Description: Background: Progesterone receptors play a key role in the development of canine mammary tumours, and recent research has focussed on their possible value as therapeutic targets using antiprogestins. Cloning and sequencing of the progesterone receptor gene has shown that the receptor has two isoforms, A and B, transcribed from a single gene. Experimental studies in human breast cancer suggest that the differential expression of progesterone receptor isoforms has implications for hormone therapy responsiveness. This study examined the effects of the antiprogestin aglepristone on cell proliferation and mRNA expression of progesterone receptor isoforms A and B in mammary carcinomas in dogs treated with 20?mg/Kg of aglepristone (n?=?22) or vehicle (n?=?5) twice before surgery. Results: Formalin-fixed, paraffin-embedded tissue samples taken before and after treatment were used to analyse total progesterone receptor and both isoforms by RT-qPCR and Ki67 antigen labelling. Both total progesterone receptor and isoform A mRNA expression levels decreased after treatment with aglepristone. Furthermore, a significant decrease in the proliferation index (percentage of Ki67-labelled cells) was observed in progesterone-receptor positive and isoform-A positive tumours in aglepristone-treated dogs. Conclusions: These findings suggest that the antiproliferative effects of aglepristone in canine mammary carcinomas are mediated by progesterone receptor isoform A.

Description: © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in De Andres, E., Slater, D. A., Otero, J., Das, S., Navarro, F., & Straneo, F. Surface emergence of glacial plumes determined by fjord stratification. Cryosphere, 14(6), (2020): 1951-1969, doi:10.5194/tc-14-1951-2020.

Description: Meltwater and sediment-laden plumes at tidewater glaciers, resulting from the localized subglacial discharge of surface melt, influence submarine melting of the glacier and the delivery of nutrients to the fjord's surface waters. It is usually assumed that increased subglacial discharge will promote the surfacing of these plumes. Here, at a western Greenland tidewater glacier, we investigate the counterintuitive observation of a non-surfacing plume in July 2012 (a year of record surface melting) compared to the surfacing of the plume in July 2013 (an average melt year). We combine oceanographic observations, subglacial discharge estimates and an idealized plume model to explain the observed plumes' behavior and evaluate the relative impact of fjord stratification and subglacial discharge on plume dynamics. We find that increased fjord stratification prevented the plume from surfacing in 2012, show that the fjord was more stratified in 2012 due to increased freshwater content and speculate that this arose from an accumulation of ice sheet surface meltwater in the fjord in this record melt year. By developing theoretical scalings, we show that fjord stratification in general exerts a dominant control on plume vertical extent (and thus surface expression), so that studies using plume surface expression as a means of diagnosing variability in glacial processes should account for possible changes in stratification. We introduce the idea that, despite projections of increased surface melting over Greenland, the appearance of plumes at the fjord surface could in the future become less common if the increased freshwater acts to stratify fjords around the Greenland ice sheet. We discuss the implications of our findings for nutrient fluxes, trapping of atmospheric CO2 and the properties of water exported from Greenland's fjords.

Description: This research has been supported by the Ministerio de Educación, Cultura y Deporte (grant no. FPU14/04109), the National Science Foundation (grant no. 1418256), the Ministerio de Economía, Industria y Competitividad, Gobierno de España (grant no. CTM2017-84441-R), and the Horizon 2020 Research and Innovation Programme (grant no. 727890).