Development of a cancer-specific histoculture drug response assay with a simulated microgravity culture system

使用模拟微重力培养系统开发癌症特异性组织培养药物反应测定

• 批准号: 16591325
• 负责人: NOSHIRO Hirokazu
• 金额: $ 2.3万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591325/
• 关键词: carcinoma tissue; histoculture drug response assay; cancer-specific; simulated microgravity culture; tumor marker; 組織感受性試験; 低重力培養; 消化器癌

This study was aimed to develop a next generation histoculture drug response assay (HDRA) that can provide information on chemosensitivity of carcinoma cells by utilizing a simulated microgravity (SM) culture system. During this study period, we analyzed 31 surgically resected carcinoma specimens and following data were obtained. We used a rotary cell culture system (RCCS-4DQ : Synthecon, Houston, TX). Carcinoma tissues of 2 mm^3 were used for this SM-HDRA. The vessel was filled completely with RPMI 1640 containing 10% FCS with or without chemotherapeutic agent such as 5-FU and CDDP. The response was evaluated by immunohistochemical analysis (Ki67 staining and TUNNEL staining) and measurement of production of tumor marker proteins such as CEA and CA19-9.Summary:Twenty-five of the 31 carcinoma specimens were successfully evaluated for SM-HDRA. Importantly, carcinoma cells secreted larger amount of tumor marker proteins such as CEA and CA19-9 under SM culture conditions in comparison with 1 g culture conditions. And, the numbers of carcinoma cells counted in SM-HDRA were well correlated with CEA and/or CA19-9 concentration in the culture supernatant collected from the vessel. Thus, because this system made it possible to use tumor marker proteins as an evaluation parameter, SM-HDRA provided information about not only the chemosensitivity of carcinoma cells without interference from normal cells but also heterogenous drug responses in the carcinoma tissue.In conclusion, this SM-HDRA may become not only a new drug response assay but also a powerful tool for development of therapeutic strategies.A part of this study has been introduced in a paper (Nakamura K et al. Preclinica,2(5):356-361,2004).

本研究旨在开发下一代组织培养药物反应测定（HDRA），它可以利用模拟微重力（SM）培养系统提供有关癌细胞化学敏感性的信息。在本研究期间，我们分析了 31 例手术切除的癌症标本，并获得了以下数据。我们使用旋转细胞培养系统（RCCS-4DQ：Synthecon，休斯顿，德克萨斯州）。 2 mm^3 的癌组织用于此 SM-HDRA。该容器完全充满含有 10% FCS 的 RPMI 1640，有或没有化疗剂，如 5-FU 和 CDDP。通过免疫组织化学分析（Ki67 染色和 TUNNEL 染色）和测量肿瘤标志物蛋白（如 CEA 和 CA19-9）的产生来评估反应。总结：31 份癌症标本中的 25 份成功评估了 SM-HDRA。重要的是，与 1 g 培养条件相比，SM 培养条件下癌细胞分泌更多的肿瘤标志物蛋白，如 CEA 和 CA19-9。并且，SM-HDRA 中计数的癌细胞数量与从容器收集的培养上清液中的 CEA 和/或 CA19-9 浓度密切相关。因此，由于该系统使得使用肿瘤标志物蛋白作为评估参数成为可能，SM-HDRA不仅提供了有关癌细胞的化学敏感性且不受正常细胞干扰的信息，而且还提供了癌组织中异质药物反应的信息。总之，该SM-HDRA不仅可能成为一种新的药物反应测定，而且可能成为制定治疗策略的有力工具。这项研究的一部分已在论文中介绍 (Nakamura K 等人 Preclinica,2(5):356-361,2004)。

项目成果

A novel histoculture drug response assay with a simulated microgravity culture system

使用模拟微重力培养系统进行新型组织培养药物反应测定

• 发表时间: 2004
• 期刊: Preclinica 2・5
• 作者: Ohkawa;T. et al.;Nakamura K. et al.
• 通讯作者: Nakamura K. et al.

Novel histoculture drug response assay with a simulated microgravity culture system

使用模拟微重力培养系统进行新型组织培养药物反应测定

• 发表时间: 2004
• 期刊: Preclinica 2・5
• 作者: Nakamura K;et al.
• 通讯作者: et al.

Novel histoculture drug response assay with a simulated Microgravity culture system.

使用模拟微重力培养系统进行新型组织培养药物反应测定。

• 发表时间: 2004
• 期刊: Preclinica 2(5)
• 作者: Nakamura K;Nakahara C;Kuga H;Yamanaka N;tasaki A;Nakashima H;Kubo M;Morisaki T;Fujii H;Sueishi K;Tanaka M;Katano M
• 通讯作者: Katano M