Volume 99 Issue 9, September 2019

The external validity of the scientific literature has come into question, referred to as the “reproducibility crisis.” Pathology is likely no exception to this problem, and may be especially prone to false positives due to commonly used observational methodologies. The authors discuss possible sources of and solutions to non-reproducible pathology studies.

This paper defines the role of the protein autophagy-related 7 (Atg7) in triple-negative breast cancer (TNBC). Atg7 inhibits proliferation and migration, and promotes apoptosis of TNBC cells. Furthermore, Atg7 prevents epithelial-mesenchymal transition through downregulation of aerobic glycolysis. Atg7 is therefore a potential prognostic marker and therapeutic target for TNBC.

In order to find a therapeutic target for triple negative breast cancer (TNBC), the authors performed a siRNA screening and identified the cell cycle regulator polo-like kinase 1 (PLK) as an essential molecule for survival of TNBC cells. PLK1 is highly expressed in TNBC tissue and inhibition of PLK1 triggers apoptosis in a series of TNBC cell lines.

The authors established a bioinformatics approach to assessing the impact of melanoma mutants, among a set of extra-cellular matrix structural proteins, on the sensitivity of matrix metalloproteinase-2 (MMP2), extensively associated with melanoma. Results indicate that tumor samples with mutant amino acids adjacent to MMP2 sites also represented a better survival rate.

In this paper, the authors show that miR-135b-5p has prognostic value for ductal carcinoma in situ with microinvasion (DCIS-Mi). The inhibition of miR-135b-5p promotes cell proliferation, epithelial–mesenchymal transition, migration and invasion by targeting (SDCBP). The MiR-135b-5p/SDCBP axis is a crucial determinant of breast cancer metastasis at a very early stage.

This paper examines whether the nuclear E3 ubiquitin ligase MDM2 and/or the cyclin-dependent kinase CDK4 produce well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS) using transformed human bone marrow stem cells through in vitro and in vivo functional experiments. The authors found that co-overexpression of MDM2 and CDK4 causes high-grade sarcoma with a dedifferentiated liposarcoma-like morphology.

Both toll-like receptors and nucleotide-binding oligomerization domain (NOD)-like receptors induce an inflammatory response at risk of causing tissue damage. However, the cross-regulation between interleukin-1 (IL-1) receptors and NOD2 is not completely understood. The authors show that IL-1α/β increase NOD2-induced inflammatory response by enhancing muramyl dipeptide-induced activation of MAPK signaling pathways via ERK, JNK, and P38.

Pirfenidone prevents lipotoxicity-induced insulin resistance and steatohepatitis by regulating immune cell accumulation and macrophage polarization in the livers of mice. Additionally, pirfenidone suppresses hepatic fibrosis by inhibiting activation of stellate cells and TGF-β1 expression; and reverses insulin resistance, hepatic inflammation, and fibrosis in mice with pre-existing nonalcoholic steatohepatitis.

CD271, also known as nerve growth factor receptor, is expressed in lung, penile, vulvar, and esophageal squamous carcinoma, but not in lung adenocarcinoma. This study determined that cell proliferation in lung squamous cell carcinoma depends on CD271, suggesting that siRNA against CD271 is a potential therapeutic strategy for certain cancers.

Lack of expression of Tgf-β1 in the embryonic lung mesenchyme led to severe lung hypoplasia, increase of cell apoptosis and reduced lung branching morphogenesis. In the mutant lung, FGF10 signaling pathway was inhibited and the vascular system was underdeveloped. This genetic mouse model will be helpful to identify the key pathogenic mechanisms underlying lung hypoplasia in humans.

The main ligands involved in lymphangiogenesis, VEGF-C and VEGF-D, are abundantly present in renal tubules at baseline and are secreted following injury with subsequent increase in serum and urinary levels. Lymphatic vessel formation is robustly induced following kidney injury and such induction is independent of the nature of insult and is a hallmark of kidney disease.

High-mobility group box 1 (HMGB1) is actively secreted from inflammatory cells and acts via a non-cell autonomous mechanism to mediating cell proliferation and migration. The authors sought to determine the role of HMGB1 in modulation of dopaminergic neurons. Their results suggest that an increase of HMGB1, released from astrocytes, upregulates TH expression in a Parkinsonian mouse model, thereby maintaining dopaminergic neuronal functions.