NDLI: Image-based evaluations of distribution and cytotoxicity of Irinotecan (CPT-11) in a multi-compartment micro-cell coculture device.

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Image-based evaluations of distribution and cytotoxicity of Irinotecan (CPT-11) in a multi-compartment micro-cell coculture device.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nakayama, Hidenari Kimura, Hiroshi Fujii, Teruo Sakai, Yasuyuki
Description	Country affiliation: Japan Author Affiliation: Nakayama H ( Institute of Industrial Science (IIS), University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.); Kimura H ( Institute of Industrial Science (IIS), University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.); Fujii T ( Institute of Industrial Science (IIS), University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.); Sakai Y ( Institute of Industrial Science (IIS), University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan. Electronic address: sakaiyas@iis.u-tokyo.ac.jp.)
Abstract	We recently developed a polydimethylsiloxane (PDMS)-based three-compartment microfluidic cocultivation device enabling real-time interactions of different cell populations as an advanced physiologically-relevant cell-based assay. This device had valves and small magnetic stirrer-based internal pumps for easy and flexible perfusion operations. In this study, we applied this device for the evaluation of Irinotecan (CPT-11) toxicity to the lung, because it is detoxified by the liver and accumulated in the fat in humans. We successfully cultured representative three different tissue model cells in each compartment under the individual culture conditions and also in entire perfusion. Growth inhibition of rat lung epithelial cell line L-2, was measured when administered with 50 µM CPT-11 under various cocultivation conditions with respect to the presences and absence of primary rat hepatocytes (liver tissue model) and adipocyte-like cells (fat tissue model) induced from a mouse fibroblast cell line, 3T3-L1. Although CPT-11 showed moderate toxicity to the pure culture of L-2 cells in the device after 72 h of perfusion culture, this was lowered mainly in the presence of the liver tissue. Inhibition of the L-2 cell growth agreed with the area under curve (AUC) values obtained from fluorescent image-based analyses in each compartment. These results demonstrate that developed simple and flexible microfluidic cocultivation device, with appropriate image-based analyses, can be used in evaluating toxicokinetic behaviors of drug candidates in systemic levels.
File Format	HTM / HTML
ISSN	13891723
Issue Number	6
Volume Number	117
e-ISSN	13474421
Journal	Journal of Bioscience and Bioengineering
Language	English
Publisher	Elsevier
Publisher Date	2014-06-01
Publisher Place	Japan
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Biomedical Engineering Discipline Microbiology Antineoplastic Agents, Phytogenic Pharmacology Camptothecin Analogs & Derivatives 3t3-l1 Cells Adipocytes Physiology Animals Metabolism Cell Proliferation Cell Survival Drug Effects Coculture Techniques Instrumentation Dimethylpolysiloxanes Chemistry Drug Screening Assays, Antitumor Hepatocytes Mice Microfluidic Analytical Techniques Microscopy, Fluorescence Rats Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Bioengineering Applied Microbiology and Biotechnology Biotechnology

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Image-based evaluations of distribution and cytotoxicity of Irinotecan (CPT-11) in a multi-compartment micro-cell coculture device.

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