Volume 99 Issue 5, May 2019

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.

Intractable pulmonary fibrosis is a major cause of death in patients with acute respiratory distress syndrome (ARDS), while lipopolysaccharide (LPS) is an important etiological factor in ARDS and pulmonary fibrosis. This study provides convincing evidence that LPS promote lung fibroblast proliferation through autophagy inhibition via activation of the PI3K-Akt-mTOR pathway. Intervention by targeting inhibition of lung fibroblast autophagy may be a constructive means for treatment of pulmonary fibrosis.

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 investigated the effects and mechanism of IL-10 in renal ischemia-reperfusion injury (IRI). Compared to wild-type mice with IRI, IL-10 knockout (IL-10 KO) mice with IRI demonstrated decreased renal function, increased mRNA expressions of the pro-inflammatory cytokines, and increased expression of the pro-apoptosis factors. Our findings demonstrate that IL-10 suppresses the production of pro-inflammatory cytokines, renal dysfunction and the expression of pro-apoptosis factors after IRI.

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.

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.