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
Mar 19, 2014·Chemistry & Biodiversity·Anisa FarhatRalf Kinscherf
Sep 14, 2015·Chemistry & Biodiversity·Vanessa Ottenhaus, Helmut Rosemeyer
Aug 19, 2000·Antiviral Chemistry & Chemotherapy·H RaslovaM Kudelova
Jul 19, 2001·Anti-cancer Drugs·M W SaifJ L Grem
Nov 8, 2002·Journal of Chemotherapy·Y ShibamotoS Nishimoto
Aug 12, 2005·Neurosurgery·Hidemitsu NakagawaYuji Fukushima
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
Mar 5, 2014·Chemistry & Biodiversity·Edith MaleckiHelmut Rosemeyer
Aug 23, 2008·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yasuhiro TsumeGordon L Amidon
Dec 12, 2013·Chemistry & Biodiversity·Edith MaleckiHelmut Rosemeyer
Aug 27, 2005·Molecular Cancer Research : MCR·Hidemitsu NakagawaKazuyuki Itoh
Apr 4, 2021·International Journal of Molecular Sciences·Chinatsu KurasakaAkira Sato
Jul 26, 2008·Molecular Pharmaceutics·Yasuhiro TsumeGordon L Amidon
Jan 18, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F FengT Wang
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