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Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer

World Journal of Gastroenterology 2016年第44期22卷 9765-9774页

作者： kenichi Iwasaki Yun-Wen Zheng Soichiro Murata Hiromu Ito ken nakayama Tomohiro Kurokawa Naoki Sano Takeshi Nowatari Myra O Villareal Yumiko N Nagano Hiroko Isoda Hirofumi Matsui Nobuhiro Ohkohchi Department of Surgery and Organ Transplantation Faculty of Medicine University of Tsukuba Regenerative Medicine Research Center Jiangsu University Hospital Department of Regenerative Medicine Graduate School of Medicine Yokohama City University Department of Gastroenterology Faculty of Medicine University of Tsukuba Faculty of Life and Environmental Sciences Alliance of Research on North Africa University of Tsukuba

AIM To investigate the anticancer mechanisms of the monoterpenoid alcohol linalool in human colon cancer cells.METHODS The cytotoxic effect of linalool on the human colon cancer cell lines and a human fibroblast cell line was examined using the WST-8 assay. The apoptosisinducing effect of linalool was measured using the terminal deoxynucleotidyl transferase d UTP nickend labeling assay and flow cytometry with Annexin V. Oxidative stress was investigated by staining for diphenyl-1-pyrenylphosphine, which is a cellular lipid peroxidation marker, and electron spin resonance spectroscopy. Sixteen SCID mice xenografted with human cancer cells were randomized into 3 groups for in vivo analysis: control and low-dose and high-dose linalool groups. The control group was administered tap water orally every 3 d. The linalool treatment groups were administered 100 or 200 μg/kg linalool solution orally for the same period. All mice were sacrificed under anesthesia 21 d after tumor inoculation, and tumors and organs were collected for immunohistochemistry using an anti-4-hydroxynonenal antibody. Tumor weights were measured and compared between groups. RESULTS Linalool induced apoptosis of cancer cells in vitro, following the cancer-specific induction of oxidative stress, which was measured based on spontaneous hydroxyl radical production and delayed lipid peroxidation. Mice in the high-dose linalool group exhibited a 55% reduction in mean xenograft tumor weight compared with mice in the control group(P < 0.05). In addition, tumor-specific lipid peroxidation was observed in the in vivo model.CONCLUSION Linalool exhibited an anticancer effect via cancerspecific oxidative stress, and this agent has potential for application in colon cancer therapy.

关键词： Colorectal cancer Linalool Oxidative stress Electron spin resonance Lipid peroxidation

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New drug delivery system for liver sinusoidal endothelial cells for ischemia-reperfusion injury

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World Journal of Gastroenterology 2015年第45期21卷 12778-12786页

作者： Naoki Sano Takafumi Tamura Naoyuki Toriyabe Takeshi Nowatari ken nakayama Tomohito Tanoi Soichiro Murata Yu Sakurai Mamoru Hyodo Kiyoshi Fukunaga Hideyoshi Harashima Nobuhiro Ohkohchi Department of Surgery Doctoral Program in Clinical Science Graduate School of Comprehensive Human Sciences University of Tsukuba Faculty of Pharmaceutical Sciences Hokkaido University

AIM: To investigate the cytoprotective effects in hepatic ischemia-reperfusion injury, we developed a new formulation of hyaluronic acid(HA) and sphingosine 1-phophate.METHODS: We divided Sprague-Dawley rats into 4 groups: control, HA, sphingosine 1-phosphate(S1P), and HA-S1 P. After the administration of each agent, we subjected the rat livers to total ischemia followed by reperfusion. After reperfusion, we performed the following investigations: alanine aminotransferase(ALT), histological findings, Td T-mediated d UTP-biotin nick end labeling(TUNEL) staining, and transmission electron microscopy(TEM). We also investigated the expressionof proteins associated with apoptosis, hepatoprotection, and S1 P accumulation. RESULTS: S1 P accumulated in the HA-S1 P group livers more than S1 P group livers. Serum ALT levels, TUNEL-positive hepatocytes, and expression of cleaved caspase-3 expression, were significantly decreased in the HA-S1 P group. TEM revealed that the liver sinusoidal endothelial cell(LSEC) lining was preserved in the HA-S1 P group. Moreover, the HA-S1 P group showed a greater increase in the HO-1 protein levels compared to the S1 P group.CONCLUSION: Our results suggest that HA-S1 P exhibits cytoprotective effects in the liver through the inhibition of LSEC apoptosis. HA-S1 P is an effective agent for hepatic ischemia/reperfusion injury.

关键词： Hyaluronic acid Sphingosine 1-phosphate Liver sinu

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Thermally activated delayed fluorescence carbazole-triazine dendrimer with bulky substituents

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Aggregate 2024年第1期5卷 236-243页

作者： Hiroki Ikebe Kohei Nakao Eri Hisamura Minori Furukori Yasuo nakayama Takuya Hosokai Minlang Yang Guanting Liu Takuma Yasuda ken Albrecht Interdisciplinary Graduate School of Engineering Sciences Kyushu UniversityFukuokaJapan Institute for Materials Chemistry and Engineering Kyushu UniversityKasugaJapan Department of Pure and Applied Chemistry Graduate School of Science and TechnologyTokyo University of ScienceNodaChibaJapan National Metrology Institute of Japan(NMIJ) National Institute of Advanced Industrial Science and Technology(AIST)TsukubaIbarakiJapan Institute for Advanced Study Kyushu UniversityNishi-kuFukuokaJapan

Carbazole-triazine dendrimers with a bulky terminal substituent were synthesized,and the thermally activated delayed fluorescence(TADF)property was investigated.Compared to unsubstituted carbazole dendrimers,dendrimers with bulky terminal substituents showed comparable to better photoluminescence quantum yields(PLQY)in neat films.Phenylfluorene(PF)-substituted dendrimers showed the highest PLQY of 81%,a smallΔEst of 0.06 eV,and the fastest reverse intersystem crossing(RISC)rate of∼1×10^(5 )s^(−1) compared to other dendrimers.Phosphorescence measurements of dendrimers and dendrons(fragments)indicate that the close proximity of the triplet energy of phenylfluorene-substituted carbazole dendrons(^(3)LE)to that of phenylfluorene-substituted dendrimers(^(1)CT,^(3)CT)contributes to RISC promotion and improves TADF efficiency.Terminal modification fine-tunes the energy level and suppresses intermolecular interactions,and this study provides a guideline for designing efficient solution-processable and non-doped TADF materials.

关键词： dendrimer OLED TADF 1 INTRODUCTION Thermally activated delayed fluorescence(TADF)materials which are inexpensive and highly efficient alternatives to fluorescent

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HYDRO:Optimizing interactive hybrid images for digital signage content

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Virtual Reality & Intelligent Hardware 2023年第6期5卷 565-577页

作者： Masanori nakayama Karin UCHINO ken NAGAO Issei FUJISHIRO Department of Information&Computer Science Keio UniversityTokyoJapan Center for Information&Computer Science Keio UniversityTokyoJapan

Background In modern society,the digital signage installed in many large-scale facilities supports daily life.However,owing to their limited screen size,it is difficult to simultaneously provide different types of information to many viewers at varying distances from the screen.Therefore,in this study,we extend the existing research on the use of hybrid images for tiled displays.Methods To facilitate smoother information selection,a new interactive display method is proposed that incorporates touch-activated widgets as high-frequency parts of hybrid images.These widgets are novel because they are more visible to viewers near the display.We developed an authoring tool called the hybrid image display resolution optimizer(HYDRO),which features two types of control functions to optimize the visibility of touch-activated widgets in terms of placement and resolution.Conclusion The effectiveness of the proposed method is demonstrated empirically through a quantitative user study and an eyetracking-based qualitative evaluation.

关键词： Digital signage Hybrid image Authoring tool Information design

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Java字节码异常处理中信息流的分析

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应用科技 2007年第2期34卷 28-31页

作者：卢丹小林良岳中山健前川守电气通信大学情报系统学研究科

为提高Java移动代码动态安全验证的准确性和实用性,通过分析Java字节码中异常处理的方式与流程,提出了追踪、记录异常处理中信息流的方法.采用字节码改写技术,将异常处理中信息流的相关数据封装在异常类当中,从而保证了所采取的处理对J... 详细信息

为提高Java移动代码动态安全验证的准确性和实用性,通过分析Java字节码中异常处理的方式与流程,提出了追踪、记录异常处理中信息流的方法.采用字节码改写技术,将异常处理中信息流的相关数据封装在异常类当中,从而保证了所采取的处理对Java虚拟机的透明性,并进一步提高了动态验证的精度.

关键词：信息流异常处理 Java字节码

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Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

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Cancer Communications 2024年第2期44卷 287-293页

作者： Kouya Shiraishi Atsushi Takahashi Yukihide Momozawa Yataro Daigo Syuzo Kaneko Takahisa Kawaguchi Hideo Kunitoh Shingo Matsumoto Hidehito Horinouchi Akiteru Goto Takayuki Honda Kimihiro Shimizu Masahiro Torasawa Daisuke Takayanagi Motonobu Saito Akira Saito Yuichiro Ohe Shun-ichi Watanabe Koichi Goto Masahiro Tsuboi Katsuya Tsuchihara Sadaaki Takata Tomomi Aoi Atsushi Takano Masashi Kobayashi Yohei Miyagi Kazumi Tanaka Hiroyuki Suzuki Daichi Maeda Takumi Yamaura Maiko Matsuda Yoko Shimada Takaaki Mizuno Hiromi Sakamoto Teruhiko Yoshida Yasushi Goto Tatsuya Yoshida Taiki Yamaji Makoto Sonobe Shinichi Toyooka Kazue Yoneda Katsuhiro Masago Fumihiro Tanaka Megumi Hara Nobuo Fuse Satoshi S.Nishizuka Noriko Motoi Norie Sawada Yuichiro Nishida Kazuki Kumada kenji Takeuchi Kozo Tanno Yasushi Yatabe Kuniko Sunami Tomoyuki Hishida Yasunari Miyazaki Hidemi Ito Mitsuhiro Amemiya Hirohiko Totsuka Haruhiko nakayama Tomoyuki Yokose Kazuyoshi Ishigaki Toshiteru Nagashima Yoichi Ohtaki Kazuhiro Imai ken Takasawa Yoshihiro Minamiya Kazuma Kobayashi kenichi Okubo kenji Wakai Atsushi Shimizu Masayuki Yamamoto Motoki Iwasaki Koichi Matsuda Johji Inazawa Yuichi Shiraishi Hiroyoshi Nishikawa Yoshinori Murakami Michiaki Kubo Fumihiko Matsuda Yoichiro Kamatani Ryuji Hamamoto Keitaro Matsuo Takashi Kohno Division of Genome Biology National Cancer Center Research InstituteTokyoJapan Department of Clinical Genomics National Cancer Center Research InstituteTokyoJapan Laboratory for Statistical Analysis Center for Integrative Medical SciencesRIKENYokohamaJapan Department of Genomic Medicine Research InstituteNational Cerebral and Cardiovascular CenterOsakaJapan Laboratory for Genotyping Development Center for Integrative Medical SciencesRIKENYokohamaJapan Center for Antibody and Vaccine Therapy Research HospitalInstitute of Medical ScienceThe University of TokyoTokyoJapan Department of Medical Oncology and Cancer Center and Center for Advanced Medicine against CancerShiga University of Medical ScienceOtsuJapan Division of Medical AI Research and Development National Cancer Center Research InstituteTokyoJapan Center for Genomic Medicine Graduate School of MedicineKyoto UniversityKyotoJapan Department of Medical Oncology Japanese Red Cross Medical CenterTokyoJapan Department of Thoracic Oncology National Cancer Center Hospital EastJapan Department of Thoracic Oncology National Cancer Center HospitalTokyoJapan Department of Cellular and Organ Pathology Graduate School of MedicineAkita UniversityAkitaJapan Department of Respiratory Medicine Tokyo Medical and Dental UniversityBunkyo-kuTokyoJapan Division of General Thoracic Surgery Department of SurgeryShinshu University School of MedicineMatsumotoNaganoJapan Department of General Surgical Science Division of General Thoracic SurgeryGunma University Graduate School of MedicineIntegrative Center of General SurgeryGunma University HospitalGunmaJapan Department of Gastrointestinal Tract Surgery Fukushima Medical University School of MedicineFukushimaJapan StaGen Co. LtdTokyoJapan Division of Thoracic Surgery National Cancer Center HospitalTokyoJapan Department of Thoracic Surgery National Cancer Center Hospital EastChibaJapan Division of Translational Informatics Exploratory Oncology Research and Clinical Trial Center(EPOC

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

关键词： adenocarcinoma lung Lung

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Genetic diversity in Japanese populations of the Eurasian Collared Dove

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Avian Research 2020年第2期11卷 133-138页

作者： Kazuya Nagai Yusuke Takahashi ken‑ichi Tokita Tomomi Anzai Kiyoshi Uchida Fumihito nakayama Faculty of Agriculture Iwate UniversityMoriokaIwate 020‑8550Japan Research and Education Centre for Natural Sciences Keio UniversityYokohamaKanagawa 223‑8521Japan Japan Wildlife Research Centre KotoTokyo 130‑8606Japan Satoyama Natural History Study Group AbikoChiba 270‑1153Japan.

Background:Eurasian Collared Dove(Streptopelia decaocto)is a species distributed in the Eurasian continent and North Africa,and inhabiting mainly in Saitama Prefecture in Japan.Eurasian Collared Dove is one of the most prosper-ous invaders in the world,and Japanese Eurasian Collared Dove has also been introduced from overseas.The Japa-nese population has declined to one-hundredth over 30 years and is being protected.In this study,we analyzed its genetic diversity in order to understand the genetic differences between wild populations of Eurasian Collared Dove and those bred in zoos.Methods:A sequence of about 1.9 kb mtDNA was determined for 20 wild Eurasian Collared Doves living in Saitama,Japan and 20 zoo-bred Eurasian Collared Doves,and population genetic analysis was performed.Results:In the COI gene,778 bp had the same sequence in all the 40 individuals examined,and no mutation sites could be confirmed.In the control region,two base substitution sites were confirmed in 1140 bp long sequence.Three haplotypes were detected in 20 individuals in wild,whereas all 20 zoo-bred individuals possessed the same haplotypes possessed in the wild population.Conclusion:Haplotypes of zoo-bred individuals were also retained among the wild individuals,confirming that no genetic problems could occur if the zoo-bred individuals were released to the wild for the Japanese Eurasian Collared Dove propagation program.

关键词： COI Control region Eurasian Collared Dove Genetic diversity mtDNA Phylogeography

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ERK phosphorylation functions in invadopodia formation in tongue cancer cells in a novel silicate fibre-based 3D cell culture system

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International Journal of Oral Science 2018年第4期10卷 253-262页

作者： Masaharu Noi ken-Ichi Mukaisho Saori Yoshida Shoko Murakami Shinya Koshinuma Takeshi Adachi Yoshisato Machida Masashi Yamori Takahisa nakayama Gaku Yamamoto Hiroyuki Sugihara Department of Oral and Maxillofacial Surgery Shiga University of Medical Science Department of Pathology Division of Molecular Diagnostic PathologyShiga University of Medical Science Dental Oral Surgery Nagahama Red Cross Hospital

To screen for additional treatment targets against tongue cancer, we evaluated the contributions of extracellular signal-related kinase(ERK), AKT and ezrin in cancer development. Immunohistochemical staining showed that ERK and ezrin expressions were significantly higher in invasive squamous cell carcinoma than in carcinoma in situ. To investigate the roles of ERK and ezrin in cancer development, we used the non-woven silica fibre sheet Cellbedwith a structure resembling the loose connective tissue morphology in a novel 3 D culture system. We confirmed that the 3 D system using CellbedTMaccurately mimicked cancer cell morphology in vivo. Furthermore, cell projections were much more apparent in 3 D-cultured tongue cancer cell lines than in 2 D cultures. Typically, under conventional 2 D culture conditions, F-actin and cortactin are colocalized in the form of puncta within cells.However, in the 3 D-cultured cells, colocalization was mainly observed at the cell margins, including the projections. Projections containing F-actin and cortactin colocalization were predicted to be invadopodia. Although suppressing ezrin expression with small interfering RNA transfection caused no marked changes in morphology, cell projection formation was decreased, and the tumour thickness in vertical sections after 3 D culture was markedly decreased after suppressing ERK activity because both the invasion ability and proliferation were inhibited. An association between cortactin activation as well as ERK activity and invadopodia formation was detected. Our novel 3 D culture systems using Cellbed? are simple and useful for in vitro studies before conducting animal experiments. ERK contributes to tongue cancer development by increasing both cancer cell proliferation and migration via cortactin activation.

关键词： ERK phosphorylation functions in invadopodia formation in tongue cancer cells in a novel silicate fibre-based 3D cell culture sy HSC

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Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

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World Journal of Gastroenterology 2014年第34期20卷 11962-11965页

作者： ken-ichi Mukaisho Tadashi Hagiwara Takahisa nakayama Takanori Hattori Hiroyuki Sugihara Department of Pathology Division of Molecular Diagnostic PathologyShiga University of Medical ScienceSeta-tsukinowa-choOtsuShiga 520-2192Japan

The long-term use of proton pump inhibitors(PPIs)exacerbates corpus atrophic gastritis in patients with Helicobacter pylori(H.pylori)infection.To identify a potential mechanism for this change,we discuss interactions between pH,bile acids,and H.pylori.Duodenogastric reflux,which includes bile,occurs in healthy individuals,and bile reflux is increased in patients with gastroesophageal reflux disease(GERD).Diluted human plasma and bile acids have been found to be significant chemoattractants and chemorepellents,respectively,for the bacillus H.pylori.Although only taurine conjugates,with a pKa of 1.8-1.9,are soluble in an acidic environment,glycine conjugates,with a pKa of 4.3-5.2,as well as taurine-conjugated bile acids are soluble in the presence of PPI therapy.Thus,the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production.In the distal stomach,the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H.pylori.In contrast,the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H.pylori to the epithelial surface.H.pylori may then colonize in the stomach body rather than in the pyloric antrum,which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H.pylori-positive patients with GERD.

关键词： Helicobacter pylori Proton pump inhibitor Corpus-p

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Squamous Cell Carcinoma Arising from Aparaurethral Region

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Case Reports in Clinical Medicine 2016年第4期5卷 154-157页

作者： Kyosuke Matsuzaki Takahiro Yoshida Yasuyuki Kobayashi ken Takeda Yasuyuki Arai Masashi nakayama ken-ichi Kakimoto Yasuhiko Tomita Kazuo Nishimura Department of Urology Osaka Medical Center for Cancer and Cardiovascular Diseases Osaka Japan Department of Pathology Osaka Medical Center for Cancer and Cardiovascular Diseases Osaka Japan

A 69-year-old man was referred to our hospital with dysuria and gross hematuria associated with a rapidly growing perineal mass. Serum squamous cell carcinoma (SCC) antigen level was high (2.4 ng/mL). Magnetic resonance imaging examination revealed a tumor posterior and inferior to the pendular urethra with a cystic lesion inside. Tumor resection together with total penectomy was performed. Pathohistological findings revealed well-differentiated SCC arising from the paraurethral region. The patient remained free of disease without adjuvant therapy at 70 months after surgery. To our knowledge, this is the second reported case of paraurethral SCC.

关键词： Paraurethral Squamous Cell Carcinoma Perineal Mass

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