Irinotecan changes gene expression in the small intestine of the rat with breast cancer

The original publication can be found at www.springerlink.comPurpose The aetiology of mucositis is complex involving change in gene expression, altered apoptosis and interaction between epithelial and subepithelial compartments. This is the first investigation using microarray to assess chemotherapy-induced changes in the gut. The aims of this study were to identify genes that are altered by irinotecan, to determine how these genes contribute to apoptosis and to identify any potential gene families and pathways that are important for mucositis development. Methods Tumour-bearing female dark Agouti rats were administered twice with 150 mg/kg of irinotecan and killed 6 h after the final dose. Jejunal tissue was harvested and RNA was isolated. cDNA was synthesised and purified, prior to hybridisation and microarray analysis. A 5-K oligo clone set was used to investigate gene expression. Results from the microarray were quantified using RT-PCR. Results Many genes were significantly up- or down-regulated by irinotecan. In particular, multiple genes implicated in the mitogen-activated protein kinase (MAPK) signalling pathway were differentially regulated following treatment. These included interleukin 1 receptor, caspases, protein kinase C and dual-specificity phosphatase 6. RT-PCR was used to confirm effects of irinotecan on caspase-1 expression in jejunal tissue and was significantly increased 6 h after treatment with irinotecan. Conclusions This study has identified MAP kinase signalling as being involved with irinotecan-induced intestinal damage and confirms previous findings with radiation-induced oral mucosal damage, which also implicated this pathway. Microarrays are emerging as a valuable tool in mucositis research by linking such findings. The common pathway of chemotherapy- and radiotherapy-induced damage, which utilises the caspase-cascade, may be a useful target to prevent apoptosis following cancer treatment.Joanne M. Bowen, Rachel J. Gibson, Adrian G. Cummins, Anna Tyskin and Dorothy M. K. Keef

Potential of DIVA vaccines for Fish

The expanding aquaculture industry continues to encounter major challenges from highly contagious viruses. Control and eradication measures for lethal and economically damaging notifiable viral diseases involve ‘stamping out’ policies and surveillance strategies. Mass-culling of stock and restricted movement of fish and fish products, used to control the spread of notifiable diseases, has considerable impacts on the trade of fish products. Although effective, these measures are expensive and ethically complex and could possibly be reduced by emulating innovative vaccination strategies used by the terrestrial livestock industry. DIVA (differentiating infected from vaccinated animal) strategies provide a basis to vaccinate and contain disease outbreaks without compromising ‘disease-free’ status, as antibodies induced during infection can be used to distinguish from those induced by vaccination. The potential and feasibility of DIVA vaccination in aquaculture is explored here with reference to DIVA strategies applied in higher vertebrates. Three economically important notifiable viruses, causing major problems in three different cultured fish industries, are considered. The increased availability and application of sophisticated biotechnology tools has enabled improved prophylaxis and serological diagnosis for control of viral haemorrhagic septicaemia in rainbow trout, infectious salmon anaemia in Atlantic salmon and koi herpesvirus disease in carp. Improving the specificity of serological diagnostics in aquaculture in conjunction with suitable vaccines could enable the application of DIVA strategies, but the immunological variation between different fish species and contrasting pathobiological characteristics of different viruses determines the feasibility and potential of such DIVA approaches for aquaculture industries