Inhibition of K562 leukemia angiogenesis and growth by expression of antisense vascular endothelial growth factor (VEGF) sequence

He, Rui; Liu, Bin; Yang, Chen; Yang, Ruyu; Tobelem, Gérard; Han, Zhongchao

doi:10.1038/sj.cgt.7700645

Cited by 30 publications

(13 citation statements)

References 27 publications

(27 reference statements)

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“…Our previous study has also shown that the antisense-VEGF ODNs can effectively inhibit K562 xenografted tumor growth in nude mice. 10 In addition, being not influenced by tumor cell cycles, the antiangiogenic therapy could be an excellent supplement to other therapeutic strategies. Therefore, combination of ASO-B3/A2 with ASO-VEGF appears to be rational and promising for future clinical use.…”

Section: Discussionmentioning

confidence: 99%

“…For measurement of survival, the MTT assays were performed as described previously (measured at 570 nm). 10 Cell proliferation assays were also performed. At 72 h, cells were harvested, and viable cells were counted using homocytometer and Trypan blue dye exclusion on triplicate samples.…”

Section: Measurement Of Cell Growth and Viabilitymentioning

confidence: 99%

“…10 In addition, Imatinib mesylate (STI-571), a tyrosine kinase inhibitor against bcr/abl, and other specific kinase targets have also been reported to reduce VEGF secretion in leukemia cells. 11 The present study was therefore designed to determine if the combination of bcr3/abl2 and VEGF antisense oligodeoxyribonucleotides (AS-ODNs) increases the susceptibility of CML cells to apoptosis-inducing stimuli in vitro and decrease in vivo growth of leukemia tumors, in an attempt to develop a novel and more effective therapy strategy for leukemia.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced growth suppression of Philadephia1 leukemia cells by targeting bcr3/abl2 and VEGF through antisense strategy

Cong

Yang

et al. 2005

Leukemia

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An antisense strategy by targeting both bcr3/abl2 and VEGF was designed to suppress the growth of Philadephia 1 leukemia cells in vitro and in vivo in mice. In vitro, although bcr3/abl2 or VEGF antisense oligodeoxyribonucleotides (AS-ODNs) alone was able to inhibit the proliferation of K562 cells, the combination of bcr3/abl2 and VEGF AS-ODNs produced an additive inhibitory effect on the growth of K562 cells and significantly enhanced the sensibility of K562 cells to apoptosis-inducing stimuli including STI571. In vivo, the nude mice xenografted with K562 cells received intratumoral injections of bcr3/abl2 and VEGF AS-ODNs showed a significant reduction in leukemia tumor size and microvessel density and an increase of apoptosis in the tumors when compared to the mice that received an individual agent. These results demonstrate that targeting both bcr3/abl2 and VEGF can result in an additive tumor-suppressive action and may represent an excellent strategy to augment the efficacy of chemotherapy in CML.

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Section: Discussionmentioning

confidence: 99%

Section: Measurement Of Cell Growth and Viabilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enhanced growth suppression of Philadephia1 leukemia cells by targeting bcr3/abl2 and VEGF through antisense strategy

Cong

Yang

et al. 2005

Leukemia

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“…Antileukemia effects following VEGF blockade with murine anti-VEGFR antibodies (8), VEGF antisense gene transfection (9), soluble antagonists (10), and small interfering (siRNA); ref (11) have confirmed the key role of VEGF/VEGFR in leukemogenesis. Unfortunately, clinical responses to VEGF inhibitors in AML patients have been modest and transient (12)(13)(14).…”

Section: Introductionmentioning

confidence: 96%

Aflibercept Exerts Antivascular Effects and Enhances Levels of Anthracycline ChemotherapyIn vivoin Human Acute Myeloid Leukemia Models

Lal

Park

Demock

et al. 2010

Molecular Cancer Therapeutics

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We examined whether potent vascular endothelial growth factor (VEGF) blockade mediated by aflibercept, a decoy VEGF receptor (VEGFR) 1/2 moiety with stronger affinity for VEGF than bevacizumab, resulted in antileukemia effects and enhanced the efficacy of systemic chemotherapy. The efficacy of aflibercept alone and in combination with doxorubicin was evaluated in human VEGF-expressing acute myeloid leukemia (AML) cell lines and primary cells xenotransplanted into immunodeficient mice. Aflibercept reduced primary VEGF/VEGFR-positive AML colony formation growth in vitro and inhibited AML xenograft growth up to 93% in association with antiangiogenic and antiproliferative effects, hypoxia, and VEGF sequestration in multiple models. High VEGF-A expression by AML cells promoted in vivo xenograft growth and aflibercept sensitivity. Aflibercept therapy slowed disease progression in two systemic human AML xenograft models and reduced peripheral leukemia disease in a primary relapsed AML model in NOD/SCID/IL2Rγnull mice. Combination aflibercept and doxorubicin enhanced antitumor effects in local xenograft models. Sequential aflibercept followed by doxorubicin resulted in progressive anthracycline accumulation in marrow and extramedullary AML sites and resulted in 2-fold higher drug levels 24 hours after administration. In contrast, tissues (tumor, plasma, marrow) treated with chemotherapy only showed progressive drug clearance over time. Combination aflibercept and doxorubicin also resulted in vascular narrowing, decreased vessel number, and perivascular apoptosis. These data suggest that inefficient drug delivery by leukemia-associated vasculature may mediate chemoresistance and support further clinical evaluation of combination aflibercept and anthracycline therapy in refractory/relapsed AML patients. Mol Cancer Ther; 9(10);

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“…60 Delivery of an anti-VEGFR-2 antibody or VEGF-antisense approaches also slowed down leukemia growth in models of promyelomonocytic leukemia and subcutaneous implanted erythroleukemia. [61][62][63] In xenotransplantation models of human AML chloromas, vascular disrupting agents, a new class of agents directly targeting proliferating ECs, increased leukemia cell apoptosis, leaving, however, a residual highly vascularized viable rim of leukemia cells. When combined with bevacizumab, this viable tumor rest was abrogated and enhanced leukemia regression was observed.…”

Section: Angiogenesis and Anti-angiogenic Therapy In Leukemiamentioning

confidence: 99%

Angiogenesis: A Target in Solid Tumors, Also in Leukemia?

Schmidt

Carmeliet

2011

Hematology

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Targeting angiogenesis has become an established therapeutic approach to fighting solid tumor growth in cancer patients. Even though increased angiogenesis has long been recognized in various types of hematologic malignancies, the molecular basis underlying this angiogenic switch in leukemias remains poorly understood. The BM stroma is gaining increasing attention for its role in promoting leukemia growth and resistance against current treatments with tyrosine kinase inhibitors. This article provides a brief overview of the role of angiogenesis in leukemias, discusses recent insights into the role of placenta growth factor (PlGF), a VEGF family member, as a novel disease candidate in chronic myeloid leukemia (CML), and highlights the therapeutic potential of PlGF blockade for imatinib-resistant CML.

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Inhibition of K562 leukemia angiogenesis and growth by expression of antisense vascular endothelial growth factor (VEGF) sequence

Cited by 30 publications

References 27 publications

Enhanced growth suppression of Philadephia1 leukemia cells by targeting bcr3/abl2 and VEGF through antisense strategy

Enhanced growth suppression of Philadephia1 leukemia cells by targeting bcr3/abl2 and VEGF through antisense strategy

Aflibercept Exerts Antivascular Effects and Enhances Levels of Anthracycline ChemotherapyIn vivoin Human Acute Myeloid Leukemia Models

Angiogenesis: A Target in Solid Tumors, Also in Leukemia?

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