Abstract
Breast
cancer
(BC)
is
the
most
frequent
malignant
diagnosis
and
a
primary
factor
for
deaths
in
women.
The
clinical
subtypes
of
BC
include
estrogen
receptor
(ER)
positive,
progesterone
(PR)
human
epidermal
growth
2
(HER2)
triple-negative
(TNBC).
Based
on
stages
BC,
various
treatment
methods
are
available
with
variations
rates
progression-free
disease
overall
survival
patients.
However,
still
faces
challenges,
particularly
terms
drug
resistance
recurrence.
study
epigenetics
has
provided
new
ideas
treating
BC.
Targeting
aberrant
epigenetic
factors
inhibitors
represents
promising
anticancer
strategy.
KDM5
family
includes
four
members,
KDM5A,
KDM5B,
KDM5C,
KDMD,
all
which
Jumonji
C
domain-containing
histone
H3K4me2/3
demethylases.
proteins
have
been
extensively
studied
where
they
involved
suppressing
or
promoting
depending
their
specific
upstream
downstream
pathways.
Several
shown
potent
inhibitory
activity
vitro
vivo,
but
challenges
exist
developing
inhibitors.
In
this
review,
we
introduce
current
therapeutic
options,
summarize
context-specific
functions
pathobiology
discuss
outlook
pitfalls
disease.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Май 24, 2023
Background
Indoleamine-2,3-dioxygenase
1
(IDO1)
is
responsible
for
tumor
immune
escape
by
regulating
T
cell-associated
responses
and
promoting
the
activation
of
immunosuppressive.
Given
vital
role
IDO1
in
response,
further
investigation
on
regulation
tumors
needed.
Methods
Herein,
we
used
ELISA
kit
to
detect
interferon-gamma
(IFN-γ),
Tryptophan
(Trp),
kynurenic
acid
(Kyn)
levels;
western
blot,
Flow
cytometry,
immunofluorescence
assays
detected
expression
proteins;
Molecular
docking
assay,
SPR
assay
Cellular
Thermal
Shift
Assay
(CETSA)
were
interaction
between
Abrine;
nano
live
label-free
system
was
phagocytosis
activity;
xenografts
animal
experiments
explore
anti-tumor
effect
flow
cytometry
cells
changes.
Results
The
important
inflammatory
response
cytokine
(IFN-γ)
up-regulated
cancer
through
methylation
6-methyladenosine
(m6A)
m6A
modification
RNA,
metabolism
Trp
into
Kyn,
JAK1/STAT1
signaling
pathway,
which
could
be
inhibited
inhibitor
Abrine.
CD47
IFN-γ-stimulated
genes
(ISGs)
prevents
macrophages,
leading
escape,
this
Abrine
both
vivo
vitro.
PD-1/PD-L1
axis
an
checkpoint
overexpression
PD-1
or
PD-L1
promotes
suppression,
while
study
inhibit
tissue.
combination
treatment
anti-PD-1
antibody
has
a
synergistic
suppressing
growth
up-regulating
CD4
+
CD8
cells,
down-regulating
Foxp3
Treg
inhibiting
IDO1,
CD47,
PD-L1.
Conclusion
Overall,
reveals
that
as
inhibition
with
HCC.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Апрель 8, 2024
Abstract
Hepatoblastomas
(HB)
display
heterogeneous
cellular
phenotypes
that
influence
the
clinical
outcome,
but
underlying
mechanisms
are
poorly
understood.
Here,
we
use
a
single-cell
multiomic
strategy
to
unravel
molecular
determinants
of
this
plasticity.
We
identify
continuum
HB
cell
states
between
hepatocytic
(scH),
liver
progenitor
(scLP)
and
mesenchymal
(scM)
differentiation
poles,
with
an
intermediate
scH/LP
population
bordering
scLP
scH
areas
in
spatial
transcriptomics.
Chromatin
accessibility
landscapes
reveal
gene
regulatory
networks
each
pole,
sequence
transcription
factor
activations
state
transitions.
Single-cell
mapping
somatic
alterations
reveals
clonal
architecture
tumor,
showing
genetic
subclone
displays
its
own
range
plasticity
across
states.
The
most
subclones,
overexpressing
stem
DNA
repair
genes,
proliferate
faster
after
neo-adjuvant
chemotherapy.
These
results
highlight
how
interplay
evolution
epigenetic
shapes
potential
subclones
respond
Abstract
Secondary
trastuzumab
resistance
represents
an
evolutionary
adaptation
of
HER2‐positive
breast
cancer
during
anti‐HER2
treatment.
Most
current
studies
have
tended
to
prioritize
HER2
and
its
associated
signaling
pathways,
often
overlooking
broader
but
seemingly
less
relevant
cellular
processes,
along
with
their
genetic
epigenetic
mechanisms.
Here,
transcriptome
data
is
not
only
characterized
also
examined
epigenomic
3D
genome
architecture
information
in
both
trastuzumab‐sensitive
secondary‐resistant
cells.
The
findings
reveal
that
the
global
metabolic
reprogramming
may
stem
from
genome‐wide
alterations
histone
modifications
chromatin
structure.
Specifically,
transcriptional
activities
key
genes
involved
lipid
metabolism
appear
be
regulated
by
variant
promoter
H3K27me3
H3K4me3
modifications,
as
well
promoter‐enhancer
interactions.
These
discoveries
offer
valuable
insights
into
how
cells
adapt
anti‐tumor
drugs
potential
impact
future
diagnostic
treatment
strategies.
Cancer Cell International,
Год журнала:
2024,
Номер
24(1)
Опубликована: Июль 11, 2024
Abstract
As
one
of
the
significant
challenges
to
human
health,
cancer
has
long
been
a
focal
point
in
medical
treatment.
With
ongoing
advancements
field
medicine,
numerous
methodologies
for
therapy
have
emerged,
among
which
oncolytic
virus
gained
considerable
attention.
However,
viruses
still
exhibit
limitations.
Combining
them
with
various
therapies
can
further
enhance
efficacy
treatment,
offering
renewed
hope
patients.
In
recent
research,
scientists
recognized
promising
prospect
amalgamating
diverse
treatments,
potentially
surmounting
restrictions
singular
approaches.
The
central
concept
this
combined
revolves
around
leveraging
incite
localized
tumor
inflammation,
augmenting
immune
response
immunotherapeutic
efficacy.
Through
approach,
patient's
system
better
recognize
and
eliminate
cells,
simultaneously
reducing
evasion
mechanisms
against
system.
This
review
delves
deeply
into
latest
research
progress
concerning
integration
treatments
its
role
types
therapy.
We
aim
analyze
mechanisms,
advantages,
potential
challenges,
future
directions
combination
By
extensively
exploring
field,
we
instill
fight
cancer.
Acta Neuropathologica,
Год журнала:
2024,
Номер
148(1)
Опубликована: Июль 16, 2024
Abstract
In
recent
years,
the
classification
of
adult-type
diffuse
gliomas
has
undergone
a
revolution,
wherein
specific
molecular
features
now
represent
defining
diagnostic
criteria
IDH-wild-type
glioblastomas,
IDH-mutant
astrocytomas,
and
1p/19q-codeleted
oligodendrogliomas.
With
introduction
2021
WHO
CNS
classification,
additional
alterations
are
integrated
into
grading
these
tumors,
given
equal
weight
to
traditional
histologic
features.
However,
there
remains
great
deal
heterogeneity
in
patient
outcome
even
within
established
tumor
subclassifications
that
is
unexplained
by
currently
codified
alterations,
particularly
astrocytoma
category.
There
also
significant
intercellular
genetic
epigenetic
plasticity
with
resulting
phenotypic
heterogeneity,
making
tumors
remarkably
adaptable
robust,
presenting
barrier
design
effective
therapeutics.
Herein,
we
review
mechanisms
consequences
instability,
including
chromosomal
instability
(CIN),
microsatellite
(MSI)/mismatch
repair
(MMR)
deficits,
underlying
biology,
tumorigenesis,
progression
astrocytomas.
We
discuss
contribution
high-resolution
transcriptomics
studies
toward
single-cell
resolution.
While
intratumoral
well-known
feature
gliomas,
various
processes
only
recently
been
considered
as
potential
driver
aggressiveness.
CIN
an
independent,
adverse
effect
on
survival,
similar
grade
homozygous
CDKN2A
deletion,
while
MMR
mutation
associated
poor
overall
survival
univariate
analysis
but
highly
correlated
higher
histologic/molecular
other
aggressive
These
forms
genomic
which
may
significantly
affect
natural
response
therapy,
ultimately
clinical
for
patients,
potentially
measurable
could
aid
diagnosis,
grading,
prognosis,
development
personalized
Analytical Chemistry,
Год журнала:
2024,
Номер
96(11), С. 4726 - 4735
Опубликована: Март 7, 2024
DNA
cytosine
methylation
(5-methylcytosine,
5mC)
is
a
predominant
epigenetic
modification
that
plays
critical
role
in
variety
of
biological
and
pathological
processes
mammals.
In
active
demethylation,
the
10-11
translocation
(TET)
dioxygenases
can
sequentially
oxidize
5mC
to
generate
three
modified
forms
cytosine,
5-hydroxymethylcytosine
(5hmC),
5-formylcytosine
(5fC),
5-carboxylcytosine
(5caC).
Beyond
being
demethylation
intermediate,
recent
studies
have
shown
5fC
has
regulatory
functions
gene
expression
chromatin
organization.
While
some
methods
been
developed
detect
5fC,
genome-wide
mapping
at
base
resolution
still
highly
desirable.
Herein,
we
propose
chemical
labeling
enrichment
deamination
sequencing
(CLED-seq)
method
for
detecting
genomic
single-base
resolution.
The
CLED-seq
utilizes
selective
5fC-containing
fragments,
followed
by
mediated
apolipoprotein
B
mRNA-editing
catalytic
polypeptide-like
3A
(APOBEC3A
or
A3A)
sequencing.
process,
while
all
C,
5mC,
5hmC
are
interpreted
as
T
during
sequencing,
read
enabling
precise
detection
DNA.
Using
proposed
method,
accomplished
mouse
embryonic
stem
cells.
study
revealed
promoter
regions
enriched
with
overlapped
H3K4me1,
H3K4me3,
H3K27ac
marks.
These
findings
suggest
correlation
between
marks
mESCs.
conclusion,
straightforward,
bisulfite-free
offers
valuable
tool
genomes
The
global
prevalence
of
obesity
has
reached
epidemic
levels,
significantly
elevating
the
susceptibility
to
various
cardiometabolic
conditions
and
certain
types
cancer.
In
addition
causing
metabolic
abnormalities
such
as
insulin
resistance
(IR),
elevated
blood
glucose
lipids,
ectopic
fat
deposition,
can
also
damage
pancreatic
islet
cells,
endothelial
cardiomyocytes
through
chronic
inflammation,
even
promote
development
a
microenvironment
conducive
cancer
initiation.
Improper
dietary
habits
lack
physical
exercise
are
important
behavioral
factors
that
increase
risk
obesity,
which
affect
gene
expression
epigenetic
modifications.
Epigenetic
alterations
occur
in
early
stage
some
reversible,
while
others
persist
over
time
lead
obesity-related
complications.
Therefore,
dynamic
adjustability
modifications
be
leveraged
reverse
obesity-associated
diseases
interventions,
drugs,
bariatric
surgery.
This
review
provides
comprehensive
summary
impact
regulation
on
initiation
cancers,
type
2
diabetes,
cardiovascular
diseases,
establishing
theoretical
basis
for
prevention,
diagnosis,
treatment
these
conditions.
