May 29, 2009
NIH Podcast Episode #0085
Balintfy: Welcome to the 85th episode of NIH Research Radio with news about the ongoing medical research at the National Institutes of Health—the nation's medical research agency. I'm your host Joe Balintfy. Coming up in this episode, some reports on skin cancer: one on how the identification of a new gene may lead to personalized treatments; another on how a specific protein plays a role in tumor growth. We'll also have a story about the importance of clinical research in general. But first, new results on a combination of drugs for kidney dialysis patients. That's next on NIH Research Radio.
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Combination of Aspirin and an Anti-Clotting Drug Reduces Risk of Dialysis Access Failure
Balintfy: People with severe kidney disease, also known as kidney failure, need some form of kidney replacement therapy to survive.
Dr. Meyers: The most common form in the United States is hemodialysis.
Balintfy: Dr. Catherine Meyers is with the National Institute of Diabetes and Digestive and Kidney Diseases.
Dr. Meyers: And as its name implies, it is a procedure that requires access to blood vessels so that blood is actually removed from the patient, is then treated in a dialysis machine, and then returned through the blood vessels to the patient.
Balintfy: Dr. Meyers explains that there are different ways for physicians to set up what is called an “access” for hemodialysis.
Dr. Meyers: One is a temporary catheter, which is typically placed in one of the large vessels near the neck area. But catheters are considered temporary, because they can become infected or readily pulled out. There are also problems with clotting; they typically don't last that long—they need to be replaced—so it's considered what we call a temporary access. By in large, patients that are treated chronically with hemodialysis need either an AV fistula or an AV graft placed typically in the skin.
Balintfy: Artery-vein access grafts, or A-V grafts, fail most often due to narrowing of blood vessels at the graft site, and subsequent clotting, which block the flow of blood. A blocked graft cannot be used for dialysis and is a major cause of worsening health in dialysis patients.
Dr. Meyers: When the graft fails, it requires either an invasive radiology procedure to try to fix the graft, or patients need another surgery. And it's quite—it's a tremendous burden on patients when an access fails, because they are therefore committed to further invasive procedures and additional surgeries.
Balintfy: Now a new study has demonstrated that using a particular drug combination—in this case, dipyridamole and aspirin—extends the life of an AV graft once it's created. Dr. Meyers adds that it's a small increase in the lifespan; an 18 percent reduction in the risk that the graft would fail once the patient was started on the drug therapy.
Dr. Meyers: But it's an important step for physicians who care for these patients, because to date there have no other therapies available to try to extend the life of grafts. And in particular, we have a pretty good notion of how drugs like dipyridamole and aspirin work on the access. And certainly additional therapies that would target that particular pathway in a graft may provide new therapies that would have even larger impact on outcomes in grafts. So it's given us a large trial with a significant effect, although it's a modest effect, but it's still is the only therapy that we have demonstrated at this point, pharmacological therapy with the drug, that shown that we can help some of these outcomes, because the failure rate is just so high with AV grafts across the board.
Balintfy: The study, by the Dialysis Access Consortium, included a total of 649 participants with new AV grafts at 13 clinical sites in the United States. They were randomly assigned to treatment with the drug combination, or to a placebo. The trial took place over a five-year period. For more information on this study and kidney disease, visit www.niddk.nih.gov.
Skin Cancer Study May Pave Way for More Individualized Treatments
Balintfy: Now a couple reports on skin cancer or melanoma. A major cause of melanoma is thought to be overexposure to the sun. The ultraviolet radiation in sunlight can damage DNA and lead to cancer-causing genetic changes in skin cells. New genetic analysis of key group of enzymes may pave the way for more individualized treatments. Wally Akinso brings us the details this first report.
Akinso: Researchers from the National Institutes of Health have identified a gene that suppresses tumor growth in melanoma, the deadliest form of skin cancer. Dr. Yardena Samuels from the National Human Genome Research Institute's Cancer Genetics Branch explains how tumor suppressor genes work.
Dr. Samuels: Tumor suppressor genes encode proteins that normally serve as a brake on cell growth. And so when such genes are mutated or genetically altered the break maybe lifted resulting in the runaway of cell growth known as cancer.
Akinso: The NIH analysis found that one-quarter of human melanoma tumors had genetic changes in key enzymes.
Dr. Samuels: What we did was a genetic analysis of a group of enzymes called a matrix metalloproteinases or MMPs for short. These have been shown to be implicated in tumor growth in a variety of cancer types in the past. We systematically looked into these genes that encode enzymes and we found out that about a quarter of human melanoma tumors have changes or mutations in genes that code for these enzymes and importantly we found a tumor suppressor gene.
Akinso: Researchers have spent decades pursuing MMPs as promising targets for cancer therapies.
Dr. Samuels: Because members of this family were thought to be oncogenes meaning they activate growth and researchers have spent many years pursuing these enzymes as promising targets for cancer therapy—therapies that never worked. We are now showing that some of these are actually suppressing growth. And so drugs that would inhibit these MMPS are not expected to work if anything, they should fail and maybe speed up tumor growth. So this study may help explain the disappointing performance of some of these drugs used in clinical trials in the past.
Akinso: Dr. Samuels adds that the findings could lay the foundation for more individualized cancer treatment strategies where MMP and other key enzymes play a functional role in tumor growth and spread of the disease. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.
Researchers Identify a Potential Target that May Provide a New Way to Treat Melanoma
Balintfy: In this next report, we learn how a new study examines a protein and shows the important role it plays in inhibiting the development and spread of melanoma tumors in mice and human skin models. This protein, SOX9, may also increase the effectiveness of a treatment used on many other types of cancer. Bill Duval has the story.
Duval: New research conducted at that National Cancer Institute shows exciting promise for the treatment of melanoma. Dr. Vincent Hearing, a researcher at the Laboratory of Cell Biology and senior author of the study, talks about the research that his laboratory is working on.
Dr. Hearing: We've been identifying various factors that regulate skin pigmentation. And one of them that we found recently was this transcription factor called SOX9 and that was found in all melanocytes, normal melanocytes in human skin.
Duval: These melanocytes are the normal pigment cells that produce pigment in your skin, hair, and eyes. It's this melanin production that we actually see as color—whether it's skin, hair, or eye color. Melanoma cells, a form of cancer that starts in these melanocytes, has been difficult to treat thus far.
Dr. Hearing: They're very resistant to treatment with normal therapies, including retinoic acid. The reason that they're resistant to retinoic acid is because they normally produce large amounts of this factor known as PRAME, which is responsible for their resistance to retinoic acid.
Duval: But Dr. Hearing's recent findings suggest that the transcription factor, SOX9, may play an important role in treating melanomas with existing technology.
Dr. Hearing: The novel findings we have was that if we are able to increase the SOX9 expression it actually decreases PRAME and thus increases the sensitivity of melanoma cells to treatment with retinoic acid, which before now has been impossible. And we actually showed that this works in skin models and in mice so we're hoping that that can be extrapolated, would actually work in a clinical situation on human melanoma patients.
Duval: Thus, an increase in SOX9 decreases PRAME in melanoma cells, which makes them more susceptible to current treatments. Dr. Hearing adds that he and his colleagues are very optimistic about potential using this pathway for the treatment of melanomas. For more information on this study, visit www.cancer.gov/ncicancerbulletin. This is William Duval at the National Institutes of Health, Bethesda, Maryland.
Balintfy: These past reports, and much of what you hear in the NIH Research Radio podcast are about the importance of clinical research. Up next, some details and perspective on why.
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The Importance of Clinical Research
Balintfy: At a recent symposium, some of the nation's foremost leaders and influencers in the Health Care sector gathered to discuss the importance of clinical research. The purpose of the symposium was to generate discussion and action for patient-oriented clinical research in the United States among the constituents that are in the strongest positions to stimulate growth. The experts discussed how doctors and scientists use clinical research to help make important medical discoveries that improve people's health and save lives, and to investigate ways to prevent disease, as well as the causes, treatments, and even cures for common and rare diseases.
Tabak: Clinical research is the engine that creates new ways of treating patients and their diseases.
Balintfy: Dr. Lawrence Tabak is the Acting Deputy Director of the National Institutes of Health, and Director of the National Institute of Dental and Craniofacial Research. He says clinical research is a two way street and that without the support of the public and individuals who are willing to participate, there would be no clinical research.
Tabak: So we view this very much as a partnership one that's essential to ensure new diagnostics and new treatments for all sorts of diseases and conditions.
Drescher: I am a cancer survivor.
Balintfy: Fran Drescher is an accomplished actress and president of the Cancer Schmancer Movement.
Drescher: I am a survivor of uterine cancer. And unfortunately it took me two years and eight doctors to get a proper diagnosis of that.
Balintfy: Dresher stresses the importance of individuals making efforts to manage their own care, as well as sharing their voice to direct the clinical research that might benefit them. Dr. Tabak acknowledges the importance of growing public awareness.
Tabak: As the public at large becomes more aware of medical issues and becomes more empowered to deal with their own medical conditions and their own health, I see a growing awareness and as a result, an increased interest in finding out about clinical research and participating in it and of course these are very, very good trends.
Balintfy: Many important health and medical discoveries of the last century resulted from clinical research. Sabine Miller had a bowel transplant in July of 2005. She hopes continuous medical research will lead to even more spectacular improvements in the area of transplant surgery, immunosuppressant drugs, and the treatment of transplant rejection.
Miller: I want my doctors to have the knowledge and resources they need to continue to do this medical research and to be able to meet any challenges we may face in the future, be it myself or others in similar situations.
Balintfy: Clinical research in the medical field helps to better understand how the human body works and to gain insight into countless diseases and disorders, from rare and unusual ones to those more familiar like cancer and the common cold. In part because of clinical research, people are living longer and better. And clinical research continues to evolve.
Hayward: It's in a state of change.
Balintfy: Dr. Anthony Haward, Director of the Division for Clinical Research Resources at the NIH, explains that in the past, researchers focused on rare diseases.
Hayward: They had a very unusual situation that allowed them to study it and learn what the underlying mechanisms are. And from there we spread out much more to be concentrating on common disease like high blood pressure, diabetes, schizophrenia, many of these enormously expensive topics that are really very complicated to understand. So to match this change, we've had to change the way in which communities get together to conduct clinical research so that more patients with the underlying problem can be identified, and take part in clinical trials.
Balintfy: Drs. Hayward and Tabak also stress the need for new researchers to get involved, with clinical trials, as well as patients. Dr. Tabak advises that a way for clinical researchers to better understand what their work means, is through patients.
Tabak: And the best way to really understand what the value and impact of your research is, is by reaching out to patient groups and interacting with them. Just listening to their life stories really gives such a greater meaning of what you're doing at the bench, or translational work.
Balintfy: Again Sabine Miller:
Miller: I know that this medical research has saved my life, and that my wellbeing and my health will always depend on it.
Balintfy: The National Institutes of Health is the primary Federal agency for conducting and supporting medical research. The NIH annually invests roughly 30-billion dollars in medical research. More than 84% of the NIH's funding is awarded through almost 50,000 competitive grants to more than 325,000 researchers at over 3,000 universities, medical schools, and other research institutions in every state and around the world. To learn more about clinical research, visit the NIH homepage at www.nih.gov. To learn more about clinical trials, and participating in medical research, visit www.clinicaltrials.gov.
That's it for this episode of NIH Research Radio. Please join us again on Friday, June 12th when our next edition will be available for download. I'm your host, Joe Balintfy. Thanks for listening.
NIH Research Radio is a presentation of the NIH Radio News Service, part of the News Media Branch, Office of Communications and Public Liaison in the Office of the Director at the National Institutes of Health in Bethesda, Maryland, an agency of the US Department of Health and Human Services.