Bevacizumab attenuates major signaling cascades and eIF4E translation initiation factor in multiple myeloma cells

Attar-Schneider, Oshrat; Drucker, Liat; Zismanov, Victoria; Tartakover-Matalon, Shelly; Rashid, Gloria; Lishner, Michael

doi:10.1038/labinvest.2011.162

Cited by 41 publications

(45 citation statements)

References 48 publications

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“…[1][2][3][4][5][6] mToR is part of the mToR1 complex (mToRC1), which is controlled by prolinerich AKT substrate of 40 kDa (PRAS40) and tuberous sclerosis (TSC)2, both inhibited by activated AKT (when phosphorylated on Thr308 and Ser473). The mToRC1 acts as an ATP and amino acid sensor to balance nutrient availability and cell growth by regulating metabolism, translation and autophagy.…”

Section: Introductionmentioning

confidence: 99%

Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study

Günther¹,

Baumann²,

Burger³

et al. 2015

Haematologica

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Section: Introductionmentioning

confidence: 99%

Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study

Günther¹,

Baumann²,

Burger³

et al. 2015

Haematologica

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“…Our results also indicate that targeting a BM microenvironmental cell (and not direct inhibition of the tumor clone) can lead to a delay in MM tumor progression. Although prior studies have shown that antiangiogenic drugs had limited activity on tumor growth in MM, 38,39 our studies suggest that targeting AMCs before their recruitment into areas of tumor progression may provide a window of opportunity for targeted antiangiogenic therapy, or AMC-targeted therapy that delays/prevents tumor progression. Further studies into the mechanisms of AMC-mediated tumor progression in MM and their specific role in inducing tumor progression are warranted.…”

Section: Discussionmentioning

confidence: 72%

CXCR7-dependent angiogenic mononuclear cell trafficking regulates tumor progression in multiple myeloma

Azab

Şahin

Azab

et al. 2014

Blood

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Key Points• AMCs home to tumor sites in MM.• CXCR7 inhibition delayed tumor progression in MM through specific regulation of AMC trafficking but not through a direct tumor effect.The CXCR4/stromal cell-derived factor-1 (SDF-1) axis is essential for cell trafficking and has been shown to regulate tumor progression and metastasis in many tumors including multiple myeloma (MM). A second chemokine receptor for SDF-1, CXCR7 was discovered recently and found on activated endothelial cells. We examined the role of CXCR7 in angiogenic mononuclear cells (AMCs) trafficking in MM. Our data demonstrate that AMCs are circulating in patients with MM and in vivo studies show that they specifically home to areas of MM tumor growth. CXCR7 expression is important for regulating trafficking and homing of AMCs into areas of MM tumor growth and neoangiogenesis. We demonstrate that the CXCR7 inhibitor, POL6926, abrogated trafficking of AMCs to areas of MM tumor progression leading to a significant inhibition of tumor progression. These effects were through regulation of endothelial cells and not through a direct tumor effect, indicating that targeting a bone marrow microenvironmental cell can lead to a delay in MM tumor progression. In conclusion, our studies demonstrate that CXCR7 may play an important role in the regulation of tumor progression in MM through an indirect effect on the recruitment of AMCs to areas of MM tumor growth in the bone marrow niche. (Blood. 2014;124(12):1905-1914

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“…A recent study reported that bevacizumab has a cytostatic effect of VEGF inhibition on multiple myeloma. This malignancy of plasma cells was determined through the attenuation of critical signaling effectors: VEGF receptor 1, mTOR, c-Myc, Akt, STAT3 and eIF4E (9). In addition, bevacizumab has a direct effect on major pathways critically activated in multiple myeloma that is independent from its established effect on angiogenesis (9).…”

Section: Discussionmentioning

confidence: 99%

Cell cycle regulation by bevacizumab in ARPE-19 human retinal pigment epithelial cells

Kuo

Chen

Lai

et al. 2012

Molecular Medicine Reports

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Abstract. Bevacizumab, a recombinant humanized monoclonal antibody, binds vascular endothelial growth factor (VEGF) and inhibits its interaction with receptors found on endothelial cells. Bevacizumab has been increasingly used as an off-label treatment for exudative age-related macular degeneration (AMD). Whether or not bevacizumab is capable of arresting the growth of human retinal pigment epithelial cells remains to be clarified. In this study, flow cytometry was used to evaluate whether bevacizumab markedly induced the G 1 /S phase arrest. The G 1 /S phase cycle-related protein analysis demonstrated that the expression of cyclin-dependent kinase (CDK)2, 4 and 6 and of cyclin D and E, as well as the phosphorylation of retinoblastoma tumor suppressor protein (ppRB) production were found to be markedly reduced by bevacizumab. By contrast, the protein levels of p53, p16, p21 and p27 were increased in bevacizumab-treated ARPE-19 cells (a human retinal pigment epithelial cell line). These events of G 1 /S arrest induced by bevacizumab in ARPE-19 cells suggest that a preventive effect of bevacizumab exists in AMD.

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Bevacizumab attenuates major signaling cascades and eIF4E translation initiation factor in multiple myeloma cells

Cited by 41 publications

References 48 publications

Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study

Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study

CXCR7-dependent angiogenic mononuclear cell trafficking regulates tumor progression in multiple myeloma

Cell cycle regulation by bevacizumab in ARPE-19 human retinal pigment epithelial cells

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