Image analysis for quantitation of solid tumor drug sensitivity.
BACKGROUND
A method of assessing chemosensitivity of tissue has been described by Rotman et al. The aim of this study was to use image analysis to provide a more rapid and quantitative means of assessing drug effect on tissue proliferative capacity.


METHODS
Fluoropyrimidine sensitive Ward rat colon adenocarcinoma tumor was implanted onto collagen impregnated cellulose fibers suspended on metal grids at an air-fluid interface and kept in a 95% air/5% CO2 incubator at 37 degrees C. The fluorescent microscopic image captured by a silicon intensified target (low light detecting) camera and linked to an image processing unit was measured for fluorescent brightness and tumor image area. Blinded 5-Fluorouracil (5-FU) drug treatment was begun 8 days after tumor explantation on the collagen-cellulose matrix. Tumor image area and fluorescent brightness were measured at 24 h pretreatment, 48 h posttreatment, and at 48 h post drug removal.


RESULTS
Nontreated tumor cultures demonstrated an increase in area and fluorescent brightness with time following tumor implantation on the collagen gel. Dose responsiveness was seen with increasing concentrations of 5-FU. At the highest clinically achievable concentration of 5-FU (500 microM), there was a 39% decrease in area compared with the nontreated group, 113%. Linear dose responsiveness was not demonstrated between 50 and 150microM 5-FU.


CONCLUSIONS
Fluoropyrimidine activity was demonstrated with the implemented image analysis system. The in vitro tumor sensitivity to FU using collagen gel was consistent with responsiveness of tumors in vivo borne by rats.
Gibbs
J F
JF
Department of Surgical Oncology, Roswell Park Cancer Institute, State University of New York at Buffalo, 14263, USA. jgibbs@sc3101.med.buffalo.edu
Slocum
H K
HK
Cao
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Rustum
Y M
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D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D008856:Microscopy, Fluorescence; D009994:Osmolar Concentration; D011743:Pyrimidines / Q000493:pharmacokinetics; D051381:Rats; D016037:Single-Blind Method
D000964:Antimetabolites, Antineoplastic; D011743:Pyrimidines; C029269:5-fluoropyrimidine; D005472:Fluorouracil