S e v e n t y -eight percent

of ovarian cancerpatients survive one

year after diagnosis. Ifdiagnosed and treated

early, the five-year rate is 95 percent. Unfortunately,

the American Cancer Societyestimates that only about 25 per-

cent of all cases are detected at thelocalized stage. If invasive cervical cancer is detected at

an early stage, it’s one of the most success-fully treated cancers with a five-year relative

survival rate of 91 percent for localized cancers.“You can see why detection is such an important

aspect of our work,” Fowler notes.“There’s still a lot of progress to be made in here, and

we’re on the front lines doing some really innovative thingsin patient education and screening mechanisms,” Fowler notes.

Here’s a look at two ground-breaking research initiativesin the GYN ONC division.

Ovarian Cancer PreventionThere’s further evidence that diet can play a significant rolein cancer prevention, according to a study undertaken byVan Le. She and her team are studying genistein, a soy-derived isoflavone phytoestrogen currently popular for a

“We’re do-ing really greatstuff.”

That’s how ButchFowler, professor andassociate chair of the de-partment of obstetrics andgynecology and head of thegynecologic oncology division,characterizes his colleagues’ work.“We’re seeing a lot of success in thelab and in the clinic—that means we’rereally doing something to help people.”

Fowler sees two challenges for GYN ONC.The first is ovarian cancer, which accounts for 4percent of all cancers and causes more deaths thanany other cancer of the female reproductive system.The American Cancer Society estimates there will be23,100 new cases and 14,000 deaths in 2000.

“This disease presents in an advanced stage because wecan’t detect it very well in earlier more treatable stages,”explains Linda Van Le, associate professor in the departmentof obstetrics and gynecology, division of gynecologic on-cology. “Thus patients are already at a disadvantage. To de-tect the disease early and improve treatment and survivalwould be a major accomplishment for our patients.”

The second is general prevention and detection. The twomost prevalent gynecological cancers — ovarian and cervi-cal — have good treatment outcomes if detected early.

U N C L i n e b e r g e r C o m p r e h e n s i v e C a n c e r C e n t e rcancerLinesUniversity of North Carolina School of Medicine & UNC Health Care Summer 2000

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NC-BCSP“Breaking the Silence”

Profile: Stuart Gold& Briefs

2Director’sMessage

LinebergerScrapbook

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8 Clinical Trials& Calendar of Events

Novel Therapies New Ways to Attack CancerA preliminary study undertaken by Bob Orlowski, assistantprofessor in the department of medicine, division of hema-tology-oncology, may lead to a more effective chemotherapyoption with few side effects for patients with hematologicmalignancies such as acute and chronic leukemias, multiplemyeloma, Hodgkin’s and non-Hodgkin’s lymphomas andcertain myelodysplastic syndromes.

“Based on laboratory and animal testing,” Orlowski says,“it seems possible that PS-341, the first of a new class ofdrugs called proteasome inhibitors, can be combined withstandard chemotherapy to improve the benefits of this treat-ment, offer an alternative treatment to people who have notbeen cured with standard chemotherapy, and cause smallerside-effects than the drugs which are currently used.”

Orlowski, an expert in proteasome research, is part of a col-laborative effort at the Cancer Center, including Al Baldwin,Jim Cusack and Claire Dees. This group is devising several newways to amplify chemotherapy’s effectiveness. Orlowski de-signed this study for patients with hematologic malignacies todiscover what side effects this new agent has, and to identifythe maximal dose that can safely be given to patients. This stepis the first in determining if a new drug will be useful in cancerchemotherapy. Once the maximal dose has been identified, asubsequent trial will apply it to determine its potential anti-tumor effectiveness.

New Treatments and Cures Laboratory studies using both cells in culture and animalmodels have shown that proteasome inhibitors can inducethe death of certain lymphoma and leukemia cells at a much

Geni

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UNC Gynecologic Cancer Team:

Warm Care,Hot Science

longer to complete. These delays len-gthen the already long time currentlyneeded to translate new discoveriesinto practice. Perhaps PresidentClinton’s recent announcement thatMedicare will cover the cost of clinicaltrials will stimulate the entire health

insurance industry to do the same, thusincreasing participation.

We need to raise awareness about the im-portance of clinical trials with practicing physi-cians and encourage patients to consider join-ing. Large comprehensive centers such as UNCLineberger need to provide networks for per-forming complex trials at UNC and less com-plex trials in cooperation with physician prac-tices. The molecular genetic discoveries — likethe one described on page 1 of this issue ofCancer Lines—hold great promise for treat-ments that work better and/or have fewer sideeffects. But, we can’t know until we test them.And, for now, clinical trials are the best way toassure that our treatments are safe and effective.

The National Cancer Institute is partneringwith the North Carolina Advisory Committeeon Cancer Control and Coordination and theCancer Information Services of the Carolinas totrain ambassadors to share information abouttaking part in a clinical trial. The pilot project istaking place in two U.S. locations—Baltimore,Maryland and North Carolina. Training ses-sions are being held throughout the state ofNorth Carolina.

The UNC Lineberger fully supports thiseffort to raise awareness about clinical trials. Inaddition, our Clinical Protocol Office (visit ourwebsite http://cancer.med.unc.edu or call 919-966-4432) can help answer your questionsabout the clinical trials available through theUNC Lineberger. They can also help direct youto other resources, such as the Cancer Informa-tion Service of the Carolinas, the National Can-cer Institute, or the American Cancer Society.

New drugs and treatment are coming fromUNC Lineberger researchers at an ever in-creasing rate. Our clinical trials apparatus mustbe ready to take advantage of these marvelousnew opportunities.•

higher rate than similar normal cells. “If the samewere true in people,” Orlowski notes,“this suggeststhat it is possible to kill these cancer cells withmuch less impact on the rest of the body.

“Since none of the currently used chemotherapydrugs kill cancer cells in the same way as proteasomeinhibitors, patients who have not been cured bythese other standard drugs might derive a benefitfrom this new class of agents,” he continues.“Thereis evidence that these inhibitors can be combinedwith drugs already used in chemotherapy to increasethe number of cancer cells killed.”

Working on the Molecular Level Orlowski’s work centers on molecular therapeu-tics, which allows researchers to develop a betterunderstanding of what is involved in the process bywhich normal cells become cancerous at thegenetic level. This knowledge will enable scientiststo identify important steps that can be targeted forblockade, either by currently available or newlydesigned drugs.

“The more we understand the development ofcancer,” he contends, “the more we have learnedthat it is a complicated, multi-step process which

2 cancerLines Summer 2000

New Class of Drugscontinued from page 1

can be very different even between two patients withthe same leukemia. It is unlikely that, in the nearfuture, we will have the resources to study each newpatient as an individual and design a treatment thatis unique for them. We must therefore identify tar-gets in cancer cells which are specific enough tothese cells that they are not present in normal cells,are important enough that their interruption willcause cancer cell death, but are present in a largeenough proportion of patients that it will be feasible

to use a relatively restricted number of treatmentcombinations in their therapy.”

Orlowski says a second challenge is using theinformation being generated on the biology oftumors and their biochemistry to design, test, andput into clinical practice new drugs that will havesignificant anti-tumor activity.

Looking Forward Over the past few decades, great strides have beenmade to improve the care of patients with hem-atologic malignancies. For instance, patients withHodgkin’s disease — once a lethal malignancy —now have an excellent possibility of cure. Butwhat’s true for some cancers is not true of all. Inmany other hematologic malignancies — includingsome of the acute and chronic leukemias, andsome of the non-Hodgkin’s lymphomas — cure ismuch less likely, and a majority of patientseventually die of their disease.

“The biggest challenges in the field of hema-tologic malignancies are, therefore, to identify newagents with activity in these diseases that mightimprove our current cure rates, and to betterunderstand the biology of these illnesses,” Orlow-ski notes. “This insight might allow us to eithermake better use of the drugs we already have, ordesign new ones, and hopefully both.”•

Director’sMessage

Director’sMessage

Imagine this.Late one night I

walk into one ofthe many activelaboratories in theLineberger build-ing. An excitedgroup shows metwo tissue culturedishes. I am star-tled. In the dishcontaining cancercells, the cells aredead or dying. Inthe dish containing

normal cells, the cells are alive and growing. Aswe switch our scientist’s garb for the physi-cian’s white coat and go to the clinic, do wegive the new substance to our cancer patients?

The answer, of course, is ‘no.’ Tissue culturedishes are not people. Experiments using tissueculture cells only give hints as to whether orhow this new ‘drug’ will work in humans. Thesubstance might work, but it could makethings worse. The doctor’s primary credo isPrimum non nocere — first, do no harm. We areexcited, but the evidence is not yet strong.

To learn more, we give the ‘drug’ to micewho have cancer. Mouse models of human can-cers are not people either, but their geneticmake-up, physiology, and immunology are sim-ilar enough for them to be good, but imperfectmodels. After our new treatment, the mice’stumors shrink and in many cases disappearaltogether. We then test it for toxicity in otheranimal models. Now do I give the new drug tomany patients?

The answer is both ‘no’ and ‘yes.’ No, wedon’t use the new agent to treat many patients.The evidence that the ‘drug’ is effective is nowmuch stronger, but there is still much that we

don’t know about how it will affect humans.But, yes, it is time to give the ‘drug’ to somepatients with advanced disease to see if it canbe suitably formulated for human use. Can it begiven orally or intravenously? Will it harm ourpatients? Now it is time for a clinical trial.

Clinical trials guard the gateway that leadsfrom the laboratory to the bedside. In a seriesof steps or tests, these trials separate the trulyeffective treatments from the merely promisingones. First, in a very small number of patientswhose disease is advanced and has resisted allattempts with current treatment. This Phase Itrial (mentioned above) identifies the maxi-mum doses that could be effective but that arealso not toxic. Second, in a larger but still smallnumber of patients, Phase II trials tell us whe-ther the treatment is effective without seriousside effects. Finally, with a large number of pa-tients, Phase III trials tell us whether the newtreatment is better than the current treatment.Only after a new treatment has passed all threetests do we let it move from the laboratory toclinical practice and the bedside.

Clinical trials are essential to improving notonly cancer treatment but also diagnosis,screening, and prevention. Virtually every re-cent advance in cancer has passed through theclinical trial gateway, which is the best way toassure that what we do to fight cancer iseffective, safe, and ethical.

Discovery is happening so fast. Literallyhundreds of drugs are moving toward andthrough the clinical trials gateway. To find out ifthese very promising drugs really work, manythousands of volunteer patients and their phy-sicians will need to participate in clinical trials.Right now, only three percent of all cancerpatients join a clinical trial. Participation is evenlower among older patients and many ethnicgroups. Low participation means that trials take

Dr. Shelton Earp

UNC Lineberger is designated acomprehensive cancer center by theNational Cancer Institute.

Cancer Lines is a semi-annualpublication of the UNC LinebergerComprehensive Cancer Center, The University of North CarolinaSchool of Medicine at Chapel Hill.

Dr. H. Shelton Earp, III, DirectorDr. Joseph S.Pagano, Director EmeritusDianne G. Shaw, Director of

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(Left to right) Drs. Small and Orlowski are studying the ways inwhich this new class of drugs kills cancer cells in the laboratory,which will help to define how best to use them in human patients.

multitude of reasons, including its ability to abatehot flashes in women preferring to avoid hormonetherapy.

The early research is exciting, Van Le says.“Genistein is not associated with major side effects,is inexpensive relative to major drugs and is readilyavailable in health food stores.”

Structurally similar to estrogen, genistein inhi-bits breast cancer cell growth in laboratory studies.“Coupled with the observation that endometrialcancer, usually a hormone dependent cancer, is lesscommon in the Asian countries where soy plays alarge part in daily diets, we undertook studies todetermine if genistein inhibits growth of endome-trial and ovarian cancers, as well. To date, our dataappear encouraging.”

While the public is fairly cognizant of ovariancancer, cancer of the uterine endometrium is lesswell-known. However, it will result in approximately6,500 deaths this year, with 36,100 expecteddiagnoses. Incidence rates are higher among whitewomen (22.4 per 100,000) than among blackwomen (15.3 per 100,000), though mortality ratesare the opposite with nearly twice as many blackwomen dying from the disease than white women.

Van Le is cautiously optimistic about genistein’spotential. Though still being studied, she concedesthat,“the results, if positive or encouraging, wouldmean ready access to this product since it is alreadyon the market. Quality of life would not be im-pacted greatly since the side effects are minimal.”

Cervical Cancer Detection & PreventionSay “Pap smear” in a room full of women andyou’re likely to be met with reactions ranging fromvague discomfort to dirty looks. But this much-maligned procedure can hold the key to early de-tection of cervical cancer, one of the leading gyne-cological cancers. In fact, since the advent of thePap smear, the rate of cervical cancer has decreasedmarkedly. Still, this year, an estimated 12,800 casesof invasive cervical cancer will be diagnosed andapproximately 4,600 women will die of thedisease.

Warm Care, Hot Sciencecontinued from page 1

The Gynecologic Cancer Team. Front row (left to right): Ann Dunlap; Dr. Leslie Walton; Susan Godfrey; Dr. Dan Veljovich; Dr. JohnBoggess; Juanita Moore. Back row (left to right): Mary Horton; Dr. Wesley Fowler; Dr. Linda Van Le; Dr. Tom Morrissey.

cancerLines Summer 2000 3

GynecologicCancerAwarenessMonthUNC Linebergerobserved the firstnational GynecologicCancer AwarenessMonth in Septemberwith a specialexhibition of quiltsmade by NorthCarolina women,honoring friends andfamily members whohave been affected by ovarian and othergynecologic cancers, as well as quilts made by members ofthe National OvarianCancer Coalition.Standing in front of

the quilt given to UNC are: (left to right) Dr. Wesley Fowler, chief, gynecologic oncology division; Karen Binder, ovarian cancer survivorand chair of the Triangle N.C. Ovarian Cancer Connection, and Marie Owens, ovarian cancer survivor, hold a proclamation fromGovernor Jim Hunt declaring September as Gynecologic Cancer Awareness Month.

Despite that, however, few women get regularcheck-ups that include this minimally invasive, in-expensive screening test.

“The last 10 patients I’ve seen with advanced cervical cancer did not have a Pap smear in 10years,” Van Le notes. “If all women could undergoscreening regularly, cervical cancer would not besuch a problem.”

John Boggess, assistant professor, obstetrics andgynecology, mirrors Van Le’s passion. He’s leadingthe charge by undertaking a combination of clinicaland basic scientific research to find new ways todetect and prevent cervical cancer.

Boggess has identified a potential biomarkerthat would enable a more accurate Pap smear.“We know that human papilloma virus (HPV)causes cervical cancer—but it’s overwhelminglycommon in women who don’t develop thecancer.”

What happens to HPV to spur cancer growth?DNA integration. The HPV breaks open and be-comes a part of a woman’s chromosomes andcauses abnormal cell cycling. This, in turn, pro-

motes the expression of telomerase, an enzymewhich is activated in almost all cervical cancers.

“If we can detect telomerase in the cervix, weknow the patient has a high risk lesion that’s morelikely to become cancer,” Boggess explains. So heand his team are attempting to integrate telomerasetesting with Pap smears to increase accuracy,reduce abnormal results and avoid unnecessarybiopsies. The new and improved Pap is currently ina 120-woman trial.

Boggess also is collaborating with Jo Ann Earp,chair of health behavior and health education at the UNC School of Public Health, to develop acommunity-based outreach program to promotePap smear screening. The program will be struc-tured similarly to Earp’s ground-breaking breastcancer screening program (see story, page 5).

“Getting more women to have Pap smears is im-portant,” Boggess says, “but it’s a challenge. Thesetests and issues are sensitive. However, we have agreat model to follow in Dr. Earp’s work with breastcancer, so we’re very encouraged.”

The Team ApproachThis cross-department collaboration is a huge benefitto researchers and patients alike. “Lineberger is awonderful place to work because I have the clinic,the molecular lab, epidemology, outreach efforts andtreatment trials right here,” Boggess says. “That kindof interaction among areas is truly exciting.”

Van Le agrees.“We have a team approach to allgynecologic cancers that integrates new findingsclinically. We are equipped, by virtue of our clinicaltrials office, to initiate new promising treatmentsquickly. With this infrastructure in place, we canoffer patients new, more promising treatmentsexpeditiously. We also have a great team! We havetwo dedicated chemo nurses, a devoted clinic staff,and offer a compassionate attitude towards all ofour patients with cancer.”

All this bodes well for the future of cancerresearch at Lineberger. “Nineteen-ninety-nine wasa very productive year for us,” Fowler notes. “I’mlooking forward to more great developments thisyear.”•Photo montage on cover includes a conventional pap smear (left).

“I could not imagine a fieldmore exciting than this,” hesays.“Working with incrediblekids and families, being ableto provide continuity of careand watching these kids growup and have families of their

own.” Somberly he adds that the most challengingpart of his job is “helping families deal with thehardships of cancer diagnosis, and unfortunatelysometimes death.” Happily, about 70 percent ofchildhood malignancies are now curable.

“Working with kids is fun,” Gold says. “The keyis not to treat them as if they are ill, to treat themas normal. They teach me a lot — especially aboutmy priorities in life.”

While he loves the patient interaction, there alsois research value to working with kids. “This groupof patients gives clues to the genetic basis of cancer— and hopefully clues to help all types of cancer.”Kids with cancer can help researchers identifycertain malignancies that run in families or havebeen identified with certain genes/chromosomeabnormalities. “That’s helped identify tumor re-lated genes.”

Gold also is a member of the Children’s CancerGroup and is the principal investigator for thegroup’s North Carolina section. “I have worked onseveral of their treatment protocols as a member of their committees for acute leukemia and brain

4 cancerLines Summer 2000

Study shows black churches canhelp improve healthy behaviorsBlack churches, long a source of spiritual comfortand community for their members, can also helpimprove people’s eating habits and other behaviorsto make them healthier, according to a major newstudy involving a dozen researchers, three Triangleuniversities and state health experts.

The study—the largest of its kind ever done—was conducted by Marci Campbell, assistant profes-sor of nutrition in the schools of public health andmedicine, and colleagues. It was intended to de-termine whether church-related activities couldchange ingrained eating habits.

Nutrition and other health experts now believereducing dietary fat and increasing fruit and vege-table consumption can cut cancer risks, which arehigher and increasing among blacks, while provid-ing other significant health benefits as well.

“We found we could boost the amount of fruitsand vegetables people in the study consumed byabout a serving a day,” said Campbell, leader ofLineberger’s cancer prevention and control pro-gram.“One serving equals a half cup of fruit orcooked vegetables, a cup of salad or six ounces of100 percent fruit juice. That doesn’t sound like alot, but when you think of this amount of changeacross the large sample of 2,500 people involved,that everyone was surveyed regardless of their level

of participation and that theeffect has lasted for at leasttwo years, it’s actually prettyimpressive.”

The study’s results pro-vide good news, showingthat eating patterns can bechanged and that church

activities are among the most effective ways ofdoing that. Similar efforts through schools andwork sites have shown smaller effects onbehavior.

NCI awards UNC-CH $5 millionfor unique prostate cancer studiesUNC researchers received $5 million from theNational Cancer Institute and the National Insti-tute on Aging to investigate prostate cancer, thesecond leading cause of cancer deaths among menin the United States. Scientists will investigatemechanisms responsible for reappearance ofhormone-independent prostate cancer in patientsfollowing treatment to remove the source of andro-gen. They also will investigate why black men de-velop prostate cancer twice as often as white men.Answering these questions should provide solidclues to the illness that will benefit both races, thescientists say.

“Prostate cancer requires male hormonesknown as androgens both to develop and to grow,and the same is true for benign prostate tissue,”said James Mohler, associate professor of surgery.“One big difference is that cancer can spread,which obviously can make it fatal. Researcherswant to determine how the cancer can grow with-out male hormones. Such information might en-

able them to effectively cure prostate cancer just bypreventing its re-growth,” the surgeon said.

“A particular focus will be on how this processis different in Caucasians and African-Americans,who are twice as likely to die from prostate cancer,even after accounting for possible differences inhealth care,” he said.

Co-principal investigators are Frank French,professor of pediatrics and director of the Labor-atories for Reproductive Biology, and Gary Smith,professor of pathology and laboratory medicine.Others involved in the project are: ElizabethWilson, professor of pediatrics and biochemistry;Sharon Presnell, assistant professor of pathologyand laboratory medicine; Desok Kim, researchassociate at the Lineberger Center, and ChristopherGregory, postdoctoral fellow in pediatrics and theLaboratories for Reproductive Biology.

Scientists find protein in Epstein-Barr virus causes B cell lymphomain laboratory miceAn international team of scientists from UNC andJapan has proven that a protein called latentmembrane protein 1 in Epstein-Barr virus causes aform of cancer known as B cell lymphoma in mice.The work is important, the scientists say, because itshows the protein’s central role in Epstein-Barrvirus’ ability to change normal cells into cancerousones. That virus already is known to cause infec-tious mononucleosis in humans and has beenassociated with such malignancies as Burkett’slymphoma, Hodgkin’s lymphoma and nose andthroat cancer. It is especially hazardous to AIDSpatients and other patients whose immunesystems have weakened.

ProfileProfile

BriefsBriefs

Pediatric Oncologist Stuart Gold Learns Life’sPriorities from His PatientsEven while growing up in Savannah, Ga., StuartGold knew his future would involve children andmedicine. “My uncle was an old-fashioned pedia-trician,” recalls Gold, associate professor of pedia-trics, in the hematology oncology division. “Hemade house calls, he was warm and compas-sionate. And he was a great role model.”

Between playing tennis, running, sailing andtaking pictures, Gold was learning the personal,compassionate aspects of patient care at his uncle’sside. “He’d even take me with him to the publichealth clinics in Atlanta,” Gold remembers.

Decades later, Gold takes care of children, too— kids with cancer and blood disorders includingsickle cell disease and hemophilia/clottingdisorders. Chatting with him, it’s clear he em-bodies the very characteristics he admired in hisuncle.

tumors.”Gold did his undergraduate work at Vanderbilt,

majoring in math with a minor in chemistry. Hemedical school there. He did his pediatric andsubspecialty training at the University of ColoradoHealth Science Center from 1981 to 1989.

When he’s not working with kids, Gold enjoysrose growing, running and cooking. In fact, hisdream is retiring and tending to his garden, whichhe claims is “the best rose garden around” withmore than 100 rose bushes.•

continued on page 7

5cancerLines Summer 2000

Breast cancer is fairly easy to detect—often at an early, treatable stage. Surpris-ingly, however, less than half of womenage 40 and older in the United Stateshave regular screening mammograms —and the number is even lower in theAfrican-American community. The inci-dence of breast cancer increases in allwomen as they grow older.

Those facts contributed to the crea-tion of the North Carolina Breast CancerScreening program (NC-BCSP), a long-term, comprehensive, multi-level com-munity intervention project designed toincrease breast cancer screening amongolder African-American women in fiverural eastern North Carolina counties.The program intended to increase initialand repeat mammography screening byblack women ages 50 years and olderand increase follow-up of positivescreening mammograms. To do that, itdeployed 160 lay health advisors (LHA), localwomen who provided social support for mammog-raphy to women within their social networks.

“In general, the increase of mammographyscreening nationwide is pretty strong,” notes JoAnne Earp, professor and chair of the departmentof health behavior and health education and prin-cipal investigator of NC-BCSP. “It was a surprise tofind that black and white women, starting frommore than a 20 percent point differential in 1994,had essentially the same screening rates in some ofthese counties at the end of just three years of ourintervention.”

Earp and her fellow researchers are currentlygathering data from the study’s second follow-up tosee whether the early progress was sustained over afive- or six-year time period.“I am betting that it willbe, as least for two or possibly three of our fivecounties where the lay health advisors continue tobe extraordinarily active,” Earp predicts.

Not only did the study show that interventionslike the LHAs could “break the silence” about theimportance of breast cancer screening in the older,rural African American community but, moreimportantly, it closed the racial gap that existed inbreast cancer screening before NC-BCSP began,Earp says.

The study also uncovered another interestingfinding. “What appeared to be a racial gap in physician recommendation for mammographyscreening turned out to be an income andeducation gap,” she explains. “Women who sawtheir doctor more often — who were younger, hadhigher incomes, and more education —were morelikely to receive a recommendation from physiciansto go for their annual screening mammogram thanwere women of the opposite characteristics—thevery women who are dying more often of breastcancer. Such a disparity in screening recom-mendation was very surprising and more than a bitunsettling.”

The Lasting ImpactThe NC-BCSP shows that adaptinginterventions for the communities,populations and groups most in need ofthem, and targeting many groups in acommunity, can “get the job done” in away that fits the norms and values of thecommunity in which it’s happening.“We can see movement towards ahealthier, better screened populationeven on a sensitive issue such as breastcancer screening,” Earp comments.

Geni Eng, a colleague on the projectand professor of health behavior andhealth education, says what really madethe difference is “tireless efforts by thewomen who were the living statisticscontributing to the higher breast cancermortality rates among black women inthese counties. If we can have this effectin these very poor, rural, poorly educated

counties of eastern North Carolina, surely othersin urban ghettos and rural areas elsewhere in theUnited States can also mount programs that willmake a difference in the public’s health.”

Spreading the WordBut to be successful they not only need an exam-ple, they need money to pay for screening fromCenters for Disease Control and state govern-ments, and money for treatment where breast can-cer is found.

To that end, Earp, Eng and the rest of the NC-BCSP team are working to get the word out abouthow natural helper lay health advisors have beensuccessful in increasing breast cancer screeningrates in eastern North Carolina.

There’s still work to be done, however. “Whilenationally we need more efforts aimed at reachingvulnerable communities where screening rates arestill low— for example the Latino community orsome Native American or Asian communities —our prevention efforts may be best targeted athealth professionals to get them to examine andchange their behavior,” Earp urges. “Certainlyhealth care providers should be sent the messageas much or more than the communities in need.”

More to ComeThese answers are just the beginning, Earp says. Soshe and her team continue to ask questions.“Whydo certain community interventions work, or workin certain populations and not others, or worksome of the time but not the rest of the time? Theimportant questions need much more attentionpaid to them than the amount of money currentlybeing put into prevention social science research,”she notes.

“The success of this project, at the highest level,is important because it may convince more policymakers to fund more generously evaluations ofprevention intervention efforts and that will be agood thing!”•

NC-BCSP Successfully“Breaks the Silence”about Breast Cancer

NC-BCSP community outreach specialists past and present, and program staff. Front, left to right:Lucille Bazemore; Georgia O’Pharro; Eva Hill; Bernice McElrath; Barbara Leary. Back, left to right:Linda Mayne, regional coordinator; Survilla Cherry, Dr. Jo Anne Earp, program director; Judy Ruffin;Dr. Eugenia Eng, program co-director; Helen Guthrie; Evelyn Neptune.

1999 PatientEducationSymposiumOrganizers of the 1999Patient Education Sym-posium (left to right):Anne Washburn, coordi-nator, Cancer PatientEducation and Support,symposium chair; Dr.Shelton Earp, LinebergerCenter director; SharonCush, neuro-oncology nurse and symposiumresearch update sessionschair; Karen Binder, quiltdisplay; Dr. Jeff White,keynote speaker, Director,Office of Cancer Comple-mentary and AlternativeMedicine, National CancerInstitute. Over 300 patientsand family members

attended the day-long meeting which included research updates for all cancer sites, a luncheon speaker on nutrition, and breakout sessionson acupuncture, massage, music therapy, nutrition and relaxation.

6 cancerLines Summer 2000

LinebergerLineberger

“We think this work is highly important becauseit should provide a whole new way of thinking aboutbasic molecular mechanisms related to cancer andto control of aging in cells,” Griffith said.

“DNA typical of the chromosome end, or telo-mere, was looped back around and attached to a dis-tant internal site on the DNA and held there by theadded protein,” Griffith said.“The loop thus formeddisguised the DNA end, keeping it cloaked or hiddenfrom the sensors that trigger the cell suicide response.”

Because chromosomes shorten as people age,many scientist believe telomeres play some unex-plained central role in the body’s lifelong biologicclock, Griffith said. Thus, telomeres may be somekind of regulator of cell death. The National Insti-tutes of Health supported the research at bothlaboratories.•

“We have shown for the first time that Epstein-Barr virus clearly can cause cancer,” said NancyRaab-Traub, professor of microbiology and immu-nology, and leader of the Lineberger’s virologyprogram.“Now we can go after the specific proteinthat is responsible and perhaps one day stop thatprotein function and prevent the cancer fromgrowing.

A National Cancer Institute grant to Raab-Traubsupports the research.

Chromosomes found to end in big loopsThe puzzle surrounding why cells’ internal repairmachinery doesn’t mistake the ends of chromo-somes for broken DNA and either “fix” or destroythem appears to have been solved by a team of re-searchers who discovered that mammals’ chromo-somes end in loops. Under intense magnification,those chromosome ends, or telomeres, look some-thing like lassos.

A report on the findings appeared as a coverstory in the journal Cell. Lead authors are JackGriffith, professor of microbiology and immunol-ogy at the UNC-CH School of Medicine and Line-berger faculty member, and Titia de Lange, profes-sor and head of Rockefeller’s Laboratory of CellBiology and Genetics.

Briefscontinued from page 5

Golf Event. The Fountain Odom golf tournament was held in October inCharlotte. (Left to right) are: Sen. Odum; Center director Dr. Shelton Earp; andSenator Tony Rand. The event raised close to $17,000 for UNC Lineberger.

2000 Club Brunch. Corporate sponsors from Wachovia Bank (left to right) Scott and Tricia Faircloth and Carol and Jud Franklin, whoop itup with Ramses at the 2000 Lineberger Club Brunch and basketball game.

OutstandingService.

Board of Visitorsmembers (left to right)Missy Julian-Fox and

Sue Moore received theOutstanding Service

Awards. Sue Moore, abreast cancer survivor,

was honored for herleadership in breast

cancer advocacy. Missy Julian-Fox, a

breast cancer survivor,was cited for her

extensive work onbehalf of the Center.

Wit. The cast and director of the Playmaker’s production of “Wit,” the play about an English professor who is diagnosed with Stage Four ovariancancer, visited with Lineberger faculty and staff to discuss issues and ideas ofthe show. (Left to right) UNC gynecologic oncology surgeon, Dr. John Boggess,“Wit” director Drew Barr;“Wit” lead actress Tandy Cronyn; Dr. WesleyFowler, chief, gynecologic oncology division.

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Vitale Visit. Sports announcer Dick Vitale visited UNC on Thursday,February 3, to talk to cancer patients and families. With Nick Valvano, CEOof the V Foundation, he presented a check from Papa John’s Pizza and the VFoundation to the Thoracic Oncology Program. During his hour-long stay, heautographed pictures and signed basketballs. (Left to right): Papa John’s Pizzarepresentative Mike Smith; V Foundation for Cancer Research CEO NickValvano; Thoracic Oncology program members Dr. Patricia Rivera; Dick Vitale;Dr. Mark Socinski; clinical nurse Ann Steagall; Dr. Frank Detterbeck.

Fellows & Preceptors. 1999 Lineberger Fellows with their preceptors.Fellows receive a $3,000 supplementary stipend to recognize the excellence oftheir research activities. The awards, begun in 1987 encourage promising newcancer researchers. This year’s fellowships were made possible by Best Distribut-ing Company in Goldsboro, NC, and the Cancer Research Foundation ofAmerica in Arlington, VA. (Left to right): Preceptor Dr. Mark Peifer, Fellow RobCavallo; Fellow Jun Nakamura; Preceptor Dr. Eng-Shang Huang; Fellow RobertJohnson; Fellow Linda Gorman; Preceptor Dr. Ryszard Kole; Fellow AnneclaireDe Roos; Preceptor Dr. Andrew Olshan.

Dedication. The Big Rock Blue Marlin office in the Lineberger buildingwas dedicated at the February Board of Visitors’ meeting. (Left to right):Ben and Sue Moore, members of the Board of Directors of the Big Rock BlueMarlin Tournament and of the UNC Lineberger Board of Visitors; and Dr.Albert Baldwin, Associate Director of Basic Research.

Walk for a Cure.North Carolina CentralUniversity studentsparticipated in “Walkfor a Cure.” The event,sponsored by thebusiness club Phi BetaLambda, Inc., raisedover $800 for the UNCBreast Center. Pictured(left to right) front: SonyaScott, student advisorto Phi Beta Lambda,UNC LCCC directorDr. Shelton Earp; secondrow: Algenon Conyers,Felicia Taylor, HulonMcIver, Jr., MelanieBishop; fourth row:Quincy Bess.

Theta Chi. Jonathan Fulcher, a cancer survivor and member of Theta ChiFraternity (Theta Omega chapter) from Appalachian State University, joins hisfraternity brothers in delivering baseball caps for pediatric oncology patients.

Floyd Relief.Lineberger faculty and staff supportedour research team ineastern North Carolinawho were impacted by Hurricane Floyd.Bags of food weredelivered during theholidays. Photo showsdelivery to Newton

Grove. Other funds donated were used for shoes, grocery, coupons, utilitymaintenance and additional needs.

For information about any of these clinicaltrials, please call 919-966-4432.

Chronic Myeloid Leukemia (STI571-102)This is an open-labeled pharmaceutical PhaseII study for Philadelphia chromosome-positiveCML patients in myeloid blast crisis.

The study is designed to evaluate the anti-leukemic activity and safety of once daily oraladministration of STI571, a protein-tyrosinekinase inhibitor. Secondarily, the study willlook at duration of response, overall survival,cytogenetic response, symptomatic improve-ment, possible mechanisms involved in resis-tance to this drug, and signal transductioninhibition in vivo.

Nationally the target accrual is 100 newlydiagnosed patients who have not received pre-vious therapy for the accelerated and blasticphases of the disease.

Limited enrollment is available for patientswho have received previous therapy for CMLin blast crisis. This population will only beevaluated for response. Statistical considera-tions are based on the previously untreatedpatient population only. PI Thomas Shea, M.D.

Melanoma (UCHSC98-533) Colorado HealthSciences is sponsoring this multi-center PhaseIII study of neoadjuvant CVD/IL-2/IFN inpatients for Stage III Malignant Melanoma.

Patients will receive two cycles of cisplatin,vinblastine, decarbazine, IL-2, and interferonfollowed by lymphadenectomy. Post-opera-tively, patients will receive an additional twocycles of this biochemotherapy regimen.Patients will be hospitalized for 5 days duringthe administration of all biochemotherapy.

Eligibility requires patients present with atleast one measurable lymph node and be bio-chemotherapy naïve.

One hundred patients will be enrolled in atwo-year accrual period. The primary objectiveis to determine the disease-free duration andoverall survival in Stage III melanoma. Cuta-neous melanoma is one of the most rapidly in-creasing rates of any cancer in the US. PIThomas Hensing, M.D.

Hematologic Malignancies (LCCC 9834)This is an investigator initiated Phase I studyusing a novel drug (PS-341) in patients withhematological malignancies refractory to allstandard therapy.

PS-341 is a proteasome inhibitor. Studieshave shown that the proteasome is absolutelynecessary for cell survival and proliferation.Disruption of this pathway has been shown tolead to apoptosis, or programmed cell death.

Patients are treated at the General ClinicalResearch Center twice weekly for four weeksfollowed by a two-week rest period. If stable,patients can continue for more treatment.

Correlative laboratory studies are looking atplasma pharmacodynamics of PS-314, protea-some inhibition, interleukin 6 levels (multiplemyeloma patients), and extent of apoptosis inperipheral blood mononuclear cells.

Candidates must be refractory to conven-tional therapy, or have a disease for which con-ventional therapy is not recognized. PI RobertOrlowski, M.D., Ph.D.

Breast Cancer (LCCC 9925) This is a PhaseI/II investigator initiated trial investigatingHerceptin® as a potential radiosensitizer in patients who have not had a complete clinicalresponse to neoadjuvant chemotherapy, orpresenting Stage IV, T4d, and N2 breast cancer.

Herceptin® will be administered weekly whilepatients receive external beam radiotherapydaily for five weeks. Effective radiosensitizers en-hance radiation-induced cell kill. Pre-clinicalstudies indicate the potential of Herceptin® as aradiosensitizer in the treatment of HER2 over-expressing breast cancer. The epidermal growthfactor receptor (EGFR) family consists of HER2.

Herceptin® was developed to interfere withHER2 signaling. Inhibitors of growth factors inconcert with DNA damaging agents may serveto increase tumor cell kill. PI Carolyn Sartor, M.D.

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O C T O B E R

13th Board of Visitors Meeting.Lineberger Cancer Center, Chapel Hill, NC.

UNC Lineberger Comprehensive Cancer CenterCB# 7295School of MedicineUniversity of North Carolina at Chapel HillChapel Hill, NC 27599-7295(919) 966-3036http://cancer.med.unc.edu

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Chapel Hill, NC 27599-1110

Clinical TrialsUnderway