Redox Biology,
Год журнала:
2025,
Номер
80, С. 103528 - 103528
Опубликована: Фев. 3, 2025
Ovarian
cancer
(OC)
is
prone
to
peritoneum
or
omentum
dissemination,
thus
giving
rise
the
formidable
challenge
of
unresectable
surgery
and
a
dismal
survival
rate.
Although
niraparib
holds
pivotal
role
in
maintenance
treatment
OC,
its
effect
on
suppressing
metastases
during
primary
intervention
remains
enigmatic.
Recently,
we
initiated
prospective
clinical
study
(NCT04507841)
order
evaluate
therapeutic
efficacy
neoadjuvant
monotherapy
for
advanced
OC
with
homologous
recombination
deficiency.
An
analysis
patient
tumor
burden
before
after
showed
remarkable
vulnerability
intraperitoneal
exposure.
This
killing
capacity
was
closely
associated
accumulation
fatty
acids
within
abdomen,
which
confirmed
by
increased
susceptibility
cells
presence
acids.
In
context
abundant
acids,
elevated
intracellular
levels
lipid
peroxidation,
leading
subsequent
cell
ferroptosis
p53
BRCA-independent
manner.
Notably,
under
exposure,
critical
acid
transporter
CD36
dramatically
upregulated
tumors,
facilitating
excessive
uptake
Pharmacological
inhibition
either
impaired
anti-tumor
activity
both
vitro
murine
ID8
models.
Our
findings
demonstrate
as
novel
mechanism
underlying
regression
induced
niraparib,
thereby
offering
tantalizing
prospects
frontline
application
this
agent
management
OC.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Янв. 28, 2025
Immune
cells
within
tumor
tissues
play
important
roles
in
remodeling
the
microenvironment,
thus
affecting
progression
and
therapeutic
response.
The
current
study
was
designed
to
identify
key
markers
of
plasma
explore
their
role
high-grade
serous
ovarian
cancer
(HGSOC).
We
utilized
single-cell
sequencing
data
from
Gene
Expression
Omnibus
(GEO)
database
immune
cell
types
HGSOC
extract
related
via
Seurat
package.
effects
on
prognosis
were
analyzed
univariate
Cox
regression,
least
absolute
shrinkage
selection
operator
(LASSO)
gene
set
variation
analysis
(GSVA)
bulk
Cancer
Genome
Atlas
(TCGA)-HGSOC
cohort.
Finally,
evaluated
Cell
Counting
Kit-8
(CCK-8),
Transwell,
colony
formation,
wound
healing,
immunofluorescence
vivo
growth
assays.
At
level,
we
detected
a
significant
increase
proportion
samples
compared
that
normal
samples.
Within
tissues,
these
found
interact
with
CD8
+
T
cells,
fibroblasts
endothelial
cells.
In
addition,
patients
high-plasma
cell-related
score
group
had
better
survival
rates
higher
epithelial‒mesenchymal
transition
(EMT),
apoptosis
scores.
Moreover,
LASSO
regression
analyses
revealed
ubiquitin-conjugating
enzyme
E2
J1
(UBE2J1)
is
prognostic
marker
HGSOC.
Further
functional
studies
overexpression
UBE2J1
promoted
proliferation,
invasion,
migration
whereas
knockdown
attenuated
abovementioned
cellular
behaviors.
Additionally,
EMT,
as
evidenced
by
alterations
protein
expression
levels
N-cadherin,
snail
family
transcriptional
repressor
2
(Slug),
Twist
BHLH
transcription
factor
1
(Twist
1)
E-cadherin.
silencing
able
inhibit
vivo.
Overall,
this
elucidated
novel
oncogene
HGSOC,
uncovering
new
mechanisms
tumorigenesis
promising
targets
for
patients.
Clinical and Translational Medicine,
Год журнала:
2025,
Номер
15(3)
Опубликована: Фев. 25, 2025
Abstract
Background
Pseudogene‐derived
lncRNAs
are
widely
dysregulated
in
cancer.
Technological
advancements
have
facilitated
the
functional
characterization
of
increasing
pseudogenes
cancer
progression.
However,
association
between
and
RNA
N6‐methyladenosine
(m
6
A)
modification
cancer,
as
well
underlying
mechanisms,
remains
largely
unexplored.
Methods
We
analyzed
expression
12
146
comprehensively
examined
m
A
RNAs
derived
from
them
their
paralogs.
Through
integrative
analysis
multi‐omics
data,
we
explored
associations
pseudogene
dysregulation
A,
identifying
critical
involved
HGSOC
Tumour
promotion
role
RPS15AP12
its
cognate
parent
gene
was
characterized
by
cell
proliferation,
transwell
assays,
scratch
assays
ovarian
cells
xenograft
nude
mice.
decay
were
used
to
reveal
participation
decreasement
lncRNA
stability.
Luciferase
reporter
performed
verify
that
enhances
RPS15A
competitively
binding
miR‐96‐3p.
Western
blot
phosphorylation
investigate
impairment
towards
sensors
MAVS
(RIG‐I
MDA5),
downstream
p‐TBK1
p‐IRF3.
Finally,
ELISA
explore
regulatory
IFN‐β
expression.
Results
M
is
distributed
across
over
a
thousand
pseudogenes,
hypomethylation
leads
upregulation
HGSOC.
identified
processed
pseudogene,
RPS15AP12,
upregulated
FTO‐mediated
demethylation.
growth
ability
metastatic
capabilities
(OC)
via
functioning
competitive
endogenous
(ceRNA)
for
host
gene,
RPS15A,
through
sequestration
Importantly,
deletion
diminishes
leading
anti‐tumour
immune
responses
activating
RIG‐I
MDA5
p‐IRF3
levels.
Conclusion
Our
findings
expand
understanding
A‐modulated
tumour
innate
immunity
OC.
Key
Points
Genome‐wide
profiling
reveals
redistribution
m6A
on
pseudogene‐derived
redistribution‐relevant
representative
up‐regulated
demethylation
acts
miRNA
sponge
promote
RPS15AP12/RPS15A
axis
inhibits
MDA5)
levels
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(6), С. 2545 - 2545
Опубликована: Март 12, 2025
The
poor
prognosis
for
high-grade
serous
ovarian
cancer
(HGSOC),
the
dominant
subtype
of
cancer,
reflects
its
aggressive
nature,
late
diagnosis,
and
highest
mortality
rate
among
all
gynaecologic
cancers.
Apart
from
main
reason
unsuccessful
treatment
is
primarily
emergence
chemoresistance
to
carboplatin.
Although
there
a
good
response
primary
treatment,
disease
recurs
in
80%
cases,
at
which
point
it
largely
resistant
introduction
novel
targeted
therapies
second
decade
21st
century
has
begun
transform
HGSOC,
although
their
impact
on
overall
survival
remains
unsatisfactory.
Targeting
specific
pathways
known
be
abnormally
activated
HGSOC
especially
difficult
due
molecular
diversity
subtypes.
Moreover,
range
changes
are
associated
with
acquired
chemoresistance,
e.g.,
reversion
BRCA1
BRCA2
germline
alleles.
In
this
review,
we
examine
advantages
disadvantages
approved
therapies,
including
bevacizumab,
PARP
inhibitors
(PARPis),
treatments
targeting
cells
neurotrophic
tyrosine
receptor
kinase
(NTRK),
B-rapidly
accelerated
fibrosarcoma
(BRAF),
rearranged
during
transfection
(RET)
gene
alterations,
as
well
antibody–drug
conjugates.
Additionally,
explore
promising
new
targets
under
investigation
ongoing
clinical
trials,
such
immune
checkpoint
inhibitors,
anti-angiogenic
agents,
phosphatidylinositol-3-kinase
(PI3K)
Wee1
ataxia
telangiectasia
Rad3-related
protein
(ATR)
platinum-resistant
disease.
Despite
development
carboplatin
fundamental
medicine
therapy.
correct
choice
strategy
better
patients
advanced
should
therefore
include
prediction
patients’
risks
developing
platinum-based
chemotherapy.
effective
therapy
requires
selection
who
likely
derive
benefit
while
minimizing
potential
adverse
effects,
underscoring
essence
precision
medicine.
Genes,
Год журнала:
2024,
Номер
15(6), С. 750 - 750
Опубликована: Июнь 7, 2024
Background:
Patients
with
advanced-stage
epithelial
ovarian
cancer
(EOC)
receive
treatment
a
poly-ADP
ribose-polymerase
(PARP)
inhibitor
(PARPi)
as
maintenance
therapy
after
surgery
and
chemotherapy.
Unfortunately,
many
patients
experience
disease
progression
because
of
acquired
resistance.
This
study
aims
to
characterize
epigenetic
genomic
changes
in
cell-free
DNA
(cfDNA)
associated
PARPi
Materials
Methods:
Blood
was
taken
from
31
EOC
receiving
before
at
during/after
treatment.
Resistance
defined
within
6
months
starting
seen
fifteen
patients,
while
sixteen
responded
for
42
months.
cfDNA
evaluated
via
Modified
Fast
Aneuploidy
Screening
Test-Sequencing
System
(mFast-SeqS
detect
aneuploidy,
Methylated
Sequencing
(MeD-seq)
find
differentially
methylated
regions
(DMRs),
shallow
whole-genome
-exome
sequencing
(shWGS,
exome-seq)
define
tumor
fractions
mutational
signatures.
Results:
Aneuploid
undetectable
pre-treatment
but
observed
six
post-treatment,
five
resistant
one
responding
patient.
Post-treatment
ichorCNA
analyses
demonstrated
shWGS
exome-seq
higher
median
(7%
9%)
than
sensitive
5%).
SigMiner
detected
predominantly
signatures
linked
mismatch
repair
DeSeq2
MeD-seq
data
revealed
three
methylation
more
tumor-specific
DMRs
both
pre-
post-treatment
samples
(274
vs.
30
DMRs,
190
57
Χ2-test
p
<
0.001).
Conclusion:
Our
genome-wide
Next-Generation
(NGS)
PARPi-resistant
identified
differences
blood
treatment,
whereas
alterations
were
frequently
progression.
The
baseline
are
especially
interesting
further
exploration
putative
predictive
biomarkers
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июнь 5, 2024
The
occurrence
of
ovarian
cancer
(OC)
is
a
major
factor
in
women’s
mortality
rates.
Despite
progress
medical
treatments,
like
new
drugs
targeting
homologous
recombination
deficiency,
survival
rates
for
OC
patients
are
still
not
ideal.
tumor
microenvironment
(TME)
includes
cells,
fibroblasts
linked
to
(CAFs),
immune-inflammatory
and
the
substances
these
cells
secrete,
along
with
non-cellular
components
extracellular
matrix
(ECM).
First,
TME
mainly
plays
role
inhibiting
growth
protecting
normal
cell
survival.
As
tumors
progress,
gradually
becomes
place
promote
progression.
Immune
have
attracted
much
attention
as
targets
immunotherapy.
checkpoint
inhibitor
(ICI)
therapy
has
potential
regulate
TME,
suppressing
factors
that
facilitate
advancement,
reactivating
immune
managing
growth,
extending
advanced
cancer.
This
review
presents
an
outline
current
studies
on
distinct
cellular
elements
within
detailing
their
main
functions
possible
signaling
pathways.
Additionally,
we
examine
immunotherapy
rechallenge
OC,
specific
emphasis
biological
reasons
behind
resistance
ICIs.
World Journal of Surgical Oncology,
Год журнала:
2025,
Номер
23(1)
Опубликована: Янв. 4, 2025
This
study
aimed
to
evaluate
and
compare
the
clinicopathologic
features
of
primary
fallopian
tubal
carcinoma
(PFTC)
high-grade
serous
ovarian
cancer
(HGSOC)
explore
prognostic
factors
these
two
malignant
tumors.
Fifty-seven
patients
diagnosed
with
PFTC
from
2006
2015
60
HGSOC
2014
complete
information
were
identified
at
Women's
Hospital
Zhejiang
University.
The
clinicopathological
surgical
data
collected,
survival
was
followed
for
5
years
after
surgery.
Cox
proportional
risk
model
used
analyze
impact
on
survival.
For
patients,
mean
age
57
(range,
35–77
years).
most
common
clinical
manifestations
abnormal
vaginal
bleeding
and/or
discharge
(61%).
A
total
72%
cases
found
early
stage,
90%
tumors
high
grade
(51
cases).
51%
before
surgery,
while
rest
misdiagnosed.
Twenty-one
relapsed.
overall
(OS)
rate
82%.
OS
significantly
related
FIGO
preoperative
serum
CA
125
level,
lymphadenectomy,
residual
tumor
size,
appendectomy,
number
cycles
chemotherapy.
However,
only
stage
an
independent
variable
OS.
HGSOC,
67%.
laterality.
size
Our
provides
important
insights
into
HGSOC.
We
as
factor
patients.
These
findings
emphasize
critical
role
accurate
staging
achieving
a
less
than
1
cm
during
research
contributes
refining
decision-making,
supporting
importance
optimal
outcomes,
guiding
personalized
treatment
strategies
improve
patient
prognosis
in
both
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 28, 2025
Abstract
Purpose
This
systematic
review
evaluates
the
oncologic
and
reproductive
outcomes
of
fertility-sparing
surgery
(FSS)
in
women
diagnosed
with
stage
I
ovarian
cancer,
as
classified
by
International
Federation
Gynecology
Obstetrics
(FIGO).
The
goal
is
to
assess
safety
effectiveness
FSS
preserving
fertility
without
compromising
survival
outcomes.
Methods
A
search
was
conducted
MEDLINE
(PubMed),
SCOPUS,
Google
Scholar
for
studies
published
English
from
2014
onward.
Studies
involving
under
50
cancer
who
opted
were
included.
Data
extraction
focused
on
(recurrence
rates)
(pregnancy
live
birth
rates).
Study
selection
followed
PRISMA
guidelines.
Results
Seventeen
comprising
1030
patients
met
inclusion
criteria.
Pregnancy
success
rates
ranged
25–91.3%,
exceeding
80%
most
studies.
Spontaneous
conception
predominant,
though
3.7–28%
required
assisted
technologies
(ART).
Despite
58%
expressing
a
desire
future
pregnancy,
only
13%
actively
attempted
conception.
Recurrence
varied
3–33.3%,
reporting
between
8%
15%.
Overall
88–100%,
disease-free
remained
above
90%.
highest
recurrence
observed
mucinous
carcinoma
FIGO
Stage
IC2/IC3
subtypes.
Conclusion
viable
alternative
radical
carefully
selected
patients,
favorable
However,
risks
challenges
highlight
need
multidisciplinary
counseling,
long-term
surveillance,
further
research
refine
criteria
optimize
preservation
techniques.
