Children with relapsed malignant brain tumours have a poor prognosis despite intensive treatment including high-dose chemotherapy with stem cell rescue [1, 2]. Angiogenesis, the formation of new blood vessels, is an important component of normal physiological processes such as wound healing and development. Moreover, tumour growth and metastasis is closely related to formation of new blood vessels [3, 4]. Antiangiogenic therapy inhibits neovascularization, thereby inhibiting tumour progression indirectly [5]. The term metronomic chemotherapy refers to the chronic administration of chemotherapeutic agents at relatively low, minimally toxic doses, and without prolonged drug-free breaks. Beside the antiangiogenic effect, metronomic chemotherapy has been shown to modulate anti-tumoural immunity and has the ability to induce tumour dormancy [6]. The combination of agents used in our metronomic antiangiogenic therapy is based on a four-drug regimen (thalidomide, celecoxib, etoposide and cyclophosphamide) published by Kieran et al. in 2005 [7]. We augmented this regimen with bevacizumab, fenofibrate, and intrathecal therapy with the goal to improve progression-free survival for patients with recurrent or refractory CNS tumours for whom no curative therapy is available. We report on our experience with an antiangiogenic metronomic chemotherapy for paediatric patients with recurrent CNS tumours of different histologies.

Objectives Cimicifuga racemosa (Actaea racemosa, black cohosh) is used as an anti-inflammatory, antipyretic and analgesic remedy in traditional medicines. The present study focuses on the effects of C. racemosa root extracts on inducible nitric oxide synthase (iNOS) in lipopolysaccharide-stimulated murine macrophages (RAW 264.7).Methods C. racemosa rhizome and phosphate-buffered saline extracts were analysed for phenolcarboxylic acids and triterpene glycosides using an HPLC photodiode array/evaporative light-scattering detector system. iNOS was characterised by measurement of iNOS protein (immunoblotting), iNOS mRNA (semiquantitative competitive RT-PCR), nitric oxide production (nitrite levels) and nuclear translocation of nuclear factor-kappa B (p65 subunit) protein.Key findings Incubation of lipopolysaccharide-stimulated macrophages with aqueous C. racemosa extracts (0-6 mg/ml) inhibited nitrite accumulation in a concentration-dependent manner. C. racemosa extracts also reduced iNOS protein expression and iNOS mRNA levels in a dose-dependent manner. C. racemosa extracts did not significantly inhibit iNOS activity and did not affect nuclear translocation of nuclear factor-kappa B (p65 subunit) protein. Incubation with the extract was associated with a concentration-dependent reduction of interferon beta and interferon regulatory factor 1 mRNA. Among the triterpene glycosides, 23-epi-26-deoxyactein was identified as an active principle in C racemosa extracts.Conclusions Extracts from the roots of C racemosa inhibit nitric oxide production by reducing iNOS expression without affecting activity of the enzyme. This might contribute to the anti-inflammatory activities of C. racemosa.