| Vascular endothelial growth factor (VEGF) can be secreted by hematological tumor cell highly according to internai and overseas studies and it is related to bone marrow angiogenesis closely. Great attention has been paid to the roal of bone marrow angiogenesis in hematological malignancies. Angiogenesis is a very complicated process which be controlled by many active and negative cell factors. Of all cell factors vascular endothelial growth factor (VEGF) is one of the strongest angiogenic cytokine that can promote endothelial cellactivation, migration, proliferation, differentiation and mature.. Hypoxia and activated oncogene is the potent factor inducing expression of VEGF and its receptor .VEGF is hardly be expressed in physiological condition of adult, but many tissue cells differentiated could secrete VEGF when they were stimulated by some stimulating factors such as hypoxia and ischemia. Tumor cell secreted VEGF when oncogene were activated. VEGF plays key role in angiogenesis of tumor, so it does in solid tumor growth . Some studies indicate that hematological malignancies cells not only produce VEGF but also express functional VEGFR,resulting in the generation of both autocrine and paracrine loop that not only support hematological malignancies cell survival and proliferation, which make bone marrow density(MVD) increase. In order to research the signifance and expression of VEGF and bone marrow microvasscle density in hematological system diseases we tested the level of VEGF In both bone marrow and plasma and MVD in patients who were newly diagnosed AML,NHL not infiltrates bone marrow and innocence anemia(IDA and MA). The aim of our research is to reveal the role and position of VEGF and MVD and there relations and affect factor in different hematological disease to establish rationale for biological targeted therapy. At the same time we compare VEGF content in bone marrow and plasma in order to search for best therapeutic route of acute myeloid leukemia. In our study bone marrow MVD in plastic-embedded section we examined using acetone-fixed bone marrow tissues embedded in glycol-methacrylate (GMA) resin. It is demonstrated again that marrow MVD increased in newly diagnosed hematological neoplasm and decreased in he group of completeremission and no remission. The MVD range in the complete remission group decrease obviously but not obviously in the no remission group. These observation suggest that the bone marrow angiogenesis plays a key role in the pathogenesis and development of hematological neoplasm. So we think bone marrow MVD may be the index of diagnosis and prognosis. The results not only show a significant increased level of VEGF In both bone marrow and plasma in patients who were newly diagnosed AML but also reflect VEGF plays a significant role in angiogenesis in hematological malignancies. Bone marrow MVD decreases to normal level during complete remission after chemotherapy,but the plasma VEGF level is significantly elevated compared with the controls and prochemotherapy. The reason of plasma VEGF level elevated may be that VEGF is secreted by normal tissue cells in response to inflammatory stimuli of either chemotherapeutic damage or infection,,or hypoxia induced by durative serious anemia after chemotherapy. VEGF of bone marrow in group both remission and nonremission. decreased slighterly not the same as MVD since bone marrow is refrained by chemicaltherapy leading to normal endothelial cells was damaged. so VEGF was secreted highly by bone marrow blastet al. . This suggests when to use anti-angiogenesismedicine .When we use it after chemicaltherapy would affect bone marrow recovery should be studied . Overall, we think VEGF would be the index of diagnosis in AML. The next step will be the prospective study of correlation between bone marrow MVD and VEGF with survival duration in order to judge if bone marrow MVD and VEGF may be a correct prognosis index. VEGF in bone marrow is related with in plasma in anemia group and newly diagnosed AML. There is no positive correlation between bone marrow blast or HGB with bone marrow MVD or plasma or marrow VEGF level. Anemia is not main factor of bone marrow angiogenesis and VEGF content increasing in newly diagnosised AML. Bone marrow of NHL as a hematological malignancies stem of hematopoietic tissues is normal when its bong marrow isn't affected, and its MVD or VEGF content in marrow is normal too. VEGF in plasma secreted by fibroblast and myofibroblast not as other tumors is increased obviously .There is a negative correlation between bone marrow MVD and VEGF. This result may reflect negative regulation function of flt-1,its mechanism should be researched furtherly. Our research demonstrates that the bone marrow angiogenesis andplasma VEGF in patients with anemia is increased obviously and shows the existence of the negative correlation between bone marrow MVD and HGB through statistical comparison. as well as plasma VEGF. There is a tend of positive correlation between bone marrow MVD and plasma VEGF level. These findings indicate a correlation in some degree between bone marrow angiogenesis and the decrease of HGB. Hypoxia is led by durative anemia state induces the secretion of VEGF in normal tissues cells that futher induced angiogenesis. The reason there is no statistical significance on positive correlation between bone marrow MVD and plasma VEGF level. may be proangiogeneic factors are induced by anemia. As an important proangiogeneic factors all the more ,plasma VEGF plays a crucial effect in angiogenesis in bloodless patients. VEGF in bone marrow is not higher in innocence anemia, but it directly correlates with that in plasma. Although bone marrow MVD of patients with anemia is higher but its degree of increase sinnificantly lower than that of patients in AML. This may reflect difference on mechanism of regulative angiogenesis. The difference is that angiogenesis of benign anemia is under orderly control of the body, then angiogenesis of tumor isout of control of the body because of over-expansion of tumor cells. AML originate from bone marrow ,so angiogenic factor including VEGF is secreted directly to the bone marrowmicroenviroment. As long as the clone of tumor cell isn't eliminated, VEGF would be secreted at all times. At the same time, downregulation of expression of angiogenesis inhibitor in the presence of activated oncogene leads to the break of negative feedback in angiogenesis. Angiogenesis in bone marrow in benign anemia is limited even though VEGF is much higher in plasma. Even though HGB in AML is the same as anemia its plasma and bone marrow VEGFlevel and marror MVD is different from anemia. Since a lot of leukemia cells secret VEGF directly into marrow microsurrounding VEGFand mvd in marrow is higher than anemia. But VEGF in plasma in anemia group is higher than in AMLgroup,because in order to satisfy marrow hemopoiesis function human body would mobilize normal cells secret VEGF. As hematological malignancies if bone marrow is affected bone marrow MVD and VEGF level is various obviously, both marrow MVD and VEGF is increased highly when marrow is affected, and marrow is normal when it is not affected. As hematological system diseases when marrow... |
PDF Full Text Request