| 1. |
|
|
| 2. |
|
|
| 3. |
- Qazi, Maleeha A, et al.
(författare)
-
Cotargeting Ephrin Receptor Tyrosine Kinases A2 and A3 in Cancer Stem Cells Reduces Growth of Recurrent Glioblastoma.
- 2018
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:17, s. 5023-5037
-
Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) carries a dismal prognosis and inevitably relapses despite aggressive therapy. Many members of the Eph receptor tyrosine kinase (EphR) family are expressed by GBM stem cells (GSC), which have been implicated in resistance to GBM therapy. In this study, we identify several EphRs that mark a therapeutically targetable GSC population in treatment-refractory, recurrent GBM (rGBM). Using a highly specific EphR antibody panel and CyTOF (cytometry by time-of-flight), we characterized the expression of all 14 EphR in primary and recurrent patient-derived GSCs to identify putative rGBM-specific EphR. EPHA2 and EPHA3 coexpression marked a highly tumorigenic cell population in rGBM that was enriched in GSC marker expression. Knockdown of EPHA2 and EPHA3 together led to increased expression of differentiation marker GFAP and blocked clonogenic and tumorigenic potential, promoting significantly higher survival in vivo Treatment of rGBM with a bispecific antibody against EPHA2/A3 reduced clonogenicity in vitro and tumorigenic potential of xenografted recurrent GBM in vivo via downregulation of AKT and ERK and increased cellular differentiation. In conclusion, we show that EPHA2 and EPHA3 together mark a GSC population in rGBM and that strategic cotargeting of EPHA2 and EPHA3 presents a novel and rational therapeutic approach for rGBM.Significance: Treatment of rGBM with a novel bispecific antibody against EPHA2 and EPHA3 reduces tumor burden, paving the way for the development of therapeutic approaches against biologically relevant targets in rGBM. Cancer Res; 78(17); 5023-37.
|
|
| 4. |
- Reddy, S. R., et al.
(författare)
-
High Strain Rate Superplastic Flow and Fracture Characteristics of a Fine-Grained Eutectic High Entropy Alloy
- 2024
-
Ingår i: Metallurgical and Materials Transactions A: Physical Metallurgy and Materials Science. - 1073-5623. ; 55, s. 173-182
-
Tidskriftsartikel (refereegranskat)abstract
- A fine-grained micro-duplex AlCoCrFeNi2.1 eutectic high entropy alloy exhibited high strain rate superplasticity with an elongation to failure of ~ 960 pct at 1173 K and a strain rate of 10-1 s-1. Optimum superplasticity was associated with a strain rate sensitivity of ~ 0.5, and there were transitions to non-superplastic flow with strain rate sensitivities of < 0.5 at both low and high strain rates. Superplasticity is attributed to grain boundary sliding with the observed retention of an equiaxed grain morphology, with some grain growth. Cavities with dimensions in the range of 1 to 5 μm were observed in specimens pulled to failure. Although analysis revealed that cavity nucleation is likely under the experimental conditions, cavity growth was slow because of control by a plasticity growth rate that was proportional to the cavity size. Graphical Abstract: [Figure not available: see fulltext.]
|
|
