A phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumours

Anthracyclines are widely used in paediatric oncology, but their use is limited by the risk of cumulative cardiac toxicity. Encapsulating anthracyclines in liposomes may reduce cardiac toxicity and possibly increase drug availability to tumours. A phase I study in paediatric patients was designed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) after a single course of liposomal daunorubicin, ‘DaunoXome', as a 1 h infusion on day 1 of a 21 day cycle. Patients were stratified into two groups according to prior treatment: Group A (conventional) and group B (heavily pretreated patients). Dose limiting toxicity was expected to be haematological, and a two-step escalation was planned, with and without G-CSF support. Pharmacokinetic studies were carried out in parallel. In all, 48 patients aged from 1 to 18 years were treated. Dose limiting toxicity was neutropenia for both groups. Maximum tolerated dose was defined as 155 mg m−2 for Group A and 100 mg m−2 for Group B. The second phase with G-CSF was interrupted because of evidence of cumulative cardiac toxicity. Cardiac toxicity was reported in a total of 15 patients in this study. DaunoXome shares the early cardiotoxicity of conventional anthracyclines in paediatric oncology. This study has successfully defined a haematological MTD for DaunoXome, but the significance of this is limited given the concerns of delayed cardiac toxicity. The importance of longer-term follow-up in patients enrolled into phase I studies has been underestimated previously, and may lead to an under-recognition of important adverse events

Application of SSR markers in the construction of Australian barley genetic maps

Simple sequence repeat ( SSR) or microsatellite markers were examined for polymorphisms among the parents of 12 barley mapping populations. Of 259 SSRs screened, 149 were mapped on 1 or more of the 12 doubled haploid populations studied. The relative genetic positions of the 149 mapped SSR markers on Australian varieties are presented in the form of a consensus map. A database was created based on the results of screenings of barley varieties with a series of SSR markers. Details of the markers are at: http:// www. scu. edu. au/ research/ cpcg/ Barley/ index. php. A procedure is suggested for mapping new populations with microsatellites using this information and information available on other databases. These 12 populations have been mapped with SSR markers that act as ' anchors' for other types of genetic markers and for traits of interest. Some challenges in mapping SSRs were detailed. Multi- locus markers can cause confusion since one marker can map at different locations. Polymorphisms should be confirmed in new mapping varieties since some variation of allele size is seen in different sources of varieties of the same name, possibly due to differences in sources of germplasm. Lack of standardisation between laboratories or between analytical systems may also lead to differences in called allele sizes. SSRs proved to be adaptable to several technologies and economical, providing a preferred marker system for mapping new barley populations and to ' anchor' other types of markers

A genetic map of 1,000 SSR and DArT markers in a wide barley cross

The original publication can be found at www.springerlink.comA high-density genetic map was developed from an F1-derived doubled haploid population generated from a cross between cultivated barley (Hordeum vulgare) and the subspecies H. vulgare ssp. spontaneum. The map comprises 1,000 loci, amplified using 536 SSR (558 loci) and 442 DArT markers. Of the SSRs, 149 markers (153 loci) were derived from barley ESTs, and 7 from wheat ESTs. A high level of polymorphism (∼70%) was observed, which facilitated the mapping of 197 SSRs for which genetic assignments had not been previously reported. Comparison with a published composite map showed a high level of co-linearity and telomeric coverage on all seven chromosomes. This map provides access to previously unmapped SSRs, improved genome coverage due to the integration of DArT and EST-SSRs and overcomes locus order issues of composite maps constructed from the alignment of several genetic maps