He added, "There is great enthusiasm to develop drugs that
can stabilize atherosclerotic plaque and reduce acute coronary events."
SAHA already is being tested as an anticancer drug, and TSA is an
antifungal antibiotic also being tested against cancer.
The research is part of a larger project, supported by a $1,793,750
grant from the National Institutes of Health, to further develop
the HDI class of drugs for the treatment and prevention of atherosclerosis,
Mishra said.
"Despite the success of lipid-lowering drugs for the prevention
of coronary artery disease and myocardial infarction (heart attacks),
atherosclerosis remains the most common cause of disease-related
death in the Western world and in developing countries," he said.
###
Mishra's co-investigators include two long-term members of the atherosclerosis
research program at the School of Medicine, John S. Parks, Ph.D.,
and Richard W. St. Clair, Ph.D., both professors of pathology-lipid
sciences, and Catrina Rankin, M.S.
Wake Forest University Baptist Medical Center is an academic health
system comprised of North Carolina Baptist Hospital and Wake Forest
University Health Sciences, which operates the university's School
of Medicine. U.S. News & World Report ranks Wake Forest University
School of Medicine 18th in family medicine, 20th in geriatrics,
25th in primary care and 41st in research among the nation's medical
schools. It ranks 35th in research funding by the National Institutes
of Health. Almost 150 members of the medical school faculty are
listed in Best Doctors in America.
Contact: Robert Conn
Wake Forest University Baptist Medical Center
Fluorescence device to diagnose atherosclerosis and tumors described
at optics conference
Main Category: Cancer / Oncology News
Article Date: 27 May 2005 - 16:00 PST
In a presentation today at the Conference on Lasers and Electro-Optics
(CLEO), researchers from Cedars-Sinai Medical Center's Biophotonics
Research and Technology Development Laboratory described recent
progress on a device that stimulates, collects and measures light
emissions from body tissues to diagnose critical atherosclerotic
plaques (vulnerable plaques) and aggressive brain tumors.
In both disease processes, early detection and precision can impact
patient outcomes. Atherosclerotic plaque builds up quietly, usually
causing no symptoms until reaching an advanced stage, and the results
take more than 1 million American lives each year. Malignant brain
tumors called gliomas grow and spread into neighboring tissues rapidly.
When "image complete" resection is accomplished - meaning
no tumor is visible on high-resolution scans - patients have a median
survival of about 70 weeks. But when surgical removal is less than
image complete, median survival drops to less than 19 weeks.
The technology to be described at CLEO is based on the fact that
when molecules in cells are stimulated by light, they respond by
becoming excited and re-emitting light of varying colors. Just as
a prism splits white light into a full spectrum of color, laser
light focused on tissues is re-emitted in colors that are determined
by the properties of the molecules. When these emissions are collected
and analyzed (fluorescence spectroscopy), they provide information
about the molecular and biochemical status of the tissue.
"Time-resolved" spectroscopy adds a greater degree of
specificity, measuring not only the wavelength of the emission but
the time that molecules remain in the excited state before returning
to the ground state. This information is valuable because some emissions
overlap on the light spectrum but have different "decay"
characteristics.
Currently, experiments are being conducted to confirm the ability
of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS)
to differentiate brain tumor tissue from normal brain tissue and
its ability to detect arterial plaque that is vulnerable to rupture,
which often leads to heart attack or stroke.
Recent atherosclerosis research has found that the composition
of plaque and its "vulnerability" to rupture may be more
significant than the degree of arterial blockage as a precursor
to heart attack and stroke. The lipid content of vulnerable plaque
is different from that of stable plaque, and areas containing vulnerable
plaque are infiltrated by immune system cells called macrophages.
This inflammatory process weakens the plaque's thin, fibrous cap,
often leading to rupture and formation of blood clots that could
plug the blood vessel. A variety of technologies are now being investigated
for their potential to detect vulnerable plaque before rupture or
to study how plaques develop and rupture.
This is believed to be the first documentation that the inflammatory
cells, macrophages, can be detected in human atherosclerotic plaque
using TR-LIFS. In a study of plaques collected from 34 patients
undergoing surgical removal of carotid plaque, with 150 plaque areas
analyzed, the TR-LIFS technique has been able to distinguish plaque
found in inflamed areas from more stable plaque with a high degree
of sensitivity and specificity.
Experiments are now being conducted on plaque that exists in patients'
blood vessels, both before and after it is removed during a surgical
procedure called endarterectomy. Results found with the spectroscopic
technique are then compared to those found when the specimens are
later analyzed in the pathology laboratory.
"Right now, the goal of our research project is to define
how well the TR-LIFS technique can detect the features of plaque
vulnerability. But our objective is to develop a minimally invasive,
intravascular probe that will monitor plaque over time or guide
therapeutic interventions to prevent plaque rupture. It may be that
our probe will be attached to an angioscope or to an intravascular
ultrasound catheter to investigate the plaque," said Laura
Marcu, Ph.D., director of the Biophotonics Research and Technology
Development Laboratory in Cedars-Sinai's Department of Surgery.
"Results of spectroscopic examinations might be used to determine
the most effective drug or treatment approach for a particular plaque.
Physicians would be able to use this technology to determine whether
plaque is stable or unstable, and they could use it to monitor the
efficacy of a therapy. One of our next steps is to develop an intravascular
catheter that will enable routine use of this technology in vivo,
or in patients," said Marcu, who will make the 10:45 a.m. presentation
titled "Applications of Time-Resolved Fluorescence Spectroscopy
to Atherosclerotic Cardiovascular Disease and Brain Tumors Diagnosis."
In tests conducted on brain tumor tissue removed from 50 patients,
TR-LIFS has been able to distinguish various types of brain tumor
tissue from normal tissue. Furthermore, preliminary data collected
from 17 patients during neurosurgery show that the technique can
detect tumor cells left behind after tumor removal.
Neurosurgeon Keith L. Black, M.D., director of Cedars-Sinai's Maxine
Dunitz Neurosurgical Institute, said he is encouraged by the clarity
that fluorescence technology may offer, especially because the most
deadly tumors aggressively infiltrate neighboring tissue and are
irregularly shaped with poorly defined borders. "Although our
surgical goal is to remove as much tumor as possible without damaging
healthy brain, distinguishing between the two can be extremely difficult,
even with the sophisticated imaging techniques currently available,"
he said.
The TR-LIFS apparatus consists of a laser, a two-way fiber-optic
probe through which the laser light is delivered to the tissue and
the fluorescence is collected, a spectrometer, a digital oscilloscope,
and a computer workstation that provides user interface, coordination
of components and interpretation software. While the components
are now small enough to fit on a portable cart that can be taken
into an operating room, additional studies on miniaturization of
components and instruments are planned. In fact, the National Institutes
of Health is providing funding for the development of microdevices.
While the basic hardware and software is the same whether brain
tumors or blood vessels are being studied, the way the system operates
is dependent on the unique characteristics of the tissue.
"Each biological system will be characterized by a distinct
chemical composition, different molecules and different ways of
identifying them," said Marcu. "Therefore, to be sure
the technology addresses particular questions and issues related
to brain tumors, we must collect data from patients, analyze the
data and define the spectral ranges of particular aspects related
to the diagnosis of brain tumors. But those are very different from
those related to atherosclerosis."
The studies presented were supported by the National Institutes
of Health, Grant #R01 HL 67377, and The Whitaker Foundation, Grant
#RG-01-0346.
The studies on atherosclerotic plaques were conducted in collaboration
with Michael C. Fishbein, M.D., and J. Dennis Baker, M.D., at UCLA
Medical School and Julie A. Freischlag, M.D., at Johns Hopkins University.
The studies on brain tumors were in collaboration with Keith L.
Black, M.D., Brian K. Pikul, M.D., and William H. Yong, M.D., at
Cedars-Sinai.
The Conference on Lasers and Electro-Optics (CLEO) is being held
in conjunction with the Quantum Electronics and Laser Science (QELS)
Conference at the Baltimore Convention Center from May 22 through
27. In addition to the May 27 presentation, Marcu was invited to
preside over a series of sessions on Microfluidics, Flow Cytometry,
and Biosensing.
One of only five hospitals in California whose nurses have been
honored with the prestigious Magnet designation, Cedars-Sinai Medical
Center is one of the largest nonprofit academic medical centers
in the Western United States. For 17 consecutive years, it has been
named Los Angeles' most preferred hospital for all health needs
in an independent survey of area residents. Cedars-Sinai is internationally
renowned for its diagnostic and treatment capabilities and its broad
spectrum of programs and services, as well as breakthroughs in biomedical
research and superlative medical education. It ranks among the top
10 non-university hospitals in the nation for its research activities
and was recently fully accredited by the Association for the Accreditation
of Human Research Protection Programs, Inc. (AAHRPP). Additional
information is available at http://www.cedars-sinai.edu.
Contact: Sandy Van
sandy@prpacific.com
1-800-880-2397
Cedars-Sinai Medical Center
http://www.csmc.edu
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