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Inflammation causes harmful molecules, called "reactive
oxygen species" to form. One such molecule is hydrogen peroxide.
When the body makes enough of it, hydrogen peroxide can hurt cells,
and cause oxidative damage — damage to DNA, which can lead to mutations,
and then to cancer.
In the prostate, one molecule, when it reacts
with oxygen, can churn out enough hydrogen peroxide to damage DNA.
This oxidized molecule is called spermine, and molecular pharmacologist
Robert Casero, Ph.D., the Irene and Bernard L. Schwartz Scholar,
is very interested in the role this chemical and the enzyme, spermine
oxidase, might play in prostate cancer. He and colleagues have recently
shown that when stomach tissue is infected by H. pylori, a nasty
form of bacteria — well-linked to inflammation, it’s also known
to cause stomach ulcers and, eventually, stomach cancer — spermine
oxidase makes hydrogen peroxide. The result is DNA damage. "These
findings may provide the link between H. pylori infection, inflammation,
and gastric cancer," notes Casero. This process in stomach cancer,
he continues, is eerily similar to what’s happening in cells that
are on the brink of becoming prostate cancer. They are in a condition
called "proliferative inflammatory atrophy," a wild mix of cells
first spotted under the microscope by Hopkins pathologists Angelo
De Marzo and Jonathan Epstein — hotspots of inflammation, mixed
with cells that appear to be dying, but are actually proliferating
very rapidly.
These findings may
provide the
link between H. pylori infection,
inflammation, and stomach
cancer—and this process is
eerily similar to what’s happening
in cells that are on the brink
of becoming prostate cancer.
"The prostate has the highest concentration of
spermine of any human tissue," Casero reports. "We believe that
inflammation-caused induction of spermine oxidase, and its resulting
damage, has the potential to cause prostate cancer." Casero is working
to nail down this link between spermine oxidase and the development
of prostate cancer, studying tissue samples to see if there’s a
correlation between spermine oxidase expression and a man’s stage
and grade of prostate cancer. "We will also try to determine exactly
how inflammation regulates spermine oxidase," and figure out whether
the oxidative damage spermine oxidase produces is enough to cause
prostate cancer.
"We hope our results will provide a link between
chronic inflammation, hydrogen peroxide production, DNA damage and
cancer-causing progression — and at the same time, provide a target
for chemo-preventive intervention."
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