[In vivo study on intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) in meningeal dissemination of malignant tumor].
FdUrd was evaluated in vivo as a potential agent for intrathecal chemotherapy of meningeal carcinomatosis. Neurotoxicity was examined pathologically in normal mice after 4 consecutive intrathecal injections of FdUrd. Using mice models of meningeal carcinomatosis, antitumor activities were studied by evaluating survival time. Pathological examination showed none of the following abnormal findings: demyelination, degeneration and destruction of ependymal linings. FdUrd also had an effect on meningeal carcinomatosis of mice (203 glioma and MM46 transplantable ascitic mammary cancer). In causing FdUrd to exhibit its efficacy, it is necessary to take into consideration the balance between the activity of two key enzymes, thymidine phosphorylase (TPase) (anabolic enzyme) and thymidine kinase (TK) (metabolic enzyme), in tumor tissues as compared with their activity in normal tissues. TPase activity which results in conversion to 5-FU was much lower in malignant glioma and metastatic brain tumors compared with tumors in other extracranial organs. TPase activity in normal brain was much less than in normal tissues in extracranial organs and its activity in gray matter (cortex) was significantly lower than that in white matter. On the other hand, TK activity in malignant brain tumors was much less than that in extracranial organs, however, its activity in normal brain was almost equal to that in normal tissues in extracranial organs. These data obtained in vivo study showed FdUrd to be a possible agent for intrathecal chemotherapy.
Nakagawa
H
H
Department of Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Yamada
M
M
Fukushima
M
M
Shimizu
K
K
Ikenaka
K
K
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001921:Brain / Q000201:enzymology; D005467:Floxuridine / Q000008:administration & dosage* / Q000009:adverse effects; D007278:Injections, Spinal; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D013937:Thymidine Kinase / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D013939:Thymidine Phosphorylase; D013937:Thymidine Kinase