Anticancer Research,
Journal Year:
2020,
Volume and Issue:
40(12), P. 6585 - 6597
Published: Dec. 1, 2020
Recently,
therapeutic
drug
monitoring
of
5-fluorouracil
(5-FU),
the
key
chemotherapeutic
for
colorectal
cancer,
has
been
applied
in
daily
clinical
practice
and
contributed
towards
improving
outcomes.
However,
current
dose
modifications
are
based
only
on
values
area
under
plasma
concentration–time
profile,
which
simply
calculated
from
5-FU
concentrations
infusion
periods.
When
dose-limiting
toxicities
occur,
dosing
is
empirically
reduced
or
discontinued,
leading
to
treatment
failure.
To
prevent
this
predictable
failure
obtain
better
outcomes,
rational
dosage-based
strategies
required
5-FU.
Combining
with
a
mathematical
approach
using
pharmacokinetic–
pharmacodynamic/toxicodynamic
model
expected
help
simulate
time-course
profiles
efficacy
drugs
degree
toxicity,
thereby
contributing
setting
individual
patients.
Therefore,
facilitate
pharmacometric
modelling
simulation
techniques
optimising
oncology
therapies,
review
focuses
pharmacometrics
approaches
personalizing
5-FU-based
chemotherapy.
Royal Society of Chemistry eBooks,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 23, 2024
Circadian
rhythms
have
been
shown
to
be
ubiquitous
and
critically
important
in
the
experimental
laboratory,
accounting
for
difference
between
life
death
response
identical
stimulus.
The
partly
endogenous
nature
of
circadian
has
well
documented
methods
their
characterisation
developed
enabling
cellular
molecular
mechanisms
understood.
Chronobiology
Chronomedicine
aims
provide
a
review
these
underlying
illustrate
role
brain’s
suprachiasmatic
nuclei
‘pace-making’
process
effects
caused
by
‘clock
genes’
present
almost
all
cells.
Beyond
involved,
book
discusses
relationship
body
systems,
disease,
proper
function;
particular,
how
disruption
rhythm
is
associated
with
ill
health
disease
status
from
observations
made
at
organismic
level.
organised
an
ideal
introduction
postgraduate
various
fields,
reviewing
developments
outlining
show
depth
breadth
chronobiology
chronomedicine,
as
invaluable
companion
researchers
healthcare
professionals
working
field
interest
developing
novel
therapeutic
approaches.
Journal of Hematology & Oncology,
Journal Year:
2022,
Volume and Issue:
15(1)
Published: March 4, 2022
The
circadian
rhythm
is
an
evolutionarily
conserved
time-keeping
system
that
comprises
a
wide
variety
of
processes
including
sleep-wake
cycles,
eating-fasting
and
activity-rest
coordinating
the
behavior
physiology
all
organs
for
whole-body
homeostasis.
Acute
disruption
may
lead
to
transient
discomfort,
whereas
long-term
irregular
will
result
in
dysfunction
organism,
therefore
increasing
risks
numerous
diseases
especially
cancers.
Indeed,
both
epidemiological
experimental
evidence
has
demonstrated
intrinsic
link
between
dysregulated
cancer.
Accordingly,
rapidly
understanding
molecular
mechanisms
rhythms
opening
new
options
cancer
therapy,
possibly
by
modulating
clock.
In
this
review,
we
first
describe
general
regulators
their
functions
on
addition,
provide
insights
into
underlying
how
several
types
(including
sleep-wake,
eating-fasting,
activity-rest)
can
drive
progression,
which
expand
our
development
from
clock
perspective.
Moreover,
also
summarize
potential
applications
treatment,
optional
therapeutic
strategy
patients.
Current Opinion in Systems Biology,
Journal Year:
2020,
Volume and Issue:
21, P. 9 - 15
Published: June 1, 2020
Chronotherapy
is
a
pharmaceutical
intervention
that
considers
the
patient's
internal
circadian
time
to
adjust
dosing
time.
Although
it
can
dramatically
improve
drug
efficacy
and
reduce
toxicity,
large
variability
in
across
within
individuals
has
prevented
chronotherapies
from
progressing
beyond
clinical
trials.
To
translate
chronotherapy
developments
into
real-world
outpatient
scenario,
personalized
characterization
analysis
of
essential.
Here,
we
describe
recent
advances
wearable
technology
enable
real-time
high-resolution
tracking
ultradian
rhythms.
We
discuss
how
integrating
data
platforms
including
systems
modeling
machine
learning
pave
way
toward
adaptive
chronotherapy.
Computational and Structural Biotechnology Journal,
Journal Year:
2021,
Volume and Issue:
19, P. 5170 - 5183
Published: Jan. 1, 2021
Scheduling
anticancer
drug
administration
over
24
h
may
critically
impact
treatment
success
in
a
patient-specific
manner.
Here,
we
address
personalization
of
timing
using
novel
mathematical
model
irinotecan
cellular
pharmacokinetics
and
–dynamics
linked
to
representation
the
core
clock
predict
toxicity
colorectal
cancer
(CRC)
model.
The
is
fitted
three
different
scenarios:
mouse
liver,
where
metabolism
mainly
occurs,
two
human
cell
lines
representing
an
vitro
experimental
system
for
progression.
Our
successfully
recapitulates
quantitative
circadian
datasets
mRNA
protein
expression
together
with
timing-dependent
cytotoxicity
data.
also
discriminates
time-dependent
between
cells,
suggesting
that
can
be
optimized
according
their
clock.
results
show
degradation
mediating
activation,
as
well
oscillation
death
rate
play
important
role
variations
toxicity.
In
future,
this
used
support
personalized
scheduling
by
predicting
optimal
based
on
patient's
gene
profile.
Biology,
Journal Year:
2023,
Volume and Issue:
12(4), P. 612 - 612
Published: April 18, 2023
The
mammalian
cell
cycle
is
governed
by
a
network
of
cyclin/Cdk
complexes
which
signal
the
progression
into
successive
phases
division
cycle.
Once
coupled
to
circadian
clock,
this
produces
oscillations
with
24
h
period
such
that
each
phase
synchronized
day-night
Here,
we
use
computational
model
for
clock
control
investigate
entrainment
in
population
cells
characterized
some
variability
kinetic
parameters.
Our
numerical
simulations
showed
successful
and
synchronization
are
only
possible
sufficient
amplitude
an
autonomous
close
h.
Cellular
heterogeneity,
however,
introduces
cells.
Many
cancer
have
disrupted
or
compromised
control.
In
these
conditions,
runs
independently
leading
lack
When
coupling
weak,
largely
impacted,
but
maintain
tendency
divide
at
specific
times
day.
These
differential
features
between
healthy
can
be
exploited
optimize
timing
anti-cancer
drug
administration
order
minimize
their
toxicity
maximize
efficacy.
We
then
used
our
simulate
chronotherapeutic
treatments
predict
optimal
drugs
targeting
Although
qualitative,
highlights
need
better
characterize
cellular
heterogeneity
populations
as
well
consequences
design
chronopharmacological
protocols.
PLoS Computational Biology,
Journal Year:
2024,
Volume and Issue:
20(2), P. e1011907 - e1011907
Published: Feb. 26, 2024
Strong
circadian
(~24h)
rhythms
in
heart
rate
(HR)
are
critical
for
flexible
regulation
of
cardiac
pacemaking
function
throughout
the
day.
While
this
flexibility
HR
is
sustained
diverse
conditions,
it
declines
with
age,
accompanied
by
reduced
maximal
performance.
The
intricate
involves
orchestration
autonomic
nervous
system
(ANS),
body
temperature
(CRBT),
and
local
rhythmicity
(LCR),
which
has
not
been
fully
understood.
Here,
we
developed
a
mathematical
model
describing
ANS,
CRBT,
LCR
sinoatrial
nodal
cells
(SANC)
that
accurately
captures
distinct
patterns
adult
aged
mice.
Our
underscores
how
alliance
among
achieves
to
cover
wide
range
firing
rates
SANC,
performance
achieve
rates,
while
preserving
robustness
generate
rhythmic
irrespective
external
conditions.
Specifically,
ANS
dominates
promoting
SANC
performance,
CRBT
act
as
primary
secondary
boosters,
respectively,
further
enhance
Disruption
age
results
impaired
but
robustness.
This
unexpected
outcome
primarily
attributed
age-related
reduction
parasympathetic
activities,
maintains
compromising
flexibility.
work
sheds
light
on
regulating
time-of-day
dysfunction,
offering
insights
into
novel
therapeutic
targets
prevention
treatment
arrhythmias.
Current Opinion in Systems Biology,
Journal Year:
2024,
Volume and Issue:
37, P. 100506 - 100506
Published: Feb. 29, 2024
The
growing
numbers
of
cancer
cases
represent
a
medical
and
societal
burden
worldwide.
More
than
half
all
patients
are
treated
with
chemotherapy.
Yet,
chemotherapeutic
drugs
kill
not
only
cells,
but
also
healthy
tissue,
causing
massive
adverse
side
effects.
Recent
research
on
circadian
medicine
suggests
that
side-effects
can
be
reduced,
treatment
efficacy
increased,
by
considering
the
biological
clock
patients.
Integrating
profiles
molecular
markers
in
personalized
mathematical
models
simulate
individual
dynamics
drug
uptake,
action
cellular
response
to
This
requires
advanced
computational
tools
balance
prediction
quality
overfitting.
Personalized
will
eventually
lead
an
optimal
alignment
timing
inner
patient,
reducing
effects,
increasing
enhancing
patient
well-being.