Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer
Published: May 13, 2024
Chemotherapy
treatment
against
pancreatic
ductal
adenocarcinoma
(PDAC)
is
thwarted
by
tumoral
activation
of
multiple
therapy-resistance
pathways.
The
growth
hormone
(GH)
–
GH
receptor
(GHR)
pair
a
covert
driver
multimodal
therapy
resistance
in
cancer,
and
overexpressed
PDAC
tumors,
yet
the
therapeutic
potential
targeting
same
has
not
been
explored.
Here,
we
report
that
GHR
expression
negative
prognostic
factor
patients
with
PDAC.
Combinations
gemcitabine
different
antagonists
(GHRAs)
markedly
improve
outcomes
nude
mice
xenografts.
Employing
cultured
cells,
mouse
xenografts,
analyses
human
transcriptome,
identified
attenuation
multidrug
transporter
epithelial-to-mesenchymal
transition
programs
tumors
underlie
observed
augmentation
chemotherapy
efficacy
GHRAs.
Moreover,
patients,
strongly
correlates
gene
signature
tumor-promotion
immune-evasion,
which
corroborate
syngeneic
wild-type
vs.
transgenic
mice.
Overall,
found
action
promoted
therapy-refractory
vivo,
can
be
effectively
attenuated
antagonism.
Our
results
collectively
present
proof
concept
towards
considering
antagonist
to
chemotherapeutic
outcome
highly
chemoresistant
Language: Английский
Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(13), P. 7438 - 7438
Published: July 6, 2024
Chemotherapy
treatment
against
pancreatic
ductal
adenocarcinoma
(PDAC)
is
thwarted
by
tumoral
activation
of
multiple
therapy
resistance
pathways.
The
growth
hormone
(GH)-GH
receptor
(GHR)
pair
a
covert
driver
multimodal
in
cancer
and
overexpressed
PDAC
tumors,
yet
the
therapeutic
potential
targeting
same
has
not
been
explored.
Here,
we
report
that
GHR
expression
negative
prognostic
factor
patients
with
PDAC.
Combinations
gemcitabine
different
antagonists
(GHRAs)
markedly
improve
outcomes
nude
mice
xenografts.
Employing
cultured
cells,
mouse
xenografts,
analyses
human
transcriptome,
identified
attenuation
multidrug
transporter
epithelial-to-mesenchymal
transition
programs
tumors
underlie
observed
augmentation
chemotherapy
efficacy
GHRAs.
Moreover,
patients,
strongly
correlates
gene
signature
tumor
promotion
immune
evasion,
which
corroborate
syngeneic
wild-type
vs.
GH
transgenic
mice.
Overall,
found
action
promoted
therapy-refractory
vivo,
can
be
effectively
attenuated
antagonism.
Our
results
collectively
present
proof
concept
toward
considering
to
chemotherapeutic
highly
chemoresistant
Language: Английский
Common and Uncommon Mouse Models of Growth Hormone Deficiency
Endocrine Reviews,
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 10, 2024
Abstract
Mouse
models
of
growth
hormone
deficiency
(GHD)
have
provided
important
tools
for
uncovering
the
various
actions
GH.
Nearly
100
years
research
using
these
mouse
lines
has
greatly
enhanced
our
knowledge
GH/IGF-1
axis.
Some
shared
phenotypes
5
“common”
GHD
include
reduced
body
size,
delayed
sexual
maturation,
decreased
fertility,
muscle
mass,
increased
adiposity,
and
insulin
sensitivity.
Since
common
outlive
their
normal-sized
littermates—and
protection
from
age-associated
disease—they
become
fixtures
in
aging
field.
On
other
hand,
12
“uncommon”
described
herein
tremendously
divergent
health
outcomes
ranging
beneficial
(similar
to
those
models)
extremely
detrimental
features
(such
as
improper
development
central
nervous
system,
numerous
sensory
organ
defects,
embryonic
lethality).
Moreover,
advancements
next-generation
sequencing
technologies
led
identification
an
expanding
array
genes
that
are
recognized
causative
agents
rare
syndromes
with
concomitant
GHD.
Accordingly,
this
review
provides
researchers
a
comprehensive
up-to-date
collection
uncommon
been
used
study
aspects
physiology
metabolism
associated
multiple
forms
For
each
line
presented,
closest
comparable
human
discussed
providing
parallels
clinic.
Language: Английский
Characterizing Hormone Secretion Patterns in PitNETs with Metabolomics: Implications for Understanding Tumor Biology
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 17, 2024
Abstract
Background
Pituitary
neuroendocrine
tumors
(PitNETs)
are
heterogeneous
neoplasms
originating
from
the
pituitary
gland.
Metabolomics,
a
comprehensive
analysis
of
small
molecules,
has
emerged
as
valuable
tool
for
studying
tumors.
In
presen
investigation,
metabolomic
methodology
was
employed
to
facilitate
more
understanding
tumor
pathogenesis.
Methods
Nuclear
Magnetic
Resonance
(NMR)
Spectroscopy
utilized
investigate
metabolic
profiles
hypophyseal
tissue
samples
obtained
22
patients
with
PitNETs,
who
underwent
excisional
surgery
and
exhibited
varying
hormone
secretion
statuses.
Results
Using
NMR
analysis,
we
identified
10
metabolites
significant
changes,
including
O-Phosphoethanolamine
(PEA),
myo-Inositol
(I),
choline,
several
amino
acids
in
samples.
non-functioning
(NF)
group,
elevated
levels
PEA,
myo-I,
Glycine,
Choline
were
observed,
whereas
Glutamate,
Phenylalanine,
Valine,
Isoleucine,
Tyrosine,
Methionine
decreased
same
group.
Phospholipid
metabolism,
inositol
phosphate
acid
metabolism
proposed
potential
mechanisms
underlying
secretory
characteristics
tissue.
Conclusions
Functioning
nonfunctioning
PitNETs
display
distinct
characteristics.
Elevated
PEA
observed
group
might
have
inhibited
synthesis
by
suppressing
mitochondrial
activity,
which
could
potentially
contribute
development
Further
research
is
warranted
validate
these
findings
explore
their
clinical
applications,
such
biomarker
discovery
therapeutic
targeting
Language: Английский
Growth Hormone Action as a Target in Cancer: Significance, Mechanisms and Possible Therapies
Endocrine Reviews,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 3, 2024
Growth
hormone
(GH)
is
a
pituitary
derived
endocrine
required
for
normal
post-natal
growth
and
development.
Hypo
or
hypersecretion
of
GH
results
in
two
pathologic
conditions,
namely
deficiency
(GHD)
acromegaly.
Additionally,
also
produced
non-pituitary
tumoral
tissues
where
it
acts
rather
as
cellular
factor
with
an
autocrine/paracrine
mode
action.
An
increasingly
persuasive
large
body
evidence
over
the
last
70
years
concur
that
action
implicit
escalating
several
cancer-associated
events,
locally
systemically.
This
pleiotropy
GH's
effects
puzzling,
but
association
cancer-risk
automatically
raises
concern
patients
acromegaly
individuals
treated
GH.
By
careful
assessment
available
knowledge
on
fundamental
concepts
cancer,
suggestions
from
epidemiological
clinical
studies,
specific
reports,
this
review
we
aimed
to
help
clarify
distinction
vs.
promoting
cancer
reconcile
discrepancies
between
experimental
data.
Along
discourse,
critically
weigh
targetability
-
firstly
by
detailing
molecular
mechanisms
which
posit
critical
node
tumor
circuitry,
secondly,
enumerating
currently
therapeutic
options
targeting
On
basis
our
discussion,
infer
targeted
intervention
appropriate
patient
population
can
benefit
sizeable
subset
current
prognoses.
Language: Английский