Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma.

Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma. Research Abstract Details 

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Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma. Abstract Text:

Qiwei Yang,Yufeng Tian,Shuqing Liu,Rana Zeine,Alexandre Chlenski,Helen R Salwen,Jack Henkin,Susan L Cohn,

In the pediatric cancer neuroblastoma, clinically aggressive disease is associated with increased levels of angiogenesis stimulators and high vascular index. We and others have hypothesized that blocking angiogenesis may be effective treatment for this pediatric malignancy. However, little is known about the efficacy of antiangiogenic agents in pediatric malignancies. Recently, promising results have been reported in an adult phase I study of ABT-510, a peptide derivative of the natural angiogenic inhibitor thrombospondin-1. Histone deacetylase inhibitors, such as valproic acid (VPA), have also been shown to have antiangiogenic activity in several cancer models. In this study, we evaluated the effects of ABT-510 and VPA on neuroblastoma tumor growth and angiogenesis. Although only VPA was capable of blocking the proliferation of neuroblastoma cells and inducing neuroblastoma cell apoptosis in vitro, treatment with VPA or ABT-510 alone significantly suppressed the growth of neuroblastoma xenografts established from two different MYCN-amplified cell lines. Combination therapy more effectively inhibited the growth of small neuroblastoma xenografts than single-agent treatment, and in animals with large xenografts, total cessation of tumor growth was achieved with this treatment approach. The microvascular density was significantly reduced in the xenografts treated with combination therapy compared with controls or tumors treated with single agents. In addition, the number of structurally abnormal vessels was reduced, suggesting that these agents may "normalize" the tumor vasculature. Our results indicate that ABT-510 combined with VPA may be an effective antiangiogenic treatment strategy for children with high-risk neuroblastoma.

Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma. Publishing Authors By Initials

Q Yang,Y Tian,S Liu,R Zeine,A Chlenski,HR Salwen,J Henkin,SL Cohn,

For similar xenograft model antitumor assays research abstracts see: xenograft model antitumor assays research

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Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer research

VOLUME: 67

Page Numbers: 1716-24

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 15

MONTH: Feb

YEAR: 2007

Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma. Keywords Mesh Terms:

KEYWORDS: Xenograft Model Antitumor Assays

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma. Information

Substance Name: Valproic Acid

Registry Number: 99-66-1

Grant and Affiliation Information for Thrombospondin-1 peptide ABT-510 combined with valproic acid is an effective antiangiogenesis strategy in neuroblastoma.

AFFILIATION: The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 5841 Maryland Avenue, Chicago, IL 60637, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS 049814

ACRONYM: NS

MEDLINETA: Cancer Res

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