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A New Method to Assess Drug Sensitivity on Breast Tumor Acute Slices Preparation
Author(s) -
MESTRES PEDRO,
MORGUET ANDREA,
SCHMIDT WERNER,
KOB AXEL,
THEDINGA ELKE
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.088
Subject(s) - respiration , drug , anaerobic glycolysis , chemistry , oxygen , cellular respiration , toxicant , biomedical engineering , pharmacology , metabolism , glycolysis , medicine , biochemistry , organic chemistry , toxicity , anatomy
A method for assessing tumor drug sensitivity is described that is based on preparation of tissue slices and use of silicon chips equipped with electrochemical sensors (multisensor array). The tumor slices (200–300 μM thick) are prepared after surgery and incubated in a medium for recovery after slicing. The advantage, compared to other preparations, is that the original three‐dimensional structure is retained. Multisensor arrays measure: ( a ) pericellular acidification (anaerobic metabolism) and ( b ) oxygen consumption (respiration). The innovative aspect is that such measurements can be made online, as opposed to using a large battery of endpoint tests on cell vitality and proliferation. Electron microscopy of slices serves to determine cell density and structure and induction of apoptosis/necrosis. Slices of more than 200 breast tumors were used. Metabolic activity was inhibited by sodium fluoride, which reduces glycolysis, and potassium cyanide, which inhibits respiration. These changes are thus reflected in the curves of acidification and oxygen consumption. In other experiments the cytostatic Taxol, an anticytoskeletal agent, was used showing dose and time‐dependent effects on acidification and oxygen consumption. In conclusion, the method presented here, is able to provide information on drug sensitivity of a tumor, which aids in designing individualized therapy and is used for drug screening.