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Stehlin
Foundation Scientific Update 2004
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Stehlin Foundation researchers continue to advance cancer
treatment, research and education. This update takes you
on a tour around the laboratory to review some recent achievements.
Chemotherapy
Stehlin researchers continue to develop an alternate, less
arduous form of chemotherapy. Our researchers are looking
for new ways to overcome
conventional chemotherapy’s limitations – typically,
chemotherapy kills normal body cells along with cancerous
cells, so it can only be administered in limited amounts.
“Metronomic Chemotherapy” is an innovative approach
of administering a prolonged, lower dose of drugs to prevent
the growth of new tumor capillaries. Destroying capillaries
cuts off the tumor’s oxygen supply and nourishment
inhibiting it’s growth.
Preliminary investigations have shown positive results,
where treated mice have had no tumor growth progression
and no noted toxicity.
Investigations are planned with different dosages and different
anticancer agents, testing against human tumors transplanted
into mice. Additional research will combine Metronomic dosing
with conventional doses and with the Stehlin lab’s
family
of camptothecins. The campthothecin compounds give patients
the added hope of destroying the established tumor, preventing
further growth and spread, without extra toxicity.
Drug Development
Stehlin researchers are developing new drug compounds with
enormous potential to become effective chemotherapy drugs
with minimum toxicity to the patient. The Stehlin lab’s
first generation Campthothecin drugs (CPT) and 9-NitroCamptothecin
(9-
NC) have demonstrated extremely high anti-cancer activity
in nude mice. When
these drugs were tried in human patients, the results were
less dramatic.
New research is underway to determine the metabolic mechanisms
of CPT and its derivatives, to find ways to increase the
drug’s potency.
In humans, a protein manufactured by the liver, serum albumin,
causes the majority of CPT to become inactive. Stehlin researchers
are exploring ways to protect CPT derivatives by adding
esters. Esters keep the drug intact and increase the duration
of it’s activity. The new compounds will be studied
for their range of activity against certain human cancers
(breast, colon, liver, lung, melanoma, ovarian and prostate)
and then compared to the best conventional drugs.
Genetic Studies
Stehlin researchers are collaborating with Dr. Louise Strong
at M.D. Anderson Hospital to find the genetic mechanisms
of a group of hereditary cancers. Much work has been done
on the Wilm’s tumor – a form of pediatric kidney
cancer. Epidemiological studies offer hope of identifying
the transmission path of the tumor gene in families.
To identify this gene and its product, DNA samples are taken
from patients and family members. Tumor biopsies are transplanted
into nude mice while blood from healthy relatives is obtained.
Lymphocytes from the blood samples are immortalized and
grown in a tissue culture allowing a continuous source of
DNA from the member of the family under investigation.
Education
Since 1981, Stehlin’s Educational Scholarship Program
has given more than 250 students hands-on experience in
cancer research and treatment. High school and college students
participate in laboratory activities such as chemotherapy
studies. They also accompany physicians on patient rounds
and observe surgery at Christus St. Joseph Hospital.
Interns are highly motivated students who enjoy meaningful
work that will enhance their resumés for graduate
school and college applications. Competition for an internship
is rigorous and the program has a track record of encouraging
alumni to continue their education. The projected operating
budget for the 2004 program exceeds $300,000.
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