Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma.

Reduction in the mRNA and protein expression of lipocalin-like prostaglandin D(2) (PGD(2)) synthase (PGDS), the main arachidonic acid metabolite produced in neurons and glial cells of the central nervous system, is a significant biological event involved in the malignant progression of astrocytomas and is predictive of poor survival. In vitro, the addition of the main PGDS metabolite, PGD(2), to A172 glioblastoma cells devoid of PGDS resulted in antiproliferative activity and cell death. In vitro PGD(2) substitution also enhanced the efficacy of cyclo-oxygenase-2 inhibitors. This finding has exciting implications for early interventional efforts for the grade 2 and 3 astrocytomas.

Resistance to amoebic gill disease (AGD) is characterised by the transcriptional dysregulation of immune and cell cycle pathways.

Amoebic gill disease (AGD) is a parasite-mediated proliferative gill disease capable of affecting a range of teleost hosts. While a moderate heritability for AGD resistance in Atlantic salmon has been reported previously, the mechanisms by which individuals resist the proliferative effects remain poorly understood. To gain more knowledge of this commercially important trait, we compared gill transcriptomes of two groups of Atlantic salmon, one designated putatively resistant, and one designated putatively susceptible to AGD. Utilising a 17k Atlantic salmon cDNA microarray we identified 196 transcripts that were differentially expressed between the two groups. Expression of 11 transcripts were further examined with real-time quantitative RT-PCR (qPCR) in the AGD-resistant and AGD-susceptible animals, as well as non-infected naïve fish. Gene expression determined by qPCR was in strong agreement with the microarray analysis. A large number of differentially expressed genes were involved in immune and cell cycle responses. Resistant individuals displayed significantly higher expression of genes involved in adaptive immunity and negative regulation of the cell cycle. In contrast, AGD-susceptible individuals showed higher expression of acute phase proteins and positive regulators of the cell cycle. Combined with the gill histopathology, our results suggest AGD resistance is acquired rather than innately present, and that this resistance is for the most part associated with the dysregulation of immune and cell cycle pathways.

Transcriptome analyses of amoebic gill disease-affected Atlantic salmon (Salmo salar) tissues reveal localized host gene suppression.

The transcriptome response of Atlantic salmon (Salmo salar) displaying advanced stages of amoebic gill disease (AGD) was investigated. Naïve smolt were challenged with AGD for 19 days, at which time all fish were euthanized and their severity of infection quantified through histopathological scoring. Gene expression profiles were compared between heavily infected and naïve individuals using a 17 K Atlantic salmon cDNA microarray with real-time quantitative RT-PCR (qPCR) verification. Expression profiles were examined in the gill, anterior kidney, and liver. Twenty-seven transcripts were significantly differentially expressed within the gill; 20 of these transcripts were down-regulated in the AGD-affected individuals compared with naïve individuals. In contrast, only nine transcripts were significantly differentially expressed within the anterior kidney and five within the liver. Again the majority of these transcripts were down-regulated within the diseased individuals. A down-regulation of transcripts involved in apoptosis (procathepsin L, cathepsin H precursor, and cystatin B) was observed in AGD-affected Atlantic salmon. Four transcripts encoding genes with antioxidant properties also were down-regulated in AGD-affected gill tissue according to qPCR analysis. The most up-regulated transcript within the gill was an unknown expressed sequence tag (EST) whose expression was 218-fold (+/- SE 66) higher within the AGD affected gill tissue. Our results suggest that Atlantic salmon experiencing advanced stages of AGD demonstrate general down-regulation of gene expression, which is most pronounced within the gill. We propose that this general gene suppression is parasite-mediated, thus allowing the parasite to withstand or ameliorate the host response.

IQGAP1 and IGFBP2: valuable biomarkers for determining prognosis in glioma patients.

Clinical treatment decisions and the survival outcomes of patients with gliomas are directly impacted by accurate tumor classification. New and more reliable prognostic markers are needed to better identify the variable duration of survival among histologically defined glioma grades. Microarray expression analysis and immunohistochemistry were used to identify biomarkers associated with gliomas with more aggressive biologic behaviors. The protein expression of IQGAP1 and IGFBP2, when used in conjunction with the World Health Organization grading system, readily identified and defined a subgroup of patients with grade III gliomas whose prognosis was poor. In addition, in patients with glioblastoma multiforme, in whom IQGAP1 and IGFBP2 were absent, long-term survival of more than 3 years was observed. The use of these markers confirmed a nonuniform distribution of survival in those with World Health Organization grade III and IV tumors. Thus, IQGAP1 and IGFBP2 immunostaining supplements current histologic grading by offering additional prognostic and predictive information.