© 1998 by Oxford University Press
A cup of tea provides an antioxidant boost that may protect against several types of cancers, but so far the link has been reliably shown only in tea-sipping rodents and test tubes -- not in people. The antioxidants in green and black tea, called catechins, are "more potent than vitamins C and E" in their ability to scavenge potentially carcinogenic compounds called free radicals, said Catherine Rice-Evans, Ph.D., of the Antioxidant Research Centre in London.
However, Rice-Evans and other tea experts cautioned that despite promising early research, better animal models and more robust epidemiological studies are needed before tea research steams toward human trials. A decade may pass before enough clinical evidence accumulates to validate or refute tea's anti-cancer potential.
"The in vitro and animal data [are] very strong," said Jeffrey Blumberg, Ph.D., who researches tea antioxidants at Tufts University in Boston. "But clinical trials are the definitive approach."
Even without much clinical evidence, the 300 tea-swilling scientists and industry representatives who gathered at the Second International Symposium on Tea & Human Health, held in Washington in September, were steeped in news from a dozen promising studies.
Most of this research focused on the basic chemistry and biology of catechins. Among the results: Tea contains more antioxidants than do most fruits and vegetables; downing a single cup of green or black tea boosts total bloodstream antioxidant activity; and steeping tea for just 5 minutes releases 80% of its catechins.
Two studies showed catechins inhibit tumor growth in rats and mice, especially in lung-cancer-prone strains dosed with nicotine-derived carcinogens. A third rodent and dog project established catechins are not toxic, even at high doses.
Study Pitfalls
Despite all this promising work, some epidemiological data comparing tea drinkers and non-tea drinkers does not support the claim that tea prevents cancer. One study even found tea drinkers have higher cancer rates than non-tea drinkers; two others showed no tea effects. Difficulties sorting out possible confounding factors, such as other diet and health-related habits, may continue to hinder scientists searching for anti-cancer effects from tea, according to a spokesman from The Lipton Tea Co., Ltd., London.
Another pitfall -- not understanding the compounds under study -- derailed a 9-week, 24-subject, Lipton-sponsored study. While looking for tea's effects on colon cancer markers, Blumberg's team from Tufts did not take into account catechins' relatively speedy metabolism. Blumberg admitted that the team tested their subjects too infrequently, thus botching any chance of detecting tea's short-term effects. In defense of the null results, Blumberg added that finding modest protective effects, like those expected from tea, is tricky, even with large study populations.
A more promising early human study, this one from Beijing Dental Hospital, won robust applause from the tea-ed up audience as well as extensive media attention. The 6-month double-blind trial found 3 grams of tea (enough for about 2 cups) plus a topical tea extract reduces the size and proliferation of leukoplakia, precancerous oral plaque. Study leader Junshi Chen, M.D., said these results "provide some direct evidence of the protective effects of tea on cancer," but that larger, longer-term studies are needed.
-- Brian Vastag
For BRCA1, the noisiest problem has been where the BRCA1 protein is located in the cell. While most researchers have found the protein in the nucleus of normal cells, some have found evidence of the protein in the cytoplasm of malignant cells, and one group has reported that BRCA1 is present in the cell membrane and in the secretory apparatus. However, in a paper recently submitted to Nature Genetics, Cindy Wilson, Ph.D., from the Division of Hematology Oncology at the University of California, Los Angeles, appears to have settled whatever ambiguity remains.
"It's in the nucleus," said Wilson. "All the antibodies that are specific show distinctive nuclear dot patterns in cells." She compared 20 antibodies from several groups using many tests -- western blotting, immunoprecipitation, immunohistochemistry, and cytochemistry on individual cells. Because BRCA1 protein is expressed at very low levels in the nucleus, very clean antibodies are required to see it.
Besides cellular location, another clue to function comes from discovering the proteins that interact with BRCA1. To date, the list has grown quite large, including several enzymes (e.g., helicase, RNA polymerase, and ubiquitin hydrolase) as well as other proteins (e.g., Rad51, p53, BARD1, and CTIP). So far, no clear consensus has emerged about which proteins are important to BRCA1's function.
Adding to the murky picture, is the inability of researchers to produce mice lacking two copies of functional BRCA1 genes, so-called knock-out mice, which frequently provide insights into the function of the missing gene. Mouse embryos lacking BRCA1 protein do not survive.
Given these problems, a paper in the Aug. 14 Science was a first -- the first direct functional evidence for BRCA1. Researchers from the Department of Radiation Oncology, University of North Carolina at Chapel Hill, showed that cells deficient in BRCA1 were unable to repair DNA that was damaged by either ionizing radiation (gamma radiation) or hydrogen peroxide. The particular kind of repair that is defective in these cells is called transcription-coupled repair (TCR) -- involving machinery that tags along with RNA polymerase and repairs actively transcribing genes.
"Our results make sense with the data that show an association between BRCA1 and RNA polymerase," said Lori Gowen, a UNC graduate student and the paper's first author. "And it is consistent with BRCA1 being a tumor suppressor gene -- mutations will accumulate if the gene is involved in repair. But it still doesn't allow us to say whether BRCA1 is a part of the repair machinery or a transcription factor that regulates transcription of genes involved in TCR."
And that seems to be precisely the problem -- developing a good system for analyzing BRCA1, either in mice or in human cancer cells. The gene's enormous size suggests that the BRCA1 protein is likely to have several functions, probably involving DNA repair, transcriptional regulation of genes, or others.
Ralph Scully, M.D., Ph.D., a researcher in David Livingston's lab at the Dana-Farber Cancer Institute, Harvard Medical School, Boston, who discovered that BRCA1 associates with Rad51, believes the only way to make progress is to develop a good genetic system.
"We need a tractable genetic system to test out key hypotheses in the field. For example, we need to be able to add back normal BRCA1 to cells lacking functional BRCA1 and show that a specific defect can be reversed," he said.
-- Nancy J. Nelson
Tens of thousands of cancer survivors, researchers, caregivers, clinicians, and relatives and friends of patients and those lost to cancer marched in Washington in late September to demand that the United States government make the defeat of this disease its number one health-care priority.
Organizers of The March -- "Coming Together to Conquer Cancer," estimated the total crowd on the Mall at about 150,000, based on the number of programs and water bottles distributed throughout the day. Participants came in pink T-shirts for breast cancer, teal-blue T-shirts for ovarian cancer, T-shirts created for The March, and T-shirts bearing the photos and names of relatives who had died of cancer. They carried placards, such as ones that said, "Families Fighting Prostate Cancer."
Some marchers wore baseball caps to hide heads with no hair from chemotherapy, while others went bald or showed scalps covered with the fuzz of new hair growing back. Some marchers used canes. Dan and Karen Graham of Castro Valley, Calif., came for their son Billy, who died of melanoma at age 22; they have established the Billy Foundation for melanoma education in his honor.
Cancer survivor Morgan O'Brien, 7, of Columbia, Md., came because she wants a future. "When I grow up I want to be a teacher and never have leukemia again," she said.
The March -- whose chanted slogan was "no more cancer" -- was the brainstorm of Ellen Stovall, executive director of the National Coalition for Cancer Survivorship and a 26-year cancer survivor. The March first became real in the public consciousness when talk-show host Larry King announced it on his CNN TV show in April 1997.
Stovall said, "What we have done in preparing the ground for The March is to open up new possibilities for the survivorship movement. Cancer is our national crisis. No more silence, no more cancer. We are the faces of cancer survivorship. We are real and we aren't going away."
Sidney Kimmel, chairman of the Jones Apparel Group, Inc., and chairman of The March, added, "The March is a historic event . . . a turning point for our nation. The people have come to demand of their government: no more cancer."
The March was endorsed by nearly 600 organizations, including the American Cancer Society, the American Society of Clinical Oncology, the American Association for Cancer Research, and the American Public Health Association. While The March was taking place, communities across the country held their own related events for people who were too sick to travel or could not come to Washington for other reasons.
Candles in the Night
The March began on Friday night, Sept. 25, when marchers and invited speakers gathered for an emotional candlelight vigil and interfaith service at the Lincoln Memorial. While marchers carried small lighted candles (actually flame-tipped white flashlights), participants on stage lighted real yellow candles designed by NCCS as a symbol of hope in memory of loved ones.
Participants in the candlelight vigil included the Rev. Jesse Jackson; Olympic figure skating gold medalist Scott Hamilton, a survivor of testicular cancer; breast cancer survivor Susan Shinagawa, of the Association of Asian Pacific Community Health Organizations in San Diego, Calif.; Dorothy I. Height, president emerita of the National Council of Negro Women; breast cancer survivor Rabbi Julie Spitzer of New York, N.Y.; Pat Spinetta, chairman of the Candlelighters Childhood Cancer Foundation; and prostate cancer survivor Gen. H. Norman Schwarzkopf, honorary chairman of The March.
Stovall said she intends to make the candlelight vigil an annual event.
Setting the tone for the next day's event, speakers at the candlelight vigil urged all present to work for unity in the fight to conquer cancer. "In a real sense, the civil rights movement taught us a lot," said Height. "We cannot afford to divide ourselves now on who is suffering the most."
Shinagawa added, "Inclusion is the solution," and said she is determined to change the stereotypical view that Asians don't get cancer. "Include all, leave no one behind," said Jackson, who led those at the vigil in a chant of "Pain to power, pain to power."
Mall of Hope
On Saturday, part of the Mall was transformed into a sea of tents and booths to provide information on cancer. The AACR offered a roster of medical and research professionals to discuss cancer research, while super-model Cindy Crawford, who lost her brother to leukemia 22 years ago, took part in the unveiling of the Children's Cancer Quilt, whose handmade squares honor victims and survivors of childhood cancer. "My mother made a square for my brother Jeff," she said.
At the No More Cancer Rally held on the Mall, speakers set a tone of hope. Vice President Al Gore drew cheers when he shed his coat and tie in the hot sun and announced, "This marks high noon for cancer," a reference to the classic showdown western film "High Noon."
Gore said, "We want to be the generation that ends the war on cancer." He urged participants to envision a day when America is cancer-free, when an immunization against cancer will be as routine as a polio shot. He said he can remember coming to Washington and being profoundly moved by the Vietnam Memorial, which has granite walls with the names of the war's dead veterans. "If we were going to honor all the people who have died of cancer, we'd have to build 10 of those Vietnam walls every year," he said.
Gore said he and President Clinton support the largest increase in cancer research funding ever proposed -- 65% over 5 years. He also said the administration wants more public involvement in cancer research, and said that by next spring the National Cancer Institute will have in place steps to ensure that the public has a "full voice" at every step of the way in the process of research funding. A recent Institute of Medicine report commended the NCI Director's Consumer Liaison Group for increasing the public's role in biomedical research.
The vice president also issued a challenge to the scientific community: develop new diagnostic techniques for every kind of cancer by the year 2000, so that all cancers can be caught at their earliest and most treatable stages. "When we crack the code, we win the war," said Gore, echoing the military metaphors used by Schwarzkopf and other speakers throughout the day.
Gore also urged researchers to streamline the enrollment process for clinical trials and greatly increase clinical trial participation -- just 3% of people with cancer participate in clinical trials today. He asked support for an administration proposal that would fund a 3-year demonstration project in which Medicare would pay for the patient care costs of cancer clinical trials.
"Mr. Vice President, we will accept the challenges you gave us today," said NCI Director Richard Klausner, M.D. "We can do what Jesse Jackson said last night, and turn pain into power. . . . This is not a sprint, and we will not tire."
-- Peggy Eastman
Tea Therapy? Out of the Cup, Into the Lab
Finding BRCA1's Function: A More Arduous Journey
Thousands March on Washington, D.C., to Increase Cancer Research Funding
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