الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Angiogenesis, the growth of new capillary blood vessels in the body is an important natural process in the body used for healing and reproduction . The hypothesis of tumor angiogenesis in malignancies was raised by Judah Folkman to grow over certain size of few millimeters in diameter solid tumor needs blood supply from surrounding vessels.Up to 2-3 mm3 solid tumor can grow without blood vessels supply. Nutrition and oxygen provided via diffusion from surrounding tissue .Above this size,diffusion becomes insufficient due to negative surface / volume ratio. Based on a balance between angiogenic and antiangiogenic growth factors, a tumor of this size can stay dormant for avery long time periode until the so called angiogenic switch occurs. Multiple myeloma (M.M.) was the first hematological malignancy in which increased angiogenesis rate was detected. M.M .is charactarized by poliferation of malignant plasma cells that accumulate in bone marrow and often produce a monoclonal immuno globulin.New vessel formation in bone marrow seems to play an important role in M.M .Angiogenesis is a constant hallmark of M.M. progression and has prognostic potential. It is induced by plasma cell via angiogenic factors with transition from monoclonal gammopathy of undermined significance (MGUS) to M.M., and probably with loss of angiogenic activity on the part of MGUS. The pathophsiology of M.M. induced angiogenesis is complex and involves direct production of angiogenic cytokines by plasma cells and their induction within the microenviroment .The latter are secreted by stromal cells, endothelial cells ( EC ) and osteoclasts , promote plasma cell growth , survival and migration , as well as paracrine cytokine secretion and angiogenesis in bone marrow milieu Angiogenesis is also supported by inflammatory cells following thier recruitment and activation by plasma cells. Finally, circulating ECand endothelial precursor cell (EPC), contribute to the neovascularization and presence of EPC suggest that vasculogenesis (new vessel formation from EPC) may also contribute to the full vascular tree . The extent of angiogenesis in bone marrow can be assessed using an immunohistochemical stain for VWF (factor VIII related antigen) using standard methods. A quantitative assessment is performed by determing the microvessel density (MVD),or the percentage of unit surface area occupied by microvessels.Such assessment can also be done using computerized image analysis .Angiogenesis has become an attractive target for drug therapy because of its key role in tumor growth. An extensive array of compounds is currently in preclinical development .