Newsletter of the Hubert H. Humphrey Cancer Research Center at Boston University School of Medicine

Hubert H. Humphrey Cancer Research Center of Boston University

Lupfer, Caroline H.

English

Boston University Institutional Repository (OpenBU)

Boston UniversityOpenBU http://open.bu.eduBU Publications The Humphrey Center Report / Humphrey Center News1988Humphrey Center News: Spring1988 v. 3, no. 1https://hdl.handle.net/2144/22162Boston UniversityA PUBLICATION OF THE HUBERT H. HUMPHREY CANCER RESEARCH CENTER OF BOSTON UNIVERSITY Volume 3, Number 1 Spring 1988 r Head and neck — cancer project yields encouraging results in prevention The Humphrey Cancer Research Center has long been known for work on understanding the basic mechanisms of cancer. Now, research being led by l^enter member Marianne Prout, M.D., an associate professor of public health, is opening up the evolving field of cancer-prevention research, or how to apply what is known about cancer so that the disease can be avoided. ' 'Applying what we know is a whole area of research that has been ignored, but it is really important," says Dr. Prout. Two years ago, the National Cancer Institute (NCI) announced that 50 percent of all cancer deaths could be avoided by the year 2000 and selected Dr. Prout to set up one of three demonstration projects in the country to show how this might be accomplished. Armed with the five-year NCI grant. Dr. Prout, a former chief of medical oncology at Boston City Hospital, and faculty from Boston University School of Public Health have created a model program using Boston's primary health-care network for the early detection and prevention of head and neck cancer. The demonstration project is timely in light of a four-year study of cancer rates in Massachusetts that revealed levels of head and neck cancer in Suffolk county, which includes Boston, to be about twice the national average. Dr. Prout, who directed the research on the Boston cases, attributes this to a higher incidence of smoking and continued on page 2 Marianne Prout, M.D., center, demonstrates head and neck cancer screening techniques to third-and fourth-year students at Boston University School of Medicine. (Photo by Gustav Freedman) Humphrey Cancer Center member moves closer to the truth about vitamin A and cancer As much as 35 percent of cancer is related to diet, studies show. Eating less fat and more fiber-containing foods, such as whole grain breads, fresh fruits and vegetables, can reduce your cancer risk—but how? To answer a part of this question, Humphrey Cancer Research Center member Richard Niles, Ph.D., is investigating the anti-tumor effects of one important dietary requirement— vitamin A. Dr. Niles and his colleagues have a number of experiments under way aimed at revealing how retinoic acid, the form vitamin A is converted to in the body, inhibits tumor growth and prompts a tumor's undifferentiated cells to retum to their normal functioning state. All the different cells that make up the body—hair, skin, bone, nerves, intemal organs, for example—originate from a few basic cell types during development in the womb. The process by which cells gain the specific characteristics that enable them to carry out the responsibilities of a liver cell or a lung cell is called differentiation. Tumors are like a reversion to the ancestral state—undifferentiated and consequently not functioning properly. A critical amount of vitamin A, then, is required for normal cell development. It also maintains cells, specifically epithelial cells, in their normal state of differentiation and, hence, normal functioning, explains Dr. Niles, who also is a professor of biochemistry at Boston University School of Medicine. Epithe-lial cells are those that line body cavities and carry out most of the functions of continued on page 2 2 HUMPHREY CENTER NEWS Vitamin A continued from page 1 various organs. Vitamin A, which we get by eating such vegetables as tomatoes, carrots and red peppers, keeps these cells in their proper state so that they can do their job. To understand how vitamin A works against tumors. Dr. Niles is looking at three cell-culture systems: • In a melanoma cell line, he is inves-tigating how retinoic acid inhibits cell growth and changes the activity of two key regulatory enzymes involved in growth and differentiation. • In a teratocarcinoma cell line derived from mouse testes, he is observing how retinoic acid plus another vital cell chemical transform the malignant cells into non-malignant cells that do not cause tumors when injected back into the mouse. • A third set of experiments involves normal cells derived from the respiratory tract of a hamster. When these epithelial Richard Niles, Ph.D., discusses his vitamin A research. (Photo by Michael McGovern) cells (the "hairy" and mucus-producing cells of the airway) are cultured, they tend to lose their differentiated characteristics and grow rapidly until they fill the culture dish. At that point, the cells reacquire their normal character. If retinoic acid is added at a time when the cells are rapidly growing (i.e., without differentiation), differentiation can largely be preserved. "This is important," says Dr. Niles, "because if you put animals on a vitamin A-deficient diet, you can observe the cells of the windpipe flatten out and lose their differentiated properties, which is characteristic of a pre-cancerous change. You can remove these cells from the animal and culture them with vitamin A and restore their normal shape and function." Dr. Niles also is developing a model to study carcinogenesis in normal epithelial cells. "About 75 percent of human cancers are derived from epithelial cells. Cancers of the breast, colon, prostate and lung all are epithelial in origin," he says. Cancer Prevention continued from page 1 drinking in the metropolitan area than in other areas of the Commonwealth. Other possible contributing factors are air pollution, exposure to asbestos and poor vitamin nutrition, she says. Although head and neck cancer carries a high mortality rate, these deaths can be significantly reduced if people at risk can be identified and screened early. Dr. Prout has established a city wide program to find out where patients who have advanced head and neck cancer have previously sought health care and to place early detection programs in those locations. ' 'We are trying to figure out where people already are going for their primary health-care needs and to place screening programs in those locations," says Dr. Prout. "Essentially, we're trying to make early detection a part of people's routine health care ." This type of front-line approach requires that primary health-care physicians, nurses and staff be educated about who is most at risk for developing head and neck cancer—^primarily people over the age of 40 who smoke and drink alcohol—and that they be given the skills necessary to do the screening directly at the clinic. Dr. Prout works closely with the staff to streamline the system so that follow-up is easy both for patients and health-care providers. " W e ' r e troubleshooters," she explains. ' 'We try to solve problems in a practical way—such as having joint luncheons to get staff from one area talking to staff from another, and having fixed appointment slots available for patients referred because of head and neck cancer screening so that it is easy for both staff and patients to make the next appointment. ' ' The cornerstone of the demonstration —project is the effic4enUand-effective use -of medical resources. "Obviously we can't screen everybody all the time for everything. Instead, we need to make sure that the providers parcel out their time and medical resources where they will do the most good," says Dr. Prout. "Eor example, we believe people who are most at risk for developing head and neck cancer are not being identified as well as they might be. Our providers are very careful about screening those patients who have been identified as smokers, but they only ask about half the people seen whether they smoke. At the same time, about two-thirds of non-smokers are being screened and it 's possible that this is an inefficient use of time and resources. What we're working on is how to get the right service to the right people quickly." Two years into the five-year project. Dr. Prout is enthusiastic about what she has seen in the neighborhood health centers in Boston. Her efforts to get early detection programs in place where they will do the most good are eagerly met by professionals who, she says, are ' 'tremendously idealistic. ' ' "These health-care providers want to do whatever they can to help patients. Most have seen the effects of advanced head and neck cancer and want to help patients avoid i t , " says Dr. Prout. Already during the first year of limited out-patient screening at one location, five early cancers have been detected. " F o e health-care providers who have seen the effects of radical therapy all of a sudden to see five people who can avoid this trauma is incredibly reinforcing," she says. While Dr. Prout is showing that much can be accomplished through the city's existing health-care system, she is using another grant from NCI to develop courses for Boston University School of Medicine and School of Public Health students and faculty to look at cancer prevention in its entirety. Dr. Prout hopes that cancer prevention measures eventually will be incorporated into routine health care, as has been done with heart disease. Ideally she wants everyone to hear the same message from their primary health-care provider: ' 'Most cancer can be avoided and here's what you can do to prevent i t ." 3 HUMPHREY CENTER NEWS Humphrey Center researcher seeks to build better monoclonal antibodies Under normal conditons, the human body can defend itself magnificently against the majority of diseases with the help of molecules called antibodies. Antibodies are specialized proteins produced as needed by certain cells to neutralize what the body views as "hos t i l e " foreign elements—called antigens—whether they stem from a common infection or from the emer-gence of a tumor. Sometimes, however, the body may not be able to raise its army of antibodies against a particular antigen, either because the immune system already is overtaxed or because the foreign invader somehow eludes the defense, as in the case of acquired immune deficiency syndrome (AIDS) or cancer. Even under normal conditions, not all antibodies attack and bind to antigens with 100-percent efficiency. For this reason, monoclonal anti-bodies, which are derived from natural antibodies obtained from a mouse or rat, represent one of the most hopeful ^ - - v developments in the treatment of disease, : especially cancer. As specially designed "magic bul le ts" that can seek out and bind to a specific target with great efficiency, monoclonal antibodies are being experimented with in both the diagnosis and treatment of various cancers. Yet, because no one fully understands what happens between antibodies and antigens at the molecular level, there is room for improvement in the design of new monoclonal antibodies. Since joining the Humphrey Cancer Research Center in 1985, Jacqueline Sharon, Ph.D., an assistant professor of pathology at Boston University School of Medicine, has been working on the problem of how to build a better monoclonal antibody. The clinical applications of her work may someday include the eradication of tumors and control of the rejection of transplanted organs. Produced in cultures in the laboratory, monoclonal antibodies are a pure strain of highly specific antibodies that react strongly and specifically with a particular antigen. But because r monoclonal antibodies are made by first raising the antibody of choice in a mouse and then fusing it with a tumor cell to produce a clone, there is a problem with rejection when the new antibody is introduced into another species, such as a human. To understand more about the fine details of the interactions between anti-bodies and antigens. Dr. Sharon introduces mutations into the gene responsible for producing an antibody and observes how the change affects the antibody's structure and, therefore, its ability to bind to the target antigen. She uses a laboratory technique that allows her to direct whatever changes she wants by making specific changes in the chemical composition of the gene. Dr. Sharon then measures the strength of the interaction between the antibody and the antigen. Her hope is to find out if there are certain positions in the anti-body sequence that are especially important to its binding ability. If so, it may be possible to manufacture an antibody with only those changes crucial to its most effective functioning, and then only this small active portion can be grafted onto the constant region of a human antibody molecule to minimize the possibility of rejection. (In all antibodies, it appears, there is a variable or active region that actually binds to an antigen, and a constant region that is not directly involved.) In her current studies. Dr. Sharon is looking at two antibodies that bind to the same antigen, but one has a binding efficiency 200 times greater than the other. A comparison of the antibodies' amino acid sequences has revealed eight differences in one area of the molecules. What Dr. Sharon wants to know is how many of these differences contribute to the stronger interaction. Possibly, she says, some differences are deleterious mutations, that is, they actually contribute to a lowering of the binding efficiency. However, it also is possible that some combination of changes in one antibody would yield an even higher binding efficiency but because of another mutation, this ability is kept to a lower level. " W e are investigating how many of these differences actually contribute to a higher binding efficiency by sequentially turning the sequence of antibody x into antibody y. At each stage we are looking at what is the effect of changing a particular amino acid ," says Dr. Sharon. Dr. Sharon is working with an experimental mouse- and rat-model system and is looking at the surface antigen on T-lymphocytes, a principal type of infection-fighting cell responsible for producing various types of antibodies. Jacqueline Sharon, Ph.D., at work in her laboratory. (Photo by Gustav Freedman) QUESTIONS... Answer to question on page 3. The question of whether non-smokers who must breathe the smoke of others' cigarettes incur a greater risk of lung cancer is of increasing controversy as cities and institutions struggle with the issue of banning smoking in public places. Several scientific studies, including a recent study by the American Cancer Society, have found an increased risk of lung cancer among nonsmoking wives of cigarette smokers. Although not all sudies have shown an effect, growing evidence indicates that "second-hand smoke" is a health hazard. Major reports by the National Academy of Sciences and the Surgeon General state that involuntary smoking is a problem, and a 1986 NAS report stated that the amount of smoke inhaled on airplane trips constitutes a hazard and recommended that cigarette smoking on airplanes be banned. An American Cancer Society Prevention study, currently under way involving more than one million Americans, will include a careful assessment of cancer risk among smokers and involuntary smokers. 4 HUMPHREY CENTER NEWS CANCER NOTES CANCER NOTE: For the average-risk woman, a Pap test for the detection of cervical cancer is recommended once every three years, although some physicians may recommend continuing annual check-ups. The Pap test is highly effective in detecting cancer of the cervix, but less effective in detecting uterine cancer. CANCER NOTE: With summertime approaching, now is a good time to remind people of the dangers of unprotected exposure to too much direct sunlight. Skin cancer can be successfully treated if it is detected early. Melanomas often start as small, molelike growths that increase in size, change color, and bleed easily from a slight injury. This simple ABCD rule will help individuals remember the warning signs of melanoma: A is for asymmetry—one half of the mole does not match the other. B is for border irregularity— edges are ragged or blurred. C is for color—the color of the mole is not uniform. D is for diameter—any sudden or continuing increase in size should be checked by a physician. The Humphrey Cancer Center News is published for the Hubert H. Humphrey Cancer Research Center of Boston University School of Medicine by the Office of Publication Services, Boston University Medical Center. Humphrey Center Director, Herbert H. Wotiz, Ph.D.; Editor, Denise Maguire; Writer, Caroline H. Lupfer. ' ' Cancer Notes ' ' information is provided courtesy of the American Cancer Society. What are the risks associated with 'second-hand smoke'? 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Humphrey Center News: Spring 1988 v. 3, no. 1

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Humphrey Center News: Spring 1988 v. 3, no. 1

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