The Angiogenesis And Vascular Endothelial Cell Growth Factor Expression In Multiple Myeloma And The Antiangiogenesis Role Of Arsenic Trioxide

Objective: The significance of angiogenesis and antiangiogenesis treatment in tumor are ascertained in today. Angiogenesis is a process of blood vessels generation from existing vessel nets. The physiological angiogenesis is a strict controlled process and pathologic angiogenesis is an unlimited, uncontrolled progress and accelerates the progress of the disease. The growth of the tumor can be divided into two stages called avascular stage and vascular stage. In the avascular stage, the delivery of nutrients and the removal of waste products from the tumor bed are transferred by simple diffusion through the surrounding tissue. So the growth of the tumor is restricted. The diameter of the tumor is less than 1～2mm at this stage；The occurrence of novel vessel in vascular stage facilitates the growth of tumor and makes it possible to transfer to the distant place. In fact, angiogenesis is crucial for the conversion to a malignant phenotype. The ability of angiogenesis in tumor determines its potency of growth, infiltration and metastasis in body. It is proved that angiogenesis has tight relation with growth, infiltration and metastasis in solid tumors. Angiogenesis is regulated by stimulating and inhibiting factors,and vascular endothelial cell growth factor (VEGF) is the most stronge and specific stimulator. VEGF can accelerate the proliferation and differentiation of the vascular endothelial cell, improve the permeability of vessels and alter extracellular matrix to facilitate the growth of the vessel afrer combining with its receptors. VEGF also can directly accelerate the proliferation of tumor cell by autocrine and paracrine. Multiple myeloma(MM) is a kind of plasma cells hematologic malignancy. Traditional therapy can not eliminate MM malignant cells completely, most MM patients will relapse in short time after remission,so it is important to find a safely and efficiently therapy for MM. In the recently years, arsenic trioxide(As2O3) has became research hot spot in international hematologic and knubbly field after treating acute promyelocytic leukemia successfuly. As2O3 is showed to have antiangiogenic role and be efficient for hematologic malignancies and solid tumor treatment in the recently research. We studied the role of angiogenesis and VEGF in the pathology of MM and the antiangiogenic role of arsenic trioxide to find a efficient and safely curing approach for MM.Methods: 1.Clinical data: 42 patients included in this study had a confirmed diagnosis of MM according to the standard criteria, VAD+IFN chemotherapy program was given to the patients,and re-examination was done at 3 weeks post-chemotherapy when bone marrow depression had recovered. Serum sample collecting: Serum sample was collected before and post chemotherapy in MM patients; The control team was collected from 18 health-examining works.Bone marrow fluid and biopsy specimen collecting: Bone marrow puncture and biopsy were done on spina iliaca posterior superior before and afrer chemotherapy in MM patients; The control team was collected from 10 ilium and rib cut down by department of orthopaedics and cardiosurgery .There were not differents in age and sex between MM patients and controls.controls excluded individuals in ill with angiogenesis.2.Display and counting of microvessel: Microvessel in bone marrow biopsy specimen is displayed by Ⅷ-R-Ag Immunohistochemistry staining. One or several endothelium cell is counted as a microvessel,and vessel cavity larger than 8 red cell with thicker muscle layer is excluded. The entire bone marrow section was systematically scanned field per field at×100 magnification to identified three areas with the highest microvessel density. These areas were considered as "hotspot". The magnification was then changed to×400(0.2376㎜2/ sight) to count the microvessels of every hotspot and the average of the three hotspots was used as the microvessel density(MVD).3.Enzyme link immunoadsorption assay (ELISA) used to assay the expression of VEGF was performed according to the manufacture?...