Monthly Archive for December, 2009Page 2 of 2

POTENTIAL NEW “TWIST” IN BREAST CANCER DETECTION

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December 4, 2009- Working with mice, scientists at Johns Hopkins publishing in the December issue of Neoplasia have shown that a protein made by a gene called “Twist” may be the proverbial red flag that can accurately distinguish stem cells that drive aggressive, metastatic breast cancer from other breast cancer cells.

Building on recent work suggesting that it is a relatively rare subgroup of stem cells in breast tumors that drives breast cancer, scientists have surmised that this subgroup of cells must have some very distinctive qualities and characteristics.

In experiments designed to identify those special qualities, the Hopkins team focused on the gene “Twist” (or TWIST1) – named for its winding shape – because of its known role as the producer of a so-called transcription factor, or protein that switches on or off other genes. Twist is an oncogene, one of many genes we are born with that have the potential to turn normal cells into malignant ones.

“Our experiments show that Twist is a driving force among a lot of other players in causing some forms of breast cancer,” says Venu Raman, Ph.D., associate professor of radiology and oncology, Johns Hopkins University School of Medicine. “The protein it makes is one of a growing collection of markers that, when present, flag a tumor cell as a breast cancer stem cell.”

Previous stem cell research identified a Twist-promoted process known as epithelial-to-mesenchymal transition, or EMT, as an important marker denoting the special subgroup of breast cancer stem cells. EMT essentially gets cells to detach from a primary tumor and metastasize. The new Hopkins research shows that the presence of Twist, along with changes in two other biomarkers – CD 24 and CD44 – even without EMT, announces the presence of this critical sub-group of stem cells.
“The conventional thinking is that the EMT is crucial for recognizing the breast cancer cell as stem cells, and the potential for metastasis, but our studies show that when Twist shows up in excess or even at all, it can work independently of EMT,” says Farhad Vesuna, Ph.D., an instructor of radiology in the Johns Hopkins University School of Medicine. “EMT is not mandatory for identifying a breast cancer stem cell.”

Working with human breast cancer cells transplanted into mice, all of which had the oncogene Twist, the scientists tagged cell surface markers CD24 and CD44 with fluorescent chemicals. Following isolation of the subpopulation containing high CD44 and low CD24 by flow cytometry, they counted 20 of these putative breast cancer stem cells. They then injected these cells into the breast tissue of 12 mice. All developed cancerous tumors.

“Normally, it takes approximately a million cells to grow a xenograft, or transplanted tumor,” Vesuna says. “And here we’re talking just 20 cells. There is something about these cells – something different compared to the whole bulk of the tumor cell – that makes them potent. That’s the acid test – if you can take a very small number of purified “stem cells” and grow a cancerous tumor, this means you have a pure population.”

Previously, the team showed that 65 percent of aggressive breast cancers have more Twist compared to lower-grade breast cancers, and that Twist-expressing cells are more resistant to radiation.
Twist is what scientists refer to as an oncogene, one that if expressed when and where it’s not supposed to be expressed, causes oncogenesis or cancer because the molecules and pathways that once regulated it and kept it in check are gone.

This finding – that Twist is integral to the breast cancer stem cell phenotype – has fundamental implications for early detection, treatment and prevention, Raman says. Some cancer treatments may kill ordinary tumor cells while sparing the rare cancer stem cell population, sabotaging treatment efforts. More effective cancer therapies likely require drugs that kill this important stem cell population.

This study was supported by the Maryland Stem Cell Research Foundation.

In addition to Vesuna and Raman, authors of the paper include Ala Lisok and Brian Kimble, also of Johns Hopkins.

fonte http://www.hopkinsmedicine.org/Press_releases/2009/12_04_09.html

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Video: Stem Cells & Diabetes

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Alan Lewis of the Juvenile Diabetes Research Foundation distinguishes type 1 and type 2 diabetes, and continues to explain how stem cells are being used today to develop new treatments for type 1 diabetes (a.k.a. juvenile diabetes). Human embryonic stem cells (hESC) are being differentiated to the beta (insulin producing) cells that type 1 diabetics lack, and are being transplanted , in animal models. Since type 1 diabetes is an auto-immune disease, the transplanted cells must be protect from destruction by the immune system. Currently, researchers are working towards that goal with encapsulating technologies and a “gentle” immuno-modulation. In order to treat a diabetic patient, access to an unlimited number of cells is necessary. Alan compares embryonic stem cells, adult stem cells, and iPS as source of cells. And finally, in a future outlook, Alan comments on the FDA’s concern for safety, the risk of creating a tumor, artificial pancreas (as an alternative approach), and cell therapy‘s potential to CURE diseases

from http://biobusiness.tv/videos/223

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Stem cell research gives hope to stroke patients

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Sections of tooth undergoing development.
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Stroke-damaged brains could be repaired within 5-10 years using adult stem cells from teeth, according to one of Australia’s leading stroke physicians who is pioneering new research in this field.

Associate Professor Simon Koblar from the University of Adelaide and The Queen Elizabeth Hospital is leading a research project that shows dental pulp stem cells extracted from teeth may prove far more beneficial for brain repair than other types of stem cells.

His research involving adult stem cells is the first of its kind in Australia and will be explained at a free public lecture at the University of Adelaide tomorrow night as part of the University’s highly successful Research Tuesdays monthly seminar series.

Stroke is the leading cause of disability in Australia, with 60,000 people suffering a stroke every year and approximately 30% of them losing their lives.

Assoc. Prof. Koblar says dental pulp stem cells have a natural ability to produce and repair neurones (nerve cells). Because they are in teeth, they can also be easily extracted and don’t pose rejection issues for patients.

In 2007 Assoc. Prof. Koblar was awarded $100,000 by the Catholic Archdiocese of Sydney for a collaborative pilot study on adult stem cells with Associate Professor Stan Gronthos from SA Pathology. Stroke SA also provided additional financial support for this project in 2009.

The two scientists are senior members of the University of Adelaide’s Centre for Stem Cell Research at the Robinson Institute.

“We have some very promising data from trials involving stroke-affected rats, who have shown an improvement in mobility when transplanted with dental pulp stem cells,” he says.

Assoc. Prof. Koblar says more research needs to be done to prove the benefit in animal models before it can be trialled in humans.

The Robinson Institute is currently working with University of Adelaide graduate and stroke victim Peter Couche to set up a Stem Cell for Stroke Foundation in his name.

“Like all research, what we can achieve will depend on how much money can be raised,” Assoc. Prof. Koblar says.

Stem cell research has great potential to affect stroke patients and benefit the Australian community as a whole, because its impact in this country is enormous. Even if all we can do is to get someone’s hand function to improve, that would be a magnificent advance.”

An inaugural $75,000 collaborative research grant from the Centre for Stem Cell Research has been awarded to Associate Professors Koblar and Gronthos to continue their research into adult stem cell therapy for stroke patients.

from http://www.adelaide.edu.au/news/news37182.html

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