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Cecal tumorigenesis in AhR-deficient mice depends on cecum-specific MAPK pathway activation and inflammation (AhRノックアウトマウスの回盲部における腫瘍発生は回盲部に特異的なMAPK経路の活性化と炎症反応に依存する). 信州大学, 2019, 博士論文.", "subitem_description_type": "Other"}]}, "item_14_dissertation_number_7": {"attribute_name": "学位授与番号", "attribute_value_mlt": [{"subitem_dissertationnumber": "13601甲第1192号"}]}, "item_14_link_74": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000509437800015"}]}, "item_14_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "信州大学"}]}, "item_14_relation_54": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "31734232"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://pubmed.ncbi.nlm.nih.gov/31734232/", "subitem_relation_type_select": "PMID"}}]}, "item_14_relation_55": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1016/j.ajpath.2019.10.005"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1016/j.ajpath.2019.10.005", "subitem_relation_type_select": "DOI"}}]}, "item_14_rights_69": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ "}]}, "item_14_select_71": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "ETD"}]}, "item_14_text_11": {"attribute_name": "学位の区分", "attribute_value_mlt": [{"subitem_text_value": "doctoral"}]}, "item_14_text_12": {"attribute_name": "学位の分野", "attribute_value_mlt": [{"subitem_text_value": "医学"}]}, "item_14_text_13": {"attribute_name": "学位の報告番号", "attribute_value_mlt": [{"subitem_text_value": "甲第1192号"}]}, "item_14_text_77": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "COLORECTAL-CANCER DEVELOPMENT; MACROPHAGE ACTIVATION; BOWEL-DISEASE; COLON-CANCER; EXPRESSION; PROGRESSION; MONOCYTES; OVEREXPRESSION; CARCINOGENESIS; IL-1-BETA"}]}, "item_14_textarea_75": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "The aryl hydrocarbon receptor (AhR) is a transcription factor known as a dioxin receptor. Recently, Ahr(-/-) mice were revealed to develop cecal tumors with inflammation and Wnt/beta-catenin pathway activation. However, whether beta-catenin degradation is AhR dependent remains unclear. To determine whether other signaling pathways function in Ahr(-/-) cecal tumorigenesis, we investigated histologic characteristics of the tumors and cytokine/chemokine production in tumors and Ahr(-/-) peritoneal macrophages. AhR expression was also assessed in human colorectal carcinomas. Of the 28 Ahr(-/-) mice, 10 developed cecal Lesions by 50 weeks of age, an incidence significantly lower than previously reported. Cecal lesions of Ahr(-/-) mice developed from serrated hyperplasia to adenoma/dysplasia-like neoplasia with enhanced proliferation. Macrophage and neutrophil infiltration into the lesions was also observed early in serrated hyperplasia, although adjacent mucosa was devoid of inflammation. Il1b, Il6, Ccl2, and Cxcl5 were up-regulated at lesion sites, whereas only IL-6 production increased in Ahr(-/-) peritoneal macrophages after lipopolysaccharide + ATP stimulation. Neither Myc (alias c-myc) up-regulation nor beta-catenin nuclear translocation was observed, unlike previously reported. Interestingly, enhanced phosphorylation of extracellular signal-regulated kinase, Src, and epidermal growth factor receptor and Amphiregulin up-regulation at Ahr(-/-) lesion sites were detected. In human serrated lesions, however, AhR expression in epithelial cells was up-regulated despite morphologic similarity to Ahr(-/-) cecal lesions. Our results suggest novel mechanisms underlying Ahr(-/-) cecal tumorigenesis, depending primarily on cecum-specific mitogen-activated protein kinase pathway activation and inflammation."}]}, "item_1627890986942": {"attribute_name": "出版タイプ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_be7fb7dd8ff6fe43", "subitem_version_type": "NA"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "open access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_abf2"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "的場, 久典", "creatorNameLang": "ja"}], "nameIdentifiers": [{"nameIdentifier": "109529", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "15MH206A_yoshi.pdf", "filesize": [{"value": "166.5 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 166500.0, "url": {"label": "内容の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/21402/files/15MH206A_yoshi.pdf"}, "version_id": "551bd815-3e57-4d93-800b-a5028ec4c832"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "15MH206A_shinsa.pdf", "filesize": [{"value": "197.0 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 197000.0, "url": {"label": "審査結果の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/21402/files/15MH206A_shinsa.pdf"}, "version_id": "6fe8a14f-b40f-4d6e-8952-293539b6784d"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-11-14"}], "displaytype": "detail", "download_preview_message": "", "file_order": 2, "filename": "15MH206A_ronbun.pdf", "filesize": [{"value": "2.9 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "© 2020. 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Cecal tumorigenesis in AhR-deficient mice depends on cecum-specific MAPK pathway activation and inflammation (AhRノックアウトマウスの回盲部における腫瘍発生は回盲部に特異的なMAPK経路の活性化と炎症反応に依存する)
http://hdl.handle.net/10091/00022159
http://hdl.handle.net/10091/000221598c1232b4-dc6f-4cc1-a7b3-be0f9812933d
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内容の要旨 (166.5 kB)
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審査結果の要旨 (197.0 kB)
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博士論文の全文 (2.9 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2020-06-15 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Cecal tumorigenesis in AhR-deficient mice depends on cecum-specific MAPK pathway activation and inflammation (AhRノックアウトマウスの回盲部における腫瘍発生は回盲部に特異的なMAPK経路の活性化と炎症反応に依存する) | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
的場, 久典
× 的場, 久典 |
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出版者 | ||||||
出版者 | 信州大学 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 的場 久典. Cecal tumorigenesis in AhR-deficient mice depends on cecum-specific MAPK pathway activation and inflammation (AhRノックアウトマウスの回盲部における腫瘍発生は回盲部に特異的なMAPK経路の活性化と炎症反応に依存する). 信州大学, 2019, 博士論文. | |||||
書誌情報 |
発行日 2019-03-31 |
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学位授与番号 | ||||||
学位授与番号 | 13601甲第1192号 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2019-03-31 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 13601 | |||||
学位授与機関名 | 信州大学(Shinshu university) | |||||
学位の区分 | ||||||
doctoral | ||||||
学位の分野 | ||||||
医学 | ||||||
学位の報告番号 | ||||||
甲第1192号 | ||||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 雑誌に発表。AMERICAN JOURNAL OF PATHOLOGY. 190(2):453-468 (2020); doi:10.1016/j.ajpath.2019.10.005. | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Thesis | |||||
PubMed | ||||||
識別子タイプ | PMID | |||||
関連識別子 | https://pubmed.ncbi.nlm.nih.gov/31734232/ | |||||
関連名称 | 31734232 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1016/j.ajpath.2019.10.005 | |||||
関連名称 | 10.1016/j.ajpath.2019.10.005 | |||||
権利 | ||||||
権利情報 | © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
出版タイプ | ||||||
出版タイプ | NA | |||||
出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||
WoS | ||||||
Web of Science | ||||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000509437800015 |