Biomedical Engineering Reference
In-Depth Information
the oral cavity due to its proximity; thus, human saliva is an ideal diagnostic medium for investigat-
ing smoking-related cancers.
The absence of definite early warning signs for most HNSCC suggests that sensitive and spe-
cific biomarkers are likely to be important for screening in high-risk patients
[99]
. DNA methyla-
tion in cells (the addition of methyl groups to cytosine residues on the DNA sequence) is an early
event that occurs during tumor initiation
[100]
. In fact, promoter DNA hypermethylation is a more
frequent mechanism of gene silencing than genetic mutation
[101]
. Unlike DNA mutations, DNA
methylation abnormalities are reversible by drugs in a laboratory setting, and this reversal allows
cancer cells to reactivate the silenced (da Silva, 2009 #3394) genes and produce tumor-suppressor
proteins. Because DNA methylation normally leads to gene silencing (a negative biological event),
a tumor-suppressor protein is not produced and thus protein detection methods cannot be used. For
a diagnostic test to be implemented clinically, the test will ideally measure a positive event occur-
ring in tumor cells de novo; therefore, by detecting DNA methylation in cells, one can turn a nega-
tive biological event into a positive clinical test. Understanding how abnormal DNA methylation
arises in cancer cells, and how this change leads to silencing of genes, is extremely important in
the development of treatments that could reverse this process as a strategy to prevent and/or treat
cancer (
Figures 22.3 and 22.4
).
With the development of noninvasive early screening tools and strategies (such as the ones that
are currently being developed in our laboratory) would enable the diagnosis of HNSCC at an earlier
stage and render treatment strategies.
22.3.3
Applications of Micro Electromechanical Systems (MEMS)/Nano
Electromechanical Systems (NEMS) in salivary diagnostics
Nanotechnology platforms are foreseen to change health care in a fundamental way by providing
novel methods for disease diagnosis and prevention, therapeutics selection and administration, tai-
lored to the patients' profile, drug delivery, and gene therapy. Nanotechnology is about manipulating
matter atom by atom. Nanodentistry is defined as the science and technology of maintaining near-
perfect oral health through the use of nanomaterials such as nano oral anesthesia inductions
[102]
,
nanodental techniques for major tooth repair, nano in-tooth repositioning, and nanorobotics
[103]
.
Nanotechnology-based NEMS biosensors result in high sensitivity and specificity for analyte
detection in complex matrices such as saliva, sensitivity of the detection system reaching down to
single molecule levels. These convert (bio)chemical to electrical signal
[104]
. As an example, the
Oral Fluid NanoSensor Test (OFNASET) technology is used for multiplex detection of salivary bio-
markers for oral cancer. A previous study has demonstrated that the combination of two salivary
proteomic biomarkers (thioredoxin and IL-8)
[105]
and four salivary mRNA biomarkers (SAT,
ODZ, IL-8, and IL-1b) can be used to detect oral cancer with high specificity and sensitivity
[106]
.
In addition, the optical nanobiosensor is a unique fiberoptics-based technology platform that allows
minimally invasive analysis of intracellular components such as cytochrome c (which regulates
apoptosis or programmed cell death and cellular energy production)
[104]
. Nanotechnology is not
only providing information on diagnosing a disease but also provides treatment opportunities. As
an example, BrachySilTM (Sivida, Australia) delivers 32P clinical trial for brachytherapy.
In summary, nanodentistry faces significant challenges in realizing its tremendous potential in revo-
lutionizing the current dental care practice. Some of the obstacles in the advancement of nanodentistry
