Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215

Some brain tumours, such as glioblastomas express high levels of receptors for bombesin/gastrin releasing peptide. We investigated whether bombesin/gastrin releasing peptide receptors found in glioblastoma cell lines can be utilised for targeting of a cytotoxic bombesin analogue, AN-215 consisting of a potent derivative of doxorubicin, 2-pyrrolino-doxorubicin (AN-201) linked to a bombesin-like peptide carrier. This study reports the effect of AN-215 on the growth of U-87MG human glioblastomas xenografted into nude mice. High affinity binding of AN-215 to U-87MG tumours was characterised by an IC50 value of 4.0±0.1 nM, as determined by radioreceptor assays. mRNA analyses revealed the presence of mRNA for BN receptor subtypes 1 and 2. Treatment with AN-215 significantly (P<0.05) extended tumour doubling time from 4.54±0.2 days to 8.18±1.8 days and inhibited tumour growth as demonstrated by a 69.6% reduction in final tumour volume (P<0.001) and a 64.6% decrease in tumour weight as compared to controls. Cytotoxic radical AN-201 at the same dose was ineffective. The antitumour effect of AN-215 could be blocked by pretreatment with an excess of a bombesin antagonist, indicating that the action of this cytotoxic analogue is receptor-mediated. Our results suggest that patients with inoperable brain tumours such as malignant gliomas may benefit from targeted chemotherapy based on cytotoxic bombesin analogue AN-215

Predicting plant metal bioaccessibility at the historic Wheal Maid tailings lagoons, Cornwall, UK

Abandoned mine sites with their metal-rich substrates pose significant challenges to naturally colonizing plants. In this study, the abandoned Sn-Cu tailings lagoons at Wheal Maid (Cornwall, UK) have been investigated to establish the bioaccessibility of metals and metalloids (As, Cd, Cu, Pb, Sb, Zn) in exposed tailings and wastes using a new plant bioaccessibility test. Four main substrate types were sampled: (1) mine waste used to construct the lagoons, a relatively uncontaminated material with variable particle size; (2) granular capping material used in the upper lagoon to cover the tailings and relatively uncontaminated; (3) grey tailings a fine to medium grained material with visible sulfides and white secondary salts, extremely high in near-total Zn concentrations; and (4) marbled tailings a fine grained brown/red/yellow material with extremely high near-total As concentrations. The analytical quality of results produced by a new plant bioaccessibility test was monitored using blanks, spiked solutions and repeat analyses. The grey tailings had the highest bioaccessible metal and metalloid content. As this material oxidizes, it will release As, Cd, Cu, Sb, Zn and to a lesser extent Pb in a form which will be more available to plants. This will inevitably delay re-vegetation at the site. The new bioaccessibility test is recommended for sulfidic rocks and waste samples and should be employed at an early mine-life stage to allow appropriate waste classification and improve mine closure outcomes