Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells
Cell stem cell,
Год журнала:
2024,
Номер
31(7), С. 989 - 1002.e9
Опубликована: Май 15, 2024
Physiologically
relevant
human
models
that
recapitulate
the
challenges
of
solid
tumors
and
tumor
microenvironment
(TME)
are
highly
desired
in
chimeric
antigen
receptor
(CAR)-T
cell
field.
We
developed
a
breast
cancer-on-chip
model
with
an
integrated
endothelial
barrier
enables
transmigration
perfused
immune
cells,
their
infiltration
into
tumor,
concomitant
monitoring
cytokine
release
during
culture
over
period
up
to
8
days.
Here,
we
exemplified
its
use
for
investigating
CAR-T
efficacy
ability
control
reaction
pharmacological
on/off
switch.
Additionally,
primary
cancer
organoids
study
patient-specific
efficacy.
The
modular
architecture
our
tumor-on-chip
paves
way
studying
role
other
types
TME
thus
provides
potential
broad
application
bench-to-bedside
translation
as
well
acceleration
preclinical
development
products.
Язык: Английский
A Network Toxicology Approach for Mechanistic Modelling of Nanomaterial Hazard and Adverse Outcomes
Advanced Science,
Год журнала:
2024,
Номер
11(32)
Опубликована: Июнь 25, 2024
Abstract
Hazard
assessment
is
the
first
step
in
evaluating
potential
adverse
effects
of
chemicals.
Traditionally,
toxicological
has
focused
on
exposure,
overlooking
impact
exposed
system
observed
toxicity.
However,
systems
toxicology
emphasizes
how
properties
significantly
contribute
to
response.
Hence,
theory
states
that
interactions
store
more
information
than
individual
elements,
leading
adoption
network
based
models
represent
complex
many
fields
life
sciences.
Here,
they
develop
a
network‐based
approach
characterize
responses
context
biological
system,
inferring
specific
networks.
They
directly
link
molecular
alterations
outcome
pathway
(AOP)
framework,
establishing
direct
connections
between
omics
data
and
toxicologically
relevant
phenotypic
events.
apply
this
framework
dataset
including
31
engineered
nanomaterials
with
different
physicochemical
two
vitro
one
vivo
demonstrate
driving
force
This
work
highlights
methods
improve
their
understanding
mechanisms
from
biology
perspective
provides
considerations
future
data‐driven
approaches
for
hazard
other
advanced
materials.
Язык: Английский
Advancing the quantitative understanding of Adverse Outcome Pathways: current status, methodologies, and future directions
Environmental Toxicology and Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 6, 2025
Abstract
An
adverse
outcome
pathway
(AOP)
framework
maps
the
sequence
of
events
leading
to
outcomes
from
chemical
exposures,
providing
a
mechanistic
understanding
often
absent
in
traditional
methods.
The
quantitative
AOP
(qAOP)
advances
by
integrating
data
and
mathematical
modeling,
thereby
more
precise
comprehension
relationships
between
molecular
initiating
events,
key
outcomes.
This
review
critically
examines
three
primary
methodologies:
systems
toxicology,
regression
Bayesian
network
highlighting
their
strengths,
limitations,
specific
requirements
within
toxicology.
Through
an
analysis
current
methodologies
challenges,
this
emphasizes
integration
experimental
computational
approaches
elucidate
event
proposes
strategies
for
overcoming
limitations
through
standardized
protocols
advanced
tools.
By
outlining
future
research
directions
potential
qAOPs
transform
risk
assessment,
aims
contribute
advancement
regulatory
science
protection
public
health
environment.
Язык: Английский
UVREK: Development and Analysis of an Expression Profile Knowledgebase of Biomolecules Induced by Ultraviolet Radiation Exposure
ACS Omega,
Год журнала:
2025,
Номер
10(2), С. 1927 - 1942
Опубликована: Янв. 8, 2025
Humans
encounter
diverse
environmental
factors
which
can
have
impact
on
their
health.
One
such
factor
is
ultraviolet
(UV)
radiation,
part
of
the
physical
component
exposome.
UV
radiation
leading
cause
skin
cancer
and
a
significant
global
health
concern.
A
large
body
published
research
has
been
conducted
to
uncover
mechanisms
underlying
adverse
outcomes
exposure
living
beings.
These
studies
involve
identifying
biomolecules
induced
upon
exposure.
few
previous
efforts
attempted
compile
this
information
in
form
database,
but
earlier
certain
limitations.
To
fill
gap,
we
present
structured
database
named
UVREK
(UltraViolet
Radiation
Expression
Knowledgebase),
containing
manually
curated
data
by
from
literature.
compiled
985
genes,
470
proteins,
54
metabolites,
77
miRNAs
along
with
metadata.
Thereafter,
an
enrichment
analysis
performed
human
gene
set
showed
importance
transcription-related
processes
UV-related
response
pathways
involved
aging.
While
significantly
contributing
toward
characterizing
exposome,
expect
that
will
serve
as
valuable
resource
for
development
better
protection
sensors
sunscreens.
Noteworthily,
only
date
compiling
varied
types
biomolecular
responses
corresponding
openly
accessible
at
https://cb.imsc.res.in/uvrek/.
Язык: Английский
Novel strategies to assess cytokine release mediated by chimeric antigen receptor T cells based on the adverse outcome pathway concept
Journal of Immunotoxicology,
Год журнала:
2024,
Номер
21(sup1)
Опубликована: Дек. 9, 2024
The
success
of
cellular
immunotherapies
such
as
chimeric
antigen
receptor
(CAR)
T
cell
therapy
has
led
to
their
implementation
a
revolutionary
treatment
option
for
cancer
patients.
However,
the
safe
translation
novel
immunotherapies,
from
non-clinical
assessment
first-in-human
studies
is
still
hampered
by
lack
suitable
in
vitro
and
vivo
models
recapitulating
complexity
human
immune
system.
Additionally,
using
cells
derived
healthy
volunteers
test
systems
may
not
adequately
reflect
altered
state
patient's
system
thus
potentially
underestimating
risk
life-threatening
conditions,
cytokine
release
syndrome
(CRS)
following
CAR
therapy.
IMI2/EU
project
imSAVAR
(immune
safety
avatar:
mimicking
effects
immunomodulatory
therapies)
aims
at
creating
platform
tools
enhanced
prediction
possible
adverse
events
associated
with
therapies.
This
shall
future
guide
early
therapeutics
thereby
also
reducing
costs
development.
Therefore,
we
review
current
opportunities
challenges
ranging
organ-on-chip
up
advanced
biomarker
screening.
Язык: Английский
UVREK: Development and analysis of an expression profile knowledgebase of biomolecules induced by ultraviolet radiation exposure
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 1, 2024
Abstract
Humans
encounter
diverse
environmental
factors
which
can
have
impact
on
their
health.
One
such
factor
is
the
ultraviolet
(UV)
radiation,
part
of
physical
component
exposome.
UV
radiation
leading
cause
skin
cancer
and
a
significant
global
health
concern.
A
large
body
published
research
has
been
conducted
to
uncover
mechanisms
underlying
adverse
outcomes
exposure
living
beings.
These
studies
involve
identifying
biomolecules
induced
upon
exposure.
few
previous
efforts
attempted
compile
this
information
in
form
database,
but
earlier
certain
limitations.
To
fill
gap,
we
present
structured
database
named
UVREK,
containing
manually
curated
data
by
from
literature.
UVREK
compiled
985
genes,
470
proteins,
54
metabolites
77
miRNAs
along
with
metadata.
Thereafter,
an
enrichment
analysis
performed
human
gene
set
showed
importance
transcription
related
processes
response,
pathways
involved
aging.
While
significantly
contributing
towards
characterizing
exposome,
expect
will
serve
as
valuable
resource
for
development
better
protection
sensors
sunscreens.
Noteworthy,
only
date,
compiling
varied
types
biomolecular
responses
corresponding
openly
accessible
at:
https://cb.imsc.res.in/uvrek/
.
Язык: Английский
A comprehensive review of the Direct Peptide Reactivity Assay in skin sensitization testing: Applicability, limitations, and considerations
Arhiv za farmaciju,
Год журнала:
2024,
Номер
74(3), С. 118 - 132
Опубликована: Янв. 1, 2024
Skin
sensitization
is
a
crucial
endpoint
in
the
safety
assessment
of
chemicals,
with
Direct
Peptide
Reactivity
Assay
(DPRA)
emerging
as
valuable
chemico
method
for
evaluating
substance's
potential.
This
review
delves
into
principles,
applicability,
and
limitations
DPRA
within
context
Adverse
Outcome
Pathway
(AOP)
framework
skin
sensitization.
We
examine
DPRA'srole
addressing
molecular
initiating
event
sensitization,
its
integration
Integrated
Approaches
to
Testing
Assessment
(IATA),
performance
predicting
sensitizers.
The
also
highlights
challenges
testing
certain
categories
chemicals
importance
considering
DPRA's
results
alongside
other
complementary
methods.
By
providing
comprehensive
overview
DPRA,
this
aims
inform
researchers,
regulators,
clinicians
about
utility
testing.
Язык: Английский
Building an Adverse Outcome Pathway network for COVID-19
Frontiers in Systems Biology,
Год журнала:
2024,
Номер
4
Опубликована: Июнь 7, 2024
The
COVID-19
pandemic
generated
large
amounts
of
data
on
the
disease
pathogenesis
leading
to
a
need
for
organizing
vast
knowledge
in
succinct
manner.
Between
April
2020
and
February
2023,
CIAO
consortium
exploited
Adverse
Outcome
Pathway
(AOP)
framework
comprehensively
gather
systematically
organize
published
scientific
literature
pathology.
project
considered
24
pathways
relevant
by
identifying
essential
key
events
(KEs)
19
adverse
outcomes
observed
patients.
While
an
individual
AOP
defines
causally
linked
perturbed
KEs
towards
outcome,
building
network
visually
reflect
interrelatedness
various
outcomes.
In
this
study,
17
those
AOPs
were
selected
based
quality
criteria
computationally
derive
network.
This
primary
highlighted
consider
tissue
specificity
helped
identify
missing
or
redundant
elements
which
then
manually
implemented
final
Such
enabled
visualization
complex
interactions
multifaceted
confirmed
central
role
inflammatory
response
disease.
addition,
study
disclosed
importance
terminology
harmonization
tissue/organ
building.
Furthermore
unequal
completeness
information
contained
tighter
implementation
FAIR
principles
improve
findability,
accessibility,
interoperability
re-usability.
Finally,
underlined
that
describing
specific
SARS-CoV-2
replication
discriminating
physiological
from
pathological
inflammation
is
necessary
but
requires
adaptations
framework.
Hence,
challenges
encountered,
we
proposed
recommendations
ongoing
future
AOP-aligned
consortia
aiming
build
biologically
meaningful
networks
context
of,
not
limited
to,
viral
diseases.
Язык: Английский
Transcriptome-centric approach to the derivation of adverse outcome pathway networks of vascular dysfunction after long-term low-level exposure of human endothelial cells to dibutyl phthalate
The Science of The Total Environment,
Год журнала:
2024,
Номер
948, С. 174918 - 174918
Опубликована: Июль 20, 2024
Язык: Английский