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Novel gene-silencing nanoparticles shown to inhibit Ewing's sarcoma

rotein that typically carries iron molecules through the bloodstream until it meets up with a transferrin receptor on the surface of another cell. The transferrin binds tightly to a receptor on the cell's surface, where it is drawn inside and surrounded by a small vesicle. The vessels are acidified, causing the nanoparticles to release its contents ?the siRNA.

"Since transferrin receptors are upregulated in tumor cells, this delivery system will home in on tumor cells, leaving normal cells in tact," Hu said.

To test their new delivery system, the scientists targeted tumor cells from the patients of Ewing's sarcoma, a rare and often deadly bone cancer that generally strikes young adults. Despite aggressive therapy, about 40 percent of patients with Ewing's family tumors and 95 percent with metastases die as a result of their disease.

Scientists now recognize that Ewing's sarcoma results when two chromosomes break and trade their genetic content in what's technically called a "translocation," activating the oncogene EWS-FLI1 which triggers the tumor growth characteristic for this cancer.

In their experiment, siRNA was delivered to this growth-promoting region of the tumor cell, effectively reducing cell replication by 80 percent.

The scientists then tried their novel technology in laboratory mice grafted with human Ewing's sarcoma tumors. Following three consecutive days of treatment, the scientists observed strong, but transient, inhibition of tumor growth.

However, when used over longer durations (twice-weekly injections up to four weeks), the results were striking.

"Long-term treatments with this delivery system markedly inhibited tumor growth, with little or no tumor growth in many animals," said Hu.

Future experiments will combine the novel delivery system with small molecular anti-tumor agents, with hopes of creating a new and effective way to treat Ewing's sarcoma and other tumors in the clinic.'"/>

Source:American Association for Cancer Research


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