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Ironjustic
Wed, Sep-26-07, 17:16
Public release date: 24-Sep-2007

Contact: Wolf Frommer wfrommer@stanford.edu 650-325-1521 x208
Carnegie Institution

Scientists discover how cancer may take hold Stanford, CA-- A
team, led by researchers at the Carnegie Institution,* has
found a key biochemical cycle that suppresses the immune
response, thereby allowing cancer cells to multiply unabated.
The research shows how the biomolecules responsible for
healthy T- cells, the body's first defenders against hostile
invaders, are quashed, permitting the invading cancer to
spread. The same cycle could also be involved in autoimmune
diseases such as multiple sclerosis. The work is published in
the September 25, 2007, issue of PLoS Biology.

The scientists used special molecular "nanosensors" for the
work. "We used a technique called fluorescence resonance
energy transfer, or FRET, to monitor the levels of,
tryptophan, one of the essential amino acids human cells need
for viability," explained lead author Thijs Kaper. "Humans get
tryptophan from foods such as grains, legumes, fruits, and
meat. Tryptophan is essential for normal growth and
development in children and nitrogen balance in adults.
T-cells also depend on it for their immune response after
invading cells have been recognized. If they don't get enough
tryptophan, the T-cells die and the invaders remain
undetected."

The scientists looked at the chemical transformations that
tryptophan undergoes as it is processed in live human cancer
cells. When tryptophan is broken down in the cancer cells, an
enzyme (dubbed IDO) forms molecules called kynurenines. This
reduces the concentration of tryptophan in the local tissues
and starves T-cells for tryptophan. A key finding of the
research was that a transporter protein (LAT1), present in
certain types of cancer cells, exchanges tryptophan from the
outside of the cell with kynurenine inside the cell, resulting
in an excess of kynurenine in the body fluids, which is toxic
to T- cells.

"It's double trouble for T-cells," remarked Wolf Frommer. "Not
only do they starve from lack of tryptophan in their
surroundings, but it is replaced by the toxic kynurenines,
which wipes T-cells out."

The scientists think that this cycle may be also be involved
in cells involved in certain autoimmune diseases. In these
cases the cells may not be able to take up or convert enough
tryptophan. Without enough of the amino acid or the IDO enzyme
to convert tryptophan, the cells cannot produce enough
kynurenine. Lacking kynurenine, the body's own T- cells cannot
be kept in check, so they rebel and attack the body.

The FRET system detects metabolites such as sugars and amino
acids using a biosensor tag. A protein is genetically fused to
tags at opposite ends of a molecule. The tags are made from
different colors of the jellyfish green fluorescent protein
(GFP). When a metabolite binds to the biosensor, it changes
the shape of the sensor's backbone, altering the position of
the fluorescent tags. When a specific wavelength of light
activates one tag, it fluoresces. When the metabolite causes
the tags to move close together, the other tag will also
fluoresce-resonating like a tuning fork. This system allows
the scientists to visually track the location and
concentration of certain biochemicals.

"Our FRET technology with the novel tryptophan nanosensor has
an added bonus," said Thijs. "It can be used to identify new
drugs that could reduce the ability of cancer cells to uptake
tryptophan or their ability to degrade it. We believe that
this technology could be a huge boost to cancer treatment."

###
Carnegie holds certain patent rights related to this
discovery, as well as other related inventions in the FRET
area. Interested individuals should contact Gary Kowalczyk at
202-939-1118, or gkowalczyk@ciw.edu.

Researchers on this project are Thijs Kaper, Carnegie
Institution's Department of Plant Biology; Loren Looger,
formerly at Carnegie Institution's Department of Plant Biology
now at Janelia Farm; Hitomi Takanaga, Carnegie Institution's
Department of Plant Biology; Michael Platten ,University
Hospital of Heidelberg; Lawrence Steinman, Stanford
University; and Wolf Frommer, Carnegie Institution's
Department of Plant Biology.

www.carnegieinstitution.org

The Carnegie Institution of Washington, a private nonprofit
organization, has been a pioneering force in basic scientific
research since 1902. It has six research departments: the
Geophysical Laboratory and the Department of Terrestrial
Magnetism, both located in Washington, D.C.; The
Observatories, in Pasadena, California, and Chile; the
Department of Plant Biology and the Department of Global
Ecology, in Stanford, California; and the Department of
Embryology, in Baltimore, Maryland.

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Turkey's Twist on Treating Multiple Sclerosis

Miranda Hitti

Nov. 3, 2005 -- A compound found in turkey may one day help
treat multiple sclerosis (MS), new research shows.

So far, scientists have tested an artificial version of the
compound on mice with an MS-like condition. The strategy they
tried reversed the paralysis caused by the mice's disease, the
researchers write in Science.

That doesn't mean that your Thanksgiving dinner will cure
or prevent
MS. But the finding may eventually prompt the development of
new drugs for MS and other diseases.

The researchers included Michael Platten, MD, now of the
neurology department of Germany's University of Tubingen, and
Lawrence Steinman, MD, of Stanford University.

Compound Clue

Platten's team focused on tryptophan, a chemical that's found
in turkey and other meats.

Specifically, they studied compounds released when tryptophan
breaks down.

In the body, tryptophan has several jobs. It helps make
serotonin (a brain chemical), as well as the B vitamin niacin.
It may be best known by the public for making some people feel
sleepy after eating turkey.

Platten's experiment focused on how tryptophan's byproducts
affect the immune system.

Calming Killer Cells

In MS, the immune system doesn't work properly.

The immune system is supposed to defend the body from things
that don't belong there (like viruses). But in MS, the immune
system attacks the body itself. That's why MS is called an
"autoimmune" disease.

The dirty work is done by "T cells," the immune system's
killer cells.

T-cells are called into action by a series of chemical
messengers. Picture an attack dog waiting in its kennel until
several layers of staffers sign off on its release.

What if those chemical orders were short-circuited? Platten's
team used tryptophan's byproducts to do that in mice with an
MS-like condition.

Tests on Mice

In one test, the food of the mice was laced with doses of
synthetic tryptophan byproducts. After eating that food, the
mice's disease-related paralysis was reversed, the
researchers report.

In another test, mice had "fewer relapses and less severe
disease" after eating the experimental food, the
researchers write.

Basically, the byproducts ordered the mice's out-of-control
immune system to calm down. They did that by boosting
chemicals that regulate the immune system. That blocked the
mice's disease from launching a dangerous cascade of T cells.

The byproducts weren't tested on people. The results may point
the way to the creation of a new class of drugs for MS and
other diseases, the researchers write.

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SOURCES: Platten, M. Science, Nov. 4, 2005; vol 310: pp
850-855. News release, Science. WebMD Medical Reference from
"What to Eat if You Have Cancer": "Protein and Cancer."

Reviewed by Louise Chang

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WebMD Health News 2005. =A9 2005 WebMD Inc.

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Marcus Aur
Wed, Sep-26-07, 17:16
The amino acid, alanine, as I remember it, inhibits the
amino-acid, tryptophan's, catabolism. The "Warburg" affect,
as I remember it, is the precipitous decline in the serum
concentration of alanine noticed in the serum of individuals
who had significant cancer. Both alanine and pyruvate, in
it's natural biological state, have the same number of
valence electrons and the same molecular weights. Thus, it
might be hypothesized that a minimal aberration in the
molecular structure of the enzyme, alanine aminto
transferase, which reversibly converts pyruvate to alanine,
results in the enzyme mistaking pyruvate for alanine with the
resultant "Warburg effect" apparant in transformed "cancer"
cells. Concommitant with the same would be the physical,
chemical, and biochemical anomalies associated with
tryptophan delineated in the original article. I hold a B.S.
in Biochemistry and am an R.N...