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Feasibility and Efficacy Study of Biweekly Irinotecan Combined with Oral Tegafur/Uracil in Advanced Colorectal Cancer

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Journal of Cancer Therapy 2013年第6期4卷 8-14页

作者： Masataka Ikeda Mitsugu Sekimoto Ichiro Takemasa Tsunekazu Mizushima Hirofumi Yamamoto hideshi ishii Yuichiro Doki Masaki Mori Department of Surgery Gastroenterological Surgery Osaka University Graduate School of Medicine Osaka Japan Department of Surgery Natinal Hospital Organization Osaka National Hospital Osaka Japan

Background: We evaluated the feasibility and efficacy of irinotecan (CPT-11) plus tegafur/uracil (UFT) combination chemotherapy in patients with advanced colorectal cancer. Patients and Methods: PK parameters were concurrently measured to confirm the presence of drug interactions in this treatment schedule. CPT-11 was administered intravenously at the dose of 150 mg/m2 on days 1, 15. UFT was administered at the dose of 375 mg/m2/day (B.I.D.) on days 3 - 7, 10 - 14, 17 - 21, 24 - 28 repeated every 5 weeks. Results: 31 patients were enrolled. PK parameters for CPT-11, FT, 5-FU and uracil are available from 5 patients. The overall response rate was 16.1%. The median time to treatment discontinuation was 3.9 months. There was no significant difference in PK parameters of CPT-11 between day 1 and day 15 and of UFT between day 3 and day 10. Conclusion: CPT-11 plus UFT combination chemotherapy exhibited a tolerable toxicity profile with acceptable efficacy. Pharmacokinetic analysis showed that there were no drug interactions in this treatment schedule.

关键词： Colorectal Neoplasms Pharmacokinetics Drug Therapy Fluorouracil Tegafur/Uracil UFT

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

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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 *** 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 *** 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 *** 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 *** quantity and quality of these samples will be compatible with omics *** 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

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~*** statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in *** surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has *** 38,000 people died of cancer in *** 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

Aszonapyrone A Isolated from Neosartorya spinosa IFM 47025 Inhibits the NF-κB Signaling Pathway Activated by Expression of the Ependymoma-Causing Fusion Protein ZFTA-RELA

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Advances in Microbiology 2024年第9期14卷 448-467页

作者： Kazuki Ishikawa Nao Kamiya Masaki ishii Takashi Yaguchi Koji Ichinose Shinya Ohata Faculty of Pharmaceutical Sciences Teikyo Heisei University Nakano Tokyo Japan Research Institute of Pharmaceutical Sciences Faculty of Pharmacy Musashino University Nishitokyo-Shi Tokyo Japan Medical Mycology Research Center Chiba University Inohana Chiba Japan

Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-translocation-associated (ZFTA, ST-EPN-ZFTA), exhibits the expression of a fusion protein comprising ZFTA and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-kappa B (NF-κB) pathway (ZFTA-RELA). The expression of ZFTA-RELA results in the hyperactivation of the oncogenic NF-κB signaling pathway, which ultimately leads to the development of ST-EPN-ZFTA. To identify inhibitors of the NF-κB signaling pathway activated by the expression of ZFTA-RELA, we used a doxycycline-inducible ZFTA-RELA-expressing NF-κB reporter cell line and found that extracts of the fungus Neosartorya spinosa IFM 47025 exhibited NF-κB inhibitory activity. We identified eight compounds [aszonapyrone A (2), sartorypyrone A (3), epiheveadride (4), acetylaszonalenin (5), (R)-benzodiazepinedione (6), aszonalenin (7), sartorypyrone E (8) and (Z, Z)-N,N’-(1,2-bis[(4-methoxyphenyl)methylene]-1,2-ethanediyl)bis-formamide (9)] from N. spinosa IFM 47025 culture extract using a variety of chromatographic techniques. The structures of these compounds were identified through the analysis of various instrumental data (1D, 2D-NMR, MS, and optical rotation). The NF-κB responsive reporter assay indicated that compounds 2, 3, 5, 7, and 9 exhibited inhibitory activity. We further evaluated the inhibitory activity of these compounds against the expression of endogenous NF-κB responsive genes (CCND1, L1CAM, ICAM1, and TNF) and found that compound 2 showed significant inhibitory activity. Further studies are required to elucidate the mechanism of action of compound 2, which may serve as a lead compound for the development of a novel therapy for ST-EPN-ZFTA.

关键词： Aszonapyrone A Neosartorya spinosa NF-κB Signaling Pathway Ependymoma ZFTA-RELA

Asymptotic behavior of solutions of defocusing integrable discrete nonlinear Schrodinger equation

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Frontiers of Mathematics in China 2013年第5期8卷 1077-1083页

作者： hideshi YAMANE Department of Mathematical Sciences Kwansei Gakuin University Sanda 669-1337 Japan

We report our recent result about the long-time asymptotics for the defocusing integrable discrete nonlinear Schrodinger equation of Ablowitz- Ladik. The leading term is a sum of two terms that oscillate with decay of... 详细信息

关键词： Discrete nonlinear Schrodinger equation Ablowitz-Ladik model,asymptotics inverse scattering transform nonlinear steepest descent

Study of Hydrogen Adsorption on Pt/WO_3-ZrO_2 through Pt Sites

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Journal of Natural Gas Chemistry 2007年第3期16卷 252-257页

作者： Sugeng Triwahyono Aishah Abdul Jalil hideshi Hattori Ibnu Sina Institute for Fundamental Science Studies Faculty of SciencesUniversiti Teknologi Malaysia81310 UTM SkudaiJohorMalaysia Faculty of Chemical & Natural Resources Engineering Universiti Teknologi Malaysia81310 UTM SkudaiJohorMalaysia Center for Advanced Research of Energy Technology Hokkaido UniversityNishi 5Kita 8Sapporo060-0808Japan

The rate determining step and the energy barrier involved in hydrogen adsorption on Pt/WO3- ZrO2 were studied based on the assumption that the hydrogen adsorption occurs only through Pt sites. The rate of hydrogen adsorption on Pt/WOa-ZrO2 was measured in the adsorption temperature range of 323-573 K and an initial hydrogen pressure of 50 Torr. The rates of hydrogen uptake were very high for the initial few minutes and the adsorption continued for more than 5 h below 523 K. The hydrogen uptake far exceeded the H/Pt ratio of unity for all adsorption temperatures, indicating that the adsorption of hydrogen involved the dissociative adsorption of hydrogen on Pt sites to form hydrogen atoms, the spillover of hydrogen atoms onto the surface of the WO3-ZrO2 catalyst, the diffusion of spiltover hydrogen atom over the surface of the WO3-ZrO2 catalyst, and the formation of protonic acid site originated from hydrogen atom by releasing an electron in which the electron may react with a second hydrogen atom to form a hydride near the Lewis acid site. The rate determining step was the spillover with the activation energy of 12.3 kJ/mol. The rate of hydrogen adsorption cannot be expressed by the rate equation based on the assumption that the rate determining step is the surface diffusion. The activity of Pt/WO3-ZrO2 was examined on n-heptane isomerization in which the increase of hydrogen partial pressure provided positive-effect on the conversion of n-heptane and negative-effect on the selectivity towards iso-heptane.

关键词： Pt/WO3-ZrO2 Pt sites hydrogen adsorption spillover n-heptane isomerization

Can early precut reduce post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with difficult bile duct cannulation?

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World Journal of Gastrointestinal Endoscopy 2024年第9期16卷 519-525页

作者： Tomohiro Tanikawa Keisuke Miyake Mayuko Kawada Katsunori ishii Takashi Fushimi Noriyo Urata Nozomu Wada Ken Nishino Mitsuhiko Suehiro Miwa Kawanaka Hidenori Shiraha Ken Haruma Hirofumi Kawamoto Department of General Internal Medicine 2 Kawasaki Medical SchoolOkayama 7008505Japan

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is associated with a variety of adverse events(AEs).One of the most important AEs is post-ERCP pancreatitis(PEP),which is most common in cases of difficult biliary *** the precut technique has been reported as a PEP risk factor,recent studies indicate that early precut could reduce PEP,and that precut itself is not a risk *** To evaluate the safety of the precut technique,especially in terms of *** We conducted a retrospective study,spanning the period from November 2011 through December *** included 1556 patients,aged≥20 years,who underwent their initial ERCP attempt for biliary disease with a naïve papilla at the Kawasaki University General Medical *** compared the PEP risk between the early precut and the delayed precut *** The PEP incidence rate did not significantly differ between the precut and nonprecut ***,the PEP incidence was significantly lower in the early precut group than the delayed precut group(3.5%vs 10.5%;P=0.02).The PEP incidence in the delayed precut group without pancreatic stent insertion(17.3%)was significantly higher compared to other cases(P<0.01).CONCLUSION Our findings indicate that early precut may reduce PEP *** the precut decision is delayed,a pancreatic stent should be inserted to prevent PEP.

关键词： Endoscopic retrograde cholangiopancreatography Post-endoscopic retrograde cholangiopancreatography pancreatitis Precut Needle-knife precut papillotomy

DISTRIBUTION OF FMRFAMIDE IN NERVOUS SYSTEM OF AMPHIOXUS——A STUDY OF THE IMMUNOHISTOCHEMISTRY

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Chinese Science Bulletin 1990年第7期35卷 580-582页

作者：方永强 hideshi KOBAYASHI Third Institute of Oceanography ASO Xiamen 361005 PRC Research Laboratory Zenyaku Kogyo Co. Ltd 2-3377 Ohizumi-machi Nerima-ku Tokyo 178 Japan

Cardioexcitatory neuropeptide （FMRFamide） was discovered in the ganglia of the clam （Macrocallista nimbosa）. Neuropeptide consisting of four kinds of amino acid, Phe-Met-Arg-Phe-NH2, has already been artificially synthesized. FMRFamide may influence the rhythmicity of the heart of mollusc and the contraction of the antenna in the snail,

关键词： amphioxus cardioexcitatory neuropeptide (FMRF amide) immunohistochemistry.

A Switching Controller System for a Wheeled Mobile Robot

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Journal of Bionic Engineering 2007年第4期4卷 281-289页

作者： Masanori Sato Atushi Kanda Kazuo ishii Department of Brain Science and Engineering Kyushu Institute of Technology Kitakyushu 808-0196 Japan

A wheeled mobile mechanism with a passive and/or active linkage mechanism for rough terrain environment is developed and evaluated. The wheeled mobile mechanism which has high mobility in rough terrain needs sophisticated system to adapt various environments. We focus on the development of a switching controller system for wheeled mobile robots in rough terrain. This system consists of two sub-systems： an environment recognition system using link angles and an adaptive control system. In the environment recognition system, we introduce a Self-Organizing Map （SOM） for clustering link angles. In the adaptive controllers, we introduce neural networks to calculate the inverse model of the wheeled mobile robot. The environment recognition system can recognize the environment in which the robot travels, and the adjustable controllers are tuned by experimental results for each environment. The dual sub-system switching controller system is experimentally evaluated. The system recognizes its environment and adapts by switching the adjustable controllers. This system demonstrates superior performance to a well-tuned single PID controller.

关键词： mobile robot rough terrain neural network Self-Organizing Map