PMID: 9524089Apr 2, 1998Paper

In vitro study on intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for meningeal dissemination of malignant brain tumors

Journal of Neuro-oncology
M YamadaK Ikenaka

Abstract

We investigated 5-fluoro-2'-deoxyuridine (FdUrd) as a potential agent for intrathecal treatment of malignant brain tumors with meningeal dissemination. We examined the neurotoxicity of FdUrd in vitro using primary cultures of neurons from C57BL/6 mice (ED14). Tumoricidal activity was also studied in four glioma cell lines and one medulloblastoma cell line. In addition, thymidine phosphorylase (TPase) and thymidine kinase (TK), which are key enzymes for FdUrd metabolism, were measured in the cerebrospinal fluid (CSF) of 36 patients with brain tumors. The antitumor activity of FdUrd for murine glioma cells was approximately 20- to 200-fold higher than that of 5-fluorouracil (5-FU). Against human cell lines, it was 3- to 500-fold higher than that of 5-FU. The neurotoxic effect of FdUrd on cultured neurons was far less than that of 5-FU or 5-fluorouridine (FUrd). Cerebrospinal fluid contained no detectable thymidine phosphorylase in most patients with brain tumors. Several studies have indicated that FdUrd is rapidly converted to 5-FU in the presence of thymidine phosphorylase, so that a high dose of FdUrd must be administered to obtain good efficacy. However, a high dose FdUrd frequently cause severe toxicity. In contrast, the dat...Continue Reading

Citations

Oct 21, 2004·Anti-cancer Drugs·M Wasif SaifRobert B Diasio
Oct 27, 2009·Cancer Chemotherapy and Pharmacology·Sharon ConroyDavid Walker
Mar 28, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yasuhiro Tsume, Gordon L Amidon
Aug 23, 2008·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yasuhiro TsumeGordon L Amidon
Aug 27, 2005·Molecular Cancer Research : MCR·Hidemitsu NakagawaKazuyuki Itoh
Apr 4, 2021·International Journal of Molecular Sciences·Chinatsu KurasakaAkira Sato
Jun 15, 2021·Frontiers in Oncology·Wanyan WangJin Huang
Apr 1, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Yasuhiro TsumeGordon L Amidon

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