Bone marrow angiogenesis and progression in multiple myeloma.
ABSTRACT Tumour growth is angiogenesis-dependent. We found a high correlation between the extent of bone marrow angiogenesis, evaluated as microvessel area, and the proliferating (S-phase) fraction of marrow plasma cells, evaluated as labelling index (LI), in patients with multiple myeloma (MM) and in those with monoclonal gammopathies of undetermined significance (MGUS). Angiogenesis itself was significantly associated with active as opposed to non-active MM and MGUS. The highest microvessel area accompanied rapidly progressive MM with the highest LI. When a cut-off value of 2% or greater of the microvessel area was used, most patients with active MM were classified correctly. The risk of active disease in patients with MM increased in parallel with the microvessel area. A causal relationship between plasma cell growth, activity phase in MM and marrow angiogenesis is suggested. Since angiogenesis proceeds in step with the enlargement of plasma cell tumours and the activity phase in MM, its measurement could be a useful prognostic marker in patients with plasma cell proliferative disorders.
Article: Levels of angiogenic factors in patients with multiple myeloma correlate with treatment response.[show abstract] [hide abstract]
ABSTRACT: Angiogenesis plays a significant role in the pathogenesis of multiple myeloma (MM). We have measured concentrations of angiogenesis activators, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and hepatocyte growth factor (HGF), and inhibitors, including endostatin, thrombospondin-1 (TSP-1), and angiostatin in the peripheral and bone marrow blood of MM patients at diagnosis and after high-dose chemotherapy. We have analyzed 96 patients with secretory MM. Serial measurements of angiogenesis factors/inhibitors were analyzed in the plasma by subgroups based on the best treatment response. Concentrations of angiogenic factors were determined in the peripheral blood and bone marrow plasma. There were significant decreases of VEGF and HGF levels and a significant increase in TSP-1 concentrations in the bone marrow plasma of patients who achieved complete or very good partial response in contrast to those who had partial or no response. VEGF and HGF levels decrease but those of TSP-1 increase after successful treatment for MM, indicating a reduction in the rate of angiogenesis.Annals of Hematology 09/2009; 89(4):385-9. · 2.62 Impact Factor
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ABSTRACT: New blood vessel formation (angiogenesis) is not only essential for the growth of solid tumors but there is also emerging evidence that progression of hematological malignancies like multiple myeloma, acute leukemias, and myeloproliferative neoplasms, also depends on new blood vessel formation. Anti-angiogenic strategies have become an important therapeutic modality for solid tumors. Several anti-angiogenic agents targeting angiogenesis-related pathways like monoclonal antibodies, receptor tyrosine kinase inhibitors, immunomodulatory drugs, and proteasome inhibitors have been entered clinical trials or have been already approved for the treatment of hematological malignancies as well and in some instances these pathways have emerged as promising therapeutic targets. This review summarizes recent advances in the basic understanding of the role of angiogenesis in hematological malignancies and clinical trials with novel therapeutic approaches targeting angiogenesis.Journal of Angiogenesis Research 01/2010; 2:10.
Article: Multiple myeloma: Implementing signaling pathways and molecular biology in clinical trials.[show abstract] [hide abstract]
ABSTRACT: Multiple Myeloma is a molecularly heterogeneous disease with a high degree of genomic instability in which specific genetic changes can be linked to clinical presentation and prognosis. Despite recent improvements in event-free survival and overall survival with the use of high dose chemotherapy and stem cell support as well as the development of novel agents such as thalidomide, lenalidomide and Bortezomib, MM remains an incurable disease. The development of effective targeted therapies requires a detailed knowledge of various genetic and signaling pathways governing MM genesis. This review will focus on the current understanding of the molecular pathogenesis of MM and the intracellular signaling pathways and their regulations, with emphasis on the rationale for identifying therapeutic targets that can be applied in the clinic.Cancer biology & therapy 11/2010; 10(9):830-8. · 2.64 Impact Factor