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The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe ken kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~1.Since statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in Japan.Cancer surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has increased.Approximately 38,000 people died of cancer in 2021.The National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

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Impact of adjustment measures on reducing outpatient waiting time in a community hospital： application of a computer simulation

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Chinese Medical Journal 2010年第5期123卷 574-580页

作者： CHEN Bai-lian LI En-dong Kazunobu Yamawuchi ken kato Shinji Naganawa MIAO Wei-jun Department of Medical Information and Management Science Graduate School of Medicine Nagoya University 65 Tsurumai-cho Showa-ku Nagoya Japan Department of Radiology Graduate School of Medicine Nagoya University 65 Tsurumai-cho Showa-ku Nagoya Japan Scientific Research Management Department Second Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong 510260 China

Background As an important determinant of patient satisfaction, waiting time, has gained increasing attention in the field of health care services. The present study aimed to illustrate the distribution characteristics of waiting time in a community hospital and explore the impact of potential measures to reduce outpatient waiting time based on a computer simulation approach. Methods Dudng a one-month study period in 2006, a cross-sectional study was conducted in a community hospital located in Shanghai, China. Baseline data of outpatient waiting time were calculated according to the records of registration time and payment time. A simulation technique was adopted to investigate the impact of perspective reform methods on reducing waiting time. Results Data from a total of 10 092 patients and 26 816 medical consultations were collected in the study and 19 947 medical consultations were included. The average of the total visit time for outpatients in this hospital was 43.6 minutes in the morning, 19.1 minutes in the afternoon, and 34.3 minutes for the whole day studied period. The simulation results suggested that waiting time for outpatients could be greatly reduced through the introduction of appointment system and flexible demand-orientated doctor scheduling according to the numbers of patients waiting at different time of the workday. Conclusion Adoption of an appointment system and flexible management of doctor scheduling may be effective way to achieve decreased waiting time.

关键词： waiting time outpatient appointment system

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Induction chemotherapy with docetaxel,cisplatin and fluorouracil followed by concurrent chemoradiotherapy for unresectable sinonasal undifferentiated carcinoma: Two cases of report

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World Journal of Clinical Cases 2019年第6期7卷 765-772页

作者： Sho Watanabe Yoshitaka Honma Naoya Murakami Hiroshi Igaki Taisuke Mori Hidekazu Hirano Natsuko Okita Hirokazu Shoji Satoru Iwasa Atsuo Takashima ken kato kenya Kobayashi Fumihiko Matsumoto Seiichi Yoshimoto Jun Itami Narikazu Boku Department of Head and Neck Medical Oncology National Cancer Center Hospital Department of Radiation Oncology National Cancer Center Hospital Department of Pathology and Clinical Laboratories National Cancer Center Hospital Department of Gastrointestinal Medical Oncology National Cancer Center Hospital Department of Head and Neck Surgery National Cancer Center Hospital

BACKGROUND Sinonasal undifferentiated carcinoma(SNUC) is a rare aggressive tumor that is often unresectable. Optimal treatment for patients with unresectable,locally advanced SNUC(LA-SNUC) has not been established,and the patient outcome remains poor. We report two cases of unresectable LA-SNUC in which induction chemotherapy with docetaxel,cisplatin and fluorouracil(TPF) followed by radiotherapy with concurrent cisplatin(CCRT),a standard treatment option for locally advanced head and neck cancer,demonstrated promising outcomes.CASE SUMMARY A 39-year-old man presented with tearing and pain in the right eye. A biopsy of the tumor invading the sinonasal cavities,right orbit and cranial base confirmed the diagnosis of LA-SNUC. Induction TPF chemotherapy induced remarkable tumor shrinkage and rapidly improved the symptoms. He subsequently received CCRT and achieved complete remission of the disease. The other case is a 21-year-old man who presented with worsening vision. The unresectable tumor involving the nasal septum and cranial base was pathologically diagnosed as SNUC. TPF chemotherapy followed by CCRT yielded complete remission of the disease with preserved visual function. Both patients have been disease-free for44 mo.CONCLUSION Induction TPF chemotherapy followed by CCRT may remarkably improve the outcomes in LA-SNUC patients.

关键词： Sinonasal undifferentiated carcinoma Chemotherapy with docetaxel, cisplatin and fluorouracil chemotherapy Docetaxel Cisplatin Fluorouracil Intensity-modulated radiotherapy Chemoradiotherapy Case report

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Impact of Oxaliplatin-Induced Neuropathy on Subsequent Paclitaxel for Advanced Gastric Cancer

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International Journal of Clinical Medicine 2020年第9期11卷 526-537页

作者： Jun Sato Satoru Iwasa Yoshitaka Honma Atsuo Takashima Natsuko Okita ken kato Tetsuya Hamaguchi Yasuhide Yamada Narikazu Boku Gastrointestinal Medical Oncology Division National Cancer Center Hospital Tokyo Japan

Purpose: Several studies have shown that fluoropyrimidine plus oxaliplatin (SOX) is non-inferior to fluoropyrimidine plus cisplatin as first-line chemotherapy for advanced gastric cancer. We investigated retrospectively the choice of second-line regimen, along with the proportion and feasibility of paclitaxel-containing regimen, in the subsequent treatment of patients with advanced gastric cancer treated with SOX as first-line chemotherapy. Materials and Methods: We retrospectively analyzed the impact of oxaliplatin-induced neuropathy on both the choice of subsequent regimens and feasibility of subsequent chemotherapy with paclitaxel, focusing on patients with advanced gastric cancer who received S-1 plus oxaliplatin as first-line chemotherapy. Results: Twenty-seven from a total of 31 patients enrolled into the phase 2 and phase 3 study assessing S-1 plus oxaliplatin were analyzed (4 patients were deemed ineligible). Among 24 patients that had received second-line treatment, paclitaxel was not selected in 2 patients due to oxaliplatin-induced neuropathy. Paclitaxel was selected as second-line chemotherapy in 16 patients, as third-line chemotherapy in 6 patients and fourth-line chemotherapy in one patient. Severity of sensory neuropathy was grade 0/1/2/3 in 11/10/2/0 patients, respectively, immediately before treatment with paclitaxel, while the worst toxicity profile during paclitaxel treatment was grade 0/1/2/3 in 7/13/1/2 patients, respectively. Although there were no patients requiring dose reductions of paclitaxel due to neuropathy, 2 patients discontinued paclitaxel use due to grade 3 sensory neuropathy after 4 or 8 administrations of paclitaxel. Conclusion: Oxaliplatin-induced neuropathy during first-line chemotherapy may affect the choice and feasibility of subsequent chemotherapy with paclitaxel in advanced gastric cancer patients.

关键词： Gastric Cancer Neuropathy Oxaliplatin Paclitaxel

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Experimental and Numerical Investigation on Compressor Cascade Flows with Tip Clearance at a Low Reynolds Number Condition

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Journal of Thermal Science 2011年第6期20卷 481-485页

作者： Hiromasa kato Hideo Taniguchi Kazunari Matsuda ken-ichi Funazaki Dai kato Guillaume Pallot Department of Mechanical Engineering Faculty of EngineeringIwate University Aerodynamic Technology Group IHI Corporation

High flow rate aeroengines typically employ axial flow compressors,where aerodynamic loss is predominantly due to secondary flow features such as tip leakage and corner vortices.In very high altitude missions,turbomachinery operates at low density ambient atmosphere,and the recent trend toward more compact engine core inevitably leads to the reduction of blade size,which in turn increases the relative height of the blade tip clearance.Low Reynolds number flowfield as a result of these two factors amplifies the relative importance of secondary flow effects.This paper focuses on the behavior of tip leakage flow,investigating by use of both experimental and numerical approaches.In order to understand the complex secondary flow behavior,cascade tests are usually conducted using intrusive probes to determine the loss.However relatively few experimental studies are published on tip leakage flows which take into account the interaction between a rotating blade row and its casing wall.Hence a new linear cascade facility has been designed with a moving belt casing in order to reproduce more realistic flowfield as encountered by a rotating compressor row.Numerical simulations were also performed to aid in the understanding of the complex flow features.The experimental results indicate a significant difference in the flowfield when the moving belt casing is present.The numerical simulations reveal that the leakage vortex is pulled by the shearing motion of the endwall toward the pressure side of the adjacent blade.The results highlight the importance of casing wall relative motion in analyzing leakage flow effects.

关键词：叶尖间隙低雷诺数数值方法压气机叶栅实验航空发动机旋转压缩机泄漏流量

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Fabrication of ZrC/ZrB₂/C Composites Having High Mechanical Properties at Elevated Temperatures

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Materials Sciences and Applications 2022年第4期13卷 232-248页

作者： Kai Matsumoto Masaki kato ken Hirota Toshiyuki Nishimura Department of Molecular Chemistry & Biochemistry Faculty of Science & Engineering Doshisha University Kyotanabe Japan National Institute for Materials Science Tsukuba Japan

Ultra-high temperature ceramics (UHTCs) are most recently getting much attention for structural parts of hypersonic missiles with their cruising speed of more than Mach 5. Most of the UHTCs are poor sinterability carbides, nitrides, and borides. Therefore, they have been studied and developed for a long time. However, there are still many problems to solve. In this paper, based on the solid-state reaction presented as an equation of (x + y)·ZrC + 2·y·B → x·ZrC + y·ZrB2 + y·C, three-phase ZrC/ZrB2/C composites have been fabricated from ZrC and amorphous B powders using pulsed electric-current pressure sintering at 1373 to 2173 K for 6.0 × 102 s under 50 MPa in a vacuum. ZrC/ZrB2/C = 30/70/C~70/30/C vol% composites with the relative densities Dr of 96.6 to 98.7% were obtained at 2073 K. The 60/40/C vol% composite revealed high bending strength σb (554 MPa), Vickers hardness Hv (19.2 GPa) and moderate fracture toughness KIC (5.25 MPa·m1/2) at room temperature. Furthermore, all composites showed elastic deformation up to 1873 K and revealed σb more than 600 MPa at this temperature, in addition, some composites showed higher σb than 900 MPa at the same temperature. These high mechanical behaviors are discussed with those of the simple binary ZrC/ZrB2 composites which were fabricated under the same conditions except for their starting materials. The best mechanical properties of binary composites were σb (474 MPa), Hv (18.5 GPa), and KIC (4.45 MPa·m1/2) at room temperature, and σb of 400 - 700 MPa at 1873 K. Overall, three-phase composites, nevertheless including soft carbon, have higher mechanical properties than the binary composites.

关键词： ZrC ZrB2 C Composites Pulsed Electric-Current Pressure Sintering Mechanical Properties

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Efficacy and Safety of the Atrial Septal Defect Closure for Patients with Absent or Malaligned Aortic Rim Using a Figulla Flex II Device Flared and Straddling Behind the Aorta

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Congenital Heart Disease 2021年第3期16卷 269-283页

作者： Masataka Kitano Kazuto Fujimoto Atsuko kato ken-ichi Kurosaki Isao Shiraishi Department of Pediatric Cardiology National Cerebral and Cardiovascular CenterOsakaJapan Department of Pediatric Cardiology Okinawa Prefectural Nanbu Medical Center&Children’s Medical CenterOkinawa PrefectureJapan

Background:Although transcatheter closure of atrial septal defect(ASD)is safe and effective for patients with sufficient rim,ASD patients with absent and/or malaligned aortic and/or superior rim have higher risks of device embolization and cardiac erosion.We have treated such high-risk patients using a Figulla Flex II(FFII)device shaped flared and straddling behind the aorta because this method would avoid such serious complications.However,its long-term efficacy and safety remain unclear.Therefore,the midterm efficacy and safety of this method were studied.Methods:We retrospectively evaluated the outcome of 47 consecutive patients with such rim(age 6–73 years,weight 17–75 kg,31 females)treated with this method at our hospital between February 2016 and September 2019.To make the flared and straddling shape,we selected a FFII 4–6 mm larger than the balloon sizing diameter by stop-flow technique.We also studied the device shape,the disc pressure to the Valsalva wall and their changes over 6 months by transesophageal echocardiography.Results:All procedures were successful,and leakage disappeared within 1 year.During a mean follow up of 37±12 months,complications included a transient sinus node dysfunction and one I°atrioventricular block within 3 months.Whole device shape changed from bulky to thin:the device waist and thickness significantly decreased by around 1.5 mm and 3.5 mm,respectively(p<0.05),but the two discs remained flared and straddling behind the aorta over 6 months;therefore,the disc edges seldom pressed the Valsalva wall perpendicularly,even though the inner plane of either disc often slightly pressed the wall.Conclusions:ASD closure using a FFII shaped flared and straddling behind the aorta is probably effective and safe for patients with absent and/or malaligned aortic and/or superior rim although requiring care for conduction disorders.

关键词： Atrial septal defect catheter intervention device embolization cardiac erosion conduction disorder

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Relationship between ghrelin, Helicobacter pylori and gastric mucosal atrophy in hemodialysis patients

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World Journal of Gastroenterology 2016年第47期22卷 10440-10449页

作者： Hitomi Ichikawa Mitsushige Sugimoto Yukitoshi Sakao Shu Sahara Naro Ohashi Akihiko kato ken Sugimoto Takahisa Furuta Akira Andoh Tadashi Sakao Hideo Yasuda First Department of Medicine Hamamatsu University School of Medicine Hamamastsu Shizuoka 431-3192 Japan Division of Digestive Endoscopy Shiga University of Medical Science Hospital Otsu Shiga 520-2192 Japan Hamana Clinic Hamana Clinic Hamamatsu Shizuoka 434-0037 Japan Blood Purification Unit Hamamatsu University School of Medicine Hamamastsu Shizuoka 431-3192 Japan Center for Clinical Research Hamamatsu University School of Medicine Hamamastsu Shizuoka 431-3192 Japan Department of Gastroenterology Shiga University of Medical Science HospitalOtsu Shiga 520-2192 Japan

AIM To investigate the relationship between plasma ghrelin level, Helicobacter pylori(H. pylori) infection status and the severity of atrophy in hemodialysis patients.METHODS One hundred eights patients who received hemodialysis and 13 non-hemodialysis H. pylori-negative controlsunderwent gastroduodenoscopy to evaluate the severity of gastric atrophy. Serum levels of pepsinogen(PG) were measured as serum markers of gastric atrophy. H. pylori infection was evaluated by anti-H. pylori IgG antibody, rapid urease test and culture test. We classified H. pylori infection status as non-infection, present infection and past infection. In addition, plasma acyl-ghrelin and desacyl-ghrelin levels were measured by enzyme-linked immunosorbent assay. RESULTS Infection rate of H. pylori was 45.4%(49/108). Acylghrelin level in the non-infection group(39.4 ± 23.0 fmol/ml) was significantly higher than in the past(23.4 ± 19.9 fmol/ml, P = 0.005) and present infection groups(19.5 ± 14.0 fmol/ml, P < 0.001). Furthermore, desacyl-ghrelin level in the non-infection group(353.2 ± 190.2 fmol/ml) was significantly higher than those in the past(234.9 ± 137.5 fmol/ml, P = 0.008) and present infection groups(211.8 ± 124.2 fmol/ml, P < 0.001). Acyl-ghrelin was positively correlated with the PG Ⅰ level and PG Ⅰ/Ⅱ ratio(|R| = 0.484, P < 0.001 and |R| = 0.403, P < 0.001, respectively). Both ghrelins were significantly decreased in accordance with the progress of endoscopic atrophy(both P < 0.001) and acyl-ghrelin was significantly lower in patients with mild, moderate and severe atrophy(24.5 ± 23.1 fmol/ml, 20.2 ± 14.9 fmol/ml and 18.3 ± 11.8 fmol/ml) than in those with non-atrophy(39.4 ± 22.2 fmol/ml, P = 0.039, P = 0.002 and P < 0.001, respectively).CONCLUSION In hemodialysis patients, plasma ghrelin level was associated with the endoscopic and serological severity of atrophy related to H. pylori infection.

关键词： Acyl-ghrelin Desacyl-ghrelin Helicobacter pylori Hemodialysis Pepsinogen

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Thermal stability of proteins in the presence of aprotic ionic liquids

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Journal of Biomedical Science and Engineering 2011年第2期4卷 94-99页

作者： Hidetaka Noritomi ken Minamisawa Reo Kamiya Satoru kato 不详

Thermal stability of lysozyme dissolved in aqueous solutions was examined in the presence of water-miscible aprotic ionic liquids consisting of 1-ethyl-3-methylimidazolium cation and several kinds of anions. Addition of ionic liquids to an aqueous solution containing lysozyme prevented unfolded proteins from aggregating irreversibly at high temperatures. The thermal denaturation curve of lysozyme with ionic liquids was entirely shifted to higher temperature, compared with that without ionic liquids. The remaining activity of lysozyme after the heat treatment was markedly dependent upon the kind and concentration of ionic liquids. The remaining activi-ties of lysozyme with 1.5 M 1-ethyl-3-methylimida-zolium tetrafluoroborate ([emim][BF4]) and 0.1 M 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([emim][Tf]) exhibited 88 and 68% after the heat treatment at 90oC for 30 min, respectively, although that without ionic liquids was perfectly lost.

关键词： Thermal Stability Lysozyme Ionic Liquid Remaining Activity

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