Volume 99 Issue 11, November 2019

Mitotic density is part of breast cancer grading yet is hampered by interobserver variability. The authors developed a deep learning algorithm which automatically locates the mitotic hotspot in breast tumors. Counting mitoses within this predefined hotspot considerably improved interobserver agreement. Mitotic counts assessed by the algorithm were comparable to the observers’ results.

Transcription factor STAT3 constitutively activated in cancer promotes tumor progression. The authors detected activated STAT3 in human metastatic melanoma cells and identified new STAT3 targets. STAT3 regulates a discrete set of genes in melanoma cells and its knockdown impairs cell migration and invasion via regulation of its transcriptional target SERPINA3.

Wnt11 is more strongly expressed in small cell lung cancer (SCLC) than in non-SCLC. Ascl1 promotes Wnt11 expression by altering H3K27Ac levels at the enhancer region of the WNT11 gene. Ascl1-induces Wnt11 regulates neuroendocrine differentiation, cell proliferation, and E-cadherin expression in SCLC. The Ascl1-Wnt11 axis has potential as a therapeutic target and supports the clinical utility of Wnt11 as a biological marker in SCLC.

This study confirms that the depletion of Thy-1 and upregulation of integrin β3 is an essential mechanism and potential therapeutic target for PI3K-Akt-mTOR pathway-associated inhibition of lung fibroblast autophagy in lipopolysaccharide-induced pulmonary fibrosis.

This study shows how telomerase reverse transcriptase (TERT) assists growth differentiation factor 11 (GDF11) to rejuvenate senescent endothelial progenitor cells via the Smad2/3 and eNOS pathways. Therapeutically, it may be possible to exploit TERT mediated-GDF11 signaling to activate senescent stem cells in the myocardial ischemic microenvironment.

TGF-β plays a key role in fibrosis. β-catenin is common transcription factor in major TGF-β profibrotic signaling pathways and binds competitively to either TCF or Foxo transcription factors. In human kidney biopsies, the authors found that β-catenin/Foxo interaction was negatively correlated, while that of β-catenin/TCF was positively correlated with kidney fibrosis. They further identified β-catenin/Foxo-dependent protection against TGF-β-induced profibrotic changes in tubular cells and kidney fibrosis.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset myopathy caused by the expansion of polyalanine in the PABPN1 gene. Abnormal accumulation of PABPN1 on the inner membrane of mitochondria was detected in mouse and cell models of OPMD. The localization of expanded PABPN1 in mitochondria may be associated with mitochondrial dysfunction.

Protein misfolding cyclic amplification (PMCA) is a technique able to detect minute amount of disease-related prion protein (PrP^D), but limited results have been obtained with human prions with the exception of variant Creutzfeldt-Jakob disease (variant CJD). The study demonstrates that the use of substrates with deglycosylated PrP strongly increases PrP^D amplification efficiency by PMCA for all tested CJD subtypes. The enhanced PMCA efficiency may allow for the developing of a sensitive, non-invasive, diagnostic tests for the different CJD subtypes based on body fluids or easily accessible peripheral tissues.

The authors propose that Wisteria floribunda agglutinin (WFA) staining on failing heart sections may be useful for quantitative assessment of cardiac fibrogenic activity. The fibrosis-specific WFA staining is mainly due to the WFA binding to fibrogenesis-related extracellular matrix N-glycoproteins. It is expected that cardiac WFA-binding glycoproteins may be circulating glyco-biomarkers for cardiac fibrogenesis.