Angiogenesis and Anti-Angiogenesis in Hematological by Domenico Ribatti

By Domenico Ribatti

It has been in general permitted that angiogenesis is all for the pathogenesis of hematological malignancies, like acute and persistent leukemia, lymphoma, myelodysplastic syndromes, myeloproliferative neoplasms and a number of myeloma. the level of angiogenesis within the bone marrow has been correlated with sickness burden, analysis and therapy final result. Reciprocal confident and detrimental interactions among tumor cells and bone marrow stromal cells, specifically hematopoietic stem cells, fibroblasts, osteoblasts/osteoclasts, endothelial cells, endothelial progenitor cells, T cells, macrophages and mast cells, mediated by way of 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 referred to as “vascular niche”, indicating a domain wealthy in blood vessels the place endothelial cells and mural cells equivalent to pericytes and soft muscle cells create a microenvironment that has effects on the habit of numerous stem and progenitor cells, in hematological malignancies.

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2002). Accordingly, only a minority of indolent lymphomas, showing histologic transformation to aggressive lymphoma, expressed VEGF-A in contrast to aggressive lymphomas (Ho et al. 2002). Inhibition of autocrine or paracrine VEGFRs-mediated loops with receptor-specific antibodies suppress the growth of lymphomas by increasing tumor apoptosis and decreasing vascularization, respectively. These results confirm the role of VEGF in lymphomagenesis and support the targeting of VEGFRs as a therapeutic approaches for aggressive lymphomas.

2005). 7 The Role of Macrophages and Mast Cells It is well known that among inflammatory cell found in tumors, tumor associated macrophages and mast cells support tumor growth and neovascularization by producing a wide array of angiogenic cytokines. Mast cell- and macrophages-derived growth factors able to promote tumor development and angiogenesis include TNF-α, TGF-β1, FGF-2, VEGF, PDGF, IL-8, osteopontin, and nerve growth factor (NGF). 7 The Role of Macrophages and Mast Cells 29 Fig. 16 A microvessel lined by flattened FVIII-RA positive multiple myeloma endothelial cells ( arrow), a FVIII-RA positive macrophage ( arrowhead) showing protrusions connected to multiple myeloma endothelial cells, and another macrophage containing double-labeled CD68 ( red arrowhead) and FVIII-RA ( green arrowhead) granules in the cytoplasm and connected to multiple myeloma endothelial cells by an FVIII-RA positive cytoplasmic protrusion ( double arrow).

1999, 2000, 2002; Chen et al. 2000). Enhanced vessel density was observed in CLL infiltrated bone marrow and lymph nodes compared with controls (Kini et al. 2000; Chen et al. 2000). Intracellular FGF-2 levels in lymphocytes of B-CLL patients correlated with stage of disease (Menzel et al. 1996; König et al. 1997), and a positive correlation was identified between serum FGF-2 levels and Bcl-2 expression (König et al. 1997; Bairey et al. 2000), resulting in increased leukemia cell survival and increased cellular FGF-2 in high-risk CLL was associated with fludarabine resistance (Menzel et al.

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