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HOUSTON—(Jan. 10, 2008)—Researchers at The University of Texas
Health Science Center at Houston can identify and quantify specific
protein markers in human saliva to provide an early, non-invasive
diagnosis of breast cancer, according to a study published in today’s
issue of the journal Cancer Investigation.
The
study describes how the onset of breast cancer produces a change in the
normal type and amount of proteins in glandular secretions from the
salivary glands. The protein profile in a healthy person is altered by
the presence of cancer.
Lead researcher Charles Streckfus,
D.D.S., a University of Texas Dental Branch at Houston professor of
diagnostic sciences with an expertise in salivary function and
molecular epidemiology, collaborated on the groundbreaking study with
William Dubinsky, Ph.D., a biochemist and professor of integrative
biology and pharmacology at The University of Texas Medical School at
Houston; and Lenora Bigler, Ph.D., clinical research professor with the
UT Dental Branch.
“Why not the dentist?” said Streckfus.
“Most folks, especially women and children, visit the dental office way
more often than they ever see the physician. Saliva is a non-invasive,
quicker way for detection.”
The study is being applied to a
“lab-on-a-chip” technology platform developed by biochemists at The
University of Texas at Austin. The ultimate goal is to bring this type
of diagnostic test, which is capable of detecting the presence of
cancer before a tumor forms, into the dental office or other health
care facilities. The technology aims to improve the ease and
effectiveness with which dental professionals and other health care
providers can provide quick, accurate diagnostic information and
physician referrals to their patients.
“The unique
collaborative opportunities at the UT Health Science Center at Houston,
the University of Texas M.D. Anderson Cancer Center and the Texas
Medical Center fostered this study and made these remarkable findings
possible,” said UT Health Science Center at Houston President James T.
Willerson, M.D. “A major strength of UT-Houston is putting together
outstanding scientists in an environment of collaboration and
cooperation. I am so very proud of Drs. Streckfus, Dubinsky and Bigler
and their colleagues at M.D. Anderson and UT Austin.”
Unlocking Saliva’s Secrets
Dubinsky
said saliva holds the codes to many medical secrets. “Saliva is a
complex mixture of proteins. We go through a process that compares
different samples by chemically labeling them in such a way that we can
not only identify the protein, but determine how much of it is in each
sample,” said Dubinsky. “This allows us to compare the levels of
150-200 different proteins in cancerous versus non-cancerous specimens
to identify possible markers for disease.”
Streckfus and
his team compared the levels of expression of proteins in the saliva of
patients with either malignant or benign tumors to saliva from normal
controls to find those that are abnormally expressed in the diseased
state. Patients’ proteins that are significantly higher or lower than
the norm were considered biomarker candidates.
In the
study, researchers analyzed saliva samples from 30 patients. They found
49 proteins that differentiated healthy patients from those with benign
breast tumors and those with malignant breast tumors.
These findings suggest that patients can be tested for breast cancer by examining certain protein markers in their saliva during a visit to a dentist’s office.
According to the Susan G. Komen for the Cure Foundation,
an estimated 25 million women globally will be diagnosed with breast
cancer, and an estimated 10 million will die from the disease in the
next 25 years if no cure is found, making early detection critical.
Current tools for detecting breast cancer include ultrasounds, regular
blood test screenings, mammograms and biopsies – all of which the
researchers hope will eventually be supplemented by salivary
diagnostics.
Streckfus also reports: “The
research found unique proteins for the fibroadenoma benign tumor – the
most common benign breast tumor. This finding is unique, as it targets
both the benign and malignant tumor, which could potentially reduce the
number of false positives and false negatives associated with current
cancer diagnostics.”
Streckfus said that being
able to chemically distinguish between benign and malignant tumors
through a saliva test eliminates possible false positive results. The
supplemental chemical confirmation could allow experts to immediately
determine the patient’s next treatment option, whether it be surgery, a
biopsy or further testing.
“Dentistry has entered an exciting new era,” said Catherine M. Flaitz,
D.D.S., dean of the UT Dental Branch at Houston. “On every front, our
researchers are exploring links between oral health and the overall
health of patients, often with astonishing findings. We’re working to
bring those discoveries out of the lab and into the real world of
dentists’ and physicians’ offices. We have a special opportunity to
collaborate with some of the most talented clinicians and scientists
within the world’s largest medical center to evaluate the significance
of oral biomarkers for predicting health and disease. It is such a
rewarding time to be part of this great profession. ”
“Lab-on-a-Chip Technology”
Biochemists
at The University of Texas at Austin are building a microfluidics
platform to analyze saliva and detect protein markers in a way that
will be practical for everyday use in dental clinics.
The McDevitt group, led by John McDevitt,
professor of chemistry and biochemistry at UT Austin, is working with
Streckfus and his colleagues to design the diagnostic device, which may
eventually be reduced from the size of a refrigerator to a cellular
phone. With a working prototype, a dentist can evaluate a patient’s
saliva sample in a routine office visit, with no delay for laboratory
work.
The device will be tested in clinical trials in collaboration with Funda Meric-Bernstam,
M.D., associate professor of surgical oncology at M.D. Anderson, and
Mark Powell, M.D., of the Health and Human Services Department in Marin County, Calif.
By
bringing the lab discoveries to the clinic, the ultimate goal of the
collaborative effort is FDA approval under the current pending patent.
The National Institute of Dental and Craniofacial Research (NIDCR), one of the National Institutes of Health, is the leading supporter of salivary diagnostic research.
“There are many practical advantages to using oral fluids and saliva for diagnostic purposes,” said Lawrence A. Tabak,
D.D.S., Ph.D., director of the NIDCR. “Further advances in
biotechnology are likely to give us ‘labs-on-a-chip’ sufficiently small
to fit into the mouth, where they will be able to monitor, in real
time, a host of biomarkers, including those useful in cancer
detection.”
As the only woman among the publishing authors
and the mother of two daughters, Bigler has a unique perspective on the
importance of the research.
“In the field of salivary
diagnostics in particular, women haven’t been in the field very long,”
said Bigler. “My position on the research team means as much to me as
the research, and I feel I owe it to myself and other women around the
world to be extra dedicated in order to improve women's health.”
Streckfus and Dubinsky are co-directors of the Proteomics Core Laboratory for the Center for Clinical and Translational Sciences (CCTS) at UT-Houston.
“UT-Houston’s
Center for Clinical and Translational Sciences, which is one of the
first national centers for clinical and translational research funded
by the NIH, is dedicated to the application of advanced molecular
technologies to support the detection and treatment of human disease,”
said Peter Davies, M.D., Ph.D., executive vice president for research
at the UT Health Science Center at Houston. “The outstanding work of
Drs. Streckfus, Dubinsky and Bigler is an example of the important new
discoveries that are being made possible by this exciting new research
program.”
Streckfus and his collaborators are continuing to
pursue salivary diagnostics for other types of cancer, such as ovarian,
endometrial, cervical and head and neck cancers.
The article, “Breast Cancer Related Proteins Are Present in Saliva and Are Modulated Secondary to Ductal Carcinoma In Situ of the Breast,” appears in the journal’s “iFirst” section online at: http://www.informaworld.com/smpp/title~content=g781940728~db=all.
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