WRITER: ARIANNE NARDO
CONTACT: BECKY SOGLIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-6660; fax (319) 335-8034
Release: Jan. 19, 2000
UI Cancer Center researchers receive American Cancer Society grants
IOWA CITY, Iowa -- Good research begins with good ideas. Faculty members
at the University of Iowa Cancer Center have both. Three researchers have
been selected as recipients in the first round of American Cancer Society
(ACS) Seed Grants for 1999-2000. The grants allow junior faculty members and
scientists to pursue new projects and make further progress in studying the
cause, prevention and treatment of cancer.
The UI recipients include Thomas S. Griffith, Ph.D., associate in urology;
Aloysius J. Klingelhutz, Ph.D., assistant professor in microbiology; and Emil
Racila, M.D., assistant research scientist in the UI Cancer Center. Each grant
recipient has received $20,000, which will fund their projects for the year.
Griffith's research, "Adenoviral Delivery of the Gene for the Apoptosis-Inducing
Cytokine, TRAIL, as a Therapy for Prostate Cancer," will focus on developing
an approach to introduce a specific gene into prostate tumor cells, so they
will die off through a natural process known as apoptosis. Apoptosis is a
biological occurrence in which the death of a cell is genetically and biochemically
"Most of the molecules essential for apoptosis are already present
in a non-active form just waiting for a sign to initiate a self-destruction
program," Griffith said. "In other words, cells appear to sense
that their presence is undesirable to the body as a whole, whereby they silently
commit suicide and are swiftly cleared by their neighbors."
The gene TRAIL (TNF-related apoptosis inducing ligand), identified as a
member of the tumor necrosis factor family, signals the death program in cells.
In preliminary tests, TRAIL was toxic against a variety of tumor types and
nontoxic to normal tissues. It has also been discovered that TRAIL can suppress
tumor growth through the apoptosis mechanism in mice that have been implanted
with human tumors.
With these promising results, the next step in Griffith's work is to develop
an adenovirus containing the human TRAIL gene and examine the effects it has
on prostate tumor cells and normal prostate cells upon infection in culture
or when growing in an animal. The UI Gene Transfer Vector Core is contributing
to the effort by producing a TRAIL-containing adenovirus.
"It is the hope that these studies will demonstrate that this viral-based
method of gene therapy will effectively deliver the TRAIL gene, and the resulting
protein product will cause the prostate tumor cells to commit suicide,"
Griffith said that the appeal of this study is that it may introduce a new
therapy that can be combined with other prostate cancer treatment protocols
to enhance the activity of the TRAIL produced. In addition, using this procedure
is an alternative to invasive surgery, which many prostate cancer patients
undergo for treatment.
Understanding cell death and the role it plays in cancer is also key to
the work of Aloysius Klingelhutz, whose project is titled, "Identification
of Genes Involved in Keratinocyte Senescence."
Klingelhutz explained that normal human cells die after a certain number
of cell divisions, while cancer cells divide indefinitely and are considered
"immortal." Senescence is the process of regulated cell death, and
it is believed to play a significant part in preventing normal cells from
turning into cancer cells. Cancer cells retain their enduring properties by
alternating DNA; they do this specifically in genes that are involved in senescence.
"The goal of the project is to identify and focus on those genes that
are involved in the senescence of human epithelial cells," Kingelhutz
said. "Over 90 percent of human cancers arise from epithelial cells,
so learning more about how these cells become immortal has the potential of
leading to better prevention, diagnosis and treatment of a number of different
The UI research team working on the project will use state-of-the-art technology
known as cDNA microarray expression analysis, available through the UI DNA
Facility. With this tool, researchers can examine the expression patterns
of thousands of genes at one time.
Emil Racila is also employing new research techniques for his project, "Detection
and Characterization of Carcinoma Cells in the Blood of Patients with Breast
The research begins with the hypothesis that cancer cells enter the blood
of most patients at an early stage in tumor development. In previous studies,
patients with various stages of breast cancer have had carcinoma cells appear
in their blood. According to statistical analyses, between 13 and 35 percent
of women with localized, no-spread breast cancer will have a recurrence and
die from their disease, even after primary tumors have been removed.
"This suggests that distant micrometastases have been missed in some
of these patients," Racila said. "The need for a more sensitive
method for evaluating the spread of carcinoma is evident."
Cancer spreads through the blood and lymph nodes. By utilizing techniques
to detect and characterize carcinoma cells in peripheral blood, researchers
are hoping to identify cancer in its early stages, when treatment is easier
and more effective.
The test involves a magnetic bead approach, in which epithelial cells are
selected. Epithelial cells form in the skin, glands and other tissues, and
are not found in the bloodstream. Blood from the patient is mixed with a colloidal
suspension of very small iron particles that are coated with antibodies specific
for epithelial cells. Magnets are then used to separate and evaluate the epithelial
While the central focus of the project is on breast cancer, Racila and his
team will also look at the detection of adenocarcinoma cells from primary
tumors in other organs and melanomas as well.
Racila said the benefit of this research is to treat early-stage tumors
and aim for a higher survival rate. Through tests such as this, Racila hopes
that more physicians can monitor the metastatic development of breast cancer
and pass on valuable information to patients when they make decisions about
treatment options and participating in clinical trials.
The UI Cancer Center in Iowa City is dedicated to cancer research, clinical
care, education, detection and prevention. The center advances cancer research
and education through the collaborative efforts of researchers and physicians
from 26 departments in six UI colleges and the UI Hospitals and Clinics. Using
knowledge gained through this research, UI physicians and other health care
professionals work together in the John and Mary Pappajohn Clinical Cancer
Center to provide the most advanced cancer care available in a manner that
recognizes each patient as an individual.
University of Iowa Health Care describes the partnership between the
UI College of Medicine and the UI Hospitals and Clinics and the patient care,
medical education and research programs and services they provide.