scholarly journals Monoclonal Antibodies for the Treatment of Multiple Myeloma—A New Paradigm

2015 ◽  
Vol 11 (02) ◽  
pp. 115
Author(s):  
Nidhi Tandon ◽  
Shaji K Kumar ◽  
◽  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Vascular Endothelial ◽  
New Paradigm ◽  
Hematopoietic Stem ◽  
New Therapies ◽  
Significant Survival ◽  
Frontline Treatment ◽  
Cluster Of Differentiation ◽  
Endothelial Growth Factor

The past decade has seen many promising new therapies emerge for the treatment of multiple myeloma (MM), resulting in improved survival of patients. Despite these improvements, the disease eventually becomes refractory to the available options and patients die of progressive disease. Development of new therapies with new modes of action remains critical for the continued improvement in outcome, and given the success of monoclonal antibodies (MoAbs) in other cancers there has been considerable interest in development of this class of drugs for MM. Past attempts with MoAbs against interleukin-6 (IL-6) as well as vascular endothelial growth factor (VEGF) targeted antibodies have not realized the potential. More recently, development of MoAbs against SLAMF7 and cluster of differentiation 38 (CD38) have demonstrated considerable activity in MM, the former in combination and the latter as a single agents. At present, it remains to be defined how MoAb therapy can be most effectively incorporated into the current therapeutic paradigms that will help to achieve longer disease control and significant survival gains in patients with MM, either as short-term induction therapy, frontline treatment in transplant ineligible patients, or long-term maintenance therapy post autologous hematopoietic stem cell transplantation (ASCT)/induction cytotoxic therapy. Ongoing studies are examining the potential of several other targets on the plasma cell, using both naked antibodies as well as toxin conjugated MoAbs.

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.

scholarly journals Scl isoforms act downstream of etsrp to specify angioblasts and definitive hematopoietic stem cells

Blood ◽  
2010 ◽  
Vol 115 (26) ◽  
pp. 5338-5346 ◽  
Author(s):  
Xi Ren ◽  
Gustavo A. Gomez ◽  
Bo Zhang ◽  
Shuo Lin
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Critical Role ◽  
Vascular Endothelial ◽  
Hematopoietic Stem ◽  
Vegf Signaling ◽  
Endothelial Growth Factor ◽  
Endothelial Development ◽  
Definitive Hematopoiesis ◽  
Runx1 Expression

Abstract Recent lineage studies suggest that hematopoietic stem cells (HSCs) may be derived from endothelial cells. However, the genetic hierarchy governing the emergence of HSCs remains elusive. We report here that zebrafish ets1-related protein (etsrp), which is essential for vascular endothelial development, also plays a critical role in the initiation of definitive hematopoiesis by controlling the expression of 2 stem cell leukemia (scl) isoforms (scl-α and scl-β) in angioblasts. In etsrp morphants, which are deficient in endothelial and HSC development, scl-α alone partially rescues angioblast specification, arterial-venous differentiation, and the expression of HSC markers, runx1 and c-myb, whereas scl-β requires angioblast rescue by fli1a to restore runx1 expression. Interestingly, when vascular endothelial growth factor (Vegf) signaling is inhibited, HSC marker expression can still be restored by scl-α in etsrp morphants, whereas the rescue of arterial ephrinb2a expression is blocked. Furthermore, both scl isoforms partially rescue runx1 but not ephrinb2a expression in embryos deficient in Vegf signaling. Our data suggest that downstream of etsrp, scl-α and fli1a specify the angioblasts, whereas scl-β further initiates HSC specification from this angioblast population, and that Vegf signaling acts upstream of scl-β during definitive hematopoiesis.

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