Requirement for YAP1 signaling in myxoid liposarcoma

Myxoid liposarcomas (MLS), malignant tumors of adipocyte origin, are driven by the FUS-DDIT3 fusion gene encoding an aberrant transcription factor. The mechanisms whereby FUS-DDIT3 mediates sarcomagenesis are incompletely understood, and strategies to selectively target MLS cells remain elusive. Here we show, using an unbiased functional genomic approach, that FUS-DDIT3-expressing mesenchymal stem cells and MLS cell lines are dependent on YAP1, a transcriptional co-activator and central effector of the Hippo pathway involved in tissue growth and tumorigenesis, and that increased YAP1 activity is a hallmark of human MLS Mechanistically, FUS-DDIT3 promotes YAP1 expression, nuclear localization, and transcriptional activity and physically associates with YAP1 in the nucleus of MLS cells. Pharmacologic inhibition of YAP1 activity impairs the growth of MLS cells in vitro and in vivo These findings identify overactive YAP1 signaling as unifying feature of MLS development that could represent a novel target for therapeutic intervention

NKX3.1 immunohistochemistry and methylome profiling in mesenchymal chondrosarcoma: additional diagnostic value for a well-defined disease?

Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive tumour of soft tissue and bone that is defined by an underlying and highly specific fusion transcript involving HEY1 and NCOA2. Histologically, the tumours show a biphasic appearance consisting of an undifferentiated blue and round cell component as well as islands of highly differentiated cartilage. Particularly in core needle biopsies, the chondromatous component can be missed and the non-specific morphology and immunophenotype of the round cell component can cause diagnostic challenges. We applied NKX3.1 immunohistochemistry which was recently reported as a highly specific marker as well as methylome and copy number profiling to a set of 45 well characterised MCS cases to evaluate their potential diagnostic value. Methylome profiling revealed a highly distinct cluster for MCS. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. NKX3.1 immunohistochemistry showed positivity in 36% of tumours, the majority of which was rather focal and weak. Taken together, NKX3.1 expression showed a low sensitivity but a high specificity in our analysis. Methylome profiling on the other hand represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. Furthermore, it can aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available

Modification of Fe-B based metallic glasses using swift heavy ions

We report on small-angle x-ray scattering (SAXS) measurements of amorphous Fe80B20, Fe85B15, Fe 81B135Si35C2, and Fe 40Ni40B20 metallic alloys irradiated with 11.1 MeV/u 132Xe, 152Sm, 197Au, and 8.2 MeV/u 238U ions. SAXS experiments are nondestructive an

Multimodal imaging techniques to evaluate the anticancer effect of cold atmospheric pressure plasma

Background: Skin cancer is the most frequent cancer worldwide and is divided into non-melanoma skin cancer, including basal cell carcinoma, as well as squamous cell carcinoma (SCC) and malignant melanoma (MM). Methods: This study evaluates the effects of cold atmospheric pressure plasma (CAP) on SCC and MM in vivo, employing a comprehensive approach using multi-modal imaging techniques. Longitudinal MR and PET/CT imaging were performed to determine the anatomic and metabolic tumour volume over three‐weeks in vivo. Additionally, the formation of reactive species after CAP treatment was assessed by non‐invasive chemiluminescence imaging of L‐012. Histological analysis and immunohistochemical staining for Ki‐67, ApopTag®, F4/80, CAE, and CD31, as well as protein expression of PCNA, caspase‐3 and cleaved‐caspase‐3, were performed to study proliferation, apoptosis, inflammation, and angiogenesis in CAP‐treated tumours. Results: As the main result, multimodal in vivo imaging revealed a substantial reduction in tumour growth and an increase in reactive species after CAP treatment, in comparison to untreated tu-mours. In contrast, neither the markers for apoptosis, nor the metabolic activity of both tumour entities was affected by CAP. Conclusions: These findings propose CAP as a potential adjuvant therapy option to established standard therapies of skin cancer

Richard Löwenherz im Museum : Menschen und Objekte in Bewegung

Irgendwo in unserem sogenannten Allgemeinwissen über das Mittelalter ist auch die Vorstellung verankert, dass das Leben früher ruhiger, gemütlicher und nicht so hektisch war wie heute. Früher, als die Welt noch ‚normal’ war, hatten die meisten Menschen einen festen Lebensmittelpunkt, waren fest verwurzelt in einer Gemeinschaft und verließen ihre Heimat nur dann, wenn es sich gar nicht vermeiden lies. Nur wenige – nämlich die besonders Überprivilegierten und die besonders Unterprivilegierten -, also die, die es sich leisten konnten oder die, die dazu gezwungen wurden, waren unterwegs. Alle anderen blieben ein Leben lang zuhause, an dem Ort, an dem sie ihren festen Lebensmittelpunkt hatten. Soweit unser intuitives Vorwissen darüber, wie es früher, also auch schon im Mittelalter, gewesen sein muss. Dieses mehr ‚gefühlte’ als wissenschaftlich erwiesene Vorwissen haben wir im Rahmen eines Hauptseminars zur Geschichte des Mittelalters im Herbst 2017 gründlich hinterfragt. Ausgangspunkt war die Ausstellung „Richard Löwenherz“, die im September am Historischen Museum der Pfalz in Speyer eröffnet wurde. Ein Seminar zum Thema führte uns auf die Spuren der im Museum gezeigten Objekte, von dort auf die Spuren der Menschen im Umfeld des berühmten Königs von England

Sarcoma treatment in the era of molecular medicine

Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult-to-treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.Peer reviewe

Advances in understanding of swift heavy-ion tracks in complex ceramics

Tracks produced by swift heavy ions in ceramics are of interest for fundamental science as well as for applications covering different fields such as nanotechnology or fission-track dating of minerals. In the case of pyrochlores with general formula A(2)B(2)O(7), the track structure and radiation sensitivity show a clear dependence on the composition. Ion irradiated Gd2Zr2O7, e.g., retains its crystallinity while amorphous tracks are produced in Gd2Ti2O7. Tracks in Ti-containing compositions have a complex morphology consisting of an amorphous core surrounded by a shell of a disordered, defect-fluorite phase. The size of the amorphous core decreases with decreasing energy loss and with increasing Zr content, while the shell thickness seems to be similar over a wide range of energy loss values. The large data set and the complex track structure has made pyrochlore an interesting model system for a general theoretical description of track formation including thermal spike calculations (providing the spatial and temporal evolution of temperature around the ion trajectory) and molecular dynamics (MD) simulations (describing the response of the atomic system). Recent MD advances consider the sudden temperature increase by inserting data from the thermal spike. The combination allows the reproduction of the core-shell track characteristic and sheds light on the early stages of track formation including recrystallization of the molten material produced by the thermal spike. (C) 2014 Elsevier Ltd. All rights reserved

Investigation of initial stage of chemical etching of ion tracks in polycarbonate

International audienceChemical track etching and the growth of nanochannels in ion-irradiated polycarbonate foils were investigated by loss of weight measurements and IR-spectroscopy. The data provided by both methods are in good agreement and allow us to shed light on the early stage of pore formation including times where the breakthrough of the pores has not yet occurred. Clear evidence is shown that the pore growth as a function of etching time depends on the irradiation fluence. For fixed etching parameters, foils containing 7 X 109 tracks/cm2 exhibit much smaller pores than samples with 2 X 108 tracks/cm2. This effect is independent of the etching temperature and appears for irradiations with Pb ions as well as for Ca–ion tracks sensitized by UV exposure. Model calculations for different etching times and fluences show that the data for low track densities can be fitted quite well by describing the radial etching rate by the track etch rate changing into the bulk etch rate with a Gaussian-shaped transition

Sputtering yield of amorphous 13C thin films under swift heavy-ion irradiation

The sputtering yield of carbon was measured in the electronic energy loss regime by 194-MeV Au ions irradiation. Due to the overall surface contamination with hydrocarbons, the determination of sputtering yields of carbon materials is quite challenging. To separate carbon omnipresent on most surfaces from sputtered carbon, we used a carbon target consisting of 86% of 13C isotope. By measuring the thickness decrease of the thin 13C film by means of high resolution online Elastic Recoil Detection Analysis (ERDA), a sputtering yield of 49 ± 15 of 13C per Au ion was found. Simultaneously with the sputter process, the 12C content of the target increased probably due to beam-induced bond breaking of hydrocarbons attached to the surface. Our experimental results are analyzed by calculations based on the two-temperature thermal spike model