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Leukemogenic Fusion Gene (p190 BCR-ABL) Transduction into Hematopoietic Stem/Progenitor Cells in the Common Marmoset

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Open Journal of Blood Diseases 2012年第1期2卷 1-10页

作者： Yan Dong Seiichiro Kobayashi Yamin Tian Manabu Ozawa Takafumi Hiramoto Kiyoko Izawa Yuansong Bai Yasushi Soda Erika Sasaki Toshio Itoh yoshiro maru Satoshi Takahashi Kaoru Uchimaru Naoki Oyaizu Arinobu Tojo Chieko Kai Kenzaburo Tani Central Institute for Experimental Animals Kawasaki Japan Department of Laboratory Medicine Research Hospital Institute of Medical Science the University of Tokyo Tokyo Japan Department of Molecular Genetics Medical Institute of Bioregulation Kyushu University Fukuoka Japan Department of Pharmacology Tokyo Woman’s Medical University Japan Division of Molecular Therapy Institute of Medical Science the University of Tokyo Tokyo Japan Laboratory Animal Research Center Institute of Medical Science the University of Tokyo Tokyo Japan.

Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In this study, we attempted to develop a leukemia nonhuman primate model that mimics various human systems. Hematopoietic stem/progenitor cells in the common marmoset were transduced with a lentiviral vector containing the p190 BCR-ABL fusion gene by ex vivo transduction or in vivo direct bone marrow injection. In the latter model, BCR-ABL gene expression was maintained for more than one and a half years. One marmoset unexpectedly developed myelofibrosis-like disease. However, none of the marmosets have developed leukemia to date. In conclusion, we successfully achieved sustained p190 BCR-ABL gene expression in vivo. However, a genetic mutation in addition to p190 BCR-ABL may be required for the malignant transformation of hematopoietic stem/progenitor cells in the common marmoset during the short observation period. This novel in vivo approach will help develop a marmoset leukemia model in the future.

关键词： Leukemia Lentiviral Vector Myelofibrosis Common Marmoset

鼠血清淀粉样蛋白A家族对肺Lewis细胞株体外迁移的作用及可能机制的初步研究

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中国癌症杂志 2010年第6期20卷 416-420页

作者：周敏欧阳建富田毅丸羲朗南京大学医学院附属鼓楼医院血液科江苏南京210009 东京女子医科大学药理学教研室日本东京162-8666

背景与目的:血清淀粉样蛋白A(serum amyloid A,SAA)通常被认为是炎症反应的主要蛋白之一,然而近来的许多研究提示SAA参与了多种恶性肿瘤的发生、发展,本研究旨在探讨鼠SAA家族所有成员在肿瘤转移中的作用和机制。方法:表达和纯化鼠SAA1-... 详细信息

背景与目的:血清淀粉样蛋白A(serum amyloid A,SAA)通常被认为是炎症反应的主要蛋白之一,然而近来的许多研究提示SAA参与了多种恶性肿瘤的发生、发展,本研究旨在探讨鼠SAA家族所有成员在肿瘤转移中的作用和机制。方法:表达和纯化鼠SAA1-GST、SAA2-GST、SAA3-GST、SAA4-GST融合蛋白,采用体外迁移实验,观察和比较鼠4种融合蛋白对Lewis肺癌(Lewis lung carcinoma,LLC)细胞、Ba/mTLR4/mMD2细胞及其对照Ba/κB细胞的迁移作用。通过蛋白免疫印迹杂交(Western blot)观察4种融合蛋白作用后LLC细胞的pIκB蛋白表达情况。结果:成功表达和纯化了鼠SAA1-GST、SAA2-GST、SAA3-GST、SAA4-GST融合蛋白。与GST相比,鼠4种融合蛋白均能显著地促进LLC细胞的迁移(P0.05)。鼠4种融合蛋白与GST相比,均能明显地促进Ba/mTLR4/mMD2细胞的迁移(P0.05)。Western blot结果显示,SAA1-GST、SAA2-GST、SAA3-GST、SAA4-GST较GST作用的LLC细胞的pIKB蛋白表达明显增强。结论:鼠SAA家族的4个成员可以促进某些细胞株细胞的体外迁移,并且它们可能通过激活由Toll样受体4(toll like receptor4,TLR4)介导的核因子kappa B(nuclear factor kappa B,NF-κB)信号转导通路发挥该作用。

关键词：血清淀粉样蛋白A 肿瘤转移迁移 toll样受体核因子kappaB

N-乙酰半胱氨酸对Rat-1/P_(185)BCR-ABL细胞锚定及非锚定生长模式的作用

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中国生化药物杂志 2009年第5期30卷 309-311页

作者：关朝阳张启国欧阳建丸羲朗南京大学医学院附属鼓楼医院血液科江苏南京210008 东京女子医科大学医学部药理分野

目的探讨N-乙酰半胱氨酸(NAC)对Rat-1/P185BCR-ABL细胞株锚定及非锚定生长模式的作用。方法对Rat-1,Rat-1/P185BCR-ABL细胞株进行普通贴壁培养、软琼脂中培养。用Alama blue法测定增殖活细胞的荧光强度,软琼脂培养法计数集落数。用台盼... 详细信息

目的探讨N-乙酰半胱氨酸(NAC)对Rat-1/P185BCR-ABL细胞株锚定及非锚定生长模式的作用。方法对Rat-1,Rat-1/P185BCR-ABL细胞株进行普通贴壁培养、软琼脂中培养。用Alama blue法测定增殖活细胞的荧光强度,软琼脂培养法计数集落数。用台盼蓝拒染试验比较不同NAC浓度下连续3 d的BaF3和BaF3/P185BCR-ABL增殖活细胞数。结果NAC对Rat-1,Rat-1/P185BCR-ABL细胞的贴壁锚定生长均无明显影响。软琼脂中Rat-1/P185BCR-ABL细胞的集落数目随NAC浓度呈剂量依赖性增加。经NAC处理后BaF3活细胞的数目在不同浓度组无差异,而BaF3/P185BCR-ABL活细胞数目呈NAC剂量依赖性增加。结论NAC对Rat-1/P185BCR-ABL非锚定生长有正性作用,对锚定生长模式无明显作用。

关键词： BCR-ABL 非锚定生长 N-乙酰半胱氨酸

人血清淀粉样蛋白A家族在肿瘤转移中的作用及机制的初步研究

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中华肿瘤防治杂志 2010年第21期17卷 1701-1704页

作者：周敏欧阳建富田毅丸羲朗南京大学医学院附属鼓楼医院血液科江苏南京210009 东京女子医科大学药理学东京162-8666

目的:探讨人血清淀粉样蛋白A家族成员在肿瘤转移中的作用和机制。方法:表达和纯化人SAA1-GST、SAA2-GST、SAA3-GST和SAA4-GST融合蛋白,采用体外迁移实验,观察和比较人SAA1-GST、SAA2-GST、SAA3-GST、SAA4-GST和GST对lewis肺癌(lewis lung carcinoma LLC)细胞、Ba/mTLR4/mMD2细胞及其对照Ba/κB细胞的迁移作用。通过蛋白质印迹法观察人SAA1-GST、SAA2-GST、SAA3-GST、SAA4-GST和GST作用后LLC细胞的IkB和pIkB蛋白表达。结果:成功表达和纯化人SAA1-GST、SAA2-GST、SAA3-GST和SAA4-GST融合蛋白。与GST对照组相比,人的4种融合蛋白均能显著促进LLC细胞的迁移,P0.05。蛋白质印迹法结果显示,人SAA1-GST、SAA2-GST、SAA3-GST和SAA4-GST较GST作用后LLC细胞pIKB蛋白表达明显增强,P<0.05。结论:人SAA家族成员都能促进肿瘤细胞的迁移,并且可能是通过激活由TLR4(toll like receptor 4)介导的NF-κB信号转导通路发挥该作用。

关键词：血清淀粉样蛋白A 肿瘤转移细胞运动

鼠血清淀粉样蛋白A家族在肿瘤转移中作用的初步研究

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现代肿瘤医学 2010年第11期18卷 2099-2101页

作者：周敏欧阳建富田毅丸義朗南京大学医学院附属鼓楼医院血液科江苏南京210009 东京女子医科大学药理学系

目的:探讨鼠血清淀粉样蛋白A(serum amyloid A,SAA)家族所有成员在肿瘤转移中的作用。方法:采用实时荧光定量PCR的方法,观察荷瘤鼠和正常对照鼠的6种组织(脑,肺,肝,肌肉,肾和脾)中SAA1,2,3,4 mRNA的表达。表达和纯化鼠SAA1,2,3,4-GST4... 详细信息

目的:探讨鼠血清淀粉样蛋白A(serum amyloid A,SAA)家族所有成员在肿瘤转移中的作用。方法:采用实时荧光定量PCR的方法,观察荷瘤鼠和正常对照鼠的6种组织(脑,肺,肝,肌肉,肾和脾)中SAA1,2,3,4 mRNA的表达。表达和纯化鼠SAA1,2,3,4-GST4种融合蛋白,通过肿瘤细胞体外迁移实验观察和比较鼠SAA1,2,3,4-GST对lewis肺癌细胞(LLC)迁移的作用。结果:LLC荷瘤鼠的6种组织中SAA1,2,3,4 mR-NA的表达是正常对照鼠相应组织的0.15-47.29倍,并且他们在肺组织中的表达较其他组织显著增加(P0.05)。结论:SAA1,2,3,4参与了肿瘤转移,对LLC肿瘤细胞的体外迁移有一定直接促进作用。

关键词：血清淀粉样蛋白A 肿瘤转移

Otolith Microstructure Analysis Reveals Different Growth Histories of Japanese Sardine (Sardinops melanostictus) in the Oyashio Waters

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Journal of Ocean University of China 2022年第1期21卷 236-242页

作者： LIU Chunlin ZHANG Chi TIAN Yongjun WANG Liangming LIN Longshan LI Yuan WATANABE yoshiro Key Laboratory of Mariculture Ministry of EducationOcean University of ChinaQingdao 266003China Frontiers Science Center for Deep Ocean Multispheres and Earth System(FDOMES) Ocean University of ChinaQingdao 266100China Laboratory for Marine Fisheries Science and Food Production Processes Pilot National Laboratory for Marine Science and TechnologyQingdao 266237China Third Institute of Oceanography Ministry of Natural ResourcesXiamen 361000China Atmosphere and Ocean Research Institute The University of TokyoKashiwa 277-8564Japan

After decades of low year classes,the stock of Japanese sardine(Sardinops melanostictus)has begun to recover since the mid-2000s.The hatch dates and otolith growth rates of age-0 juvenile sardine,which were collected in the subarctic Oyashio waters in autumn 2018,were determined from an otolith microstructure analysis.The sardines were hatched from late January to late April,while mostly in February and March.The otolith growth rate increased continuously up to 60 d after hatching and thereafter de-creased.The revealed growth rate in a crucial growth period is faster than that reported for juvenile sardines collected in the 1990s,which is coincided with the recent recovery trend of the sardine stock.Two groups with different hatch dates,growth histories,and migration routes were identified using unsupervised random forest clustering analysis.They were considered inshore and offshore migration individuals in accordance with recent researches.In the offshore group,a high proportion of sardine juveniles hatched late and grew faster in the Kuroshio-Oyashio transitional waters,a finding consistent with the hypothesis of growth-rate-dependent re-cruitment.This finding on the population composition and growth rate of juvenile sardine in the Oyashio waters can be a basis for an improved prediction of their survival and provides us with valuable information on the recruitment processes of this stock during the period of stock recovery.

关键词： Sardinops melanostictus otolith microstructure growth history unsupervised random forest clustering recruitment

Characteristics of In-Hospital Patients with Congenital Heart Disease Requiring Rapid Response System Activations: A Japanese Database Study

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Congenital Heart Disease 2022年第1期17卷 31-43页

作者： Taiki Haga Tomoyuki Masuyama yoshiro Hayashi Takahiro Atsumi Kenzo Ishii Shinsuke Fujiwara Department of Pediatric Critical Care Medicine Osaka City General HospitalOsaka534-0021Japan Department of Emergency and Critical Care Medicine Jichi Medical University Saitama Medical CenterSaitama330-8503Japan Department of Intensive Care Medicine Kameda Medical CenterChiba296-8602Japan Department of Emergency Medicine Seirei Hamamatsu General HospitalShizuoka430-8558Japan Department of Anesthesiology Intensive Care UnitFukuyama City HospitalHiroshima721-8511Japan Department of Emergency Medicine NHO Ureshino Medical CenterSaga843-0393Japan

Objectives:This study aimed to study the characteristics of in-hospital deterioration in patients with congenital heart disease who required rapid response system activation and identify risk factors associated with 1-month mortality.Methods:We retrospectively analysed data from a Japanese rapid response system registry with 35 participating hospitals.We included consecutive patients with congenital heart disease who required rapid response system activation between January 2014 and March 2018.Logistic regression analyses were performed to examine the associations between 1-month mortality and other patient-specific variables.Results:Among 9,607 patients for whom the rapid response system was activated,only 82(0.9%)had congenital heart disease.Only few patients with congenital heart disease were being treated at the cardiology and cardiovascular surgery departments(12.3%and 9.9%,respectively).Moreover,the incidences of rapid-response events after intensive care unit discharge or surgery were low(6.8% and 12.2%,respectively).The most common reason for rapid response system activation was respiratory dysfunction(desaturation:35.4%,tachypnoea:25.6%,and new dyspnoea:19.5%).Rapid response system interventions and intensive care unit transfers were required for 65.9% and 20.7%of patients,respectively.The mortality rate was 1.2% at the end of the rapid response system intervention and 11.0% after 1 month.Moreover,decreased respiratory rate and decreased heart rate at rapid response system activation were associated with increased 1-month mortality.The adjusted odds ratio was 1.10(95% confidence interval 1.02–1.19)and 1.02(95% confidence interval,1.00–1.04) for respiratory rate and heart rate,respectively.Conclusions:Rapid response systems were rarely activated after cardiac surgery and intensive care unit discharge,which were situations with a high risk of sudden deterioration in patients with congenital heart disease.Therefore,encouraging the use of the rapid response system in these departments will enable interventio

关键词： Heart defects congenital emergencies clinical deterioration hospital rapid response team critical care This

Direct-acting antivirals for hepatitis C virus-infected patients with hepatocellular carcinoma

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World Journal of Hepatology 2022年第6期14卷 1190-1199页

作者： Kazuto Tajiri Hiroyuki Ito Kengo Kawai yoshiro Kashii Yuka Hayashi Aiko Murayama Masami Minemura Terumi Takahara Yukihiro Shimizu Ichiro Yasuda Department of Gastroenterology Toyama University HospitalToyama 930-0194Japan Department of Gastroenterology Takaoka Municipal HospitalTakaoka 933-8550Japan Gastroenterology Center Nanto Municipal HospitalNanto 932-0211Japan Department of Gastroenterology Saiseikai Toyama HospitalToyama 931-8533Japan

BACKGROUND Hepatocellular carcinoma(HCC)in hepatitis C virus(HCV)-infected patients has a high risk of recurrence.Although eradication of HCV is expected to reduce this risk,the risk in patients with a history of HCC may be high after treatment with direct-acting antivirals(DAAs).AIM To determine the risk factors for HCC recurrence in patients with HCV and a history of HCC.METHODS The risk of HCC recurrence in patients with a history of HCC and/or of HCC occurrence in patients without a history of HCC after DAA therapy was retrospectively analyzed in 311 HCV patients treated at our institution and several neighboring hospitals.The frequency and predictors of HCC recurrence/occurrence after DAA treatment were included in these analyses.The clinical course of HCC before and after DAA treatment was also evaluated.RESULTS HCV patients with a history of HCC were older and had greater progression of liver fibrosis and diabetes than patients without a history of HCC.Median recurrence-free survival(RFS)was 1092 d in patients with a history of HCC,and post-DAA HCC recurrence/occurrence was observed in 29 patients(53.7%)with and 5(1.9%)without a history of HCC over 6 years(P<0.001).RFS in patients with a history of HCC did not differ significantly before and after DAA treatment.The frequency of HCC recurrence/occurrence in patients with a history of HCC was lower after than before DAA treatment.Multivariate analysis showed that the incidence rate of HCC recurrence/occurrence before DAA treatment was the only independent predictor of HCC recurrence/occurrence after DAA treatment.Liver function was well preserved and clinical course was good in patients with HCC recurrence/occurrence after DAA therapy.CONCLUSION DAA therapy in patients infected with HCV is also effective in patients with a history of HCC.Curative treatment for HCC is desirable before DAA therapy.The frequency of HCC recurrence/occurrence before DAA therapy was associated with a significantly increased risk of HCC recurrence after DAA therapy.Careful observat

关键词： Direct-acting antivirals Hepatitis C virus Hepatocellular carcinoma Recurrence Liver fibrosis Curative treatment

Review of oral and pharyngolaryngeal benign lesions detected during esophagogastroduodenoscopy

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World Journal of Gastrointestinal Endoscopy 2023年第7期15卷 496-509页

作者： Masaya Iwamuro Kenta Hamada Seiji Kawano yoshiro Kawahara Motoyuki Otsuka Department of Gastroenterology and Hepatology Okayama University Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama 700-8558Japan Department of Practical Gastrointestinal Endoscopy Okayama University Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama 700-8558Japan

Recent advancements in endoscopy equipment have facilitated endoscopists’detection of neoplasms in the oral cavity and pharyngolaryngeal regions.In particular,image-enhanced endoscopy using narrow band imaging or blue laser imaging play an integral role in the endoscopic diagnosis of oral and pharyngolaryngeal cancers.Despite these advancements,limited studies have focused on benign lesions that can be observed during esophagogastroduodenoscopy in the oral and pharyngolaryngeal regions.Therefore,this mini-review aimed to provide essential information on such benign lesions,along with representative endoscopic images of dental caries,cleft palate,palatal torus,bifid uvula,compression by cervical osteophytes,tonsil hyperplasia,black hairy tongue,oral candidiasis,oral and pharyngolaryngeal ulcers,pharyngeal melanosis,oral tattoos associated with dental alloys,retention cysts,papilloma,radiation-induced changes,skin flaps,vocal cord paresis,and vocal fold leukoplakia.Whilst it is imperative to seek consultation from otolaryngologists or dentists in instances where the diagnosis cannot be definitively ascertained by endoscopists,the merits of attaining foundational expertise pertaining to oral and pharyngolaryngeal lesions are unequivocal.This article will be a valuable resource for endoscopists seeking to enhance their understanding of oral and pharyngolaryngeal lesions.

关键词： Benign diseases Diagnosis Esophagogastroduodenoscopy Non-neoplastic lesions Oral lesions Pharyngolaryngeal lesions