NDLI: Quantifying the astrocytoma cell response to candidate pharmaceutical from F-ACTIN image analysis

Content Provider	IEEE Xplore Digital Library
Author	Chi Cui JaJa, J. Turbyville, T. Beutler, J. Gudla, P. Nandy, K. Lockett, S.
Copyright Year	2009
Description	Author affiliation: Molecular Targets Development Program, National Cancer Institute, Frederick (Beutler, J.) \|\| Optical Microscopy and Analysis Laboratory NCI-Frederick (Turbyville, T.; Gudla, P.; Nandy, K.; Lockett, S.) \|\| Department of Electrical and Computer Engineering, University of Maryland, College Park (Chi Cui; JaJa, J.)
Abstract	The distribution, directionality and motility of the actin fibers control cell shape, affect cell function and are different in cancer versus normal cells. Quantification of actin structural changes is important for further understanding differences between cell types and for elucidation of the effects and dynamics of drug interactions. We have developed an image analysis framework for quantifying F-actin organization patterns in confocal microscope images in response to different candidate pharmaceutical treatments. The main problem solved was to determine which quantitative features to compute from the images that both capture the visually-observed F-actin patterns and correlate with predicted biological outcomes. The resultant numerical features were effective to quantitatively profile the changes in the spatial distribution of F-actin and facilitate the comparison of different pharmaceuticals. The validation for the segmentation was done through visual inspection and correlation to expected biological outcomes. This is the first study quantifying different structural formations of the same protein in intact cells. Preliminary results show uniquely significant increases in cortical F-actin to stress fiber ratio for increasing doses of OSW-1 and Schweinfurthin A(SA) and a less marked increase for cephalostatin 1 derivative (ceph). This increase was not observed for the actin inhibitors: cytochalasin B (cytoB) and Y-27632 (Y). Ongoing studies are further validating the algorithms, elucidating the underlying molecular pathways and will utilize the algorithms for understanding the kinetics of the F-actin changes. Since many anti-cancer drugs target the cytoskeleton, we believe that the quantitative image analysis method reported here will have broad applications to understanding the mechanisms of action of candidate pharmaceuticals.
Starting Page	5768
Ending Page	5771
File Size	1520025
Page Count	4
File Format	PDF
ISBN	9781424432967
ISSN	1557170X
DOI	10.1109/IEMBS.2009.5332528
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2009-09-03
Publisher Place	USA
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Pharmaceuticals Image analysis Shape control Drugs Cancer Microscopy Biology computing Image segmentation Inspection Proteins
Content Type	Text
Resource Type	Article
Subject	Signal Processing Biomedical Engineering Health Informatics Computer Vision and Pattern Recognition

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