Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C1855645 (
KPC
)
1,473
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Dinaciclib is a small molecule
cyclin-dependent kinase inhibitor
with the potential to treat multiple cancers. To better understand its cytotoxic action in pancreatic ductal adenocarcinoma (PDAC), we evaluated dinaciclib therapeutic effects in the transgenic mouse model (
LSL-Kras
G12D/+
;
LSL-Trp53
R172H/+
;
Pdx-1-Cre
mice;
KPC
mice). Tumor growth and microenvironment were dynamically monitored by magnetic resonance imaging (MRI). Dinaciclib therapy significantly delayed tumor progression (P < 0.001) and prolonged survival (P = 0.007) in
KPC
mice.
In vitro
assays showed that dinaciclib exerted antiproliferative effects on PDAC cells by increasing surface calreticulin expression and release of ATP. Dinaciclib treatment inhibited proliferation and induced apoptosis in
KPC
tumor as assessed by Ki67 and cleaved caspase 3, respectively. Particularly, the tumor infiltrating CD8
+
T cells were increased after dinaciclib treatment in
KPC
mice. Additionally, the mean apparent diffusion coefficient values of
KPC
tumor calculated from diffusion weighted MR images were significantly lower after dinaciclib treatment (P = 0.033). These finding suggest that dinaciclib as a single agent can inhibit tumor growth and improve the overall survival in
KPC
mice.
...
PMID:Dinaciclib prolongs survival in the
LSL-Kras
G12D/+
;
LSL-Trp53
R172H/+
;
Pdx-1-Cre
(KPC) transgenic murine models of pancreatic ductal adenocarcinoma. 3226 32
