Expression of vascular endothelial growth factor and its receptors in multiple myeloma and other hematopoietic malignancies

2001 ◽  
Vol 28 (6) ◽  
pp. 551-559 ◽  
Author(s):  
William T. Bellamy
Keyword(s):  
Multiple Myeloma ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Hematopoietic Malignancies ◽  
Endothelial Growth Factor

scholarly journals The VAD Scheme versus Thalidomide plus VAD for Reduction of Vascular Endothelial Growth Factor in Multiple Myeloma: A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Gan-Lin He ◽  
Duo-Rong Xu ◽  
Wai-Yi Zou ◽  
Sui-Zhi He ◽  
Juan Li
Keyword(s):  
Multiple Myeloma ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Meta Analysis ◽  
Biomedical Literature ◽  
Cochrane Library ◽  
Vascular Endothelial ◽  
China National Knowledge Infrastructure ◽  
Significant Difference ◽  
Endothelial Growth Factor

The VAD (vincristine-doxorubicin-dexamethasone) regimen has been used for decades to treat multiple myeloma (MM). Based on reports that vascular endothelial growth factor- (VEGF-) mediated angiogenesis is critical for MM pathogenesis, the antiangiogenic compound thalidomide has been added to VAD (T-VAD). However, it remains unclear whether T-VAD is more efficacious than VAD for serum VEGF reduction or if the difference influences clinical outcome. Pubmed, Cochrane library, China Biomedical Literature (CBM) database, China National Knowledge Infrastructure (CNKI) database, Vip database, and Wanfang database were searched for relevant studies published up to June 2017. RevMan5.2 was used for methodological quality evaluation and data extraction. Thirteen trials (five randomized, seven nonrandomized, and one historically controlled) involving 815 cases were included. Serum VEGF was significantly higher in MM cases than non-MM controls (MD=353.01, [95%CI 187.52–518.51], P<0.01), and the overall efficacy of T-VAD was higher than that of VAD (RR=1.36, [1.21–1.53], P <0.01). Further, T-VAD reduced VEGF to a greater extent than VAD does ([MD=-49.85, [-66.28− -33.42], P<0.01). The T-VAD regimen also reduced VEGF to a greater extent in newly diagnosed MM patients than it did in recurrent patients ([MD=-120.20, [-164.60–-39.80], P<0.01). There was no significant difference in VEGF between T-VAD patients (2 courses) and nontumor controls (MD=175.94, [-26.08–377.95], P=0.09). Greater serum VEGF reduction may be responsible for the superior efficacy of T-VAD compared to VAD.

Neutralization Of Vascular Endothelial Growth Factor-A Induced CD138-Expression In Bone Marrow Cells From Multiple Myeloma Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5331-5331
Author(s):  
Ryosuke Shirasaki ◽  
Takuji Matsuo ◽  
Yoko Oka ◽  
Jun Ooi ◽  
Naoki Shirafuji
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Poor Prognosis ◽  
Bone Marrow Cells ◽  
Vascular Endothelial ◽  
Normal Individuals ◽  
Endothelial Growth Factor ◽  
Marrow Cells

Abstract Background We previously reported that when adult human dermal fibroblasts were cultured with interleukin (IL)-1-b, vascular endothelial growth factor (VEGF)-A was produced significantly (54th ASH). And, when antihuman VEGF-A neutralizing antibody (VEGF-A Ab) was added to the cultures, CD138 (Syndecan-1) expressed significantly. CD138 is a member of cell-surface transmembrane haparan sulfate proteoglycans, and expresses in plasma cells from multiple myeloma (MM) cases. Membrane-anchoring CD138 shows a better prognosis in an immunodeficiency murine transplantation model in vivo; however, when extra-domain of CD138 is digested by heparanase to be shed from the cell-surface, MM cells invade to various kinds of tissues, and the patients show poor prognosis. Aims To validate a biological implication of inhibition of VEGF-A-signaling in MM cells, we observed effects of VEGF-A Ab to bone marrow cells from MM patients. Cell-proliferations as well as morphological changes were also observed time-dependently. Materials and Methods Institutional ethical committee approved our study, and bone marrow cells were obtained from the informed MM patients as well as normal individuals. Cells were separated with gravity-sedimentation method, and the prepared mononuclear cells were cultured with or without VEGF-A Ab, and the expression of specific genes was analyzed. Results Twenty MM patients were eligible, in which three showed significant poor prognosis, and worsened after underwent intensive chemotherapy or allogeneic hematopoietic stem cells transplantation. Thirteen out of twenty expressed CD138, and when cells were cultured with VEGF-A Ab for four days, CD138-expression increased significantly in all cases. Four did not express CD138; however, CD138-expression was observed after 4 day’s culture with VEGF-A Ab. In three progressed cases CD138-expression decreased in accordance with the disease-progression; however, when VEGF-A Ab was added to the cell-cultures, CD138 was induced to express. Heparanase-expression was observed in 10 cases out of 20, which were down-regulated when VEGF-A Ab was added to the cultures. In contrast, in bone marrow cells from seven normal individuals CD138-expression was very low, which was down-regulated with the addition of VEGF-A Ab. Heparanase-expression was not observed in these normal cells, and were induced to be observed in four out of seven when VEGF-A Ab was added to the cultures. Discussion Expression of CD138 is induced in fibroblast by the addition of fibroblast growth factor-2, and in keratinocytes by epidermal growth factor and keratinocyte growth factor; however, an induction of CD138 by the VEGF-A Ab has not been reported. Several cytokines including VEGF-A influence plasma cell-proliferation; however, little is reported on cytokine-suppression therapy. Inhibition of the signaling of VEGF receptors by the chemicals including solafenib is not specific for VEGF-A. Currently we validate the efficacy of the inhibition of VEGF-A-signaling to MM cells and their environmental cells using RNA interference. Disclosures: No relevant conflicts of interest to declare.

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