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Archive for the ‘Stem Cell Negative’ Category

'Cell shield' for cancer patients

Friday, May 11th, 2012

9 May 2012 Last updated at 14:14 ET By James Gallagher Health and science reporter, BBC News

It may be possible to use "stem cell shielding" to protect the body from the damaging effects of chemotherapy, early results from a US trial suggest.

Chemotherapy drugs try to kill rapidly dividing cancer cells, but they can also affect other healthy tissues such as bone marrow.

A study, in Science Translational Medicine, used genetically modified stem cells to protect the bone marrow.

Cancer Research UK said it was a "completely new approach".

The body constantly churns out new blood cells in the hollow spaces inside bone. However, bone marrow is incredibly susceptible to chemotherapy.

The treatment results in fewer white blood cells being produced, which increases the risk of infection, and fewer red blood cells, which leads to shortness of breath and tiredness.

Researchers at the Fred Hutchinson Cancer Research Center, in Seattle, said these effects were "a major barrier" to using chemotherapy and often meant the treatment had to be stopped, delayed or reduced.

They have tried to protect the bone marrow in three patients with a type of brain cancer, glioblastoma.

One of the researchers, Dr Jennifer Adair, said: "This therapy is analogous to firing at both tumour cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumour cells are unshielded."

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Stem cells jab 'helps brain cancer patients tolerate chemotherapy'

Friday, May 11th, 2012

By Daily Mail Reporter

PUBLISHED: 16:01 EST, 9 May 2012 | UPDATED: 01:37 EST, 10 May 2012

Stem cells have been transplanted into brain cancer patients for the first time in a bid to protect them against the toxic side effects of chemotherapy.

In a study involving three patients, scientists found that two of them survived longer than predicted following the surgery while the other has seen no disease progression after three years of treatment.

The study was carried out by the Fred Hutchinson Cancer Research Centre in the United States.

Breakthrough: Scientists have transferred stem cells into brain cancer sufferers in a bid to protect them against the harmful effects of chemotherapy

The centre's Dr Hans-Peter Kiem said: 'We found that patients were able to tolerate the chemotherapy better and without negative side effects after transplantation of the gene-modified stem cells.

'This compares with patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells.'

Dr Kiem added that a major barrier to effective use of chemotherapy to treat cancers such as glioblastoma, which all three patients had, has been the toxicity of chemotherapy drugs to other organs, primarily bone marrow.

This results in decreased blood cell counts, increased susceptibility to infections and other side effects.

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Transplanted Gene-Modified Blood Stem Cells Protect Brain Cancer Patients From Toxic Side Effects of Chemotherapy

Friday, May 11th, 2012

Study is first to show feasibility and efficacy of a new use for autologous stem cell transplant

Newswise SEATTLE For the first time, scientists at Fred Hutchinson Cancer Research Center have transplanted brain cancer patients own gene-modified blood stem cells in order to protect their bone marrow against the toxic side effects of chemotherapy. Initial results of the ongoing, small clinical trial of three patients with glioblastoma showed that two patients survived longer than predicted if they had not been given the transplants, and a third patient remains alive with no disease progression almost three years after treatment.

We found that patients were able to tolerate the chemotherapy better and without negative side effects after transplantation of the gene-modified stem cells than patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells, said Hans-Peter Kiem, M.D., senior and corresponding author of the study published in the May 9 issue of Science Translational Medicine.

Kiem, a member of the Clinical Research Division at the Hutchinson Center, said that a major barrier to effective use of chemotherapy to treat cancers like glioblastoma has been the toxicity of chemotherapy drugs to other organs, primarily bone marrow. This results in decreased blood cell counts, increased susceptibility to infections and other side effects. Discontinuing or delaying treatment or reducing the chemotherapy dose is generally required, but that often results in less effective treatment.

In the current study, Kiem and colleagues focused on patients with glioblastoma, an invariably fatal cancer. Many of these patients have a gene called MGMT (O6-methylguanine-DNA-methyltransferase) that is turned on because the promoter for this gene is unmethylated. MGMT is a DNA repair enzyme that counteracts the toxic effect of some chemotherapy agents like temozolomide. Patients with such an unmethylated promoter status have a particularly poor prognosis.

A drug called benzylguanine can block the MGMT gene and make tumor cells sensitive to chemotherapy again, but when given with chemotherapy, the toxic effects of this combination are too much for bone marrow cells, which results in marrow suppression.

By giving bone marrow stem cells P140K, which is a modified version of MGMT, those cells are protected from the toxic effects of benzylguanine and chemotherapy, while the tumor cells are still sensitive to chemotherapy. P140K can repair the damage caused by chemotherapy and is impervious to the effects of benzylguanine, Kiem said.

This therapy is analogous to firing at both tumor cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumor cells are unshielded, said Jennifer Adair, Ph.D., who shares first authorship of the study with Brian Beard, Ph.D., both members of Kiems lab.

The three patients in this study survived an average of 22 months after receiving transplants of their own circulating blood stem cells. One, an Alaskan man, remains alive 34 months after treatment. Median survival for patients with this type of high-risk glioblastoma without a transplant is just over a year.

Glioblastoma remains one of the most devastating cancers with a median survival of only 12 to 15 months for patients with unmethylated MGMT, said Maciej Mrugala, M.D., the lead neuro oncologist for this study.

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New England Journal of Medicine Reports on Three Phase III REVLIMID® (lenalidomide) Trials in Patients with Newly …

Friday, May 11th, 2012

BOUDRY, Switzerland--(BUSINESS WIRE)--

Celgene International Srl, a subsidiary of Celgene Corporation (NASDAQ: CELG - News), today announced that results from three phase III studies evaluating the use of continuous REVLIMID (lenalidomide) treatment in newly diagnosed multiple myeloma (MM) patients or maintenance treatment with lenalidomide following autologous stem cell transplant were published online in the May 10, 2012 edition of the New England Journal of Medicine. All three publications highlight the expanding body of clinical evidence supporting lenalidomide treatment in these areas.

Continuous Lenalidomide Therapy (non-transplant eligible population):

The first article highlights a Celgene-sponsored study of continuous lenalidomide treatment in elderly patients newly diagnosed with multiple myeloma.

Continuous Lenalidomide Treatment for Newly Diagnosed Multiple Myeloma (MM-015)

This double-blind, phase III, multicenter, randomized study conducted by Celgene compared melphalanprednisonelenalidomide induction followed by lenalidomide maintenance (MPR-R), with melphalanprednisonelenalidomide (MPR), or melphalanprednisone (MP) followed by placebo in 459 patients aged 65 years with newly-diagnosed myeloma who were not eligible for autologous stem-cell transplant.

http://www.nejm.org/doi/full/10.1056/NEJMoa1112704

Post-transplant maintenance

The two additional articles published in the edition highlighted cooperative group studies that evaluated the use of lenalidomide maintenance following autologous stem cell transplant (ASCT).

In each of the studies, one funded by the National Cancer Institute and conducted by the Cancer and Leukemia Group B (CALGB) and one by the Intergroupe Francophone du Myelome (IFM), maintenance treatment with lenalidomide following ASCT resulted in delayed time to disease progression or death compared to placebo.

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Boston scientists grow lung tissue from cystic fibrosis patients’ skin cells

Friday, May 11th, 2012

By Carolyn Y. Johnson, Globe Staff

Two teams of Boston scientists have developed new ways to turn stem cells into different types of lung tissue, surmounting a major hurdle for scientists trying to harness the power of stem cell biology to study and develop treatments for major lung diseases.

One team then used skin cells from cystic fibrosis patients to create embryonic-like stem cells, then working in lab dishes used those cells to grow tissue that lines the airways and contains a defect responsible for the rare, fatal disease. The technique -- essentially a recipe for growing such lung tissue -- could provide a powerful platform to screen drugs and study the biology of the disease.

Growing lung tissue in the laboratory has long been a goal of stem cell scientists, but has been more technically difficult than growing other types of tissues, such as brain cells or heart cells. Such lung tissue is valuable because it could be used to screen potential drugs and more closely probe the problems that underlie diseases such as asthma, emphysema, and rare genetic diseases. Such techniques may also one day help researchers grow replacement tissues and devise ways to restore or repair injured lung tissue.

A team led by Massachusetts General Hospital researchers created lung tissue from a patient with the genetic mutation that most commonly underlies cystic fibrosis and researchers hope the technique will also be a powerful tool to study other diseases that affect the airway tissue, such as asthma and lung cancer. The other team, led by Boston University School of Medicine scientists, was able to derive cells that form the delicate air sacs of the lung from mouse embryonic stem cells. The team is hoping to refine the recipe for making the cells so that they can be used to derive lung tissue from a bank of 100 stem cell lines of patients with lung disease. Both papers were published Thursday in the journal Cell Stem Cell.

Vertex Pharmaceuticals, a Cambridge biotechnology company, earlier this year received approval for Kalydeco -- the first drug to directly target the underlying cause of cystic fibrosis. That compound was discovered by screening massive numbers of potential drugs against cells engineered to carry the same defect that underlies cystic fibrosis.

We had to use engineered cells, and certainly using more native human cells ... would be potentially beneficial, said Dr. Frederick Van Goor, head of biology for Vertexs cystic fibrosis research program. We had to rely on donor tissue obtained from patients with cystic fibrosis, and its a bit more challenging, because the number of donor lungs you can get and the number of cells you can derive from there are more limited.

Van Goor said it was too soon to say whether the company would use the new technology in screening, but noted that the tests the company had used to determine whether a drug was likely to work against the disease had, in some cases, given scientists false leads. Some molecules that worked on the engineered cells did not work in the complicated biology of the lung.

Its a significant event for the lung field, said Dr. Thiennu Vu, associate professor of medicine at the University of California San Francisco, who was not involved in the research. She added that much work remains before such cells could be used to repair or replace damaged tissue, and even before such cells would necessarily be useful for drug screening. It will be important, she said, to refine the recipe to ensure that the technique yields pure populations of the specific types of functional lung cells.

In the competitive world of science, where credit for being the first to do something is crucially important, the two research teams accomplishments are an unusual example of competitors turning into collaborators -- forging a relationship that both teams felt helped speed up progress.

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Stem cell jab cuts chemo side effects

Friday, May 11th, 2012

Transplanting gene-modified stem cells into brain cancer patients can prevent development of chemotherapys toxic side effects in them.

Researchers at the US Fred Hutchinson Cancer Research Centre have for the first time transplanted stem cells into patients with brain cancer to protect them against the toxic side effects of a chemotherapy drug called temozolomide.

The study included three patients with a form of brain cancer called glioblastoma, two of whom survived longer than doctors expected. No disease progression has been seen in the third patient after three years of treatment, scientists reported in the journal Science Translational Medicine.

We found that patients were able to tolerate the chemotherapy better and without negative side effects after transplantation of the gene-modified stem cells, said senior researcher Dr. Hans-Peter Kiem.

This compares with patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells.

One of the major barriers to effective use of chemotherapy drugs is their toxic effects on other organs, primarily bone marrow, which produces blood cells.

Damages to bone marrow make patients susceptible to infections due to lack of immune cells while lower production of red blood cells which carry oxygen in blood causes shortness of breath and tiredness.

To prevent those side effects, researchers isolated samples of blood producing stem cells of each patients bone marrow before chemotherapy. A virus was then used to deliver the cells a gene which protected them against the chemotherapy drug. The cells were then put back into the patient.

"This therapy is analogous to firing at both tumor cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumor cells are unshielded," said co-author Dr Jennifer Adair.

Researchers say the method should be tested on more volunteers but it has already showed that the new approach can not only be used for patients receiving temozolomide but also for those taking other chemotherapy drugs.

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Gene-modified stem cell transplant protects patients from toxic side effects of chemotherapy, study suggests

Friday, May 11th, 2012

ScienceDaily (May 9, 2012) For the first time, scientists at Fred Hutchinson Cancer Research Center have transplanted brain cancer patients' own gene-modified blood stem cells in order to protect their bone marrow against the toxic side effects of chemotherapy. Initial results of the ongoing, small clinical trial of three patients with glioblastoma showed that two patients survived longer than predicted if they had not been given the transplants, and a third patient remains alive with no disease progression almost three years after treatment.

"We found that patients were able to tolerate the chemotherapy better and without negative side effects after transplantation of the gene-modified stem cells than patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells," said Hans-Peter Kiem, M.D., senior and corresponding author of the study published in the May 9 issue of Science Translational Medicine.

Kiem, a member of the Clinical Research Division at the Hutchinson Center, said that a major barrier to effective use of chemotherapy to treat cancers like glioblastoma has been the toxicity of chemotherapy drugs to other organs, primarily bone marrow. This results in decreased blood cell counts, increased susceptibility to infections and other side effects. Discontinuing or delaying treatment or reducing the chemotherapy dose is generally required, but that often results in less effective treatment.

In the current study, Kiem and colleagues focused on patients with glioblastoma, an invariably fatal cancer. Many of these patients have a gene called MGMT (O6-methylguanine-DNA-methyltransferase) that is turned on because the promoter for this gene is unmethylated. MGMT is a DNA repair enzyme that counteracts the toxic effect of some chemotherapy agents like temozolomide. Patients with such an unmethylated promoter status have a particularly poor prognosis.

A drug called benzylguanine can block the MGMT gene and make tumor cells sensitive to chemotherapy again, but when given with chemotherapy, the toxic effects of this combination are too much for bone marrow cells, which results in marrow suppression.

By giving bone marrow stem cells P140K, which is a modified version of MGMT, those cells are protected from the toxic effects of benzylguanine and chemotherapy, while the tumor cells are still sensitive to chemotherapy. "P140K can repair the damage caused by chemotherapy and is impervious to the effects of benzylguanine," Kiem said.

"This therapy is analogous to firing at both tumor cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumor cells are unshielded," said Jennifer Adair, Ph.D., who shares first authorship of the study with Brian Beard, Ph.D., both members of Kiem's lab.

The three patients in this study survived an average of 22 months after receiving transplants of their own circulating blood stem cells. One, an Alaskan man, remains alive 34 months after treatment. Median survival for patients with this type of high-risk glioblastoma without a transplant is just over a year.

"Glioblastoma remains one of the most devastating cancers with a median survival of only 12 to 15 months for patients with unmethylated MGMT," said Maciej Mrugala, M.D., the lead neuro oncologist for this study.

As many as 50 percent to 60 percent of glioblastoma patients harbor such chemotherapy-resistant tumors, which makes gene-modified stem cell transplant therapy applicable to a large number of these patients. In addition, there are also other brain tumors such as neuroblastoma or other solid tumors with MGMT-mediated chemo resistance that might benefit from this approach.

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Gene-modified stem cell transplant protects patients from toxic side effects of chemotherapy

Friday, May 11th, 2012

Public release date: 9-May-2012 [ | E-mail | Share ]

Contact: Dean Forbes dforbes@fhcrc.org 206-667-2896 Fred Hutchinson Cancer Research Center

SEATTLE For the first time, scientists at Fred Hutchinson Cancer Research Center have transplanted brain cancer patients' own gene-modified blood stem cells in order to protect their bone marrow against the toxic side effects of chemotherapy. Initial results of the ongoing, small clinical trial of three patients with glioblastoma showed that two patients survived longer than predicted if they had not been given the transplants, and a third patient remains alive with no disease progression almost three years after treatment.

"We found that patients were able to tolerate the chemotherapy better and without negative side effects after transplantation of the gene-modified stem cells than patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells," said Hans-Peter Kiem, M.D., senior and corresponding author of the study published in the May 9 issue of Science Translational Medicine.

Kiem, a member of the Clinical Research Division at the Hutchinson Center, said that a major barrier to effective use of chemotherapy to treat cancers like glioblastoma has been the toxicity of chemotherapy drugs to other organs, primarily bone marrow. This results in decreased blood cell counts, increased susceptibility to infections and other side effects. Discontinuing or delaying treatment or reducing the chemotherapy dose is generally required, but that often results in less effective treatment.

In the current study, Kiem and colleagues focused on patients with glioblastoma, an invariably fatal cancer. Many of these patients have a gene called MGMT (O6-methylguanine-DNA-methyltransferase) that is turned on because the promoter for this gene is unmethylated. MGMT is a DNA repair enzyme that counteracts the toxic effect of some chemotherapy agents like temozolomide. Patients with such an unmethylated promoter status have a particularly poor prognosis.

A drug called benzylguanine can block the MGMT gene and make tumor cells sensitive to chemotherapy again, but when given with chemotherapy, the toxic effects of this combination are too much for bone marrow cells, which results in marrow suppression.

By giving bone marrow stem cells P140K, which is a modified version of MGMT, those cells are protected from the toxic effects of benzylguanine and chemotherapy, while the tumor cells are still sensitive to chemotherapy. "P140K can repair the damage caused by chemotherapy and is impervious to the effects of benzylguanine," Kiem said.

"This therapy is analogous to firing at both tumor cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumor cells are unshielded," said Jennifer Adair, Ph.D., who shares first authorship of the study with Brian Beard, Ph.D., both members of Kiem's lab.

The three patients in this study survived an average of 22 months after receiving transplants of their own circulating blood stem cells. One, an Alaskan man, remains alive 34 months after treatment. Median survival for patients with this type of high-risk glioblastoma without a transplant is just over a year.

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Gene-modified stem cell transplant protects patients from toxic side effects of chemotherapy

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Stem cell shield may protect body from chemotherapy side effects

Friday, May 11th, 2012

A new study suggests stem cells may be able to act as a shield to protect the body from the harmful side effects of chemotherapy, the BBC News reported.

As chemotherapy drugs attempt to kill cancer drugs, they can also affect the bone marrow and other healthy tissues.

In a new study, however, researchers from the Fred Hutchinson Cancer Research Center in Seattle were able to use genetically modified stem cells to protect the bone marrow.

The bone marrow is very susceptible to chemotherapy, and in response to the treatment, produces less blood cells. This leaves the body more prone to infection and fatigue.

Stem cell shielding appeared to stave off some of these negative side effects. Researchers took bone marrow from patients with brain cancer and isolated the stem cells. They infected the cells with a virus which carried a gene to protect the cells against a chemotherapy drug, and then re-implanted the cells into the patients.

"We found that patients were able to tolerate the chemotherapy better, and without negative side effects, after transplantation of the gene-modified stem cells than patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells, Professor Hans-Peter Kiem told the BBC News.

All three patients lived longer than the average survival time of 12 months. One patient was still alive 34 months after treatment, according to the BBC.

Click here to read more from the BBC News.

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Gentium Receives Day 180 List of Outstanding Issues From the CHMP for Defibrotide MAA

Friday, May 4th, 2012

VILLA GUARDIA, Italy, May 4, 2012 (GLOBE NEWSWIRE) -- Gentium S.p.A. (GENT - News) (the "Company") announced today that it has received the Day 180 List of Outstanding Issues (the "LoOIs") from the European Medicines Agency's ("EMA") Committee for Medicinal Products for Human Use ("CHMP") in connection with the Company's Marketing Authorization Application (MAA) for Defibrotide to treat and prevent hepatic veno-occlusive disease (VOD) in adults and children undergoing haematopoietic stem cell transplantation therapy.

The Company plans to submit its responses to the LoOls within 60 days, in line with the regulatory timetable. If the written responses satisfy the issues raised in the LoOIs and the CHMP does not require further explanation or clarification, a recommendation on the approval of Defibrotide could be made as early as the third quarter of 2012. If oral explanations are required, a clock stop may be imposed. The CHMP is expected to reach its final opinion no later than Day 210, based on the EMA review process timeline.

"We believe we have made good progress in working with the E.U. Rapporteurs to address the issues raised in their Day 120 List of Questions," said Dr. Khalid Islam, Chairman & Chief Executive Officer of the Company. "We plan to continue working closely with the EMA towards the approval of Defibrotide and to resolve any remaining open issues."

About the EMA Review Process:

EMA guidelines permit companies in receipt of LoOIs to respond within one month. More information can be obtained from the EMA website http://www.ema.europa.eu.

About VOD

Veno-occlusive disease (VOD) is a potentially life-threatening condition, which typically occurs as a significant complication of stem cell transplantation. Certain high-dose conditioning regimens used as part of stem cell transplantation can damage the lining cells of hepatic blood vessels and result in VOD, a blockage of the small veins in the liver that leads to liver failure and can result in significant dysfunction in other organs such as the kidneys and lungs (so-called severe VOD). Stem cell transplantation is a frequently used treatment modality following high-dose chemotherapy and radiation therapy for hematologic cancers and other conditions in both adults and children. At present there is no approved agent for the treatment or prevention of VOD in the United States or the European Union.

About Gentium

Gentium S.p.A., located in Como, Italy, is a biopharmaceutical company focused on the development and manufacture of drugs to treat and prevent a variety of diseases and conditions, including vascular diseases related to cancer and cancer treatments. Defibrotide, the Company's lead product candidate, is an investigational drug that has been granted Orphan Drug status by the U.S. Food and Drug Administration (FDA) and Orphan Medicinal Product Designation by the European Medicines Agency, both to treat and to prevent VOD, as well as Fast Track Designation by the U.S. FDA to treat VOD.

The Gentium S.p.A. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=12669

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Bacterin Secures Accounts Receivable Credit Facility

Wednesday, April 25th, 2012

BELGRADE, Mont., April 24, 2012 /PRNewswire/ --Bacterin International Holdings, Inc. (NYSE Amex: BONE), a leader in the development of revolutionary bone graft material and antimicrobial coatings for medical applications, has secured an accounts receivable credit facility with Midcap Financial LLC and Silicon Valley Bank. The revolving loan credit facility allows Bacterin to borrow up to $5 million through January 1, 2015. The facility allows borrowings based upon a predetermined formula of up to 80% of Bacterin's eligible accounts receivable, as defined in the credit and security agreement.

"Due to the high working capital needs of our business associated with the necessity for our inventory to be consigned to our hospital accounts, the accounts receivable facility is an efficient way for Bacterin to access cash, from time to time, without diluting equity," said Guy Cook, Chairman and CEO of Bacterin. "Our strong relationships with Silicon Valley Bank and Midcap Financial helped us to secure this non-dilutive financing option, as we prepare for the next stage of growth at Bacterin International."

About Bacterin International Holdings

Bacterin International Holdings, Inc. (NYSE Amex: BONE) develops, manufactures and markets biologics products to domestic and international markets. Bacterin's proprietary methods optimize the growth factors in human allografts to create the ideal stem cell scaffold to promote bone, subchondral repair and dermal growth. These products are used in a variety of applications including enhancing fusion in spine surgery, relief of back pain, promotion of bone growth in foot and ankle surgery, promotion of cranial healing following neurosurgery and subchondral repair in knee and other joint surgeries.

Bacterin's Medical Device division develops, employs, and licenses bioactive coatings for various medical device applications. Bacterin's strategic coating initiatives include antimicrobial coatings designed to inhibit biofilm formation and microbial contamination. For further information, please visit http://www.bacterin.com.

About MidCap Financial, LLC

MidCap Financial is a commercial finance company focused on middle market lending in the broad national healthcare industry. MidCap specializes in $5 million to $200 million loans. The company is headquartered in Bethesda, MD, with offices in Chicago and Los Angeles, and focuses in four areas:

-Asset-Based working capital loans to healthcare providers collateralized by third-party accounts receivable and other assets;

-Leveraged loans to healthcare companies backed by private equity sponsors;

-Life Sciences loans to VC-backed and public pharmaceutical, biotech, and medical device companies;

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Apple to the Rescue

Wednesday, April 25th, 2012

It was a mixed day on the market, as tech stocks lagged. Outside of tech, it was a nice bounce back for stocks, and we'd expect sentiment around Apple's (AAPL - News) strong earnings to help influence the market's mood tomorrow. In general, we're still looking for a spring/summer pullback, but continue to view it as a buying opportunity. Apple's pullback, though, may have already occurred, and once again it looks like the company is proving the skeptics wrong.

The Stem Cell Stocks Index was the top performing tickerspy Index on the day, led by BioTime (BTX - News) with a 14% gain. The Discount Retailer Stocks Index was the day's worst performing tickerspy Index, with Big Lots (BIG - News) down -24%.

Stocks finished mixed, with the Dow the lone loser off -9 points to 2,962. The Dow climbed 74 points to 13,002, while the Nasdaq rose 5 points to 1,372. Oil edged up 44 cents to $103.55 a barrel, while gold jumped $11.20 to $1,643.80 an ounce.

In economic news, the Conference Board said April's consumer confidence reading slid to 69.2 from a downwardly revised 69.5 in March. Economists had expected a reading of 69.7. Elsewhere, The S&P/Case-Shiller Home Price Index showed the 10- and 20-city measures both fell -0.8% month over month in February and slid -3.6% and -3.5%, respectively, year over year. The Census Bureau and the Department of Housing and Urban Development, meanwhile, said new home sales fell -7.1% last month to a seasonally adjusted annual rate of 328,000. The February number was revised higher to 353,000 from 313,000. Economics were looking for a March rate of 318,000.

In earnings news, shares of Coach (COH - News), the maker of high-end handbags, slipped -4.3% after the company posted a fiscal third-quarter profit of $225 million, or 77 cents per share, compared with $186 million, or 62 cents a share, a year earlier. Revenue climbed 17% to $1.11 billion. Same-store sale rose 6.7%, but that was down from a year-earlier increase of 8.8%. Analyst had expected EPS of 75 cents on sales of $1.1 billion.

Shares of Align Technology (ALGN - News) surged 15.7% after the company said its first-quarter profit rose to $21.0 million, or 26 cents per share, from $15.8 million, or 20 cents per share, a year earlier. Revenue climbed to $135.1 million from $104.9 million. Analysts had expected a profit of 22 cents per share on $128.2 million in revenue. Align forecast an adjusted second-quarter profit of 26-28 cents per share on $140.2-143.7 million in sales. Analysts were expecting a profit of 24 cents per share and $135.6 million in revenue.

Dow component 3M (MMM - News), the maker of Post-its and other products, said its first-quarter profit climbed to $1.13 billion, or $1.59 per share, easily topping the $1.48 per share analysts expected. Revenue increased 2% to $7.49 billion, matching analyst estimates. Minnesota-based 3M raised its full-year guidance to $6.35-$6.50 a share from $6.25-$6.50. Shares of 3M rose 1.6%. More than 150 pros held 3M in their portfolios at the end of Q4 and more than 1,000 tickerspy members own the stock in their portfolios.

Shares of BigLots plunged -24.1% after the closeout retailer said its first-quarter same-store sales figure will be slightly negative, news that is in stark contrast to a previous forecast calling for a 2-4% gain. The company's fiscal first quarter ends on April 28. Fifteen pros counted BigLots among their top holdings at the end of Q1 and nearly 160 tickerspy members own the stock in their portfolios.

Shares of Buffalo Wild Wings (BWLD - News) fell -5.9% after the company accidently released its Q1 results in an 8-K about an hour before the market closed. EPS jumped 21% to 98 cents, while sales climbed 38% to $251.1 million. Analysts were looking for EPS of 95 cents on revenue of $251.2 million.

Fun and informative, tickerspy.com is a free investing website where you can track multiple stock portfolios and compare against 250 proprietary Indexes tracking themes from dividends to ETFs to green energy to precious metals. Best of all, tickerspy.com lets you spy on the portfolios of nearly 3,000 Wall Street institutions and hedge funds and see graphs of their performance. Try tickerspy.com today and find out how you stack up against investing legends like Warren Buffett!

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Apple to the Rescue

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Bacterin International Holdings, Inc. Schedules First Quarter 2012 Financial Earnings Conference Call

Wednesday, April 25th, 2012

BELGRADE, Mont., April 24, 2012 /PRNewswire/ -- BacterinInternational Holdings, Inc. (BONE), a leader in the development of revolutionary bone graft material and antimicrobial coatings for medical applications, will release its financial results for the three months ended March 31, 2012 after the close of regular market trading on Thursday, May 3, 2012. A conference call will follow at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time).

Conference Call Details:

Date: Thursday, May 3, 2012 Time: 4:30 p.m. Eastern time (1:30 p.m. Pacific time) Dial-In Number: 1-877-941-1429 International: 1-480-629-9857 Conference ID#: 4535021

The conference call will be broadcast simultaneously and available for replay here and at the investor section of the company's Web site at http://www.bacterin.com/index.htm.

Please call the conference telephone number 5-10 minutes prior to the start time. An operator will register your name and organization. If you have any difficulty connecting with the conference call, please contact Hayden IR at 1-646-755-7412.

A replay of the call will be available after 7:30 p.m. Eastern time on the same day and until June 3, 2012.

Replay number: 1-877-870-5176 International replay number: 1-858-384-5517 Replay pin number: 4535021

About Bacterin International Holdings Bacterin International Holdings, Inc. (BONE) develops, manufactures and markets biologics products to domestic and international markets.Bacterin's proprietary methods optimize the growth factors in humanallografts to create the ideal stem cell scaffold to promote bone,subchondral repair and dermal growth. These products are used in a variety of applications including enhancing fusion in spine surgery, relief of back pain, promotion of bone growth in foot and ankle surgery, promotion of cranial healing following neurosurgery andsubchondral repair in knee and other joint surgeries.

Bacterin'sMedical Device division develops, employs, and licenses bioactive coatings for various medical device applications.Bacterin's strategic coating initiatives include antimicrobial coatings designed to inhibitbiofilm formation and microbial contamination. For further information, please visit http://www.bacterin.com.

Important Cautions Regarding Forward-looking Statements This news release contains certain disclosures that may be deemed forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to significant risks and uncertainties. Forward-looking statements include statements that are predictive in nature, that depend upon or refer to future events or conditions, or that include words such as "continue," "efforts," "expects," "anticipates," "intends," "plans," "believes," "estimates," "projects," "forecasts," "strategy," "will," "goal," "target," "prospects," "potential," "optimistic," "confident," "likely," "probable" or similar expressions or the negative thereof. Statements of historical fact also may be deemed to be forward-looking statements. We caution that these statements by their nature involve risks and uncertainties, and actual results may differ materially depending on a variety of important factors, including, among others: the Company's ability to launch beta and full product releases, the Company's ability to obtain FDA concurrence use for anti-microbial coatings in a timely manner; the Company's ability to meet its obligations under existing and anticipated contractual obligations; the Company's ability to develop, market, sell and distribute desirable applications, products and services and to protect its intellectual property; the ability of the Company's sales force to achieve expected results; the ability of the Company's customers to pay and the timeliness of such payments, particularly during recessionary periods; the Company's ability to obtain financing as and when needed; changes in consumer demands and preferences; the Company's ability to attract and retain management and employees with appropriate skills and expertise; the impact of changes in market, legal and regulatory conditions and in the applicable business environment, including actions of competitors; and other factors. Additional risk factors are listed in the Company's Annual Report on Form 10-K under the heading "Risk Factors." The Company undertakes no obligation to release publicly any revisions to any forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, except as required by law.

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Bacterin International Holdings, Inc. Schedules First Quarter 2012 Financial Earnings Conference Call

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Are Cancer Stem Cells Ready for Prime Time?

Sunday, April 1st, 2012

By Suling Liu, Hasan Korkaya, and Max S. Wicha | April 1, 2012

Inthe 30-year battle waged since the initiation of the war on cancer, there have been substantial victories, with cures for childhood malignancies among the most important. Our ever-expanding understanding of cellular and molecular biology has provided substantial insights into the molecular underpinnings of the spectrum of diseases we call cancer. Yet, while researchers view this as tremendous progress, many patients have seen only limited improvement. In fact, the relatively modest gains achieved in treating the most common malignancies have caused some to say that we are actually losing the war on cancer.

Based on new intelligence, oncologists are making informed battle plans to attack a particularly pernicious enemythe cancer stem cell. Controversial though they are, cancer stem cells are an incredibly promising target. If treatment-resistant cancer, and the metastases that transplant the cancer throughout the body, could be attributed to the actions of a single cell type, it could explain many of the treatment failures and provide a novel way to attack the disease.

The idea that cancers are driven by cells with embryonic features is an old one. Many cancers regress to a less differentiated state, expressing proteins that are usually expressed only in the embryo or during early development. It is only in the past 20 years or so, however, that additional observations led to the hypothesis that these embryonic-like cells were a separate subpopulation that fueled tumor expansion, much the same way that stem cells churn out the cells that make up a particular organ.

A number of groups, including our own, have identified cancer stem cell markers enabling the isolation and characterization of these cells. In addition, the development of in vitro and mouse functional assays has led to a veritable explosion of research on cancer stem cells from both blood-derived malignancies and solid tumors., However, the limitations of these markers and assays have generated heated debate regarding which tumors follow a stem cell model, and which do not. New data from our lab and from others is helping to clarify some of these areas of debate with the goal of better understanding how these cells can be identified and characterized.

A cancer stem cell (CSC) is defined as a cell that has the ability to self-renew, dividing to give rise to another malignant stem cell, as well as to produce the phenotypically diverse, differentiated tumor cells that form the bulk of the tumor. Evidence for CSCs was first documented in leukemia, where it was clear that only a small subset of cancer cells was capable of perpetuating the cancer upon serial transplantation from one mouse to another. Extensive knowledge of normal blood stem cells facilitated our recognition and understanding of leukemia stem cells. Evidence for CSCs in solid tumors has been more controversial, because it is more technically challenging to divide a solid mass into individual cells without damage or alteration, and knowledge of the properties of normal-tissue stem cells in these organs is more limited. However, some of the areas of contention may be resolved by continuing research into the biology of these CSCs.

Relatively modest gains achieved in treating the most common malignancies have caused some to say that we are actually losing the war on cancer.

One of the points of confusion in CSC biology is the question of where these cells come from. Do they arise from normal stem cells that have become cancerous through mutation, or do they arise from partially differentiated tissue-progenitor cells that have acquired the ability to self-renew? Recent evidence suggests CSCs may arise from either source.

A second misconception is that the definition of CSCs precludes the possibility that cancers arise from sequential mutations that accumulate over many cell generations and are selected for through a Darwinian processthe so-called clonal evolution model. Some have proposed that the CSC model is a competing theory of carcinogenesis. In fact, both models may be correct. There is evidence that CSCs may also be genetically unstable, resulting in clonal evolution that generates several distinct CSC clones in a tumor.

While the identification of CSC markers and the development of in vitro and mouse models have led to important advances in the field, each of these markers and models has limitations that have fueled debate. Markers used to isolate cancer stem cells, such as CD44, CD24, CD133, aldehyde dehydrogenase (ALDH), and Hoechst dye exclusion, have proven useful for identifying these cell populations in tumor samples. However, expression of these markers is highly dependent on experimental conditions such as culture medium and oxygen concentration. Similarly, in vitro assays that rely on the ability to form spherical colonies in suspension can be useful, but are notoriously inaccurate. Since the definition of CSCs is ultimately an operational one, the most reliable assay for these cells has been their ability to initiate tumors when transplanted into mouse models. Because the immune system will reject any implanted foreign tissue, researchers have had to use immunosuppressed mice to test for human CSCs. In some tumor types, such as melanoma, the proportion of cells capable of initiating tumors is dependent on the degree of immunosuppression in the mouse models utilized. However, the more immunosuppressed mouse models may actually overestimate the true frequency of CSCs.

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ImmunoCellular Therapeutics to Present on Cancer Stem Cell Targeting at the AACR Annual Meeting

Tuesday, March 27th, 2012

LOS ANGELES--(BUSINESS WIRE)--

ImmunoCellular Therapeutics, Ltd. (ImmunoCellular or the Company) (OTCBB: IMUC.OB - News), a biotechnology company focused on the development of novel immune-based cancer therapies, announced today that the Company will deliver a presentation on the identification and characterization of immunogenic epitopes from CD133 and their potential for use to immunologically target cancer stem cells (CSCs) at the Annual Meeting of the American Association for Cancer Research, which will be held from March 31 to April 4, 2012 at McCormick Place in Chicago, Illinois.

CD133 is a marker that identifies CSCs on many solid tumors and its expression has been correlated with shortened survival. Potential Cytotoxic T Lymphocytes (CTL) epitopes were identified by computer algorithms to predict binding to HLA-A2 tissue type on white blood cells. Studies with human cells in vitro demonstrated immunogenicity of two lead peptides and in vivo studies in mice confirmed the safety and immunogenicity of these peptides as a potential vaccine to target CD133 CSCs. The Company plans to incorporate these peptides into its second product, ICT-121, for recurrent glioblastoma as the initial indication, followed by additional solid tumors.

To evaluate the potential for autoimmunity, mouse homolog peptides of the lead epitopes that were shown to have high affinity binding to human HLA-A2 were used to immunize HLA-A2 transgenic mice. Mice were immunized 3 times at 3 week intervals and spleens were harvested and stimulated in vitro for one week with peptide pulsed antigen presentation cells. Interferon Gamma assays showed immune responses to the two lead peptides in 35% and 40% of mice. Organs, including heart, lung, liver, kidney, stomach, intestine, brain, bone marrow, gonads, and eyes from mice with immune responses were found to be negative for lymphocytic infiltrations supporting a lack of autoimmunity related to the immune response to these peptides. Together these studies support the safety and immunogenicity of these peptides as a potential vaccine to target CD133 cancer stem cells.

The Company will deliver its presentation titled Identification and characterization of immunogenic epitopes from CD133 and their potential for use to immunologically target cancer stem cells on Sunday, April 1, 2012, from 1:00 pm 5:00 pm CST in McCormick Place West (Hall F), Poster Section 19.

About ImmunoCellular Therapeutics, Ltd.

ImmunoCellular Therapeutics is a Los Angeles-based clinical-stage company that is developing immune-based therapies for the treatment of brain and other cancers. The Company recently commenced a Phase II trial of its lead product candidate, ICT-107, a dendritic cell-based vaccine targeting multiple tumor associated antigens for glioblastoma. To learn more aboutIMUC, please visitwww.imuc.com.

Forward-Looking Statements

This press release contains certain forward-looking statements that are subject to a number of risks and uncertainties, including the need for substantial additional capital to fund development of ICT-121 through to commercialization; the risk that safety and efficacy results for ICT-121 will not be confirmed in the human clinical trials; the risk that the FDA may impose additional testing requirements before proceeding to the clinical trials; the risks associated with adhering to projected preclinical or clinical timelines and the uncertainties of outcomes of development work for product candidates; and the risk of obtaining patent coverage for the ICT-121 vaccine or that any patents covering this vaccine will provide commercially significant protection for this product candidate. Additional risks and uncertainties are described in IMUC's most recently filed SEC documents, such as its most recent annual report on Form 10-K, all quarterly reports on Form 10-Q and any current reports on Form 8-K. IMUC undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

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Bioheart Labs and Stemlogix Veterinary Products Featured in Media

Friday, March 23rd, 2012

SUNRISE, Fla., March 22, 2012 (GLOBE NEWSWIRE) -- Bioheart, Inc. (OTCBB:BHRT.OB - News), a company focused on developing stem cell therapies for heart disease, previously announced that they entered into an agreement with Stemlogix, LLC, a veterinary regenerative medicine company, to provide additional cellular products and services to the veterinary market. Under this agreement, the companies are offering stem cell banking for veterinary patients (pets). WPLG, channel 10 featured this exciting technology in a news segment which aired in the South Florida area. A small sample of tissue can be obtained from the animals during a routine procedure such as a spay or neuter. The stem cells are isolated and cryopreserved for future use as needed.

"We are excited to bring our expertise in stem cell therapy to the veterinary community," said Mike Tomas, Bioheart's President and CEO. "Stem cell therapies represent new opportunities for various types of patients and the ability to bank a pet's cells when they are young and healthy could be very valuable for future use."

WPLG, Channel 10 in Miami/South Florida featured this new technology in a news segment which aired March 15, 2012. Please see the link below:

http://www.local10.com/thats-life/health/Pet-stem-cells-frozen-banked-for-future-use/-/1717022/9285894/-/apcx9rz/-/index.html

About Bioheart, Inc.

Bioheart is committed to maintaining its leading position within the cardiovascular sector of the cell technology industry delivering cell therapies and biologics that help address congestive heart failure, lower limb ischemia, chronic heart ischemia, acute myocardial infarctions and other issues. Bioheart's goals are to cause damaged tissue to be regenerated, when possible, and to improve a patient's quality of life and reduce health care costs and hospitalizations.

Specific to biotechnology, Bioheart is focused on the discovery, development and, subject to regulatory approval, commercialization of autologous cell therapies for the treatment of chronic and acute heart damage and peripheral vascular disease. Its leading product, MyoCell, is a clinical muscle-derived cell therapy designed to populate regions of scar tissue within a patient's heart with new living cells for the purpose of improving cardiac function in chronic heart failure patients. For more information on Bioheart, visit http://www.bioheartinc.com.

About Stemlogix, LLC

Stemlogix is an innovative veterinary regenerative medicine company committed to providing veterinarians with the ability to deliver the best possible stem cell therapy to dogs, cats and horses at the point-of-care. Stemlogix provides veterinarians with the ability to isolate regenerative stem cells from a patient's own adipose (fat) tissue directly on-site within their own clinic or where a patient is located. Regenerative stem cells isolated from adipose tissue have been shown in studies to be effective in treating animal's suffering from osteoarthritis, joint diseases, tendon injuries, heart disorders, among other conditions. Stemlogix has a highly experienced management team with experience in setting up full scale cGMP stem cell manufacturing facilities, stem cell product development & enhancement, developing point-of-care cell production systems, developing culture expanded stem cell production systems, FDA compliance, directing clinical & preclinical studies with multiple cell types for multiple indications, and more. For more information about veterinary regenerative medicine please visit http://www.stemlogix.com.

Forward-Looking Statements: Except for historical matters contained herein, statements made in this press release are forward-looking statements. Without limiting the generality of the foregoing, words such as "may," "will," "to," "plan," "expect," "believe," "anticipate," "intend," "could," "would," "estimate," or "continue" or the negative other variations thereof or comparable terminology are intended to identify forward-looking statements.

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NCCN Presents New Guidelines for Acute Lymphoblastic Leukemia

Wednesday, March 21st, 2012

FORT WASHINGTON, Pa.--(BUSINESS WIRE)--

The National Comprehensive Cancer Network (NCCN) has issued its first ever NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Acute Lymphoblastic Leukemia (ALL). The new guidelines were presented by the co-chairs of the NCCN ALL Panel, Joseph C. Alvarnas, MD, Director of Medical Quality and Associate Director in the Division of Hematology and Hemapoietic Cell Transplantation at the City of Hope Comprehensive Cancer Center and Patrick A. Brown, MD, Associate Professor of Oncology and Pediatrics/Director of the Pediatric Leukemia Program, at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

We felt that it was very important to develop a clear standard of treatment for adult acute lymphoblastic leukemia (ALL), said Dr. Brown. We now have consistent data demonstrating that young adults - those between the ages of 15 and 39 - with ALL benefit significantly from treatments inspired by those used for children with ALL. The main reason for this is that younger adult patients can tolerate the intensive therapies that we use for our pediatric patients, and this translates into better outcomes. We hope that these new NCCN Guidelines will give oncologists the information they need to ensure that young adult ALL patients receive these intensive therapies.

Dr. Brown noted that there had been considerable cross-over and discussion between his group and the panel which just released the new NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology headed by Peter F. Coccia, MD, of the UNMC Eppley Cancer Center at The Nebraska Medical Center. Both the NCCN ALL and AYA Guidelines emphasize the importance of providing expert, comprehensive supportive care and the importance of increasing the enrollment of young adult patients into clinical trials.

The NCCN Guidelines also address treatment for older ALL patients, a group that Dr. Brown said is often more difficult to treat successfully than the younger patients. This is in large part due to the higher frequency of poor-risk cytogenetic abnormalities observed among older adults with ALL. One such abnormality is a translocation that results in the Philadelphia chromosome (Ph), which leads to the formation of the BCR-ABL fusion gene. Given the poor prognosis associated with Ph-positive ALL, the NCCN Guidelines initially stratify patients (both in AYA and adults) based on the presence of this abnormality. Regardless of age group, patients with Ph-positive ALL benefit from treatment regimens that incorporate BCR-ABL-targeting tyrosine kinase inhibitors.

The role of allogeneic stem cell transplantation (SCT) in treating ALL was also discussed. The NCCN Guidelines recommend allogeneic SCT as a consolidation option in patients with Ph-positive ALL, although the optimal role of SCT in this setting is yet to be defined. In addition, consolidation with allogeneic SCT is strongly recommended in patients with Ph-negative ALL with high-risk features. Evaluation of minimal residual disease can provide further risk stratification following initial induction therapy, and may help to identify patients who could potentially benefit from allogeneic SCT. Older adult patients, however, may not be appropriate candidates for SCT or intensive therapy options. Dr. Alvarnas discussed that in older adults, presence of comorbid factors such as organ dysfunction, limits the use of intensive regimens, which significantly impacts on the outcomes for this population. Dr. Brown pointed to the emergence of novel immune based therapies as new hope for increased remission rates and longer disease-free survival in older ALL patients.

Both Dr. Brown and Dr. Alvarnas emphasized the need for adequate central nervous system (CNS)-directed treatment to prevent CNS relapse for all patients with ALL, and the importance of comprehensive supportive care measures tailored to the needs of each patient.

ALL is the rarest form of leukemia in adults, Dr. Brown said. Its treatment poses many challenges and requires expertise and experience in a number of medical disciplines and supportive care areas. We recommend that ALL patients be referred to specialized treatment centers, and if possible, enrolled on clinical trials.

About the National Comprehensive Cancer Network

The National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the worlds leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives.

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Cancer Paradigm Shift: Biomarker Links Clinical Outcome with New Model of Lethal Tumor Metabolism

Thursday, March 15th, 2012

Newswise PHILADELPHIA Researchers at the Kimmel Cancer Center at Jefferson have demonstrated for the first time that the metabolic biomarker MCT4 directly links clinical outcomes with a new model of tumor metabolism that has patients feeding their cancer cells. Their findings were published online March 15 in Cell Cycle.

To validate the prognostic value of the biomarker, a research team led by Agnieszka K. Witkiewicz, M.D., Associate Professor of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, and Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology and Regenerative Medicine at Jefferson, analyzed samples of patients with triple negative breast cancer, one of the most deadly of breast cancers, with fast-growing tumors that often affect younger women.

A retrospective analysis of over 180 women revealed that high levels of the biomarker MCT4, or monocarboxylate transporter 4, were strictly correlated with a loss of caveolin-1 (Cav-1), a known marker of early tumor recurrence and metastasis in several cancers, including prostate and breast.

The whole idea is that MCT4 is a metabolic marker for a new model of tumor metabolism and that patients with this type of metabolism are feeding their cancer cells. It is lethal and resistant to current therapy, Dr. Lisanti said. The importance of this discovery is that MCT4, for the first time, directly links clinical outcome with tumor metabolism, allowing us to develop new more effective anti-cancer drugs.

Analyzing the human breast cancer samples, the team found that women with high levels of stromal MCT4 and a loss of stromal Cav-1 had poorer overall survival, consistent with a higher risk for recurrence and metastasis, and treatment failure.

Applying to a Triple Threat Today, no such markers are applied in care of triple negative breast cancer, and as a result, patients are all treated the same. Identifying patients who are at high risk of failing standard chemotherapy and poorer outcomes could help direct them sooner to clinical trials exploring new treatments, which could ultimately improve survival.

The idea is to combine these two biomarkers, and stratify this patient population to provide better personalized cancer care, said Dr. Witkiewicz

The findings suggest that when used in conjunction with the stromal Cav-1 biomarker, which the authors point out has been independently validated by six other groups worldwide, MCT4 can further stratify the intermediate-risk group into high and low risk.

Since MCT4 is a new druggable target, researchers also suggest that MCT4 inhibitors should be developed for treatment of aggressive breast cancers, and possibly other types. Targeting patients with an MCT4 inhibitor, or even simple antioxidants, may help treat high-risk patients, who otherwise may not respond positively to conventional treatment, the researchers suggest.

Paradigm Shift But the work stems beyond triple negative breast cancer, challenging an 85-year-old theory about cancer growth and progression.

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BGI Demos Single-Cell Exome Sequencing Method on Tumor Cell Lines, Patient Samples

Wednesday, March 7th, 2012

By Monica Heger

Researchers at BGI have published two papers in Cell outlining a single-cell exome sequencing technique that they demonstrated on cell lines, a previously sequenced genome, and cancer patient samples.

The papers show that single-cell analysis can provide a much finer-grained genetic characterization of heterogeneous tissues than bulk tissue sequencing and also point toward the use of the method in areas beyond cancer, such as stem cell research and preimplantation genetic diagnosis, according to the BGI researchers.

Moving forward, the team plans to improve the technique and use it to analyze single cells from different cancer types to study "metastasis, recurrence, and [tumors] before and after therapy," Luting Song, project manager at BGI and a co-author on the papers, told In Sequence in an e-mail.

Single-cell sequencing is thought to be especially useful in cancer samples because tumors are heterogeneous and bulk sequencing may miss rare clonal types. Additionally, sequencing individual cells could help study tumor evolution or be used to monitor relapse by sequencing circulating tumor cells in patients' blood.

However, sequencing single cells is tricky because it is difficult to capture the entire genome of a single cell and amplification strategies introduce bias. Nevertheless, a number of researchers and companies have been working on strategies to sequence single cells, including a team from Cold Spring Harbor Laboratory, which developed a strategy that uses degenerate oligonucleotide-primed PCR to amplify the genome (IS 5/18/2010), and Rubicon Genomics, which uses a technique called thermal cycle library formation that enables the creation of multiple copies of a library from one template strand (IS 3/22/2011).

The BGI team described its method in two papers published in Cell last week. In one, the researchers first validated the approach in two lymphoblastoid cell lines, and then performed single-cell exome sequencing on 90 cells from a patient with a myeloproliferative tumor.

In the second paper, the team demonstrated the single-cell exome sequencing method on 25 cells from a patient with clear cell renal cell carcinoma.

The BGI method relies on multiple displacement amplification, which uses the enzyme phi29 to amplify the DNA in a linear fashion. According to Song, compared to the degenerate oligonucleotide-primed PCR method, MDA generates larger amplicons on average 10 kilobases compared to 1 kilobase with DOP which "results in significantly higher genome recovery" and "allows greater resolution."

The greater resolution of MDA enables single-nucleotide variants to be called, while DOP can only reliably call copy number variations, Song added. The CSHL team that initially published the DOP method is now using it to analyze copy number variation from prostate cancer patients.

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This is the only time bad breath is a good thing

Thursday, March 1st, 2012

By Andrew Winner

There are those who say theres a use for every little thing in this world, no matter how vile or off-putting. An enterprising dentist is doing his part to prove that's true. Japanese dental researchers have found that halitosis -- that is, bad breath -- is an ideal incubator for cultivating hepatic (liver) cells.

In a finding that could have far-reaching impacts on diseases such as Alzheimers and Parkinsons, stem cells harvested from human dental pulp became liver cells at an astonishing rate when incubated with hydrogen sulphide, the chemical compound responsible for bad breath.

Talk about the ultimate silver lining. The study was published Monday in IOP Publishing's Journal of Breath Research.

Stem cell therapy treats damaged tissue by introducing new cells, but it can sometimes be difficult to safely and effectively produce these new cells. Study author Dr. Ken Yagaeki and his team at Nippon Dental University believe the use of stem cells from dental pulp could eventually replace existing methods of stem cell production, two of which use human bone marrow and fetal bovine serum as source material. In fact, Yagaeki went out on a limb to show that dental pulp is a viable source of stem cells.

For Yagaeki, observing the resilience of teeth plagued by cavities made him wonder if there werent more stem cells in dental pulp than previously thought. Despite some skepticism from colleagues, he reports that 60-80 percent of human dental pulp cells are stem cells, up markedly from the previous estimate of 1 percent.

Although nobody reported regeneration of those tissues from dental pulp, I had a hypothesis that dental pulp would be a good source of somatic stem cells, Dr. Yagaeki wrote in an e-mail. Of course all people denied my hypothesis. In the meeting of International Association for Dental Research, a chairman of my session called us as stupid.

After this vindicating discovery, Yagaeki looked to test the impact of halitosis on the development of stem cells into hepatic cells.

After stem cells were harvested from the center of human teeth (dont worry the teeth extractions were part of normal dental treatments), the samples were then split into test and control groups. Using a battery of tests, researchers were able to show that a very high percentage of the stem cells incubated in an environment with hydrogen sulphide successfully became hepatic cells.

It was a lucky discovery. Initially, Yagaeki had attempted to learn about negative effects of hydrogen sulphide on the samples before noticing that in small concentrations, the compound had the opposite effect.

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