ACS Nano,
Journal Year:
2020,
Volume and Issue:
14(4), P. 4816 - 4828
Published: March 18, 2020
Hepatocellular
carcinoma
(HCC)
resistant
to
both
chemotherapy
and
immunotherapy
is
among
the
deadliest
malignancies.
Doxorubicin
widely
used
in
transarterial
HCC
can
induce
immunogenic
cell
death
(ICD),
but
resulting
immunogenicity
still
weak.
We
aim
seek
a
strategy
for
improving
efficacy
of
ICD
based
on
an
immunoregulatory
drug
called
icaritin.
Icaritin
induced
mitophagy
apoptosis
provoke
mouse
Hepa1-6
human
Huh7
cells.
A
combination
icaritin
doxorubicin
with
molar
ratio
1:2
played
synergistic
role
induction.
The
poly
lactic-co-glycolic
acid
(PLGA)-polyethylene
glycol
(PEG)-aminoethyl
anisamide
(AEAA)
nanoparticle
(NP)
targeted
codelivery
remodeled
immunosuppressive
tumor
microenvironment
triggered
robust
immune
memory
response,
which
efficiently
improved
anti-HCC
effect
at
early
stage
model.
In
addition,
combo
PLGA-PEG-AEAA
NP
together
lenvatinib
significantly
prolonged
survival
time
mice
advanced
HCC.
Collectively,
our
findings
reveal
mechanism
provide
effective
immune-based
therapeutic
Scientific Reports,
Journal Year:
2018,
Volume and Issue:
8(1)
Published: June 11, 2018
Multiple
studies
suggested
using
different
miRNAs
as
biomarkers
for
prognosis
of
hepatocellular
carcinoma
(HCC).
We
aimed
to
assemble
a
miRNA
expression
database
from
independent
datasets
enable
an
validation
previously
published
prognostic
HCC.
A
was
established
by
searching
the
TCGA
(RNA-seq)
and
GEO
(microarray)
repositories
identify
with
available
clinical
data.
PubMed
search
performed
uni-
multivariate
Cox
regression
analysis
validate
significance
these
miRNAs.
The
Limma
R
package
applied
compare
between
tumor
normal
tissues.
uncovered
214
publications
containing
223
identified
potential
In
survival
analysis,
levels
55
84
were
significantly
correlated
overall
in
RNA-seq
gene
chip
datasets,
respectively.
most
significant
hsa-miR-149,
hsa-miR-139,
hsa-miR-3677
hsa-miR-146b-3p,
hsa-miR-584,
hsa-miR-31
microarray
dataset.
Of
studied,
altered
102
tumors
compared
liver
summary,
we
set
up
integrated
validated
Journal of Clinical Oncology,
Journal Year:
2020,
Volume and Issue:
38(26), P. 2960 - 2970
Published: July 27, 2020
PURPOSE
The
immunomodulatory
effect
of
lenvatinib
(a
multikinase
inhibitor)
on
tumor
microenvironments
may
contribute
to
antitumor
activity
when
combined
with
programmed
death
receptor-1
(PD-1)
signaling
inhibitors
in
hepatocellular
carcinoma
(HCC).
We
report
results
from
a
phase
Ib
study
plus
pembrolizumab
(an
anti–PD-1
antibody)
unresectable
HCC
(uHCC).
PATIENTS
AND
METHODS
In
this
open-label
multicenter
study,
patients
uHCC
received
(bodyweight
≥
60
kg,
12
mg;
<
8
mg)
orally
daily
and
200
mg
intravenously
day
1
21-day
cycle.
included
dose-limiting
toxicity
(DLT)
an
expansion
(first-line
patients).
Primary
objectives
were
safety/tolerability
(DLT
phase),
objective
response
rate
(ORR)
duration
(DOR)
by
modified
RECIST
(mRECIST)
version
1.1
(v1.1)
per
independent
imaging
review
(IIR;
phase).
RESULTS
A
total
104
enrolled.
No
DLTs
reported
(n
=
6)
the
DLT
phase;
100
(expansion
n
2
phase)
had
no
prior
systemic
therapy
Barcelona
Clinic
Liver
Cancer
stage
B
29)
or
C
disease
71).
At
data
cutoff,
37%
remained
treatment.
Median
follow-up
was
10.6
months
(95%
CI,
9.2
11.5
months).
Confirmed
ORRs
IIR
46.0%
36.0%
56.3%)
mRECIST
26.6%
46.2%)
v1.1.
DORs
8.6
6.9
not
estimable
[NE])
12.6
NE)
progression-free
survival
9.3
overall
22
months.
Grade
3
treatment-related
adverse
events
occurred
67%
(grade
5,
3%)
patients.
new
safety
signals
identified.
CONCLUSION
Lenvatinib
has
promising
uHCC.
Toxicities
manageable,
unexpected
signals.
Nature Reviews Gastroenterology & Hepatology,
Journal Year:
2021,
Volume and Issue:
18(8), P. 525 - 543
Published: April 13, 2021
Hepatocellular
carcinoma
(HCC)
is
a
prevalent
disease
with
progression
that
modulated
by
the
immune
system.
Systemic
therapy
used
in
advanced
stage
and
until
2017
consisted
only
of
antiangiogenic
tyrosine
kinase
inhibitors
(TKIs).
Immunotherapy
checkpoint
has
shown
strong
anti-tumour
activity
subset
patients
combination
anti-PDL1
antibody
atezolizumab
VEGF-neutralizing
bevacizumab
or
will
soon
become
standard
care
as
first-line
for
HCC,
whereas
anti-PD1
agents
nivolumab
pembrolizumab
are
after
TKIs
several
regions.
Other
strategies
such
adoptive
T-cell
transfer,
vaccination
virotherapy
have
not
yet
demonstrated
consistent
clinical
activity.
Major
unmet
challenges
HCC
immunotherapy
discovery
validation
predictive
biomarkers,
advancing
treatment
to
earlier
stages
disease,
applying
liver
dysfunction
more
effective
combinatorial
sequential
approaches.
Combinations
other
systemic
local
treatments
perceived
most
promising
opportunities
some
already
under
evaluation
large-scale
trials.
This
Review
provides
up-to-date
information
on
best
use
currently
available
immunotherapies
therapeutic
development.
Immunotherapeutic
interventions
might
be
tools
hepatocellular
carcinoma.
carcinoma,
mechanisms
response
resistance,
Cells,
Journal Year:
2020,
Volume and Issue:
9(4), P. 875 - 875
Published: April 3, 2020
Liver
fibrosis
due
to
viral
or
metabolic
chronic
liver
diseases
is
a
major
challenge
of
global
health.
Correlating
with
disease
progression,
key
factor
for
outcome
and
risk
hepatocellular
carcinoma
(HCC).
Despite
different
mechanism
primary
injury
disease-specific
cell
responses,
the
progression
fibrotic
follows
shared
patterns
across
main
etiologies.
Scientific
discoveries
within
last
decade
have
transformed
understanding
mechanisms
fibrosis.
Removal
elimination
causative
agent
such
as
control
cure
infection
has
shown
that
reversible.
However,
reversal
often
occurs
too
slowly
infrequent
avoid
life-threatening
complications
particularly
in
advanced
Thus,
there
huge
unmet
medical
need
anti-fibrotic
therapies
prevent
HCC
development.
while
many
candidate
agents
robust
effects
experimental
animal
models,
their
clinical
trials
been
limited
absent.
no
approved
therapy
exists
In
this
review
we
summarize
cellular
drivers
molecular
fibrogenesis
discuss
impact
development
urgently
needed
therapies.
