Public release date: 7-Dec-2006
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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
Blood pressure drugs could help halt pancreatic cancer spread,
Jefferson researchers find
(PHILADELPHIA) Common blood pressure medications might help block the
spread of pancreatic cancer, researchers at the Kimmel Cancer Center at
Thomas Jefferson University in Philadelphia have found. The scientists
showed in laboratory studies that two types of pressure-lowering drugs
- ACE inhibitors and AT1R blockers - may help reduce the
development of tumor-feeding blood vessels, a process called
angiogenesis. Such drugs, they say, may become part of a novel strategy
to control the growth and spread of cancer.
According to Hwyda Arafat, M.D., Ph.D., assistant professor of surgery
at Jefferson Medical College, previous studies have linked a lower
cancer incidence with the inhibition of the pancreas hormone
angiotensin II (Ang II) by either ACE (Angiotensin I converting enzyme)
inhibitors or AT1R (Ang II type 1 receptor) blockers. Ang II increases
the production of VEGF, a vascular factor that promotes blood vessel
growth in a number of cancers. High VEGF levels have been correlated
with poor cancer prognosis and early recurrence. ACE is the enzyme that
converts Ang I to Ang II.
Dr. Arafat and her co-workers examined the protein of both invasive
pancreatic cancer and normal pancreatic tissue, analyzing the
expression of ACE and AT1R in relation to VEGF. They also looked at the
effects of blood pressure drugs
captopril, an ACE inhibitor, and
losartan, an AT1R blocker, on VEGF production in cancer cell lines.
They found that protein levels in ACE and AT1R were significantly
higher in 75 percent of the cancer tissue examined. VEGF expression was
higher in cases where there was strong ACE and AT1R levels. In the test
tube, Ang II significantly enhanced VEGF production in AT1R-positive
cells. Captopril and losartan both blocked this effect.
"Our data show for the first time that both ACE and AT1R are
functionally expressed in pancreatic ductal adenocarcinoma and suggest
their involvement in tumor angiogenesis," Dr. Arafat says. She presents
her results December 5, 2006 at the Southern Surgical Association
meeting in Palm Beach, FL.
"High VEGF levels correspond with lymph node metastasis and worse
prognosis in many cancers," Dr. Arafat says. "High levels of
angiotensin II might mean high levels of VEGF and pancreatic cancer. We
have a treatment to block it."
"We are continuing to analyze how angiotensin affects VEGF, and the
signaling pathways involved," she says. Her team is looking at the
effect of angiotensin on cell proliferation and programmed cell death,
and would like to develop an animal model.
"Patients have chemotherapy and radiation sometimes before surgery,"
she says. "I would imagine this would be useful either for unresectable
tumors or after surgical removal of the pancreatic cancer. It might be
used in maintenance."
"These are well tested, safe drugs," Dr. Arafat notes, "so the
translation of our work from the animal model to the clinical trial can
be fast. This is very promising." Pancreatic cancer is the fourth
leading cause of cancer death in the United States, with some 32,000
deaths a year. Only five percent of patients live at least one year
after diagnosis.
###
Now if you look at this article .. erythrocytosis / increased red blood
cell production is decreased by the use of the above drugs.
Soooo .. are they simply lowering the red blood cell counts .. ?
Is the incidence of pancreatic cancer .. higher .. in those with KNOWN
... erythrocytosis .. ?
<<snip>>
erythrocytosis after successful renal transplantation, secondary
polycythemia of chronically hypoxemic COPD patients, erythrocytosis
associated with renovascular hypertension, severe cardiac or renal
failure, the hematocrit-lowering effect of angiotensing-converting
enzyme inhibitors and angiotensin receptor blocker may be profound
<<snip>>
Hematocrit-lowering Effect Following Inactivation of Renin-Angiotensin
System with Angiotensin Converting Enzyme Inhibitors and Angiotensin
Receptor Blockers
Authors: Marathias, K. P.1; Agroyannis, B.1; Mavromoustakos, T.1;
Matsoukas, J.1; Vlahakos, D. V.1
Source: Current Topics in Medicinal Chemistry, Volume 4, Number 4,
February 2004, pp. 483-486(4)
Publisher: Bentham Science Publishers
Abstract:
Several clinical and experimental observations suggest that an intact
and activated renin-angiotensin system (RAS) may be an important
determinant of erythropoiesis in a variety of clinical conditions,
including hypertension, chronic renal insufficiency or failure, chronic
obstructive pulmonary disease, and congestive heart failure.
Accordingly, RAS inactivation may confer susceptibility to the
hematocrit-lowering effects of angiotensin-converting enzyme inhibitors
or angiotensin receptor blockers. Indeed, a dose-dependent decrease in
hematocrit is observed within the first month of such therapy. In the
majority of patients with hypertension decreases in hematocrit values
after RAS inactivation are small and not clinically important. In
extreme conditions, however, such as erythrocytosis after successful
renal transplantation, secondary polycythemia of chronically hypoxemic
COPD patients, erythrocytosis associated with renovascular
hypertension, severe cardiac or renal failure, the hematocrit-lowering
effect of angiotensing-converting enzyme inhibitors and angiotensin
receptor blocker may be profound and even lead to or worsen anemia.
Hematocrit reachs its nadir value within three months, and then it
remains stable during long-term observations. After discontinuation of
RAS blockade, hematocrit values rise gradually over the next three to
four months towards the pretreatment levels. The mechanism(s) related
to this phenomenon is not yet fully understood, but angiotensin II
seems to be responsible for inappropriately sustaining secretion of
erythropoietin despite hematocrit elevation and capable to directly
stimulate the erythroid progenitors in bone marrow to produce
erythrocytes.
Keywords: Hematocrit-lowering Effect; erythrocytes; erythropoietin;
Renin-Angiotensin
Document Type: Review article
DOI: 10.2174/1568026043451311
Affiliations: 1: Aretaieion University Hospital, Division of
Nephrology, 76 Vas. Sofias Ave., Athens 115 28, Greece.
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