2023/10/05 更新

写真a

キシダ ショウセイ
岸田 昭世
KISHIDA Shosei
所属
医歯学域医学系 医歯学総合研究科 健康科学専攻 発生発達成育学講座 教授
医歯学域医学系 医学部  
職名
教授

学位

  • 博士(医学) ( 1995年3月   神戸大学 )

研究キーワード

  • シグナル伝達 Wntシグナル Dvl 神経伝達物質放出機構 蛋白質間相互作用 翻訳後修飾

研究分野

  • ライフサイエンス / 分子生物学

  • ライフサイエンス / 細胞生物学

経歴

  • 鹿児島大学   教授

    2007年2月 - 現在

  • 鹿児島大学    

    2007年2月 - 現在

所属学協会

  • 日本外科学会

    2015年10月 - 現在

  • 日本分子生物学会

    2015年10月 - 現在

  • 日本癌学会

    2015年10月 - 現在

  • 日本生化学会

    2015年10月 - 現在

 

論文

  • Yusuke Ono, Takao Fuchigami, Michiko Kishida, Hirofumi Koyama, Mikio Iijima, Kazuki Oishi, Toshiro Kibe, Kiyohide Ishihata, Yoshiaki Nishizawa, Tohru Kiyono, Norifumi Nakamura, Shosei Kishida .  Interleukin-1α promotes matrix metalloproteinase-9 expression, cellular motility, and local invasiveness of ameloblastoma cells .  Oral Science International   2023年5月査読

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    担当区分:責任著者  

    DOI: doi.org/10.1002/osi2.1193

  • Betzler A.C., Strobel H., Abou Kors T., Ezić J., Lesakova K., Pscheid R., Azoitei N., Sporleder J., Staufenberg A.R., Drees R., Weissinger S.E., Greve J., Doescher J., Theodoraki M.N., Schuler P.J., Laban S., Kibe T., Kishida M., Kishida S., Idel C., Hoffmann T.K., Lavitrano M., Grassilli E., Brunner C. .  BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression .  Cancers15 ( 1 )   2023年1月

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    記述言語:日本語   出版者・発行元:Cancers  

    Here, we describe the expression of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients.

    DOI: 10.3390/cancers15010310

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  • Ono Y., Fuchigami T., Kishida M., Koyama H., Iijima M., Oishi K., Kibe T., Ishihata K., Nishizawa Y., Kiyono T., Nakamura N., Kishida S. .  Interleukin-1α promotes matrix metalloproteinase-9 expression, cellular motility, and local invasiveness of ameloblastoma cells .  Oral Science International   2023年

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    記述言語:日本語   出版者・発行元:Oral Science International  

    Aim: Although ameloblastoma is a benign tumor, its local invasiveness and recurrence rate are both high. Thus, the regulation of the invasiveness of ameloblastoma cells into the surrounding tissue is required to understand its pathogenesis. Ameloblastoma cells secrete several matrix metalloproteinases (MMPs); however, the factors inducing their secretion remain unclear. We previously suggested that interleukin (IL)-1α derived from ameloblastoma cells triggers the production of inflammatory cytokines by stromal fibroblasts. In this study, we estimated whether IL-1α affects the behavior of ameloblastoma cells. Methods: The gene expression of MMP-9 was assessed by real-time reverse transcription–polymerase chain reaction (RT-PCR). The secretion of MMP-9 was assessed by enzyme-linked immunosorbent assay (ELISA). The motility of AM-3 ameloblastoma and Raw264.7 (macrophage derived cells) cells and the invasiveness of AM-3 cells were calculated using the Boyden chamber. The invasiveness of AM-3 cells toward human foreskin fibroblast (HFF)-2 fibroblasts were assessed using modified double-layered collagen gel hemisphere (DL-CGH). Results: The mRNA expression and secretion of MMP-9 by AM-3 ameloblastoma cells were significantly increased by IL-1α stimulation. The motilities of AM-3 and RAW264.7 macrophage derived cells and the invasiveness of AM-3 cells were significantly enhanced by IL-1α and suppressed by an IL-1 receptor antagonist (IL-1Ra). The invasiveness of AM-3 cells towards HFF-2 fibroblasts in a DL-CGH model was suppressed by a treatment with IL-1Ra or an anti-IL-1α neutralizing antibody. Conclusion: IL-1α itself or the IL-1α-dependent production of unidentified chemo attractants by stromal cells may be important for the local invasiveness of ameloblastoma cells, and IL-1α might be a therapeutic target of the ameloblastoma.

    DOI: 10.1002/osi2.1193

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  • Fujii S., Fujimoto T., Hasegawa K., Nagano R., Ishibashi T., Kurppa K.J., Mikami Y., Kokura M., Tajiri Y., Kibe T., Wada H., Wada N., Kishida S., Higuchi Y., Kiyoshima T. .  The Semaphorin 3A-AKT axis-mediated cell proliferation in salivary gland morphogenesis and adenoid cystic carcinoma pathogenesis .  Pathology Research and Practice236   153991   2022年8月

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    記述言語:日本語   出版者・発行元:Pathology Research and Practice  

    We recently demonstrated that Semaphorin 3 A (Sema3A), the expression of which is negatively regulated by Wnt/β-catenin signaling, promotes odontogenic epithelial cell proliferation, suggesting the involvement of Sema3A in tooth germ development. Salivary glands have a similar developmental process to tooth germ development, in which reciprocal interactions between the oral epithelium and adjacent mesenchyme proceeds via stimulation with several growth factors; however, the role of Sema3A in the development of salivary glands is unknown. There may thus be a common mechanism between epithelial morphogenesis and pathogenesis; however, the role of Sema3A in salivary gland tumors is also unclear. The current study investigated the involvement of Sema3A in submandibular gland (SMG) development and its expression in adenoid cystic carcinoma (ACC) specimens. Quantitative RT-PCR and immunohistochemical analyses revealed that Sema3A was expressed both in epithelium and in mesenchyme in the initial developmental stages of SMG and their expressions were decreased during the developmental processes. Loss-of-function experiments using an inhibitor revealed that Sema3A was required for AKT activation-mediated cellular growth and formation of cleft and bud in SMG rudiment culture. In addition, Wnt/β-catenin signaling decreased the Sema3A expression in the rudiment culture. ACC arising from salivary glands frequently exhibits malignant potential. Immunohistochemical analyses of tissue specimens obtained from 10 ACC patients showed that Sema3A was hardly observed in non-tumor regions but was strongly expressed in tumor lesions, especially in myoepithelial neoplastic cells, at high frequencies where phosphorylated AKT expression was frequently detected. These results suggest that the Sema3A-AKT axis promotes cell growth, thereby contributing to morphogenesis and pathogenesis, at least in ACC, of salivary glands.

    DOI: 10.1016/j.prp.2022.153991

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  • Chairani E., Fuchigami T., Koyama H., Ono Y., Iijima M., Kishida M., Kibe T., Nakamura N., Kishida S. .  Intercellular signaling between ameloblastoma and osteoblasts .  Biochemistry and Biophysics Reports30   101233   2022年7月

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    記述言語:日本語   出版者・発行元:Biochemistry and Biophysics Reports  

    Ameloblastoma is an odontogenic tumor located in the bone jaw with clinical characteristics of extensive bone resorption. It is a locally invasive tumor with a high recurrence rate despite adequate surgical removal. In bone disease, tumors and other cells including osteoblasts, osteoclasts, and osteocytes in the bone microenvironment contribute to the pathogenesis of tumor growth. However, the effect of osteoblasts on ameloblastoma cells is not well-understood, and there has been limited research on interactions between them. This study investigated interactions between ameloblastoma cells and osteoblasts using a human ameloblastoma cell line (AM-3 ameloblastoma cells) and a murine pre-osteoblast cell line (MC3T3-E1 cells). We treated each cell type with the conditioned medium by the other cell type. We analyzed the effect on cytokine production by MC3T3-E1 cells and the production of MMPs by AM-3 cells. Treatment with AM-3-conditioned medium induced inflammatory cytokine production of IL-6, MCP-1, and RANTES from MC3T3-E1 cells. The use of an IL-1 receptor antagonist suppressed the production of these inflammatory cytokines by MC3T3-E1 cells stimulated with AM-3-conditioned medium. The MC3T3-E1-conditioned medium triggered the expression of MMP-2 from AM-3 cells. Furthermore, we have shown that the proliferation and migration activity of AM-3 cells were accelerated by MC3T3-E1 conditioned media. In conclusion, these intercellular signalings between ameloblastoma cells and osteoblasts may play multiple roles in the pathogenesis of ameloblastoma.

    DOI: 10.1016/j.bbrep.2022.101233

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  • 野中 美希, 上野 晋, 柿木 亮, 岸田 昭世, 呉林 なごみ, 村山 尚, 宮野 加奈子, 寺脇 潔, 櫻井 隆, 上園 保仁 .  がん悪液質性心機能障害に対する自発運動による治療効果の検討:Cardio-oncologyの観点からのアプローチ .  日本薬理学会年会要旨集95 ( 0 ) 1-P-046   2022年

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    記述言語:日本語   出版者・発行元:公益社団法人 日本薬理学会  

    <p>Recently, the interdisciplinary field of cardio-oncology has emerged to study the mechanisms of cardiac dysfunction associated with cancer treatment and how to prevent it. In this study, we investigated possible therapeutic effects of voluntary wheel running (VWR) on cardiac dysfunction observed in a cancer-cachexia model mice established by our laboratory. VWR starting from 2 to 6 wks after implantation of tumor cells significantly suppressed the loss of heart and skeletal muscle weight as well as general symptoms of cachexia. Moreover, left ventricular ejection fraction significantly increased in cachexia group with VWR, compared to those without VWR. Microarray analysis revealed that the expression of gene &quot;X&quot;, which is an enzyme belonging to E3 ubiquitin ligase family and has not been reported to be related to skeletal muscular atrophy, increased in the myocardium of cachexia mice, and that this increase was suppressed by VWR. These results suggest that the mechanism of myocardial impairment may be different from that of skeletal muscle atrophy, and that VWR may improve not only cachexia symptoms but also cachexia-induced cardiac dysfunction. In addition, the gene &quot;X&quot; may be one of key factors which are associated with myocardial atrophy and cardiac dysfunction on cancer cachexia. The pathway mediated by the gene &quot;X&quot; is currently being further analyzed.</p>

    DOI: 10.1254/jpssuppl.95.0_1-p-046

  • Chairani E, Fuchigami T, Koyama H, Ono Y, Iijima M, Kishida M, Kibe T, Nakamura N, Kishida S. .  Intercellular signaling between ameloblastoma and osteoblasts. .  Biochemistry and Biophysics Reports   2022年査読

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbrep.2022.101233.

  • 野中 美希, 柿木 亮, 岸田 昭世, 大島 佳織, 後藤 元秀, 上園 保仁, 上野 進 .  がん悪液質モデルマウスに出現する心機能障害と自発運動負荷がもたらす治療的効果 .  日本毒性学会学術年会49.1 ( 0 ) P-154   2022年

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    記述言語:日本語   出版者・発行元:日本毒性学会  

    <p>【目的】がん悪液質は心機能障害を伴うことが報告されているが、ヒトの臨床像を反映する適切なモデル動物が少ないため、がん悪液質と心機能との関連は未だ不明な点が多い。我々はヒト胃がん細胞株85As2を移植したマウスが、ヒト悪液質と類似した症状を示すモデルになることを見出している。本研究では同モデルを用い、心機能障害の分子メカニズムとともに自発運動(回し車)による治療効果についても検討を行った。</p><p>【方法】85As2細胞を8週齢の雄性BALB/cヌードマウスの両腹皮下に移植し、移植後2週目より悪液質症状を呈するモデルを作製した。本研究では移植後2週目を前悪液質群、移植後8週目を悪液質群と定義し、同週齢対照群との比較から心機能を含む悪液質病態の評価、ならびにこれらに対する自発運動負荷の効果を検討した。</p><p> 【結果】同齢の対照群と比較し、前悪液質群ならびに悪液質群ではともに心重量が有意に減少し、特に悪液質群では減少が顕著であった。さらに左室駆出率(LVEF)についても前悪液質群、悪液質群で有意に減少していた。一方、マウスの心筋を用いてマイクロアレイ解析を行ったところ、心不全との関連性が報告されていないE3ユビキチンリガーゼに属する酵素 Xの遺伝子発現量が増加していた。また、回し車による自発運動負荷により、悪液質モデルの摂餌量と心重量の低下は抑制され、さらにはXの遺伝子発現量増加の抑制も認められ、LVEFも改善した。</p><p> 【結語】85As2細胞移植によるがん悪液質モデルマウスにおいて、自発運動負荷は悪液質症状のみならず心機能障害も改善することが明らかとなった。またマイクロアレイ解析で変動のあった酵素Xの遺伝子発現量は、心筋萎縮とともに増加し自発運動負荷により減少することから、がん悪液質に伴う心機能障害と関連があると考えられる。現在、酵素Xを介する経路についてさらに解析を進めている。</p>

    DOI: 10.14869/toxpt.49.1.0_p-154

  • Bakkalci D., Jay A., Rezaei A., Howard C.A., Haugen H.J., Pape J., Kishida S., Kishida M., Jell G., Arnett T.R., Fedele S., Cheema U. .  Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation .  Scientific Reports11 ( 1 ) 24088   2021年12月

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    記述言語:日本語   出版者・発行元:Scientific Reports  

    Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm2 and average height of 92.37 ± 7.96 μm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.

    DOI: 10.1038/s41598-021-03484-5

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  • Tellez C.S., Juri D.E., Phillips L.M., Do K., Thomas C.L., Willink R., Dye W.W., Wu G., Zhou Y., Irshad H., Kishida S., Kiyono T., Belinsky S.A. .  Comparative Genotoxicity and Mutagenicity of Cigarette, Cigarillo, and Shisha Tobacco Products in Epithelial and Cardiac Cells .  Toxicological Sciences184 ( 1 ) 67 - 82   2021年11月

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    記述言語:日本語   出版者・発行元:Toxicological Sciences  

    Epidemiology studies link cigarillos and shisha tobacco (delivered through a hookah waterpipe) to increased risk for cardiopulmonary diseases. Here we performed a comparative chemical constituent analysis between 3 cigarettes, 3 cigarillos, and 8 shisha tobacco products. The potency for genotoxicity and oxidative stress of each product's generated total particulate matter (TPM) was also assessed using immortalized oral, lung, and cardiac cell lines to represent target tissues. Levels of the carcinogenic carbonyl formaldehyde were 32-to 95-fold greater, while acrolein was similar across the shisha aerosols generated by charcoal heating compared to cigarettes and cigarillos. Electric-mediated aerosol generation dramatically increased acrolein to levels exceeding those in cigarettes and cigarillos by up to 43-fold. Equivalent cytotoxic-mediated cell death and dose response for genotoxicity through induction of mutagenicity and DNA strand breaks was seen between cigarettes and cigarillos, while minimal to no effect was observed with shisha tobacco products. In contrast, increased potency of TPM from cigarillos compared to cigarettes for inducing oxidative stress via reactive oxygen radicals and lipid peroxidation across cell lines was evident, while positivity was seen for shisha tobacco products albeit at much lower levels. Together, these studies provide new insight into the potential harmful effects of cigarillos for causing tobacco-associated diseases. The high level of carbonyls in shisha products, that in turn is impacted by the heating mechanism, reside largely in the gas phase which will distribute throughout the respiratory tract and systemic circulation to likely increase genotoxic stress.

    DOI: 10.1093/toxsci/kfab101

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  • Fuchigami T. .  Molecular biological findings of ameloblastoma .  Japanese Dental Science Review57   27 - 32   2021年11月

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    記述言語:日本語   出版者・発行元:Japanese Dental Science Review  

    Ameloblastoma is benign odontogenic tumours that mainly occur in the jawbone. This tumour induces aggressive invasion into the surrounding bone and has a high recurrence rate after surgery. Therefore, mandibular resection is performed in many patients with this tumour, causing aesthetic and functional problems. It is necessary to develop a novel treatment strategy for ameloblastoma, but there are currently no innovative treatments. Although our understanding of the molecular biological mechanisms of ameloblastoma is still insufficient, there have been many recent reports of new molecular biological findings on ameloblastoma. Therefore, bioactive factors that have potential for novel therapeutic methods, such as molecular targeted therapy, have been discovered in ameloblastoma. In this review, we summarize the molecular biological findings of ameloblastoma reported over several decades, focusing on factors involved in invasion into surrounding tissues and disease-specific gene mutations. We also mention the effect of the interaction between tumour cells and stromal components in ameloblastoma on tumour development. Scientific field of dental Science: Oral surgery, Odontogenic tumor, Ameloblastoma.

    DOI: 10.1016/j.jdsr.2020.12.003

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  • Tellez C.S. .  Cytotoxicity and genotoxicity of E-cigarette generated aerosols containing diverse flavoring products and nicotine in oral epithelial cell lines .  Toxicological Sciences179 ( 2 ) 220 - 228   2021年2月査読

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    記述言語:日本語   出版者・発行元:Toxicological Sciences  

    Electronic cigarettes are the most commonly used nicotine containing product among teenagers. The oral epithelium is the first site of exposure and our recent work revealed considerable diversity among e-liquids for composition and level of chemical constituents that impact nicotine deposition in a human oral-trachea cast and affect the formation of reactive carbonyls. Here, we evaluate the dose response for cytotoxicity and genotoxicity of e-cigarette-generated aerosols from 10 diverse flavored e-liquid products with and without nicotine compared with unflavored in 3 immortalized oral epithelial cell lines. Three e-liquids, Blue Pucker, Love Potion, and Jamestown caused ≥20% cell toxicity assessed by the neutral red uptake assay. Nine products induced significant levels of oxidative stress up to 2.4-fold quantified by the ROS-Glo assay in at least 1 cell line, with dose response seen for Love Potion with and without nicotine across all cell lines. Lipid peroxidation detected by the thiobarbituric acid reactive substances assay was less common among products; however, dose response increases up to 12-fold were seen for individual cell lines. Micronuclei formation indicative of genotoxicity was increased up to 5-fold for some products. Blue Pucker was the most genotoxic e-liquid, inducing micronuclei across all cell lines irrespective of nicotine status. A potency score derived from all assays identified Blue Pucker and Love Potion as the most hazardous e-liquids. These in vitro acute exposure studies provide new insight about the potential for some flavored vaping products to induce significant levels of oxidative stress and genotoxicity.

    DOI: 10.1093/toxsci/kfaa174

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  • Bakkalci D, Jay A, Rezaei A, Howard CA, Haugen HJ, Pape J, Kishida S, Kishida M, Jell G, Arnett TR, Fedele S, Cheema U. .  Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation. .    11 ( 1 ) 24088   2021年査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-021-03484-5.

  • Tellez CS, Juri DE, Phillips LM, Do K, Thomas CL, Willink R, Dye WW, Wu G, Zhou Y, Irshad H, Kishida S, Kiyono T, Belinsky SA. .  Comparative Genotoxicity and Mutagenicity of Cigarette, Cigarillo, and Shisha Tobacco Products in Epithelial and Cardiac Cells. .  Toxicolgical Sciences.184 ( 1 ) 67 - 82   2021年査読 国際共著

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-021-03484-5.

  • Alshargabi R. .  SPOCK1 is a novel inducer of epithelial to mesenchymal transition in drug-induced gingival overgrowth .  Scientific Reports10 ( 1 ) 9785   2020年12月

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    出版者・発行元:Scientific Reports  

    DOI: 10.1038/s41598-020-66660-z

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  • Hook S.C. .  TBC1D1 interacting proteins, VPS13A and VPS13C, regulate GLUT4 homeostasis in C2C12 myotubes .  Scientific Reports10 ( 1 ) 17953   2020年12月

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    出版者・発行元:Scientific Reports  

    DOI: 10.1038/s41598-020-74661-1

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  • Al-Tayar B.A. .  Cytotoxic effects of betel quid and areca nut aqueous extracts on mouse fibroblast, human mouth-ordinary-epithelium 1 and human oral squamous cell carcinoma cell lines .  Asian Pacific Journal of Cancer Prevention21 ( 4 ) 1005 - 1009   2020年4月

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    出版者・発行元:Asian Pacific Journal of Cancer Prevention  

    DOI: 10.31557/APJCP.2020.21.4.1005

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  • Fujii S. .  The TRPV4-AKT axis promotes oral squamous cell carcinoma cell proliferation via CaMKII activation .  Laboratory Investigation100 ( 2 ) 311 - 323   2020年2月

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    出版者・発行元:Laboratory Investigation  

    DOI: 10.1038/s41374-019-0357-z

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  • Suzuki H. .  Ameloblastoma cell lines derived from different subtypes demonstrate distinct developmental patterns in a novel animal experimental model .  Journal of Applied Oral Science28   1 - 7   2020年

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    出版者・発行元:Journal of Applied Oral Science  

    DOI: 10.1590/1678-7757-2019-0558

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  • Matsumoto, M., Kubota, T., Fujita S., Shiozaki, K., Kishida, S., Yamamoto, A. .  Elucidation of the interleukin 12 production mechanism during intracellular bacterial infection in Amberjack, Seriola Dumerili .  Infection and Immunity87 ( 11 )   2019年10月

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    出版者・発行元:Infection and Immunity  

    DOI: 10.1128/IAI.00459-19

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  • Sarkar R. .  Effect of cigarette smoke extract on mitochondrial heme-metabolism: An in vitro model of oral cancer progression .  Toxicology in Vitro60   336 - 346   2019年10月

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    出版者・発行元:Toxicology in Vitro  

    DOI: 10.1016/j.tiv.2019.06.016

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  • Nonaka Miki, Uezono Yasuhito, Kurebayashi Nagomi, Murayama Takashi, Sugihara Masami, Hosoda Hiroshi, Kishida Shosei, Uzu Miaki, Kangawa Kenji, Sakurai Takashi .  Therapeutic effects of ghrelin and des-acyl ghrelin on anthracycline doxorubicin-induced cardiac toxicit .  日本薬理学会年会要旨集2018 ( 0 ) PO1 - 2-30   2018年

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    出版者・発行元:公益社団法人 日本薬理学会  

    <p>[Background] </p><p> Anthracycline doxorubicin (DOX), which has been used for cancer chemotherapy, often causes cardiotoxicity. Recent reports indicate that orexigenic hormone ghrelin and des-acyl ghrelin, which is a non-octanoylated form of ghrelin, inhibit DOX-induced cardiotoxicity. However, molecular mechanisms of ghrelin and des-acyl ghrelin remain unclear. In the present study, to provide mechanistic experimental evidence of these peptides against DOX-induced cardiotoxicity, we examined the effects of ghrelin and des-acyl ghrelin on cell damage, cell death, apoptosis, and cardiac dysfunction using an in vitro and in vivo system. </p><p>[Methods and Results] </p><p> Effects of ghrelin and des-acyl ghrelin were evaluated using H9C2 cardiomyocytes. H9C2 cells were treated with DOX (0-1 μM) for 72h with or without ghrelin or des-acyl ghrelin (1 μM each). Ghrelin and des-acyl ghrelin significantly reduced the DOX-induced cell damage and cell death, with greater effects at des-acyl ghrelin. In addition, ghrelin and des-acyl ghrelin prevented cell damage and cell death through apoptosis, and des-acyl ghrelin but not ghrelin significantly decreased ROS generation. In in vivo experiment, DOX was administered once at a dose of 15 mg/kg to 8 weeks old male C57BL/6 mice intraperitoneally. At 1 day before DOX treatment, we started subcutaneous administration to mice twice daily with des-acyl ghrelin (100 mg/kg) for 8 consecutive days. Treatment with DOX in mice caused left ventricular systolic dysfunction. On the other hand, mice treated with DOX with des-acyl ghrelin significantly improved systolic dysfunction. In addition, non-phosphorylated Cx43 was increased in the mice treated with DOX alone, and DOX with des-acyl ghrelin treated mice were markedly decreased expression levels of non-phosphorylated Cx43. These results suggest that des-acyl ghrelin prevented the progression in left ventricular ejection fraction decrease in DOX-treated mice probably because of the decrease expression levels of non-phosphorylated Cx43. </p><p>[Conclusions] </p><p> Our study showed that ghrelin and des-acyl ghrelin may have therapeutic effects in DOX-induced cardiotoxicity. Further, des-acyl ghrelin may have greater beneficial effects for the reduction of cellular ROS generation and expression level of non-phosphorylated Cx43. Further studies are required to clarify the mechanisms how des-acyl ghrelin prevents the DOX-induced cardiotoxicity and such experiments are underway.</p>

    DOI: 10.1254/jpssuppl.WCP2018.0_PO1-2-30

  • Fuchigami T. .  Fibroblasts promote the collective invasion of ameloblastoma tumor cells in a 3D coculture model .  FEBS Open Bio7 ( 12 ) 2000 - 2007   2017年12月

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    出版者・発行元:FEBS Open Bio  

    DOI: 10.1002/2211-5463.12313

    Scopus

    PubMed

  • Harada Takeshi, Yamamoto Hideki, Kishida Shosei, Kishida Michiko, Awada Chihiro, Takao Toshifumi, Kikuchi Akira .  Wnt5B関連エクソソームは癌細胞の遊走と増殖を促進する(Wnt5b-associated exosomes promote cancer cell migration and proliferation) .  Cancer Science108 ( 1 ) 42 - 52   2017年1月

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    出版者・発行元:John Wiley & Sons Australia, Ltd  

    癌進展におけるWnt5Bの役割を明らかにするため、Wnt5Bの生化学的特性と、癌細胞からのWnt5B分泌モードについて調べた。その結果、Wnt5Bは三つのアスパラギン残基がグリコシル化し、一つのセリン残基では脂質が付加されており、これらの翻訳後修飾がWnt5Bの分泌に不可欠であることが明らかになった。精製したWnt5BはDvl2リン酸化とRac活性化能においてWnt5aと同等であった。PANC-1膵癌細胞では、分泌されたWnt5Bの55%はエクソソームに関係していた。野生型PANC-1細胞のエクソソームはCHO細胞でWnt5Bシグナル系を活性化し、A549肺腺癌細胞の遊走と増殖を刺激した。これはエクソソーム関連Wnt5Bに活性があることを示唆していた。CHO細胞に取り込まれたエクソソームを免疫顕微鏡で調べた結果、Wnt5Bは確かにエクソソームに関連していた。Wnt5B関連エクソソームは膵癌において癌細胞の増殖と遊走を促進することが示唆された。

    DOI: 10.1111/cas.13109

  • Macha MA, Rachagani S, Qazi AK, Jahan R, Gupta S, Patel A, Seshacharyulu P, Lin C, Li S, Wang S, Verma V, Kishida S, Kishida M, Nakamura N, Kibe T, Lydiatt WM, Smith RB, Ganti AK, Jones DT, Batra SK, Jain M. .  Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting cancer stem cells. .    8   20961 - 20973   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.18632/oncotarget.15468

  • Nonaka Miki, Kangawa Kenji, Sakurai Takashi, Uezono Yasuhito, Kurebayashi Nagomi, Murayama Takashi, Sugihara Masami, Terawaki Kiyoshi, Shiraishi Seiji, Miyano Kanako, Hosoda Hiroshi, Kishida Shosei .  Therapeutic potential of ghrelin and des-acyl ghrelin against chemotherapy-induced cardiotoxicity .  Endocrine Journal64 ( 0 ) S35 - S39   2017年

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    出版者・発行元:一般社団法人 日本内分泌学会  

    Cancer was considered an incurable disease for many years; however, with the development of anticancer drugs and state-of-the art technologies, it has become curable. Cardiovascular diseases in patients with cancer or induced by cancer chemotherapy have recently become a great concern. Certain anticancer drugs and molecular targeted therapies cause cardiotoxicity, which limit the widespread implementation of cancer treatment and decrease the quality of life in cancer patients significantly. The anthracycline doxorubicin (DOX) causes cardiotoxicity. The cellular mechanism underlying DOX-induced cardiotoxicity include free-radical damage to cardiac myocytes, leading to mitochondrial injury and subsequent death of myocytes. Recently, circulating orexigenic hormones, ghrelin and des-acyl ghrelin, have been reported to inhibit DOX-induced cardiotoxicity. However, little is known about the molecular mechanisms underlying their preventive effects. In the present study, we show the possible mechanisms underlying the effects of ghrelin and des-acyl ghrelin against DOX-induced cardiotoxicity through <i>in vitro</i> and <i>in vivo</i> researches.

    DOI: 10.1507/endocrj.64.S35

    Scopus

    PubMed

  • Macha M.A. .  Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting cancer stem cells .  Oncotarget8 ( 13 ) 20961 - 20973   2017年

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    出版者・発行元:Oncotarget  

    DOI: 10.18632/oncotarget.15468

    Scopus

    PubMed

  • 野中 美希, 櫻井 隆, 上園 保仁, 杉原 匡美, 呉林 なごみ, 村山 尚, 白石 成二, 宮野 加奈子, 細田 洋司, 岸田 昭世, 寒川 賢治 .  ドキソルビシン心毒性に対するデスアシルグレリンの治療効果の検討 .  日本毒性学会学術年会43 ( 0 ) P - 63   2016年

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    出版者・発行元:日本毒性学会  

    ドキソルビシン(DOX)は、様々な新規抗がん剤が開発されている現在においても重要な抗がん剤として多くのがん腫に使用されている。しかし、腫瘍以外の組織、特に心筋組織への重篤な有害作用のため、その使用が制限されている。現在のところ、DOXの心毒性に対する画期的な予防薬は見当たらず、その開発が求められている。摂食促進ホルモングレリンにはアシル化修飾のないもう一つの分子型デスアシルグレリンがあり、グレリン受容体への結合能はない。デスアシルグレリンが、近年DOXによって起こる心筋アポトーシスを抑制することが報告され、心筋症予防能を有する可能性が示唆されている。しかし未だデスアシルグレリン特異的受容体が未同定のため、詳細な分子メカニズム解析は行われておらず、DOX心筋症等の新規心不全治療薬としての開発情報はほとんどない。本研究では、ラット心筋由来H9C2細胞を用いて、DOXによる心筋障害および心筋アポトーシスへのデスアシルグレリンの効果をlive-cell imagingシステムであるIncuCyte ZOOM<sup>®</sup>を用いて解析した。H9C2細胞にDOX( 0.1、0.3、0.5 µM)とデスアシルグレリン1 µMを同時処置し72時間incubateすると、デスアシルグレリンはDOX単独処置で認められる細胞障害を有意に抑制した。Caspase 3/7 kitを用いたアポトーシスアッセイでは、DOXによる細胞障害はアポトーシスによるものであり、デスアシルグレリンは、DOXによるアポトーシスを有意に抑制することを明らかにした。以上より、DOXはH9C2細胞においてアポトーシスを誘導するが、デスアシルグレリンはそのアポトーシスを抑制することを見出した。本学会では、DOXによるアポトーシスをデスアシルグレリンが抑制するメカニズムについても併せて紹介したい。

    DOI: 10.14869/toxpt.43.1.0_P-63

  • FUCHIGAMI Takao., KOYAMA Hirofumi., KISHIDA Shosei., IIJIMA Mikio., NISHIZAWA Yoshiaki., HIJIOKA Hiroshi., FUJII Tomomi., UEDA Masahiro., NAKAMURA Norifumi., KIYONO Touru., KISHIDA Michiko. .  Regulation of IL-6 and IL-8 Production by Reciprocal Cell-to-CellInteractions between Tumor Cells and Stromal Fibroblasts through IL-1<alpha> inAmeloblastoma .  Biochemical and Biophysical Research Communications451 ( 4 ) 491 - 496   2014年9月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Habu M., Koyama H., Kishida M., Kamino M., Iijima M., Fuchigami T., Tokimura H., Ueda M., Koriyama C., Hirano H., Arita K. and Kishida S. .  Ryk is essential for Wnt-5a-dependent invasiveness in human glioma. .  Journal of Biochemistry156 ( 1 ) 29 - 38   2014年7月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Hirano H, Yonezawa H, Yunoue S, Habu M, Uchida H, Yoshioka T, Kishida S, Kishida M, Oyoshi T, Fujio S, Sugata S, Yamahata H, Hanaya R, Arita K. .  Immunoreactivity of Wnt5a, Fzd2, Fzd6, and Ryk in glioblastoma: evaluative methodology for DAB chromogenic immunostaining. .  Brain Tumor Pathol.31 ( 2 ) 85 - 93   2014年4月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Kibe T, Fuchigami T, Kishida M, Iijima M, Ishihata K, Hijioka H, Miyawaki A, Semba I, Nakamura N, Kiyono T, Kishida S. .  A novel ameloblastoma cell line (AM-3) secretes MMP-9 in response to Wnt-3a and induces osteoclastogenesis. .  Oral Surg Oral Med Oral Pathol Oral Radiol.115   780 - 788   2013年1月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • HAYASHI Takehiro, KISHIDA Michiko, NISHIZAWA Yoshiaki, IIJIMA Mikio, KORIYAMA Chihaya, NAKAMURA Masayuki, SANO Akira, KISHIDA Shosei. .  Subcellular localization and putative role of VPS13/chorein in dopaminergic neuronal cells .  Biochemical and Biohysical Research Communications. Elsevier419   511 - 516   2012年2月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • KIBE Toshiro, KISHIDA Michiko, KAMINO Masayuki, IIJIMA Mikio, CHEN Lin, HABU Mika, MIYAWAKI Akihiko, HIJIOKA Hiroshi, NAKAMURA Norifumi, KIYONO Tohru, KISHIDA Shosei .  Immortalization and characterization of normal oral epithelial cells without using HPV and SV40 genes .  Oral science international : official journal of the Japanese Stomatological Society8 ( 1 ) 20 - 28   2011年5月

  • KIBE Toshiro, KISHIDA Michiko, KAMINO Masayuki, IIJIMA Mikio, CHEN Lin, HABU Mika, MIYAWAKI Akihiko, HIJIOKA Hiroshi, NAKAMURA Norifumi, KIYONO Tohru, KISHIDA Shosei .  Immortalization and Characterization of Nomal Oral Epithelial Cells without Using HPV and SV40 genes .  Oral Science International 8   20 - 28   2011年4月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • KAMINO Masayuki, KISHIDA Michiko, KIBE Toshiro, IKOMA Kyoko, IIJIMA Mikio, HIRANO Hirofumi, TOKUDOME Mai, CHEN Lin, KORIYAMA Chihaya, YAMADA Katsushi, ARITA Kazunori, KISHIDA Shosei .  Wnt-5a signaling is correlated with infiltrative activity in human glioma by inducing cellular migration and MMP-2 .  Cancer science102 ( 3 ) 540 - 548   2011年3月

  • Masayuki Kamino, Michiko Kishida, Toshiro Kibe, Kyoko Ikoma, Mikio Iijima,Hirofumi Hirano, Mai Tokudome,Lin Chen, Chihaya Koriyama,Katsushi Yamada, Kazunori Arita, Shosei Kishida .  Wnt-5a Signaling is Correlated with Infiltrative Activity in Human Glioma by Inducing Cellular Migration and MMP-2. .  Cancer Science102 ( 3 ) 540 - 548   2011年3月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • 岸田 昭世 .  Dvlと相互作用する新規蛋白質の解析 (助成研究報告) .  神戸大学医学部神緑会学術誌25   69 - 71   2009年8月

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    出版者・発行元:神戸大学  

  • Tabata Ayako, Sheng Jian-Sheng, Ushikai Miharu, SONG Yuan-Zong, GAO Hong-Zhi, LU Yao-Bang, OKUMURA Fumihiko, IIJIMA Mikio, MUTOH Kozo, KISHIDA Shosei, SAHEKI Takeyori, KOBAYASHI Keiko .  Identification of 13 novel mutations including a retrotransposal insertion in SLC25A13 gene and frequency of 30 mutations found in patients with citrin deficiency .  Journal of human genetics53 ( 6 ) 534 - 545   2008年6月

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    出版者・発行元:Springer Japan  

  • 池田 さやか, 小林 圭子, 大浦 敏博, 河野 嘉文, 岸田 昭世, 佐伯 武頼 .  Citrin 欠損症における追跡調査の現状と発育成長に及ぼす影響 .  日本先天代謝異常学会雑誌23 ( 1 )   2007年10月

  • Kishida, S.,, Hamao, K., Inoue, M., Hasegawa, M., Matsuura, Y., Mikoshiba, K., Fukuda, M., and Kikuchi, A. .  Dvl regulates endo- and exocytotic processes through binding to synaptotagmin .  Genes Cells12   49 - 61   2007年1月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Tsukamoto S, Ihara R, Aizawa A, Kishida S, Kikuchi A, Imai H, Minami N. .  Oog1, an oocyte-specific protein, interacts with Ras and Ras-signaling proteins during early embryogenesis. .  Biochem Biophys Res Commun19   1105 - 1112   2006年1月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Sugiyama, S., Kishida, S., and Kikuchi, A. .  Ubiquitin-interacting motifs of Epsin are involved in the regulation of insulin-dependent endocytosis .  J Biochem137   355 - 364   2005年1月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Hirabayashi, S., Nishimura, W., Iida, J., Kansaku, A., Kishida, S., Kikuchi, A., Tanaka, N., and Hata, Y. .  Synaptic scaffolding molecule interacts with axin .  J Neurochem90   332 - 339   2004年1月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • 岸田昭世 .  新規Dvl結合蛋白質Dapleの同定とそのWntシグナル伝達経路に対する作用の解析 .  平成15年度文部科学省科学研究費補助金特定領域研究(A)研究成果報告書 発生システムのダイナミズム(研究課題番号:13044001)   46 - 47   2004年1月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)  

  • Sato, A., Kishida, S., Tanaka, T., Kikuchi, A., Kodama, T., Asashima, M., and Nishinakamura, R. .  Sall1, a causative gene for Townes-Brocks syndrome, enhances the canonical Wnt signaling by localizing to heterochromatin .  Biochem Biophys Res Commun319   103 - 113   2004年1月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Kishida, S., Yamamoto, H., and Kikuchi, A. .  Wnt-3a and Dvl induce neurite retraction by activating Rho-associated kinase .  Molecular and Celllular Biology24   4487 - 4501   2004年1月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

▼全件表示

書籍等出版物

  • プロテインキナーゼ関連阻害剤

    岸田昭世 、菊池章( 担当: 共著)

    阻害剤活用ハンドブック、秋山徹、河府和義 編  2006年1月 

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    記述言語:日本語 著書種別:学術書

MISC

  • エナメル上皮腫の分子生物学的所見(Molecular biological findings of ameloblastoma)

    Fuchigami Takao, Ono Yusuke, Kishida Shosei, Nakamura Norifumi

    The Japanese Dental Science Review   57   27 - 32   2021年11月

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    記述言語:英語   出版者・発行元:日本歯科医学会  

  • Multiplicity of the interactions of Wnt proteins and their receptors. 査読

    Kikuchi A, Yamamoto H, and Kishida S.

    Cell Signal   19   659 - 671   2007年1月

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    記述言語:英語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

  • ユビキチン化を介するβ-カテニンの分解制御とその異常による発がんの分子機構

    菊池章、岸田昭世

    蛋白質核酸酵素   51   1271 - 1276   2006年1月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

  • Regulation of Wnt signaling by protein-protein interaction and post-translational modifications. 査読

    Kikuchi, A, Kishida, S, and Yamamoto, H.

    Exp Mol Med.   38   1 - 10   2006年1月

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    記述言語:英語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

講演・口頭発表等

  • KAMINO MASAYUKI, KIBE TOSHIRO, NAKAMURA YOKO, IKOMA KYOKO, TAKEDA YASUO, YAMADA KATSUSHI, KISHIDA MICHIKO, IIJIMA MIKIO, HIRANO HIROFUMI, KISHIDA SHOSEI .  GliomaにおけるWntシグナル分子の発現解析 .  第32回日本分子生物学会  第32回日本分子生物学会

     詳細を見る

    開催年月日: 2009年12月

    記述言語:日本語  

    開催地:神奈川  

    国内学会

  • 泉 七衣、岸田 昭世、菊池 章 .  GSK-3結合タンパク質GCP5(γ-tubulin ring complex構成因子)の同定 .  第28回日本分子生物学会フォーラム  第28回日本分子生物学会フォーラム

     詳細を見る

    開催年月日: 2006年12月

    記述言語:日本語  

    開催地:名古屋  

    国内学会

  • 菊池 章、岸田 昭世、山本 英樹、日野 真一郎 .  Wntシグナルネットワークによる多彩な細胞機能制御 .  第78回日本組織培養学会大会シンポジウム  第78回日本組織培養学会大会シンポジウム

     詳細を見る

    開催年月日: 2006年5月

    記述言語:日本語  

    開催地:※  

    国内学会

  • 中村光宏、岸田昭世、岸田想子、菊池 章 .  骨・軟骨分化におけるWntシグナルの役割 .  日本分子生物学会フォーラム  日本分子生物学会フォーラム

     詳細を見る

    開催年月日: 2006年1月

    記述言語:日本語  

    開催地:名古屋  

    国内学会

  • 岸田想子、岸田昭世、菊池 章 .  Wnt-11とWnt-4のコンディションドメディウムの作製と活性の解析 .  日本分子生物学会フォーラム  日本分子生物学会フォーラム

     詳細を見る

    開催年月日: 2006年1月

    記述言語:日本語  

    開催地:名古屋  

    国内学会

  • 岸田昭世、岸田想子、菊池 章 .  Wnt-5bの精製と生理機能の解析 .  日本分子生物学会フォーラム  日本分子生物学会フォーラム

     詳細を見る

    開催年月日: 2006年1月

    記述言語:日本語  

    開催地:名古屋  

    国内学会

  • 野中 美希, 柿木 亮, 岸田 昭世, 大島 佳織, 後藤 元秀, 上園 保仁, 上野 進 .  がん悪液質モデルマウスに出現する心機能障害と自発運動負荷がもたらす治療的効果 .  The Journal of Toxicological Sciences  2022年6月  (一社)日本毒性学会

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    記述言語:日本語  

  • 野中 美希, 呉林 なごみ, 村山 尚, 杉原 匡美, 宮野 加奈子, 白石 成二, 細田 洋司, 岸田 昭世, 寒川 賢治, 櫻井 隆, 上園 保仁 .  抗がん剤ドキソルビシの心毒性に対するグレリン・デスアシルグレリン治療効果の検討 .  産業衛生学雑誌  2017年5月  (公社)日本産業衛生学会

  • 野中 美希, 宮野 加奈子, 岸田 昭世, 白石 成二, 宇津 美秋, 上園 保仁 .  ドキソルビシンの心毒性に対するデスアシルグレリン治療効果の検討 .  日本癌学会総会記事  2017年9月  (一社)日本癌学会

  • 岸田 昭世, 小山 浩史, 西澤 芳明, 飯島 幹雄, 岸田 想子, 平野 宏文, 有田 和徳 .  グリオーマ由来細胞上清によるマクロファージPD-L1誘導の解析 .  日本生化学会大会プログラム・講演要旨集  2018年9月  (公社)日本生化学会

  • 渕上 貴央, 岸田 昭世, 岐部 俊郎, 石畑 清秀, 中村 典史 .  エナメル上皮腫細胞におけるIL-1α依存性のMMP-9分泌は腫瘍細胞の浸潤に重要である .  日本口腔科学会雑誌  2017年7月  (NPO)日本口腔科学会

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