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Biomedical subjects

Giulia Di Pietro

Publications and source records attributed to Giulia Di Pietro.

4 recordsLinked to original sources

Loss of inhibitory semaphorin 3A (SEMA3A) autocrine loops in bone marrow endothelial cells of patients with multiple myeloma.

Vascular endothelial growth factor165 (VEGF165) and semaphorin3A (SEMA3A) elicit pro- and antiangiogenic signals respectively in endothelial cells (ECs) by binding to their receptors VEGFR-2, neuropilin-1 (NRP1), and plexin-A1. Here we show that the VEGF165-driven angiogenic potential of multiple myeloma (MM) ECs is significantly higher than that of monoclonal gammopathy of undetermined significance (MGUS) ECs (MGECs) and human umbilical vein (HUV) ECs. This is probably due to a constitutive imbalance of endogenous VEGF165/SEMA3A ratio, which leans on VEGF165 in MMECs but on SEMA3A in MGECs and HUVECs. Exogenous VEGF165 induces SEMA3A expression in MGECs and HUVECs, but not in MMECs. Moreover, by counteracting VEGF165 activity as efficiently as an anti-VEGFR-2 antibody, exogenous SEMA3A restrains the over-angiogenic potential of MMECs. Our data indicate that loss of endothelial SEMA3A in favor of VEGF165 could be responsible for the angiogenic switch from MGUS to MM.

Bone Marrow Cells↗

Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma.

PURPOSE: To study the antiangiogenic effect of thalidomide. PATIENTS AND METHODS: The expression of key angiogenic genes was studied in bone marrow endothelial cells (ECs) of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies unattributed/unassociated (MG[u]), diffuse large B-cell non-Hodgkin's lymphoma, in a Kaposi's sarcoma (KS) cell line, and in healthy human umbilical vein ECs (HUVECs) following exposure to therapeutic doses of thalidomide. RESULTS: Thalidomide markedly downregulates the genes in a dose-dependent fashion in active MMECs and KS cell line, but upregulates them or is ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs. Secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor also diminishes according to the dose in culture conditioned media (CM) of active MMECs and KS, whereas it does not change in the other CM. CONCLUSION: Inhibition by thalidomide is probably confined to the genes of active MMECs and KS. This would account for its higher efficacy in these diseases.

Adult↗

Bone marrow endothelial cells in multiple myeloma secrete CXC-chemokines that mediate interactions with plasma cells.

Bone marrow endothelial cells (EC) from patients with multiple myeloma (MM) were found to express and secrete higher amounts of the CXC-chemokines CXCL8/interleukin (IL)-8, CXCL11/interferon-inducible T-cell alpha chemoattractant (I-TAC), CXCL12/stromal cell-derived factor (SDF)-1alpha, and CCL2/monocyte chemotactic protein(MCP)-1 than EC from human umbilical vein (HUVEC), considered as a healthy counterpart. Paired plasma cells and several MM cell lines expressed cognate receptors of each chemokine to a variable extent. When cells were exposed to chemokines, CXCL8/IL-8 and CXCL12/SDF-1alpha stimulated their proliferation and all chemokines stimulated cell chemotaxis. It is suggested that angiogenesis also favours MM progression through the release of CXC-chemokines.

Adult↗

Serum levels of angiogenic cytokines decrease after antineoplastic radiotherapy.

Serum levels of angiogenic cytokines decrease after radiotherapy in patients with cancer and their may have an impact on response to treatment and progression-free survival. Here, we have evaluated sera of patients before and after radiotherapy for various tumour types for levels of soluble fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) to assess whether these factors decrease after radiotherapy, and whether their diminution is related to the radiation dose, tumour type, age and haemoglobin level. We demonstrate that levels of FGF-2 and VEGF, but not HGF, decrease significantly, and that the extent of their diminution is related to the radiation dose and response.

Adult↗