Molecular Oncology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Chondrosarcomas
are
common
bone
sarcomas
frequently
resistant
to
radiation
and
chemotherapy,
with
high
recurrence
rates,
development
of
metastatic
disease,
death.
Fibrosarcomas
soft
tissue
associated
poor
outcomes.
Translocase
outer
mitochondrial
membrane
receptor
20
(TOMM20)
is
a
protein
cancer
aggressiveness
in
many
subtypes,
but
the
mechanisms
remain
poorly
understood.
Here,
we
studied
effects
TOMM20
overexpression
downregulation
on
redox
state,
oxidative
phosphorylation
(OXPHOS),
tumor
growth
using
fibrosarcoma
chondrosarcoma
models.
increased
OXPHOS,
NADH,
NADPH
reduced
cellular
reactive
oxygen
species
(ROS).
induced
resistance
apoptosis,
including
BCL-2
OXPHOS
complex
IV
inhibitors,
sensitivity
an
I
inhibitor.
Also,
cell
migration
vitro
promoted
vivo.
Conversely,
knocking
down
CRISPR-Cas9
vivo
both
mouse
In
conclusion,
driver
by
apoptosis
resistance,
maintenance
state.
Dissolution
dynamic
nuclear
polarization
(dDNP)
increases
the
sensitivity
of
magnetic
resonance
imaging
by
more
than
10,000
times,
enabling
in
vivo
metabolic
to
be
performed
noninvasively
real
time.
Here,
we
are
developing
a
group
dDNP
polarized
tracers
based
on
nicotinamide
(NAM).
We
synthesized
1-15N-NAM
and
1-15N
nicotinic
acid
hyperpolarized
them
with
dDNP,
reaching
(13.0
±
1.9)%
15N
polarization.
found
that
lifetime
is
strongly
field-
pH-dependent,
T1
being
as
long
41
s
at
pH
12
1
T
while
short
few
seconds
neutral
fields
below
T.
The
remarkably
low
drove
us
establish
unique
neutralization
procedure.
Using
an
inexpensive
rodent
probe
designed
in-house,
acquired
MRI
(previously
for
hour)
less
s.
Reduced
nicotinamide
adenine
dinucleotide
phosphate
(NADPH)
is
a
crucial
reducing
cofactor
for
reductive
biosynthesis
and
protection
from
oxidative
stress.
To
fulfill
their
heightened
anabolic
power
demands,
cancer
cells
must
boost
NADPH
production.
Progrowth
mitogenic
protein
kinases
promote
the
activity
of
cytosolic
NAD
kinase
(NADK),
which
produces
NADP
+
,
limiting
precursor.
However,
molecular
architecture
mechanistic
regulation
human
NADK
remain
undescribed.
Here,
we
report
cryo–electron
microscopy
structure
NADK,
both
in
its
apo-form
complex
with
substrate
(nicotinamide
dinucleotide),
revealing
tetrameric
organization
distinct
structural
features.
We
discover
that
amino
(N)-
carboxyl
(C)-terminal
tails
have
opposing
effects
on
enzymatic
cellular
NADP(H)
levels.
Specifically,
C-terminal
region
critical
activity,
whereas
N-terminal
exhibits
an
inhibitory
role.
This
study
highlights
insights
into
vital
enzyme
governing
American Journal of Cancer Research,
Год журнала:
2025,
Номер
15(1), С. 248 - 270
Опубликована: Янв. 1, 2025
Isocitrate
dehydrogenase
(IDH)
is
a
pivotal
enzyme
responsible
for
catalyzing
the
oxidative
decarboxylation
of
isocitrate
into
α-ketoglutarate
(α-KG).
This
serves
as
crucial
regulator
in
tricarboxylic
acid
cycle
(TCA
cycle),
acting
rate-limiting
step.
Its
role
extends
beyond
mere
metabolic
function,
influencing
cellular
homeostasis
and
overall
cell
function.
In
past
decade,
prominent
research
cancer
genetics
has
revealed
that
genes
encoding
are
commonly
mutated
across
various
human
malignancies.
Significant
field
shown
these
mutations
found
diseases
like
glioma,
acute
myeloid
leukemia
(AML),
cholangiocarcinoma
(CCA),
chondrosarcoma,
thyroid
(TC).
As
on
IDH
progresses,
deeper
insights
biological
effects
have
been
gained,
unveiling
their
potential
tumorigenesis.
addition,
mutants'
unique
activities
creates
new
pathways
tumor
metabolism,
gene
rearrangement,
therapeutic
resistance.
Currently,
innovative
molecular
targeting
strategies
bearing
devised
to
enhance
efficacy
against
cancers
harboring
mutations.
These
methods
represent
promising
avenue
improving
treatment
outcomes
IDH-mutated
article
mainly
summarizes
related
glioma
caused
by
mutation,
focuses
characteristics
transformation
IDH.
Molecular Oncology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Chondrosarcomas
are
common
bone
sarcomas
frequently
resistant
to
radiation
and
chemotherapy,
with
high
recurrence
rates,
development
of
metastatic
disease,
death.
Fibrosarcomas
soft
tissue
associated
poor
outcomes.
Translocase
outer
mitochondrial
membrane
receptor
20
(TOMM20)
is
a
protein
cancer
aggressiveness
in
many
subtypes,
but
the
mechanisms
remain
poorly
understood.
Here,
we
studied
effects
TOMM20
overexpression
downregulation
on
redox
state,
oxidative
phosphorylation
(OXPHOS),
tumor
growth
using
fibrosarcoma
chondrosarcoma
models.
increased
OXPHOS,
NADH,
NADPH
reduced
cellular
reactive
oxygen
species
(ROS).
induced
resistance
apoptosis,
including
BCL-2
OXPHOS
complex
IV
inhibitors,
sensitivity
an
I
inhibitor.
Also,
cell
migration
vitro
promoted
vivo.
Conversely,
knocking
down
CRISPR-Cas9
vivo
both
mouse
In
conclusion,
driver
by
apoptosis
resistance,
maintenance
state.
