Basic research on cell-biological feature of multidrug resistant osteosarcoma and overcoming of resistance

多重耐药骨肉瘤细胞生物学特征及克服耐药性的基础研究

• 批准号: 07457340
• 负责人: KUSUZAKI Katsuyuki
• 金额: $ 4.8万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457340/
• 关键词: osteosarcoma; multidrug-resistance; overcoming of multidrug-resistance; mouse osteosarcoma cell; adriamycine; DNA ploidy; P-glycoprotein; electoron magmetic field; P糖蛋白質; 薬剤感受性試験; アドリアマイシン結合能

Result of DNA ploidy analysis in the study revealed that non-diploid (including aneuploid and euploid-polyploid) osteosarcoma was more sensitive to chemotherapy than diploid one. Adriamycin binding study showed that adriamycin binding ability was closely correlated with histological response to chemotherapy in human osteosarcomas. Multigrug resistant mouse osteosarcoma cells which was established in the study was resistant not only adriamycine also vincristin, bleomycine, mitomycine etc. This cell line was found to be useful for experimental study on overcoming of resistance. In various overcoming methods for resistance, verapamil, cyclosporin A,MS 209, Tween 20 or 80, electoron magnetic field, radiation were useful in mouse osteosarcoma. However, clinically electron magnetic field and MS 209 may available, because two of these were not toxic for human body.

本研究中DNA倍体分析结果显示，非二倍体（包括非整倍体和整倍体-多倍体）骨肉瘤比二倍体骨肉瘤对化疗更敏感。阿霉素结合研究表明，阿霉素结合能力与人骨肉瘤化疗的组织学反应密切相关。本研究建立的多重耐药小鼠骨肉瘤细胞不仅对阿霉素还耐药，还对长春新碱、博来霉素、丝裂霉素等耐药。该细胞系被发现可用于克服耐药性的实验研究。在克服耐药性的多种方法中，维拉帕米、环孢素A、MS 209、吐温20或80、电子磁场、放射治疗对小鼠骨肉瘤有效。然而，临床上可以使用电磁场和MS 209，因为其中两种对人体没有毒性。

项目成果

楠崎 克之: "肺転移を生じた骨肉腫の原発巣と転移巣のDNAプロイディ解析" 臨床整形外科. 32・1. 23-30 (1997)

Katsuyuki Kusuzaki：“转移至肺部的原发性和转移性骨肉瘤肿瘤的 DNA 倍体分析”《临床骨科》32・1（1997）。

H.Takeshita, M.C.Gerhardt, D.S.Springfield, K.Kusuzaki, H.J.Mankin: "Experimental models for the study of drug resistance in osteosarcoma : P-glycoprotein-positive, murine osteosarcoma cell lines." J.Bone Joint Surg. [Am]. 78-A(3). 366-375 (1996)

H.Takeshita、M.C.Gerhardt、D.S.Springfield、K.Kusuzaki、H.J.Mankin：“研究骨肉瘤耐药性的实验模型：P-糖蛋白阳性的小鼠骨肉瘤细胞系。”

福本和生: "Adriamycin binding assayの悪性骨軟部腫瘍に対する薬剤感受性試験としての有用性" 京都府立医科大学雑誌. 104. 1199-1215 (1995)

Kazuo Fukumoto：“阿霉素结合测定作为恶性骨和软组织肿瘤药物敏感性测试的有用性”京都府立医科大学杂志 104. 1199-1215 (1995)。

Kusuzaki,Katsuyuki: "Relationship between cellulan adriamycin binding ability to nuclean DNA and hisological hesponse to preoperative chenotherapy in human osteosarcoma" Camcer. (in press). (1998)

Kusuzaki，Katsuyuki：“纤维素阿霉素与核 DNA 的结合能力与人骨肉瘤术前化疗的组织学反应之间的关系”Camcer。

福本和生: "骨肉腫における化学療法の骨髄抑制と予後の関連" 中部整災誌. 38. 353-354 (1995)

Kazuo Fukumoto：“骨肉瘤中化疗引起的骨髓抑制与预后之间的关系”Chubu Seisai Journal 38. 353-354 (1995)。