Antitumor activity of brequinar sodium (Dup-785) against human head and neck squanmous cell carcinoma xenografts

B. J.M. Braakhuis, G. A.M.S. van Dongen, G. J. Peters, M. van Walsum, G. B. Snow

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The effect of Brequinar sodium on the growth of xenografts established from head and neck squamous cell carcinomas (HNSCC) was assessed. Brequinar sodium is a novel drug, known to inhibit dihydroorotic acid dehydrogenase (DHO-DH), resulting in a decrease of the pyrimidine de novo synthesis. The drug was administered i.p. to tumor-bearing nude mice, once a day, during 5 days at a maximum tolerated dose of 50 mg/kg/day. Statistically significant growth delaying effects were observed in 4 out of 5 lines tested. In 3 of these lines the effect was moderate and short lasting, whereas in one line (HNX-LP) tumor growth rate was totally inhibited for a 17-day period. In this line, Brequinar sodium was superior to 5 drugs known to be active in HNSCC patients. In two tumor lines DHO-DH activity could be measured and the results are in agreement with the concept that there is a relation between Brequinar sodium sensitivity and enzyme activity.

Original languageEnglish
Pages (from-to)133-137
Number of pages5
JournalCancer Letters
Volume49
Issue number2
DOIs
Publication statusPublished - 1 Jan 1990

Cite this

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title = "Antitumor activity of brequinar sodium (Dup-785) against human head and neck squanmous cell carcinoma xenografts",
abstract = "The effect of Brequinar sodium on the growth of xenografts established from head and neck squamous cell carcinomas (HNSCC) was assessed. Brequinar sodium is a novel drug, known to inhibit dihydroorotic acid dehydrogenase (DHO-DH), resulting in a decrease of the pyrimidine de novo synthesis. The drug was administered i.p. to tumor-bearing nude mice, once a day, during 5 days at a maximum tolerated dose of 50 mg/kg/day. Statistically significant growth delaying effects were observed in 4 out of 5 lines tested. In 3 of these lines the effect was moderate and short lasting, whereas in one line (HNX-LP) tumor growth rate was totally inhibited for a 17-day period. In this line, Brequinar sodium was superior to 5 drugs known to be active in HNSCC patients. In two tumor lines DHO-DH activity could be measured and the results are in agreement with the concept that there is a relation between Brequinar sodium sensitivity and enzyme activity.",
keywords = "brequinar sodium, head and neck cancer, pyrimidine de novo, squamous cell carcinoma, xenografts",
author = "Braakhuis, {B. J.M.} and {van Dongen}, {G. A.M.S.} and Peters, {G. J.} and {van Walsum}, M. and Snow, {G. B.}",
year = "1990",
month = "1",
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doi = "10.1016/0304-3835(90)90149-R",
language = "English",
volume = "49",
pages = "133--137",
journal = "Cancer Letters",
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Antitumor activity of brequinar sodium (Dup-785) against human head and neck squanmous cell carcinoma xenografts. / Braakhuis, B. J.M.; van Dongen, G. A.M.S.; Peters, G. J.; van Walsum, M.; Snow, G. B.

In: Cancer Letters, Vol. 49, No. 2, 01.01.1990, p. 133-137.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Braakhuis, B. J.M.

AU - van Dongen, G. A.M.S.

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AU - van Walsum, M.

AU - Snow, G. B.

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AB - The effect of Brequinar sodium on the growth of xenografts established from head and neck squamous cell carcinomas (HNSCC) was assessed. Brequinar sodium is a novel drug, known to inhibit dihydroorotic acid dehydrogenase (DHO-DH), resulting in a decrease of the pyrimidine de novo synthesis. The drug was administered i.p. to tumor-bearing nude mice, once a day, during 5 days at a maximum tolerated dose of 50 mg/kg/day. Statistically significant growth delaying effects were observed in 4 out of 5 lines tested. In 3 of these lines the effect was moderate and short lasting, whereas in one line (HNX-LP) tumor growth rate was totally inhibited for a 17-day period. In this line, Brequinar sodium was superior to 5 drugs known to be active in HNSCC patients. In two tumor lines DHO-DH activity could be measured and the results are in agreement with the concept that there is a relation between Brequinar sodium sensitivity and enzyme activity.

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