"If we had a way to detect early on in the apoptotic process whether or not a drug was working, patients would not have to wait weeks to months to find out," Ostrander said. "The idea that you could shine a light at a tumor and use the light-scattering pattern to measure the success of drugs is a big step forward."
For their experiments, the Duke team studied a well-known cell culture line of human breast cancer. The cells were exposed to two common chemotherapy drugs, doxorubicin and paclitaxel. Using the a/LCI technology, the researchers looked for specific patterns, which indicate that structural changes have occurred.
The researchers found that when compared to control cells, the paclitaxel-treated cells began showing significant increases in a pattern called fractal dimension within 90 minutes. Doxorubicin-treated cells exhibited the same increases within three hours. Interestingly, the fractal dimensions began decreasing at six hours, only to increase again within 12 hours of treatment.
"The fact that the changes in structure appear over two distinct time scales suggests that multiple mechanisms are involved in these early events in apoptosis," Wax said. "Further analysis showed the early changes we observed were taking place in the mitochondria, while the changes in the structure of the nucleus were responsible for the later ones."
Ostrander said that this technology will help laboratory investigators like her determine how cancer cells become resistant to apoptosis, and therefore are resistant to drugs. Before this technique can be employed for human breast cancer, further studies will be carried out in animals.
Wax and colleagues at the University of North Carolina at Chapel Hill are currently conducting a pilot clinical trial in humans using a similar technology for e
|Contact: Richard Merritt|