Monocomponent chemoembolization in oral and oropharyngeal cancer using an aqueous crystal suspension of cisplatin.

Intensification of intra-arterial chemotherapy with high-dose cisplatin and concomitant reduction of toxicity under the conditions of the head and neck was aimed at by combination of antineoplastic activity and embolizing effect in the same pharmacon. A cisplatin suspension in normal saline (5 mg in 1 ml) with precipitation of microembolizing cisplatin crystals was prepared. No additional pharmacons. Cisplatin dosage was 150 mg m(-2), maximum absolute dose 300 mg, maximum amount of fluid 60 ml. Thirty patients (UICC-Classification of tumours: I/2 patients, II/6, III/2; IV/20) were treated in a neoadjuvant setting with superselective chemoembolization using the cisplatin suspension. A control group (n=30) with the same tumour and nodal staging was treated with a usual cisplatin solution (150 mg m(-2) dissolved in 500 ml saline). In both groups, parallel intravenous infusion of sodium thiosulphate (9 g m(-2)). Endpoints were toxicity and response. Continuation of treatment by surgery or radiation. Overall remission was 70% in the study group and 46.7% in the control group after one cycle respectively. Systemic side-effects were very low (grade I WHO) in both groups. Side-effects were found to be similar to post-embolization syndrome (swelling, mild to moderate pain, leucocytosis without fever) in the study group. Chemoembolization in the head and neck area can be carried out routinely using this method.

Purification, partial amino acid sequence and structure of the product of raucaffricine-O-beta-D-glucosidase from plant cell cultures of Rauwolfia serpentina.

Plant cell suspension cultures of Rauwolfia produce within 1 week approximately 250 nkat/l of raucaffricine-O-beta-D-glucosidase. A five step procedure using anion exchange chromatography, chromatography on hydroxylapatite, gel filtration and FPLC-chromatography on Mono Q and Mono P delivered in a yield of 0.9% approximately 1200-fold enriched glucosidase. A short protocol employing DEAE sepharose, TSK 55 S gel chromatography and purification on Mono Q gave a 5% recovery of glucosidase which was 340-fold enriched. SDS-PAGE showed a Mr for the enzyme of 61 kDa. The enzyme is not glycosylated. Structural investigation of the enzyme product, vomilenine, demonstrated that the alkaloid exists in aqueous solutions in an equilibrium of 21(R)- and 21(S)-vomilenine in a ratio of 3.4:1. Proteolysis of the pure enzyme with endoproteinase Lys C revealed six peptide fragments with 6-24 amino acids which were sequenced. The two largest fragments showed sequences, of which the motif Val-Thr-Glu-Asn-Gly is typical for beta-glucosidases. Sequence alignment of these fragments demonstrated high homologies to linamarase from Manihot esculenta (81% identity) or to beta-glucosidase from Prunus avium (79% identity). Raucaffricine-O-beta-D-glucosidase seems to be a new member of the family 1 of glycosyl hydrolases.