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Hello again, Some more news to come out of AACOR this week and all encouraging. file:///C|/windows/temp/nscomm40/tmp/tmp3/edt1.htm God Bless You, marty auslanderTitle: Internet Home - American Association for Cancer Research (AACR)
Potential Cancer Markers: Early Data Indicate Prognostic Promise
for Tß15 and
Future Research Directions for Angiostatin
- Angiostatin in Circulating System Suggests
New Research Directions -
- New Test May
Detect Which Prostate Cancers Will Spread -
Research Results from AACR 91st Annual Meeting
SAN FRANCISCO, April 1, 2000 -- For the first time, researchers
have determined
that angiostatin, a weapon in the body's arsenal against disease,
is present in the
circulatory system of both healthy control subjects and patients
with tumors. This finding
opens avenues of research that may one day produce noninvasive
aids to diagnosis and
prognosis in human cancer.
"The finding that healthy people produce angiostatin, and that
some non-tumorous
conditions may increase its production, implies that eventually
we may be able to induce
the human body to increase its own internal supply of an anti-angiogenic
drug," explained
Johan R. Westphal, Ph.D., a postdoctoral fellow in the Department
of Pathology,
University Medical Center St. Radboud, in Nijmegen, The Netherlands.
"Before that can
happen, however, we need more information on how the body generates
angiostatin and
the factors that control this process."
Since its discovery in 1994, angiostatin has excited scientists
with its tumor-starving
potential. This naturally occurring protein demonstrates the
ability to block the formation
of blood vessels that feed tumor growth - a process referred
to as anti-angiogenesis.
Data on Presence of Angiostatin in Circulatory System Suggest
Research
Directions to Define Clinical Utility
The research team tested for angiostatin in a range of body fluids
in several groups:
healthy control subjects, patients with various brain tumors,
patients with cancers of other
sites, and patients with assorted benign conditions and cancers.
Angiostatin was found in
all fluid samples from brain tumor patients, but not in their
urine after surgical removal of
the tumor; in all fluids but urine from healthy people; in cerebrospinal
fluid from subjects
with cancerous and noncancerous conditions, including benign
brain tumors; and in ascites
(fluid in the abdominal cavity), and pleural fluids from cancer
patients and people with
inflammatory disorders.
"At the moment, the value of angiostatin as a biomarker or therapeutic
agent is limited.
Although the potential is exciting, it is still highly speculative,"
Dr. Westphal cautioned.
"Despite the limitations of a small and highly diverse study
population, our data suggest
potentially fruitful areas for further investigation."
The researchers are conducting a related study of body fluids
taken before and after
surgery from colon cancer patients. In this study, the researchers
are adding tests for
endostatin (another natural angiogenesis-inhibiting protein)
and VEGF (vascular
endothelial growth factor), which is associated with angiogenesis.
They will try to correlate
data on these substances with the vascular (blood vessel) densities
of tumors -- a valuable
prognostic indicator. Because blood vessels act as feeding tubes
for tumors and escape
hatches for marauding cancer cells, the greater the vascular
density of the tumor, the
poorer the prognosis. The traditional procedure to determine
vascular density requires a
tissue sample of the tumor.
"By determining the levels of VEGF and other factors in the circulation
from cancer
patients, we hope to be able to predict the vascular density
of a tumor, and thus obtain
important prognostic information in a noninvasive way," Dr. Westphal
said.
Improvements in the ability of clinicians to predict the course
of disease have important
implications for cancer staging, treatment, and prognosis. At
the 91st Annual Meeting of
the American Association for Cancer Research (AACR), researchers
describe
encouraging new findings with two high-potential proteins: Tß15
and angiostatin.
Novel Test May Help Predict Which Prostate Cancers Will Spread
Preliminary data on a new test show promising results in predicting
which men are at high
risk for metastatic prostate cancer and, who therefore, may be
candidates for early
systemic treatment, before the disease takes hold in other sites.
For more than 50 percent of men diagnosed with locally confined
prostate cancer, the
disease later spreads. Clinicians rely on tumor classifications
based on a spectrum of
"histologic grades" to guide treatment decisions. At diagnosis,
however, most prostate
cancers are "moderately differentiated" -- meaning that they
don't yet display the
distinguishing features that help determine appropriate therapy.
If clinicians could foresee
which prostate cancers would metastasize, they could recommend
therapies designed for
nomadic malignant cells and spare other patients the effects
of unnecessary treatment.
According to researchers who investigated the predictive value
of a protein called
thymosin ß15 (Tß15) for spread of the disease, the
substance showed a high degree of
accuracy as an early warning signal for metastasis. Tß15
is thought to enhance the
metastatic potential of prostate cancer cells.
The research team at Massachusetts General Hospital and Harvard
Medical School in
Boston examined Tß15 in biopsy specimens from 32 men with
clinically localized,
moderately differentiated prostate cancers who were treated only
with radiation therapy,
not surgery or chemotherapy, and then followed the men for a
period of six years.
Investigators scored the staining intensity of Tß15 from
3+ (the strongest) to 1+ (the
weakest). Of the patients whose initial biopsy specimens stained
3+, 63 percent
experienced spread of their prostate cancer to bone, and 75 percent
of men with 3+
scores showed elevated prostate-specific antigen (PSA) within
five years. Rising PSA
levels are currently used to determine if the disease has spread
-- probably to the bone,
the most common metastatic site in prostate cancer.
"If a larger study supports our results, a low-cost Tß15
test can be used at initial diagnosis
to advise patients on the potential need for systemic therapy,
which is the only curative
treatment for clinically occult, micrometastatic disease," said
Arnab Chakravarti, M.D.,
Harvard Medical School. "The same test may help patients decide
against radical local
treatment, such as surgery, if they show a low probability of
distant failure."
Dr. Chakravarti and his research team are the principal investigators
for the
multi-institutional Radiation Therapy Oncology Group, which will
conduct a larger,
two-part study involving approximately 100 patients who will
be monitored for 10-15
years. The first study will examine Tß15 in moderately
differentiated prostate cancers: the
second study will broaden to a larger range of histologic grades.
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