Background Intrinsic or acquired resistance to HER2-targeted therapy is often a problem when small molecule tyrosine kinase inhibitors or antibodies are used to treat patients with HER2 positive breast cancer. Therefore, the identification of new targets and therapies for this patient group is warranted. Activated choline metabolism, characterized by elevated levels of choline-containing compounds, has been previously reported in breast cancer. The glycerophosphodiesterase EDI3 (GPCPD1), which hydrolyses glycerophosphocholine to choline and glycerol-3-phosphate, directly influences choline and phospholipid metabolism, and has been linked to cancer-relevant phenotypes in vitro. While the importance of choline metabolism has been addressed in breast cancer, the role of EDI3 in this cancer type has not been explored. Methods EDI3 mRNA and protein expression in human breast cancer tissue were investigated using publicly-available Affymetrix gene expression microarray datasets (n = 540) and with immunohistochemistry on a tissue microarray (n = 265), respectively. A panel of breast cancer cell lines of different molecular subtypes were used to investigate expression and activity of EDI3 in vitro. To determine whether EDI3 expression is regulated by HER2 signalling, the effect of pharmacological inhibition and siRNA silencing of HER2, as well as the influence of inhibiting key components of signalling cascades downstream of HER2 were studied. Finally, the influence of silencing and pharmacologically inhibiting EDI3 on viability was investigated in vitro and on tumour growth in vivo. Results In the present study, we show that EDI3 expression is highest in ER-HER2 + human breast tumours, and both expression and activity were also highest in ER-HER2 + breast cancer cell lines. Silencing HER2 using siRNA, as well as inhibiting HER2 signalling with lapatinib decreased EDI3 expression. Pathways downstream of PI3K/Akt/mTOR and GSK3β, and transcription factors, including HIF1α, CREB and STAT3 were identified as relevant in regulating EDI3 expression. Silencing EDI3 preferentially decreased cell viability in the ER-HER2 + cells. Furthermore, silencing or pharmacologically inhibiting EDI3 using dipyridamole in ER-HER2 + cells resistant to HER2-targeted therapy decreased cell viability in vitro and tumour growth in vivo. Conclusions Our results indicate that EDI3 may be a potential novel therapeutic target in patients with HER2-targeted therapy-resistant ER-HER2 + breast cancer that should be further explored.

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Interest in environmental-pollutant-induced oxidative stress and knowledge of the interactions between reactive oxygen species and cellular systems have increased in toxicology and microbial ecology considerably in recent decades. These reactive oxidants are produced by a variety of environmental sources: ionizing radiations, ultraviolet light, redox cycling drugs, hyperoxia, ischemia and redox-active xenobiotics or during metabolism of environmental pollutants, such as heavy metals in mining industries, dyes in wastewater of textile industries, pesticides and polycyclic hydrocarbons, i.e. foreign materials. In this study, the effect of dye on the antioxidative defence system of Phanerochaete chrysosporium was investigated, and we showed the ability of Phanerochaete chrysosporium to antioxidative response and defence system exposed to Astrazone Red FBL. Catalase, glutathione reductase, glutathione s-transferase activities and level of glutathione decreased, depending on the period of growth in each exposure to low and high concentration group (20 and 50 ppm) compared with the control group.

The toxic effects of an acetamiprid-based insecticide (ABI) on Gambusia holbrooki were evaluated after 24 and 96-h exposure periods. The 24 and 96-h median lethal concentration (LC 50) values of ABI were determined as 75.9 and 42.2 mg/L active ingredient (AI)/L, respectively. In addition, the activity of five biochemical marker enzymes, including glutathione S-transferase (GST), glutathione reductase (GR), carboxylesterase (CaE), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) was measured after 24 and 96-h exposure to three different concentrations of the ABI to evaluate its sublethal effects. The acetamiprid concentrations in the exposure media were measured using liquid chromatographytandem mass spectrometry. Our results showed that GST and LDH activities were increased and there were concentration-dependent changes in the integrated biomarker response (IBR) indexes after 24-h ABI exposure. However, the examined biomarkers were not useful for examining the effects of the ABI exposure for 96-h exposure periods, even at the highest concentration.

In this study, 48, 72 and 96 hours LC 50 values were determined in order to investigate the acute toxic effect of acetamiprite and imidaclopride on Gammarus kischineffensis from neonicotinoid pesticides, an important class of organic xenobiotics.At the dose interval used; LC 50 value for acetamiprid was 1.687 and 0.517 μg L-1 for 72 and 96 hours, respectively; LC 50 values at 48, 72 and 96 hours for imdacloprid were determined as 9764.4, 4546.7 and 1560.9 μg L-1 .