Targeting the vascular endothelial growth factor in hematologic malignancies

Paesler, Julian; Gehrke, Iris; Poll-Wolbeck, Simon Jonas; Kreuzer, Karl‐Anton

doi:10.1111/ejh.12009

Cited by 16 publications

(7 citation statements)

References 119 publications

(204 reference statements)

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“…Angiogenesis factors are involved in the pathogenesis of most of the hematologic malignancies, and raised circulating VEGF levels have been described in chronic myeloid leukemia, chronic myelomonocytic leukemia, chronic lymphocytic leukemia, and lymphoma, often in correlation with disease activity. 12 – 14 The VEGF level has previously been found elevated in multiple myeloma (MM), 15 but our study found lower sVEGF concentrations in this group in comparison to other HD groups and to patients with no HD; this finding might be due to a large proportion (16/18) of treated patients in our cohort. 15 Increased VEGF levels has also been described in WM in 1 study.…”

Section: Discussioncontrasting

confidence: 66%

Raised VEGF

Pihan

Keddie

D’Sa

et al. 2018

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo investigate the sensitivity and the specificity of serum vascular endothelial growth factor (sVEGF) for the diagnosis of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome in patients with a neuropathy (NP) and to identify confounding causes of raised vascular endothelial growth factor (VEGF) in this context to improve accuracy.MethodsWe studied the specificity and sensitivity of sVEGF for the diagnosis of POEMS syndrome in a cohort of 195 consecutive patients with an NP in serum samples from June 2009 to November 2013, including 27 untreated patients with POEMS syndrome. We then studied VEGF in other neuropathies and analyzed causes of elevated VEGF in a multiple logistic regression analysis in a larger cohort of 236 patients including 168 with a non-POEMS NP and 68 without NP.ResultsThe sensitivity of elevated sVEGF for the diagnosis of POEMS was 100%. Its specificity was 91% in patients with an NP and 92% in patients with an NP and a paraproteinemia. sVEGF was much higher in POEMS before treatment. sVEGF was not significantly elevated in any non-POEMS NP or hematologic disease group. Multiple logistic regression showed that anemia with low iron was a significant predictor for elevated sVEGF and that chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea-hypopnoea syndrome were significant predictors for very elevated sVEGF.InterpretationWe confirmed the high sensitivity and specificity of an elevated VEGF for the diagnosis of POEMS. However, VEGF testing should be repeated, particularly after acute illnesses. Raised sVEGF should be interpreted with caution unless anemias with low iron, sleep apnea, COPD, cancers, vasculitis, and chronic inflammatory diseases are excluded.Classification of evidenceThis study provides class IV evidence that elevated sVEGF levels accurately identifies patients with POEMS syndrome.

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Section: Discussioncontrasting

confidence: 66%

Raised VEGF

Pihan

Keddie

D’Sa

et al. 2018

Neurol Neuroimmunol Neuroinflamm

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“…Intriguingly, the OGU1 cells expressed VEGF mRNA and protein in the cell culture supernatant. The expression of VEGF and VEGFR has been reported in various hematological malignancies including lymphomas . However, it is not completely understood how VEGF contributes to the pathogenesis of the lymphomas.…”

Section: Discussionmentioning

confidence: 99%

Establishment and characterization of a novel VEGF‐producing HHV‐8‐unrelated PEL‐like lymphoma cell line, OGU1

Kawauchi

Ogasawara

Aiba

et al. 2015

European J of Haematology

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Primary effusion lymphoma (PEL) is a rare B-cell lymphoma subtype that is characterized by lymphomatous effusion without the presence of masses, and it typically occurs in human immunodeficiency virus (HIV)-infected individuals. Lymphoma cells are universally positive for human herpesvirus 8 (HHV-8). Recently, a cavity-based effusion lymphoma that is similar to PEL without HHV-8 infection, called HHV-8-unrelated PEL-like lymphoma, has been reported in non-HIV-infected individuals. However, the pathophysiology of this lymphoma is largely undefined. We established a novel B-cell line OGU1 derived from a patient with HHV-8-unrelated PEL-like lymphoma. Notably, OGU1 cells produced vascular endothelial growth factor (VEGF) and expressed VEGF receptor 1, whose inhibitors retarded cell growth. Because VEGF acts as a vascular permeability and growth factor, it could play a role, at least in part, in the pathogenesis of this unique lymphoma. Thus, the OGU1 cell line is useful for the investigation of HHV-8-unrelated PEL-like lymphoma.

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“…All these proangiogenic agents act through distinct membrane receptors [28,29] which result in the activation of extensively overlapping intracellular cascades finally activating common effector molecules, such as NF-κB or HIF-1 [28]. In addition, recent evidences indicate that direct interactions may occur between integrin activated pathways and signalling from VEGF receptors [30] and EGF receptors [31]. Collectively, in the light of such observations, our results support the ability of cyclo [DKP-RGD] 1 to block common mechanisms, resulting in the effective inhibition of angiogenesis triggered by multiple agents.…”

Section: Discussionmentioning

confidence: 99%

Effects of a novel cyclic RGD peptidomimetic on cell proliferation, migration and angiogenic activity in human endothelial cells

et al. 2014

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BackgroundCyclic RGD peptidomimetics containing a bifunctional diketopiperazine scaffold are a novel class of high-affinity ligands for the integrins αVβ3 and αVβ5. Since integrins are a promising target for the modulation of normal and pathological angiogenesis, the present study aimed at characterizing the ability of the RGD peptidomimetic cyclo[DKP-RGD] 1 proliferation, migration and network formation in human umbilical vein endothelial cells (HUVEC).MethodsCell viability was assessed by flow cytometry and annexin V (ANX)/propidium iodide (PI) staining. Cell proliferation was evaluated by the ELISA measurement of bromodeoxyuridine (BrdU) incorporation. Network formation by HUVEC cultured in Matrigel-coated plates was evaluated by optical microscopy and image analysis. Integrin subunit mRNA expression was assessed by real time-PCR and Akt phosphorylation by western blot analysis.ResultsCyclo[DKP-RGD] 1 does not affect cell viability and proliferation either in resting conditions or in the presence of the pro-angiogenic growth factors VEGF, EGF, FGF, and IGF-I. Addition of cyclo[DKP-RGD] 1 however significantly decreased network formation induced by pro-angiogenic growth factors or by IL-8. Cyclo[DKP-RGD] 1 did not affect mRNA levels of αV, β3 or β5 integrin subunits, however it significantly reduced the phosphorylation of Akt.ConclusionsCyclo[DKP-RGD] 1 can be a potential modulator of angiogenesis induced by different growth factors, possibly devoid of the adverse effects of cytotoxic RGD peptidomimetic analogues.

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Targeting the vascular endothelial growth factor in hematologic malignancies

Cited by 16 publications

References 119 publications

Raised VEGF

Raised VEGF

Establishment and characterization of a novel VEGF‐producing HHV‐8‐unrelated PEL‐like lymphoma cell line, OGU1

Effects of a novel cyclic RGD peptidomimetic on cell proliferation, migration and angiogenic activity in human endothelial cells

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