|Interview with Dr. Louis Staudt, NCI|
Bill Schmalfeldt: From the National Institutes of Health in Bethesda, Maryland, this is NIH Research Radio.
Welcome to Episode 25 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, Bill Schmalfeldt. Coming up on this edition, I'll wander over to the Clinical Research Center to visit with Doctor Louis Staudt, Chief of the Lymphoid Malignancy Section, Metabolism Branch, with the Center for Cancer Research at the National Cancer Institute. He's going to explain why we need to know more about genomic profiling. Wally Akinso has a report on an NCI study that shows an improvement in survival of adults with an uncommon form of leukemia.
February 7th was National Black HIV/AIDS Awareness and Information Day. We'll hear from Doctor Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases. Wally has a story about a new and improved Web site offered by the National Institute of Nursing Research. We'll talk about a new study that shows that women who take folic acid supplements early in their pregnancy can substantially reduce their baby's chances of being born with a facial cleft. And which imaging technology does a better job of diagnosing acute ischemic stroke: MRI or CT. But first, Wally tells us about the creation of the Working Group on Women in Biomedical Careers, designed to help women fulfill their potential as scientists and engineers. That's next on NIH Research Radio.
Want to know more about the important cancer research going on at the National Cancer Institute? Would you like to hear from the experts and ask questions? Then take part in NCI's toll-free teleconference series. All you need is a phone, there's no registration and it's free. Coming up Tuesday, February 20th from one to two P.M. Eastern, the topic will be the importance of the NCI bypass budget and strategic plan for patient advocates, featuring Ms. Sherri Nichols, Director of the Office of Science Planning and Assessment at the NCI. Call 800-857-6584. The passcode is the word, "budget." For more information about the toll free teleconference series, call the NCI Office of Liaison Activities at 301-594-3194 or visit ola.cancer.gov. The NCI toll-free teleconference series. Once again that telephone number, 800-857-6584. The passcode is the word, "budget."
The NIH is leading an effort to help women achieve their full potential in medicine and science. Wally Akinso has this report:
Wally Akinso: The director of the National Institutes of Health, Doctor Elios Zerhouni has announced the creation of the Working Group on Women in Biomedical Careers, designed to help women fulfill their potential as scientists and engineers. Doctor Vivian Pinn, Director of the Office of Research on Women's Health and Co-Chair of the working group, said there are a number of issues to overcome, but the group is ready to tackle the issues head-on by developing innovative strategies and tangible actions to promote the advancement of women in research careers both within the NIH intramural community and throughout the extramural research community.
Dr. Vivian Pinm: There are a number of obstacles that have been identified for girls and women to think about entering biomedical careers or advancing in biomedical careers and we have dealt with a number of these over the years. Looking at the fact that we still see disparities in rewards, and by rewards I mean salaries for men and women at the same level of achievement or at the same faculty level or in the same position. In terms of promotions, it has been documented that very often, men and women starting at the same time, perhaps with the same credentials and with the same abilities, do not seem to be promoted at the same rank. We hope these factors are changing, but we see those continuing.
We see another factor, and that is the fact that so many women are involved in their dual responsibilities and have more family responsibilities. They have to be the family person, they have to be the mother, unfortunately with all of our science, we haven't yet learned how to have men have the babies, so we're still having women carrying most of the childcare and family care responsibilities, even though I'm pleased to say men are participating more in this. And at the same time, we're seeing more women enter into scientific career positions. So that dual responsibility that so many women have to face can not only affect their success, but probably has a major impact on their advancement in their careers, especially within the area of academia where also there is a limited time that men and women have to gain promotion or to become tenured faculty.
Wally Akinso: The barriers that women face in hiring and promotion at research universities in many fields are identified in a recent National Academies report "Beyond Advice and Barriers, Fulfilling the Potential of Women in Science and Engineering". The report, funded by the ORWH, called for an urgent broad national effort to maximize the potential of women scientists and engineers in academia. Doctor Pinn talked about how this may help a young woman who has an interest in science.
Dr. Vivian Pinm: To any young girl who's interested in pursuing science, I would say hang in there, do it, it's so exciting. Just to imagine having an opportunity to be involved in a career where you may discover some truth about healing lives or about living or even about the world, about our ecology, about science in general that's never been found before is an excitement that is just hard to dream about, but can be just so stimulating, really can just make you feel so good. If you decide to go into a career in medicine, or dentistry, or pharmacy, or nursing that I hope that they will consider research, because research is so important to furthering the science. But as speaking for myself, I can't think of any career opportunity that could provide a more exciting and stimulating life as well as really make you feel that you're making a contribution to humankind than being in science.
Wally Akinso: For more information about the NIH Working Group on Women in Biomedical Careers, visit http://orwh.od.nih.gov. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.
Bill Schmalfeldt: February 7th marks the seventh annual observance of National Black HIV/AIDS Awareness and Information Day. Although African-Americans account for only 13 percent of the U.S. population, in 2005, they represented about 50 percent of new HIV/AIDS diagnoses. Doctor Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases called that figure startling and suggested some reasons for such a disproportionate rate of infection in the African-American community.
Dr. Anthony Fauci: It is not a just a uni-dimensional phenomenon. There are multiple reasons that go into it, ranging from, for example, being in the wrong place at the wrong time. For example, to be living in certain regions in the areas where there's a high degree of injection drug use; where there's a high level of sexually transmitted diseases; where you have a density of HIV infected so that the chances of an African-American man or woman coming into contact with an HIV infected individual in the milieu in which they live is far greater than if you were a white middle class person in Iowa or something like that. When you talk about inner city areas; drug use, it self-propagates.
Bill Schmalfeldt: Doctor Fauci pointed to another reason why some African-American males may be hesitant to get tested or seek treatment.
Dr. Anthony Fauci: Gay men in the black community are not as open about their gayness or are they accepted in their own society, being gay, as opposed to a white population in which they're well organized, they're open about it; they counsel each other; they help each other. It is a greater stigma, in some respects, in the African-American community. It makes the prevention measures really much more difficult to deliver.
Bill Schmalfeldt: The Centers for Disease Control and Prevention estimates that more than 211,000 African-American men and women with AIDS have died since the epidemic began. According to the NIAID, advances in research over the years have had a positive effect. Recent studies indicate that at least three million years of life have been saved in the U.S. since the advent of combination anti-retroviral therapy in the mid 1990s. Doctor Fauci said events like National Black HIV/AIDS Awareness and Information Day have a part to play in getting out the word and encouraging African-Americans to participate not only in their own healthcare, but to take part in the research effort in whatever way possible, as scientists, clinicians, community educators, advocates and study volunteers. The key, he said, is awareness.
Dr. Anthony Fauci: Well, what we want to do is to raise awareness among the community and to spur on leaders in the community to outreach to the African-American community and to encourage them, for example, to get tested. This past year, the CDC has modified significantly their guidelines to make testing a part of routine medical care because, you know, of the million people HIV infected in this country, 25 percent of them don't know they're infected. And if you don't know whether you're infected, you can't get counseling about treatment for yourself or about how you can avoid infecting others. So we really need to be much more transparent, much more open.
Bill Schmalfeldt: You can find more information about National Black HIV/AIDS Awareness and Information Day online at www.blackaidsday.org. Information about prevention, treatment, and vaccine clinical trials can be found at www.aidsinfo.nih.gov.
When we come back, I'll travel the winding halls of the Clinical Research Center and try to locate the office of Doctor Louis M. Staudt to get the lowdown on genomic profiling and why this is something you need to know about at. That's straight ahead on NIH Research Radio.
Aristotle had this problem, so did Thomas Jefferson. And they went on to do great things. If you stutter, you can do something great too, by participating in a National Institutes of Health Stuttering study. Participants will be compensated, travel assistance is available, and all study-related tests are provided at no cost. Call 866-999-5553 or visit clinicaltrials.gov. Do something great. The NIH is a nonprofit government agency of the Department of Health and Human Services.
Bill Schmalfeldt: It took me a while to get here: every time I come to the Clinical Center here at the Campus of the National Institutes of Health, I find myself lost in the wandering, labyrinth-type hallways. And after the third set of directions, I finally found my way to the office of Doctor Louis M. Staudt. He's the Chief of the Lymphoid Malignancy Section of the Metabolism Branch at the Center for Cancer Research of the National Cancer Institute. And the reason we're sitting down today is to discuss the concept and the applications of genomic profiling. Now if you're listening to the Podcast, obviously you're interested in science on a layman's level or even as a professional. But for a layman such as myself, as soon as I hear the words, "genomic profiling," my eyes glaze over a little bit and it feels to me like somebody's going to be talking about something and I have no idea what they're talking about. Could you give us a quick layman one-on-one discussion on what we mean by genomic profiling?
Dr. Louis Staudt: Sure. Well, as a consequence of the completion of the human genome project, we've been blessed with the knowledge of 20 to 30,000 genes encoded in our DNA. And the basic idea is that every cell in our body has that same DNA, those same 20 to 30,000 genes. And they're instructions for how a cell works, but why is it then, that a brain cell is different from a white blood cell? It's quite simply that the brain cell chooses a different subset of the 20,000 genes to create its unique properties to be able to signal and make memories and the like. Whereas the white blood cells chooses a different set of those genes and they're, including genes and coding, antibodies that are used to fight off infections. So because we have such a diversity of cells in the body, we use, we make subsets of the genes active. And gene expression profiling is a technology that allows us to determine which subset of the genome is active in a given cell type at a given time.
Bill Schmalfeldt: Well, in the treatment of diseases, how can genomic profiling be turned into a very important tool?
Dr. Louis Staudt: We were struck by the fact that cancer was a very heterogeneous disease and that although we are able to cure some individuals with cancer, others unfortunately succumb to the disease. And so, an early idea that we had was whether the -- by profiling the activity of genes in cancer biopsy samples from individual patients, could we discover why it was that one cancer is curable and the other not. And that turns out to be case.
So in our particular work, we've looked at lymphomas, cancers of the B-lymphocyte. In particular, the most common type of B-cell lymphoma is called diffuse large B-cell lymphoma. It's a very aggressive disease, but fortunately can be cured with combination chemotherapy these days. But approximately 50 percent of individuals with this disease are cured and the other 50 percent, not. So by collecting biopsy samples from hundreds of patients with diffuse large B-cell lymphoma, we then looked at the activity of genes in those samples by gene expression profiling. And were easily able to discern two major subgroups within the diffuse large B-cell lymphomas. And then when we looked at the clinical response of those patients to chemotherapy, we found one subgroup had a much more favorable response to chemotherapy and the other subgroup had a cancer that was much more difficult to cure.
Bill Schmalfeldt: So if I'm understanding this then, by looking at the blueprint of the gene, you're better able to answer some of the questions as to why a cell acts in a certain way, and that helps in the treatment of such a disease as lymphoma.
Dr. Louis Staudt: That's right. In essence, the wiring diagrams inside the cancer cells of one patient will be different than the cancer cells in another patient. And the gene expression patterns that we see are sort of the outcome of that different wiring and also create the different wiring within the cancer cell. So it is in fact, as you put it, a blueprint for differences in the wiring diagrams of cancer cells.
Bill Schmalfeldt: Now, do you envision a day, as this science progresses, that a person will go in to -- for a regular visit, to a doctor, and have his blood drawn, give a urine sample, and maybe submit some tissue for genomic profiling?
Dr. Louis Staudt: So we're working to that end very vigorously. So my view is that, within five years, most cancer types will be diagnosed with this so-called molecular diagnosis. So currently cancer is diagnosed by the appearance the tumor, by the appearance of the cells within the tumor under the microscope. But this is not a quantitative method and in many cases, may lend itself to incorrect diagnoses, whereas the gene expression profiling being quantitative, being highly reproducible, has the potential to transform the diagnosis of cancer. So we and other groups are working to make designer DNA microarrays that could be used for the diagnosis of cancer. And so the sample of tissue taken from the cancer would be plopped onto, in a test tube and frozen on dry ice and sent off to a reference laboratory, which would perform the gene expression profiling on this designer microarray. And the diagnosis, calculated mathematically, in fact, would be delivered back to the physician, who would then relay that to the patient and determine the course of treatment.
Bill Schmalfeldt: Maybe I'm talking science fiction here, somewhere down the road, but is there a day in the future, foreseeable, where a person can undergo genomic profiling and be identified as having a particular risk for a certain kind of cancer?
Dr. Louis Staudt: So that's a definite possibility, certain genes predisposed to certain types of cancer. And in fact, we do that on a gene-by-gene basis now in certain cancer families, or patients with families that are at risk for, let's say, colon cancer or breast cancer. More broadly though, we're now able to look at variation in genes across the genome. This is a little different than I was talking to you about before, though. This is not necessarily the expression of the genes, but also their function. And in the human population, they're very many different forms, if you will, of the same genes, slight variants. And these are caused by single changes in the DNA sequence in the same gene in different individuals. And that indeed could be used in the future to assess one's risk for not just cancer, but many different types of disease.
Bill Schmalfeldt: What are some of the big, unanswered questions at this point?
Dr. Louis Staudt: The unanswered questions are how we can go towards finding better cures, based on this knowledge. They're not completely unanswered, because we have -- we're approaching that question so we use other aspects of the human genome to find out which are the critical pathways that a cancer cell depends on for its overabundant proliferation and its inappropriate survival as a cell. And we have methods by which we can inactivate single genes within the cancer cell and ask what happens. So we can find which genes are so critical for the survival of cancer that they could be called the Achilles heel of the cancer cell. And of course, if one could attack the protein products of those genes with a drug, then that might be a successful new way to cure the cancer.
Bill Schmalfeldt: And the voyage of discovery goes on here at the National Institutes of Health. Doctor Louis M. Staudt, Chief of the Lymphoid Malignancy Section, Metabolism Branch, Center for Cancer Research here at the National Cancer Institute. Thanks for spending some time with us today on NIH Research Radio.
Dr. Louis Staudt: It's been a pleasure.
Bill Schmalfeldt: Another institute at the NIH has come up with a new, improved, user-friendly Web site. Wally Akinso has the report.
Wally Akinso: Want to find out how nursing research is working to improve the health of the nation? Access to information about this vital area of science and the programs of the National Institute of Nursing Research just got easier with the launch of their improved Web site, www.ninr.nih.gov. Doctor Patricia A. Grady, NINR Director, said the Web site will be a valuable research to anyone who visits, from the general public to nursing professionals and the entire science community.
Dr. Patricia Grady: The new Web site that we have is user friendly. It has a great deal more information, it is interactive. For example, for one of our large communities, the extramural community, it has a course that's online that they can take that will help them to develop into nurse scientists, so those who are scientists, or who want to be, can learn a great deal from that course. It even has continuing education credits.
Wally Akinso: A new feature gives visitors access to NINR Podcasts, to prerecorded audio and video presentations, and meetings that can be viewed or listened to on the computer or a portable media player. Dr. Grady says the NINR recognizes the importance of providing up-to-date information on nursing science and scientific finding in an easily accessible and comprehensive format.
Dr. Patricia Grady: The Web site also has accessibility to all of the funded programs that we have. So I think there's a lot of information for people who might be interested in science as a career, as to what's going on, what's happening, et cetera. There are also a number of opportunities on campus in the intramural program, as well as across the country, that they will become familiar with by using the Web site.
Wally Akinso: Dr. Grady says she's excited about the revitalized Web site and urges the public and future scientists to check it out.
Dr. Patricia Grady: You should visit it soon and visit it often. People who visit it once always come back.
Wally Akinso: Once again, the improved Web site is www.ninr.nih.gov. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.
Bill Schmalfeldt: A new study finds that women who take folic acid supplements early in their pregnancy can substantially reduce their baby's chances of being born with a facial cleft. Researchers at the National Institute of Environmental Health Sciences found that 0.4 milligrams a day of folic acid reduced by one third the baby's risk of isolated cleft lip, with or without cleft palate. Doctor Alan J. Wilcox, lead NIEHS author on the new study, published online in the British Medical Journal, said the reasons for this finding remains something of a mystery.
Dr. Alan Wilcox: It's an interesting question, the biological mechanism that's going on here is not clear. We know that folic acid has an essential role in the body's manufacture of DNA, which of course is the molecule that makes up our genes. And so we can't survive without folic acid, but exactly how that mechanism works in the embryonic growth to create the cleft lip and palate, at this point, we don't know.
Bill Schmalfeldt: Researchers examined the association between facial clefts and mothers intake of folic acid supplements, multivitamins, and folates in diet. The researchers found that folic acid supplementation of 400 micrograms or more per day reduced the risk of isolate cleft lip, with or without cleft palate, by one third, but had no apparent affect on the risk of cleft palate alone. Doctor Wilcox said the time for women who are thinking about having a baby to start taking folic acid is now.
Alan Wilcox: Well, I think one of the really important things for women to realize is that if they wait until they know that they're pregnant to start taking these vitamins, including folic acid, that it may be too late. It may be after the early embryo has already formed or not formed these essential structures that create the neural tube or the face. And so it's very important for women who might be pregnant or who are planning to get pregnant to start taking folic acid before they conceive. And that way they can be absolutely sure that they will be protected during the crucial time that the embryo is forming.
Bill Schmalfeldt: Folic acid is a B vitamin found in leafy vegetables, citrus fruits, beans and whole grains. It can also be taken as a vitamin supplement and as added to flour and other fortified foods. For more information on this study, visit www.niehs.nih.gov.
When we come back, Wally Akinso will fill us in on some exciting news in the field of leukemia research. That's next on NIH Research Radio.
Maybe you've heard of tai chi, an ancient form of Chinese exercise. The National Institutes of Health is conducting a clinical research study to see if tai chi improves physical fitness and well being for cancer survivors in the Washington, D.C. Metro area. If that's you and you're between the ages of 18 and 60 and your last treatment was two or more years ago, call 866-999-1116 or log on to clinicaltrials.gov. The NIH is a nonprofit government agency, part of the Department of Health and Human Services.
It's an uncommon form of leukemia. And now an institute at the NIH finds a new treatment increases the chances of survival for patients stricken with the disease. Wally Akinso has the story.
Wally Akinso: Results of a National Cancer Institute study show an improvement in survival of adults with an uncommon form of leukemia. According to the study, adult patients with previously untreated acute promyelocytic leukemia, known as APL, who had standard chemotherapy to induce remission of their disease and then received the chemotherapy drug arsenic trioxide to maintain remission had a better overall survival rate than those who received only standard therapy. Doctor Tony Murgo, head of the NCI's Early Clinical Trials Development Division of Cancer Treatment and Diagnosis said this positive outcome demonstrates the benefits of clinical trials and will hopefully serve as encouragement for others to join such trials.
Dr. Anthony Murgo: Arsenic trioxide is already FDA approved for the treatment of APL, but only in patients after failure of standard therapy. The results of this trial are a remarkable demonstration of the beneficial effects of arsenic trioxide combined with standard therapy in the treatment of newly diagnosed patients with APL.
Wally Akinso: APL accounts for approximately 1,500 cases per year in the United States. It is most often diagnosed in young and middle-aged adults, but it also occurs in children and older adults. Standard chemotherapy regiments produce complete remission rates of approximately 70 percent and show a five-year survival without the recurrence of disease in 35 to 45 percent of patients. Doctor Murgo said these results indicate that arsenic trioxide should be considered as a part of the initial treatment of patients with APL. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.
Bill Schmalfeldt: Which imaging technique does a better job at diagnosing an acute stroke? CT or MRI? That's the question researchers at the National Institute of Neurological Disorders and Stroke sought to answer when they compared the two technologies side to side. And when it came to giving a more sensitive diagnosis for acute ischemic stroke, that's the kind of stroke caused by a blocked blood vessel, the winner was the MRI. The study showed non-contrast MRI is about five times more sensitive than, and twice as accurate as, immediate, non-contrast CT for diagnosing ischemic stroke. Here's Doctor Steven Warach, Director of the NINDS Stroke Diagnostics and Therapeutic Section, Senior Investigator of the study.
Dr. Steven Warach: What our study did is, it really looked at the real world experience. We took a consecutive series of patients, a large number, 356, who came to the hospital emergency room with a diagnosis of possible stroke. And this is how it happens in the real world: you don't know before the patient comes to the emergency department, whether they really have or not. The first encounter is not with a stroke specialist but with an emergency physician. And at most hospitals, there is not a stroke center or a stroke team, so you have non-specialists all the way up and down looking at the patient. And so then we said, if we do the same scans on everybody, a non-contrast CT and a diffusion weighted MRI and then have four independent experts review, which scan will reveal the stroke and then what proportions will the scans reveal the stroke?
Bill Schmalfeldt: Study leaders hope that because of its increased diagnostic accuracy, MRI may lead to better patient outcomes and ultimately decrease the cost of stroke care through increased use of acute treatments and earlier initiation of secondary prevention.
Dr. Steven Warach: That won't happen overnight, but I do anticipate that over time, this will replace CT as the routine screen for question stroke. One reason it won't happen overnight is most hospitals are geared up to do the emergency CT and even hospitals that have the MRI, their radiology department schedule and all that, they've not historically made that available, and so it's going to have to take some change in hospital policies and hospital routines for that to happen.
Bill Schmalfeldt: The findings appear in the January 27th, 2007 edition of The Lancet.
And with that, we come to the end of this episode of NIH Research Radio. Please join us on Friday, February 23, when Episode 26 of NIH Research Radio will be available for download. These stories are also available on the NIH Radio News Service Web site, www.nih.gov/news/radio/index.htm. Our daily 60-second feature, NIH Health Matters is heard on nearly 1000 radio stations nationwide, as well on XM Satellite Radio and the HealthStar Radio Network.
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