A new method to assess drug sensitivity on breast tumor acute slices preparation.
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 microM 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.
Mestres
Pedro
P
Department of Anatomy and Cell Biology, University Hospital, Building 61, University of Saarland, D-66421 Homburg/Saar, Germany. anpmes@uniklinikum-saarland.de
Morguet
Andrea
A
Schmidt
Werner
W
Kob
Axel
A
Thedinga
Elke
E
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015194:Diffusion Chambers, Culture / Q000295:instrumentation / Q000379:methods; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006801:Humans; D008867:Microtomy; D017239:Paclitaxel / Q000378:metabolism; D011190:Potassium Cyanide / Q000378:metabolism; D012969:Sodium Fluoride / Q000378:metabolism; D013997:Time Factors; D014021:Tissue Preservation
D012969:Sodium Fluoride; D011190:Potassium Cyanide; D017239:Paclitaxel