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Nanoscale gene 'ignition switch' may help spot and treat cancer
Date:12/15/2010

In a proof of principal study in mice, scientists at Johns Hopkins and the Virginia Commonwealth University (VCU) have shown that a set of genetic instructions encased in a nanoparticle can be used as an "ignition switch" to rev up gene activity that aids cancer detection and treatment.

The switch, called a promoter, is a set of chemical letters that interacts with DNA to turn on gene activity. In this case, the scientists used a promoter called PEG-Prom, cloned by VCU researcher Paul Fisher, Ph.D. PEG-Prom is activated only when inside cancer cells, not in normal ones.

"With current imaging devices like CT and PET, we can tell if something is wrong in a patient, but we don't have definitive tools to distinguish cancer from inflammation or infection," says Martin Pomper, M.D., Ph.D., professor of radiology at Johns Hopkins. "It generally takes at least one month after giving patients certain cancer treatments before existing imaging tools can measure the patient's response to the therapy."

To differentiate cancer cells from normal cells, Johns Hopkins scientists connected PEG-Prom to either a gene that produces firefly luciferase, the substance that make fireflies glow, or a gene called HSV1tk, which initiates a chemical reaction with radioactive labels inside the cell that can be detected by imaging devices. Once inside a cancer cell, the PEG-Prom switch is turned on, and it activates either the luciferase or HSV1tk gene.

Then, they stuffed the PEG-Prom/gene combination into tiny spheres about 50,000 times smaller than the head of a pin and intravenously injected the nanoparticles into mice with either metastatic breast cancer or melanoma.

The findings, reported in the December 12 online edition of Nature Medicine, reveal a 30-fold difference in identifying cancer cells containing luciferase and normal cells that did not contain the substance. Similar results were observed in cancer cells filled with
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Contact: Vanessa Wasta
wasta@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
Source:Eurekalert

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