CancerStemCellNicheWords

--Sacking the Cancer Stem Cell Neighborhood--

[This article was posted on "Science Magazine's" website today, to coincide with the embargoed release of a paper from "Cancer Cell."]

Scientists have found the Achilles heel of a special class of cells that jump starts tumor growth. According to a new study, targeting the niche where they live is the key to destroying these previously invincible cells. This insight paves the way for more effective cancer therapy.

Until recently, researchers believed that all cells in a tumor were pretty much the same. But in the early 1990s, a team at the University of Toronto found some interesting characters hanging out in a population of leukemia cells: instead of rapidly dividing like their companions, about one in every million leukemia cells was capable of maintaining itself in a culture dish without differentiating and then initiating tumor growth when transplanted. These were indications that the cell was likely a stem cell.

Since then, researchers have discovered similar stem cells—including those behind acute myeloma leukemia, two brain cancers, and breast cancer—but no drug to date has successfully eliminated CSCs, which infinitely renew themselves and generate cells to replenish the tumor even after the bulk of it has been eliminated by chemotherapy or radiation. CSCs can do this in part because they grow at a sluggish rate, rendering them insensitive to conventional therapies designed to target rapidly dividing cells.

Now, researchers lead by neurobiologist Richard Gilbertson at St. Jude Children's Research Hospital in Memphis, Tennessee, have found a way to target cancer stem cells independently from the bulk of the tumor. They did so by looking for similarities between these stem cells and non-cancerous neural stem cells. Neural stem cells—immature cell masses that give rise to more specialized cells that form nerve tissue—are concentrated in blood vessel-rich regions called "vascular niches." These regions are lined with endothelial cells, which secrete chemical signals that promote stem cell survival. Gilbertson's team inferred that cancer stem cells might require a similar niche.

Sure enough, after examining a large cohort of human brain tumors, the researchers found that cancer stem cells were frequently located close to capillaries—the body's tiniest blood vessels. When the researchers injected human brain tumor cells called medulloblastomas together with endothelial cells in mice, the animals sprouted larger tumors than mice receiving tumor cells alone, the team reports today in Cancer Cell. This experiment further supports the role of endothelial cells and the vascular niche in providing signals that promote tumor growth.

Additionally, in tumor-bearing mice, drugs used to deplete blood vessels caused a significant drop in CSCs and subsequently inhibited tumor growth. The same vessel-killing drugs hardly effected the survival of cells in rest of the tumor, confirming that CSCs require a vascular niche.

"This study is an excellent example of bringing stem cell insight to cancer," says Richard Wechsler-Reya, a cancer biologist at Duke University Medical Center in Durham, North Carolina. "I think this is going to be the beginning of a really popular approach to treating cancer stem cells."

.MGW.

Gotta See About a MountainWords

[Fiction]

Manhattan smelled of snow the morning I decided to leave it---not for eternity though, just for the weekend. The weather was right for skiing.

And without thinking about the work I'd miss or the stories needing my time, I threw my warmest fleece in a backpack, grabbed the pod, and sat down at my MAC: "Dear Editor and colleagues, I'll talk to you next week. Gotta see about a mountain, Meagan."

That morning, as New York highways turned into New Hampshire roads, the wintery sky above my car was as resistant to categorization as any sunrise scene I'd ever known. Gray clouds--fat and stoic--formed castles in the air, while whiter, wispy things lingered oddly outside their gates. Together these fat and small clouds barely veiled a pink sun, and I looked at it often and in spurts--a routine I kept up all the way to New Hampshire.

The cloud castle gates had closed on the sun when my car finally stopped. I wasn't in a parking lot though. And I wasn't at a ski resort. I had stopped at a footpath leading to a mountain named by no map. Just a mountain somewhere. I'd seen it from a distance once and thought it might want to be visited by someone willing to climb.

Snow made my climb especially quiet that dark afternoon; no sounds but my own deep breaths and the occasional hawk. The hawks were watching me but I was watching the view, and the way the mountain slope was slipping into a misty depth with my each upward step.

It was a steep mountain, that's for certain, but I hoped it would slip steeper still on the opposite face. When I got there and threw down my pack, I was glad to see just that. It was peace enough for the moment--hunting and finding a great decline. So I enjoyed it, but not by skiing down on the skis I'd brought. Instead, I opened my backpack and took out a book.

Like the mountaintop, this book had no name. Its pages weren't filled and there was no preface. There was no author either--not until the pink sun peeked out from cloud castle gates and blinded all wild eyes on the mountaintop. That's when I was moved to pen something--fast and strong--on those very blank pages. I authored the book, writing something so raw and true it might have been just like a hawk's pulse in flight.

I felt easy...

Before too long, I grabbed the book and my pack and flew down the mountain on a slope skiied only by wintering deer. And perhaps it was the wind's kiss or the birds closely watching, but I had never felt so alive.

.MGW.

Scientist As RebelWords

Freeman Dyson may be short in stature--or so he seemed when I met him last year--but his accomplishments are undeniably tall. A former member of England's Royal Air Force, a longtime physics professor at Princeton, and a distinguished scientist with a bent for elegant mathematics, this Brit also has a way with words; he is lovely writer.

In Dyson's newest book, The Scientist as Rebel, the seasoned physicist speaks to the nature of scientists throughout the ages. "From Galileo to today's amateur astronomers, scientists have been rebels," he writes. They are free spirits, like artists and poets, casting off the restrictions their cultures impose. In their hunt for Nature's truths, they are guided as much by imagination as by reason, and their brightest theories have the uniqueness and beauty of great works of art.

Dyson affirms that the best way to understand science is by understanding those who practice it. He tells stories of scientists at work, and looks with a skeptical eye at fashionable scientific trends.

Dyson also reflects on broader philosophical issues--the limits of reductionism, the morality of nuclear bombing, the preservation of the environment...

This charming scientist offers a fresh and eloquent perspective on today's topics of scientific debate, as well as a narrative that highlights the finer linings of some of the greatest minds of all time.

.MGW.

InterestAndStrengthWords

“Love many things, for therein lies the true strength, and whosoever loves much performs much, and can accomplish much, and what is done in love is done well.” --Vincent Van Gogh

"A large volume of adventures may be grasped within this little span of life, by him who interests his heart in everything." --Laurence Sterne

I aspire.

.MGW.

WildernessWords

Caledonia-my home sweet home






"In wilderness lies the preservation of the world." HD Thoreau

Anti-CancerWords

In the pipeline...

Researchers at Hopkins have created a hybrid molecule that causes cancer cells to self-destruct. The recipe: a sugar + a fatty acid called butyrate.

Butyrate slows the spread ofcancer cells, which scientists have known for 20 years. Unfortunately, attempts to use this molecule as a general drug for tumors haven't worked well because of the need for exceedingly high doses.

To get around the dosage problem, scientists have tried to make butyrate more potent by modifying it or joining it to other compounds. Results have been disappointing though; there are toxic side effects associated with partner molecules.

Now, Gopalan Sampathkumar, a postdoctoral fellow in JHU's Department of Biomedical Engineering, has found that when butyrate is matched with just the right sugar, the resultant hybrid molecule acts like a cancer-killing weapon, wiping out every cancer cell in its immediate path within about 15 days.

This is not the first time scientists have tried combining butyrate with sugars, but the sugars used previously just eased the delivery process, helping the hybrid molecule get into the cancer cell. Sampathkumar was more selective. He chose a sugar called cetyl-D-mannosamine, or ManNAc, which acts like ammunition in the cancer-killing process. It helps enzymes to resume the normal assembly of sugar molecules, which often goes awry when cancer occurs.

Meanwhile, the butyrate half of the hybrid molecule corrects aberrant gene expression. The result is a double attack, triggering just what the doctors ordered: cancer cell suicide.

More to come after I talk with the docs. This hasn't yet been tested in humans or animals and I'd like to know what the prospects are for this cancer-killing strategy in our generation.

.MGW.