| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-98 |
Sentence |
denotes |
Context- and cell-dependent effects of Delta-like 4 targeting in the bone marrow microenvironment. |
| T2 |
99-311 |
Sentence |
denotes |
Delta-like 4 (Dll4) is a ligand of the Notch pathway family which has been widely studied in the context of tumor angiogenesis, its blockade shown to result in non-productive angiogenesis and halted tumor growth. |
| T3 |
312-494 |
Sentence |
denotes |
As Dll4 inhibitors enter the clinic, there is an emerging need to understand their side effects, namely the systemic consequences of Dll4:Notch blockade in tissues other than tumors. |
| T4 |
495-609 |
Sentence |
denotes |
The present study focused on the effects of systemic anti-Dll4 targeting in the bone marrow (BM) microenvironment. |
| T5 |
610-928 |
Sentence |
denotes |
Here we show that Dll4 blockade with monoclonal antibodies perturbs the BM vascular niche of sub-lethally irradiated mice, resulting in increased CD31(+), VE-Cadherin(+) and c-kit(+) vessel density, and also increased megakaryocytes, whereas CD105(+), VEGFR3(+), SMA(+) and lectin(+) vessel density remained unaltered. |
| T6 |
929-1129 |
Sentence |
denotes |
We investigated also the expression of angiocrine genes upon Dll4 treatment in vivo, and demonstrate that IGFbp2, IGFbp3, Angpt2, Dll4, DHH and VEGF-A are upregulated, while FGF1 and CSF2 are reduced. |
| T7 |
1130-1273 |
Sentence |
denotes |
In vitro treatment of endothelial cells with anti-Dll4 reduced Akt phosphorylation while maintaining similar levels of Erk 1/2 phosphorylation. |
| T8 |
1274-1544 |
Sentence |
denotes |
Besides its effects in the BM vascular niche, anti-Dll4 treatment perturbed hematopoiesis, as evidenced by increased myeloid (CD11b(+)), decreased B (B220(+)) and T (CD3(+)) lymphoid BM content of treated mice, with a corresponding increase in myeloid circulating cells. |
| T9 |
1545-1677 |
Sentence |
denotes |
Moreover, anti-Dll4 treatment also increased the number of CFU-M and -G colonies in methylcellulose assays, independently of Notch1. |
| T10 |
1678-1813 |
Sentence |
denotes |
Finally, anti-Dll4 treatment of donor BM improved the hematopoietic recovery of lethally irradiated recipients in a transplant setting. |
| T11 |
1814-2039 |
Sentence |
denotes |
Together, our data reveals the hematopoietic (BM) effects of systemic anti-Dll4 treatment result from qualitative vascular changes and also direct hematopoietic cell modulation, which may be favorable in a transplant setting. |
