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

Anthony, Richard P.

Hubert H. Humphrey Cancer Research Center of Boston University

English

Boston University Institutional Repository (OpenBU)

Boston UniversityOpenBU http://open.bu.eduBU Publications The Humphrey Center Report / Humphrey Center News1989Humphrey Center News: Fall 1989v. 4, no. 2https://hdl.handle.net/2144/22225Boston UniversityNEWS BERTH. HU Volume 4, Number 2 Fall 1989 Researchers explore why the effectiveness of the immune system declines with age Is it possible to bolster the immune systems of elderly individuals, and in so doing reduce the increased risks of cancer and other ailments that accompany old age? Members of the Hubert H. Humphrey Cancer Research Center are among scientists nationwide who are doing basic research into age-related immune changes that could help to answer that question. There's no doubt that the immune system's effectiveness declines with age, says Richard A. Miller, M.D., Ph.D., a Humphrey Center member and a professor of pathology at Boston University School of Medicine. The important white cells called T cells are a particular interest of Dr. Miller's. ("T" stands for thymus, and reflects the fact that these white cells become targeted to specific disease-causing agents in the thymus gland, which is located in the neck.) T-cell production undergoes a decline that actually begins in childhood, says the scientist. "The number of T cells that leave the thymus is highest in newborns and young children," he notes, "and by the time someone reaches young adulthood it has declined roughly tenfold." This decline, which apparently continues into old age, is only one of several age-related changes. The T-cell population in older individuals is much ^ more heavily weighted towards \" cells—^those that have already encountered the specific type of virus, bacteria, or diseased cell they're targeted to attack—than are the T cells in young Richard A. Miller, M.D., Ph.D., studies age-related changes in the immune system. (Photo by Bradford F. Herzog) people. Researchers have also shown that T cells in the elderly lose some capacity to secrete interleukin-2, a substance whose role is activating other white cells. One of Dr. Miller's main research goals is to pinpoint still other age-related changes by comparing cells from older rodents with cells from young animals. "We've found that the cells from older animals are less able to increase their calcium levels," he notes. "That's important, because calcium is required for all sorts of cellular activities." Such findings don't necessarily explain the fact that cancer is, for the most part, a disease of the elderly. Other considerations undoubtedly play a role, including the fact that many cancers can continued on page 2 Growing evidence suggests depression poses little if any risk of cancer If scientific studies often seem to be the source of disturbing news about cancer, such studies can sometimes produce reassuring results, too. That's the case with a series of recent studies focusing on whether individuals with symptoms of depression face a higher cancer risk than those who aren't depressed. The latest of these epidemiological studies, carried out by a group of scientists at the National Institute on Aging in Baltimore, involved checking cancer patterns among more than 6,400 individuals across the nation who were first tested for signs of depression in the 1970s. According to Bernard H. Fox, Ph.D., a member of the Hubert H. Humphrey Cancer Research Center and a professor of psychiatry at Boston University School of Medicine, the researchers found that the depressed individuals had no greater risk of cancer than those without symptoms of depression. That finding, combined with those of other studies, largely puts to rest the idea that depression is a significant risk factor for cancer, says Dr. Fox. "It's likely that the relationship between depressive symptoms and later cancer is at best weak, and may indeed be non-existent," says Dr. Fox, an expert on the connections between mental states and cancer. continued on page 3 2 H U M P H R E Y C E N T E R NEWS Steven H. Zeisel, M.D., PhD., discusses the role of diet in the formation of nitrosamines. (Photo by Bradford F. Herzog) . .^...^....-^-^^^ ^^ Humphrey Center group is exploring how cancer-causing nitrosamines are formed Immune System continued from page 1 grow for years before they begin causing symptoms. Still, the evidence that the immune system is involved in controlling cancer is quite convincing, says Dr. Miller. "There's a reasonable likelihood that at least some forms of malignant tumors are sought out and destroyed in the early stages by the immune system," he says. Even as scientists continue seeking to understand the nature of the immune system's role in attacking tumors, the first efforts are being made to strengthen the immune system's ability to combat advanced cancers. Dr. Miller notes that physicians at several medical centers are exploring whether interleukin-2, in combination with white cells, can shrink or eliminate tumors. Yet even if such efforts yield encouraging results, it could still be some time before scientists feel they know enough about the immune system to try enhancing the system's effectiveness in older individuals as a shield against cancer and other diseases. Nevertheless, says the researcher, the idea is increasingly viewed as a realistic prospect. One approach, he says, would be to find ways to boost the levels of interleukin-2 and other immune-system agents in elderly populations. As a prelude to such a strategy, says the researcher, scientists are working to overcome interleukin-2's natural tendency to break down in the bloodstream. "An equally promising approach," says Dr. Miller, "is to learn enough about how the immune system produces good, functioning immune cells to allow us to stimulate the system in an elderly person to produce more of these cells. I think it's likely that something along these lines will be ready in a decade or two." A decade or so ago, sodium nitrite was the focus of intense news media attention. The coverage was the result of findings that the substance, used as a preservative in bacon, hot dogs and other products, is a precursor for powerful cancer-causing agents. Once consumed, scientists reported, the nitrite part of the compound bonds with other chemicals in the body to form substances called nitrosamines. And these, research suggested, can cause many different kinds of cancer. Though the publicity has long since subsided, the concern is still very much alive, says Steven H. Zeisel, M.D., Ph.D., a Hubert H. Humphrey Cancer Research Center member and an ^sociate professor of pathology and pediatrics at Boston University School of Medicine. "Nobody in the field would question that nitrosamines are among the most potent carcinogens known," he says. Animal experiments show that even in small doses, nitrosamines can trigger cancer. In humans, the impact of the substances is less clear-cut, mainly because it's unethical to do experiments that involve giving people potentially dangerous agents. Still, says Dr. Zeisel, there's strong evidence that the nitrosamines in tobacco smoke are a major cause of oral cancer, and there is strong suspicion that the substances play a role in many other types of cancer as well. Though the situation might seem to point to a need for a ban on sodium nitrite, such a move isn't practical right now, says Dr. Zeisel. "We don't have good alternatives," he says, "and given a choice between the long-term risk of cancer and the immediate threat of botulism, public-health people have decided we've got to keep using these preservatives." Another strategy, though, is to look for ways to slow the formation of nitrosamines in the body. Dr. Zeisel and his associates are doing research that could help reveal whether such a strategy makes sense. His group is focusing on the "-amines" part of nitrosamines. Specifically, they're trying to find out how the body makes these substances, known T technically as methylamines. One source of methylamine is choline, a substance present in many foods. Methylamine emerges in the intestines when bacteria that are harbored there break down the choline we consume. It would be very tough to cut down on choline consumption, says Dr. Zeisel, and it wouldn't make sense in any case. "We have to consume a certain amount of choline," says the scientist. "Our bodies need it to form cell membranes and to make the neurotransmitter, acetylcholine." A more direct source of methylamine, though, is fish. Indeed, says Dr. Zeisel, it's these substances that give fish their distinctive odor. The scientist and his associates have discovered that when we consume fish, it can markedly raise our continued on next page 3 H U M P H R E Y CENTER NEWS Nitrosamines continued from previous page /ody levels of methylamines. "We fed five volunteers a diet that was very high in fish," notes the scientist, "and compared methylamine levels in their urine to the levels when they were on a non-fish diet. The increase resulting from the fish was quite dramatic." Such findings don't mean consumers should start cutting down on fish, particularly in light of the recent discovery that certain oils in fish may help protect against heart attacks. On the other hand, says the scientist, the findings do suggest the need to explore the body's systems for handling nitrite, its close cousin nitrate, and methylamine. "If most of our exposure to methylamine comes from internal processes," says the scientist, "then changing the amount of fish we eat wouldn't matter much. On the other hand, if it should turn out that fish or other components of the diet are a major source of these substances, we might have to think about dietary changes." One of his group's goals is to explore whether the liver is a major producer of ^nethylamines, since determining that ould help resolve the issue of how ifiuch diet matters. Until more is understood about this process, though. Dr. Zeisel says that simple prudence dictates keeping our consumption of foods that may boost the formation of nitrosamines at moderate levels. That applies to fish, he says, and it also applies to foods preserved with sodium nitrite. "The extra exposure you get from eating something like a hot dog or a piece of bacon probably isn't that great," he says, "but if you eat significant amounts of those foods every day, you might be substantially increasing your exposure." Depression continued from page 1 Yet the scientist, who wrote an accompanying commentary for the journal that carried the results of the latest study, says that while the cumulative weight of scientific evidence points to a lack of any cancer-depression link, the issue isn't closed. Some anomalies in the studies leave open the possibility there's a modest connection of some type, says Dr. Fox. For example, says the scientist, it's possible that individuals with signs of depression are at an increased risk of cancer, but that the increase is so slight it can't be readily measured by the kinds of studies done to date. "Another possibility," he says, "is that there may be subgroups with a particular susceptibility to depression-associated cancers." Dr. Fox, while emphasizing that there's no evidence as yet to support either theory, says that there is evidence that depression can alter the immune system. The evidence, he says, comes from studies of patients with depression severe enough to require hospitalization. "Severe depression," says the scientist, "is known to bring about an increase in the hormones called corticosteroids in about half the patients affected." The rise in hormones, he adds, suppresses the activity of certain types of disease-fighting white cells. According to Dr. Fox, something^ similar could be affecting a smaller proportion of individuals who are less severely depressed, though presumably the hormonal increases in such individuals—and therefore the effects on their white cells—would not be as great. Even if some mildly depressed people do have impaired immune systems, though, the scientist notes that there's little direct evidence linking the suppression of subgroups of white cells to cancer in humans. One of the few signs of such a link, he adds, is the fact that AIDS patients, in whom certain types of white cells become diseased, are prone to a rare form of cancer known as Kaposi's sarcoma. Dr. Fox emphasizes that, given the tenuous nature of the evidence for any kind of a depression-cancer link, the principal need at this point is for additional research into the matter. Meanwhile, he says, depression-prone individuals needn't concern themselves with the possibility that their mental state may be increasing their cancer risks. "If there is a link between depressive symptoms and cancer in some individuals, it's probably a weak one," notes Dr. Fox, "so my advice to people is that they just not worry about it." QUESTIONS... Answer to question on back panel. A • The rates of two types of cancer have dropped markedly over recent decades. One is stomach cancer. The other is uterine cancer, which includes cancer of the cervix and cancer of the uterus. The American Cancer Society estimates that uterine cancer will claim about 10,000 lives this year, which represents a drop of 70 percent over four decades. Stomach cancer will claim about 13,000 lives, representing a fall-off of similar magnitude. In the case of uterine cancer, the main reason for the drop-off is the Pap test, in which a sample taken from the mucous membrane of the cervix can reveal early signs of cancer. Scientists don't know what accounts for the progress against stomach cancer, but suspect that one factor may be an increased consumption of frozen as opposed to canned foods. What is an oncogene? A • An oncogene is a normal gene that has been altered in one way or another so that it no longer works normally. Some oncogenes, for example, have undergone changes in structure. Others appear in excessive quantities in cells. More than 50 oncogenes have been identified so far. Not all of these have been linked to human cancer, however. In most instances, the versions of the oncogenes identified have been those found in viruses or in animal tumors, not in human tumors. Scientists believe that the normal versions of most oncogenes are involved in cell growth or differentiation. When the genes are altered or multiplied, it sets the stage for uncontrolled growth. Scientists have also found, though, that it usually takes at least two oncogenes to make a cell cancerous. And still further steps may be needed to enable a tumor to mature and begin spreading to new sites in the body. Scientists hope that identifying oncogenes will eventually lead to new strategies for controlling malignant growth. 4 H U M P H R E Y C E N T E R NEWS CANCER NOTES CANCER NOTE: Cancer of the pancreas is one of the most lethal forms of the disease. Patients with this cancer, which claims an estimated 25,000 lives annually, have only about a 4-percent five-year survival rate, compared to a 13-percent rate for those with lung cancer. Scientists are working hard to develop more effective treatments for pancreatic cancer. CANCER NOTE: Physicians are increasingly trying combined forms of therapy in treating cancer. In one such combination, tumors are treated with heat, which weakens the cells, before the application of radiation or drugs. CANCER NOTE: Vitamin C is thought to prevent the forming of nitrosamines. which are potent cancer-causing agents. (See article on page 2). There's no evidence, however, that massive doses of the vitamin protect against cancer. The American Cancer Society recommends including ample amounts of vitamin C in the diet by consuming foods like citrus fruit, but advises against taking large quantities of vitamin C supplements. CANCER NOTE: The treatment of testicular cancer is a major success story. It's estimated that more than 90 percent of the 5,700 Americans expected to be afflicted by that form of cancer in 1989 will survive at least five years. That compares to just over 60 percent 20 years ago. New diagnostic techniques and therapies are the main reason for the improved outlook. CANCER NOTE: The main factor that increases a woman's risk of ovarian cancer is advancing age. Most women who contract the disease are 65 or older. Women who haven't had children are at a somewhat higher risk for the disease than mothers, and women who have taken birth-control pills seem to hold a slight advantage over those who haven' t. 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, Michael Rabin; Writer, Richard P. Anthony. "Cancer Notes" information is provided courtesy of the — American Cancer Society. Humphrey Center member Nadia Rosenthal, Ph.D., right, an assistant professor of biochemistry, recently received a grant from Aid for Cancer Research (ACR) to support her research in the regulation of gene expression in animal muscle cells. With the grant. Dr. Rosenthal was able to purchase a laminar flow hood. Shown here with Dr. Rosenthal are ACR presentation chairperson Barbara Goodman-Oray and Herbert Wotiz, Ph.D., director of the Humphrey Center. (Photo by David Keough, BUSM Educational Media Support Center) What types of cancer have declined most? ANSWER ON PAGE 3 

Humphrey Center News: Fall 1989 v. 4, no. 2

https://open.bu.edu/bitstream/2144/22225/1/HumphreyCenterNews1989v4n2.pdf

Humphrey Center News: Fall 1989 v. 4, no. 2

Abstract

Similar works

Full text

Available Versions

Boston University Institutional Repository (OpenBU)