{"created":"2023-05-15T14:41:36.300043+00:00","id":22,"links":{},"metadata":{"_buckets":{"deposit":"cf65f4f6-2c1b-46b0-8065-760b9a49fd8f"},"_deposit":{"created_by":18,"id":"22","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"22"},"status":"published"},"_oai":{"id":"oai:konan-u.repo.nii.ac.jp:00000022","sets":["3:5"]},"author_link":["5"],"control_number":"22","item_10006_alternative_title_1":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"テロメア及びテロメラーゼを標的としたがん治療法及びがん診断法の開発","subitem_alternative_title_language":"ja"}]},"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2014-03-31"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"甲南大学"}],"subitem_degreegrantor_identifier":[{}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(理工学)","subitem_degreename_language":"ja"}]},"item_10006_description_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_description":"平成25年度(2013年度)","subitem_description_language":"ja"}]},"item_10006_description_17":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"テロメラーゼによるテロメアDNA伸長反応（テロメラーゼ反応）は細胞のがん化を導く。そこで本研究では、テロメラーゼ反応の阻害によるがん治療法及び、    テロメラーゼ活性測定を介したがん診断法の開発を行った。\n１．がん治療法の開発：テロメアDNAにより形成されるG-quadruplex構造に結合するリガンドは、テロメラーゼ反応を阻害することが知られている。しかし従来のG-quadruplexリガンドの多くは、細胞内では染色体二本鎖DNAとも非特異的に結合するため、競合的にG-quadruplexへの結合が阻害される。さらに最近、細胞内の分子クラウディング（Molecular Crowding：MC）環境による水の活量低下も、G-quadruplexリガンドの結合を阻害することが報告された。そこでこれら阻害要因に対するG-quadruplexリガンドの官能基、中心金属、π平面の大きさの影響について系統的に解析した。その結果、アニオン性官能基を有するフタロシアニンは、    二本鎖DNAとは静電的に反発するため、G-quadruplexへの特異性が高いことが見出された。さらにアニオン性フタロシアニンはG-quadruplexに結合する際に水分子を取り込まないため、水の活量低下によるG-quadruplexへの結合阻害が生じないことが示された。そのためアニオン性フタロシアニンは、大量の二本鎖DNA存在下    及びMC条件下においてもテロメラーゼ反応を効率よく阻害することが示された。以上の結果は、アニオン性フタロシアニンが細胞核内においても効率よくテロメアDNAのG-quadruplexに結合し、テロメラーゼ反応を阻害することを示唆している。\n２．がん診断法の開発：従来のテロメラーゼ活性測定技術は、テロメラーゼ反応とPolymerase Chain Reaction（PCR）を組み合わせた手法である。そのため生体試料中のPCR阻害分子によって擬陰性結果が生じることがあった。そこで本研究では、テロメラーゼ反応後の反応産物を磁性ビーズ上に固定化、洗浄することで、PCR阻害分子を取り除く手法を開発した。さらにその後に行うPCRの産物をサイクリングプローブ法によって高感度に検出する方法を開発した。その結果、これらの手法を組み合わせることによってPCR阻害分子である胆汁酸、ビリルビン、ヘモグロビン存在下においても、阻害の影響を受けることなくがん細胞中のテロメラーゼ活性を測定できることが示された。また、検出感度50細胞という非常に高い感度でがん細胞を検出できることが示された。","subitem_description_language":"ja","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第85号"}]},"item_10006_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.14990/00000020","subitem_identifier_reg_type":"JaLC"}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open 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MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","objectType":"fulltext","url":"https://konan-u.repo.nii.ac.jp/record/22/files/H00011.pdf"},"version_id":"1c7c6757-04cf-44d9-946f-bfa2106811c9"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2015-03-13"}],"displaytype":"detail","filename":"H00011_2.pdf","filesize":[{"value":"159.2 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"論文内容の要旨及び論文審査の結果の要旨","objectType":"abstract","url":"https://konan-u.repo.nii.ac.jp/record/22/files/H00011_2.pdf"},"version_id":"280d33df-0efa-42d2-9190-f97fc6619ae2"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Telomere","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Telomerase","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cancer therapeutics","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cancer diagnostics","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Anionic phthalocyanine","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cell-nuclei mimicking condition","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Molecuar crowding","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"PCR inhibitor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cycling probe technology","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Telomere","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Telomerase","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cancer therapeutics","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cancer diagnostics","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Anionic phthalocyanine","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cell-nuclei mimicking condition","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Molecuar crowding","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"PCR inhibitor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cycling probe technology","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral 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