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By The Associated Press

Published: 9:59 PM - 08/01/12 Last updated: 10:00 PM - 08/01/12

NEW YORK How can a cancer come back after it's apparently been eradicated? Three new studies are bolstering a long-debated idea: that tumors contain their own pool of stem cells that can multiply and keep fueling the cancer, seeding regrowth.

If that's true, scientists will need to find a way to kill those cells, apart from how they attack the rest of the tumor.

Stem cells in healthy tissues are known for their ability to produce any kind of cell. The new research deals with a different kind, cancer stem cells. Some researchers, but not all, believe they lurk as a persisting feature in tumors.

Over the past decade, studies have found evidence for them in tumors like breast and colon cancers. But this research has largely depended on transplanting human cancer cells into mice that don't have immune systems, an artificial environment that raises questions about the relevance of the results.

Now, three studies reported online Wednesday in the journals Nature and Science present evidence for cancer stem cells within the original tumors. Again, the research relies on mice. That and other factors mean the new findings still won't convince everyone that cancer stem cells are key to finding more powerful treatments.

But researcher Luis Parada, of the University of Texas Southwestern Medical Center in Dallas, believes his team is onto something. He says that for the type of brain tumor his team studied, "we've identified the true enemy."

If his finding applies to other cancers, he said, then even if chemotherapy drastically shrinks a tumor but doesn't affect its supply of cancer stem cells, "very little progress has actually been made."

The three studies used labeling techniques to trace the ancestry of cells within mouse tumors.

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Cancer debate: Are tumors fueled by stem cells?

Published: Wednesday, August 1, 2012, 9:06 p.m.

If that's true, scientists will need to find a way to kill those cells, apart from how they attack the rest of the tumor.

Stem cells in healthy tissues are known for their ability to produce any kind of cell. The new research deals with a different kind, cancer stem cells. Some researchers, but not all, believe they lurk as a persisting feature in tumors.

Over the past decade, studies have found evidence for them in tumors like breast and colon cancers. But this research has largely depended on transplanting human cancer cells into mice that don't have immune systems, an artificial environment that raises questions about the relevance of the results.

Now, three studies reported online Wednesday in the journals Nature and Science present evidence for cancer stem cells within the original tumors. Again, the research relies on mice. That and other factors mean the new findings still won't convince everyone that cancer stem cells are key to finding more powerful treatments.

But researcher Luis Parada, of the University of Texas Southwestern Medical Center in Dallas, believes his team is onto something. He says that for the type of brain tumor his team studied, "we've identified the true enemy."

If his finding applies to other cancers, he said, then even if chemotherapy drastically shrinks a tumor but doesn't affect its supply of cancer stem cells, "very little progress has actually been made."

The three studies used labeling techniques to trace the ancestry of cells within mouse tumors.

Collectively, they give "very strong support" to the cancer stem cell theory, said Jeffrey M. Rosen, a professor of molecular and cellular biology at Baylor College of Medicine in Houston. He did not participate in the work but supports the theory, which he said is widely accepted.

Another scientist who's skeptical about the theory, and said he has plenty of company, said the new papers did not change his mind.

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Tumors could be fueled by stem cells

For the first time, researchers can trace cell lineage within a growing tumour. In this skin tumour, the cells labelled red all arose from a single stem cell.

G. Driessens

Cancer researchers can sequence tumour cells genomes, scan them for strange gene activity, profile their contents for telltale proteins and study their growth in laboratory dishes. What they have not been able to do is track errant cells doing what is more relevant to patients: forming tumours. Now three groups studying tumours in mice have done exactly that13. Their results support the ideas that a small subset of cells drives tumour growth and that curing cancer may require those cells to be eliminated.

It is too soon to know whether these results obtained for tumours of the brain, the gut and the skin will apply to other cancers, says Luis Parada at the University of Texas Southwestern Medical Center in Dallas, who led the brain study2. But if they do, he says, there is going to be a paradigm shift in the way that chemotherapy efficacy is evaluated and how therapeutics are developed. Instead of testing whether a therapy shrinks a tumour, for instance, researchers would assess whether it kills the right sorts of cell.

Underlying this scenario is the compelling but controversial hypothesis that many tumours are fuelled by cancer stem cells that produce the other types of cancer cell, just as ordinary stem cells produce normal tissues. Previous studies have tested this idea by sorting cells from a cancer biopsy into subsets on the basis of factors such as cell-surface markers, and injecting them into laboratory mice. In principle, those cells that generate new tumours are the cancer stem cells. But sceptics point out that transplantation removes cells from their natural environment and may change their behaviour. You can see what a cell can do, but not what cells actually do, says Cdric Blanpain of the Free University of Brussels, who co-led the skin study1.

All three research groups tried to address this knowledge gap by using genetic techniques to track cells. Parada and his co-workers began by testing whether a genetic marker that labels healthy adult neural stem cells but not their more specialized descendents might also label cancer stem cells in glioblastoma, a type of brain cancer. When they did so, they found that all tumours contained at least a few labelled cells presumably stem cells. Tumours also contained many unlabelled cells2. The unlabelled cells could be killed with standard chemotherapy, but the tumours quickly returned. Further experiments showed that the unlabelled cells originated from labelled predecessors. When chemotherapy was paired with a genetic trick to suppress the labelled cells, Parada says, the tumours shrank back into residual vestiges that did not resemble glioblastoma.

Meanwhile, Hans Clevers, a stem-cell biologist at the Hubrecht Institute in Utrecht, the Netherlands, and his colleagues focused on the gut. They had previously shown that a genetic marker that labels healthy gut stem cells also labels stem cells in benign intestinal tumours, which are precursors of cancer4. In their latest study3, he and his team engineered mice to carry a gene for a drug-inducible marker that, when activated, causes labelled cells to make molecules that fluoresce one of four colours. This experiment yielded single-colour tumours consisting of several cell types, suggesting that each tumour arose from a single stem cell. To check that stem cells continued to fuel the tumours, Clevers added a second, low dose of the drug, triggering a few of the stem cells to change colour. This produced streams of cells in the new colour, showing that stem cells were consistently producing the other cell types.

For the skin study, Blanpain and his group labelled individual tumour cells, without targeting stem cells specifically1. They found that cells showed two distinct patterns of division: they either produced a handful of cells before petering out, or went on to produce many cells. Once again, the results pointed to a distinct subset of cells as the engine of tumour growth. Whats more, as tumours became more aggressive, they were more likely to produce new stem cells which can divide indefinitely and less likely to produce differentiated cells, which can divide only a limited number of times. That could be a key to halting tumour development early, says Blanpain. Rather than eradicating cancer stem cells, for example, therapies could try to coax them to differentiate into non-dividing cells.

The papers provide clear experimental evidence that cancer stem cells exist, says Robert Weinberg, a cancer researcher at the Whitehead Institute in Cambridge, Massachusetts. They have made a major contribution to validating the concept of cancer stem cells, he says. But cancer cells probably also act in more complex ways than those observed, he warns. For example, non-stem cells within the tumour might de-differentiate into stem cells.

The next step, the three groups say, is figuring out how the cells tracked in these experiments relate to putative cancer stem cells identified by years of transplantation studies. Researchers are already busy hunting for ways to kill these cells; now they have more tools to tell whether such a strategy will work.

Excerpt from:
Cancer stem cells tracked

When cancers are treated, tumors may shrink but then come roaring back. Now studies on three different types of tumors suggest a key reason why: The cancers are fueled by stem cells that chemotherapy drugs don't kill.

The findings made by independent research teams that used mice to study tumors of the brain, intestines and skin could change the approach to fighting cancers in humans, experts said.

Properties of these so-called cancer stem cells can be investigated so researchers can devise strategies for killing them off, said Luis F. Parada, a molecular geneticist at the University of Texas Southwestern Medical Center in Dallas and senior author of one of the studies published Wednesday.

"Everything has a soft underbelly once you understand it well," Parada said. "With all the modern molecular techniques and modern approaches we have, we should be able to find their soft underbelly."

Cancer researchers have long suspected and some pioneering studies have strongly suggested that specific cells within tumors are responsible for their continued growth. But the earlier experiments hadn't convinced everyone, and the hypothesis has been controversial.

The three papers published by the journals Nature and Science "really should seal the deal," said cancer biologist Owen Witte, director of the Broad Stem Cell Research Center at UCLA.

"People can stop arguing," he said. "Now they can say, 'OK, the cells are here. We now need to know how to treat them.' "

All three studies used molecular tricks that allowed scientists to mark certain tumor cells with bright colors. When these marked cells divided, all of the daughter cells were similarly colored. This permitted the researchers to see whether any old cell in a tumor can continue to fuel its growth or if only a subset of cells is responsible.

The three groups used different experimental approaches and different kinds of cancer, but all of them found the latter to be true.

Parada's group, whose work was published in Nature, studied an aggressive cancer called glioblastoma that arises when brain cells called glia turn rogue. The scientists started with a hunch if a cancer stem cell existed, it would have biological similarities to the stem cells that normally exist in the brain.

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Stem cell findings point toward new cancer treatments

NEW YORK (AP) -- How can a cancer come back after it's apparently been eradicated? Three new studies are bolstering a long-debated idea: that tumors contain their own pool of stem cells that can multiply and keep fueling the cancer, seeding regrowth.

If that's true, scientists will need to find a way to kill those cells, apart from how they attack the rest of the tumor.

Stem cells in healthy tissues are known for their ability to produce any kind of cell. The new research deals with a different kind, cancer stem cells. Some researchers, but not all, believe they lurk as a persisting feature in tumors.

Over the past decade, studies have found evidence for them in tumors like breast and colon cancers. But this research has largely depended on transplanting human cancer cells into mice that don't have immune systems, an artificial environment that raises questions about the relevance of the results.

Now, three studies reported online Wednesday in the journals Nature and Science present evidence for cancer stem cells within the original tumors. Again, the research relies on mice. That and other factors mean the new findings still won't convince everyone that cancer stem cells are key to finding more powerful treatments.

But researcher Luis Parada, of the University of Texas Southwestern Medical Center in Dallas, believes his team is onto something. He says that for the type of brain tumor his team studied, "we've identified the true enemy."

If his finding

The three studies used labeling techniques to trace the ancestry of cells within mouse tumors.

Collectively, they give "very strong support" to the cancer stem cell theory, said Jeffrey M. Rosen, a professor of molecular and cellular biology at Baylor College of Medicine in Houston. He did not participate in the work but supports the theory, which he said is widely accepted.

Another scientist who's skeptical about the theory, and said he has plenty of company, said the new papers did not change his mind.

Read more here:
Cancer debate: Are tumors fueled by own stem cells?

In April, The Scientist asked, Are Cancer Stem Cells Ready for Prime Time? The controversial hypothesis posits that cells with stem-cell-like characteristicssuch as the ability to self-renew and give rise to more tumor cellscontribute to cancers ability to evade traditional therapies. But despite previous investigations, which found subsets of tumor cells with the ability to grow in immunocompromised mice, not everyone is convinced that endogenous tumor development is stimulated by cells with self-renewal capacity.

Now, using genetic labeling techniques, three new studies trace cell lineages in new tumors to provide strong evidence for the existence of cancer stem cells. Published today (August 1) in Nature and Science, the technically elegant studies provide support for the cancer stem cell model across three different types of solid tumorsskin, intestinal, and brainsaid Max Wicha, an oncologist at the University of Michigan who helped develop the cancer stem cell hypothesis and in 2004 co-founded OncoMed Pharmaceuticals to develop therapies targeting cancer stem cells, but was not involved in the research.

The cancer stem cell hypothesis states that cells in tumors display a similar hierarchy to normal tissues that are renewed by stem cells, like the skin or intestinal epithelium, explained Sunit Das, a neurobiologist at the University of Toronto who did not participate in the research. Stem cells self-renew slowly, spending long periods in a quiescent non-dividing state, and produce a variety of faster-growing cell types. Because radiation and chemotherapy therapies target fast-growing cells, slow-growing cancer stem cells are thought to survive treatment, only to later repopulate the tumor.

Previous studies examining the existence and function of cancer stem cells used transplantation models, said Cdric Blanpain at the Universit Libre de Bruxelles, who led one of the two Nature studies. In the past, researchers would isolate different tumor cell populations and transplant them into immunocompromised mice, Blanpain explained. They found that some tumor fractions grow better than others. They called them cancer stem cells, thinking the cells were feeding pure tumor growth.

But critics argued that rather than demonstrating the existence of cancer stem cells, this just showed selection of cells capable of growing in the new environment. Luis Parada, whose group at University of Texas Southwestern Medical Center published the second Nature paper, noted that these criticisms are especially valid for solid tumors, which need a great deal of manipulation before any subsets of cells can be transplanted. The question we wanted to address was, Is it possible to probe the existence of cancer stem cells in a natural setting, where the cancer arose naturally and spontaneously without manipulation?

To identify and track cancer stem cells directly, all three groups used genetics. Blanpains group engineered mice so skin tumor cells would express a fluorescent protein after administration of the carcinogen tamoxifen and tracked the growth dynamics of the glowing tumor cells. Shortly after being exposed to the carcinogen, the mice developed non-malignant papillomas on their skin, in which Blanpain and his colleagues identified two major cell types: a progenitor population with a limited ability to differentiate and a surprisingly short life span, and stem-cell-like cells, which were long-lived and could self-renew or divide to produce new progenitors.

Its generally accepted that cancer cells acquire excessive proliferative abilities, so Blanpain expected the progenitor cells to be immortal, he said. But only the cancer stem cells survived long term, highlighting their importance for supporting tumor growth.

Work by a group in The Netherlands provided similar evidence in intestinal cancer, published in Science. This team used a combination of genetic mutations that promoted colon cancer development from intestinal stem cells, and again marked the tumor cells with fluorescence. Tracing the lineage of the marked cells, the researchers showed that the many different cell types of a tumor were all derived from the cancer stem cells, said co-first author Hugo Snippert at University Medical Center Utrecht. We saw that the cancer stem cells were producing new cells so fast they were taking over the tumor.

White arrows point to a subset of glioblastoma cells that express green fluorescent protein (GFP) but rarely stain for Ki67, a marker of proliferation. This indicates that the tumor cells that appear green are in a resting state. Nature

The third study, published in Nature by Paradas group, examined the brain cancer glioblastoma, and provided evidence for another facet of the cancer stem cell hypothesisthat cells with stem-cell-like properties promote cancer recurrence after treatment. Once again, the researchers used fluorescent markers in mice to show that after chemotherapy, stem-cell-like cells drove regrowth of the tumor. Engineering this population of cells to be sensitive to the anti-viral drug ganciclovir, the scientists were able to selectively kill the cancer stem cells in the tumor. Doing so slowed the progression of pre-cancerous lesions and prevented malignancies from infiltrating surrounding normal brain tissue. Combining ganciclovir with chemotherapy significantly prolonged the mices lives.

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Cancer Stem Cells Really Do Exist?

How can a cancer come back after it's apparently been eradicated? Three new studies are bolstering a long-debated idea: that tumors contain their own pool of stem cells that can multiply and keep fueling the cancer, seeding regrowth.

If that's true, scientists will need to find a way to kill those cells, apart from how they attack the rest of the tumor.

Stem cells in healthy tissues are known for their ability to produce any kind of cell. The new research deals with a different kind, cancer stem cells. Some researchers, but not all, believe they lurk as a persisting feature in tumors.

Over the past decade, studies have found evidence for them in tumors like breast and colon cancers. But this research has largely depended on transplanting human cancer cells into mice that don't have immune systems, an artificial environment that raises questions about the relevance of the results.

Now, three studies reported online Wednesday in the journals Nature and Science present evidence for cancer stem cells within the original tumors. Again, the research relies on mice. That and other factors mean the new findings still won't convince everyone that cancer stem cells are key to finding more powerful treatments.

But researcher Luis Parada, of the University of Texas Southwestern Medical Center in Dallas, believes his team is onto something. He says that for the type of brain tumor his team studied, "we've identified the true enemy."

If his finding applies to other cancers, he said, then even if chemotherapy drastically shrinks a tumor but doesn't affect its supply of cancer stem cells, "very little progress has actually been made."

The three studies used labeling techniques to trace the ancestry of cells within mouse tumors.

Collectively, they give "very strong support" to the cancer stem cell theory, said Jeffrey M. Rosen, a professor of molecular and cellular biology at Baylor College of Medicine in Houston. He did not participate in the work but supports the theory, which he said is widely accepted.

Another scientist who's skeptical about the theory, and said he has plenty of company, said the new papers did not change his mind.

More:
Stem Cells Could Fuel Cancer Growth

July 29, 2012, 3 a.m.

Up for a walk ... Denise Stuckey, with her dog, Bella, who has had stem cell treatment from vet Joe Sulyok.

Stem cell injections in dogs will become routine in the next two years and will probably cost less than $1000.

The first data, collated last week, into the use of the procedure where cultured cells are injected into the joints of dogs with hip dysplasia or canine osteoarthritis has shown a success rate of 96 per cent.

The procedure will be made available to veterinary clinics, promoted at dog shows and possibly in a television campaign.

It has been transformed in little more than a year with stem cells from one animal used to treat other dogs.

Previously, an invasive procedure was necessary, with incisions to remove subcutaneous or fatty tissue from the affected dog and stem cells isolated in a laboratory before being injected back into the dog.

The procedure resulted in a culture containing only about 10 per cent to 15 per cent stem cells, while the culture from a donor in a breed with a genetic line clear of arthritis can been screened to provide a culture containing 100 per cent stem cells.

The figures were collected from vets by Australian Veterinary Stem Cells, which supplies stem cell treatments and has a partnership with the immunology and stem cell research department at Monash University in Melbourne.

The sample size for the study was small at 150 but only about 1000 animals have had the treatment.

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Lame dogs brought to heal with stem cells Save

Editor's Choice Main Category: Stem Cell Research Also Included In: Biology / Biochemistry Article Date: 31 Jul 2012 - 14:00 PDT

Current ratings for: Stem Cell Therapy Only Works With Younger Hearts

The researchers, using mice as their subjects, came to the conclusion that undifferentiated precursor cells grow new heart cells in a two-day-old mouse, but not in adult mice. This finding settled a decades-old debate whether or not stem cells can play a role in the recovery of the adult mammalian heart after infarction (when heart tissue dies due to a local lack of oxygen).

Stem cells are biological cells found in all multicellular organisms. They are characterized by the ability to divide through mitosis and differentiate into diverse specialized cell types. They can self-renew to produce more stem cells.

Michael Kotlikoff, dean of Cornell's College of Veterinary Medicine and senior author of the paper that will appear August 29th in the Proceedings of the National Academy of Sciences, said:

According to Kotlikoff and team, the two-day old mice were able to grow new heart cells and almost completely recover from infarction, which proved that the injury did not stop stem cells from growing new heart cells. The results also showed that adults do not have the requisite stem cells to create new heart cells, called myocytes, because when when the same procedure was carried out on them, no new heart cells formed. However, new blood vessels were created.

Kotlikoff explained that the stem cells in the adult heart "have lost the ability to become heart cells, and are only capable of forming new vessels." At the start of life, single stem cells differentiate into all tissues, but as time goes on these cells become "developmentally restricted" or specialized to form only certain tissues.

Written by Sarah Glynn Copyright: Medical News Today Not to be reproduced without permission of Medical News Today

MLA

n.p. "Stem Cell Therapy Only Works With Younger Hearts." Medical News Today. MediLexicon, Intl., 31 Jul. 2012. Web. 31 Jul. 2012. <http://www.medicalnewstoday.com/articles/248478.php>

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Stem Cell Therapy Only Works With Younger Hearts

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Contact: Laura Bailey baileylm@umich.edu 734-647-1848 University of Michigan

ANN ARBOR, Mich.In the first human study of its kind, researchers found that using stem cells to re-grow craniofacial tissuesmainly boneproved quicker, more effective and less invasive than traditional bone regeneration treatments.

Researchers from the University of Michigan School of Dentistry and the Michigan Center for Oral Health Research partnered with Ann Arbor-based Aastrom Biosciences Inc. in the clinical trial, which involved 24 patients who required jawbone reconstruction after tooth removal.

Patients either received experimental tissue repair cells or traditional guided bone regeneration therapy. The tissue repair cells, called ixmyelocel-T, are under development at Aastrom, which is a U-M spinout company.

"In patients with jawbone deficiencies who also have missing teeth, it is very difficult to replace the missing teeth so that they look and function naturally," said Darnell Kaigler, principal investigator and assistant professor at the U-M School of Dentistry. "This technology and approach could potentially be used to restore areas of bone loss so that missing teeth can be replaced with dental implants."

William Giannobile, director of the Michigan Center for Oral Health Research and chair of the U-M Department of Periodontics and Oral Medicine, is co-principal investigator on the project.

The treatment is best suited for large defects such as those resulting from trauma, diseases or birth defects, Kaigler said. These defects are very complex because they involve several different tissue typesbone, skin, gum tissueand are very challenging to treat.

The main advantage to the stem cell therapy is that it uses the patient's own cells to regenerate tissues, rather than introducing man-made, foreign materials, Kaigler said.

The results were promising. At six and 12 weeks following the experimental cell therapy treatment, patients in the study received dental implants. Patients who received tissue repair cells had greater bone density and quicker bone repair than those who received traditional guided bone regeneration therapy.

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Stem cell therapy could offer new hope for defects and injuries to head, mouth