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5 December 2013 11:26 am ,
Vol. 342 ,
An animal rights group known as the Nonhuman Rights Project filed lawsuits in three New York courts this week in an...
Researchers have been hot on the trail of the elusive Denisovans, a type of ancient human known only by their DNA and...
Thousands of scientists in the Russian Academy of Sciences (RAS) are about to lose their jobs as a result of the...
Dyslexia, a learning disability that hinders reading, hasn't been associated with deficits in vision, hearing, or...
Exotic, elusive, and dangerous, snakes have fascinated humankind for millennia. They can be hard to find, yet their...
Researchers have sequenced and analyzed the first two snake genomes, which represent two evolutionary extremes. The...
Snake venoms are remarkably complex mixtures that can stun or kill prey within minutes. But more and more researchers...
At age 30, Dutch biologist Freek Vonk has built up a respectable career as a snake scientist. But in his home country,...
- 5 December 2013 11:26 am , Vol. 342 , #6163
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A Shield Against Chemotherapy
9 May 2012 2:32 pm
Chemotherapy saves lives, but it can take a considerable toll on the body. Now, by inserting a mutated gene into cancer patients, researchers have found a way to protect them against the side effects of chemotherapy and boost their odds of surviving a particularly aggressive type of cancer.
Patients with glioblastoma, a fast-growing and usually fatal brain cancer, face overwhelming odds. Half die within 13 months of diagnosis, and very few survive long-term. Treatment is part of the problem. Many glioblastomas are resistant to chemotherapy because they harbor an overactive gene called MGMT, which repairs the cancer cells after chemotherapy damages them. To counteract the gene, physicians sometimes add an MGMT-blocking drug, benzylguanine, to the chemotherapy regimen to make the cancer cells easier to kill. But benzylguanine also makes healthy blood and bone marrow cells easy to kill.
"Without those cells, patients become very susceptible to infections," says Hans-Peter Kiem, an oncologist and stem cell biologist with the Fred Hutchinson Cancer Research Center in Seattle, Washington. "Then they can't get the appropriate amount of chemotherapy because they have to stop treatment."
To find a way around these severe side effects, Kiem and colleagues zeroed in on a mutated version of MGMT called P140K. The gene enables cells to resist chemotherapy and benzylguanine. The team wondered what would happen if healthy cells had P140K.
The researchers obtained blood stem cells, which are found in bone marrow, from three glioblastoma patients and inserted the gene coding for the mutant P140K into the cells. Immediately after a chemotherapy session that wiped out some of the patients' healthy cells, the team infused the tweaked stem cells back into each patient. Within weeks, the stem cells had developed into mature blood and marrow cells, with 40% to 60% of them carrying the mutated gene. Armed with the mutation, patients were able to undergo chemotherapy with benzylguanine without losing healthy cells. The protected cells survived, while unprotected tumor cells died.
The three patients survived an average of 22 months, surpassing the median survival for glioblastoma, the team reports online today in Science Translational Medicine. One patient remains alive 3 years after treatment, and still carries the mutated gene.
"He's home, he's working-it's wonderful," says Kiem. "This diagnosis is like a death sentence, so we're really happy."
Although a larger-scale study is needed, says Stan Gerson, a hematology oncologist with Case Western Reserve University in Cleveland, Ohio, and the discoverer of P140Kthe team's technique could eventually benefit patients suffering from glioblastoma and other MGMT-overactive cancers, like colon and lung cancer. "This study establishes the proof of concept for the first time," Gerson says. "That's a big leap. And this is the very first step."