Activity of the Vascular-Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid against Human Head and Neck Carcinoma Xenografts

Mukund Seshadri; Richard Mazurchuk; Joseph A. Spernyak; Arup Bhattacharya; Youcef M. Rustum; David A. Bellnier

doi:10.1593/neo.06295

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Activity of the Vascular-Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid against Human Head and Neck Carcinoma Xenografts

Journal article

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Activity of the Vascular-Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid against Human Head and Neck Carcinoma Xenografts

Mukund Seshadri, Richard Mazurchuk, Joseph A. Spernyak, Arup Bhattacharya, Youcef M. Rustum and David A. Bellnier

Neoplasia (New York, N.Y.), Vol.8(7), pp.534-542

07/2006

DOI: 10.1593/neo.06295

PMCID: PMC1601938

PMID: 16867215

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Abstract

Head and neck squamous cell carcinomas (HNSCC) constitute a majority of the tumors of the upper aerodigestive tract and continue to present a significant therapeutic challenge. To explore the potential of vascular-targeted therapy in HNSCC, we investigated the antivascular, antitumor activity of the potent vascular-disrupting agent (VDA) 5,6-dimethylxanthenone-4-acetic acid (DMXAA) against two HNSCC xenografts with markedly different morphologic and vascular characteristics. Athymic nude mice bearing subcutaneous FaDu (human pharyngeal squamous cell carcinoma) and A253 (human submaxillary gland epidermoid carcinoma) tumors were administered a single dose of DMXAA (30 mg/kg, i.p). Changes in vascular function were evaluated 24 hours after treatment using contrast-enhanced magnetic resonance imaging (MRI) and immunohistochemistry (CD31). Signal enhancement (E) and change in longitudinal relaxation rates (ΔR1) were calculated to measure alterations in vascular perfusion. MRI showed a 78% and 49% reduction in vascular perfusion in FaDu and A253 xenografts, respectively. CD31-immunostaining of tumor sections revealed three-fold (FaDu) and two-fold (A253) reductions in microvessel density (MVD) 24 hours after treatment. DMXAA was equally effective against both xenograffs, with significant tumor growth inhibition observed 30 days after treatment. These results indicate that DMXAA may be beneficial in the management of HNSCC, alone or in combination with other treatments.

antivascular therapies

DMXAA

Head and neck cancers

MRI

tumor vasculature

Details

Title: Subtitle: Activity of the Vascular-Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid against Human Head and Neck Carcinoma Xenografts
Creators: Mukund Seshadri - Roswell Park Cancer Institute
Richard Mazurchuk - Roswell Park Cancer Institute
Joseph A. Spernyak - Roswell Park Cancer Institute
Arup Bhattacharya - Roswell Park Cancer Institute
Youcef M. Rustum - Roswell Park Cancer Institute
David A. Bellnier - Roswell Park Cancer Institute
Resource Type: Journal article
Publication Details: Neoplasia (New York, N.Y.), Vol.8(7), pp.534-542
DOI: 10.1593/neo.06295
PMID: 16867215
PMCID: PMC1601938
NLM abbreviation: Neoplasia
ISSN: 1476-5586
eISSN: 1476-5586
Publisher: Elsevier Inc
Language: English
Date published: 07/2006
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359908902771

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