Giant worm-shaped ESCRT scaffolds surround actin-independent integrin clusters.

Endosomal Sorting Complex Required for Transport (ESCRT) proteins can be transiently recruited to the plasma membrane for membrane repair and formation of extracellular vesicles. Here, we discovered micrometer-sized worm-shaped ESCRT structures that stably persist for multiple hours at the plasma membrane of macrophages, dendritic cells, and fibroblasts. These structures surround clusters of integrins and known cargoes of extracellular vesicles. The ESCRT structures are tightly connected to the cellular support and are left behind by the cells together with surrounding patches of membrane. The phospholipid composition is altered at the position of the ESCRT structures, and the actin cytoskeleton is locally degraded, which are hallmarks of membrane damage and extracellular vesicle formation. Disruption of actin polymerization increased the formation of the ESCRT structures and cell adhesion. The ESCRT structures were also present at plasma membrane contact sites with membrane-disrupting silica crystals. We propose that the ESCRT proteins are recruited to adhesion-induced membrane tears to induce extracellular shedding of the damaged membrane.

Adenocarcinoma of the ampulla of Vater metastasising into the right ventricle.

A 43-year-old woman, after resected adenocarcinoma of the ampulla of Vater, presented dyspnoea and beginning signs of right heart failure. Echocardiography revealed a mass within the right ventricle (RV) suspicious for a metastasis of the known adenocarcinoma. The decision for surgical resection was made by cardiovascular MR, which was able to delineate the infiltrative growth of a metastasis. An extensive resection had to be performed. Parts of the intraventricular septum as well as the tricuspid valve had to be resected. After six cycles of adjuvant systemic chemotherapy with gemcitabine and nab-paclitaxel, the patient had no macroscopic tumour recurrence. To our knowledge, this is the first report of a pancreatobiliary tumour metastasising exclusively to the RV of the heart. We conclude that in this special case aggressive surgical management following chemotherapy was very effective in controlling the disseminated adenocarcinoma of the ampulla of Vater.

Vitamin C inhibits NO-induced stabilization of HIF-1alpha in HUVECs.

HIF-1alpha represents the oxygen-regulated sub-unit of the transcription factor HIF-1, which regulates the transcription of numerous genes involved in cellular response to hypoxia and oxidative stress. It is shown here that nitric oxide (NO) induces HIF-1alpha stabilization in human endothelial cells from umbilical cords (HUVECs) under normoxic conditions. HIF-1alpha protein was increased approximately 36-fold after incubation with 500 microM DETA-NO, which releases a steady state NO concentration of roughly one thousandth of the initial concentration of the donor. Loading of the cells with vitamin C counteracted NO-induced HIF-1alpha accumulation. Based on the observations that oxidative and nitrosative stress can influence the activity of the proteasomal system, which is responsible for the non-lysosomal degradation of proteins, among them HIF-1alpha, it was investigated whether NO-induced stabilization of HIF-1alpha might be due to reduced 20S proteasomal activity. This hypothesis could not be proved, because NO concentrations to inhibit 20S proteasomal activity were about one order of magnitude higher than that to inhibit HIF-1alpha degradation.