Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model.

Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. Research Abstract Details 

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Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. Abstract Text:

Sai-Ching J Yeung,Miaorong She,Huiling Yang,Jingxuan Pan,Lily Sun,David Chaplin,

CONTEXT: Anaplastic thyroid cancer (ATC) is extremely aggressive, and no effective treatment is available. Combretastatin A4 phosphate (CA4P), a vascular disrupting agent, has limited activity against ATC in a clinical trial, and so does paclitaxel. OBJECTIVE: We hypothesized that a triple-drug combination including CA4P and paclitaxel would improve efficacy against ATC. Therefore, we evaluated two such combinations in vivo. SETTING: We used a nude mouse xenograft model with ARO and KAT-4 cells. INTERVENTIONS: The first combination consisted of CA4P, paclitaxel, and manumycin A (a farnesyltransferase inhibitor), and the second, CA4P, paclitaxel, and carboplatin. MAIN OUTCOME MEASURES: Main outcome measures included tumor growth curves and tumor weights. RESULTS: Tumor growth curve analysis (linear mixed models, P < 0.05) and xenograft weight analysis (Kruskal-Wallis one-way ANOVA on ranks, post hoc pairwise comparison, Dunn's test, P < 0.05) demonstrated that both triple-drug combinations were significantly better than placebo for both cell lines. Anti-bromodeoxyuridine immunostaining of xenograft sections from animals injected with bromodeoxyuridine before being killed showed that CA4P alone did not inhibit DNA synthesis, but manumycin A and paclitaxel did. CA4P decreased the depth of the viable outer rim of tumor cells on xenograft sections. Using electron microscopy, we found blebbing/budding of endothelial cells into capillary lumens and autophagy of tumor cells in CA4P-treated xenografts. CONCLUSIONS: Both triple-drug combinations demonstrated excellent antineoplastic activity against ATC. The correlative findings in xenografts were consistent with vascular disruption but not direct inhibition of cell proliferation as the primary antineoplastic mechanism contributed by CA4P. These regimens warrant further investigation in clinical trials for ATC.

Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. Publishing Authors By Initials

SC Yeung,M She,H Yang,J Pan,L Sun,D Chaplin,

For similar surgical procedures, operative: transplantation: transplantation, heterologous research abstracts see: surgical procedures, operative: transplantation: transplantation, heterologous research

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Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. Journal Published:

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

Journal: The Journal of clinical endocrinology and metaboli

VOLUME: 92

Page Numbers: 2902-9

Journal Abbreviation: J. Clin. Endocrinol. Metab.

ISSN: 0021-972X

DAY: 5

MONTH: 06

YEAR: 2007

Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 375362

Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. Keywords Mesh Terms:

KEYWORDS: Transplantation, Heterologous

MESH TERMS: pathology

Chemical & Substance for Abstract: Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. Information

Substance Name: Bromodeoxyuridine

Registry Number: 59-14-3

Grant and Affiliation Information for Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model.

AFFILIATION: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 437, Houston, Texas 77030, USA. syeung@mdanderson.org

Country: United States

AGENCY: United States NCI

GRANT: CA16672

ACRONYM: CA

MEDLINETA: J Clin Endocrinol Metab

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