Fundamental Research on Hybrids of MRI Contrast Agents and Antitumor Agents to Innovate in Diagnosis and Curing Cancers Efficiently at the Very Early Stage

MRI 造影剂和抗肿瘤剂混合的基础研究，以创新癌症早期有效诊断和治疗

• 批准号: 21650108
• 负责人: YAMASHITA Mitsuji
• 金额: $ 2.24万
• 依托单位: Shizuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21650108/
• 关键词: がん早期発見; がん早期治療; MRI造影剤; リン糖抗がん剤; 複合機能化

The project contained three sub-research thema(1).(3) and the progress of the research was 80% completion.(1) R & D of sugar dendritic Gd-DTAP complex for MRI contrast agents DEN-OH and the modification was 80% successful to develop novel blood pool MRI contrast agents and DEN-OH(prepared via hydrolysis route) drew clear blood vessels and liver cancers. The r1 value for DEN-OH and modified sugar Dendritic Gd-DTPA complexes were 20. 31[mmol-1・s-1], which are superior to clinically used Gd-DTPA(r1=3. 5[mmol-1・s-1]) by 10 times.(2) Phospha sugar antitumor agents were developed. Among them, TBMPP and DBMPP were most active and the analogs showed 10-1000 times more active than Gleevec(clinically used drug). TBMPP suppressed the expression of Cdc25B, which is a common factor of cell cycle for various kinds of cancer cells. Therefore, phospha sugars must most probably be developed as new"Multiple Type Molecular Targeted Antitumor Agents"and the drug may cure various types of cancer patients by the single drug.(3) The application of the results(1) and(2) provided new drugs for diagnosing and curing cancers in the sub-research thema, whose results will not be disclosed at the present stage.

该项目包含三个子研究主题（1）、（3），研究进度已完成80%。（1）MRI造影剂用糖树枝状Gd-DTAP复合物的研发及修饰80%成功开发新型血池MRI造影剂和DEN-OH（通过水解途径制备）绘制清晰的血管和肝癌DEN-OH和修饰糖Dendritic的r1值。 Gd-DTPA配合物为20. 31[mmol-1·s-1]，优于临床使用的Gd-DTPA(r1=3. 5[mmol-1·s-1])10倍。(2)开发了磷酸糖类抗肿瘤药物，其中TBMPP和DBMPP活性最强，其类似物的活性比临床使用的格列卫高10-1000倍。 TBMPP抑制Cdc25B的表达，Cdc25B是多种癌细胞的细胞周期的共同因子，因此，磷酸糖很可能被开发为新的“多型分子靶向抗肿瘤剂”，并且该药物可以治愈多种癌症。 （3）结果（1）和（2）的应用为该子研究主题提供了诊断和治疗癌症的新药，现阶段不会披露其结果。

项目成果

Preparation of phosphosugar analogs and their evaluation as novel anticancer agents

磷糖类似物的制备及其作为新型抗癌药物的评价

• 发表时间: 2011
• 期刊: Phosphorus, Sulfur and Silicon and the Related Elements
• 作者: Kenji Tsunekawa;Mitsuji Yamashita;Michio Fujie;Taishi Niimi;Takuya Suyama;Kazuhide Asai;SatoruIto;Junko Yamashita;Manabu Yamada;Nobuhisa Ozaki;and Satoki Nakamura
• 通讯作者: and Satoki Nakamura

がんの早期発見・早期治療の技術革新のための医工連携による医用材料開発研究

通过医工合作研发医用材料，实现癌症早发现、早治疗的技术创新

• 发表时间: 2009
• 作者: 山下純子;山田学;尾崎伸久;清藤圭太;常川謙二;浅井一秀;陶山卓也;新美大志;杉山雅紀;Uma Ravi Sankar Arigala;山岡真弓;澤田亜李歩;戸田三津夫;田中康隆;木村元彦;山下光司;藤江三千男;中村悟己;竹原康雄;阪原晴海
• 通讯作者: 阪原晴海

Preparation of phospha sugar analogues and their evaluation as novel molecular targeting anticancer agents

磷糖类似物的制备及其作为新型分子靶向抗癌药物的评价

• 发表时间: 2011
• 期刊: Phosphorus, Sulfur and Silicon and the Related Elements
• 作者: Tsunekawa;Kenji;et. al.;他10名(Corresponding Author : Yamashita;Mitsuji)
• 通讯作者: Mitsuji)

Research and Development of Medicinal Materials for Diagnosing and Curing Cancer(3)-Synthesis and Evaluation of Novel Phospha Sugar Anti-cancer Agents

诊治癌症药用材料的研发（三）——新型磷糖抗癌药物的合成与评价

• 发表时间: 2011
• 作者: M. Yamashita;et. al.
• 通讯作者: et. al.

Preparation of Phospha Sugar Analogues and Their Evaluation as Novel Molecular Targeting Anti-cancer Agents

磷糖类似物的制备及其作为新型分子靶向抗癌药物的评价

• 发表时间: 2010
• 作者: Kenji Tsunekawa;et. al.;他10名(Corresponding Author : Yamashita;Mitsuji)
• 通讯作者: Mitsuji)