Angiogenesis in Multiple Myeloma

Vacca, Angelo; Ria, Roberto; Reale, Antonia; Ribatti, Doménico

doi:10.1159/000353312

Cited by 46 publications

(58 citation statements)

References 88 publications

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“…Multiple myeloma is characterized by an increased bone marrow angiogenesis [18], based on various factors, most prominently by increased Vascular Endothelial Growth Factor (VEGF) and BasicFibroblast Growth Factor-2 (bFGF) levels, but also mediated by Angiopoietins, Metalloproteases, Osteopontin, Hepatocyte Growth Cereblon binds a multitude of proteins. We used an anti-CRBN antibody to immunoprecipitate CRBN and its associated proteins as well as Ni charged (Ni1) beads and identified 10 CRBN-associated proteins shared between the chosen methods.…”

Section: Angiogenesismentioning

confidence: 99%

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Cereblon binding molecules in multiple myeloma

Kortüm¹,

Zhu²,

Shi³

et al. 2015

Blood Reviews

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Section: Angiogenesismentioning

confidence: 99%

“…CRBN complex associated proteins identified by co-IP and pull-down assays (Zhu et Factor (HGF), Syndecan-1, Heparanase, Interleukin 6 and Interleukin 8 [18]. The known anti-angiogenic properties of THAL provided the rationale to investigate its efficacy in MM.…”

Section: Angiogenesismentioning

confidence: 99%

Cereblon binding molecules in multiple myeloma

Kortüm¹,

Zhu²,

Shi³

et al. 2015

Blood Reviews

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“…Since angiogenesis is associated with progression of MM [38], we first examined the effect of PGJ on HBMEC cell viability. As shown in Figure 2A, PGJ inhibited cell proliferation in a dose- and time-dependent manner by 18% and 19% at 48 h and 72 h, respectively, in the presence of 3% PGJ.…”

Section: Resultsmentioning

confidence: 99%

Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM)

et al. 2016

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Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ) contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment.

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“…The pathophysiology of MM-induced angiogenesis is complex and involves a plethora of soluble factors, cellular players, and mechanisms, resulting in the direct production of angiogenic cytokines by plasma cells and their induction within the BM microenvironment cells as well [26,78]. Moreover, the hypoxic microenvironment inside the BM might significantly contribute to the induction and maintenance of a proangiogenic profile, given the well-known role of hypoxia in promoting angiogenesis in all its forms [78,79,80]. …”

Section: Discussionmentioning

confidence: 99%

Microvessel Density as a Surrogate Prognostic Marker in Patients with Multiple Myeloma: A Meta-Analysis

Ntellas

Perivoliotis²,

Dadouli³

et al. 2017

Acta Haematol

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Background/Aims: Bone marrow (BM) angiogenesis is considered a hallmark of multiple myeloma (MM) development and progression, and can be quantified with the use of microvessel density (MVD). The purpose of this study is to provide a review and a meta-analysis of the current literature regarding the prognostic value of MVD in the overall survival (OS) of MM patients. Methods: MEDLINE was screened for studies evaluating the OS of MM patients with regard to their MVD count in BM trephine. The pooled hazard ratio (HR) and its associated 95% confidence interval (CI) among MM patients with a high and low MVD count was the primary end point. Secondary outcomes included odds ratios (OR) for 12-, 36-, and 60-month survival. Results: Ten eligible trials were identified for the analysis of the primary end point and 9 for the secondary end points. Pooled HR for OS was 1.85 (95% CI: 1.25-2.73, p = 0.002). The pooled OR of survival were 1.59 (95% CI: 1.02-2.46, p = 0.04) at 12 months, 2.90 (95% CI: 1.68-5.03, p = 0.0001) at 36 months, and 3.42 (95% CI: 2.41-4.85, p < 0.00001) at 60 months, in favor of the low MVD group. Conclusion: This meta-analysis provides persuasive evidence that MVD has significant impact on the clinical outcome of MM patients.

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Angiogenesis in Multiple Myeloma

Cited by 46 publications

References 88 publications

Cereblon binding molecules in multiple myeloma

Cereblon binding molecules in multiple myeloma

Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM)

Microvessel Density as a Surrogate Prognostic Marker in Patients with Multiple Myeloma: A Meta-Analysis

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