|
Leukemia, T-Cell
|
|
0.010 |
GeneticVariation
|
BEFREE |
To study the impact of oncogenic K-Ras on T-cell leukemia/lymphoma development and progression, we made use of a conditional K-Ras(G12D) murine knockin model, in which oncogenic K-Ras is expressed from its endogenous promoter.
|
18663146 |
2008 |
|
Hypocholesterolemia
|
|
0.010 |
GeneticVariation
|
BEFREE |
We show that chronic cholesterol depletion achieved with lipoprotein-deficient serum (LPDS) and 25-hydroxycholesterol (25-HC) treatment results in a significant increase in apoptosis in HT-29 and Colo-205 cells containing the (V600E)B-RAF mutation, but not in HCT-116 and LoVo cells harbouring the (G13D)Ras mutation, or BE cells, which possess two mutations, (G13D)Ras and (G463V)B-RAF.
|
19700418 |
2009 |
|
Neoplasm Metastasis
|
|
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 |
|
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 |
|
Lung Neoplasms
|
|
0.010 |
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 |
|
Primary malignant neoplasm
|
|
0.020 |
GeneticVariation
|
BEFREE |
Moreover, all mice with Kras(G12D) activation and Pten homozygous deletion succumbed to cancer by 3 weeks of age.
|
20807812 |
2010 |
|
Malignant Neoplasms
|
|
0.020 |
GeneticVariation
|
BEFREE |
Moreover, all mice with Kras(G12D) activation and Pten homozygous deletion succumbed to cancer by 3 weeks of age.
|
20807812 |
2010 |
|
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 |
|
Tumor Progression
|
|
0.020 |
GeneticVariation
|
BEFREE |
We hypothesized that tumor progression was because of concomitant activation of the mitogen-activated protein kinase pathway downstream of Kras(G12D) expression promoting cell survival and that the therapeutic effect of PF-04691502 would be enhanced by combinatory inhibition of MEK using PD-0325901.
|
21632463 |
2011 |
|
ovarian neoplasm
|
|
0.010 |
GeneticVariation
|
BEFREE |
In vivo activity of combined PI3K/mTOR and MEK inhibition in a Kras(G12D);Pten deletion mouse model of ovarian cancer.
|
21632463 |
2011 |
|
Malignant neoplasm of ovary
|
|
0.010 |
GeneticVariation
|
BEFREE |
In vivo activity of combined PI3K/mTOR and MEK inhibition in a Kras(G12D);Pten deletion mouse model of ovarian cancer.
|
21632463 |
2011 |
|
Carcinoma, Ovarian Epithelial
|
|
0.010 |
GeneticVariation
|
BEFREE |
In vivo activity of combined PI3K/mTOR and MEK inhibition in a Kras(G12D);Pten deletion mouse model of ovarian cancer.
|
21632463 |
2011 |
|
Non-Small Cell Lung Carcinoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
NSCLC cell lines with mutant KRas-Gly12Asp had activated phosphatidylinositol 3-kinase (PI-3-K) and mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) signaling, whereas those with mutant KRas-Gly12Cys or mutant KRas-Gly12Val had activated Ral signaling and decreased growth factor-dependent Akt activation.
|
22247021 |
2012 |
|
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 |
|
Tumor Progression
|
|
0.020 |
GeneticVariation
|
BEFREE |
Additionally, we tested efficacy of PD-0325901 in Kras(G12D-LSL) conditional GEMMs (genetically engineered mouse models) which are a valuable tool in translational research to study tumor progression.
|
22684718 |
2012 |
|
Adenocarcinoma of lung (disorder)
|
|
0.010 |
GeneticVariation
|
BEFREE |
Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lung adenocarcinoma tumors in Kras(G12D-LSL) mice.
|
22684718 |
2012 |
|
Adenocarcinoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
Similar to H460 tumors, PD-0325901 as single agent or in combination with PF-04691502 significantly inhibited growth of tumor lesions in lungs in Kras(G12D-LSL) mice when treatment started at adenocarcinoma stage (at 14 weeks post-Adeno-Cre inhalation).
|
22684718 |
2012 |
|
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 |
|
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 |
|
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 |
|
Follicular thyroid carcinoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
We have generated mouse models that develop ATC ([Pten, p53](thyr-/-) mice) and follicular thyroid cancer with areas of poor differentiation (Pten(thyr-/-),Kras(G12D) mice).
|
23509868 |
2013 |
|
Thyroid cancer, follicular
|
|
0.010 |
GeneticVariation
|
BEFREE |
We have generated mouse models that develop ATC ([Pten, p53](thyr-/-) mice) and follicular thyroid cancer with areas of poor differentiation (Pten(thyr-/-),Kras(G12D) mice).
|
23509868 |
2013 |
|
Anaplastic thyroid carcinoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
We have generated mouse models that develop ATC ([Pten, p53](thyr-/-) mice) and follicular thyroid cancer with areas of poor differentiation (Pten(thyr-/-),Kras(G12D) mice).
|
23509868 |
2013 |
|
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 |
|
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 |