Biology Reference
In-Depth Information
squamous cell carcinoma (21), bronchioloalveo-
lar carcinoma (4), metastatic colon cancer (2),
carcinoid biopsy (1), and plasma cell granuloma
(1), with a focus on adenocarcinoma and squa-
mous cell carcinoma for clinical analysis. Subse-
quent to on-tissue tryptic digestion and IMS,
statistical analyses were carried out and
a support vector machine algorithm made up
of 73 peaks was generated that could accurately
classify all of the cancerous cores into their
designated subtypes. It was also found from
this analysis that there was a subset of squa-
mous cell carcinoma cores that could be differ-
entiated from the others based on the
expression of a peptide identi
with respect to spatial localization indicating
that it is being produced by the metabolism of
dynorphin B. Other peptides, such as dynorphin
A (1-8), dynorphin A (1-17), and substance P
showed no treatment induced changes.
LIPID ANALYSIS
Lipids are an emerging area of interest to
the IMS community as they have been associated
with a variety of biological and disease processes
including signal
transduction,
56
kinase path-
ways,
57
s disease,
60
and
embryo implantation,
22
as well as being highly
expressed in every organ of the body, especially
the brain.
61
Sample preparation protocols have
helped to improve ionization of lipids while
decreasing ambiguity due to coordination with
multiple cations. Addition of lithium to the
matrix solution has been used to drive lipids to
their lithiated form enhancing sensitivity as
well as improving fragmentation ef
cancer,
58,59
Alzheimer
'
ed as being
from cytokeratin 5. TMA analysis by IMS has
also
pancreatic,
52
been
demonstrated
in
gastric,
53
and prostate
54
cancers.
Endogenous peptide level variations were
shown in a rat model of Parkinson
s disease
(PD).
55
PDwas induced in rats through the unilat-
eral injection of 6-OHDA-HCl into the substantia
nigra with saline administered to control animals
followed by treatment with L-DOPA to alleviate
PD symptoms and induce levels of dyskinesia.
Coronal sections of the ventral midbrain contain-
ing the substantia nigra were coated with DHB
using a chemical inkjet printer and imaged. Two
peptides in particular, dynorphin B and alpha-
neoendorphin (aNeo), were found to be signifi-
'
ciency.
62
Washing tissue with ammonium formate prior
to matrix application and mass spectral analysis
has proven to enhance lipid signals particularly
in negative ion mode.
63
Menger et al. have recently demonstrated the
role that lipids play in myocardial infarction.
64
A rat model of infarction was generated by
surgically ligating the left anterior descending
coronary artery. The rats were sacri
-
cantly elevated in the lesioned substantia nigra
in the animals with high dyskinesia as compared
to animals with low dyskinesia and controls. In
particular, these peptides showed considerably
higher levels (1.75 fold higher for dynorphin B
and 2 fold higher for aNeo) in the lateral portion
of the lesioned sustantia nigra as compared to
the contralateral side. Additionally, the peptide
metabolites Leu-Enk-Arg, Leu-Enk-Arg-Arg,
and aNeo (1-7) showed similar trends in expres-
sion of being higher in the lateral portion of
the substantia nigra in the lesioned side of the
brain as compared to intact but did not show
a strong correlation with dyskinesia. Leu-Enk-
Arg showed opposite trends with dynorphin B
ced and
the hearts dissected 24 hours later. Transverse
sections were collected from the infarcted
heart containing the damaged area. Areas of
damage were con
rmed by staining with
2,3,5-triphenyltetrazolium chloride (TTC) as
infarcted tissue lacks the dehydrogenase that
converts TTC to formazan. Samples were coated
with DHB containing alkali metals to help drive
the ionization of lipids to a single species. MS
and MS/MS imaging were then carried out
using a Thermo Scienti
c LTQ XL in positive
ion mode. Infarcted areas could be clearly differ-
entiated from normal areas based on the absence
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