|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Despite this achievement, general principles from proposed systems pharmacokinetic modeling for intracellular processing of ADCs indicate potential shortcomings of T-DM1: (i) <i>C</i><sub>max</sub> limited by toxicities; (ii) slow internalization rate; (iii) resistance mechanisms due to defects in intracellular trafficking [loss of lysosomal transporter solute carrier family 46 member 3, (SLC46A3)], and increased expression of drug transporters MDR1 and MRP1; and (iv) lack of payload bystander effects limiting utility in tumors with heterogeneous HER2 expression.
|
31582515 |
2020 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
These data demonstrate estrogen ability to modulate chemo-sensitivity of MDM4-expressing tumors and to impinge on intracellular trafficking.
|
31547268 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Our findings highlight the critical role of p53 as a tumor suppressor in Burkitt lymphoma and identify MDM4 as a functional target of 1q gain in a wide range of cancers that is therapeutically targetable.
|
31000522 |
2019 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Notably, the present results revealed that MDM4 transcript levels were increased in the majority of tumor samples and the nuclear MDM4 levels were significantly increased in tumor tissue compared to their adjacent non‑neoplastic liver tissue.
|
31322272 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
These results support dual targeting of MDM2 and MDM4 in virus-positive MCC and other p53 wild-type tumors.
|
30598450 |
2019 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
We concluded that MDM4 rs4245739 polymorphism is significantly associated with tumor HPV status and survival of SCCOP, especially in HPV16-positive SCCOP patients treated with definitive radiotherapy; nevertheless, prospective larger studies are warranted.
|
31513313 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Together, these studies identify a genetic connection between mutations in the SWI/SNF chromatin-remodeling complex and the tumor suppressor gene <i>TP53</i> and provide preclinical evidence to support the targeting of MDM2 and MDM4 in this often-fatal pediatric cancer.
|
30755442 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Knocking down MDMX or MDM2 in MDA-MB-231 cells reduced cell migration and CTC detection, but only MDMX knockdown reduced tumor volumes at early time points.
|
30642351 |
2019 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Lymphoma cells grown in this model exhibited excellent biomimetic properties compared to conventional 2D culture including (1) enhanced chemotherapy resistance, (2) suppressed rate of apoptosis, (3) upregulated expression of drug resistance genes (MDR1, MRP1, BCRP and HIF-1α), (4) elevated levels of tumor aggressiveness factors including Notch (Notch-1, -2, -3, and -4) and its downstream molecules (Hes-1 and Hey-1), VEGF and MMPs (MMP-2 and MMP-9), and (5) enrichment of a lymphoma stem cell population.
|
29416753 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Erratum: In-Tether Chiral Center Induced Helical Peptide Modulators Target p53-MDM2/MDMX and Inhibit Tumor Growth in Stem-Like Cancer Cell: Erratum.
|
30555571 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
MRP1 expression was found to be significantly associated with sex, histological type and tumor differentiation, while platelet count was significantly associated with smoking behavior, histological type and clinical stage.
|
30061938 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
High expression of MRP1 (89%, 8/9 tumors), TUBB3 (86%, 18/21 tumors), PTEN (85%, 28/33 tumors), TOP2A (84%, 26/31 tumors), thymidylate synthase (TS; 80%, 24/30 tumors), RRM1 (71%, 15/21 tumors), and TOP1 (63%, 19/30 tumors) were found in medulloblastoma.
|
29869738 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
MRP1 silencing in GBM tumour using MRP1-siRNA loaded pSiNPs was demonstrated in mice (82% reduction at the protein level 48 h post-injection), and it also produced antiproliferative effect in GBM by reducing the population of proliferative cells.
|
29653579 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
High expression and constitutive activation of multidrug resistance protein 1 (MRP1) has been associated with the development of resistance to anticancer drugs in a number of tumor types.
|
29928376 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In-Tether Chiral Center Induced Helical Peptide Modulators Target p53-MDM2/MDMX and Inhibit Tumor Growth in Stem-Like Cancer Cell.
|
29158845 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
However, the MDM2-related MDM4 has also been proposed to abrogate p53-mediated tumor surveillance in the absence of detectable MDM2 in retinoblastoma cells, bringing into question the importance of high-level MDM2 versus MDM4 expression.
|
27748758 |
2017 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Whereas the overall survival times of p53-null mice with and without the Mdm4 transgene were similar, male mice with both alterations showed significantly shorter survival than p53-null male mice, and showed differences in tumour spectrum, demonstrating a p53-independent function of Mdm4 in tumourigenesis.
|
27925213 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Increased levels of inhibitors of the p53 tumor suppressor such as Mdm2 and Mdm4 drive tumor development and thus serve as targets for therapeutic intervention.
|
29262616 |
2017 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Whole exome sequencing of the patient's postmortem tumor revealed a novel KDR (G681R) mutation, and focal high-level amplification at chromosome 1q encompassing MDM4, a negative regulator of TP53.
|
28056866 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The PERK/Nrf2/MRP1 axis is responsible for the resistance to ER stress and chemotherapy, and may represent a good therapeutic target in aggressive and resistant tumors.
|
28499449 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Overall, these data identify MDM4 as a nutrient-sensor able to inhibit mTORC1 and highlight its metabolism-related tumor-suppressing function.
|
28270148 |
2017 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Among the most frequent alterations conferring resistance, we observed somatic and insertional loss-of-function mutations in transformation-related protein 53 (<i>Trp53</i>) in 54% of tumors and transposon-mediated gain-of-function alterations in B-cell lymphoma-extra large (<i>Bcl-xL</i>), <i>Mdm4</i>, and two <i>TP53</i> family members, resulting in expression of the TP53 dominant negative truncations <i>ΔNTrp63</i> and <i>ΔNTrp73.</i> Enhanced BCL-xL and MDM4 protein expression was confirmed in resistant tumors, as well as in HDM201-resistant patient-derived tumor xenografts.
|
28265066 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Previous results suggested that the MDM4-S isoform could be an important driver of tumor development.
|
28230750 |
2017 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
We conclude that Mdm4-S overexpression is a consequence of splicing defects in tumor cells rather than a cause of tumor evolution.
|
28460439 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The optimal dose of cisplatin, the novel role of PIC and the side effects of the combined chemotherapy were determined <i>in vitro</i> and in distinct human tumor models <i>in vivo</i> The results <i>in vitro</i> indicated that preculture with PIC downregulated drug transporters (e.g., P-gp and MRP-1) and increased the cytoplasmic residence of cisplatin, and dramatically strengthened the low-dose cisplatin-induced cell death in TLR3- and caspase-3-dependent manner.
|
28138030 |
2017 |