamoto University Division of Cancer Research The Institute of Medical ScienceThe University of Tokyo Division of Gastroenterology and Hepatology Department of Internal MedicineSt.Marianna University School of Medicine

AIM: To investigate insulin-like growth factor 2 (IGF2) differentially methylated region (DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions.

关键词： BRAF Colon polyp Colorectal neoplasia Colorectum Genome Insulin-like growth factor Long interspersed nucleotide element-1 Microsatellite instability Serrated pathway

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Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors

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Cancer Communications 2023年第4期43卷 415-434页

作者： Hiroyuki suzuki Hideki Iwamoto Takahiro Seki Toru Nakamura Atsutaka Masuda Takahiko Sakaue Toshimitsu Tanaka Yasuko Imamura Takashi Niizeki Masahito Nakano Shigeo Shimose Tomotake Shirono Yu Noda Naoki Kamachi Miwa Sakai Kazutoyo Morita Masamichi Nakayama Tomoharu Yoshizumi Ryoko Kuromatsu Hirohisa Yano Yihai Cao hironori Koga Takuji Torimura Division of Gastroenterology Department of MedicineKurume University School of MedicineKurume CityFukuokaJapan Liver Cancer Research Division Research Center for Innovative Cancer TherapyKurume UniversityKurume CityFukuokaJapan Iwamoto Internal Medicine Clinic Kitakyushu CityFukuokaJapan Department of Microbiology Tumor and Cell biologyKarolinska InstitutetStockholmSweden Department of Surgery and Science Graduate School of Medical ScienceKyushu UniversityFukuoka CityFukuokaJapan Department of Pathology Kurume University School of MedicineKurume CityFukuokaJapan

Background:Antiangiogenic tyrosine kinase inhibitors(TKIs)provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma(HCC).However,patients with HCC often develop resistance toward antiangiogenic TKIs,and the underlying mechanisms are not *** aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in ***:We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC *** evaluated the prognosis,therapeutic response,and serum insulin-like growth factor-binding protein-1(IGFBP-1)levels of 31 lenvatinib-treated HCC *** on the array of results,a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were ***,in vivo genetic and pharmacological gain-and loss-of-function experiments were ***:In the patient cohort,IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall ***,antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor ***-1 stimulated angiogenesis through activation of the integrinα5β1-focal adhesion kinase ***,loss of IGFBP-1 and integrinα5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib ***:Together,our data shed light onmechanisms underlying acquired resistance of HCC to antiangiogenic *** TKIs induced an increase of tumor IGFBP-1,which promoted angiogenesis through activating the IGFBP-1-integrinα5β1 *** data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors.

关键词： hepatocellular carcinoma hypoxia IGFBP-1 lenvatinib molecular targeting resistance tyrosine kinase inhibitors

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Clinical Course of Lung Cancer Patients with Subcutaneously Implanted Central Venous Access Device Ports from the Time of Receiving Chemotherapy to the Endpoint of Cancer

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Journal of Cancer Therapy 2016年第7期7卷 519-529页

作者： Tomonori Hirashima Teppei Tsumori Kenichi Sakai Makoto Fujishima Yukie Yamakawa Noriko Ryouta Masumi Sandoh Takayuki Shiroyama Motohiro Tamiya Naoko Morishita Hidekazu suzuki Norio Okamoto Sho Goya hironori Shigeoka Departments of Thoracic Malignancy Osaka Prefectural Medical Center for Respiratory and Allergic Diseases Osaka Japan Departments of Palliative Medicine Osaka Prefectural Medical Center for Respiratory and Allergic Diseases Osaka Japan Tsumori Clinic Osaka Japan Departments of Gastroenterological and Breast Surgery Osaka Prefectural Medical Center for Respiratory and Allergic Diseases Osaka Japan Departments of Nursing Osaka Prefectural Medical Center for Respiratory and Allergic Diseases Osaka Japan Departments of Pharmacy Osaka Prefectural Medical Center for Respiratory and Allergic Diseases Osaka Japan

Background: As the prognosis of lung cancer (LC) patients improves, subcutaneously implanted central venous access device ports (CV-ports) have frequently been used for continuing chemotherapy (CC) or palliative care (PC). In this study, we examined the clinical course of LC patients with subcutaneously implanted CV-ports from the time of receiving chemotherapy to the endpoint of cancer. Materials and Methods: We retrospectively reviewed the clinical data and treatment history of LC patients with subcutaneously implanted CV-ports between June 2008 and November 2013 using clinical records and a pharmacy database. Results: Of the 132 LC patients with subcutaneously implanted CV-ports, 79 (59.8%) had CV-ports for CC (the CC group) and 53 (40.2%) had CV-ports for PC (the PC group). After CV-port implantation, LC patients in the CC group received a median of two regimens with a median of 6 cycles. The median survival time of patients in the CC and PC groups was 457 and 44 days, respectively. In the CC group, the median survival time of small cell and non-small cell LC patients was 342 (95% confidence interval, 235 - 627) and 563 (95% confidence interval, 368 - 728) days, respectively. Nine patients (6.8%) had their CV-ports removed due to complications. Forty (30.3%) of the 132 enrolled patients were referred for at-home PC. The at-home death rate observed among these 40 patients was 30.0% (N = 12). Conclusion: CV-ports may contribute to seamless oncological care.

关键词： Clinical Course At-Home Death Rate Implanted Central Venous Access Device Port Lung Cancer Seamless Oncological Care

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The Relationship between Neck and Shoulder Pain and the Sagittal Alignment of the Spine in Standing in Younger Generation

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Open Journal of Orthopedics 2015年第11期5卷 337-344页

作者： Tomonori Kenmoku Takane suzuki Nobuyasu Ochiai Tatsuki Ebata Genyo Miyajima Naoshige Nagura Mitsufumi Nakawaki Ryo Tazawa Sho Hiramatsu hironori Yamazaki Yu Sasaki Takeshi Yamaguchi Eiko Hashimoto Kenji Onuma Naonobu Takahira Kazuhisa Takahashi Masashi Takaso Department of Orthopedic Surgery Kitasato University School of Medicine Sagamihara Japan Sakura Orthopaedic Hospital Sakura Japan Department of Bioenvironmental Medicine Graduate School of Medicine Chiba Japan Department of Orthopaedic Surgery Chiba University Graduate School of Medicine Chiba Japan Department of Orthopedic Surgery Kitasato Medical Center Kitamoto Japan School of Allied Health Science Kitasato University Sagamihara Japan

Background: The relationship between chronic neck and shoulder pain and posture remains controversial. The purpose of this study was to investigate the relationship between chronic neck and shoulder pain and spinal sagittal alignment in standing posture in younger generation. Methods: Subjects included 57 females and 32 males (average age, 29.9 ± 5.7 years). All subjects were 20s or 30s. Spinal curvature was assessed using SpinalMouse. The subjects were also divided into a normal group (VAS zero group) and a pain group by VAS results. Statistical analysis was performed by Student’s t-test. Significance was defined as p < 0.05. Results: The normal group and pain group included 29 and 60 subjects, respectively. In terms of location of pain, thirty-one subjects felt neck pain, 50 felt pain above the scapula, and 17 felt pain between the thoracic spine and scapula. Thoracic kyphosis and lumbar lordosis in the pain group were significantly higher than those in the normal group (p = 0.013 and p = 0.020, respectively). Thoracic kyphosis in subjects with neck pain or pain above scapula was significantly higher than that in subjects without pain (p = 0.0075 and p = 0.025, respectively). Lumbar lordosis in subjects with pain above the scapula or interscapula was significantly higher than that in subjects without pain (p = 0.016).

关键词： Choronic Neck and Shoulder Pain Sagittal Alignment of the Spine Thoracic Kyphosis Lumber Lordosis

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Youngest case of an early gastric cancer after successful eradication therapy

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World Journal of Gastrointestinal Endoscopy 2013年第6期5卷 300-303页

作者： hironori Konuma Ichiro Konuma Kuangi Fu Satoshi Yamada Yutaka suzuki Akihisa Miyazaki Department of Gastroenterology Juntendo Univerity Nerima Hospital Konuma Clinic Yamada Clinic Department of Surgery International University of Health and Welfare Hospital

A 28-year-old woman visited our clinic with a chief complaint of epigastralgia. She had received successful Helicobacter pylori (H. pylori ) eradication therapy 5 years before. We repeated esophagogastroduodenoscopy, and a discolored depressed area with reddish spots and converging folds, 20 mm in size, was detected. No atrophic change including intestinal metaplasia or nodular gastritis was seen endoscopically. Two endoscopic biopsies revealed undifferentiated adenocarcinoma. No H. pylori was found, and the 13 C-urea breath test was also negative. Abdominal computed tomography demonstrated no nodal involvement, distant metastasis or fluid collection. She underwent a laparoscopyassisted distal gastrectomy. Histologically, the resected specimen revealed an early undifferentiated gastric cancer that had invaded deeply into the submucosal layer. Nodal involvement was histologically *** atrophic change or H. pylori infection was evident histologically. This is the youngest patient ever reported to have developed a node-positive early gastric cancer after eradication of H. pylori .

关键词： Early gastric cancer Helicobacter pylori Eradication therapy Undifferentiated adenocarcinoma Intestinal-type adenocarcinoma Point of no return theory

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