Cancer lines

              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
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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
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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.”
• •
• •