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The authors show that fibroblast activation protein (FAP) induces the tumor promoting phenotype of fibroblasts through secretion of several cytokines. It activates tumor cells, recruits macrophages and polarizes them into the M2 phenotype. FAP may therefore be a valuable prognostic marker and specific target of anti-cancer therapy.
Fibroblast-like synoviocytes (FLS) are major contributors to joint inflammation in rheumatoid arthritis (RA). Here, the authors identified a previously unknown signaling circuit that contributes to tumor necrosis factor (TNF)-induced activation of FLS. The authors show that FOXO3 and its modulator PIK3IP1 are crucial for the TNF-driven interferon (IFN) response in RA-FLS.
The authors developed a rat model for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), using a minimal future liver remnant considered to be insufficient for survival. An in situ split combined with portal vein ligation boosts liver hypertrophy, and hepatectomy induces a higher level of hepatocyte proliferation, resulting in increased liver mass recovery and survival after ALPPS. This robust model should be valuable for studying the physiological mechanisms leading to accelerated regeneration.
The authors show that EBV-encoded oncoprotein LMP1 up-regulates cyclin-dependent kinase 1 (CDK1) and survivin expression in nasal NK/T-cell lymphoma (NNKTL). CDK1 and survivin inhibitors, including mithramycin, reduce the proliferation of NNKTL cells. Mithramycin further induces anti-tumor effects in an NNKTL xenograft mouse model. These results suggest that CDK1 and survivin may be potential therapeutic targets for NNKTL.
Systemic inflammation generates oxidized high-density lipoprotein (oxHDL) inducing endothelial malfunction mediated by the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). OxHDL interacts with LOX-1 and increases LOX-1 levels to the plasma membrane through the NOX-2/ROS/NF-κB pathway. Oxidative stress is able to induce LOX-1 expression in absence of oxHDL. Also, oxHDL induces TNF-α expression increase, which induces LOX-1 expression.
Theralin, which simultaneously fixes and decalcifies bone tissue, was compared with formalin fixation with acid decalcification in primary bone cancer cases. Use of theralin improved (a) sample processing time, (b) tissue histomorphology, (c) protein and DNA extractability, and (d) enabled standard FISH staining in bone. This unlocks the molecular archive within bone for the standard tissue analysis pipeline.
The authors developed a high-content, quantitative analysis of breast cancer tissues based on microfluidic staining and image processing, to characterize both HER2 overexpression and amplification at the cellular level. This study paves the way for evaluatation of intratumoral heterogeneity with unprecedented accuracy with standard staining methods such as immunofluorescence and FISH.
The role of neddylatin in inflammatory arthritis is not well understood. Here we reveal that NEDD8 and CULLIN-1 are significantly upregulated in the synovium of patients with RA. Neddylation activation is crucial for the pathobiology of collagen-induced arthritis. Mechanistically, TRAF6 neddylation at Lys124 is essential for IL-17A-induced NF-κB activation in synoviocytes.