Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Aug. 17, 2023
Abstract
Neoadjuvant
chemotherapy
(NAC)
followed
by
surgery
is
a
standard
approach
for
management
of
locally
advanced
esophageal
squamous
cell
carcinoma
(ESCC).
Patients
who
do
not
respond
well
to
NAC
have
poor
prognosis.
Despite
extensive
research,
the
mechanisms
chemoresistance
in
ESCC
remain
largely
unknown.
Here,
we
established
paired
tumor
organoids
–
designated
as
PreNAC-O
and
PostNAC-O
from
one
patient
before
after
NAC,
respectively.
Although
two
did
exhibit
significant
differences
proliferation,
morphology
or
drug
sensitivity
vitro,
tumorigenicity
vivo
was
significantly
higher
than
that
PreNAC-O.
Xenografts
tended
keratinization,
while
those
displayed
conspicuous
necrotic
areas.
The
xenografts
during
comparable
without
treatment.
Furthermore,
gene
expression
profiles
suggested
genes
involved
EMT
and/or
hypoxia
response
might
be
related
PostNAC-O.
Our
data
residual
cancer
had
been
enhanced,
outweighing
effects
chemotherapy,
rather
being
attributable
intrinsic
chemoresistance.
Further
studies
are
required
clarify
extent
which
cancers
share
common
mechanism
similar
revealed
here.
Frontiers in Bioscience-Landmark,
Journal Year:
2023,
Volume and Issue:
28(10)
Published: Oct. 24, 2023
Cancer
whose
major
problems
are
metastasis,
treatment
resistance,
and
recurrence
is
the
leading
cause
of
death
worldwide.
Tumor-initiating
stem
cells
(TiSCs)
a
subset
tumor
population
responsible
for
resistance
relapse.
Understanding
characteristics
shared
features
between
tumor-initiating
long-lived
postmitotic
may
hold
key
to
better
understanding
biology
cancer.
Postmitotic
have
exited
cell
cycle
transitioned
into
non-dividing
terminally
differentiated
state
with
specialized
function
within
tissue.
Conversely,
cancer
TiSC
feature
can
divide
produce
variety
progenies,
disease
progression,
therapy
immune
system
Surprisingly,
our
comprehensive
evaluation
TiSCs
suggests
common
post-mitotic
cells.
They
similar
in
structure
(primary
cilia,
high
mitochondrial
content,
being
protected
by
barrier),
metabolism
(autophagy
senescence),
(immunoescape
and/or
immune-privileged
blood
barrier).
In-depth
exploration
showed
how
contributes
these
features,
including
energy
demands
arising
from
ciliary
microtubular
functionality,
increased
metabolic
activity,
movement.
These
findings
assist
decoding
remaining
properties
which
offer
insights
TiSCs,
potential
implications
enhancing
strategies
patient
prognosis.
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Feb. 13, 2024
Abstract
Pharmacological
activation
of
hypoxia-inducible
factor
1
(HIF-1),
a
hypoxia-responsive
transcription
factor,
has
attracted
increasing
attention
due
to
its
efficacy
not
only
in
renal
anemia
but
also
various
disease
models.
Our
study
demonstrated
that
HIF-1
activator
enhanced
extracellular
vesicle
(EV)
production
from
cultured
endothelial
cells
synergistically
with
adiponectin,
an
adipocyte-derived
through
both
transcriptional
induction
and
posttranscriptional
stabilization
adiponectin
binding
partner,
T-cadherin.
Increased
EV
levels
were
observed
wild-type
mice
T-cadherin
null
after
consecutive
administration
roxadustat.
Adiponectin-
T-cadherin-dependent
increased
may
be
involved
the
pleiotropic
effects
activators.
Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Aug. 17, 2023
Abstract
Neoadjuvant
chemotherapy
(NAC)
followed
by
surgery
is
a
standard
approach
for
management
of
locally
advanced
esophageal
squamous
cell
carcinoma
(ESCC).
Patients
who
do
not
respond
well
to
NAC
have
poor
prognosis.
Despite
extensive
research,
the
mechanisms
chemoresistance
in
ESCC
remain
largely
unknown.
Here,
we
established
paired
tumor
organoids
–
designated
as
PreNAC-O
and
PostNAC-O
from
one
patient
before
after
NAC,
respectively.
Although
two
did
exhibit
significant
differences
proliferation,
morphology
or
drug
sensitivity
vitro,
tumorigenicity
vivo
was
significantly
higher
than
that
PreNAC-O.
Xenografts
tended
keratinization,
while
those
displayed
conspicuous
necrotic
areas.
The
xenografts
during
comparable
without
treatment.
Furthermore,
gene
expression
profiles
suggested
genes
involved
EMT
and/or
hypoxia
response
might
be
related
PostNAC-O.
Our
data
residual
cancer
had
been
enhanced,
outweighing
effects
chemotherapy,
rather
being
attributable
intrinsic
chemoresistance.
Further
studies
are
required
clarify
extent
which
cancers
share
common
mechanism
similar
revealed
here.