Endostatin induces tumor stabilization after chemo- or ANTI-CD20 therapy of high-grade non-hodgkin's lymphoma (Nhl)

Fusetti, Lisa; Mancuso, Patrizia; Gobbi, A.; Corsini, Chiara; Ferrucci, Pier Francesco; Martinelli, Giovanni; Pruneri, Giancarlo

doi:10.1016/s0301-472x(00)00296-4

Cited by 27 publications

(33 citation statements)

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“…22 Bertolini et al 28 showed that administering endostatin after chemotherapy or RTX treatment stabilized the growth of Burkitt lymphoma in preclinical models. However, the potential clinical benefits of endostatin as an antiangiogenic agent for lymphoma are unclear because elevated serum endostatin levels in lymphoma patients correlated with poor overall survival.…”

Section: Discussionmentioning

confidence: 99%

“…27 When tumor volumes approached 100 mm 3 , mice were divided into experimental groups of 5 to 10 mice per group and were treated by intraperitoneal injection with 800 g immunoglobulin (IVIG) 3 times a week, 400 g IMC-1C11 or IMC-2C6 twice a week, 400 g DC101 3 times a week, 800 g MF-1 twice a week, 800 g 6.12 twice a week, and 25 mg/kg chimeric murine/human monoclonal antibody against CD20 antigen twice a week (Rituxan; IDEC Pharmaceuticals, San Diego, CA). 28 Methotrexate (MTX) was given at the maximally tolerated dose of 40 mg/kg intraperitoneally twice weekly for 4 doses based on previous data. 29,30 Combination regimens of antibodies and chemotherapy used the same dosing regimens and intervals.…”

Section: Lymphoma Xenograft Experimentsmentioning

confidence: 99%

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Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo

Wang

Teruya‐Feldstein

et al. 2004

Blood

121

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The role of angiogenesis in lymphoproliferative diseases is not well established. We demonstrate here that human lymphoma cells secrete vascular endothelial growth factor (VEGF) and express VEGF receptor 1 (VEGFR-1) and VEGFR-2. Proliferation of non-Hodgkin lymphoma (NHL) cells under serum-free conditions was enhanced by the addition of VEGF and was blocked by VEGFR-1-and VEGFR-2-specific antibodies. To differentiate between VEGF-mediated autocrine and paracrine effects on lymphoma growth, NOD/ SCID mice engrafted with human diffuse large B-cell lymphoma (DLBCL) were treated with species-specific antibodies against human VEGFR-1 (6.12), human VEGFR-2 (IMC-1C11), murine VEGFR-1 (MF-1), or murine VEGFR-2 (DC101). Treatment with 6.12 or DC101 (targeting tumor VEGFR-1 and host VEGFR-2) reduced established DLBCL xenograft growth, whereas treatment with IMC-1C11 or MF-1 (targeting tumor VEGFR-1 and host VEGFR-1) had no effect. Decreased tumor volumes after 6.12 and DC101 treatment correlated with increased tumor apoptosis and reduced vascularization, respectively, supporting the presence of autocrine VEGFR-1-and paracrine VEGFR-2-mediated pathways in lymphomagenesis. Inhibition of paracrine VEGF interactions (DC101) in these models was equivalent to their inhibition with rituximab. Combining DC101 with therapeutic agents (rituximab, 6.12, methotrexate) consistently improved tumor responses over those of single-agent therapy. These data support the further clinical development of VEGFR-targeted approaches for the therapy of aggressive DLBCL. (Blood.

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Section: Discussionmentioning

confidence: 99%

Section: Lymphoma Xenograft Experimentsmentioning

confidence: 99%

Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo

Wang

Teruya‐Feldstein

et al. 2004

Blood

121

View full text Add to dashboard Cite

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“…We used either VPA (150 mg/kg twice a day) or romidepsin (0.1 mg/kg once a day) as an HDAC inhibitor. On the basis of previous studies, 30,31 rituximab was given through the tail vein at 25 mg/kg at 48 h after the administration of HDAC inhibitors. All animal studies were approved by the Animal Ethics Committee of Jichi Medical University, and performed in accordance with the Jichi Medical University Guide for Laboratory Animals, following the Guide for the Care and Use of Laboratory Animals formulated by the National Academy of Sciences.…”

Section: Mouse Lymphoma Modelsmentioning

confidence: 99%

HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells

et al. 2010

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Anti-CD20 antibody rituximab is now essential for the treatment of CD20-positive B-cell lymphomas. Decreased expression of CD20 is one of the major mechanisms underlying both innate and acquired resistance to rituximab. In this study, we show that histone deacetylase (HDAC) inhibitors augment the cytotoxic activity of rituximab by enhancing the surface expression of CD20 antigen on lymphoma cells. HDAC inhibitors, valproic acid (VPA) and romidepsin, increased CD20 expression at protein and mRNA levels in B-cell lymphoma cell lines with relatively low CD20 expression levels. The VPA-mediated increase in CD20 expression occurred at 1 mM, which is clinically achievable and safe, but insufficient for inducing cell death. Chromatin immunoprecipitation assays revealed that HDAC inhibitors transactivated the CD20 gene through promoter hyperacetylation and Sp1 recruitment. HDAC inhibitors potentiated the activity of rituximab in complementdependent cytotoxic assays. In mouse lymphoma models, HDAC inhibitors enhanced CD20 expression along with histone hyperacetylation in transplanted cells, and acted synergistically with rituximab to retard their growth. The combination with HDAC inhibitors may serve as an effective strategy to overcome rituximab resistance in B-cell lymphomas.

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“…19 -21 Endostatin inhibited the proliferation of NHL cells in a mouse model of human high-grade lymphoma. 22 It has been found that serum endostatin (S-endostatin) concentrations are elevated in patients with malignant disease (e.g., renal carcinoma and soft tissue sarcoma). 23,24 To our knowledge, the clinical and prognostic significance of S-endostatin has not been investigated in patients with lymphoproliferative disorders, and little is known about the association between S-endostatin levels and the levels of serum proangiogenic growth factors.…”

mentioning

confidence: 99%

Elevated serum endostatin is associated with poor outcome in patients with non‐Hodgkin lymphoma

Bono

Teerenhovi

Joensuu

2003

Cancer

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BACKGROUNDEndostatin is a cleaved fragment of collagen Type XVIII and has antiangiogenic activity. The clinical significance of circulating, soluble endostatin (S‐endostatin) is not known.METHODSPretreatment S‐endostatin and serum vascular endothelial growth factor (S‐VEGF) levels were measured in 143 patients with non‐Hodgkin lymphoma (NHL) using competitive enzyme immunoassays and were compared with the levels from a control group (n = 24 participants).RESULTSS‐endostatin levels varied widely from 4.5 ng/mL to 116 ng/mL (median, 29.6 ng/mL), and the median level was higher in patients with NHL compared with patients in the control group (16.4 ng/mL; P = 0.05). High S‐endostatin levels were associated with advanced disease stage (P < 0.0001) and high serum VEGF levels at diagnosis (P = 0.017). The median 5‐year survival rate for patients who had S‐endostatin concentrations within the highest tertile (> 36.0 ng/mL) was only 34% compared with 57% in patients who had lower S‐endostatin levels (P = 0.019). A high S‐endostatin level also was associated with a poor outcome in patients with large cell diffuse and immunoblastic lymphoma, which was the largest subgroup within the series (n = 60 patients). Patients who had high pretreatment levels of both S‐VEGF and S‐endostatin had particularly poor outcomes. High S‐endostatin levels had an independent, adverse influence on survival it was entered as a factor into a multivariate analysis together with the factors included in the International Prognostic Index (relative risk, 1.80; 95% confidence interval, 1.08–2.98; P = 0.0024).CONCLUSIONSHigh pretreatment levels of S‐endostatin are associated with high serum VEGF levels and poor survival in patients with NHL. Prospective studies are warranted to establish the clinical value of longitudinal S‐endostatin measurements. Cancer 2003;97:2767–75. © 2003 American Cancer Society.DOI 10.1002/cncr.11399

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Endostatin induces tumor stabilization after chemo- or ANTI-CD20 therapy of high-grade non-hodgkin's lymphoma (Nhl)

Cited by 27 publications

References 0 publications

Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo

Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo

HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells

Elevated serum endostatin is associated with poor outcome in patients with non‐Hodgkin lymphoma

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