Biology Reference
In-Depth Information
fluid,
from an area of interest has also been examined
in recent studies using MS-based proteomic
pro
Similar to whole tissue samples, human
Alzheimer
is disease, it is generally accepted
that a mutation that encodes for the presenilin
enzymes is involved in amyloid-
'
(a
) produc-
b
b
ling. Differential protein expression was
determined for gastric
tion. The aggregation of a
is a possible cause
of the symptoms (memory loss) of this disease.
The different isomers of a
b
fluids that were acidic
(less than pH of 3) and neutral (pH of 7 or
greater).
98
, such as a C-terminal
truncation, are thought to affect the amount of
a
b
The interstitial
fluid, along with
ascites (peritoneal
fluid), of patients with epithe-
lial ovarian cancer was examined for potential
biomarker discovery.
99,100
Collection of
. This study measures the enzymes thought
to control the a
b
truncation.
106
Changes in post-translational modi
b
these
cations
can also be indicative of a disease or its
progression. In chronic heart failure, the phos-
phorylation of cardiac troponin I was shown to
be potentially predictive.
107
The glycation of
proteins in diabetes was also pro
two
fluids is complicated and invasive. Urine,
on the other hand, is of great interest in
biomarker discovery because of its pain-free
and easy collection. Urine can be considered
a proximal
fluid for bladder cancer as
discussed in the following hypothesis-driven tar-
geted MS study to quantify the analytes of
interest.
101
For non
e
small cell lung carcinoma,
urine would not be considered a proximate
led to identify
targets.
108
novel
Aberrant glycosylation of
proteins was pro
led in esophageal adenocarci-
noma revealing several subsets of glycans as
potential markers.
109
fluid,
In pro
ling, cystic
fibrosis
but pro
ling of the urine proteome yielded
a potential biomarker for the disease.
102
It should
be noted that simple protein fraction techniques
are unlikely to be ef
(CF)
plasma, an imbalance of
protease/antiprotease levels compared to the
controls was discovered.
110
To evaluate the tar-
geted protein mutation, multiple reaction moni-
toring (MRM) MS quantitation of cystic
patients
'
cient for identifying new
biomarker proteins.
A slightly more painful way of biomarker
analysis sampling, but routine procedure, is
blood draw collection via venous puncture. A
recent analysis of human blood isolates platelets
to
fibrosis
transmembrane conductance regulator (CFTR)
can be performed.
111
Abnormal Protein Activities as Emerging
Biomarkers
Activity-based protein pro
find proteome changes in patients with acute
coronary syndrome (ACS).
103
The more popular
part of blood for biomarker discovery is plasma.
Potential plasma biomarkers for obesity were
found by comparing obese [body mass index
(BMI) greater than 25 kg/m
2
] and non-obese
(BMI less than 25 kg/m
2
) patients.
104
Human
liver carboxylesterase 1 was found for hepatocel-
lular carcinoma after quantitatively comparing
protein levels in the tumor to adjacent non-
tumor tissue in liver. The researchers then specif-
ically evaluated patients
ling (ABPP) allows
for proteome-wide investigations of enzymatic
and protein
e
drug interaction events.
112
e
116
This
technology uses small molecule probes, repre-
sented by activity-based probes (ABPs), which
typically have the reactive, recognizing, and
reporting moieties with inert linkers in between.
ABPs also have the potential to develop irrevers-
ible inhibitor-type therapeutics.
117
With respect to
potential biomarker applications, stable isotope-
coded ABPs
118,119
allow for easy implementation
of MS-based quantitative proteomics in human
samples. ABPs have recently been used to deter-
mine why a certain small molecule is cytotoxic,
120
to evaluate potential drug candidates,
121
and to
reduce the sample complexity in pro
'
plasma
for
the
potential biomarker.
105
Disease-Specific Protein Isomers
A
finding or relative change of a protein
isomer can be predictive for disease systems. In
ling
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