I am not very adept at a cut and paste job, but I thought that this
research report from a recent Northwestern University alumni newsletter
would be interesting to the group.
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Northwestern News [text only] Last updated 09/30/2003 Megan
Fellman at (847) 491-3115 or fellman@northwestern.edu
September 30, 2003
Research May Aid Cancer Diagnosis
EVANSTON, Ill. Scientists at Northwestern University have developed
an ultra-sensitive technology based on gold nanoparticles and DNA that
can detect prostate specific antigen (PSA) when present at extremely low
levels in a blood sample. This promising new protein-detection method
could be used to monitor prostate cancer patients following surgery and
to detect the early signs of breast cancer.
Prostate cancer in men and breast cancer in women are the second leading
causes of cancer deaths in the United States. (Only lung cancer is more
deadly.) The life-saving potential of early detection has been well
established for years, and improved cancer screening methods have helped
to reduce the threat.
The researchers have demonstrated that their method is a million times
more sensitive than conventional methods, a feature that promises to
change dramatically the way proteomics (the study and analysis of
protein structure and function) and medical diagnostics are done. The
results are published in the Sept. 26 issue of the journal Science.
"The polymerase chain reaction, which duplicates DNA so it can be
analyzed, revolutionized forensics, medicine and biotechnology," said
Chad A. Mirkin, director of Northwestern's Institute for Nanotechnology,
who led the research team, "but we haven't had anything of comparable
sensitivity for proteins. Now we do. This technology will change the way
we do cancer diagnostics and treatment."
Biomarkers, like PSA, are known for hundreds of diseases. Using these
protein targets, the new method could detect diseases at earlier stages
than is possible now. For example, if disease should return in a
prostate cancer patient after surgery, Mirkin's method could detect the
rise in PSA early on. Also, PSA is found in extremely low concentrations
in breast cancer patients, requiring an ultrasensitive screening test
for effective detection.
Because proteins, unlike DNA, cannot be chemically duplicated yet, the
Northwestern researchers had to develop a method of signaling the
presence of a protein. They chose to use DNA as their signal because it
can be amplified and read using a number of methods.
Using commercially available materials, the team outfitted a magnetic
microparticle and a gold nanoparticle each with the antibody of the
protein target, PSA. When in solution, the antibodies "recognize" and
bind to PSA, sandwiching the protein between the two particles.
The key is that attached to each tiny gold nanoparticle (just 30
nanometers in diameter) are hundreds to thousands of identical strands
of DNA. Mirkin calls this "bar-code DNA" because they have designed it
as a label specific to the protein target. After the
"particle-protein-particle" sandwich is removed magnetically from
solution, the DNA is removed from the sandwich and read using standard
DNA detection methodologies.
In the experiments conducted by Mirkin's team, the amount of PSA present
was calculated based on the amount of bar-code DNA. The researchers
detected approximately 20 PSA molecules in a 10-microliter sample, an
illustration of the method's extraordinary sensitivity.
"For each molecule of captured PSA, thousands of DNA strands are
released, which is our way of amplifying the signal for a protein target
of interest," said Mirkin, also George B. Rathmann Professor of
Chemistry. "There is power in its simplicity. Instead of detecting PSA
our method detects the DNA, which gives us a substantial increase in the
signal."
Using the new method, a test could be developed for any protein target
with a known antibody. A unique "bar-code DNA" label can be created for
each target. The technology could be commercially available in two
years.
In addition to Mirkin, other authors on the Science paper are Jwa-Min
Nam and C. Shad Thaxton, from Northwestern University. The research was
supported by the Air Force Office of Scientific Research, the Defense
Advanced Research Projects Agency and the National Science Foundation.
University
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Dick Winters
Leonard Evens - 21 Oct 2003 16:36 GMT
> I am not very adept at a cut and paste job, but I thought that this
> research report from a recent Northwestern University alumni newsletter
[quoted text clipped - 79 lines]
>
> Dick Winters
I've seen this before. One problem is that it will take several years
at least to determine just what the results of such tests mean
clinically. It will probably turn out that many men after surgery will
show some PSA, even rising PSA, but it may never mean anything
clinically. For example, it might be possible that some small number of
prostate cancer cells survive treatment but are kept under control by
the body's defense mechanisms. Even in cases where the cancer will
indeed recur, knowing it many years in advance may not be of any use
clinically. It is my impression from what Walsh says that usually, one
can wait until conventional means show something is going on before
undertaking followup treatment. If an ultra-ultra sensitive PSA test
shows your cancer may recur in 20 years, and you are 70, it is not clear
how useful that information is. Meanwhile, it is best to take the
results of such tests with a grain of salt.
Bill Denton - 22 Oct 2003 16:10 GMT
I totally agree, Leonard. Unless and until it is determined that
starting salvage treatment earlier than PSA .2 or .3 or 2.0 is
beneficial, who cares (other than peace of mind) whether PSA is .001
or .01 or even .1.
Bill Denton
RP 2/12/02
Memphis