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The first Japanese case of intraductal cancer of the prostate with checkpoint kinase 2 mutation

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Asian Journal of Urology 2022年第4期9卷 480-482页

作者： hiroshi hongo Takeo Kosaka Kohei Nakamura Shuji Mikami hiroshi Nishihara Mototsugu Oya Department of Urology Keio University School of MedicineJapan Genomics Unit Keio Cancer CenterKeio University School of MedicineJapan Department of Diagnostic Pathology Keio University HospitalJapan

Dear editor:Intraductalcarcinomaoftheprostate(IDC-P)ischaracterized by expansive growth of cancer cells in normal prostatic ducts with basal cell layer and associated with high grade invasive prostate cancer(PCa).However,the molecular profile or clinical character of IDC-P in progressive castration-resistant PCa(CRPC)was not fully characterized yet.

关键词： cancer clinical prostatic

The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

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International Journal of Oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando Masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang Minglu Yan Ryunosuke Muro Kazutaka Nakamura Masatsugu Komagamine Noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura Akira Yamaguchi Kazuyuki Ishihara hiroshi Takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Department of Microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam Department of Oral and Maxillofacial Surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan Department of Laboratory Animal Medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

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A developmental biological study of aldolase gene expression in Xenopus laevis

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Cell Research 2002年第2期12卷 85-96页

作者： KOICHIRO SHIOKAWA, ERI KAJITA, hiroshi HARA, HITOMI YATSUKI, KATSUJI HORI1 Laboratory of Molecular Embryology, Department of Biological Sciences, Graduate School of Science, TheUniversity of Tokyo, hongo 7-3-1, Bunkyo ku, Tokyo 113-0033, Japan 2Medical Re Department of Biological Sciences Graduate School of Science The University of Tokyo Japan. xlshioka@io.ocn.ne.jp

We cloned cDNAs for Xenopus aldolases A, B and C. These three aldolase genes are localized on different chromosomes as a single copy gene. In the adult, the aldolase A gene is expressed extensively in muscle tissues, whereas the aldolase B gene is expressed strongly in kidney, liver, stomach and intestine, while the aldolase C gene is expressed in brain, heart and ovary. In oocytes aldolase A and C mRNAs, but not aldolase B mRNA, are extensively transcribed. Thus, aldolase A and C mRNAs, but not B mRNA, occur abundantly in eggs as maternal mRNAs, and strong expression of aldolase B mRNA is seen only after the late neurula stage. We conclude that aldolase A and C mRNAs are major aldolase mRNAs in early stages of Xenopus embryogenesis which proceeds utilizing yolk as the only energy source, aldolase B mRNA, on the other hand, is expressed only later in development in tissues which are required for dietary fructose metabolism. We also isolated the Xenopus aldolase C genomic gene (ca. 12 kb) and found that i

关键词： aldolase A B and C mRNAs embryo-type aldolase mRNA composition tissue specific expression pattern.

Pediatric Primary Malignant Lymphoma of the Spine: A Case Report

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Open Journal of Orthopedics 2012年第3期2卷 85-89页

作者： Daisuke Kudo Naohisa Miyakoshi Michio hongo Yuji Kasukawa Yoshinori Ishikawa hiroshi Aonuma Yoichi Shimada Department of Orthopedic Surgery Akita University Graduate School of Medicine Akita Japan

Background: Cases of primary malignant lymphomas of the bone are rare and account for about <1% of all lymphomas and 5% of extranodal non-Hodgkin’s lymphomas. Furthermore, most reports have described the occurrence of this disease in the middle-aged population, pediatric malignant lymphomas originating in the bone, particularly in the spine is rare. Methods: A 10-year-old boy presented with low back pain caused by T12 vertebral compression fracture due to sustaining a fall. A month later, he still presented with prolonged low back pain that intensified after exercise. A neoplastic lesion in T12 vertebral body was identified after spine computed tomography (CT) and magnetic resonance imaging. Results: We performed CT-guided biopsy, and he was diagnosed with primary malignant lymphoma of the vertebral body. He was treated with multiagent chemotherapy without irradiation, and complete remission was maintained at the 5-year follow-up. Moreover, the height of the deformed vertebral body improved as he grew. Conclusions: Herein, we report a rare case of pediatric primary malignant lymphoma of the spine with successful clinical and radiological outcome.

关键词： Malignant Lymphoma Pediatrics CT Guided Biopsy Wrap around Sign Chemotherapy Irradiation

A novel visual test for hydrogen sulfide on the tongue dorsum

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Open Journal of Stomatology 2012年第4期2卷 314-321页

作者： Takashi Kanehira Hirohisa hongo Junji Takehara Kozo Asano Kazumi Osada hiroshi Izumi Yoshihiro Fujii Wataru Sakamoto Applied Microbiology Applied Bioscience Graduate School of Agricul-ture Hokkaido University Sapporo Japan Department of Physiology School of Dentistry Health Sciences University of Hokkaido Ishikari-Tobetsu Japan Division of Preventive Dentistry Graduate School of Dental Medicine Hokkaido University Sapporo Japan Institute of QOL Fuji Women’s University Ishikari Japan

Objective: The purpose of this study was to develop a novel colorimetric system for direct detection of hydrogen sulfide on the tongue dorsum from subjects with complaints of halitosis. Method: An assay system comprised of a cotton swab impregnated with zinc sulfate, attached chromatography paper, stabilizing solution, and coloring reagents for the methylene blue technique was developed. Using this system we investigated on the visualization of the hydrogen sulfide on the solid phase and possibility for evaluating the origin of oral malodor on the tongue dorsum. Results: The assay system made possible visualization of a linear curve ranging from 5.3 ng to 85 ng of hydrogen sulfide, with low reagent consumption and miniaturization. However, the sensitivity was different for gaseous and fluid samples. The biofilm of the tongue dorsum from subjects with complaints of halitosis showed different shades of methylene blue depending on the concentration of hydrogen sulfide. A positive correlation was found between hydrogen sulfide on the tongue dorsum and the concentration of VSC hydrogen sulfide in mouth breath as measured using an Oral Chroma semiconductor gas sensor. Conclusion: The results of this study suggest that the novel assay system can be used as a visual warning sensor for halitosis by measuring hydrogen sulfide on the tongue dorsum.

关键词： Halitosis Tongue dorsum VSC Hydrogen Sulfide Methylene Blue

Parallel-core-type polarization rotator for silicon wire waveguide platform

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Photonics Research 2014年第3期2卷 S0014-S0018页

作者： hiroshi Fukuda Kazumi Wada The University of Tokyo School of Material Engineering7-3-1 HongoChiyodaTokyoJapan NTT Microsystem Integration LaboratoriesMorinosato-WakamiyaAtsugiKanagawaJapan

We describe a polarization rotator based on a parallel-core structure consisting of a silicon nanowire waveguide and a silicon-nitride *** 60-μm-long rotator provides a polarization extinction ratio of more than 10 dB with excess loss of less than 1 *** addition,the extremely wide bandwidth of more than 150 nm expected from calculations is confirmed in experiments.A study of the fabrication tolerance of our rotator indicates that fabrication error of around 25 nm is allowable.

关键词： polarization extinction fir

Simultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1αsignaling

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Bone Research 2022年第4期10卷 770-783页

作者： Takehito Ono Ryosuke Denda Yuta Tsukahara Takashi Nakamura Kazuo Okamoto hiroshi Takayanagi Tomoki Nakashima Department of Cell Signaling Graduate School of Medical and Dental SciencesTokyo Medical and Dental University(TMDU)Yushima 1-5-45Bunkyo-kuTokyo 113-8549Japan Department of Orthopaedic Surgery The Jikei University School of Medicine3-25-8 Nishi-ShimbashiMinato-kuTokyo 105-8461Japan School of Dentistry Tokyo Medical and Dental University(TMDU)Yushima 1-5-45Bunkyo-kuTokyo 113-8549Japan Department of Biochemistry Tokyo Dental CollegeKandamisakicho 2-9-18Chiyoda-kuTokyo 101-0061Japan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyo 113-0033Japan Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyo 113-0033Japan

Impaired locomotion has been extensively studied worldwide because those afflicted with it have a potential risk of becoming *** exercise at times can be an effective remedy for frailty,but exercise therapy cannot be applied in all clinical *** is safer than exercise,but there are no drugs that reinforce both muscle and bone when administered *** medications increase the risk of adverse events;thus,there is a need for individual drugs targeting both *** this end,we established a novel sequential drug screening system and identified an aminoindazole derivative,locamidazole(LAMZ),which promotes both myogenesis and osteoblastogenesis while suppressing *** of this drug enhanced locomotor function,with muscle and bone significantly ***,LAMZ induced Mef2c and PGC-1αin a calcium signaling–dependent *** this signaling is activated upon physical exercise,LAMZ mimics physical ***,LAMZ is a promising therapeutic drug for locomotor diseases,including sarcopenia and osteoporosis.

关键词： drugs clinical diseases

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Overexpression of S-adenosylmethionine decarboxylase(SAMDC)in Xeno-pus embryos activates maternal program of apoptosis as a "fail-safe"mechanism of early embryogenesis

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Cell Research 2003年第3期13卷 147-158页

作者： MASATAKEKAI,CHIKARAKAITO,hiroshiFUKAMACHI,TAKAYASUHIGO,EIJI TAKAYAMA,hiroshi HARA,YOSHIKAZU OHYA,KAZUEI IGARASHI,KOICHIRO SHIOKAWA Laboratory of Molecular Embryology Department of Biological Sciences Graduate School of Science University of Tokyo hongo 7-3-1 Bunkyo-ku Tokyo 113-0033 Japan Laboratory of Molecular Embryology Department of Biological Sciences Graduate School of Science University of Tokyo hongo 7-3-1 Bunkyo-ku Tokyo 113-0033 Japan Laboratory of Molecular Embryology Department of Biological Sciences Graduate School of Science University of Tokyo hongo 7-3-1 Bunkyo-ku Tokyo 113-0033 Japan Laboratory of Molecular Embryology Department of Biological Sciences Graduate School of Science University of Tokyo hongo 7-3-1 Bunkyo-ku Tokyo 113-0033 Japan Department of Parasitology National Defense Medical College Namiki 3-2 Tokorozawa Saitama 359-8843 Japan Medicinal Research Laboratories Taisho Pharmaceutical Co. Ltd. 1-403 Yoshino-cho Kita-ku Saitama 331-9530 Japan Department of Integrated Biosciences Graduate School of Frontier Sciences University of Tokyo 5-1-5 Kashiwanoha Kashiwa Chiba 277-8562 Japan Faculty of Pharmaceutical Sciences Chiba University Yayoi-cho 1-33 Inage-ku Chiba 263-8522 Japan Laboratory of Molecular Embryology Department of Biological Sciences Graduate School of Science University of Tokyo hongo 7-3-1 Bunkyo-ku Tokyo 113-0033 Japan

In Xenopus, injection of S-adenosylmethionine decarboxylase (SAMDC) mRNA into fertilized eggs or2-cell stage embryos induces massive cell dissociation and embryo-lysis at the early gastrula stage due toactivation of the maternal program of apoptosis. We injected SAMDC mRNA into only one of the animal side blastomeres of embryos at different stages of cleavage, and examined the timing of the onset of theapoptotic reaction. In the injection at 4- and 8-cell stages, a considerable number of embryos developed intotadpoles and in the injection at 16- and 32-cell stages, all the embryos became tadpoles, although tadpolesobtained were sometimes abnormal. However, using GFP as a lineage tracer, we found that descendant cellsof the blastomere injected with SAMDC mRNA at 8- to 32-cell stages are confined within the blastocoel atthe early gastrula stage and undergo apoptotic cell death within the blastocoel, in spite of the continueddevelopment of the injected embryos. These results indicate that cells overexpress

关键词： SAMDC overexpression maternal apoptosis program processing-defective SAMDC mutant MBT fail-safe mechanism.

Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis

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Bone Research 2019年第1期7卷 66-75页

作者： Yuta Nakai Kazuo Okamoto Asuka Terashima Shogo Ehata Jun Nishida Takeshi Imamura Takashi Ono hiroshi Takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyoJapan Department of Orthodontic Science Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityYushima 1-5-45Bunkyo-kuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyoJapan Department of Molecular Pathology Graduate School of MedicineThe University of TokyoHongo 7-3-1Bunkyo-kuTokyoJapan Department of Molecular Medicine for Pathogenesis Ehime University Graduate School of MedicineShitsukawaToonEhimeJapan

Bone is one of the preferred sites for the metastasis of malignant tumours,such as breast cancer,lung cancer and malignant *** cells colonizing bone have the capacity to induce the expression of receptor activator of nuclear factor-κB ligand(RANKL),which promotes osteoclast differentiation and ***-induced osteoclastic bone resorption leads to a vicious cycle between tumours and bone cells that fuels osteolytic tumour growth,causing bone pain and ***,RANKL contributes to bone metastasis by acting as a chemoattractant to bone for tumour cells that express its receptor,*** inhibition of the RANKL–RANK pathway is a promising treatment for bone metastasis,and a human monoclonal anti-RANKL antibody,denosumab,has been used in the ***,orally available drugs targeting RANKL must be developed to increase the therapeutic benefits to *** we report the efficacy of the small-molecule RANKL inhibitor AS2676293 in treating bone metastasis using mouse *** administration of AS2676293 markedly inhibited bone metastasis of human breast cancer cells MDA-MB-231-5a-D-Luc2 as well as tumour-induced ***2676293 suppressed RANKLmediated tumour migration in the transwell assay and inhibited bone metastasis of the murine cell line B16F10,which is known not to trigger osteoclast *** on the results from this study,RANKL inhibition with a small-molecule compound constitutes a promising therapeutic strategy for treating bone metastasis by inhibiting both osteoclastic bone resorption and tumour migration to bone.

关键词： Bone tumours metastasis

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