|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
This knowledge can aid in improving our understanding of the molecular classification of PDAC and might guide the development of therapeutic strategies for PDAC, especially for SMAD4-negative PDAC.
|
31177911 |
2020 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
This study supports the key role of SMAD4 as a tumour suppressor gene in PDAC and shows that SMAD4 Y353C is associated with poor progression of PDAC.
|
31684910 |
2019 |
|
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 |
Biomarker
|
disease |
BEFREE |
Notably, in SMAD4-negative PDAC, nuclear PGK1 preferentially drives cell metastasis via mitochondrial oxidative phosphorylation induction, whereas cytoplasmic PGK1 preferentially supports proliferation by functioning as a glycolytic enzyme.
|
31611300 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
CDX2 expression and SMAD4 mutation indicate a poor outcome in patients with LM of PDAC.
|
31542399 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this study, we demonstrate that in PDAC SMAD4 status and tumor stromal content can be predicted using radiomic analysis of preoperative CT imaging.
|
31243486 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Cancer hallmark enrichment and pathway analysis suggested that the upregulation of cell cycle-related genes in SMAD4-deleted PDAC.
|
31569425 |
2019 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
Smad4 immunolabeling was interpretable in 61 cases and 59 (97%) cases showed concordant labeling between COD and invasive PDAC.
|
30212393 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Proteins involved in TGF-β signaling pathway (SMAD4 or TGF-βRII) are frequently mutated in PDAC (50⁻80%).
|
30065235 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
SMAD4 mutational status correlates with pancreatic ductal adenocarcinoma (PDAC) failure pattern.
|
28983662 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
KRAS, CDKN2A, TP53 and SMAD4 are the 4 "mountains" (high-frequency driver genes) which have been known to earliest somatic alterations for PDAC while relatively less frequent in PAC.
|
30258276 |
2018 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
These results suggest that inactivation of TP53 and SMAD4 are late genetic alterations, predominantly occurring in invasive PDAC.
|
28188630 |
2017 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
The objective of this study was to investigate the role of genetic status of DPC4 in recurrence patterns of resected pancreatic ductal adenocarcinoma (PDAC).
|
28160547 |
2017 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
SMAD4 loss was significantly associated with poor overall survival in patients with PDAC, Hazard Ratio was 0.61 with 95% confidence interval 0.38-0.99, p=0.05.
|
28053288 |
2017 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
A model including three intratumoral infiltrating immune markers (CD15+, CD206+ and CD117+) and a SMAD4 mutation can be used to predict recurrence and survival in patients after surgery for PDAC.
|
27256393 |
2016 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this study, PPM1A and Smad4 immunohistochemistry was assessed in 180 R0 resected human PDACs.
|
27195906 |
2016 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The frequent loss of SMAD4 and FHIT due to genomic rearrangements strongly implicates these genes as key drivers of PDAC, thus highlighting the strengths of an integrated genomic and transcriptomic approach for identifying mechanisms underlying disease initiation and progression.
|
26676757 |
2016 |
|
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 |
AlteredExpression
|
disease |
BEFREE |
Microarray analysis of gene expression at 8, 24, and 48 hours after SMAD4 expression characterized the regulatory impact of SMAD4 expression in a SMAD4-null PDAC cell line and identified novel targets of TGF-β signaling.
|
26284758 |
2015 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In an in vitro study, the regulation of GRP78 in the PDAC cell lines affected the proliferation, migration, and invasion of PDAC cells through the regulation of CyclinD1, cyclin-dependent kinase (CDK) 4, CDK6, phospho-signal transducer, activator of transcription 3 (p-STAT3), janus kinase 2 (JAK2), ras homolog gene family member A (RhoA), Rho-associated kinase 1 (ROCK1), and sterile alpha motif domain containing protein 4 (Smad4).
|
26530532 |
2015 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
From this analysis, alterations in the known oncogenes associated with PDAC were observed, including Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (93.7%) and inactivation of cyclin‑dependent kinase inhibitor 2A (CDKN2A) (50%), mothers against decapentaplegic homolog 4 (SMAD4) (50%), and tumor protein 53 (TP53) (56%).
|
26397140 |
2015 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In contrast, SMAD4 loss in PDAC leads to increased expression of E-cadherin, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and CD133.
|
24625091 |
2014 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
Biomarker
|
disease |
BEFREE |
SMAD4, which plays a key role in transforming growth factor-β (TGF-β) signaling, is inactivated in approximately half of PDAC cases.
|
24709776 |
2014 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
It is proposed that loss of Smad4 may convert TGF-β from a tumor suppressor to a tumor promoter by causing the upregulation of AGR2, which then leads to increased MUC1 expression, at which point both AGR2 and MUC1 facilitate mPanIN initiation and progression to PDAC.
|
22945649 |
2013 |
|
ANOPHTHALMIA AND PULMONARY HYPOPLASIA
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The TGF-β1/Smad4 pathway induced nestin protein expression in PDAC cells in a Smad4-dependent manner.
|
23552743 |
2013 |