Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 25, 2024
Abstract
Background
The
main
reasons
pancreatic
cancer
(PC)
is
difficult
to
treat
are
high
tissue
fibrosis
and
a
strong
immunosuppressive
microenvironment.
Therefore,
it
necessary
elucidate
the
cause
mechanism
of
tumour
microenvironment
formation.
High-mobility
group
Box
1
(HMGB1)
highly
conserved
nuclear
protein
that
widely
distributed
in
mammalian
cells
plays
an
important
role
tumours.
However,
functions
mechanisms
HMGB1
PC
remain
controversial.
Here,
we
report
novel
for
formation
immune
Methods
In
this
study,
expression
level
samples
was
detected
patients
TCGA
database.
relative
serum
tissues
evaluated
by
enzyme-linked
immunosorbent
assay
(ELISA).
Flow
cytometry
used
detect
infiltration
myeloid-derived
suppressor
(MDSCs)
regulatory
T
tumours
from
xenograft
mouse
models
treated
with
HMGB1.
Vascular
density
cytokine
levels
were
measured
immunohistochemistry
(IHC).
HMGB1-associated
differentially
expressed
genes
GEPIA
database
analyse
GO
terms
KEGG
pathways.
Subsequently,
related
proteins
Western
blotting.
Results
higher
than
normal
tissues.
High
predict
poor
overall
survival
patients,
suggesting
its
potential
clinical
significance
prognosis.
model
results
show
significantly
promotes
growth.
We
further
found
CD69
+
CD8
markedly
decreased
HMGB1-treated
mice.
Furthermore,
after
treatment
HMGB1,
into
increased.
IHC
showed
promoted
intracellular
inflammatory
factors
neovascularization.
Mechanistically,
indicated
enhanced
CXCL2
chemokines
attract
MDSCs
upregulates
through
MAPK
pathway.
Conclusion
conclusion,
unexpected
metastasis
promoting
microvessel
mediated
pathway
recruit
MDSC
aggregation,
which
turn
creates
Thus,
may
be
mediator
therapeutic
target
regulating
progression.
(1)
Background:
Breast
cancer
is
a
frequent
heterogeneous
disorder
diagnosed
in
woman
and
high
cause
of
mortality
them
reason
to
rapid
metastasis
disease
recurrence.
Ferroptosis
can
inhibit
breast
cell
growth,
improve
the
sensitivity
chemotherapy
radiotherapy
distant
metastases
so
potentially
acts
on
tumor
micro-environment;
(2)
Methods:
Ferroptosis/Extracellular
matrix
remodeling
literature
text-mining
results
were
integrated
transcriptome
cohort
according
their
relapse
free
survival
(DRFS)
under
adjuvant
therapy
(anthracyclin+taxanes)
also
MDA-MB-231
functional
experiments
with
ferroptosis
activations
(GSE173905);
(3)
Results:
identified
910
associated
genes
at
list
10
articles.
Univariate
Cox
analyses
censored
(GSE25066)
selected
252
individual
significant
171
found
an
adverse
expression.
Functional
enrichment
these
predicted
basal
signatures.
By
some
shared
citations
domain
ECM
such
as:
TNF,
IL6,
SET,
CDKN2A,
EGFR,
HMGB1,
KRAS,
MET,
LCN2,
HIF1A,
TLR4.
A
molecular
score
based
expression
eleven
was
predictive
worst
prognosis
univariate
level:
subtype,
short
DRFS,
grade
values
3
4,
estrogen
progesterone
receptors
negative
nodal
stages
2
3.
This
gene
signature
validated
as
regulated
by
inductors
(erastin
RSL3)
triple
cellular
model
MDA-MB-231.;
(4)
Conclusions:
Crosstalk
between
remodeling-Ferroptosis
functionalities
allowed
define
which
have
been
characterized
independent
parameter
patients.
Gene
this
be
erastin/RSL3
activators.
could
promising
evaluate
impact
target
therapies
cancer.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 23, 2024
Abstract
Purpose
Acute
myeloid
leukemia
(AML)
is
a
refractory
hematologic
malignancy
that
poses
serious
threat
to
human
health.
Exploring
alternative
therapeutic
strategies
capable
of
inducing
modes
cell
death,
such
as
ferroptosis,
holds
great
promise
viable
and
effective
intervention.
Methods
We
analyzed
online
database
data
collected
clinical
samples
verify
the
expression
function
BMAL1
in
AML.
conducted
experiments
on
AML
proliferation,
cycle,
chemotherapy
resistance
by
overexpressing/knocking
down
using
assays
MDA
detection
BODIPY
581/591
C11
staining.
validated
transcriptional
regulation
HMGB1
through
ChIP
assay,
luciferase
RNA
level
detection,
western
blotting.
Finally,
we
confirmed
results
our
at
animal
level.
Results
up-regulation
an
observed
phenomenon
patients.
Furthermore,
there
existed
strong
correlation
between
elevated
levels
inferior
prognosis
individuals
with
found
knocking
inhibited
growth
blocking
cycle.
Conversely,
overexpressing
promoted
proliferation.
Moreover,
research
revealed
ferroptosis
cells
BMAL1-HMGB1-GPX4
pathway.
can
enhance
efficacy
certain
first-line
cancer
drugs,
including
venetoclax,
dasatinib,
sorafenib.
Conclusion
Our
suggest
plays
crucial
regulatory
role
drug
resistance,
ferroptosis.
could
be
potential
important
target
for
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 25, 2024
Abstract
Background
The
main
reasons
pancreatic
cancer
(PC)
is
difficult
to
treat
are
high
tissue
fibrosis
and
a
strong
immunosuppressive
microenvironment.
Therefore,
it
necessary
elucidate
the
cause
mechanism
of
tumour
microenvironment
formation.
High-mobility
group
Box
1
(HMGB1)
highly
conserved
nuclear
protein
that
widely
distributed
in
mammalian
cells
plays
an
important
role
tumours.
However,
functions
mechanisms
HMGB1
PC
remain
controversial.
Here,
we
report
novel
for
formation
immune
Methods
In
this
study,
expression
level
samples
was
detected
patients
TCGA
database.
relative
serum
tissues
evaluated
by
enzyme-linked
immunosorbent
assay
(ELISA).
Flow
cytometry
used
detect
infiltration
myeloid-derived
suppressor
(MDSCs)
regulatory
T
tumours
from
xenograft
mouse
models
treated
with
HMGB1.
Vascular
density
cytokine
levels
were
measured
immunohistochemistry
(IHC).
HMGB1-associated
differentially
expressed
genes
GEPIA
database
analyse
GO
terms
KEGG
pathways.
Subsequently,
related
proteins
Western
blotting.
Results
higher
than
normal
tissues.
High
predict
poor
overall
survival
patients,
suggesting
its
potential
clinical
significance
prognosis.
model
results
show
significantly
promotes
growth.
We
further
found
CD69
+
CD8
markedly
decreased
HMGB1-treated
mice.
Furthermore,
after
treatment
HMGB1,
into
increased.
IHC
showed
promoted
intracellular
inflammatory
factors
neovascularization.
Mechanistically,
indicated
enhanced
CXCL2
chemokines
attract
MDSCs
upregulates
through
MAPK
pathway.
Conclusion
conclusion,
unexpected
metastasis
promoting
microvessel
mediated
pathway
recruit
MDSC
aggregation,
which
turn
creates
Thus,
may
be
mediator
therapeutic
target
regulating
progression.