Document Detail


Characterization of an in vitro cell culture bioreactor system to evaluate anti-neoplastic drug regimens.
MedLine Citation:
PMID:  16502018     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A dynamic 3-dimensional tissue culture system has been developed that will allow for control of gemcitabine exposure to mimic concentration-time profiles measured from biologic samples. Gemcitabine was infused into a central reservoir. Media is mixed and delivered through hollow fiber capillaries, where it diffuses into the extracapillary space containing anchorage-dependent MDA-231 cells. To test for control of gemcitabine concentration-time profiles, drug was first infused through bioreactors without cells, and gemcitabine concentrations were measured with HPLC. Concentrations could be controlled to simulate 30-min and 2.5 h infusions, and were similar in both the lumen and extracapillary space. MDA-231 cells were then seeded into control (n = 4) and gemcitabine treatment (n = 4) groups, and maintained in culture for 2 weeks. Gemcitabine (5.3 mg) was infused over 30 min to the treatment group, and blank media to the control group. Accuracy of measured gemcitabine maximum concentration (Cmax) was 83.4%, and area under the curve (AUC), 106.2%, relative to pre-experimental theoretical values. With cells present, gemcitabine AUC in the extracapillary space was 32% of the value in the lumen. For the control group, 21.2 million cells (94.3% viable) were recovered, and for the gemcitabine-treated group, 16.8 million cells (87.1 % viable). Flow cytometry showed that 13.3 % of cells in the control group were in S-phase and 34.3 % in the gemcitabine-treated group were in S-phase (p = 0.003). In conclusion, gemcitabine concentration-time profiles could be accurately controlled through dosage, infusion rate, and pump flow rate, and cells could be recovered afterward to evaluate drug treatment.
Authors:
Mark N Kirstein; Richard C Brundage; William F Elmquist; Rory P Remmel; Paul H Marker; Dan E Guire; Douglas Yee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  96     ISSN:  0167-6806     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-10     Completed Date:  2006-10-26     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  217-25     Citation Subset:  IM    
Affiliation:
Department of Experimental and Clinical Pharmacology, College of Pharmacy and Comprehensive Cancer Center, University of Minnesota, Minneapolis 55455, USA.
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MeSH Terms
Descriptor/Qualifier:
Antimetabolites, Antineoplastic / administration & dosage*
Area Under Curve
Bioreactors*
Breast Neoplasms / drug therapy*,  pathology
Cell Line, Tumor
Cell Survival / drug effects
Deoxycytidine / administration & dosage,  analogs & derivatives*,  pharmacokinetics
Female
Flow Cytometry
Humans
Lactic Acid / biosynthesis
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 50-21-5/Lactic Acid; 951-77-9/Deoxycytidine; B76N6SBZ8R/gemcitabine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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