Laboratory Leonard Zone at Boston Children's Hospital has long been studying the blood stem cells. In search of such cells in the zebrafish, they turned to gene MYB, a marker of blood stem cells. To do this, Joseph Mandelbaum added to the MYB green fluorescent dye, which is easily seen in the transparent zebrafish embryos. MYB is not only a marker of blood stem cells, but also oncogene.
Another researcher, Jeff Kaufman, founded in 2005, the Research Foundation of adenoid cystic carcinoma. Usually the tumor begins in the salivary glands, but may also occur in the larynx, trachea and lacrimal gland. "We know that MYB is the main driver carcinoma", - says Kaufman. He tried to figure out how to disable the MYB.
The results, published last week in the Journal of Experimental Medicine, laid the groundwork for clinical trials in patients with carcinoma in the Cancer Institute Dana-Farber.
Despite numerous clinical trials for the treatment of carcinoma is no standard treatment regimens or drugs. About half of the patients suffering from metastasis.
Zones, Mandelbaum and his colleagues have created a drug screening system. MYB genes each zebrafish embryo were labeled with green fluorescent protein. Using an automated cell imaging system, they looked at whether any chemical "switch off the green."
As a result, 22 chemicals disconnected MYB, of which retinoic acid and its derivatives were the most effective. Retinoic acid is a derivative of vitamin A. Team further confirmed the effectiveness of retinoic acid in human tumor cells. The researchers turned to the line of human myeloid leukemia, which also expresses MYB at high levels. Retinoic acid inhibited MYB in just one hour. Additional experiments in mice have shown that retinoic acid (in particular, a drug called ATRA) slows tumor growth. The scientists also found out how the retinoic acid. ATRA - the first drug that is directly aimed at MYB.
Mandelbaum and regions presented the results of the study at a meeting of oncologists Cancer Institute Dana-Farber. The researchers plan to test the ATRA for 12 patients. ATRA is already used for the treatment of promyelocytic leukemia, so patients with carcinoma will receive the same dose.
Changes in the MYB are associated with various cancers, including leukemia, glioma, colorectal cancer, breast and prostate. But experiments with zebrafish will allow to go further.
"Potentially, if the cancer is controlled by a particular gene, you can use it in a zebrafish model, create a chemical genetic screen, and then see that inhibits the development of tumors, - says Mandelbaum. - chemical screening in zebrafish - a very powerful and fast system. "