New Cancer Stem Cell Identified
A Potential Metastatic Disease Target?
Researchers from Weill Cornell Medical College have identified a type of cancer stem cell that might initiate metastatic cancer, which spreads beyond the original, primary tumor site and to other locations within the body. For the first time, scientists have revealed that the molecular profiles of these cancer stem cells are much different than those located in primary tumors. The study's senior author Dr. Shahin Rafii -- the Arthur B. Belfer Professor in Genetic Medicine and director of the Ansary Center for Stem Cell Therapeutics at Weill Cornell and a noted investigator at the Howard Hughes Medical Institute -- believes that these findings pave the way for research into a new subset of metastatic cancer stem cells, previously unidentified.
It has long been thought that a protein called CD133 is produced by all cancer stem cells, which are responsible for the creation and maintenance of tumors. But now, the research team found that certain metastatic stem cells (CD133-negative) do not produce this well-known protein. The scientists studied colon cancer cells within a mouse model to make their observations. Moving forward, the findings may spur research to identify new biomarkers, specific to metastatic cancer stem cells, which may lead to the development of drugs that target metastatic cancer. The study's results were released as a special "highlighted" article in a recent issue of the Journal of Clinical Investigation.
Learn more at: http://news.med.cornell.edu/wcmc/wcmc_2008/05_27b_08.shtml
Easing the Pain of Diabetes
Studying a Depression Drug for Common Nerve Condition
To ease pain and numbness associated with diabetes, NewYork-Presbyetrian/Weill Cornell physician-scientists are studying a drug previously used for depression to treat peripheral neuropathy. Diabetics often suffer from this condition because of high blood sugar levels that damage nerve cells. Those with peripheral neuropathy often endure chronic pain, cramping and sleepless nights that prevent them from living a normal lifestyle.
But now, scientists believe that a drug called reboxetine may alleviate their symptoms. The compound works by boosting the level of the neurotransmitter norepinephrine between nerve cells. But it also works by inhibiting the neurotransmitter's degradation within the nerve, where it is stored within the cell for later use.
Dr. Bassem Masri -- a cardiologist and diabetes specialist at New York-Presbyterian/Weill Cornell and Helen and Robert Appel Clinical Scholar and assistant professor of clinical medicine at Weill Cornell Medical College -- is studying the drug's effectiveness in a Phase II trial in subjects who have been diagnosed with diabetes for at least one-year and who have peripheral neuropathy.
For more information: Please contact Ivanka Zaprianov at 212-746-2349.
Wii-habilitation: Using Video Games to Heal Burns
Also Using "Guitar Hero" Game
Video games -- often regarded as nothing more than mindless entertainment for lethargic kids and teens -- are proving to be an effective, new tool to motivate patients to perform rehabilitation exercises. Rehabilitation therapists from the William Randolph Hearst Burn Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center are using the motion-sensitive Nintendo Wii video game console, along with traditional methods, to help patients recover from life-changing injuries.
Patients hold wireless remotes that control actions on screen. Players swing the controller to simulate realistic motions, like swinging a tennis racquet, swatting a baseball for a homerun, among countless other motions. For burn patients or any patient with a skin graft, moving and stretching the skin is very painful, but imperative for a successful recovery.
The Burn Center is also employing a special add-on to the Nintendo Wii system, Guitar Hero III. The controller for the game resembles a miniature guitar. Patients strum a bar on the guitar's body and press color-coded buttons that resemble notes. Therapists hope that Guitar Hero will help patients with burns on their hands, arms and shoulders to regain fine-motor control.
Avoiding Spleen Removal for Cooley's Anemia Sufferers
Weill Cornell Researchers May Have Identified Key Gene Responsible for Mutated Red Blood Cells
Researchers from Weill Cornell Medical College may have discovered the precise role of a gene in one of the world's most common blood disorders, beta-thalassemia, commonly known as Cooley's anemia. Along with sickle-cell anemia, Cooley's anemia is the most commonly inherited disease in the world, affecting many people of Mediterranean descent, and 20 out of every 100,000 African-Americans. The World Health Organization estimates that between 50,000-100,000 children are born with the disease each year.
The research is published in a recent issue of the journal Blood, the official publication of the American Society of Hematology (ASH).
In Cooley's anemia, hemoglobin -- the oxygen-carrying molecule on red blood cells -- is mutated and non-functioning, resulting in a low red-blood-cell count. Common symptoms of the disease include fatigue, shortness of breath and an enlarged spleen, called splenomegaly, caused by a buildup of malformed red blood cells within the body. The spleen works to filter out these unhealthy cells in order to protect the body from harm, such as in a stroke, but eventually the spleen becomes over-stuffed and is commonly surgically removed (splenectomy) in order to prevent a potentially fatal burst. Unfortunately, after the spleen is removed, patients are at a much greater risk for stroke and infections.
Dr. Stefano Rivella, the study's senior author and assistant professor of genetic medicine in pediatrics at Weill Cornell Medical College, believes that he and his collaborators may have found a way around splenectomy. After giving mice with Cooley's a compound called JAK2 inhibitor, the researchers found that the mice's spleens shrunk to normal sizes, and they began to produce normal red blood cells. The chemical (a similar compound is already in a Phase I clinical trial for myelodysplastic syndromes -- another blood disorder) blocks the activity of the JAK2 gene that is highly expressed in Cooley's anemia, and is believed to play a crucial role in the malformation of red blood cells.
Learn more at: http://news.med.cornell.edu/wcmc/wcmc_2008/05_22_08.shtml
Striking at the Heart of Hepatitis B Virus
A New Drug May Wipe-Out Infection in More Patients
NewYork-Presbyterian/Weill Cornell clinician-scientists are studying how a new drug might be used to treat chronic hepatitis B infection (HBV). Clevudine is a compound that may provide a longer lasting viral suppression after treatment is stopped, compared to drugs currently prescribed to treat HBV. This new compound is being studied in subjects with chronic HBV who have never been treated before by one of the current standard medications for HBV. The drug blocks an enzyme called DNA polymerase in order to stop the replication of the HBV virus.
Dr. Ira Jacobson -- principal investigator of the study, chief of the Division of Gastroenterology and Hepatology at NewYork-Presbyterian/Weill Cornell, and Vincent Astor Distinguished Professor of Clinical Medicine at Weill Cornell Medical College -- says that the new drug may help many patients with HBV avoid a lifetime of taking drugs to control the infection.
For more information: Please contact Arline Loh at 646-962-4731 or email her at arl2005@med.cornell.edu.
A Shortcut for Communication Between Brain Cells
Understanding How Neurons Communicate May Help Treat Brain Disorders
For the first time, Weill Cornell scientists have learned important details illustrating how neuronal cells in the brain communicate at a microcellular level. Such knowledge may help in the development of drug compounds used to treat disorders caused by malfunctions in communication between brain cells, such as schizophrenia, epilepsy, Parkinson's and Alzheimer's disease. Their findings are published in the June 25 issue of the Journal of Neuroscience.
To communicate between cells, tiny transport vesicles package and ship neurotransmitter-chemicals to the end (terminals) of the cell and then across synapses, or gaps in-between neurons. Adjacent neurons then receive the signal. To do this, these transport-vesicles must be recycled quickly -- especially during boosts in brain activity, but it has never been understood exactly how such critical recycling works.
Observing proteins within cellular vesicles labeled with a fluorescent marker in the lab, for easy identification, the researchers saw that about 20 vesicles can be simultaneously manufactured right at the end of the neuron -- like milk bottles, lined up and waiting to be filled for shipment. The new findings show that calcium ions, which help to send the signal across the synapse to another neuron, also control the cell's ability to rebuild the vesicles at the cell's terminal end.
According to the researchers, the explanation for this cellular feat is a simple matter of distance. "Think of the cell body as New York City and the axon [the long narrow stretch between the cell body and cell terminal] as a highway leading to Boston," explains lead researcher, Dr. Tim Ryan, from the Department of Biochemistry at Weill Cornell Medical College. "It takes far too long for the vesicles to move from all the way in the cell body to another cell. These vesicles are made in New York and slowly transported to the cell's terminal end, but some are made right in Boston for immediate use." Dr. Ryan hopes that by understanding the mechanics of the cellular trafficking machine, he and other scientists will ultimately be able to identify and repair numerous neurologic malfunctions.
News About Inflammatory Bowel Disease, Crohn's Disease:
Stem Cells Heal Chronic Inflammation in the Gut
May Help Restore Immune System to Normal Function for Crohn's Disease
Stem cells are being studied at NewYork-Presbyterian/Weill Cornell to heal the gut in subjects suffering from Crohn's disease. Physician-scientists believe that these cells might help to restore the ability of the immune system to control inflammation by secreting anti-inflammatory proteins into the digestive tract, allowing for regeneration of tissue and prevention of scar tissue. It is believed that Crohn's disease results from a malfunctioned immune response, leading to uncontrolled inflammation in the tissues of the intestine. Diarrhea, painful cramping, blood in stool, ulcers and other wounds in the digestive tract are all possible symptoms of the disease.
Patients who have previously failed to benefit from medications for Crohn's disease are enrolled in the trial to test the safety and efficacy of the procedure. Each subject receives four infusions -- intravenous transplantation -- of mesenchymal stem cells, which are universally compatible in all people, like type-O blood.
For more information: Please contact Cynthia Cabral at 212-746-5118.
Drug for Treatment of Inflammatory Bowel Disease
New Formula Allows for Greater Absorption, Fewer Doses
Physician-scientists from NewYork-Presbyterian/Weill Cornell, involved in clinical trials for a new drug for those who suffer from inflammatory bowel disease (IBD), say it is the best option among available drugs. Gaizo is a reformulation of the active ingredient 5-ASA in currently available drugs. However, the researchers found that 99 percent of the active ingredient in the new pill is released in the colon compared to only 70 percent in other common IBD drugs.
Dr. Ellen Scherl -- the Jill Roberts Associate Professor of IBD and director of the Jill Roberts Center for IBD at NewYork-Presbyterian Hospital/Weill Cornell Medical Center -- led the trial, and found that the greatest benefit to Gaizo is the lowered pill burden for patients. Because there is more of the active drug per pill, patients can take the drug less frequently. In the past, patients would have to take three pills between three and four times each day. But now, patients only need to take the drug twice daily. This is especially important because most IBD-sufferers are young teens or in their 20s, and are the most likely patient-group to miss a dose.
IBD includes two diseases: ulcerative colitis and Crohn's disease. Both cause inflammation in the gastrointestinal (GI) tract, leading to bloody diarrhea, abdominal pain and weight loss. Drugs to treat IBD are designed to decrease the inflammation in the mucosal lining of the colon.
NewYork-Presbyterian Hospital/Weill Cornell Medical Center
NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances -- from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial for gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and, most recently, the world's first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient. NewYork-Presbyterian, which is ranked sixth on the U.S.News & World Report list of top hospitals, also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree oversees and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit www.nyp.org and www.med.cornell.edu.