Abstract
Frizzled
(Fzd)
proteins
are
Wnt
receptors
and
play
essential
roles
in
development,
homeostasis,
oncogenesis.
How
Wnt/Fzd
signaling
is
coupled
to
physiological
regulation
remains
unknown.
Cholesterol
reported
as
a
molecule
regulating
morphogen
such
Hedgehog
signaling.
Despite
the
elusiveness
of
in‐depth
mechanism,
it
well‐established
that
pancreatic
cancer
specially
requires
abnormal
cholesterol
metabolism
levels
for
growth.
In
this
study,
unexpectedly
found
among
ten
Fzds,
Fzd5
has
unique
capacity
bind
specifically
through
its
conserved
extracellular
linker
region.
Cholesterol‐binding
enables
palmitoylation,
which
indispensable
receptor
maturation
trafficking
plasma
membrane.
Wnt‐addicted
ductal
adenocarcinoma
(PDAC),
stimulates
tumor
growth
via
Fzd5‐mediated
Wnt/
β
‐catenin
A
natural
oxysterol,
25‐hydroxylsterol
competes
with
inhibits
signaling,
thereby
alleviating
PDAC
This
cholesterol‐receptor
interaction
ensuing
lipidation
uncover
novel
mechanism
by
acts
sensor
pivotal
connection
coupling
lipid
These
findings
further
suggest
cholesterol‐targeting
may
provide
new
therapeutic
opportunities
treating
Wnt‐dependent
cancers.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Янв. 16, 2023
Abstract
Microorganisms,
including
bacteria,
viruses,
fungi,
and
other
eukaryotes,
play
critical
roles
in
human
health.
An
altered
microbiome
can
be
associated
with
complex
diseases.
Intratumoral
microbial
components
are
found
multiple
tumor
tissues
closely
correlated
cancer
initiation
development
therapy
efficacy.
The
intratumoral
microbiota
may
contribute
to
promotion
of
the
progression
cancers
by
DNA
mutations,
activating
carcinogenic
pathways,
promoting
chronic
inflammation,
complement
system,
initiating
metastasis.
Moreover,
not
only
enhance
antitumor
immunity
via
mechanisms
STING
signaling
activation,
T
NK
cell
TLS
production,
microbiota-derived
antigen
presenting,
but
also
decrease
immune
responses
promote
through
pathways
upregulation
ROS,
an
anti-inflammatory
environment,
inactivation,
immunosuppression.
effect
on
is
dependent
composition,
crosstalk
between
cancer,
status
cancers.
regulate
physiology
response
different
β-catenin,
TLR,
ERK,
NF-κB,
STING,
among
others.
These
viewpoints
help
identify
as
diagnosis
or
prognosis
evaluation
cancers,
new
therapeutic
strategy
potential
targets
for
therapy.
Science Immunology,
Год журнала:
2022,
Номер
7(75)
Опубликована: Сен. 9, 2022
The
composition
of
the
gut
microbiome
can
control
innate
and
adaptive
immunity
has
emerged
as
a
key
regulator
tumor
growth,
especially
in
context
immune
checkpoint
blockade
(ICB)
therapy.
However,
underlying
mechanisms
for
how
affects
growth
remain
unclear.
Pancreatic
ductal
adenocarcinoma
(PDAC)
tends
to
be
refractory
therapy,
including
ICB.
Using
nontargeted,
liquid
chromatography–tandem
mass
spectrometry–based
metabolomic
screen,
we
identified
microbe–derived
metabolite
trimethylamine
N
-oxide
(TMAO),
which
enhanced
antitumor
PDAC.
Delivery
TMAO
intraperitoneally
or
via
dietary
choline
supplement
orthotopic
PDAC-bearing
mice
reduced
associated
with
an
immunostimulatory
tumor-associated
macrophage
(TAM)
phenotype,
activated
effector
T
cell
response
microenvironment.
Mechanistically,
potentiated
type
I
interferon
(IFN)
pathway
conferred
effects
IFN–dependent
manner.
Delivering
TMAO-primed
macrophages
intravenously
produced
similar
effects.
Combining
ICB
(anti-PD1
and/or
anti-Tim3)
mouse
model
PDAC
significantly
burden
improved
survival
beyond
alone.
Last,
levels
bacteria
containing
CutC
(an
enzyme
that
generates
trimethylamine,
precursor)
correlated
long-term
patients
anti-PD1
melanoma.
Together,
our
study
identifies
microbial
driver
lays
groundwork
potential
therapeutic
strategies
targeting
TMAO.
Abstract
Gut
microbiota‐derived
metabolites
are
key
hubs
connecting
the
gut
microbiome
and
cancer
progression,
primarily
by
remodeling
tumor
microenvironment
regulating
signaling
pathways
in
cells
multiple
immune
cells.
The
use
of
microbial
radiotherapy
chemotherapy
mitigates
severe
side
effects
from
treatment
improves
efficacy
treatment.
Immunotherapy
combined
with
effectively
activates
system
to
kill
tumors
overcomes
drug
resistance.
Consequently,
various
novel
strategies
have
been
developed
modulate
metabolites.
Manipulation
genes
involved
metabolism
using
synthetic
biology
approaches
directly
affects
levels
metabolites,
while
fecal
transplantation
phage
affect
altering
composition
microbiome.
However,
some
harbor
paradoxical
functions
depending
on
context
(e.g.,
type
cancer).
Furthermore,
metabolic
microorganisms
certain
anticancer
drugs
such
as
irinotecan
gemcitabine,
render
ineffective
or
exacerbate
their
adverse
effects.
Therefore,
a
personalized
comprehensive
consideration
patient's
condition
is
required
when
employing
treat
cancer.
purpose
this
review
summarize
correlation
between
cancer,
provide
fresh
ideas
for
future
scientific
research.
Probiotics and Antimicrobial Proteins,
Год журнала:
2023,
Номер
15(6), С. 1626 - 1643
Опубликована: Фев. 10, 2023
With
the
emphasis
on
intestinal
health,
probiotics
have
exploded
into
a
vast
market
potential.
However,
new
scientific
evidence
points
out
that
beneficial
health
benefits
of
are
not
necessarily
directly
related
to
viable
bacteria.
metabolites
or
bacterial
components
live
bacteria
driving
force
behind
promotion.
Therefore,
scientists
gradually
noticed
effects
based
itself,
metabolites,
cell
lysates,
and
these
factors
officially
named
"postbiotics"
by
ISAPP.
Postbiotic
diverse
outperform
in
terms
technology,
safety,
cost
due
their
good
absorption,
metabolism,
organismal
distribution.
Postbiotics
been
shown
bioactivities
such
as
antimicrobial,
antioxidant,
anti-inflammatory,
anti-proliferative,
immunomodulation.
Moreover,
numerous
studies
revealed
significant
potential
postbiotics
for
disease
treatment.
This
paper
first
presents
production
classification
with
examples
from
lactic
acid
(LAB),
followed
mechanisms
action
most
recent
pre-clinical
clinical
wide
range
non-clinical
applications
postbiotics.
Furthermore,
current
future
prospects
postbiotic
commercial
available
products
discussed.
Finally,
we
comment
knowledge
gaps
several
examples.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Янв. 10, 2024
Abstract
Human
microorganisms,
including
bacteria,
fungi,
and
viruses,
play
key
roles
in
several
physiological
pathological
processes.
Some
studies
discovered
that
tumour
tissues
once
considered
sterile
actually
host
a
variety
of
which
have
been
confirmed
to
be
closely
related
oncogenesis.
The
concept
intratumoural
microbiota
was
subsequently
proposed.
Microbiota
could
colonise
through
mucosal
destruction,
adjacent
tissue
migration,
hematogenic
invasion
affect
the
biological
behaviour
tumours
as
an
important
part
microenvironment.
Mechanistic
demonstrated
potentially
promote
initiation
progression
by
inducing
genomic
instability
mutations,
affecting
epigenetic
modifications,
promoting
inflammation
response,
avoiding
immune
regulating
metabolism,
activating
metastasis.
Since
more
comprehensive
profound
insights
about
intratumoral
are
continuously
emerging,
new
methods
for
early
diagnosis
prognostic
assessment
cancer
patients
under
examination.
In
addition,
interventions
based
on
show
great
potential
open
chapter
antitumour
therapy,
especially
immunotherapy,
although
there
some
inevitable
challenges.
Here,
we
aim
provide
extensive
review
concept,
development
history,
sources,
heterogeneity,
carcinogenic
mechanisms
explore
role
microorganisms
prognosis,
discuss
current
treatment
regimens
target
research
prospects
limitations
this
field.
Cancers,
Год журнала:
2023,
Номер
15(1), С. 321 - 321
Опубликована: Янв. 3, 2023
Due
to
the
absence
of
hormone
receptor
(both
estrogen
receptors
and
progesterone
receptors)
along
with
human
epidermal
growth
factor
2
(HER-2)
amplification,
treatment
triple-negative
breast
cancer
(TNBC)
cannot
benefit
from
endocrine
or
anti-HER-2
therapy.
For
a
long
time,
chemotherapy
was
only
systemic
for
TNBC.
lack
effective
options,
prognosis
TNBC
is
extremely
poor.
The
successful
application
immune
checkpoint
inhibitors
(ICIs)
launched
era
immunotherapy
in
However,
current
findings
show
modest
efficacy
programmed
cell
death-
(ligand)
1
(PD-(L)1)
monotherapy
small
proportion
patients
can
this
approach.
Based
on
basic
principles
characteristics
tumor
microenvironment
(TIME)
TNBC,
combination
therapy
expected
further
enhance
expand
beneficiary
population
patients.
Given
diversity
drugs
that
be
combined,
it
important
select
biomarkers
identify
target
population.
Moreover,
side
effects
associated
multiple
should
also
considered.
