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8 cancerLines Spring 2001 caolfe nedvaernts J U N E 9th Susan G. Komen Breast Cancer Foundation NC Triangle Race for the Cure. Raleigh, NC. S E P T E M B E R 20th Pink Ribbons Project Dancers in Motion Against Breast Cancer Performance/ Benefit. Carolina Theatre, Durham, NC. O C T O B E R 5th Board of Visitors Meeting. Lineberger Cancer Center, Chapel Hill, NC. 13th Patient/Family Symposium. Friday Center, Chapel Hill, NC. UNC Lineberger Comprehensive Cancer Center CB# 7295 School of Medicine University of North Carolina at Chapel Hill Chapel Hill, NC 27599-7295 (919) 966-3036 http://cancer.med.unc.edu Return Forwarding, and Return Postage Guaranteed. Address Correction Requested. Nonprofit Organization U.S. Postage PAID Permit No. 71 Chapel Hill, NC 27599-1110 Like Columbuses of latter day We chart the genome’s DNA We splice, we snip, we recombine On risks of cancer, boldly opine Perhaps with the Tarheel basketball team We could tweak a chromosome or splice a gene To make a eugenic team of dreams Coached by a young clone of Dean’s But genetics has its darker side For if the wrong experiment’s tried We might end up with a player or two Who bleeds a deeper shade of blue... As his patron, Michelangelo Had the Medicis long ago And backing Walter Raleigh’s team Was fair Elizabeth, England’s Queen Vasco de Gama had the King of Portugal But we lucked out ...We have you all The future of medicine, pundits say Lies within our DNA But without you our noble mission Would be forlorn, an empty vision So, from gene and cell and chromosome, We wish to make our thanks well known, We sing your praises on this special day, From the bottom of our DNA Dr. Jim Evans and his “Ode of a Geneticist” Dr. Jim Evans, associate pro-fessor of medicine and leader of the Lineberger Cancer Genetics program, spoke at the Lineberger Club meeting. He ended his talk with a poem he wrote for the occasion: LU N C L i n ecb e r g e ria C o mnpnr e h e n seicv e C aesn c e r Cre n t e r University of North Carolina School of Medicine & UNC Hospitals Spring 2001 “Physicians have been using X-rays to detect breast cancer for years,” notes Etta Pisano, professor of radi-ology and director of breast imaging at the UNC Lineberger Comprehensive Cancer Center. Studies have shown that between 80 and 90 percent of malig-nancies are visible on mammography. “It would be foolish to supplant a technology that’s known to reduce breast cancer mortality.” But Pisano and her colleagues are working with a technology that might further reduce mortality and potentially improve the early diagnosis of breast cancer—digital mammography. Current technology misses some 15,000 to 45,000 breast cancers in the more than 32.5 million mam-mograms performed annually in the United States. Prior studies and early clinical experience have shown that digital mammography offers better visibility, particularly near the skin line and the chest wall, and in dense breast tissue. The digital mammography machine used at UNC, in addition to easier detection and better imaging, can reduce exam time by half that of traditional film-based mam-mograms. Improved images also may eliminate many of the call-backs necessary with traditional mammography. That’s important because approximately one in eight the inside line up ... 5 4 6 Head & Neck Cancer and Clinical Trials Profile: Terry Van Dyke & Briefs 2Director’s Message Lineberger Scrapbook continued on page 3 continued on page 2 8“Ode of a Geneticist” and Calendar of Events American women will develop breast cancer in her lifetime. With more than 180,000 cases diagnosed each year, it’s the second most common cancer in women after skin cancer and the leading cause of cancer death among women 40 to 55. According to the American Cancer Society, the 5-year survival rate after treatment for localized breast cancer is Colon Cancer Screening: Not As “Accepted��� By Public, But Vital and Effective “All adults over age 50 are at sufficient risk for colorectal cancer to warrant screening,” says Michael Pignone, Assistant Professor of Medicine in the Division of General Internal Medicine.“While some groups are at higher risk because of a family history of colorectal cancer or the presence of in-flammatory bowel disease, the absence of a high-risk condi-tion does not mean that one is at low or no risk.” According to the American Cancer Society, an estimated 47,700 people died of colon cancer in 2000, the third most common cancer in men and women. When detected in an early, localized stage, the 5-year relative survival rate is 90 per-cent; however, only 37 percent of colorectal cancers are dis-covered at that stage. Early detection is critical. After the cancer has spread to adjacent organs or lymph nodes, the rate drops to 65 percent or to 8 percent in patients with distant metastases. Despite that, only 25-35 percent of adults have had a screening test recently for colorectal cancer. “The low rates of screening are a consequence of poor communication,” Pignone notes. More Effective Mammography: Is Digital the Answer? Dr. Etta Pisano views a digital mammogram. “Many patients do not realize they are at risk and many providers do not routinely offer screening to patients over age 50.” And many people don’t have access to regular, affordable health care, so they don’t have the opportunity to be screened. “Another reason may be apathy,” adds David Ransohoff, professor of medicine, Lineberger member and an epide-miologist. “For reasons we don’t fully understand, colorectal cancer screening is much less popular, or ‘accepted,’ by the public than, say, screening for prostate cancer, or mam-mography for women 40-49, even though the evidence is strong that colorectal cancer screening reduces mortality and has very few side-effects.” For all these reasons, researchers at UNC are engaged in a number of initiatives to increase screening for colorectal cancers and improve prevention.“This is a point of emphasis for North Carolina and its advisory committee on cancer control and coordination,” says Dr. Joseph Pagano, Director Emeritus and chair of the state committee. cancer cell. Dr. Dell Yarbrough is doing just that with a new therapy for head and neck cancers. He is using a cold virus to deliver therapy that will only be amplified in cells carrying a mutated protein, the kind found in certain can-cers. Modifications in this delivery approach are being developed in Dr. Yarbrough’s lab for a second generation of clinical trials. We’re teaming up with the new UNC Genomics program led by Dr. Terry Magnuson and will tell you more about this new Carolina initiative in the next issue of Cancer Lines. In the meantime, enjoy a wonderful summer: please remember to wear sun-screen.• At UNC, Pignone and others developed and tested a video-based decision aid for patients that informs them about the options for screening and helps them discuss screening with their doctors. The study, one of the largest trials ever done on the effectiveness of decision aids in real clinical practices, found that the video increased screening rates significantly. The test was so successful they are developing a similar program for the Web that they plan to test next year. Additionally, the Internal Medicine clinic has instituted a reminder system for patients under-going fecal occult blood testing. The system has increased return rates by 10-15 percent over baseline. Research shows that five simple activities can lower the risk of colon cancer by as much as 70 percent, according to Robert Sandler, professor of medicine and co-director of UNC-CH’s Center for Gastrointestinal Biology and Disease and Linberger member. To reduce colorectal cancer people should: Avoid obesity Engage in regular physical activity 2 cancerLines Spring 2001 Colon Cancer continued from page 1 Limit alcohol consumption and don’t smoke Eat a sensible diet high in vegetables and fruit and low in red meat Consider using supplements of calcium and folic acid Taking calcium or folic acid supplements can reduce polyps from which it’s estimated 90 per-cent or more of colon cancers evolve. In a 1999 national study, Sandler and his colleagues found that calcium supplements moderately reduce the risk of recurring polyp growth in the colon and may reduce the risk of colon cancer. Researchers found overall a 24 percent decrease in the number of polyps and a 19 percent decrease in the risk of polyp recurrence. Approximately 20 epidemiologic studies have found that people who regularly use aspirin and other non-steroidal anti-inflam-matory drugs have 40 to 50 per-cent lower risk of colorectal cancer and adenomatous polyps. However, no randomized trials have yet proven that aspirin-like drugs cause this reduction. Two studies, funded by the National Cancer Institute, are underway at UNC to determine the link. Sandler and others also are working on a population-based study to determine the impact of risk factors, access to health care and insurance and poverty on colon cancer mortality rates; and a study on diet and its effect on the colon’s lining. Approaching colon cancer prevention and screening from several disciplines results in more comprehensive research and clinical treatment. “Multidisciplinary collaboration is important be-cause it unites people with different types of exper-tise to work together to solve a problem. To best tackle colon cancer screening and prevention, we need expertise in psychology, health education/ behavior change, epidemiology, physician learning, gastroenterology, information sciences and oncol-ogy,” Pignone concludes. “Lineberger helps us do that.”• MeDsisreactgor’es What do a digi-tal camera and the Trojan horse have in com-mon? They’re both prototypes for new technol-ogy to help make cancer diagnostic tests and therapies more precise. UNC Lineber-ger is a leader in meeting this challenge. To make one of the tests that diag-nose breast cancer more precise, Dr. Etta Pisano is pioneering a promising new technology called digital imaging. This process uses a computer image of the breast rather than a film x-ray. The new technology is the same as that used for digital cameras. This advance means potentially better images and in-formation. For patients it means less radiation since additional views aren’t necessary: the image captured by the computer can be manipulated and re-examined by the radiologist. To answer definitively whether digital imaging is superior to film x-ray at de-tecting breast abnormalities, Dr. Pisano will lead a 19-center three-year study funded by the National Cancer Institute involving 49,500 women. The $27 mil-lion grant is the largest ever awarded to a radiologist. In related news, Dell Computer and Microsoft have made a gift of 100 high-end computers and software to be used in parallel computation by Dr. Julian Rosenman in his quest to obtain faster and more accurate 3-dimensional images of a particular tumor. This will allow precise focusing of multiple radiation beams converging on the tumor while sparing normal tissue. Julian’s and Etta’s work are both results of the highly successful collaborations with UNC’s internationally renowned computer science department. Such collaboration and teamwork are the hallmarks of a multidisciplinary cancer program at a great university. On another front, ideal cancer therapy targets tumor cells while spar-ing healthy ones. But how do you sneak the therapy into cells but only have it attack the cancer cells? Pack the therapy in a genetically altered cold virus—a Trojan Horse—that can multiply in a Dr. Shelton Earp UNC Lineberger is designated a comprehensive cancer center by the National Cancer Institute. Cancer Lines is a semi-annual publication of the UNC Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine at Chapel Hill. Dr. H. Shelton Earp, III, Director Dr. Joseph S.Pagano, Director Emeritus Dianne G. Shaw, Director of Communications/Executive Editor Margot Carmichael Lester, Editor Please remove me from your mailing list Name Please add the following to the Cancer Center’s mailing list. Name Address City, State, Zip UNC Lineberger Comprehensive Cancer Center CB# 7295 School of Medicine University of North Carolina at Chapel Hill Chapel Hill, NC 27599-7295 (919) 966-3036 http://cancer.med.unc.edu Printed on Recycled Paper (Left to right) Drs. Michael Pignone, David Ransohoff and Robert Sandler. cancerLines Spring 2001 7 Scrapbook Seed Grant Recipients. UNC Lineberger Seed Grant recipients were honored at a recent Board of Visitors meeting. (Left to right) back row: Dr. David Ollila; Dr. Jozef Spychala; Dr. Shelton Earp, Center director; Dr. Beverly Mitchell, Center associate director; front: Dr. Carol Shores; Dr. Valerie Murrah and Dr. Bill Funkhouser. The grants support new and growing UNC-CH research projects in innovative areas. The grant program helps launch smaller projects that could lead to more in-depth studies in the future. The grants were made possible by: the Schechter Foundation, the Brody Brothers Foundation and the Felix Harvey Foundation, all of Kinston; the Foundation for the Carolinas of Charlotte; the A.E. Finley Foundation Inc. of Raleigh; the Cemala Foundation Inc. and the Hillsdale Fund Inc., both of Greensboro. Lineberger Fellows. Six Lineberger fellows were honored for demon-strated excellence in research. The Board of Visitors began the program in 1987 to promote and encourage graduate students to pursue cancer research. The fellowships are made possible by Best Distributing Company in Goldsboro; the Cancer Resesearch Foundation of America in Arlington, VA; and Mr. and Mrs. Sanford Doxey, Jr. of Wilmington. Pictured (left to right): Helena Furberg–public health science, preceptor Dr. Robert Millikan; Jennifer David Peck–public health science, preceptor Dr. Barbara Hulka; Nathan Felix–laboratory science, pre-ceptor Dr. Jenny Ting; Susan Steck-Stoff–public health science, preceptor Lenore Arab; Wolfgang Resch–laboratory science, preceptor Dr. Ron Swanstrom; and Betty P. Liu–laboratory science, preceptor Dr. Keith Burridge. Larry and Sarah Tomlinson of Charlotte are not your ordinary Carolina couple. Like many alumni, they were both born and raised within a few miles of Chapel Hill and have parents, siblings, and now children, who attended UNC. While at UNC Mr. Tomlinson played on the tennis team and was a member of the SAE fraternity, and he is a member of Carolina Living Legends. The Tomlinsons have been lifelong supporters of the place that is so near to their hearts, but their roots here at the Univer-sity run much deeper. Mrs. Tomlinson’s grand-father was Dr. Francis P. Venable, chemistry profes-sor and then president of the University from 1900 to 1914, who was instrumental in laying the solid foundation on which UNC has built its scientific research programs. Mr. and Mrs. Tomlinson have been very active supporters of UNC for many years. However, it was not until Mr. Tomlinson’s brother, Carroll, was diagnosed with prostate cancer in 1983 that they were introduced to the Lineberger Comprehensive Cancer Center. In1985, after Carroll Tomlinson lost his life to cancer, the Tomlinsons joined the Cen-ter’s Board of Visitors and the fight against this disease. The Tomlinsons’ most recent gift will benefit UNC’s scientific community. Their generous gift to the University is a charitable remainder trust, which has funded the Larry and Sarah Tomlinson Lab in the Lineberger Comprehensive Cancer Center. The Lab will be home to Dr. Terry Van Dyke and her team of 20 scientists. Dr. Van Dyke is director of the Animal Models Core here at UNC and is co-chair of the National Cancer Institute’s Mouse Models of Human Cancer Consortium. One of the main projects in her lab is the development of mouse models that produce human cancers, such as breast and prostate cancer, and lymphoma. The Tomlinson Lab is the result of one of many different kinds of planned gifts. Gifts to Lineberger can be made in forms from property to stocks, retirement plan assets to trusts. Although dona-tions of outright gifts such as cash and property are fairly simple, the benefits of making gifts such as annuities and trusts can be attractive options. Depending on which type of planned gift one chooses, tax benefits can be immediately realized or they are delayed to benefit one’s heirs. Gifts can be designed so that income payments from an investment benefit Lineberger while ownership of the asset is retained (a charitable lead trust), or so that the property is transferred to Lineberger but a beneficiary receives a predetermined income pay-ment from the trust, as is the case with the Tomlin-sons’ charitable remainder trust. The array of gift planning opportunities available does cover a wide assortment of options. For more information on planned gifts for Lineberger, please call the Development Office at (919) 966-5905 to request information. Though the benefits are dif-ferent for the various types of planned gifts, the one constant is the benefit of helping the clinicians and scientists at Lineberger work toward a cure for this disease that touches all our lives.• Tomlinson Lab Continues Tradition “When you start your lab, you have to be very focused, like a horse with blinders,” she recalls. “About the time I got tenure is when I took a deep breath and asked myself ‘now what do I want to do?’ There weren’t many people at Pittsburgh at that time doing what I was interested in, so my hus-band ( Jude Samulski, director of the UNC Gene Therapy Center) and I started looking around and were attracted to the intellectual climate at UNC. We’ve been here about seven and a half years now.” Van Dyke continues to pursue her love of fig-uring things out through her research in cancer cell biology. “As a researcher, the thing that’s fascinating about cancer is that it’s not a single disease, but hundreds of diseases and it takes different things for different cells to become a cancer,” she explains. “What we’d like to understand is exactly what goes wrong in the cells so that people who do drug design can actually develop ways to inhibit the cancers.” Currently, Van Dyke and her team are devel-oping a therapy by genetically manipulating mice. “You can do in the mouse pretty much what you can do in a test tube,” she says.“You can go in and alter a specific gene and say ‘what happens if I make this alteration?’ Things you see happening in human cells you can mimic in the mouse and ask ‘does it really lead to cancer?’” The problem with cancer research in humans is that scientists study the disease after the fact and cannot establish cause and effect relationships. 4 cancerLines Spring 2001 Study offers new evidence that garlic protects against cancers A new study at UNC by Lenore Arab and col-leagues shows that people who consume raw or cooked garlic regularly face about half the risk of stomach cancer and two thirds the risk of colorectal cancer as people who eat little or none. Their study was a meta-analysis, a mathematical combination of numerous other studies to develop a clearer picture of such issues as cancer and heart disease. The group reviewed 300 scientific papers related to diet and cancer and then combined and analyzed data from 22 describing the best, most relevant human research related to garlic from around the world. Previous research has shown that a compound in garlic called allium partially protects animals against cancer, and some scientists believe it has the same effect in humans. “After controlling for various risk-factors, we found that when we pooled the results, this preventive effect was largely con-firmed,” says Lenore Arab, professor of epidemi-ology and nutrition at the UNC-CH schools of public health and medicine and Linebeger mem-ber. “We didn’t have enough information to be able to say the same about garlic’s possible effects on other forms of cancer.” Researchers could not show similar benefits from taking garlic supplements, possibly because the active ingredients are destroyed by processing or by sitting on store shelves for a long time. “Many scientists believe garlic helps prevent stomach cancer because it has anti-bacterial effects against a bacterium, Helicobacter pylori, found in the stomach and known to promote cancer there,” Arab says. Study shows why muscle decays mysteriously in cancer, AIDS and other illnesses Scientists at UNC-CH’s Lineberger Comprehen-sive Cancer Center believe they have discovered a major reason why muscles often decay in patients with cancer, AIDS, late-stage heart disease, severe burns and numerous chronic diseases. Their re-search focuses on cachexia, an important syn-drome that could lead to an effective treatment for the condition. The new study shows that cachexia, which kills an estimated one third of cancer patients, results from activation of a factor, NF-kappa B. This natur-al substance attaches to DNA inside cell nuclei and turns genes on and off like a switch. In this instance it prevents expression of a key regulatory protein called MyoD from replenishing muscle tissue as it does in healthy people. “Cancer cachexia, which causes patients to literally waste away, has been documented for at least 100 years, but it wasn’t until about 20 years ago that researchers discovered a cytokine protein called tumor necrosis factor and that the factor could elicit cachexia,” notes postdoctoral fellow Denis Guttridge.“What we have done is to identify a key part of what’s happening mechanistically inside muscle cells to cause cachexia.” “Since we now know how to inhibit NF-kappa B, this will lead to therapies for reducing cachexia, which may well lead to significant improvement in the quality of life of patients who have chronic diseases like cancer and AIDS,” Guttridge says. Studies plumb tumor resistance to treatment Cancer tumors with cells low in oxygen often survive and continue to grow despite the treat-ments thrown at them. Mahesh Varia, professor of radiation oncology at UNC-CH and a Lineberger member, has developed a method of identifying these hypoxic tumors which may lead to a greater understanding of treatment resistance and help doctors more effectively predict the outcome of cancer therapies. James Raleigh, professor of radiation oncology and Lineberger member, invented the one clinically advanced method, the pimonidazole hypoxia marker, that identifies tumor hypoxia at the cellular level. “We spent a number of years proving it in the laboratory and with animals in a veterinary setting Profile Briefs Trailblazer in Mouse Model Research Terry Van Dyke didn’t always want to be a cancer researcher. “When I was 5, I decided I wanted to be a nurse,” recalls the professor of Biochemistry and Biophysics at UNC. “But in my spare time, I wanted to be a cowgirl. My mom says that kids from the neighborhood used to come around our house and ask for ‘Dale.’ I had told everyone my name was Dale Evans!” Encouraged by an inspirational biology teacher in 10th grade, Van Dyke let go of her nursing and cowgirl aspirations and decided to pursue mole-cular biology.“Asking questions and getting answers through experimentation has always been fasci-nating to me,” she says. “I’ve always loved trying to figure things out.” Van Dyke received her BS and PhD in molecular biology from the University of Florida. She did her post doc work at the University of New York at Stony Brook with Arnold J. Levine and then followed Levine to Princeton. In 1986, she got the opportunity to run her own laboratory at the Uni-versity of Pittsburgh—where she stayed for 7 years and earned tenure. “That’s why our mouse model studies are so cool,” Van Dyke says. “The technologies have developed tremendously over the last 20 years and it’s just exhilarating the different kinds of things we can do.” As a professor, wife and the mother of two teen-agers, she admits she doesn’t have a lot of spare time. “But I do enjoy playing tennis, reading, and the occasional artsy-craftsy project.” Van Dyke is also currently co-chairing a national consortium funded by the NCI and has been very involved in trying to build the field of genetics at UNC. “I guess you could say my days are pretty jam-packed!”• continued on page 6 metastasis in head and neck cancer,” Yarbrough says.“The advantage of sentinel node biopsy, if it proves to be accurate, would be that by removing only one or a few lymph nodes from the neck we would be able to accurately determine if the neck needs further treatment. This would allow us to avoid the unwanted side effects associated with treating patients without neck disease.” The team also is evaluating a molecular method of determining if a head and neck cancer has spread to neck nodes.“The theoretical advantage is that the molecular technique (RT-PCR) should be more accurate and less costly than standard pathologic examination,” Yarbrough says. Last year, the team discovered that CAT scanning can be used to determine if surgery will be necessary after chemotherapy and radiation therapy. The Head and Neck Program includes physi-cians, researchers and staff from the Departments of Otolaryngology/Head and Neck Surgery, Radia-tion Oncology, Hematology Oncology, Plastic and Reconstructive Surgery, Dentistry, Radiology, Pathology, and Speech Pathology. Says Yarbrough, “This is a truly multidisciplinary team working together to advance knowledge regarding the treat-ment of head and neck cancer and to provide total care for the head and neck cancer patient.”• Dr. Dell Yarbrough examines a patient for the clinical trial. cancerLines Spring 2001 5 Cancers of the head and neck are the fifth-most common in the U.S. with 65,000 new cases and 18,000 deaths annually. Tobacco and ethanol use and abuse account for 75 percent of these cancers. The standard therapy for early cancers is surgery or radiation therapy alone; advanced tumors are treated with combination therapy (either surgery plus radiation or radiation plus chemotherapy). One promising new treatment involves the cancer-killing adenovirus CI-1042 (also known as ONYX-015). This is a souped-up cold virus de-signed to infect and selectively destroy cancer cells. In February, researchers in the UNC Multi-disciplinary Head and Neck Oncology Program embarked on a clinical trial using the oncolytic virus to treat recurrent head and neck squamous cell carcinoma. Adenoviruses are 20-sided viruses that contain DNA and replicate by rupturing the host cell’s membrane, killing the host cell and releasing new viral particles. Normal cells can deactivate the virus using the p53 protein. This important cell regulator (p53) is lost in 50 percent of head and neck cancers meaning that the cancer cells can no longer protect themselves from the virus. “Since cancer cells are the only cells within the body that have altered p53 activity this virus (CI-1042) selectively kills cancer cells while sparing their normal neighbors,” explains Dell Yarbrough, assistant professor, Otolaryngology/ Head and Neck Surgery and Biochemistry and Bio-physics. Dr. Yarbrough is a long-term Chapel Hill resident, having arrived as a Morehead scholar and subsequently graduated from UNC’s medical school and housestaff training program. This trial further investigates the use of chemotherapy alone versus chemotherapy plus CI- 1042. “Earlier trials have shown that 60 percent of previously treated cancers will respond to the combination of CI-1042 and chemotherapy,” Yarbrough says. Research studies also suggest that adenovirus and chemotherapy may have syner-gistic anti-tumor activity. Additionally, there was no increased chemotherapeutic toxicity associated with the addition of the adenovirus. “The adenovirus can be associated with transient fevers and chills (flu like symptoms), but in general the chemo-therapy side effects are not increased by addition of the adenovirus, ” Yar-brough says. That could mean a more effective treatment and increased survival rates. In addition to the ONYX-015 trial, the program team is actively involved in developing organ preservation protocols (pri-marily for tongue and larynx cancer using a com-bination of chemotherapy and radiation therapy. “We are also evaluating whether or not sentinel node technology is accurate to predict cervical New Studies for Head and Neck Cancers Solid Tumors (LCCC 9903) This is a Phase I UNC Lineberger-developed trial designed to determine the highest dose of paclitaxel that can be safely tolerated when it is given as a weekly 1-hour infusion on a 2 out of 3 week schedule. Another purpose of this Phase I study is to understand how the paclitaxel is absorbed, distributed, used and removed from the body. This trial will be open to patients with solid tumors (i.e. breast, ovarian, head and neck, prostate, lung, gastrointestinal) who have had previous therapy for their disease. This trial will be open for accrual first part of March 2001. PI, Claire Dees, MD Hematologic and Solid Tumors (LCCC 2020) This is a Phase I UNC Lineberger-developed trial designed to determine the highest dose of PS-341 that can be safely tolerated while receiving Doxil. While patients with hematologic malignancies and those with solid tumors will be treated in separate groups, all will receive the same drug and follow the same schedule of dose escalation. Patients who have had previous therapy and relapsed will be eligible for this trial. This trial will be open for accrual end of March 2001. PIs, Robert Orlowski, MD and Claire Dees, MD Hodgkin’s and Non-Hodgkin’s Lymphoma (LCCC 9929) This is a Phase II UNC Line-berger- developed trial designed to determine the efficacy of three chemotherapy drugs (ifosfamide, carboplatin, etoposide) adminis-tered one after another three weeks apart. Another purpose of this study is to assess the ability of this sequence of chemotherapy drugs to mobilize and harvest stem cells for future use. This trial is open for accrual at UNC and will be open at four other cancer centers. PI, Thomas Shea, MD Non-small Cell Lung Cancer Stage I/II (LCCC 2012) This is a Phase II UNC Line-berger- developed trial designed to determine the efficacy of using a combination of chemo-therapeutic drugs (gemcitabine, carboplatin, paclitaxel). This treatment will be repeated every 21 days for three cycles prior to surgery in patients with limited disease. This trial will be open for accrual the first part of March 2001. PI, Mark Socinski, MD For information about these and other clinical trials, call 919-966-4432 or visit the UNC LCCC website at http://cancer.med.unc.edu under “Patient Resources.” clinical triualsnderway Atomic-force microscope image showing DNA unfolding out of an adenovirus. PHOTO COURTESY OF ATSUKO NEGISHI, UNC PHYSICS AND ASTRONOMY. Outstanding Service. Board of Visitors member Dee Dee McKay of Charlotte received the Center’s Outstanding Serv-ice Award. She was cited for her service in many vital capacities over the years—as Board chair, as an advocate for the Center, and “as an amazing source of op-timism, strength and grace.” 6 cancerLines Spring 2001 Lineberger particularly in patients with lung, head or neck cancers.” Monte Carlo simulations have helped calculate radiation doses since nuclear testing began in the 1940s. But on regular computers, Monte Carlo simulations are notoriously slow, requiring a week’s worth of 24-hour-a-day computing just to calculate one radiation dose. As a result, Monte Carlo simulations are not practical for setting dose codes for cancer patients. But perhaps with faster, parallel-operating computers, they could be, Rosenman said. “We have always felt that if we could just get the calculations up and running fast enough, we could use Monte Carlo simulations in a clinical setting,” Rosenman said. “To the best of my knowledge, no one is yet ready to use Monte Carlo code clinically. We could be the first.” As surgical and chemother-apy treatments for cancer become more sophis-ticated, Rosenman notes, radiation therapy needs to move forward as well. “We need faster, more accurate computing ability. It’s one more reason why this partnership with Microsoft and Dell is so important.”• and found it was feasible and low-tech,” says Raleigh. Now, the U.S. Food and Drug Adminis-tration has given the go-ahead to test as a diag-nostic tool the pimonidazole hypoxia marker in human tumors. “Our interest in tumor hypoxia is twofold: One, if these tumors don’t do as well with radiation, chemotherapy or surgery, then it’s important that we assess that before we embark on treatment,” Varia explains. “The other important interest is in finding out why these hypoxic tumors are behaving badly.” Varia, Raleigh and their collaborators have demonstrated that the pimonidazole marker is a valuable approach to studying the mechanisms of hypoxia-associated poor prognosis. Tumors from more than 200 patients worldwide are being tested for hypoxia using this method. Beyond cancer treatment planning, clinical inves-tigators at UNC-CH and elsewhere are looking at the hypoxia marker for studying alcohol-associated liver damage, wound healing and liver transplant success. “It’s a very novel tool that can be applied not only in cancer research but widely in medical investigations,” Raleigh noted. UNC, Dell, Microsoft partnership could dramatically improve cancer radiation treatments UNC has received a large computer cluster for a clinical study to determine possible ways in which radiation therapy can be more effectively tailored for individuals. Dell Computer Corp. and Micro-soft Corp. provided the technology that could one day enable research that dramatically improves the accuracy of radiation therapy treatments through the use of parallel-computing processes and Monte Carlo simulations. Julian Rosenman, professor of radiation oncol-ogy and a member of the UNC Lineberger Com-prehensive Cancer Center, is principal investigator for the new study. “Medicine’s current methods for calculating radiation doses, while highly sophisti-cated, are just not good enough,” Rosenman said. “We know that dose calculations can contain errors as large as 10 to 15 percent in some situations. These errors could adversely affect survival rates, Briefs continued from page 4 Hammond Chair in Childhood Cancer Established. A $1.5 million gift will establish the G. Denman Hammond Chair in Childhood Cancer, honoring Dr. G. Denman Hammond, president and CEO of the National Childhood Cancer Foundation and the founding director of the University of Southern California Comprehensive Cancer Center. The professorship is made possible by a gift from an anonymous donor in honor of Dr. Hammond. A national recruitment to fill the endowed chair will begin this summer. Dr. Hammond, a distinguished alumnus of the University of North Carolina at Chapel Hill, was a student at the UNC School of Medicine, then only a two-year program, who subsequently received the M.D. degree from the University of Pennsylvania. “This is an outstanding legacy for one of the University of North Carolina at Chapel Hill’s most distinguished undergraduate and medical school alumni,” said Shelton Earp. “Dr. Hammond’s extraordinary career helped change the way we treat children with cancer.” Shown here (left to right) Dr. Hammond; Dr. Julie Blatt, chief, pediatric oncology; and Dr. Shelton Earp, Center director. Carolina Cancer Focus. At the January 14th women’s basketball game against NC State, members of Carolina Cancer Focus handed out over 7000 ribbons in honor of ovarian cancer and informational flyers about cancer prevention. Pictured (left to right): Shanna Fox, James Haltom, Shelley Koon, Michael Abel, Lisa Wald, Brennan Bouma and Krishna Gelot. more than 95 percent, but it drops significantly to less than 20 percent after treatment for metastatic breast cancer. Early detection, then, is crucial. Film Versus Digital In conventional mammography, differences in tis-sue densities and composition show up as con-trasting areas in the image, enabling physicians to see tumors or changes in tissue. However, tradi-tional film presents two challenges to radiologists. First, it cannot be altered after it’s acquired. To get different perspectives, technologists have to take more pictures, exposing the patient to more radiation. Or radiologists have to use a hot light and magnifying glass to get a different look. Second, because breast tumors and healthy breast tissue are very similar in density, up to 20 percent of cancers cannot be detected at all on X-ray film. In addition, when suspicious lesions are found on a mammogram, doctors generally choose to do a breast biopsy to make a clear determi-nation. The annual breast biopsy volume in the U.S. is approaching almost 1,000,000 per year, with benign diagnoses made between 80 and 90 percent of the time. By contrast, digital mammography offers an image that can be manipulated after it is acquired. “If you’ve ever used a digital camera, you know how simple it is to adjust the image after you’ve taken the picture,” says Pisano, who also serves as head of the International Digital Mammography Development Group.“You can easily rotate, zoom or adjust the contrast or brightness.” Digital mam-mography offers the same functionality for tech-nicians and the digital pictures are easier to store, retrieve and transport, particularly via the Internet. Putting it into Practice While it seems likely digital imaging could improve cancer detection, Pisano and the FDA want quanti-fiable proof before they give up on the traditional screen-film technology. “We don’t know that digital mammography is better yet,” Pisano cautions.“We’re still very early in its history. From a physics perspective, we certainly think it should provide earlier detection in dense-breasted women. But while early studies suggest reduced false positives, we don’t know yet that dig-ital mammography will find more breast cancer.” That’s why Pisano is leading an international More Effective Mammography continued from page 1 Mammograms of the same breast using digital mamography (A) and conventional X-ray (B). Dr. Pisano’s study will help determine whether digital mammography has the potential to give more precise information about the breast possibly leading to fewer callbacks for false positive or unclear results. cancerLines Spring 2001 3 study of 49,500 women in the United States and Canada to evaluate whether digital mammography is as good as or better than traditional mammog-raphy in detecting breast cancers. Nineteen centers in the United States and Canada, including UNC Lineberger, are participating in the study funded by the National Cancer Insti-tute. The study is expected to enroll patients for 3 years. That’s all good news for radiologists who tend to pre-fer digital images over film because they provide better information on which to base diagnoses, according to a small study led by Pisano last year. She and her team asked 12 certified, working radiologists in Chapel Hill, Dur-ham, Raleigh and Graham to look at, compare and grade images from tradi-tional X-rays and digital mammography for screen-ing and diagnosis of breast masses and calcifications. “It was clear that the radiologists preferred to look at different versions of the image for each of the three tasks,” Pisano says. “What they liked for screening is not the same thing they liked for diag-nosis of masses or diagnosing calcifications. The bottom line is that they need multiple versions of the same image to get as much information out of each image as they can.With digital mammog-raphy,” she says, “they can take different looks at the same image to get exactly the information they need without exposing the patient to additional radiation.” Pioneering Technology “In general, radiology technology has moved to digital over the last 20 years,” explains Pisano. “Mammography is the last field to go digital.” Tests and clinical trials of digital breast imaging began in 1992, but the technology didn’t receive FDA approval until Feb-ruary 2000. Currently, only GE’s Senographe has the FDA’s stamp of approval, but Pisano expects one or two other manufacturers to receive the green light this year. At present, there are only 20 to 30 places in the country using digital mam-mography and only a hand-ful use it in a clinical setting, and UNC was one of the pioneers. “For some time, re-searchers in the Computer Science department have been working on image processing—how to get increased information in images,” Pisano says. “That gave us a significant head start for the work we’re doing with digital mammography.” In fact, the algorithm used to help the troubled Hubble telescope see better is the same one that will probably be used in the future to help digital mammography see cancers better in the breast. “UNC is one of the world leaders in image proc-essing research, computer science and biomedical engineering.” • Hatchell Donation. UNC women’s basketball Coach Sylvia Hatchell donated $5,000 to gynecologic cancer research at UNC Lineberger at halftime of the January 14th game against NC State. Last summer she had a cancer “scare.” After her experience and to express her gratitude, she had pledged to donate $5.00 for each women’s basketball season ticket sold. Shown with her are (above, left to right): Dr. Linda Van Le, UNC Lineberger gynecologic oncology program; Dr. Bill Nebel, Coach Hatchell’s Chapel Hill gynecologist; Dr. Shelton Earp, Center director; Dr. John Boggess, UNC Lineberger gynecologic oncology program. “With digital mammog-raphy they can take different looks at the same image to get exactly the information they need without exposing the patient to additional radiation.” • • • •
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Full Text | 8 cancerLines Spring 2001 caolfe nedvaernts J U N E 9th Susan G. Komen Breast Cancer Foundation NC Triangle Race for the Cure. Raleigh, NC. S E P T E M B E R 20th Pink Ribbons Project Dancers in Motion Against Breast Cancer Performance/ Benefit. Carolina Theatre, Durham, NC. O C T O B E R 5th Board of Visitors Meeting. Lineberger Cancer Center, Chapel Hill, NC. 13th Patient/Family Symposium. Friday Center, Chapel Hill, NC. UNC Lineberger Comprehensive Cancer Center CB# 7295 School of Medicine University of North Carolina at Chapel Hill Chapel Hill, NC 27599-7295 (919) 966-3036 http://cancer.med.unc.edu Return Forwarding, and Return Postage Guaranteed. Address Correction Requested. Nonprofit Organization U.S. Postage PAID Permit No. 71 Chapel Hill, NC 27599-1110 Like Columbuses of latter day We chart the genome’s DNA We splice, we snip, we recombine On risks of cancer, boldly opine Perhaps with the Tarheel basketball team We could tweak a chromosome or splice a gene To make a eugenic team of dreams Coached by a young clone of Dean’s But genetics has its darker side For if the wrong experiment’s tried We might end up with a player or two Who bleeds a deeper shade of blue... As his patron, Michelangelo Had the Medicis long ago And backing Walter Raleigh’s team Was fair Elizabeth, England’s Queen Vasco de Gama had the King of Portugal But we lucked out ...We have you all The future of medicine, pundits say Lies within our DNA But without you our noble mission Would be forlorn, an empty vision So, from gene and cell and chromosome, We wish to make our thanks well known, We sing your praises on this special day, From the bottom of our DNA Dr. Jim Evans and his “Ode of a Geneticist” Dr. Jim Evans, associate pro-fessor of medicine and leader of the Lineberger Cancer Genetics program, spoke at the Lineberger Club meeting. He ended his talk with a poem he wrote for the occasion: LU N C L i n ecb e r g e ria C o mnpnr e h e n seicv e C aesn c e r Cre n t e r University of North Carolina School of Medicine & UNC Hospitals Spring 2001 “Physicians have been using X-rays to detect breast cancer for years,” notes Etta Pisano, professor of radi-ology and director of breast imaging at the UNC Lineberger Comprehensive Cancer Center. Studies have shown that between 80 and 90 percent of malig-nancies are visible on mammography. “It would be foolish to supplant a technology that’s known to reduce breast cancer mortality.” But Pisano and her colleagues are working with a technology that might further reduce mortality and potentially improve the early diagnosis of breast cancer—digital mammography. Current technology misses some 15,000 to 45,000 breast cancers in the more than 32.5 million mam-mograms performed annually in the United States. Prior studies and early clinical experience have shown that digital mammography offers better visibility, particularly near the skin line and the chest wall, and in dense breast tissue. The digital mammography machine used at UNC, in addition to easier detection and better imaging, can reduce exam time by half that of traditional film-based mam-mograms. Improved images also may eliminate many of the call-backs necessary with traditional mammography. That’s important because approximately one in eight the inside line up ... 5 4 6 Head & Neck Cancer and Clinical Trials Profile: Terry Van Dyke & Briefs 2Director’s Message Lineberger Scrapbook continued on page 3 continued on page 2 8“Ode of a Geneticist” and Calendar of Events American women will develop breast cancer in her lifetime. With more than 180,000 cases diagnosed each year, it’s the second most common cancer in women after skin cancer and the leading cause of cancer death among women 40 to 55. According to the American Cancer Society, the 5-year survival rate after treatment for localized breast cancer is Colon Cancer Screening: Not As “Accepted��� By Public, But Vital and Effective “All adults over age 50 are at sufficient risk for colorectal cancer to warrant screening,” says Michael Pignone, Assistant Professor of Medicine in the Division of General Internal Medicine.“While some groups are at higher risk because of a family history of colorectal cancer or the presence of in-flammatory bowel disease, the absence of a high-risk condi-tion does not mean that one is at low or no risk.” According to the American Cancer Society, an estimated 47,700 people died of colon cancer in 2000, the third most common cancer in men and women. When detected in an early, localized stage, the 5-year relative survival rate is 90 per-cent; however, only 37 percent of colorectal cancers are dis-covered at that stage. Early detection is critical. After the cancer has spread to adjacent organs or lymph nodes, the rate drops to 65 percent or to 8 percent in patients with distant metastases. Despite that, only 25-35 percent of adults have had a screening test recently for colorectal cancer. “The low rates of screening are a consequence of poor communication,” Pignone notes. More Effective Mammography: Is Digital the Answer? Dr. Etta Pisano views a digital mammogram. “Many patients do not realize they are at risk and many providers do not routinely offer screening to patients over age 50.” And many people don’t have access to regular, affordable health care, so they don’t have the opportunity to be screened. “Another reason may be apathy,” adds David Ransohoff, professor of medicine, Lineberger member and an epide-miologist. “For reasons we don’t fully understand, colorectal cancer screening is much less popular, or ‘accepted,’ by the public than, say, screening for prostate cancer, or mam-mography for women 40-49, even though the evidence is strong that colorectal cancer screening reduces mortality and has very few side-effects.” For all these reasons, researchers at UNC are engaged in a number of initiatives to increase screening for colorectal cancers and improve prevention.“This is a point of emphasis for North Carolina and its advisory committee on cancer control and coordination,” says Dr. Joseph Pagano, Director Emeritus and chair of the state committee. cancer cell. Dr. Dell Yarbrough is doing just that with a new therapy for head and neck cancers. He is using a cold virus to deliver therapy that will only be amplified in cells carrying a mutated protein, the kind found in certain can-cers. Modifications in this delivery approach are being developed in Dr. Yarbrough’s lab for a second generation of clinical trials. We’re teaming up with the new UNC Genomics program led by Dr. Terry Magnuson and will tell you more about this new Carolina initiative in the next issue of Cancer Lines. In the meantime, enjoy a wonderful summer: please remember to wear sun-screen.• At UNC, Pignone and others developed and tested a video-based decision aid for patients that informs them about the options for screening and helps them discuss screening with their doctors. The study, one of the largest trials ever done on the effectiveness of decision aids in real clinical practices, found that the video increased screening rates significantly. The test was so successful they are developing a similar program for the Web that they plan to test next year. Additionally, the Internal Medicine clinic has instituted a reminder system for patients under-going fecal occult blood testing. The system has increased return rates by 10-15 percent over baseline. Research shows that five simple activities can lower the risk of colon cancer by as much as 70 percent, according to Robert Sandler, professor of medicine and co-director of UNC-CH’s Center for Gastrointestinal Biology and Disease and Linberger member. To reduce colorectal cancer people should: Avoid obesity Engage in regular physical activity 2 cancerLines Spring 2001 Colon Cancer continued from page 1 Limit alcohol consumption and don’t smoke Eat a sensible diet high in vegetables and fruit and low in red meat Consider using supplements of calcium and folic acid Taking calcium or folic acid supplements can reduce polyps from which it’s estimated 90 per-cent or more of colon cancers evolve. In a 1999 national study, Sandler and his colleagues found that calcium supplements moderately reduce the risk of recurring polyp growth in the colon and may reduce the risk of colon cancer. Researchers found overall a 24 percent decrease in the number of polyps and a 19 percent decrease in the risk of polyp recurrence. Approximately 20 epidemiologic studies have found that people who regularly use aspirin and other non-steroidal anti-inflam-matory drugs have 40 to 50 per-cent lower risk of colorectal cancer and adenomatous polyps. However, no randomized trials have yet proven that aspirin-like drugs cause this reduction. Two studies, funded by the National Cancer Institute, are underway at UNC to determine the link. Sandler and others also are working on a population-based study to determine the impact of risk factors, access to health care and insurance and poverty on colon cancer mortality rates; and a study on diet and its effect on the colon’s lining. Approaching colon cancer prevention and screening from several disciplines results in more comprehensive research and clinical treatment. “Multidisciplinary collaboration is important be-cause it unites people with different types of exper-tise to work together to solve a problem. To best tackle colon cancer screening and prevention, we need expertise in psychology, health education/ behavior change, epidemiology, physician learning, gastroenterology, information sciences and oncol-ogy,” Pignone concludes. “Lineberger helps us do that.”• MeDsisreactgor’es What do a digi-tal camera and the Trojan horse have in com-mon? They’re both prototypes for new technol-ogy to help make cancer diagnostic tests and therapies more precise. UNC Lineber-ger is a leader in meeting this challenge. To make one of the tests that diag-nose breast cancer more precise, Dr. Etta Pisano is pioneering a promising new technology called digital imaging. This process uses a computer image of the breast rather than a film x-ray. The new technology is the same as that used for digital cameras. This advance means potentially better images and in-formation. For patients it means less radiation since additional views aren’t necessary: the image captured by the computer can be manipulated and re-examined by the radiologist. To answer definitively whether digital imaging is superior to film x-ray at de-tecting breast abnormalities, Dr. Pisano will lead a 19-center three-year study funded by the National Cancer Institute involving 49,500 women. The $27 mil-lion grant is the largest ever awarded to a radiologist. In related news, Dell Computer and Microsoft have made a gift of 100 high-end computers and software to be used in parallel computation by Dr. Julian Rosenman in his quest to obtain faster and more accurate 3-dimensional images of a particular tumor. This will allow precise focusing of multiple radiation beams converging on the tumor while sparing normal tissue. Julian’s and Etta’s work are both results of the highly successful collaborations with UNC’s internationally renowned computer science department. Such collaboration and teamwork are the hallmarks of a multidisciplinary cancer program at a great university. On another front, ideal cancer therapy targets tumor cells while spar-ing healthy ones. But how do you sneak the therapy into cells but only have it attack the cancer cells? Pack the therapy in a genetically altered cold virus—a Trojan Horse—that can multiply in a Dr. Shelton Earp UNC Lineberger is designated a comprehensive cancer center by the National Cancer Institute. Cancer Lines is a semi-annual publication of the UNC Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine at Chapel Hill. Dr. H. Shelton Earp, III, Director Dr. Joseph S.Pagano, Director Emeritus Dianne G. Shaw, Director of Communications/Executive Editor Margot Carmichael Lester, Editor Please remove me from your mailing list Name Please add the following to the Cancer Center’s mailing list. Name Address City, State, Zip UNC Lineberger Comprehensive Cancer Center CB# 7295 School of Medicine University of North Carolina at Chapel Hill Chapel Hill, NC 27599-7295 (919) 966-3036 http://cancer.med.unc.edu Printed on Recycled Paper (Left to right) Drs. Michael Pignone, David Ransohoff and Robert Sandler. cancerLines Spring 2001 7 Scrapbook Seed Grant Recipients. UNC Lineberger Seed Grant recipients were honored at a recent Board of Visitors meeting. (Left to right) back row: Dr. David Ollila; Dr. Jozef Spychala; Dr. Shelton Earp, Center director; Dr. Beverly Mitchell, Center associate director; front: Dr. Carol Shores; Dr. Valerie Murrah and Dr. Bill Funkhouser. The grants support new and growing UNC-CH research projects in innovative areas. The grant program helps launch smaller projects that could lead to more in-depth studies in the future. The grants were made possible by: the Schechter Foundation, the Brody Brothers Foundation and the Felix Harvey Foundation, all of Kinston; the Foundation for the Carolinas of Charlotte; the A.E. Finley Foundation Inc. of Raleigh; the Cemala Foundation Inc. and the Hillsdale Fund Inc., both of Greensboro. Lineberger Fellows. Six Lineberger fellows were honored for demon-strated excellence in research. The Board of Visitors began the program in 1987 to promote and encourage graduate students to pursue cancer research. The fellowships are made possible by Best Distributing Company in Goldsboro; the Cancer Resesearch Foundation of America in Arlington, VA; and Mr. and Mrs. Sanford Doxey, Jr. of Wilmington. Pictured (left to right): Helena Furberg–public health science, preceptor Dr. Robert Millikan; Jennifer David Peck–public health science, preceptor Dr. Barbara Hulka; Nathan Felix–laboratory science, pre-ceptor Dr. Jenny Ting; Susan Steck-Stoff–public health science, preceptor Lenore Arab; Wolfgang Resch–laboratory science, preceptor Dr. Ron Swanstrom; and Betty P. Liu–laboratory science, preceptor Dr. Keith Burridge. Larry and Sarah Tomlinson of Charlotte are not your ordinary Carolina couple. Like many alumni, they were both born and raised within a few miles of Chapel Hill and have parents, siblings, and now children, who attended UNC. While at UNC Mr. Tomlinson played on the tennis team and was a member of the SAE fraternity, and he is a member of Carolina Living Legends. The Tomlinsons have been lifelong supporters of the place that is so near to their hearts, but their roots here at the Univer-sity run much deeper. Mrs. Tomlinson’s grand-father was Dr. Francis P. Venable, chemistry profes-sor and then president of the University from 1900 to 1914, who was instrumental in laying the solid foundation on which UNC has built its scientific research programs. Mr. and Mrs. Tomlinson have been very active supporters of UNC for many years. However, it was not until Mr. Tomlinson’s brother, Carroll, was diagnosed with prostate cancer in 1983 that they were introduced to the Lineberger Comprehensive Cancer Center. In1985, after Carroll Tomlinson lost his life to cancer, the Tomlinsons joined the Cen-ter’s Board of Visitors and the fight against this disease. The Tomlinsons’ most recent gift will benefit UNC’s scientific community. Their generous gift to the University is a charitable remainder trust, which has funded the Larry and Sarah Tomlinson Lab in the Lineberger Comprehensive Cancer Center. The Lab will be home to Dr. Terry Van Dyke and her team of 20 scientists. Dr. Van Dyke is director of the Animal Models Core here at UNC and is co-chair of the National Cancer Institute’s Mouse Models of Human Cancer Consortium. One of the main projects in her lab is the development of mouse models that produce human cancers, such as breast and prostate cancer, and lymphoma. The Tomlinson Lab is the result of one of many different kinds of planned gifts. Gifts to Lineberger can be made in forms from property to stocks, retirement plan assets to trusts. Although dona-tions of outright gifts such as cash and property are fairly simple, the benefits of making gifts such as annuities and trusts can be attractive options. Depending on which type of planned gift one chooses, tax benefits can be immediately realized or they are delayed to benefit one’s heirs. Gifts can be designed so that income payments from an investment benefit Lineberger while ownership of the asset is retained (a charitable lead trust), or so that the property is transferred to Lineberger but a beneficiary receives a predetermined income pay-ment from the trust, as is the case with the Tomlin-sons’ charitable remainder trust. The array of gift planning opportunities available does cover a wide assortment of options. For more information on planned gifts for Lineberger, please call the Development Office at (919) 966-5905 to request information. Though the benefits are dif-ferent for the various types of planned gifts, the one constant is the benefit of helping the clinicians and scientists at Lineberger work toward a cure for this disease that touches all our lives.• Tomlinson Lab Continues Tradition “When you start your lab, you have to be very focused, like a horse with blinders,” she recalls. “About the time I got tenure is when I took a deep breath and asked myself ‘now what do I want to do?’ There weren’t many people at Pittsburgh at that time doing what I was interested in, so my hus-band ( Jude Samulski, director of the UNC Gene Therapy Center) and I started looking around and were attracted to the intellectual climate at UNC. We’ve been here about seven and a half years now.” Van Dyke continues to pursue her love of fig-uring things out through her research in cancer cell biology. “As a researcher, the thing that’s fascinating about cancer is that it’s not a single disease, but hundreds of diseases and it takes different things for different cells to become a cancer,” she explains. “What we’d like to understand is exactly what goes wrong in the cells so that people who do drug design can actually develop ways to inhibit the cancers.” Currently, Van Dyke and her team are devel-oping a therapy by genetically manipulating mice. “You can do in the mouse pretty much what you can do in a test tube,” she says.“You can go in and alter a specific gene and say ‘what happens if I make this alteration?’ Things you see happening in human cells you can mimic in the mouse and ask ‘does it really lead to cancer?’” The problem with cancer research in humans is that scientists study the disease after the fact and cannot establish cause and effect relationships. 4 cancerLines Spring 2001 Study offers new evidence that garlic protects against cancers A new study at UNC by Lenore Arab and col-leagues shows that people who consume raw or cooked garlic regularly face about half the risk of stomach cancer and two thirds the risk of colorectal cancer as people who eat little or none. Their study was a meta-analysis, a mathematical combination of numerous other studies to develop a clearer picture of such issues as cancer and heart disease. The group reviewed 300 scientific papers related to diet and cancer and then combined and analyzed data from 22 describing the best, most relevant human research related to garlic from around the world. Previous research has shown that a compound in garlic called allium partially protects animals against cancer, and some scientists believe it has the same effect in humans. “After controlling for various risk-factors, we found that when we pooled the results, this preventive effect was largely con-firmed,” says Lenore Arab, professor of epidemi-ology and nutrition at the UNC-CH schools of public health and medicine and Linebeger mem-ber. “We didn’t have enough information to be able to say the same about garlic’s possible effects on other forms of cancer.” Researchers could not show similar benefits from taking garlic supplements, possibly because the active ingredients are destroyed by processing or by sitting on store shelves for a long time. “Many scientists believe garlic helps prevent stomach cancer because it has anti-bacterial effects against a bacterium, Helicobacter pylori, found in the stomach and known to promote cancer there,” Arab says. Study shows why muscle decays mysteriously in cancer, AIDS and other illnesses Scientists at UNC-CH’s Lineberger Comprehen-sive Cancer Center believe they have discovered a major reason why muscles often decay in patients with cancer, AIDS, late-stage heart disease, severe burns and numerous chronic diseases. Their re-search focuses on cachexia, an important syn-drome that could lead to an effective treatment for the condition. The new study shows that cachexia, which kills an estimated one third of cancer patients, results from activation of a factor, NF-kappa B. This natur-al substance attaches to DNA inside cell nuclei and turns genes on and off like a switch. In this instance it prevents expression of a key regulatory protein called MyoD from replenishing muscle tissue as it does in healthy people. “Cancer cachexia, which causes patients to literally waste away, has been documented for at least 100 years, but it wasn’t until about 20 years ago that researchers discovered a cytokine protein called tumor necrosis factor and that the factor could elicit cachexia,” notes postdoctoral fellow Denis Guttridge.“What we have done is to identify a key part of what’s happening mechanistically inside muscle cells to cause cachexia.” “Since we now know how to inhibit NF-kappa B, this will lead to therapies for reducing cachexia, which may well lead to significant improvement in the quality of life of patients who have chronic diseases like cancer and AIDS,” Guttridge says. Studies plumb tumor resistance to treatment Cancer tumors with cells low in oxygen often survive and continue to grow despite the treat-ments thrown at them. Mahesh Varia, professor of radiation oncology at UNC-CH and a Lineberger member, has developed a method of identifying these hypoxic tumors which may lead to a greater understanding of treatment resistance and help doctors more effectively predict the outcome of cancer therapies. James Raleigh, professor of radiation oncology and Lineberger member, invented the one clinically advanced method, the pimonidazole hypoxia marker, that identifies tumor hypoxia at the cellular level. “We spent a number of years proving it in the laboratory and with animals in a veterinary setting Profile Briefs Trailblazer in Mouse Model Research Terry Van Dyke didn’t always want to be a cancer researcher. “When I was 5, I decided I wanted to be a nurse,” recalls the professor of Biochemistry and Biophysics at UNC. “But in my spare time, I wanted to be a cowgirl. My mom says that kids from the neighborhood used to come around our house and ask for ‘Dale.’ I had told everyone my name was Dale Evans!” Encouraged by an inspirational biology teacher in 10th grade, Van Dyke let go of her nursing and cowgirl aspirations and decided to pursue mole-cular biology.“Asking questions and getting answers through experimentation has always been fasci-nating to me,” she says. “I’ve always loved trying to figure things out.” Van Dyke received her BS and PhD in molecular biology from the University of Florida. She did her post doc work at the University of New York at Stony Brook with Arnold J. Levine and then followed Levine to Princeton. In 1986, she got the opportunity to run her own laboratory at the Uni-versity of Pittsburgh—where she stayed for 7 years and earned tenure. “That’s why our mouse model studies are so cool,” Van Dyke says. “The technologies have developed tremendously over the last 20 years and it’s just exhilarating the different kinds of things we can do.” As a professor, wife and the mother of two teen-agers, she admits she doesn’t have a lot of spare time. “But I do enjoy playing tennis, reading, and the occasional artsy-craftsy project.” Van Dyke is also currently co-chairing a national consortium funded by the NCI and has been very involved in trying to build the field of genetics at UNC. “I guess you could say my days are pretty jam-packed!”• continued on page 6 metastasis in head and neck cancer,” Yarbrough says.“The advantage of sentinel node biopsy, if it proves to be accurate, would be that by removing only one or a few lymph nodes from the neck we would be able to accurately determine if the neck needs further treatment. This would allow us to avoid the unwanted side effects associated with treating patients without neck disease.” The team also is evaluating a molecular method of determining if a head and neck cancer has spread to neck nodes.“The theoretical advantage is that the molecular technique (RT-PCR) should be more accurate and less costly than standard pathologic examination,” Yarbrough says. Last year, the team discovered that CAT scanning can be used to determine if surgery will be necessary after chemotherapy and radiation therapy. The Head and Neck Program includes physi-cians, researchers and staff from the Departments of Otolaryngology/Head and Neck Surgery, Radia-tion Oncology, Hematology Oncology, Plastic and Reconstructive Surgery, Dentistry, Radiology, Pathology, and Speech Pathology. Says Yarbrough, “This is a truly multidisciplinary team working together to advance knowledge regarding the treat-ment of head and neck cancer and to provide total care for the head and neck cancer patient.”• Dr. Dell Yarbrough examines a patient for the clinical trial. cancerLines Spring 2001 5 Cancers of the head and neck are the fifth-most common in the U.S. with 65,000 new cases and 18,000 deaths annually. Tobacco and ethanol use and abuse account for 75 percent of these cancers. The standard therapy for early cancers is surgery or radiation therapy alone; advanced tumors are treated with combination therapy (either surgery plus radiation or radiation plus chemotherapy). One promising new treatment involves the cancer-killing adenovirus CI-1042 (also known as ONYX-015). This is a souped-up cold virus de-signed to infect and selectively destroy cancer cells. In February, researchers in the UNC Multi-disciplinary Head and Neck Oncology Program embarked on a clinical trial using the oncolytic virus to treat recurrent head and neck squamous cell carcinoma. Adenoviruses are 20-sided viruses that contain DNA and replicate by rupturing the host cell’s membrane, killing the host cell and releasing new viral particles. Normal cells can deactivate the virus using the p53 protein. This important cell regulator (p53) is lost in 50 percent of head and neck cancers meaning that the cancer cells can no longer protect themselves from the virus. “Since cancer cells are the only cells within the body that have altered p53 activity this virus (CI-1042) selectively kills cancer cells while sparing their normal neighbors,” explains Dell Yarbrough, assistant professor, Otolaryngology/ Head and Neck Surgery and Biochemistry and Bio-physics. Dr. Yarbrough is a long-term Chapel Hill resident, having arrived as a Morehead scholar and subsequently graduated from UNC’s medical school and housestaff training program. This trial further investigates the use of chemotherapy alone versus chemotherapy plus CI- 1042. “Earlier trials have shown that 60 percent of previously treated cancers will respond to the combination of CI-1042 and chemotherapy,” Yarbrough says. Research studies also suggest that adenovirus and chemotherapy may have syner-gistic anti-tumor activity. Additionally, there was no increased chemotherapeutic toxicity associated with the addition of the adenovirus. “The adenovirus can be associated with transient fevers and chills (flu like symptoms), but in general the chemo-therapy side effects are not increased by addition of the adenovirus, ” Yar-brough says. That could mean a more effective treatment and increased survival rates. In addition to the ONYX-015 trial, the program team is actively involved in developing organ preservation protocols (pri-marily for tongue and larynx cancer using a com-bination of chemotherapy and radiation therapy. “We are also evaluating whether or not sentinel node technology is accurate to predict cervical New Studies for Head and Neck Cancers Solid Tumors (LCCC 9903) This is a Phase I UNC Lineberger-developed trial designed to determine the highest dose of paclitaxel that can be safely tolerated when it is given as a weekly 1-hour infusion on a 2 out of 3 week schedule. Another purpose of this Phase I study is to understand how the paclitaxel is absorbed, distributed, used and removed from the body. This trial will be open to patients with solid tumors (i.e. breast, ovarian, head and neck, prostate, lung, gastrointestinal) who have had previous therapy for their disease. This trial will be open for accrual first part of March 2001. PI, Claire Dees, MD Hematologic and Solid Tumors (LCCC 2020) This is a Phase I UNC Lineberger-developed trial designed to determine the highest dose of PS-341 that can be safely tolerated while receiving Doxil. While patients with hematologic malignancies and those with solid tumors will be treated in separate groups, all will receive the same drug and follow the same schedule of dose escalation. Patients who have had previous therapy and relapsed will be eligible for this trial. This trial will be open for accrual end of March 2001. PIs, Robert Orlowski, MD and Claire Dees, MD Hodgkin’s and Non-Hodgkin’s Lymphoma (LCCC 9929) This is a Phase II UNC Line-berger- developed trial designed to determine the efficacy of three chemotherapy drugs (ifosfamide, carboplatin, etoposide) adminis-tered one after another three weeks apart. Another purpose of this study is to assess the ability of this sequence of chemotherapy drugs to mobilize and harvest stem cells for future use. This trial is open for accrual at UNC and will be open at four other cancer centers. PI, Thomas Shea, MD Non-small Cell Lung Cancer Stage I/II (LCCC 2012) This is a Phase II UNC Line-berger- developed trial designed to determine the efficacy of using a combination of chemo-therapeutic drugs (gemcitabine, carboplatin, paclitaxel). This treatment will be repeated every 21 days for three cycles prior to surgery in patients with limited disease. This trial will be open for accrual the first part of March 2001. PI, Mark Socinski, MD For information about these and other clinical trials, call 919-966-4432 or visit the UNC LCCC website at http://cancer.med.unc.edu under “Patient Resources.” clinical triualsnderway Atomic-force microscope image showing DNA unfolding out of an adenovirus. PHOTO COURTESY OF ATSUKO NEGISHI, UNC PHYSICS AND ASTRONOMY. Outstanding Service. Board of Visitors member Dee Dee McKay of Charlotte received the Center’s Outstanding Serv-ice Award. She was cited for her service in many vital capacities over the years—as Board chair, as an advocate for the Center, and “as an amazing source of op-timism, strength and grace.” 6 cancerLines Spring 2001 Lineberger particularly in patients with lung, head or neck cancers.” Monte Carlo simulations have helped calculate radiation doses since nuclear testing began in the 1940s. But on regular computers, Monte Carlo simulations are notoriously slow, requiring a week’s worth of 24-hour-a-day computing just to calculate one radiation dose. As a result, Monte Carlo simulations are not practical for setting dose codes for cancer patients. But perhaps with faster, parallel-operating computers, they could be, Rosenman said. “We have always felt that if we could just get the calculations up and running fast enough, we could use Monte Carlo simulations in a clinical setting,” Rosenman said. “To the best of my knowledge, no one is yet ready to use Monte Carlo code clinically. We could be the first.” As surgical and chemother-apy treatments for cancer become more sophis-ticated, Rosenman notes, radiation therapy needs to move forward as well. “We need faster, more accurate computing ability. It’s one more reason why this partnership with Microsoft and Dell is so important.”• and found it was feasible and low-tech,” says Raleigh. Now, the U.S. Food and Drug Adminis-tration has given the go-ahead to test as a diag-nostic tool the pimonidazole hypoxia marker in human tumors. “Our interest in tumor hypoxia is twofold: One, if these tumors don’t do as well with radiation, chemotherapy or surgery, then it’s important that we assess that before we embark on treatment,” Varia explains. “The other important interest is in finding out why these hypoxic tumors are behaving badly.” Varia, Raleigh and their collaborators have demonstrated that the pimonidazole marker is a valuable approach to studying the mechanisms of hypoxia-associated poor prognosis. Tumors from more than 200 patients worldwide are being tested for hypoxia using this method. Beyond cancer treatment planning, clinical inves-tigators at UNC-CH and elsewhere are looking at the hypoxia marker for studying alcohol-associated liver damage, wound healing and liver transplant success. “It’s a very novel tool that can be applied not only in cancer research but widely in medical investigations,” Raleigh noted. UNC, Dell, Microsoft partnership could dramatically improve cancer radiation treatments UNC has received a large computer cluster for a clinical study to determine possible ways in which radiation therapy can be more effectively tailored for individuals. Dell Computer Corp. and Micro-soft Corp. provided the technology that could one day enable research that dramatically improves the accuracy of radiation therapy treatments through the use of parallel-computing processes and Monte Carlo simulations. Julian Rosenman, professor of radiation oncol-ogy and a member of the UNC Lineberger Com-prehensive Cancer Center, is principal investigator for the new study. “Medicine’s current methods for calculating radiation doses, while highly sophisti-cated, are just not good enough,” Rosenman said. “We know that dose calculations can contain errors as large as 10 to 15 percent in some situations. These errors could adversely affect survival rates, Briefs continued from page 4 Hammond Chair in Childhood Cancer Established. A $1.5 million gift will establish the G. Denman Hammond Chair in Childhood Cancer, honoring Dr. G. Denman Hammond, president and CEO of the National Childhood Cancer Foundation and the founding director of the University of Southern California Comprehensive Cancer Center. The professorship is made possible by a gift from an anonymous donor in honor of Dr. Hammond. A national recruitment to fill the endowed chair will begin this summer. Dr. Hammond, a distinguished alumnus of the University of North Carolina at Chapel Hill, was a student at the UNC School of Medicine, then only a two-year program, who subsequently received the M.D. degree from the University of Pennsylvania. “This is an outstanding legacy for one of the University of North Carolina at Chapel Hill’s most distinguished undergraduate and medical school alumni,” said Shelton Earp. “Dr. Hammond’s extraordinary career helped change the way we treat children with cancer.” Shown here (left to right) Dr. Hammond; Dr. Julie Blatt, chief, pediatric oncology; and Dr. Shelton Earp, Center director. Carolina Cancer Focus. At the January 14th women’s basketball game against NC State, members of Carolina Cancer Focus handed out over 7000 ribbons in honor of ovarian cancer and informational flyers about cancer prevention. Pictured (left to right): Shanna Fox, James Haltom, Shelley Koon, Michael Abel, Lisa Wald, Brennan Bouma and Krishna Gelot. more than 95 percent, but it drops significantly to less than 20 percent after treatment for metastatic breast cancer. Early detection, then, is crucial. Film Versus Digital In conventional mammography, differences in tis-sue densities and composition show up as con-trasting areas in the image, enabling physicians to see tumors or changes in tissue. However, tradi-tional film presents two challenges to radiologists. First, it cannot be altered after it’s acquired. To get different perspectives, technologists have to take more pictures, exposing the patient to more radiation. Or radiologists have to use a hot light and magnifying glass to get a different look. Second, because breast tumors and healthy breast tissue are very similar in density, up to 20 percent of cancers cannot be detected at all on X-ray film. In addition, when suspicious lesions are found on a mammogram, doctors generally choose to do a breast biopsy to make a clear determi-nation. The annual breast biopsy volume in the U.S. is approaching almost 1,000,000 per year, with benign diagnoses made between 80 and 90 percent of the time. By contrast, digital mammography offers an image that can be manipulated after it is acquired. “If you’ve ever used a digital camera, you know how simple it is to adjust the image after you’ve taken the picture,” says Pisano, who also serves as head of the International Digital Mammography Development Group.“You can easily rotate, zoom or adjust the contrast or brightness.” Digital mam-mography offers the same functionality for tech-nicians and the digital pictures are easier to store, retrieve and transport, particularly via the Internet. Putting it into Practice While it seems likely digital imaging could improve cancer detection, Pisano and the FDA want quanti-fiable proof before they give up on the traditional screen-film technology. “We don’t know that digital mammography is better yet,” Pisano cautions.“We’re still very early in its history. From a physics perspective, we certainly think it should provide earlier detection in dense-breasted women. But while early studies suggest reduced false positives, we don’t know yet that dig-ital mammography will find more breast cancer.” That’s why Pisano is leading an international More Effective Mammography continued from page 1 Mammograms of the same breast using digital mamography (A) and conventional X-ray (B). Dr. Pisano’s study will help determine whether digital mammography has the potential to give more precise information about the breast possibly leading to fewer callbacks for false positive or unclear results. cancerLines Spring 2001 3 study of 49,500 women in the United States and Canada to evaluate whether digital mammography is as good as or better than traditional mammog-raphy in detecting breast cancers. Nineteen centers in the United States and Canada, including UNC Lineberger, are participating in the study funded by the National Cancer Insti-tute. The study is expected to enroll patients for 3 years. That’s all good news for radiologists who tend to pre-fer digital images over film because they provide better information on which to base diagnoses, according to a small study led by Pisano last year. She and her team asked 12 certified, working radiologists in Chapel Hill, Dur-ham, Raleigh and Graham to look at, compare and grade images from tradi-tional X-rays and digital mammography for screen-ing and diagnosis of breast masses and calcifications. “It was clear that the radiologists preferred to look at different versions of the image for each of the three tasks,” Pisano says. “What they liked for screening is not the same thing they liked for diag-nosis of masses or diagnosing calcifications. The bottom line is that they need multiple versions of the same image to get as much information out of each image as they can.With digital mammog-raphy,” she says, “they can take different looks at the same image to get exactly the information they need without exposing the patient to additional radiation.” Pioneering Technology “In general, radiology technology has moved to digital over the last 20 years,” explains Pisano. “Mammography is the last field to go digital.” Tests and clinical trials of digital breast imaging began in 1992, but the technology didn’t receive FDA approval until Feb-ruary 2000. Currently, only GE’s Senographe has the FDA’s stamp of approval, but Pisano expects one or two other manufacturers to receive the green light this year. At present, there are only 20 to 30 places in the country using digital mam-mography and only a hand-ful use it in a clinical setting, and UNC was one of the pioneers. “For some time, re-searchers in the Computer Science department have been working on image processing—how to get increased information in images,” Pisano says. “That gave us a significant head start for the work we’re doing with digital mammography.” In fact, the algorithm used to help the troubled Hubble telescope see better is the same one that will probably be used in the future to help digital mammography see cancers better in the breast. “UNC is one of the world leaders in image proc-essing research, computer science and biomedical engineering.” • Hatchell Donation. UNC women’s basketball Coach Sylvia Hatchell donated $5,000 to gynecologic cancer research at UNC Lineberger at halftime of the January 14th game against NC State. Last summer she had a cancer “scare.” After her experience and to express her gratitude, she had pledged to donate $5.00 for each women’s basketball season ticket sold. Shown with her are (above, left to right): Dr. Linda Van Le, UNC Lineberger gynecologic oncology program; Dr. Bill Nebel, Coach Hatchell’s Chapel Hill gynecologist; Dr. Shelton Earp, Center director; Dr. John Boggess, UNC Lineberger gynecologic oncology program. “With digital mammog-raphy they can take different looks at the same image to get exactly the information they need without exposing the patient to additional radiation.” • • • • |
OCLC number | 29042636 |