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Stem cells: A weapon in war on 'chemobrain'?

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By PAT BRENNAN / ORANGE COUNTY REGISTER

Survival for brain-cancer patients treated with chemotherapy comes with a dark side: "chemobrain," the debilitating loss of memory and mental function that often follows.

Now scientists at the UCI Medical Center are preparing a new weapon that could one day clear the cognitive fog.By manipulating stem cells, researchers Daniela Bota and Mark Linskey, both doctors who also treat cancer patients, say they may be able to place a bull's eye over tumor cells and wipe them out, while leaving the brain intact.

Their successes so far have all taken place in a petri dish, and it will likely be years before they can try their method on human patients.

But already, one expert is calling their discovery "the first truly novel approach to brain tumor therapy in more than four decades."

"Our cause and our passion is to take care of patients," Bota told a recent visitor to her lab on the hospital's campus in Orange. "That always comes first."

The first step would be to modify chemotherapy drugs so they can kill cancer without killing the brain cells around it.

But the two scientists, who are part of the hospital's Comprehensive Brain and Spinal Cord Tumor Program, have far bigger ideas.

"We hope to be able to do transplantation with human neural stem cells, and try to re-create memory and cognition," Linskey said. "That is sort of our big dream."

Their potential treatment hinges on the bizarre similarities between tumors and healthy tissues in the human body.

Both, for example, have their own versions of stem cells, the precursors that give rise to a variety of organs and other structures.

In normal tissues, these cells receive chemical signals that prompt them to become one thing or another.

The vast potential of stem cells, in fact, is driving an explosion of discoveries, Bota's and Linskey's among them.

The world's first trial of a treatment for acute spinal cord injuries using human embryonic stem cells, developed by UC Irvine stem-cell researchers Hans Keirstead and Gabriel Nistor, is now underway.

Many other conditions, from Alzheimer's to fatal childhood diseases, could one day be treated using stem cells.

But the "stem cells" in tumors are of a decidedly destructive variety.

Instead of differentiating into brains or bones or kidneys, they proliferate wildly, their chaotic growth becoming the tumors that disrupt the body and brain, and eventually kill.

Stem cells are also the tumor's greatest weakness.

By aiming chemical weapons at features found only on the tumor stem cells – a protein, for example, on the surface of the cell – Bota and Linskey hope to turn the tables on tumors, disrupting their mad growth while having little or no effect on normal cells.

Their early work on the problem is already making waves in the scientific community, with other researchers seeking out the two scientists and their co-authors by phone or email, and comments and references showing up in scientific journals.

In March, they published their highly suggestive findings. They found that two commonly used chemotherapy drugs did profound damage to neural stem cells, provided by Dr. Philip Schwartz at the Children's Hospital of Orange County and grown in their laboratory.

But the drugs had little effect on the tumor stem cells, or "glioma stem-like cells."

Meanwhile, two newer chemotherapy drugs had the opposite effect, causing little damage to the neural cells but knocking down tumor stem cells.

It's a long way from the petri dish to trials in human patients; tests on laboratory rats will come first.

And the findings by themselves also don't prove the connection between the resistance of tumors to some forms of chemotherapy and the "chemobrain" that later plagues patients.

But if the theory stands up to scientific scrutiny, it could make a huge difference in the lives of cancer survivors -- not only brain-cancer patients, but those who beat other forms of cancer and also suffer chemobrain.

Among them are breast-cancer patients, who show a 70 percent rate of memory loss after chemotherapy.

Children could be among the biggest beneficiaries of a chemobrain treatment, Bota said. They can have as high as an 80 percent survival rate after chemotherapy for brain cancer.

But the cognitive deficits that result can lower their quality of life and make it difficult, and perhaps impossible, to get on with their young lives: go to school, get a job.

"What you see at the end is the tumor in remission, the patient in dementia," Bota said.

For adults, such effects might explain why divorce rates among brain cancer patients are high.

"What we hear over and over again is, 'This is not the person that they used to be,'" she said.

It gets down to what Linskey believes could become a fundamental shift in the standards doctors use to decide whether or not a treatment is successful.

"The brain defines who we are as a person," he said. "The goal is to have the same person at the end of the treatment as you had when you started."

Article Tab: Cancer doctors Mark Linskey and Daniela Bota look over plans for experiments at the UC Irvine Medical Center. They hope to do battle with chemobrain, a loss of memory and mental function that can follow chemotherapy treatment.
Cancer doctors Mark Linskey and Daniela Bota look over plans for experiments at the UC Irvine Medical Center. They hope to do battle with "chemobrain," a loss of memory and mental function that can follow chemotherapy treatment.



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