|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
A murine PDAC cell line was established from a transgenic mouse with pancreas-specific mutations in KRAS and p53.
|
30463776 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Initiation of pancreatic ductal adenocarcinoma (PDAC) is driven by oncogenic KRAS mutation, and disease progression is associated with frequent loss of tumor suppressors.
|
21984975 |
2011 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
As miR-216/-217 are acinar enriched, reduced in human PDAC and target KRAS, we hypothesized that they may maintain acinar differentiation or represent tumor suppressive miRNAs.
|
27541609 |
2017 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In conclusion, mutant KRAS promotes endosomal degradation in PDAC cell lines, which is impaired by KRAS silencing.
|
28867190 |
2017 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Inactivating mutations in tumor suppressor genes such as CDKN2A/p16, TP53, and SMAD4 cooperate with KRAS mutations to cause aggressive PDAC tumor growth.
|
27865459 |
2016 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Recent large-scale genomic analyses of PDAC revealed that KRAS is the most frequently mutated driver gene in this entity.
|
30286473 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our results demonstrate that BET inhibition displays significant therapeutic impact in genetic mouse models of KRAS-driven PDAC and NSCLC, reducing both tumor area and tumor grade.
|
29721157 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We used droplet digital polymerase chain reaction (ddPCR) to detect the expression of KRAS-mutated genes in plasma samples of 65 PDAC patients who underwent IRE.
|
29940591 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
However, in pancreatic ductal adenocarcinoma (PDAC) there are only four abundantly common driver mutations (KRAS, CDKN2A, TP53, and SMAD4), which are not currently actionable.
|
31639254 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Activating mutations in the KRAS oncogene are prevalent in pancreatic ductal adenocarcinoma (PDAC).
|
25250570 |
2014 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
K-RAS also impacts tumor microenvironment and PDAC metabolism reprogramming.
|
28259298 |
2017 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Furthermore, CRISPR-Cas9-based genome editing of PDAC driver genes (KRAS, CDKN2A, SMAD4, and TP53) demonstrated non-genetic acquisition of Wnt niche independence during pancreas tumorigenesis.
|
29337182 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
In the present study, we determined the mutational status of KRAS in plasma cfDNA using multiplex picoliter-droplet digital PCR in 259 patients with PDAC.
|
26669280 |
2015 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In mice, a high-fat diet (HFD) and expression of oncogenic KRAS lead to development of invasive pancreatic ductal adenocarcinoma (PDAC) by unknown mechanisms.
|
31352001 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
PDAC is associated with mutations in major driver genes, including KRAS, TP53, CDKN2A/p16 and SMAD4/DPC4.
|
27256393 |
2016 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Accordingly, Kras-inhibited cells displayed prominent focal adhesion plaque structures, enhanced adherence properties, and increased dependency on adhesion for viability <i>in vitro</i> Overall, our results call into question the degree to which PDAC cells are addicted to activated KRAS, by illustrating adaptive nongenetic and nontranscriptional mechanisms of resistance to Kras blockade.
|
29279356 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Yet, the specific roles of KRAS-stimulated signaling pathways in the transformation of pancreatic ductal epithelial cells (PDEC), putative cells of origin for PDAC, remain unclear.
|
22871572 |
2012 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
The mutational status of GNAS and KRAS was evaluated by cycle sequencing in PDACs and pre-/coexisting IPMNs.
|
23532108 |
2013 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Collectively, these data underscore the potential for PDAC resistance to even the very best KRAS inhibitors and provide insights into mechanisms of response and resistance to KRAS inhibition.
|
29061961 |
2017 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The most frequent oncogenic mutations in PDAC are loss-of function mutations in p53 and gain-of-function mutations in KRAS.
|
27542263 |
2017 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
In a KRAS-induced orthotopic PDAC model, coadministration of iRGD enhanced the uptake of an irinotecan-loaded silicasome carrier that comprises lipid bilayer-coated mesoporous silica nanoparticles (MSNPs); this uptake resulted in enhanced survival and markedly reduced metastasis.
|
28414297 |
2017 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The low KRAS mutation rate and its prognostic role may suggest the further survival benefit in Korean PDAC patients.
|
25513781 |
2015 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Combinatorial targeting of eIF5A hypusination and the RAS-ERK signaling pathway cooperated to attenuate KRAS expression and its downstream signaling along with cell growth <i>in vitro</i> and tumor formation <i>in vivo</i> Collectively, our findings highlight a new mechanistic strategy to attenuate KRAS expression as a therapeutic strategy to target PDAC and other human cancers driven by KRAS activation.<b>Significance:</b> These findings highlight a new mechanistic strategy to attenuate KRAS expression as a therapeutic strategy to target human cancers driven by KRAS activation.<i></i>.
|
29321164 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In explant cells derived from these PDX tumor models with a KRAS G12R mutation, treatment with inhibitors of CDKs (including CDK9) reduced phosphorylation of a marker of CDK9 activity (phospho-RNAPII CTD Ser2/5) and reduced viability/growth of explant cells derived from PDAC PDX models.
|
26934555 |
2016 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Recently, the deubiquitinating protease USP9X has been shown to behave as an oncogene in a number of neoplasms, including those of breast, brain, colon, esophagus and lung, as well as KRAS wild-type PDAC.
|
24841553 |
2014 |