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Cancer research targets a key cell protein

Blocking "don't destroy me" signals that normally sit on the surface of tumor cells and render them resistant to immune-cell attack slows the growth of a broad range of human cancers when they're implanted in mice, researchers have found.

The approach, reported by immunologists at the Stanford University School of Medicine, was effective against ovarian, breast, colon, bladder, liver, prostate and brain cancer cells. If the work can be repeated in people, the approach may someday help doctors marshal defender cells in patients' own bodies to fight cancers, the researchers said.

Key to the work is a cell protein called CD47, which is already being investigated in the treatment of leukemia.

CD47 sits on cell membranes and communicates with various immune cells, including macrophages, which gobble up foreign invaders in the body. It plays an important role in the normal life cycle of healthy red blood cells, telling macrophages to leave the cells alone.

In the study, the scientists injected the animals with antibodies that bind to CD47 and block out its protective signal.

"If we can block this signal, we can get the immune system to eat [the cancer cells] up," said Stephen Willingham, a postdoctoral researcher in the laboratory of immunologist Dr. Irving Weissman at Stanford and first author of a paper about the work.

The Stanford team examined cancer cells removed from patients with a variety of types of solid tumors. They found that CD47 studded the membranes of almost all of the cancer cells in their sample, suggesting that it is a molecule common to all cancers.

Placing the cells in lab dishes, the team administered an antibody: a protein that binds to CD47 and blocks it from warding off immune system cells. Macrophages ate the cells.

The researchers then implanted human tumor cells in mice for further study. They allowed the cancers to grow, and administered the antibody against CD47.

Antibody treatment inhibited the growth of almost all of the solid tumors and was able to wipe out some smaller cancers altogether, according to the report, which was published Monday in the journal Proceedings of the National Academy of Sciences.

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Cancer research targets a key cell protein

Bone marrow stem cells improve heart function, study finds

Public release date: 24-Mar-2012 [ | E-mail | Share ]

Contact: Traci Klein newsbureau@mayo.edu 507-284-5005 Mayo Clinic

CHICAGO -- A research network led by a Mayo Clinic physician found that stem cells derived from heart failure patients' own bone marrow and injected into their hearts improved the function of the left ventricle, the heart's pumping chamber. Researchers also found that certain types of the stem cells were associated with the largest improvement and warrant further study.

The results were presented today at the 2012 American College of Cardiology Meeting in Chicago. They will also be published online in the Journal of the American Medical Association.

This Phase II clinical trial, designed to test this strategy to improve cardiac function, is an extension of earlier efforts in Brazil in which a smaller number of patients received fewer stem cells. For this new network study, 92 patients received a placebo or 100 million stem cells derived from the bone marrow in their hips in a one-time injection. This was the first study in humans to deliver that many bone marrow stem cells.

"We found that the bone marrow cells did not have a significant impact on the original end points that we chose, which involved reversibility of a lack of blood supply to the heart, the volume of the left ventricle of the heart at the end of a contraction, and maximal oxygen consumption derived through a treadmill test," says Robert Simari, M.D., a cardiologist at Mayo Clinic in Rochester, Minn. He is chairman of the Cardiovascular Cell Therapy Research Network (CCTRN), the network of five academic centers and associated satellite sites that conducted the study. The CCTRN is supported by the National Heart, Lung, and Blood Institute, which also funded the study.

"But interestingly, we did find that the very simple measure of ejection fraction was improved in the group that received the cells compared to the placebo group by 2.7 percent," Dr. Simari says. Ejection fraction is the percentage of blood pumped out of the left ventricle during each contraction.

Study principal investigators Emerson Perin, M.D., Ph.D., and James Willerson, M.D., of the Texas Heart Institute, explain that even though 2.7 percent does not seem like a large number, it is statistically significant and means an improvement in heart function for chronic heart failure patients who have no other options.

"This was a pretty sick population," Dr. Perin says. "They had already had heart attacks, undergone bypass surgery, and had stents placed. However, they weren't at the level of needing a heart transplant yet. In some patients, particularly those who were younger or whose bone marrows were enriched in certain stem cell populations, had even greater improvements in their ejection fractions."

The average age of study participants was 63. The researchers found that patients younger than 62 improved more. Their ejection fraction improved by 4.7 percent. The researchers looked at the makeup of these patients' stem cells from a supply stored at a biorepository established by the CCTRN. They found these patients had more CD34+ and CD133+ type of stem cells in their mixture.

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Bone marrow stem cells improve heart function, study finds

Vatican Calls Off Stem-Cell Conference

Nature | Health

A Monsignor and Officer for Studies at the Pontifical Academy for Life called the cancellation a "sad event." Attendees are set to receive an official explanation

March 26, 2012|

By Ewen Callaway of Nature magazine

The Vatican has abruptly cancelled a controversial stem-cell conference that was set to be attended by the Pope next month.

The Third International Congress on Responsible Stem Cell Research, scheduled for 25-28 April, was to focus on clinical applications of adult and reprogrammed stem cells. But a number of the invited speakers, including Alan Trounson, president of the California Institute for Regenerative Medicine in San Francisco, and keynote speaker George Daley, a stem-cell scientist at Children's Hospital Boston in Massachusetts, are involved in research using human embryonic stem cells, which the Catholic Church considers unethical. The previous two congresses had also included scientists who worked on such cells, without generating much controversy.

Father Scott Borgman, secretary of the Church's Pontifical Academy for Life, one of the conference organizers, says that logistical, organizational and financial factors forced the cancellation, which was announced on 23 March. The academy weighs in on bioethical and theological issues that are relevant to Church teachings.

The Catholic News Agency, an independent news service based in Englewood, Colorado, quoted an unnamed academy member who called the cancellation an "enormous relief to many members of the Pontifical Academy for Life, who felt that the presence on its program of so many speakers, including the keynote speaker, committed to embryonic stem cell research, was a betrayal of the mission of the Academy and a public scandal".

"I think the only interpretation is that we are being censored. It is very disappointing that they are unwilling to hear the truth," says Trounson. He had hoped to provide a "balanced perspective" on the potential clinical applications of stem cells, both adult and embryonic.

Meanwhile, some European scientists, who had called for a boycott because they believed the conference unfairly maligned embryonic stem cell research, cheered its cancellation.

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Vatican Calls Off Stem-Cell Conference

Midlands Vet Uses Stem Cell Therapy for Pets in Pain

Columbia, SC (WLTX) --What if your pet couldn't walk anymore? One Midlands vet is using stem cell therapy to help.

For Beth Phibbs it's almost like a turning back of the hands of time.

"I call her my little miracle dog, because she's doing things she used to do," said Phibbs. "Now she's not on any medication, and she can go up and down the steps and she runs and jumps and things that she used to do when she was five."

Phibbs has spent the last 13 years loving and looking after her pet dog Maggie, and when she pet began to develop arthritis and a limp she had to take action. But when the first treatments stopped working, Phibbs and Maggie had to look to another options, dog stem cell therapy.

"I had no idea that animals were able to have they type of procedures," she said.

Dr. Kenneth Banks a veterinarian with the Bank Animal Hospital, performed the surgery for Maggie using her own stem cells in the one day procedure.

Banks said the stem cell therapy not only cost less than some other options, but was less invasive and had a quicker recovery time as well.

Still with about three similar procedures under his belt, even he didn't expect to see a such change in maggie just 40 days after the surgery.

"I wasn't sure we were gonna get the results this fast, we were expecting results, maybe not a good as she's done. We're real happy with her results," said Banks.

Now, after three years on medication and walking with a limp, Maggie's getting used to a new way of life -- one with out pain in her golden years.

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Midlands Vet Uses Stem Cell Therapy for Pets in Pain

Stem cell therapy possibly helpful in heart failure patients

Public release date: 24-Mar-2012 [ | E-mail | Share ]

Contact: Beth Casteel bcasteel@acc.org 240-328-4549 American College of Cardiology

CHICAGO -- A new study found that using a patient's own bone marrow cells may help repair damaged areas of the heart caused by heart failure, according to research presented today at the American College of Cardiology's 61st Annual Scientific Session. The Scientific Session, the premier cardiovascular medical meeting, brings cardiovascular professionals together to further advances in the field.

Millions of Americans suffer from heart failure, the weakening of the heart muscle and its inability to pump blood effectively throughout the body. If medications, surgery, or stents fail to control the disease, doctors often have few treatment options to offer.

This is the largest study to date to look at stem cell therapy, using a patient's own stem cells, to repair damaged areas of the heart in patients with chronic ischemic heart disease and left ventricular dysfunction. Researchers found that left ventricular ejection fraction (the percentage of blood leaving the heart's main pumping chamber) increased by a small but significant amount (2.7 percent) in patients who received stem cell therapy. The study also revealed that the improvement in ejection fraction correlated with the number of CD34+ and CD133+ cells in the bone marrow information that will be helpful in evaluating and designing future therapies and trials.

"This is the kind of information we need in order to move forward with the clinical use of stem cell therapy," said Emerson Perin, MD, PhD, director of clinical research for cardiovascular medicine at the Texas Heart Institute and the study's lead investigator.

This multi-center study was conducted by the Cardiovascular Cell Therapy Research Network and took place between April 2009 and 2011. At five sites, 92 patients were randomly selected to receive stem cell treatment or placebo. The patients, average age 63, all had chronic ischemic heart disease and an ejection fraction of less than 45 percent along with heart failure and/or angina, and were no longer candidates for revascularization.

"Studies such as these are able to be completed much faster because of the team approach of the network," said Sonia Skarlatos, PhD, deputy director of the division of cardiovascular sciences at the National, Heart, Lung and Blood Institute, and program director of the network.

Bone marrow was aspirated from the patients and processed to obtain just the mononuclear fraction of the marrow. In patients randomly selected to receive stem cell therapy, doctors inserted a catheter into the heart's left ventricle to inject a total of 3 ccs comprising 100 million stem cells into an average of 15 sites that showed damage on the electromechanical mapping image of the heart. Dr. Perin said the procedure is relatively quick and painless, involving only an overnight stay at the hospital.

The study used electromechanical mapping of the heart to measure the voltage in areas of the heart muscle and create a real-time image of the heart.

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Stem cell therapy possibly helpful in heart failure patients

Houston study shows stem-cell's potential for heart treatment

Houston researchers are reporting that adult stem cells have a modest benefit in younger patients with heart failure, the first large-scale evidence that the controversial yet promising new therapy can be developed to help millions of people with the disease.

In a study presented at a cardiology conference Saturday, Texas Heart Institute doctors presented results of a clinical trial showing that cells derived from patients' own bone marrow produce a small but significant increase in the heart's ability to pump oxygen-rich blood.

"This study moves us one step closer to being able to help patients with severe heart failure who lack other alternatives," said Dr. James Willerson, president of the Texas Heart Institute and the study's principal investigator. "It also points to a future in which stem cells regenerate the heart."

The study did not find improvements in a number of heart function measures, but Willerson and other study leaders said it yielded key information about the specific adult stem cells with the greatest therapeutic potential. The trial used a number of stem cell types.

Transplants limited

About 6 million people in the United States have heart failure, a progressive and eventually fatal disease in which the heart loses the ability to effectively pump sufficient amounts of blood to the body's organs. Better therapy is needed because the limited availability of donor hearts makes transplants an option for only about 2,300 people in the United States annually.

Adult stem cells have become the subject of studies for a variety of conditions - the Texas Heart Institute has many involving the heart - since laboratory research in the late 1990s showed they have the ability to grow into most any kind of tissue. This is the first intermediate-stage study in the United States, characterized by multiple centers and many dozens of patients.

The idea of therapy involving adult stem cells formerly was considered non-controversial, a more ethical alternative to destroying embryos to obtain their stem cells. But it has come under fire recently because it is increasingly being used outside of research studies and for profit, particularly in Texas, where Gov. Rick Perry received it last year for his ailing back. The unregulated activity has prompted complaints to the U.S. Food and Drug Administration and a Texas Medical Board draft policy requiring oversight for any use of experimental drugs.

3.1 percent increase

The new study, presented at an American College of Cardiology conference and to be published in the Journal of the American Medical Association, involved 92 patients at five locations - two-thirds at the Texas Heart Institute - whose hearts were pumping at less than 45 percent of capacity and could not be treated with surgery. Doctors injected patients' own stem cells or placebos into their hearts.

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Houston study shows stem-cell's potential for heart treatment

Stem cell, heart heath study

HOUSTON -

Doctors from the Texas Heart Institute at St. Luke's Episcopal Hospital have found that patients with heart failure may be able to repair the damaged areas of the heart with stem cells from the patient's own bone marrow.

Doctors presented the findings at the American College of Cardiologys 61st Annual Scientific Session Saturday.

The results are from a multi-center clinical study that measured the possible benefits of using a patients own bone marrow cells to repair damaged areas of the heart suffering from severe heart failure, a condition that affects millions of Americans.

The study, which was the largest such investigation to date, found that the hearts of the patients receiving bone marrow derived stem cells showed a small but significant increase in the ability to pump oxygenated blood from the left ventricle, the hearts main pumping chamber, to the body.

The expectation is that the study will pave the way for potential new treatment options and will be important to designing and evaluating future clinical trials.

This is exactly the kind of information we need to move forward with the clinical use of stem cell therapy, said Emerson Perin, MD, PhD, Director of Clinical Research for Cardiovascular Medicine at THI, and one of the studys lead investigators.

The bone-marrow derived stem cells are helpful to the injured heart when they are themselves biologically active, added Dr. James T. Willerson, the studys principal investigator and President and Medical Director of THI.

This study moves us one step closer to being able to help patients with severe heart failure who have no other alternatives.

The study was conducted by the Cardiovascular Cell Therapy Research Network, the national consortium to conduct such research funded by the National Institutes of Healths National Heart, Lung, and Blood Institute.

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Stem cell, heart heath study

Bone Marrow Stem Cell Therapy Trial – Clues, But No Answers

(RTTNews.com) - An important clinical trial, which evaluated the use of autologous bone-marrow-cell therapy in patients with chronic ischemic heart failure, has failed to meet the prespecified end points of improvement in most measures of heart function, according to the results presented at the American College of Cardiology 2012 Scientific Sessions.

The trial dubbed, FOCUS - a phase II study, is the largest study to date to investigate if a patient's own bone marrow cells improved myocardial perfusion, reduced left ventricular end-systolic volume or enhanced maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina. The FOCUS trial was undertaken by the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network.

Ninety two patients with chronic ischemic heart disease , having a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography, or SPECT, who were no longer candidates for revascularization, were enrolled in the trial. Sixty one patients in the study were administered bone marrow cells through transendocardial injections while thirty one patients were administered placebo.

An assessment of primary endpoints at 6 months has revealed that there is no statistically significant difference between the treatment group and placebo arm in left ventricular end-systolic volume assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. The secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement, also has not exhibited any difference between the two arms.

However, according to the study authors, exploratory analyses have revealed that left ventricular ejection fraction improved in the treatment group compared with the placebo group by 2.7%.

The authors, led by Emerson Perin, concluded that the findings provide evidence for further studies to determine the relationship between the composition and function of bone marrow product and clinical end points. Understanding these relationships will improve the design and interpretation of future studies of cardiac cell therapy, the authors noted.

The results were published online March 24 in the Journal of the American Medical Association.

For comments and feedback: contact editorial@rttnews.com

http://www.rttnews.com

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Bone Marrow Stem Cell Therapy Trial - Clues, But No Answers