Olaparib
(AZD2281)
is
used
as
a
first-line
maintenance
treatment
for
patients
with
ovarian
cancer
(OC)
breast
susceptibility
gene
(BRCA)
mutation.
Fatty
acid
binding
protein
4
(FABP4)
may
serve
an
important
role
in
cancer,
but
its
olaparib-treated
OC
BRCA
mutation
requires
further
clarification.
To
explore
the
function
of
FABP4
and
enhance
efficacy
AZD2281
OC,
cell
counting
kit-8,
apoptosis,
cycle,
colony
formation,
transfection,
western
blotting,
reverse
transcription-quantitative
polymerase
chain
reaction,
chromatin
immunoprecipitation,
seahorse
reactive
oxygen
species
assays
were
performed.
In
present
study,
significantly
promoted
inhibited
cycle
progression
formation
COV362
cells.
addition,
upregulated
levels
CCAAT
enhancer
α
(CEBPα),
peroxisome
proliferator
activated
receptor
γ
(PPARγ)
FABP4.
markedly
fold
enrichment
CEBPα
promoters
PPARγ
Furthermore,
overexpression
decreased
apoptosis
formation.
contrast,
knockdown
demonstrated
opposite
effects.
regulated
species,
adenosine
triphosphate,
aerobic
glycolysis,
basal
respiration
rate
fatty
oxidation.
The
combination
inhibitor
BM
S309403
increased
conclusion,
findings
study
that
enhanced
expression,
leading
to
diminished
antitumor
cells
by
regulating
CEBPα-PPARγ.
Conversely,
heightened
effectiveness,
presenting
promising
therapeutic
strategy
treating
International Journal of Cancer,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 7, 2024
AST-3424
is
a
novel
and
highly
tumor-selective
prodrug.
activated
by
AKR1C3
to
release
toxic
bis-alkylating
moiety,
AST
2660.
In
this
study,
we
have
investigated
the
essential
role
of
DNA
repair
in
mediated
pharmacological
activities
vitro
vivo.
We
show
here
that
effective
as
single
therapeutic
agent
against
cancer
cells
induce
cytotoxicity,
damage,
apoptosis
cell
cycle
arrest
at
G2
phase
dose-
AKR1C3-dependent
manner
both
p53-proficient
H460
(RRID:CVCL_0459)
p53-deficient
HT-29
(RRID:CVCL_0320).
The
combination
abrogators
checkpoint
with
was
only
synergistic
but
not
cells.
enhanced
activity
due
impaired
ability
via
attenuation
reduced
RAD51
expression.
Furthermore,
utilized
BRCA2
deficient
line
two
PDX
models
BRCA
deleterious
mutations
study
increased
AST-3424.
results
showed
exhibited
cytotoxicity
superior
durable
vivo
anti-tumor
effects
protein
BRCA2.
summary,
report
when
capacity
reduced,
can
be
further
enhanced,
thus
providing
supporting
evidence
for
evaluation
clinic.
The Journal of Pathology Clinical Research,
Год журнала:
2024,
Номер
10(6)
Опубликована: Окт. 29, 2024
Abstract
Homologous
recombination
deficiency
(HRD)
represents
an
impairment
in
the
homologous
repair
(HRR)
pathway,
crucial
for
repairing
DNA
double‐strand
breaks
and
contributing
to
genomic
instability
cancer.
The
HRD
score
may
be
a
more
reliable
biomarker
than
HRR‐related
gene
mutations
identifying
patients
sensitive
poly(ADP‐ribose)
polymerase
inhibitors.
Despite
its
relevance
various
cancers,
remains
underexplored
esophageal
squamous
cell
carcinoma
(ESCC).
We
retrospectively
analyzed
scores
96
ESCC
patients,
examining
correlations
with
clinical
characteristics
survival
outcomes,
validated
our
findings
using
TCGA
dataset.
Genomic
sequencing
utilized
custom
superHRD
next‐generation
panel,
were
calculated
from
54,000
single‐nucleotide
polymorphisms
Kruskal–Wallis
rank‐sum
tests
two
cut‐off
points
analysis.
Higher
correlated
advanced
tumor
stages,
recurrence,
TP53
ABCB1
,
while
APC
linked
lower
scores.
Patients
high
had
significantly
shorter
disease‐free
(
p
=
0.013)
trend
toward
overall
(OS)
0.005),
particularly
those
not
receiving
adjuvant
therapy.
Conversely,
HRD‐high
undergoing
therapy
showed
longer
OS
0.015).
Multivariate
analysis
identified
as
independent
prognostic
factor
(hazard
ratio
2.814
Validation
dataset
supported
these
findings.
This
study
highlights
associations
between
scores,
characteristics,
ESCC,
suggesting
potential
biomarker.
assessment
aid
patient
stratification
personalized
treatment
strategies,
warranting
further
investigation
validate
therapeutic
implications
of
ESCC.
Olaparib
(AZD2281)
is
used
as
a
first-line
maintenance
treatment
for
patients
with
ovarian
cancer
(OC)
breast
susceptibility
gene
(BRCA)
mutation.
Fatty
acid
binding
protein
4
(FABP4)
may
serve
an
important
role
in
cancer,
but
its
olaparib-treated
OC
BRCA
mutation
requires
further
clarification.
To
explore
the
function
of
FABP4
and
enhance
efficacy
AZD2281
OC,
cell
counting
kit-8,
apoptosis,
cycle,
colony
formation,
transfection,
western
blotting,
reverse
transcription-quantitative
polymerase
chain
reaction,
chromatin
immunoprecipitation,
seahorse
reactive
oxygen
species
assays
were
performed.
In
present
study,
significantly
promoted
inhibited
cycle
progression
formation
COV362
cells.
addition,
upregulated
levels
CCAAT
enhancer
α
(CEBPα),
peroxisome
proliferator
activated
receptor
γ
(PPARγ)
FABP4.
markedly
fold
enrichment
CEBPα
promoters
PPARγ
Furthermore,
overexpression
decreased
apoptosis
formation.
contrast,
knockdown
demonstrated
opposite
effects.
regulated
species,
adenosine
triphosphate,
aerobic
glycolysis,
basal
respiration
rate
fatty
oxidation.
The
combination
inhibitor
BM
S309403
increased
conclusion,
findings
study
that
enhanced
expression,
leading
to
diminished
antitumor
cells
by
regulating
CEBPα-PPARγ.
Conversely,
heightened
effectiveness,
presenting
promising
therapeutic
strategy
treating
