Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer

The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively. In contrast, loss of EPCAM defines clones arrested in a mesenchymal state, with concomitant suppression of tumorigenicity and metastatic potential. This dichotomy results from distinct clonal trajectories impacting global epigenetic programs that are determined by the interplay between human ZEB1 and its target GRHL2. Collectively, our results indicate that susceptibility to irreversible EMT restrains clonal propagation, whereas resistance to mesenchymal reprogramming sustains disease spread in multiple models of human metastatic breast cancer, including patient-derived cells in vivo

Lake ice detection in low-resolution optical satellite images

Monitoring and analyzing the (decreasing) trends in lake freezing provides important information for climate research. Multi-temporal satellite images are a natural data source to survey ice on lakes. In this paper, we describe a method for lake ice monitoring, which uses low spatial resolution (250 m–1000 m) satellite images to determine whether a lake is frozen or not. We report results on four selected lakes in Switzerland: Sihl, Sils, Silvaplana and St. Moritz. These lakes have different properties regarding area, altitude, surrounding topography and freezing frequency, describing cases of medium to high difficulty. Digitized Open Street Map (OSM) lake outlines are back-projected on to the image space after generalization. As a pre-processing step, the absolute geolocation error of the lake outlines is corrected by matching the projected outlines to the images. We define the lake ice detection as a two-class (frozen, non-frozen) semantic segmentation problem. Several spectral channels of the multi-spectral satellite data are used, both reflective and emissive (thermal). Only the cloud-free (clean) pixels which lie completely inside the lake are analyzed. The most useful channels to solve the problem are selected with xgboost and visual analysis of histograms of reference data, while the classification is done with non-linear support vector machine (SVM). We show experimentally that this straight-forward approach works well with both MODIS and VIIRS satellite imagery. Moreover, we show that the algorithm produces consistent results when tested on data from multiple winters.ISSN:1682-1750ISSN:2194-9034ISSN:1682-177

Probabilistic approach to cloud and snow detection on Advanced Very High Resolution Radiometer (AVHRR) imagery

Derivation of probability estimates complementary to geophysical data sets has gained special attention over the last years. Information about a confidence level of provided physical quantities is required to construct an error budget of higher-level products and to correctly interpret final results of a particular analysis. Regarding the generation of products based on satellite data a common input consists of a cloud mask which allows discrimination between surface and cloud signals. Further the surface information is divided between snow and snow-free components. At any step of this discrimination process a misclassification in a cloud/snow mask propagates to higher-level products and may alter their usability. Within this scope a novel probabilistic cloud mask (PCM) algorithm suited for the 1 km × 1 km Advanced Very High Resolution Radiometer (AVHRR) data is proposed which provides three types of probability estimates between: cloudy/clear-sky, cloudy/snow and clear-sky/snow conditions. As opposed to the majority of available techniques which are usually based on the decision-tree approach in the PCM algorithm all spectral, angular and ancillary information is used in a single step to retrieve probability estimates from the precomputed look-up tables (LUTs). Moreover, the issue of derivation of a single threshold value for a spectral test was overcome by the concept of multidimensional information space which is divided into small bins by an extensive set of intervals. The discrimination between snow and ice clouds and detection of broken, thin clouds was enhanced by means of the invariant coordinate system (ICS) transformation. The study area covers a wide range of environmental conditions spanning from Iceland through central Europe to northern parts of Africa which exhibit diverse difficulties for cloud/snow masking algorithms. The retrieved PCM cloud classification was compared to the Polar Platform System (PPS) version 2012 and Moderate Resolution Imaging Spectroradiometer (MODIS) collection 6 cloud masks, SYNOP (surface synoptic observations) weather reports, Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) vertical feature mask version 3 and to MODIS collection 5 snow mask. The outcomes of conducted analyses proved fine detection skills of the PCM method with results comparable to or better than the reference PPS algorithm

A Multisensor Approach to Global Retrievals of Land Surface Albedo

Satellite-based retrievals offer the most cost-effective way to comprehensively map the surface albedo of the Earth, a key variable for understanding the dynamics of radiative energy interactions in the atmosphere-surface system. Surface albedo retrievals have commonly been designed separately for each different spaceborne optical imager. Here, we introduce a novel type of processing framework that combines the data from two polar-orbiting optical imager families, the Advanced Very High-Resolution Radiometer (AVHRR) and Moderate Resolution Imaging Spectroradiometer (MODIS). The goal of the paper is to demonstrate that multisensor albedo retrievals can provide a significant reduction in the sampling time required for a robust and comprehensive surface albedo retrieval, without a major degradation in retrieval accuracy, as compared to state-of-the-art single-sensor retrievals. We evaluated the multisensor retrievals against reference in situ albedo measurements and compare them with existing datasets. The results show that global land surface albedo retrievals with a sampling period of 10 days can offer near-complete spatial coverage, with a retrieval bias mostly comparable to existing single sensor datasets, except for bright surfaces (deserts and snow) where the retrieval framework shows degraded performance because of atmospheric correction design compromises. A level difference is found between the single sensor datasets and the demonstrator developed here, pointing towards a need for further work in the atmospheric correction, particularly over bright surfaces, and inter-sensor radiance homogenization. The introduced framework is expandable to include other sensors in the future

Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer

The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively. In contrast, loss of EPCAM defines clones arrested in a mesenchymal state, with concomitant suppression of tumorigenicity and metastatic potential. This dichotomy results from distinct clonal trajectories impacting global epigenetic programs that are determined by the interplay between human ZEB1 and its target GRHL2. Collectively, our results indicate that susceptibility to irreversible EMT restrains clonal propagation, whereas resistance to mesenchymal reprogramming sustains disease spread in multiple models of human metastatic breast cancer, including patient-derived cells in vivo.ISSN:2666-3864ISSN:2211-124

Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue.

Fertility-preserving measures are becoming important for patients receiving oncological treatment. One method involves cryopreservation of ovarian tissue and transplanting it when treatment is completed. We report complications resulting from surgical and fertility medicine, and the results of procedures for the removal and transplantation of ovarian tissue carried out within the FertiProtekt network. A survey using a structured questionnaire was conducted among the FertiProtekt network centres between November 2015 and June 2016. The analysis included surgical techniques used to remove and transplant ovarian tissue, surgical complications and results. Laparoscopic removal and transplantation of ovarian tissue have a low risk of complications. Surgical complications occurred in three of the network's 1373 ovarian tissue removals (n = 1302) and transplantations (n = 71); two complications (0.2%) occurred during removal and one during transplantation. Menstruation resumed in 47 out of 58 women (81%) who underwent ovarian tissue transplantation. Hormonal activity occurred in 63.2% of transplantations with a follow-up of 6 months or over. Sixteen pregnancies occurred in 14 patients, with nine births. The risks and complications of removal and transplantation of ovarian tissue are similar to those of standard laparoscopy. These procedures are becoming standard for fertility protection in cancer patients

Concept Paper on the Technique of Cryopreservation, Removal and Transplantation of Ovarian Tissue for Fertility Preservation.

The cryopreservation of ovarian tissue with subsequent transplantation of the tissue represents an established method of fertility protection for female patients who have to undergo gonadotoxic therapy. The procedure can be performed at any point in the cycle and thus generally does not lead to any delay in oncological therapy. With the aid of this procedure, more than 130 births to date worldwide have been able to be recorded. The birth rate is currently approximately 30% and it can be assumed that this will increase through the further optimisation of the cryopreservation and surgical technique. The concept paper presented here is intended to provide guidance for managing cryopreservation and transplantation of ovarian tissue to German-speaking reproductive medicine centres