Volume 99 Issue 10, October 2019

The biologic features of diffuse large B-cell lymphoma (DLBCL) with PD-L1 expression remains unknown. This study demonstrates that DLBCL with PD-L1 expression features an activated B-cell receptor signal pathway, and that inhibiting BCR and blocking PD-L1 expression may synergize to target DLBCL.

The authors employed a monoclonal antibody, 297-11A, to determine preferential display of sialyl 6′-sulfo N-acetyllactosamine-capped O-glycans on high endothelial venules (HEVs) in human peripheral lymph nodes. These glycans were also displayed on HEV-like vessels in tumor-infiltrating lymphocyte aggregates in various cancers. Thus, 297-11A-positive sulfated glycans likely function in physiologic and pathologic lymphocyte trafficking.

********The authors engineered and constructed a circRNA containing both miR-21 and miR-93 binding sites, then deployed it against esophageal carcinoma. This novel multi-miR circular sponge significantly inhibits endogenous miR-21 and miR-93 activities, suppresses cellular proliferation, migration and tumor growth. These findings suggest an entirely new area of research based on developing synthetic circular RNA sponges as tools for miR-directed molecular therapy.

Trp53 null and R270H mutations had comparable effects on tumor phenotypes in a genetically engineered mouse model of colorectal cancer (CRC). The mouse tumors with Trp53 null or R270H mutations as well as human CRCs with null or codon R273 missense mutations had similar gene expression profiles. These findings raise questions about a general role for gain-of-function effects for mutant p53 proteins in CRC.

RXRα phosphorylation-deficient mutant mice with the mutation Thr 167 to Ala exhibit altered regulation of metabolic pathway gene expression in white adipose tissue. This result, combined with data on muscle and liver gene expression, suggest that the RXRα Thr 167 phosphorylation signal coordinates these three organs for regulation of energy metabolism and maintenance of glucose homeostasis.

The authors report a previously unappreciated miR-26a-mediated regulatory model in which miR-26a promotes invasion/metastasis by inhibiting the phosphatase PTEN and inhibits cell proliferation by repressing the methyltransferase EZH2 in hepatocellular carcinoma. Although therapeutic miR-26a delivery significantly suppresses tumorigenesis in mice, further studies are warranted before it is a relevant as a target for HCC therapy.

The authors present a rare case of intracranial solitary fibrous tumors/hemangiopericytomas (SFT/HPC) with intraspinal metastasis. A DSTYK mutation (Met296Ile) was identified as a potential driver of intraspinal metastasis. This DSTYK mutation promotes cell migration and invasion of SFT/HPC cells via activation of ERK1/2/MMP2/9 signaling, which may provide new biological insights for SFT/HPC study.

In this work, the authors propose a new framework based on deep-learning to comprehensively assess the microvascular condition of the glioma patients by automated analysis of the H&E stained whole slide images. They show that microvascularity has a tight relationship with the diagnosis of glioma and can be used as an important prognostic indicator.

The authors examined the feasibility of co-staining miRNAs by fluorescent miRNA in situ hybridization (miRisH) and their target proteins by immunohistofluorescence (IHF) on tissue microarrays from prostate cancer patients, which would allow for the study of miRNA expression patterns and their target proteins at the single-cell level. The miRNAs and corresponding target proteins include the pairs miR-145/ERG, miR-143/uPAR and miR-375/SEC23A.

A new technical pipeline describes a combined approach of HER2/CEP17 fluorescence in situ hybridization (FISH) analysis with MALDI imaging on the very same section of formalin-fixed and paraffin-embedded (FFPE) tissue. Combining molecules detected by MALDI imaging with the gene copy number detected by HER2/CEP17 FISH, we found a synergistic effect which enhances patient prognosis.

In this paper, the authors dissected the temporal sequence of three early events in diabetic retinopathy. They show that vascular degeneration is the initiating cellular change during the development of retinopathy in the diabetic Nile rat. Focusing on vascular events, they conducted a detailed longitudinal study and showed that the Nile rat exhibits a wide range of retinal lesions remarkably similar to the human condition.

Mass spectrometry imaging (MSI) is a potential adjunct to histopathology. However, studies have yet to adequately test its performance and reliability. Using over 900 MSI spectra, the authors establish and validate an accurate, high-resolution metabolic profile of prostate cancer, supporting the incorporation of MSI tools into surgical pathology.

The authors present the first in-depth analyses of liver pathology in a murine model of classical Farber disease. Characterizing their previously developed acid ceramidase-deficient Farber mice, they identify inflammation, fibrosis, and abnormal lipid profiles in livers/hepatocytes and highlight altered inflammatory, lipid, and sphingolipid gene expression pathways.