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| 1 | An updated review of gastric cancer in the next-generation sequencing era:Insights from bench to bedside and vice versa显示文摘Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets. | Hiroyuki Yamamoto Yoshiyuki Watanabe Tadateru Maehata Ryo Morita Yoshihito Yoshida Ritsuko Oikawa Shinya Ishigooka Shun-ichiro Ozawa Yasumasa Matsuo Kosuke Hosoya Masaki Yamashita Hiroaki Taniguchi Katsuhiko Nosho Hiromu Suzuki Hiroshi Yasuda Yasuhisa Shinomura Fumio Itoh | 2014 | World Journal of Gastroenterology2014，20，14： | 12 |
| 2 | Boron neutron capture therapy for vulvar melanoma and genital extramammary Paget’s disease with curative responses显示文摘Background:Although the most commonly recommended treatment for melanoma and extramammary Paget’s disease(EMPD)of the genital region is wide surgical excision of the lesion,the procedure is highly invasive and can lead to functional and sexual problems.Alternative treatments have been used for local control when wide local exci-sion was not feasible.Here,we describe four patients with genital malignancies who were treated with boron neutron capture therapy(BNCT).Methods:The four patients included one patient with vulvar melanoma(VM)and three with genital EMPD.They underwent BNCT at the Kyoto University Research Reactor between 2005 and 2014 using para-boronophenylalanine as the boron delivery agent.They were irradiated with an epithermal neutron beam between the curative tumor dose and the tolerable skin/mucosal doses.Results:All patients showed similar tumor and normal tissue responses following BNCT and achieved complete responses within 6 months.The most severe normal tissue response was moderate skin erosion during the first 2 months,which diminished gradually thereafter.Dysuria or contact pain persisted for 2 months and resolved com-pletely by 4 months.Conclusions:Treating VM and EMPD with BNCT resulted in complete local tumor control.Based on our clinical expe-rience,we conclude that BNCT is a promising treatment for primary VM and EMPD of the genital region. | Junichi Hiratsuka Nobuhiko Kamitani Ryo Tanaka Eisaku Yoden Ryuji Tokiya Minoru Suzuki Rolf F.Barth Koji Ono | 2018 | Cancer Communications2018，38，1： | 10 |
| 3 | Liver cirrhosis induced by long-term administration of a daily low dose of amiodarone: A case report显示文摘The anti-arrhythmic agent amiodarone (AD) is associated with numerous adverse effects, but serious liver disease is rare. The improved safety of administration of daily low doses of AD has already been established and this regimen is used for long-term medication. Nevertheless,asymptomatic continuous liver injury by AD may increase the risk of step-wise progression of non-alcoholic fatty liver disease. We present an autopsy case of AD-induced liver cirrhosis in a patient who had been treated with a low dose of AD (200 mg/d) daily for 84 mo. The patient was a 85-year-old male with a history of ischemic heart disease.Seven years after initiation of treatment with AD, he was admitted with cardiac congestion. The total dose of AD was 528 g. Mild elevation of serum aminotransferase and hepatomegaly were present. Liver biopsy specimens revealed cirrhosis, and under electron microscopy numerous lysosomes with electron-dense, whorled, lamellar inclusions characteristic of a secondary phospholipidosis were observed. Initially, withdrawal of AD led to a slight improvement of serum aminotransferase levels, but unfortunately his general condition deteriorated and he died from complications of pneumonia and renal failure.Long-term administration of daily low doses of AD carries the risk of progression to irreversible liver injury. Therefore,periodic examination of liver function and/or liver biopsy is required for the management of patients receiving long-term treatment with AD. | Hiroki Oikawa Chihaya Maesawa Ryo Sato Kanta Oikawa Hiroyuki Yamada Seizo Oriso Sadahide Ono Akiko Yashima-Abo Koji Kotani Kazuyuki Suzuki Tomoyuki Masuda | 2005 | World Journal of Gastroenterology2005，11，34： | 4 |
| 4 | gastrointestinal symptom prevalence depends on disease duration and gastrointestinal region in type 2 diabetes mellitus显示文摘AIM To unravel relationships between gastrointestinal(GI)symptoms impairing quality of life(QOL)and clinical profiles of diabetes mellitus(DM)patients. METHODS We enrolled 134 outpatients with type 2 DM.Mean age was 64.7 years,mean body mass index was 24.7 RESULTS Lower abdominal symptoms were found to be more frequent than those affecting the upper abdomen.Diabetic duration and medications showed associations with GI symptoms.We identified differences in peak prevalences of the five symptoms.Gastralgia(P=0.02vs 10-14 years)and total GI symptoms(P=0.01 and P=0.02 vs 5-9 years and 10-14 years,respectively)peaked at a diabetes duration of 15-19 years.Heartburn(P=0.004)and postprandial fullness(P=0.03)tended to increase with disease duration.Constipation and diarrhea showed bimodal peaks,with the first early and the second late(e.g.,P=0.03 at 15-19 years vs 10-14years for diarrhea)in the disease course.Finally,GI symptoms showed clustering that reflected the region of the GI tract affected,i.e.,constipation and diarrhea had similar frequencies(P<0.0001). CONCLUSION Our study highlights the importance of questioning patients about QOL impairment due to abdominal symptoms,especially in the early and the late periods of diabetes. | Midori Fujishiro Akifumi Kushiyama Hiroki Yamazaki Sunao Kaneko Yuko Koketsu Takeshi Yamamotoya Takako Kikuchi Hideyuki Sakoda Ryo Suzuki Takashi Kadowaki | 2017 | World Journal of Gastroenterology2017，23，36： | 4 |
| 5 | Thrombomodulin in the management of acute cholangitisinduced disseminated intravascular coagulation显示文摘AIM: To evaluate the need for thrombomodulin(r TM) therapy for disseminated intravascular coagulation(DIC) in patients with acute cholangitis(AC)-induced DIC. METHODS: Sixty-six patients who were diagnosedwith AC-induced DIC and who were treated at our hospital were enrolled in this study. The diagnoses of AC and DIC were made based on the 2013 Tokyo Guidelines and the DIC diagnostic criteria as defined by the Japanese Association for Acute Medicine, respectively. Thirty consecutive patients who were treated with r TM between April 2010 and September 2013(r TM group) were compared to 36 patients who were treated without r TM(before the introduction of r TM therapy at our hospital) between January 2005 and January 2010(control group). The two groups were compared in terms of patient characteristics at the time of DIC diagnosis(including age, sex, primary disease, severity of cholangitis, DIC score, biliary drainage, and anti-DIC drugs), the DIC resolution rate, DIC score, the systemic inflammatory response syndrome(SIRS) score, hematological values, and outcomes. Using logistic regression analysis based on multivariate analyses, we also examined factors that contributed to persistent DIC. RESULTS: There were no differences between the r TM group and the control group in terms of the patients' backgrounds other than administration. DIC resolution rates on day 9 were higher in the r TM group than in the control group(83.3% vs 52.8%, P < 0.01). The mean DIC scores on day 7 were lower in the r TM group than in the control group(2.1 ± 2.1 vs 3.5 ± 2.3, P = 0.02). The mean SIRS scores on day 3 were significantly lower in the r TM group than in the control group(1.1 ± 1.1 vs 1.8 ± 1.1, P = 0.03). Mortality on day 28 was 13.3% in the r TM group and 27.8% in the control group; these rates were not significantly different(P = 0.26). Multivariate analysis identified only the absence of biliary drainage as significantly associated with persistent DIC(P < 0.01, OR = 12, 95%CI: 2.3-60). Although the difference did not reach statistical significance, primary diseases(malignancies)(P = 0.055, OR = 3.9, 95%CI: 0.97-16) and the non-use of r TM had a tendency to be associated with persistent DIC(P = 0.08, OR = 4.3, 95%CI: 0.84-22).CONCLUSION: The add-on effects of r TM are anticipated in the treatment of AC-induced DIC, although biliary drainage for AC remains crucial. | Keigo Suetani Chiaki Okuse Kazunari Nakahara Yosuke Michikawa Yohei Noguchi Midori Suzuki Ryo Morita Nozomi Sato Masaki Kato Fumio Itoh | 2015 | World Journal of Gastroenterology2015，21，2： | 4 |
| 6 | Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma显示文摘AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma(HCC).METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers,including alpha fetoprotein(AFP) and proteins induced by vitamin K absence Ⅱ(PIVKA Ⅱ) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher's exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model.RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification,all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9,lung metastasis; 7,brain metastasis; 9,portal vein invasion;4,hepatic vein invasion; 4,bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%,respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP(HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA Ⅱ(HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo(95%CI: 5-15 mo). Terminal stage disease(HR = 9.809; 95%CI: 2.589-37.17,P < 0.001) and an AFP of more than 400 ng/m L(HR = 2.548; 95%CI: 1.070-6.068,P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy(HR = 0.274; 95%CI: 0.093-0.7541,P = 0.012) was associated with better survival. In the 52 cases of bone metastasis,36 patients(69%) achieved pain relief. One patient had cerebral bleeding and another patient had an esophageal ulcer after treatment.CONCLUSION: The Cyberknife can be safely administered to patients with advanced or terminal stage HCC. High AFP levels were associated with worse survival,but a higher radiation dose improved the survival. | Hiroyuki Kato Hideo Yoshida Hiroyoshi Taniguch Ryutaro Nomura Kengo Sato Ichiro Suzuki Ryo Nakata | 2015 | World Journal of Gastroenterology2015，21，46： | 3 |
| 7 | 硼中子俘获治疗外阴黑色素瘤和生殖器乳腺外Paget病的疗效显示文摘背景与目的尽管目前对生殖器区的黑色素瘤和乳腺外Paget病(extramammary Paget’s disease,EMPD)最常推荐的治疗方法是广泛性手术切除病变,但该方法侵害性极高并可导致功能性和性方面的问题。当扩大局部切除术不可行的情况下,替代疗法已被用于进行局部控制。本研究描述了4例接受硼中子俘获治疗(boron neutron capture therapy,BNCT)的生殖器恶性肿瘤患者。方法 4例患者中包括1例外阴黑色素瘤(vulvar melanoma,VM)和3例生殖器EMPD患者。他们于2005至2014年间在Kyoto大学研究堆接受了对二羟基硼酰苯丙氨酸作为硼携带剂的BNCT治疗。他们接受了介于治愈性肿瘤剂量和可耐受的皮肤/黏膜剂量之间的超热中子束照射。结果所有患者在BNCT治疗后均表现出相似的肿瘤和正常组织反应,并在6个月内达到完全缓解。最严重的正常组织反应前2个月内出现,随后逐渐减弱的中度皮肤糜烂,排尿困难或接触性疼痛持续2个月,完全解决需4个月。结论 BNCT治疗VM和EMPD后局部肿瘤得到完全控制。根据我们的临床经验,我们认为BNCT是治疗生殖器区原发性VM和EMPD的一种有前景的方法。 | Junichi Hiratsuka Nobuhiko Kamitani Ryo Tanaka Eisaku Yoden Ryuji Tokiya Minoru Suzuki Rolf F.Barth Koji Ono | 2018 | 癌症2018，37，7： | 3 |
| 8 | Induction of human cardiomyocyte-like cells from fibroblasts by defined factors显示文摘 | Rie Wada Naoto Muraoka Kohei Inagawa Hiroyuki Yamakawa Kazutaka Miyamoto Taketaro Sadahiro Tomohiko Umei Ruri Kaneda Tomoyuki Suzuki Kaichiro Kamiya Shugo Tohyama Shinsuke Yuasa Kiyokazu Kokaji Ryo Aeba Ryohei Yozu Hiroyuki Yamagishi Toshio Kitamura Keiic | 2013 | Proceedings of the National Academy of Sciences2013，，31： | 2 |
| 9 | Synergistic effect of ultrasound and antibiotics against Chlamydia trachomatis -infected human epithelial cells in vitro显示文摘 | Yurika Ikeda-Dantsuji Loreto B. Feril Katsuro Tachibana Koichi Ogawa Hitomi Endo Yoshimi Harada Ryo Suzuki Kazuo Maruyama | 2010 | Ultrasonics - Sonochemistry2010，，1： | 1 |
| 10 | Residual Urinary Concentrating Ability and AQP2 Expression in a Rat Model for Chronic Renal Failure显示文摘 | Katsuya Suzuki Ryo Hatano Mari Michimata | 2005 | Nephron Physiol2005，，99： | 1 |
| 11 | Different Roles of PPAR-γ Activity on Physiological and Pathological Alteration After Myocardial Ischemia显示文摘 | Ayako Nagashima Ryo Watanabe Masahito Ogawa Jun-ichi Suzuki Mayumi Masumura Keiichi Hishikari Tomoko Shimizu Kiyoshi Takayama Yasunobu Hirata Ryozo Nagai Mitsuaki Isobe | 2012 | Journal of Cardiovascular Pharmacology2012，，2： | 1 |
| 12 | Stable and unstable sets for evolution equations of parabolic and hyperbolic type 显示文摘 | Ikehata Ryo Suzuki Takashi | 1996 | Hiroshima Math J1996，26，： | 1 |
| 13 | A Study on Accuracy of Fixed Point Arithmetic FDTD Method 显示文摘 | Yamaguchi Ryo Suzuki Hidetoshi Takagi Yuta Uebayashi Shinji | 2006 | IEIC Technical Report (S0913-5685)2006，106，40： | 1 |
| 14 | A novel strategy utilizing ultrasound for antigen delivery in dendritic cell-based cancer immunotherapy显示文摘 | Ryo Suzuki Yusuke Oda Naoki Utoguchi Eisuke Namai Yuichiro Taira Naoki Okada Norimitsu Kadowaki Tetsuya Kodama Katsuro Tachibana Kazuo Maruyama | 2008 | Journal of Controlled Release2008，，3： | 1 |
| 15 | Responses of leaf photosynthesis and plant growth to altered sourceionships in fruit trees, ese and a Dutch tomato cultivar显示文摘 | Ryo Matsuda Katsumi Suzuki Akimasa Nakano | 2011 | Scientia Horticulturae2011，127，： | 1 |
| 16 | Cdc42 is required for chondrogenesis and interdigital programmed cell death during limb development显示文摘 | Ryo Aizawa Atsushi Yamada Dai Suzuki Tadahiro Iimura Hidetoshi Kassai Takeshi Harada Masayuki Tsukasaki Gou Yamamoto Tetsuhiko Tachikawa Kazuki Nakao Matsuo Yamamoto Akira Yamaguchi Atsu Aiba Ryutaro Kamijo | 2012 | Mechanisms of Development (-)2012，，1： | 1 |
| 17 | Estimation of inorganic gas permeability through an MFI-type silicalite membrane by a molecular simulation technique combined with permeation theory显示文摘 | Ryo Nagumo Hiromitsu Takaba Shigejirou Suzuki Shin-ichi Nakao | 2001 | Microporous and Mesoporous Materials2001，48，： | 1 |
| 18 | Effective anti-tumor activity of oxaliplatin encapsulated in transferrin–PEG-liposome显示文摘 | Ryo Suzuki Tomoko Takizawa Yasuhiro Kuwata Mahito Mutoh Nobuyuki Ishiguro Naoki Utoguchi Atsuko Shinohara Masazumi Eriguchi Hironobu Yanagie Kazuo Maruyama | 2007 | International Journal of Pharmaceutics2007，，1： | 1 |
| 19 | On the sterile F1 hybrids between the genera pseudogobio and gnathopogon(Cyprinidae)显示文摘 | RYO SUZUKI | 1973 | Japanese Journal of Ichthyology1973，20，4： | 1 |
| 20 | Effective anti-tumor activity ofoxaliplatin encapsulated in transferrin-PEG-lip- osome显示文摘 | Ryo Suzuki Tomoko Takizawa Yasuhiro Kuwata | 2008 | International Journal of Pharmaeeutics2008，346，12： | 1 |
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