92 research outputs found
Reading Across Cultures: Global Narratives, Hotels and Railway Stations
This is the final version of the article. Available from Springer Verlag via the DOI in this record.This article takes its cue from the English critic, novelist and painter John Berger. He argues that what we know determines what we see. Hotels and railway stations, though they differ in size, design and appearance, are places of temporary national and international congress that are recognized by everyone. They become visible or even iconic once their history or their role is turned into at least part of a wider narrative—in literature, film or in other arts. This provides a representative focus by which we may read a city’s or a nation’s past. In exemplifying such connections I focus first on the long-term history of Friedrichstraße station and some of the surrounding hotels in the context of the history of Berlin, situating them within the national and, by implication, also the international context. Secondly, I will consider the outbreak of the First World War in 1914 as an event in which the role of railway stations generated both personal and collective memories across cultures and over several decades
BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling
Tumors initiate by mutations in cancer cells, and progress through interactions of the cancer cells with non-malignant cells of the tumor microenvironment. Major players in the tumor microenvironment are cancer-associated fibroblasts (CAFs), which support tumor malignancy, and comprise up to 90% of the tumor mass in pancreatic cancer. CAFs are transcriptionally rewired by cancer cells. Whether this rewiring is differentially affected by different mutations in cancer cells is largely unknown. Here we address this question by dissecting the stromal landscape of BRCA-mutated and BRCA Wild-type pancreatic ductal adenocarcinoma. We comprehensively analyze pancreatic cancer samples from 42 patients, revealing different CAF subtype compositions in germline BRCA-mutated vs. BRCA Wild-type tumors. In particular, we detect an increase in a subset of immune-regulatory clusterin-positive CAFs in BRCA-mutated tumors. Using cancer organoids and mouse models we show that this process is mediated through activation of heat-shock factor 1, the transcriptional regulator of clusterin. Our findings unravel a dimension of stromal heterogeneity influenced by germline mutations in cancer cells, with direct implications for clinical research
- …