Ceramide species are elevated in human breast cancer and are associated with less aggressiveness

• Material Type: 博士論文
• Title: Ceramide species are elevated in human breast cancer and are associated with less aggressiveness
• Author/Editor: Moro, Kazuki
• Publication, Distribution, etc.: 新潟大学
• Publication Date: 2018-09-20
• Publication Date (W3CDTF): 2018-09-20
• Alternative Title: Ceramide species are elevated in human breast cancer and are associated with less aggressiveness; セラミド濃度はヒト乳癌組織において上昇し、セラミド濃度と腫瘍増殖とは負の関連を有する
• Degree grantor/type: 新潟大学
• Date Granted: 2018-09-20
• Date Granted (W3CDTF): 2018-09-20
• Dissertation Number: 甲第4499号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第4499号
• Text Language Code: eng
• Subject Heading: breast cancer; ceramide; metabolism; prognosis; sphingolipid
• Note (General): Sphingolipids have emerged as key regulatory molecules in cancer cell survival and death. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients are yet to be revealed. The aim of this study was to investigate the ceramide levels and its biosynthesis pathways in human breast cancer patients. Breast cancer, peri-tumor and normal breast tissue samples were collected from surgical specimens from a series of 44 patients with breast cancer. The amount of sphingolipid metabolites in the tissue were determined by mass spectrometry. The Cancer Genome Atlas was used to analyze gene expression related to the sphingolipid metabolism. Ceramide levels were higher in breast cancer tissue compared to both normal and peri-tumor breast tissue. Substrates and enzymes that generate ceramide were significantly increased in all three ceramide biosynthesis pathways in cancer. Further, higher levels of ceramide in breast cancer were associated with less aggressive cancer biology presented by Ki-67 index and nuclear grade of the cancer. Interestingly, patients with higher gene expressions of enzymes in the three major ceramide synthesis pathways showed significantly worse prognosis. This is the first study to reveal the clinical relevance of ceramide metabolism in breast cancer patients. We demonstrated that ceramide levels in breast cancer tissue were significantly higher than those in normal tissue, with activation of the three ceramide biosynthesis pathways. We also identified that ceramide levels have a significant association with aggressive phenotype and its enzymes have prognostic impact on breast cancer patients.; 学位の種類: 博士（医学）. 報告番号: 甲第4499号. 学位記番号: 新大院博（医）甲第836号. 学位授与年月日: 平成30年9月20日; Oncotarget. 2018, 9(28), 19874-19890.; 新大院博（医）甲第836号
• DOI: info:doi/10.18632/oncotarget.24903; https://doi.org/info:doi/10.18632/oncotarget.24903
• Persistent ID (NDL): info:ndljp/pid/11217062; https://dl.ndl.go.jp/pid/11217062
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2019-01-04T08:16:43+09:00
• Date Created (W3CDTF): 2019-09-10
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10191/50772
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp