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Erschienen in: Journal of Neuro-Oncology 1/2018

06.04.2018 | Laboratory Investigation

Evidence for intrathecal sodium butyrate as a novel option for leptomeningeal metastasis

verfasst von: Hidemitsu Nakagawa, Yoshihiro Yui, Satoru Sasagawa, Kazuyuki Itoh

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2018

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Abstract

Introduction

The prognosis for leptomeningeal metastasis (LM) remains extremely poor regardless of intrathecal chemotherapy with various drugs, and thus, new treatments are necessary. Butyrate is an endogenous 4-carbon saturated fatty acid, has been investigated as an anti-tumor agent because of its multiple suppressive effects on several tumors. In this study, we investigated the cellular basis of sodium butyrate (SB), a sodium salt compound of butyrate, in vitro and evaluated the clinical potential of intrathecal SB administration for LM in vivo.

Methods

We examined SB’s effects on Walker 256 rat mammary tumor cells with regard to cytotoxicity, cell morphology, colony formation, migration, and invasion. We also examined SB’s neurotoxicity for primary neurons and primary astrocytes. We finally evaluated the potency of continuous intrathecal SB administration in rats with intrathecally transplanted breast tumors as an LM model.

Results

Physiological SB concentrations (2–4 mM) induced growth suppression, morphological changes, and inhibition of migration and invasion, but did not exhibit neurotoxic effects on primary neurons and astrocytes. Continuous intrathecal SB administration in a rat LM model significantly increased survival periods with little neurotoxicity.

Conclusions

Continuous intrathecal SB administration significantly improved prognoses in a rat LM model, which suggests that SB is a promising therapy for LM.
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Metadaten
Titel
Evidence for intrathecal sodium butyrate as a novel option for leptomeningeal metastasis
verfasst von
Hidemitsu Nakagawa
Yoshihiro Yui
Satoru Sasagawa
Kazuyuki Itoh
Publikationsdatum
06.04.2018
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 1/2018
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-018-2852-2

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