Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
168, С. 115711 - 115711
Опубликована: Окт. 24, 2023
Esophageal
squamous
cell
carcinoma
(ESCC)
is
the
most
common
pathological
type
of
esophageal
cancer
in
China,
accounting
for
more
than
90
%.
Most
patients
were
diagnosed
with
advanced-stage
ESCC,
whom
new
adjuvant
therapy
recommended.
Therefore,
it
urgent
to
explore
therapeutic
targets
ESCC.
Ferroptosis,
a
newly
discovered
iron-dependent
programmed
death,
has
been
shown
play
an
important
role
carcinogenesis
by
many
studies.
This
study
explored
effect
Polo
like
kinase
1
(PLK1)
on
chemoradiotherapy
sensitivity
ESCC
through
ferroptosis
METHODS:
In
this
study,
we
knocked
out
expression
PLK1
(PLK1-KO)
lines
(KYSE150
and
ECA109)
CRISPR/CAS9.
The
effects
PLK1-knock
G6PD,
rate-limiting
enzyme
pentose
phosphate
pathway
(PPP),
downstream
NADPH
GSH
explored.
lipid
peroxidation
was
observed
flow
cytometry,
changes
mitochondria
transmission
electron
microscopy.
Next,
CCK-8
assay
clone
formation
assay,
cobalt
60
rays,
paclitaxel,
cisplatin
assessed
after
out,
nude
mouse
tumorigenesis
experiment
further
verified
it.
regulation
transcription
factor
YY1
evaluated
dual
luciferase
reporter
assay.
correlation
YY1,
their
impact
prognosis
analyzed
300
cases
from
GEO
database
our
center.
Finally,
above
results
proved
single-cell
sequencing.After
knockout,
G6PD
dimer
level
KYSE150
ECA109
cells
significantly
decreased.
Accordingly,
increased,
became
smaller,
membrane
density
likely
occur.
However,
stimulation
exogenous
(10
mM),
there
no
significant
difference
between
PLK1-KO
group
control
group.
After
ionizing
radiation,
had
higher
ratio,
sensitive
while
mM)
could
eliminate
difference.
Similar
also
be
when
receiving
paclitaxel
combined
chemoradiotherapy.
PLK1,
dimer,
KYSE150,
ECA109,
293
T
stably
transfected
YY1-shRNAs
decreased,
radiotherapy
chemotherapy.
center,
positively-correlated,
survival
high
shorter.
Further
analysis
sequencing
specimens
center
confirmed
results.In
down-regulation
can
inhibit
PPP,
reduce
GSH,
thereby
promoting
improving
Transcription
positive
regulatory
expressions
positively
correlated.
may
target
predicting
enhancing
Frontiers in Molecular Biosciences,
Год журнала:
2022,
Номер
9
Опубликована: Апрель 8, 2022
Hybrid
epithelial/mesenchymal
cells
(E/M)
are
key
players
in
aggressive
cancer
metastasis.
It
remains
a
challenge
to
understand
how
these
cell
states,
which
mostly
non-existent
healthy
tissue,
become
stable
phenotypes
participating
collective
migration.
The
transcription
factor
Nrf2,
is
associated
with
tumor
progression
and
resistance
therapy,
appears
be
central
this
process.
Here,
using
combination
of
immunocytochemistry,
single
biosensors,
computational
modeling,
we
show
that
Nrf2
functions
as
phenotypic
stability
for
hybrid
E/M
by
inhibiting
complete
epithelial-mesenchymal
transition
(EMT)
during
We
also
demonstrate
EMT
signaling
spatially
coordinated
near
the
leading
edge.
In
particular,
analysis
an
Nrf2-EMT-Notch
network
experimental
modulation
pharmacological
treatment
or
CRISPR/Cas9
gene
editing
reveal
stabilizes
phenotype
maximally
observed
interior
region
immediately
behind
further
enhances
Dll4
Jagged1
expression
at
edge,
correlates
formation
leader
protruding
tips.
Altogether,
our
results
provide
direct
evidence
acts
restricting
plays
important
role
coordinating
Stem Cell Reviews and Reports,
Год журнала:
2022,
Номер
18(7), С. 2209 - 2233
Опубликована: Июль 25, 2022
The
physiological
state
of
the
tumor
microenvironment
(TME)
plays
a
central
role
in
cancer
development
due
to
multiple
universal
features
that
transcend
heterogeneity
and
niche
specifications,
like
promoting
progression
metastasis.
As
result
their
preponderant
involvement
growth
maintenance
through
several
microsystemic
alterations,
including
hypoxia,
oxidative
stress,
acidosis,
TMEs
make
for
ideal
targets
both
diagnostic
therapeutic
ventures.
Correspondingly,
methodologies
target
have
been
investigated
this
past
decade
as
stratagems
significant
potential
genre
focused
treatment.
Within
targeted
oncotherapy,
nanomedical
derivates-nanocarriers
(NCs)
especially-have
emerged
present
notable
prospects
enhancing
targeting
specificity.
Yet,
one
major
issue
application
NCs
microenvironmental
directed
therapy
is
are
too
broad
spectrum
possibilities
these
carriers
be
effectively
employed.
However,
stem
cells
(CSCs)
might
portend
solution
above
conundrum:
aside
from
being
quite
heavily
invested
tumorigenesis
resistance,
CSCs
also
show
self-renewal
fluid
clonogenic
properties
often
define
specific
TME
niches.
Further
scrutiny
relationship
between
points
towards
mechanisms
underly
tumoral
characteristics
metastasis,
malignancy,
even
resistance.
This
review
summarizes
recent
advances
NC-enabled
more
holistic
strikes
against
discusses
current
challenges
hinder
clinical
strategies
well
avenues
can
further
CSC-targeting
initiatives.
Central
regulation
cellular
components
within
TME.
Frontiers in Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Март 14, 2023
Spinal
cord
injury
is
a
serious
traumatic
disease.
As
Ferroptosis
has
been
increasingly
studied
in
recent
years,
it
found
to
be
closely
related
the
pathophysiological
processes
of
spinal
injury.
Iron
overload,
reactive
oxygen
species
accumulation,
lipid
peroxidation
and
glutamate
accumulation
associated
with
are
all
present
injury,
thus
thought
involved
pathological
secondary
This
article
highlights
relationship
between
lists
substances
that
improve
by
inhibiting
Ferroptosis,
concludes
discussion
problems
may
encountered
clinical
translation
inhibitors
as
means
enabling
their
faster
use
treatment.
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
168, С. 115711 - 115711
Опубликована: Окт. 24, 2023
Esophageal
squamous
cell
carcinoma
(ESCC)
is
the
most
common
pathological
type
of
esophageal
cancer
in
China,
accounting
for
more
than
90
%.
Most
patients
were
diagnosed
with
advanced-stage
ESCC,
whom
new
adjuvant
therapy
recommended.
Therefore,
it
urgent
to
explore
therapeutic
targets
ESCC.
Ferroptosis,
a
newly
discovered
iron-dependent
programmed
death,
has
been
shown
play
an
important
role
carcinogenesis
by
many
studies.
This
study
explored
effect
Polo
like
kinase
1
(PLK1)
on
chemoradiotherapy
sensitivity
ESCC
through
ferroptosis
METHODS:
In
this
study,
we
knocked
out
expression
PLK1
(PLK1-KO)
lines
(KYSE150
and
ECA109)
CRISPR/CAS9.
The
effects
PLK1-knock
G6PD,
rate-limiting
enzyme
pentose
phosphate
pathway
(PPP),
downstream
NADPH
GSH
explored.
lipid
peroxidation
was
observed
flow
cytometry,
changes
mitochondria
transmission
electron
microscopy.
Next,
CCK-8
assay
clone
formation
assay,
cobalt
60
rays,
paclitaxel,
cisplatin
assessed
after
out,
nude
mouse
tumorigenesis
experiment
further
verified
it.
regulation
transcription
factor
YY1
evaluated
dual
luciferase
reporter
assay.
correlation
YY1,
their
impact
prognosis
analyzed
300
cases
from
GEO
database
our
center.
Finally,
above
results
proved
single-cell
sequencing.After
knockout,
G6PD
dimer
level
KYSE150
ECA109
cells
significantly
decreased.
Accordingly,
increased,
became
smaller,
membrane
density
likely
occur.
However,
stimulation
exogenous
(10
mM),
there
no
significant
difference
between
PLK1-KO
group
control
group.
After
ionizing
radiation,
had
higher
ratio,
sensitive
while
mM)
could
eliminate
difference.
Similar
also
be
when
receiving
paclitaxel
combined
chemoradiotherapy.
PLK1,
dimer,
KYSE150,
ECA109,
293
T
stably
transfected
YY1-shRNAs
decreased,
radiotherapy
chemotherapy.
center,
positively-correlated,
survival
high
shorter.
Further
analysis
sequencing
specimens
center
confirmed
results.In
down-regulation
can
inhibit
PPP,
reduce
GSH,
thereby
promoting
improving
Transcription
positive
regulatory
expressions
positively
correlated.
may
target
predicting
enhancing
