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Establishment and characterization of esophageal squamous cell carcinoma patient-derived xenograft mouse models for preclinical drug discovery.
[esophageal carcinoma]
The
purpose
of
this
study
was
to
establish
and
characterize
patient-derived
esophageal
squamous
cell
carcinoma
xenograft
(
PDECX
)
mice
for
utilization
in
antitumor
drug
discovery
.
A
total
of
96
esophageal
squamous
cell
carcinoma
(
ESCC
)
tissues
from
Chinese
patients
were
transplanted
subcutaneously
into
immunodeficient
mice
.
Histology
,
EGFR
,
K-
ras
,
B-
raf
,
and
PIK
3
CA
mutations
,
and
HER
2
gene
amplifications
were
analyzed
in
both
patient
tumors
and
mouse
xenograft
tissues
using
immunohistochemistry
,
mutant-enriched
liquid
chip
sequencing
and
fluorescence
in
situ
hybridization
assays
,
respectively
.
Furthermore
,
in
vivo
efficacy
studies
using
five
PDECX
mice
harboring
a
variety
of
genetic
aberrations
were
performed
using
the
chemotherapy
agents
5
-
fluorouracil
(
5
-
FU
)
and
cisplatin
.
Thirty
-
seven
PDECX
mouse
models
were
successfully
established
in
immunodeficient
mice
.
Pathological
analysis
revealed
similar
histological
architecture
and
degrees
of
differentiation
between
patient
ESCC
and
xenografted
tumors
.
No
mutations
were
identified
in
EGFR
,
K-
ras
,
and
B-
raf
genes
in
either
xenograft
models
or
patient
ESCC
tissues
.
In
contrast
,
PIK
3
CA
gene
mutations
were
detected
in
12
.
5
%
(
12
/
96
)
ESCC
patients
and
18
.
9
%
(
7
/
37
)
PDECX
models
.
Interestingly
,
patient
ESCC
tissues
exhibiting
HER
2
overexpression
or
gene
amplification
were
unable
to
survive
in
immunodeficient
mice
.
Further
analysis
showed
that
PDECX
models
carrying
HER
2
2
+
expression
had
no
response
to
5
-
FU
/
cisplatin
,
compared
with
HER
2
-
negative
models
.
In
conclusion
,
a
panel
of
PDECX
mouse
models
,
which
include
PIK
3
CA
mutant
and
HER
2
-
positive
models
,
was
established
and
characterized
thus
mimicking
the
current
clinical
genetic
setting
of
esophageal
carcinoma
.
The
sensitivity
of
HER
2
-
negative
ESCC
models
to
chemotherapy
supports
stratification
approaches
in
the
treatment
of
esophageal
carcinoma
patients
and
warrants
further
investigation
of
the
impact
of
PI
3
KCA
on
treatment
response
.
Diseases
Validation
Diseases presenting
"squamous cell carcinoma"
symptom
carcinoma of the gallbladder
child syndrome
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
junctional epidermolysis bullosa
kallmann syndrome
kindler syndrome
liposarcoma
monosomy 21
oculocutaneous albinism
oral submucous fibrosis
papillon-lefèvre syndrome
This symptom has already been validated