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Intrathecal or intracavitary administration of sodium butyrate
to treat neoplastic meningitis and malignant glioma Hidemitsu
Nakagawa
Osaka Medical Center for Cancer &
Cardiovascular Diseases, Osaka, Japan. E-mail: nakagawa-hi@mc.pref.osaka.jp
Purpose. Sodium butyrate is a naturally present four-carbon saturated fatty acid
that has usually been used for growth inhibition, promotion of differentiation
and gene translation in various kinds of tumor cells in vitro.
Clinical use of
this product for differentiation, apoptosis and inhibition of cell invasion has
been expected because of its high concentration presence in human intestinal
membrane as a metabolite of food.
However, its effect on tumor cells is
reversible and an effective tumoral concentration has not been obtained because
of its short half life of 6 minutes.
Therefore, continuous local administration
at an effective dose is needed.
The half life of sodium butyrate in
cerebrospinal fluid and the cavity of malignant glioma is supposed to be longer
than that after systemic administration.
Here, we evaluated the clinical
potential of intrathecal and intracavitary administration of sodium butyrate for
neoplastic meningitis and malignant glioma.
Experimental Design. We examined the cytotoxicity in vitro and in a rats
models of neoplastic meningitis receiving continuous intrathecal administration
and in a rat model of malignant brain tumor receiving continuous intratumoral
infusion.
Neurotoxicity was examined using a primary culture of ED14 neurons in
vitro and in normal rats receiving continuous intrathecal administration and
continuous brain infusion.
We also investigated the inhibitory effect of this
compound on tumor cell invasion in vitro using the Matrigel invasion assay and
in vivo using a rat meningeal carcinomatosis model employing mini-osmotic pump
perfusion.
Results. Sodium butyrate showed a good cytotoxic effect in vitro and in rat
neoplastic meningitis and rat brain tumor, minimal neurotoxicity in vitro and in
vivo, and also demonstrated a significant inhibitory effect on tumor cell
invasion in vitro (rat Walker 256 carcinoma & human A-172 glioblastoma
cells) and in vivo.
Conclusion. Continuous intrathecal or intracavitary administration of sodium
butyrate is suggested to be a promising therapeutic method for combination with
radiation therapy to treat neoplastic meningitis or malignant glioma.
Copyright © 2004 American Association for Cancer Research. All rights
reserved.
Source: http://aacr04.agora.com/planner/displayabstract.asp?presentationid=155
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