| Autor: |
Kieslich, M., Schwabe, D., Cinatl Jr., J., Driever, P. Hernáiz |
| Předmět: |
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| Zdroj: |
Pediatric Hematology & Oncology; Jan/Feb2003, Vol. 20 Issue 1, p15, 8p |
| Abstrakt: |
Differentiation induction is a distinct concept in the treatment of malignant diseases, considering that malignant cells share many features with immature progenitor cells that are capable of terminal differentiation. Treatment of tumor cells with short chain fatty acids leads to cytostasis and differentiation induction both in vitro and in vivo. Similarly, short-chain fatty acid treatment of erythroid progenitors in vitro and in vivo induces cellular differentiation resulting in γ-globin i.e., fetal hemoglobin synthesis. Valproic acid (VPA ) is a branched-chain fattty acid that is able to inhibit growth of human and rodent tumor cells and to induce a mature phenotype. The antitumoral effects observed in preclinical studies were reached at concentrations that are readily achieved in patients treated with VPA for epilepsy. Hypothesizing that anticonvulsive VPA levels may be used for antitumoral differentiation induction therapy of pediatric malignant tumors, the authors studied fetal hemoglobin-inducing capacity of VPA in children treated with VPA for epilepsy. Fetal hemoglobin was significantly increased in 30 children with epilepsy treated with VPA monotherapy for at least 3 months when compared to untreated control patients. Furthermore, fetal hemoglobin levels correlated with VPA serum levels. The study confirms the dose-dependent stimulating effect of VPA on fetal hemoglobin ,synthesis at anticonvulsive doses. The results suggest that nontoxic VPA levels reached in pediatric epilepsy patients should be capable of inducing cellular differentiation pediatric malignant tumors for therapeutic purposes. Broad clinical experience with VPA and its low toxicity further encourage the evaluation of VPA in pediatric oncology for differentiation induction therapy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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