Proceedings of the National Academy of Sciences,
Journal Year:
2016,
Volume and Issue:
113(7), P. 1778 - 1783
Published: Feb. 1, 2016
Cancer
cells
reprogram
their
metabolism
to
promote
growth
and
proliferation.
The
genetic
evidence
pointing
the
importance
of
amino
acid
serine
in
tumorigenesis
is
striking.
gene
encoding
enzyme
3-phosphoglycerate
dehydrogenase
(PHGDH),
which
catalyzes
first
committed
step
biosynthesis,
overexpressed
tumors
cancer
cell
lines
via
focal
amplification
nuclear
factor
erythroid-2-related
2
(NRF2)-mediated
up-regulation.
PHGDH-overexpressing
are
exquisitely
sensitive
ablation
pathway.
Here,
we
report
discovery
a
selective
small
molecule
inhibitor
PHGDH,
CBR-5884,
identified
by
screening
library
800,000
drug-like
compounds.
CBR-5884
inhibited
de
novo
synthesis
was
selectively
toxic
with
high
biosynthetic
activity.
Biochemical
characterization
revealed
that
it
noncompetitive
showed
time-dependent
onset
inhibition
disrupted
oligomerization
state
PHGDH.
identification
PHGDH
not
only
enables
thorough
preclinical
evaluation
as
target
cancers,
but
also
provides
tool
study
metabolism.
Angiogenesis,
Journal Year:
2018,
Volume and Issue:
21(3), P. 425 - 532
Published: May 15, 2018
The
formation
of
new
blood
vessels,
or
angiogenesis,
is
a
complex
process
that
plays
important
roles
in
growth
and
development,
tissue
organ
regeneration,
as
well
numerous
pathological
conditions.
Angiogenesis
undergoes
multiple
discrete
steps
can
be
individually
evaluated
quantified
by
large
number
bioassays.
These
independent
assessments
hold
advantages
but
also
have
limitations.
This
article
describes
vivo,
ex
vitro
bioassays
are
available
for
the
evaluation
angiogenesis
highlights
critical
aspects
relevant
their
execution
proper
interpretation.
As
such,
this
collaborative
work
first
edition
consensus
guidelines
on
to
serve
current
future
reference.
CA A Cancer Journal for Clinicians,
Journal Year:
2021,
Volume and Issue:
71(4), P. 333 - 358
Published: May 13, 2021
Abstract
Cancer
has
myriad
effects
on
metabolism
that
include
both
rewiring
of
intracellular
to
enable
cancer
cells
proliferate
inappropriately
and
adapt
the
tumor
microenvironment,
changes
in
normal
tissue
metabolism.
With
recognition
fluorodeoxyglucose‐positron
emission
tomography
imaging
is
an
important
tool
for
management
many
cancers,
other
metabolites
biological
samples
have
been
spotlight
diagnosis,
monitoring,
therapy.
Metabolomics
global
analysis
small
molecule
like
‐omics
technologies
can
provide
critical
information
about
state
are
otherwise
not
apparent.
Here,
authors
review
how
therapies
interact
with
at
cellular
systemic
levels.
An
overview
metabolomics
provided
a
focus
currently
available
they
applied
clinical
translational
research
setting.
The
also
discuss
could
be
further
leveraged
future
improve
patients
cancer.
BMC Bioinformatics,
Journal Year:
2019,
Volume and Issue:
20(1)
Published: Feb. 19, 2019
The
investigation
of
intracellular
metabolism
is
the
mainstay
in
biotechnology
and
physiology
settings.
Intracellular
metabolic
rates
are
commonly
evaluated
using
labeling
pattern
identified
metabolites
obtained
from
stable
isotope
experiments.
or
mass
distribution
vector
describes
fractional
abundances
all
isotopologs
with
different
masses
as
a
result
isotopic
labeling,
which
typically
resolved
spectrometry.
Because
naturally
occurring
isotopes
impurity
also
contribute
to
measured
signals,
patterns
must
be
corrected
obtain
patterns.
Since
contaminant
same
nominal
can
modern
spectrometers
high
resolution,
correction
process
should
resolution
dependent.Here
we
present
software
tool,
ElemCor,
perform
such
data
resolution-dependent
manner.
tool
based
on
difference
theory
(MDT)
information
unlabeled
samples
(ULS)
account
for
effects.
MDT
mathematical
only
requires
chemical
formulae
correction.
ULS
semi-empirical
additional
measurement
samples.
We
validate
both
methods
show
their
improvement
accuracy
comprehensiveness
over
existing
simulated
experimental
Saccharomyces
cerevisiae.
available
at
https://github.com/4dsoftware/elemcor
.We
two
methods,
ULS,
correct
LC-MS
experiments
natural
abundance
impurity.
recommend
low-mass
compounds
cost
efficiency
experiments,
high-mass
relatively
large
spectral
inaccuracy
that
tracked
by
standards.
Nature Communications,
Journal Year:
2017,
Volume and Issue:
8(1)
Published: May 11, 2017
Abstract
Metastases
are
the
leading
cause
of
mortality
in
patients
with
cancer.
Metastasis
formation
requires
cancer
cells
to
adapt
their
cellular
phenotype.
However,
how
metabolism
supports
this
adaptation
is
poorly
defined.
We
use
2D
versus
3D
cultivation
induce
a
shift
phenotype
breast
cells.
discover
that
proline
catabolism
via
dehydrogenase
(Prodh)
growth
culture.
Subsequently,
we
link
vivo
metastasis
formation.
In
particular,
find
PRODH
expression
and
increased
metastases
compared
primary
cancers
mice.
Moreover,
inhibiting
Prodh
sufficient
impair
lung
orthotopic
4T1
EMT6.5
mouse
models,
without
adverse
effects
on
healthy
tissue
organ
function.
conclusion,
potential
drug
target
for
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: Feb. 4, 2020
Abstract
Profound
metabolic
changes
are
characteristic
of
macrophages
during
classical
activation
and
have
been
implicated
in
this
phenotype.
Here
we
demonstrate
that
nitric
oxide
(NO)
produced
by
murine
is
responsible
for
TCA
cycle
alterations
citrate
accumulation
associated
with
polarization.
13
C
tracing
mitochondrial
respiration
experiments
map
NO-mediated
suppression
metabolism
to
aconitase
(ACO2).
Moreover,
find
inflammatory
reroute
pyruvate
away
from
dehydrogenase
(PDH)
an
NO-dependent
hypoxia-inducible
factor
1α
(Hif1α)-independent
manner,
thereby
promoting
glutamine-based
anaplerosis.
Ultimately,
NO
leads
loss
electron
transport
chain
(ETC)
complexes.
Our
data
reveal
rewiring,
vitro
vivo,
dependent
on
targeting
specific
pathways,
resulting
reduced
production
mediators.
findings
require
modification
current
models
macrophage
biology
reprogramming
should
be
considered
a
result
rather
than
mediator
