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'Stem cell' test could identify most aggressive breast cancers

Testing breast cancer cells for how closely they resemble stem cells could identify women with the most aggressive disease, a new study suggests.

Researchers found that breast cancers with a similar pattern of gene activity to that of adult stem cells had a high chance of spreading to other parts of the body.

Assessing a breast cancer's pattern of activity in these stem cell genes has the potential to identify women who might need intensive treatment to prevent their disease recurring or spreading, the researchers said.

Adult stem cells are healthy cells within the body which have not specialised into any particular type, and so retain the ability to keep on dividing and replacing worn out cells in parts of the body such as the gut, skin or breast.

A research team from The Institute of Cancer Research, London, King's College London and Cardiff University's European Cancer Stem Cell Research Institute identified a set of 323 genes whose activity was turned up to high levels in normal breast stem cells in mice.

The study is published today (Wednesday) in the journal Breast Cancer Research, and was funded by a range of organisations including the Medical Research Council, The Institute of Cancer Research (ICR), Breakthrough Breast Cancer and Cancer Research UK.

The scientists cross-referenced their panel of normal stem cell genes against the genetic profiles of tumours from 579 women with triple-negative breast cancer - a form of the disease which is particularly difficult to treat.

They split the tumour samples into two categories based on their 'score' for the activity of the stem cell genes.

Women with triple-negative tumours in the highest-scoring category were much less likely to stay free of breast cancer than those with the lowest-scoring tumours. Women with tumours from the higher-scoring group had around a 10 per cent chance of avoiding relapse after 10 years, while women from the low-scoring group had a chance of around 60 per cent of avoiding relapse.

The results show that the cells of aggressive triple-negative breast cancers are particularly 'stem-cell-like', taking on properties of stem cells such as self-renewal to help them grow and spread. They also suggest that some of the 323 genes could be promising targets for potential cancer drugs.

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'Stem cell' test could identify most aggressive breast cancers

Infants with rare bone disease improve bone formation after cell transplantation

Severe hypophosphatasia generally fatal during infancy, bone marrow transplant along with mensenchymal stem cell transplants offers hope

Putnam Valley, NY. (Feb 9, 2015) - Recent research carried out by a team of researchers in Japan has investigated the use of bone marrow transplants (BMTs) to treat hypophosphatasia (HPP). In this study, the researchers carried out BMT for two infants with HPP in combination with allogenic (other-donated) mesenchymal stem cell transplants (MSCTs). The allogenic MSC donors were a parent of the infant.

The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1337_Taketani_et_al

"Hypophosphatasia" (HPP) is a rare and most often fatal genetic bone disease affecting infants that has no current treatment. The disease is caused by mutations in the ALPL gene, which encodes alkaline phosphatase (ALP). Patients with severe HPP develop bone impairment and have extremely low levels of ALP activity, an enzyme necessary for bone mineralization.

Although there are mild and more severe forms, severe hypophosphatasia prevents proper bone mineralization during perinatal development. When the disease develops perinatally, many infants are still-born, with little evidence of bone mineralization. HPP can also appear in later infancy, generally before an infant reaches the age of six months, with the result that most afflicted infants do not live past the age of six months. Milder forms of HPP can present in later youth or in adulthood.

"Mesenchymal stem cells (MSCs) reside in bone marrow and other tissues and have a self-renewal capacity so that after transplantation they can differentiate into various cell lineages, including bone and cartilage," said Dr. Takeshi Taketani of the Division of Blood Transfusion at Shimane University Hospital in Shimane, Japan. "We performed multiple infusions of MSCs for two infant patients with severe HPP who had already undergone BMT. The adverse events from the BMT were managed and there were no adverse events from the MSC infusions."

After each infant had undergone BMT, one infant received four MSCTs and a second infant received nine MSCTs. Previous research had revealed that MSCT without a prior BMT was ineffective.

The researchers reported that the two infants receiving both BMT and MSCTs improved not only in terms of bone mineralization, but also saw improvements in muscle mass, respiratory function and mental development. Both children continue to survive at age three.

"Our data suggest that allogenic MSCT combined with BMT might be one of the safer and more effective remedies for patients with severe HPP, although long-term effectiveness remains unknown and warrants further study," concluded the researchers. "We need to establish curative, MSC-based treatment strategies that can maintain the long-term survival and differentiation capabilities of transplanted allo-MSCs."

"This study highlights the promise of stem cells in presenting a new frontier for regenerative medicine, with an improvement of HPP-associated symptoms and survival following BMT and MSCT." said Dr. David Eve, Cell Transplantation associate editor, and Instructor of neurosurgery and brain repair at the University of South Florida School of Medicine. "In order to elucidate the mechanisms behind recovery and further extrapolate the study to all HPP patients, a larger cohort and more long term follow-up are needed."

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Infants with rare bone disease improve bone formation after cell transplantation

Registries seek to match donors with rising marrow demand

WATERTOWN, Conn. (AP) - A year ago, Nancy Demers, 71, was diagnosed with myelodysplastic syndrome, a deficiency in the bone marrow. The disease can eventually become leukemia.

Its treated as if it were cancer but there is no cure for it, said her son, Scott Demers.

Now Nancy Demers has a new chance at life, thanks to advances in bone marrow stem cell transplants.

If I didnt do this, once I went out of remission - its not if, its when - I would go into acute leukemia and there will be nothing there to help me, Nancy Demers said. This will save my life and give me time.

Demers is one of a rapidly growing number of people looking to depend on strangers to donate marrow since she doesnt have a match within her family.

The rising number of patients seeking bone marrow has created new demands on registries that seek to match patient needs with willing donors.

Each sibling has a 25 percent chance of being a transplant match, according to Dr. Joseph Antin, chief and program director of the adult stem cell transplantation program at Dana Farber Brigham and Womens Hospital in Boston.

In the United States, about 30 percent of patients find a donor within their family, according to Be the Match. Those who dont must turn to international registries to find an unrelated donor.

Around 15 years ago, doctors couldnt do a transplant on anyone over the age of 50, according to Dr. Leslie Lehmann, clinical director of the Stem Cell Transplant Center at Dana Farber.

Its a big stress on the body, Lehmann said.

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Registries seek to match donors with rising marrow demand

Helping a little boy live life to the Max

By Andrew MeenahanFeb. 10, 2015, 10 a.m.

He has already beaten the odds by defying death, but the next year is just as critical for young Max McIntyre.

Max McIntyre ... before he lost his sight he was drawn to things yellow.

HE has already beaten the odds by defying death for 12 long months since suffering severe brain damage and blindness from bacterial meningitis, but the next year is just as critical for young Max McIntyre.

Maxs story has brought out the best in people across western NSW as his parents Amy and Rob and friends such as Bathursts Paul Twohill have harnessed the power of social media in a fundraising campaign they hope will save and improve the quality of his life.

Rob and Amy are fighting on two fronts.

The fundraising challenge is daunting they need at least $100,000 for stem cell treatment to help improve Maxs quality of life. But at least that is clear cut.

On the other battle front, the couple is desperately trying to find out if this treatment can even be performed and if anyone, anywhere, will do it for them.

Where do you even start to research this information? Google? Asking doctors? Trying to contact researchers?

They soon discovered no one performs the surgery in Australia and have tentatively narrowed it down to London, Philadelphia and Toronto but the complications and hurdles involved with such a procedure are daunting.

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Helping a little boy live life to the Max

Human skin may harbor obesity cure

Researchers have recently converted human skin cells into appetite controlling neurons for the first time ever, which might eventually provide obesity cure.

The study, led by researchers at Columbia University Medical Center (CUMC) and at the New York Stem Cell Foundation (NYSCF), found that cells provided individualized model for studying obesity and testing treatments.

To make the neurons, human skin cells were first genetically reprogrammed to become induced pluripotent stem (iPS) cells. Like natural stem cells, iPS cells are capable of developing into any kind of adult cell when given a specific set of molecular signals in a specific order.

The iPS cell technology has been used to create a variety of adult human cell types, including insulin-producing beta cells and forebrain and motor neurons.

The CUMC/NYSCF team determined which signals are needed to transform iPS cells into arcuate hypothalamic neurons, a neuron subtype that regulates appetite. The transformation process took about 30 days.

The neurons were found to display key functional properties of mouse arcuate hypothalamic neurons, including the ability to accurately process and secrete specific neuropeptides and to respond to metabolic signals such as insulin and leptin.

The study is published in the Journal of Clinical Investigation. (ANI)

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Human skin may harbor obesity cure

Mast cell – Wikipedia, the free encyclopedia

A mast cell (also known as a mastocyte or a labrocyte[1]) is derived from the myeloid stem cell and a part of the immune system that contains many granules rich in histamine and heparin. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing and defense against pathogens.[2]

The mast cell is very similar in both appearance and function to the basophil, another type of white blood cell. They differ in that mast cells are tissue resident, e.g., in mucosal tissues, while basophils are found in the blood.[3]

Mast cells were first described by Paul Ehrlich in his 1878 doctoral thesis on the basis of their unique staining characteristics and large granules. These granules also led him to the incorrect belief that they existed to nourish the surrounding tissue, so he named them Mastzellen (from German Mast, meaning "fattening", as of animals).[4][5] They are now considered to be part of the immune system.

Mast cells are very similar to basophil granulocytes (a class of white blood cells) in blood. Both are granulated cells that contain histamine and heparin, an anticoagulant. Both cells also release histamine upon binding to immunoglobulin E.[6] These similarities have led many to speculate that mast cells are basophils that have "homed in" on tissues. Furthermore they share a common precursor in bone marrow expressing the CD34 molecule. Basophils leave the bone marrow already mature, whereas the mast cell circulates in an immature form, only maturing once in a tissue site. The site an immature mast cell settles in probably determines its precise characteristics.[2] The first in vitro differentiation and growth of a pure population of mouse mast cells has been carried out using conditioned medium derived from concanavalin A-stimulated splenocytes.[7] Later, it was discovered that T cell-derived interleukin 3 was the component present in the conditioned media that was required for mast cell differentiation and growth.[8]

Mast cells in rodents are classically divided into two subtypes: connective tissue-type mast cells and mucosal mast cells. The activities of the latter are dependent on T-cells.[9]

Mast cells are present in most tissues characteristically surrounding blood vessels and nerves, and are especially prominent near the boundaries between the outside world and the internal milieu, such as the skin, mucosa of the lungs, and digestive tract, as well as the mouth, conjunctiva, and nose.[2]

Mast cells play a key role in the inflammatory process. When activated, a mast cell rapidly releases its characteristic granules and various hormonal mediators into the interstitium. Mast cells can be stimulated to degranulate by direct injury (e.g., physical or chemical [such as opioids, alcohols, and certain antibiotics such as polymyxins]), cross-linking of immunoglobulin E (IgE) receptors, or complement proteins.[2]

Mast cells express a high-affinity receptor (FcRI) for the Fc region of IgE, the least-abundant member of the antibodies. This receptor is of such high affinity that binding of IgE molecules is in essence irreversible. As a result, mast cells are coated with IgE, which is produced by plasma cells (the antibody-producing cells of the immune system). IgE molecules, like all antibodies, are specific to one particular antigen.

In allergic reactions, mast cells remain inactive until an allergen binds to IgE already in association with the cell (see above). Other membrane activation events can either prime mast cells for subsequent degranulation or act in synergy with FcRI signal transduction.[10] In general, allergens are proteins or polysaccharides. The allergen binds to the antigen-binding sites, which are situated on the variable regions of the IgE molecules bound to the mast cell surface. It appears that binding of two or more IgE molecules (cross-linking) is required to activate the mast cell. The clustering of the intracellular domains of the cell-bound Fc receptors, which are associated with the cross-linked IgE molecules, causes a complex sequence of reactions inside the mast cell that lead to its activation. Although this reaction is most well-understood in terms of allergy, it appears to have evolved as a defense system against intestinal worm infestations (tapeworms, etc.)[citation needed].

The molecules released into the extracellular environment include:[2]

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Mast cell - Wikipedia, the free encyclopedia

Achieving gender equality in science, engineering and medicine

(March 5, 2015) - Gender equality has not yet been achieved in science, medicine, and engineering, but The New York Stem Cell Foundation (NYSCF), through its Initiative on Women in Science and Engineering, is committed to making sure progress is made. NYSCF convened the Inaugural Meeting of its Initiative on Women in Science and Engineering (IWISE) Working Group in February 2014, where the group put forward seven actionable strategies for advancing women in science, medicine, and engineering, and reconvened in February 2015 to further develop the strategies.

NYSCF began this initiative after an analysis of its own programs. "We found that the ratio of men and women in our own programs was OK but it could certainly be improved," said Susan L. Solomon, CEO and Co-Founder, of NYSCF. "We wanted to take action and actually make tangible progress, so we brought together many of the leading men and women who have already committed time, energy, and resources towards this problem."

Today, the recommendations were published in Cell Stem Cell. They were divided into three categories: direct financial support strategies, psychological and cultural strategies, and major collaborative and international initiatives. The group chose to highlight the most high-impact and implementable strategies from a larger list developed during the meeting. They also sought to promote promising, long-term initiatives that will require significant collaboration among multiple stakeholders with the aim of connecting potential partners.

"Advancing women in science and medicine is of critical importance to the academic and research enterprise in our country," said Dr. Marc Tessier-Lavigne, President of Rockefeller University. "This paper is important as it not only brings attention to this key issue but also outlines creative strategies that can help break down barriers to gender equality in science."

Changing financing structures, embedded cultural norms, and tying funding to gender balance to enact real change are the pillars underlying the seven strategies recommended by the Working Group.

"The brain power provided by women in science is essential to sustaining a thriving US society and economy. It is time to move beyond just lamenting its loss and embrace the actions called for in this timely report," Dr. Claire Pomeroy, President, the Lasker Foundation and a member of the IWISE Working Group.

The seven strategies include:

1) Implement flexible family care spending 2) Provide "extra hands" awards 3) Recruit gender-balanced external review committees and speaker selection committees 4) Incorporate implicit bias statements 5) Focus on education as a tool 6) Create an institutional report card for gender equality 7) Partner to expand upon existing searchable databases of women in science, medicine, and engineering

The IWISE Working Group reconvened in February 2015 to continue to work on the Institutional Report Card for Gender Equality. The paper published today includes the proposed Phase 1 Institutional Report Card, and the group plans to release the Phase 2 report card once finalized.

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Achieving gender equality in science, engineering and medicine

Seven strategies to advance women in science

Despite the progress made by women in science, engineering, and medicine, a glance at most university directories or pharmaceutical executive committees tells the more complex story. Women in science can succeed, but they are succeeding in fields that may not even be conscious of the gender imbalances. These imbalances manifest themselves in the number of women that are invited to speak at conferences, the percentage of grants awarded to women scientists, and the higher rates of attrition of women at every stage of the career ladder compared to those of men.

In the March 5 issue of the journal Cell Stem Cell, the Initiative on Women in Science and Engineering Working Group, a collection of more than 30 academic and business leaders organized by the New York Stem Cell Foundation, present seven strategies to advance women in science, engineering, and medicine in this modern landscape.

"We wanted to think about broad ways to elevate the entire field, because when we looked at diversity programs across our organizations we thought that the results were okay, but they really could be better," said Susan L. Solomon, co-founder and CEO of the New York Stem Cell Foundation and a member of the working group. "We've identified some very straightforward things to do that are inexpensive and could be implemented pretty much immediately."

The working group's seven strategies are broken into three categories: the first two are direct financial support strategies, the next three are psychological and cultural strategies, and the final two are major collaborative and international initiatives.

1. Implement flexible family care spending

Make grants gender neutral by permitting grantees to use a certain percentage of grant award funds to pay for childcare, eldercare, or family-related expenses. This provides more freedom for grantees to focus on professional development and participate in the scientific community.

2. Provide "extra hands" awards

Dedicate funds for newly independent young investigators who are also primary caregivers to hire technicians, administrative assistants, or postdoctoral fellows.

3. Recruit gender-balanced review and speaker selection committees

Adopt policies that ensure that peer review committees are conscious of gender and are made up of a sufficient number of women.

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Seven strategies to advance women in science

Gordie Howes Son Says Dads Recovery No Fluke, Excited For Future Of Stem Cell Treatment

By Ashley Dunkak @AshleyDunkak

CBS DETROIT Murray Howe, the head of the radiology department at ProMedica Toledo Hospital, understands the skepticism of those who question the stem cell treatment his father Gordie, also known as Mr. Hockey, received in December in Tijuana, Mexico.

Gordies health had been slowly declining even before the stroke he suffered in late October, and he was essentially bedridden when Murray and his brother Marty took him to Mexico to participate in a clinical trial. They did not have high hopes he was so far gone, Murray recalled but after each step of the two-part process, Gordie improved rapidly, once again able to walk and talk, repossessed of his wit and humor. Murray and his siblings were floored. So were the therapists who had been working with Gordie after his stroke.

Some physicians have scoffed at the idea of stem cells helping an individual who has had a stroke, but Murray a doctor himself says his fathers recovery after treatment opened his eyes to stem cells as a potential game-changer.

Speaking as a medical professional, its so frustrating when you cant really do anything for a patient, said Howe, the head of the radiology department at Toledo Hospital. You give them kind of a death sentence and you say, Well thats all you get. Theres nothing we can really offer. Its so sad. So now to be able to have on the brink of some huge hope for these patients is really, really exciting. As a medical professional, to me, theres never been anything more exciting in my entire career than this.

Murray does not blame people for being skeptical, and he agrees more research on the capabilities of stem cells is needed to show definitively what they can do. To say Murray is optimistic, however, would be a serious understatement.

Theres quite a few individuals out there who are calling themselves stem cell experts or this or that, kind of saying that theres no data to support that stem cells work on ischemic strokes, but thats really not true at all, Murray said. Theres at least 50 clinical studies that are going on across the world that are demonstrating its safety and working on demonstrating its efficacy, and the preliminary results on the ones that Ive seen are tremendous, so the data is clearly there. I think that people across the world in the next couple years are going to be as blown away as I was with our father when they see the power of stem cells and what they do for patients with not just stroke but with dementia and traumatic brain injuries and spinal cord injuries.

My dads case is by no means the only one, Murray continued. Hes kind of like in the middle. Theres examples of patients that have had a far greater result. Im so thrilled for my dad, but by no means was my dad a fluke or a random event. The studies are ongoing, and I think the point of any of the, I guess, naysayers is that Gordie Howe may be anecdotal and we need more research, and I totally agree with that. In fact, based on what weve seen with my father, I would say that we as a country and as a world should make a concerted effort to put as much time and energy as we can into investigating the power of stem cells because I really think that based on what Im seeing this is going to be a game-changer for medicine and a game-changer for quality of life for so many people that have non-option diseases like stroke or dementia.

Heading to Tijuana for treatment was a last-ditch effort to save Gordie, but it was not one the family undertook on a whim, Murray said.

Im well aware of hucksters and con games and this type of thing, and our family has never been about traveling the world to find the miracle cure, Murray said. Im a very mainstream physician. Ive always relied heavily on data and on long-term studies to prove the safety and efficacy of any treatment. For our father, we just our goal has always just been quality of life and comfort. When my mom was sick with her dementia that was our only priority was just keep her comfortable, keep her healthy, as healthy as possible, and keep her safe, and that was it. We had a number of people contact us saying, You know, we could help your mom with this pill and that pill, and I looked at everything that anybody presented to us, but to me there was nothing that showed any data that would made me want to experiment, if you will, with my mom.

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Gordie Howes Son Says Dads Recovery No Fluke, Excited For Future Of Stem Cell Treatment