|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Furthermore, isoform-selective inhibitors showed a similar pattern of the isoform dependence in established Kras(G12D)/PTEN-deficient tumors.
|
24737887 |
2014 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Treatment of Kras(G12D) mice with either of two distinct small molecule Pak inhibitors (PF3758309 and FRAX597) caused tumor regression and loss of Erk and Akt activity.
|
22983922 |
2012 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Moreover, we show that KRAS(G12D)- and BRAF(V600E)-induced tumor formation in an orthotopic model requires IGF1R.
|
22871572 |
2012 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Most genes from this signature are also upregulated in poorly differentiated tumors developing in Pten(thyr-/-),Kras(G12D) mice.
|
23509868 |
2013 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Finally, m-CT imaging in live Kras(G12D-LSL) mice showed reduction of tumor burdens in PD-0325901-treated animals at sub-MTD dose.
|
22684718 |
2012 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
We analyzed tumor growth in mice that expressed the oncogenic form of KRAS (KRAS(G12D)) in pancreatic precursor cells, as well as sst2+/- and sst2-/-, and in crossed KRAS(G12D);sst2+/- and KRAS(G12D);sst2-/- mice.
|
25683115 |
2015 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
In LSL-K-ras(G12D/+)Pten(loxP/loxP) mice with established intraperitoneal tumor disease, oral administration of NVP-BEZ235 decreased pAkt, p4E-BP1 and Ki67 in tumor tissue, and resulted in significantly longer survival compared to control animals (P < 0.05).
|
21372221 |
2011 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
GeneticVariation
|
BEFREE |
PIK3CA mutations were detected in 25% of tumors and 26% of cell lines with a significant excess of helical domain mutations (E542K and E545K).
|
19789314 |
2009 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
GeneticVariation
|
BEFREE |
Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p.H1047R and p.E545K) by qPCR, and (2) expression of Ki-67, EGFR, MUC4, HER3 and PTEN by immunohistochemistry.
|
28123607 |
2017 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
GeneticVariation
|
BEFREE |
The E545K mutation promoted proliferation, migration and invasion of GBC cells in vitro and tumor proliferation in vivo.
|
27317099 |
2016 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
GeneticVariation
|
BEFREE |
As a proof of the concept, we present the case of a metastatic patient with a PIK3CA wild-type primary tumor in which the PIK3CA E545K mutation was identified in both the circulating-free DNA obtained from a peripheral blood sample and in the formalin-fixed, paraffin-embedded liver metastasis.
|
26001593 |
2015 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
GeneticVariation
|
BEFREE |
Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC.
|
25839328 |
2015 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
GeneticVariation
|
BEFREE |
Similarly, in human HCC cell lines, silencing of SGK3 reduced PIK3CA(E545K) -but not PIK3CA(H1047R)- induced accelerated tumor cell proliferation.
|
30975125 |
2019 |
|
rs752742313
|
|
Malignant neoplasm of breast
|
|
0.030 |
GeneticVariation
|
BEFREE |
We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where tandem mass spectrometry detected and quantitatively measured the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K activation.
|
21775521 |
2011 |
|
rs752742313
|
|
Malignant neoplasm of breast
|
|
0.030 |
GeneticVariation
|
BEFREE |
Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p.H1047R and p.E545K) by qPCR, and (2) expression of Ki-67, EGFR, MUC4, HER3 and PTEN by immunohistochemistry.
|
28123607 |
2017 |
|
rs752742313
|
|
Malignant neoplasm of breast
|
|
0.030 |
GeneticVariation
|
BEFREE |
Using a variety of physiologically relevant model systems with defined natural or knock-in PIK3CA mutations and/or PI3K hyperactivation, we show that PIK3CA-E545K mutations (found in ∼20% of PIK3CA-mutant breast cancers), but not PIK3CA-H1047R mutations (found in 55% of PIK3CA-mutant breast cancers), preferentially activate AKT1.
|
27197157 |
2016 |
|
rs752742313
|
|
Breast Carcinoma
|
|
0.020 |
GeneticVariation
|
BEFREE |
Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p.H1047R and p.E545K) by qPCR, and (2) expression of Ki-67, EGFR, MUC4, HER3 and PTEN by immunohistochemistry.
|
28123607 |
2017 |
|
rs752742313
|
|
Liver carcinoma
|
|
0.020 |
GeneticVariation
|
BEFREE |
PIK3CA missense mutations were found in one of 11 intrahepatic CCA (E545K, 9%), one of 23 gallbladder carcinomas (E542K, 4%), and one of 50 hepatocellular carcinomas (H1047R, 2%).
|
18181165 |
2008 |
|
rs752742313
|
|
Gallbladder Carcinoma
|
|
0.020 |
GeneticVariation
|
BEFREE |
Mutations in exons 9 (E542K, E545G, E545K) and 20 (H1047L and H1047R) of PI3K were determined by direct sequencing in 130 cases of GBC.
|
26947513 |
2016 |
|
rs752742313
|
|
Breast Carcinoma
|
|
0.020 |
GeneticVariation
|
BEFREE |
We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where tandem mass spectrometry detected and quantitatively measured the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K activation.
|
21775521 |
2011 |
|
rs752742313
|
|
Liver carcinoma
|
|
0.020 |
GeneticVariation
|
BEFREE |
Similarly, in human HCC cell lines, silencing of SGK3 reduced PIK3CA(E545K</span>) -but not PIK3CA(H1047R)- induced accelerated tumor cell proliferation.
|
30975125 |
2019 |
|
rs752742313
|
|
Gallbladder Carcinoma
|
|
0.020 |
GeneticVariation
|
BEFREE |
The E545K mutation promoted GBC progression through enhanced binding to EGFR and activating downstream akt activity.
|
27317099 |
2016 |
|
rs752021744
|
|
Carcinogenesis
|
|
0.020 |
GeneticVariation
|
BEFREE |
Administration of a CXCL16-neutralizing antibody to KRAS(G12D) mice reduced activation of PI3K signaling to AKT and NF-κB, blocking carcinogenesis.
|
25683115 |
2015 |
|
rs752021744
|
|
Carcinogenesis
|
|
0.020 |
GeneticVariation
|
BEFREE |
Tumorigenesis was measured in the Kras(G12D/+);Ptf1a(Cre/+) mouse model of PDA; these mice were crossed with mice with pancreas-specific disruption of genes encoding PI3K p110α (Pik3ca), p110β (Pik3cb), or RAC1 (Rac1).
|
25311989 |
2014 |
|
rs752021744
|
|
Secondary Neoplasm
|
|
0.020 |
GeneticVariation
|
BEFREE |
In mice, Lkb1 deletion and activation of Kras(G12D) results in lung tumors with a high penetrance of lymph node and distant metastases.
|
20541700 |
2010 |