When a person dying of cancer, the culprit is usually not the original tumor, but the cancer cells that spread throughout the body and replicate in distant organs, a process called metastasis. Researchers have long known that cancer cells metastasize slip their obligations and avoid immune detection by changing the sugars on their surfaces. They even come with a medication would be to avoid such sugar modifications. But this compound interferes with the sugars necessary on normal cells, too, with fatal results in animals. Now Dutch researchers say they have packaged the drug in nanoparticles targeted exclusively to cancer cells, and showed that this combination prevents cancer cell metastasis in mice.
The new therapy nanotechnology still has a long way to go before becoming a drug, including pass safety testing and efficacy in humans. Nevertheless, "it is promising," said Cory Rillahan, a chemical biologist at Memorial Sloan Kettering Cancer Center in New York who was not connected to the study. Rillahan, which it 3 years ago was part of the team the first report of anti-metastatic drug compound, known as P-3F ax -Neu5Ac said the compound was designed to block a family of 20 enzymes that modify sugars known sialic acids. often sialic acids cap long chains of other sugar molecules that are attached to proteins or lipids that the cell surfaces of the uprights. These channels have been shown to be involved in cell adhesion and recognition, the key processes coopted by metastatic cancer cells.
Several types of cancer cells overexpress enzymes that add sialic acid to sugar chains. But closing off all these enzymes can be dangerous. Last year, a team led by James Paulson, a chemist at the Scripps Research Institute in San Diego, California, who heads the lab where Rillahan did his work on P-3F ax -Neu5Ac , found that the drug caused fatal kidney damage in mice when injected into the bloodstream. So for P-3F ax -Neu5Ac to have a shot as antimetastasis drug, it must target cancer cells.
This is the step that researchers led by Gosse Adema, immunologist of the tumor at the University Medical Centre Radboud in Nijmegen, Netherlands, have now taken. In an article published online this month in ACS Nano Adema and colleagues report package P-3F ax -Neu5Ac nanoscale, biodegradable vesicles made from poly ( lactic- co -glycolic acid) or PLGA, an approved compound for use by the Food and Drug administration of the United States. They then vesicles coated with antibodies that home on a protein overexpressed on the surface of melanoma cells. The melanoma cells often metastasize to the lungs. Thus, in their study, Adema and his colleagues tested whether melanoma cells spread to the lungs in mice.
It is difficult for laboratory researchers to quickly study solid tumor metastasis, because they might have to wait months for rogue cells spinning. So to speed things up, the team of Adema is based on a standard procedure of injecting cancer cells and anti-metastatic drug in the veins of the mouse tail and wait two weeks to see if the cells began to form new tumor nodules. After 14 days, the Dutch team found that the mice that received the drug loaded nanovesicles developed 75% fewer tumor nodules in their lungs than mice not given nanovesicles empty.
Whether this therapy will be successful in humans remains uncertain, because most drugs that work in mice do not in people. The synthesis of sugar chains on cells called glycosylation differs between human and mouse, so that any potential drug should prevent glycosylation in human cancer cells. Still, Paulson said the new finding "opens the door" to the prospect of drugs that inhibit glycosylation as an alternative, or additional, strategy against metastatic cancer. Such a discovery will not make a remedy against day after cancer. But it could help researchers learn how to prevent the spread of cancer, the most lethal weapon of the disease.
0 Komentar