Download Angiogenesis and Anti-Angiogenesis in Hematological by Domenico Ribatti PDF

By Domenico Ribatti

It has been mostly approved that angiogenesis is occupied with the pathogenesis of hematological malignancies, like acute and protracted leukemia, lymphoma, myelodysplastic syndromes, myeloproliferative neoplasms and a number of myeloma. the level of angiogenesis within the bone marrow has been correlated with illness burden, diagnosis and therapy end result. Reciprocal optimistic and damaging interactions among tumor cells and bone marrow stromal cells, particularly hematopoietic stem cells, fibroblasts, osteoblasts/osteoclasts, endothelial cells, endothelial progenitor cells, T cells, macrophages and mast cells, mediated through an array of cytokines, receptors and adhesion molecules, modulate the angiogenic reaction in hematological tumors. extra lately, it's been emphasised the pro-angiogenic position of the so known as “vascular niche”, indicating a domain wealthy in blood vessels the place endothelial cells and mural cells resembling pericytes and tender muscle cells create a microenvironment that is affecting the habit of a number of stem and progenitor cells, in hematological malignancies.

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2005). High VEGF and VEGFR-1 expression identified a subgroup of patients affected by DLBCL with improved overall survival and progression-free survival when treated with anthracycline-based chemotherapy, suggesting that the autocrine signaling via VEGFR-1 may be susceptible to this therapeutic approach (Gratzinger et al. 2008). When immunodeficient mice engrafted with human DLBCL were treated with antibodies against human or murine VEGFR-1 or VEGFR-2, a significant tumor reduction of 50 % was observed after treatment with human anti-VEGFR-1, but not with murine anti-VEGFR-1.

2010) demonstrated that both PDGF and VEGF were elevated in plasma of CLL patients with a positive association for high-risk factors and more advanced stage. Moreover, PDGF induced VEGF production in mesenchymal stromal cells. Maffei et al. (2010a) demonstrated that in CLL increased expression of Ang-2 was positively correlated with enhanced bone marrow angiogenesis and that high Ang-2 level was an independent prognostic factor for shorter time to first treatment. Moreover, Maffei et al. (2010b) found a significant association between high level of Ang-2 and advanced clinical stage, high β2-microglobulin, un-mutated status of the IgVH and cytogenetic risk factors.

In contrast, the levels of VEGF did not significantly differ between leukemic and normal bone marrow plasma. This discrepancy between serum levels of FGF-2 and VEGF could depend by the fact that there is a lot of VEGF in platelets and ALL patients at diagnosis are thrombocytopenic. Serum level of an endogenous antiangiogenic factor, namely endostatin, was significantly higher in childhood ALL than control at diagnosis and in remission (Schneider et al. 2007). As concerns the association with prognostic factors and the outcome of patients, significantly higher VEGF levels in patients at relapse, and lower levels at diagnosis in association with a longer overall survival have been found (Koomagi et al.

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