Volume 102 Issue 6, June 2022
Inside the USCAP Journals
Generation of a recessive dystrophic epidermolysis bullosa mouse model with patient-derived compound heterozygous mutations
Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin disease caused by mutations in the gene COL7A1. The authors developed a strategy to investigate the impact of each pathogenic mutation on skin integrity using CRISPR-mediated genome editing in mice in order to create a reliable animal model for the study of this devastating disease.
Mammals exhibit epidermal patterning, as seen in mouse tail scales and human skin microtopography. In this article, the authors demonstrate that type XVII collagen (COL17), a niche for epidermal stem cells, modulate epidermal patterning in mice and humans. COL17 further prevents wound-induced epidermal deformation. This study paves the way for elucidating the role of the stem cell niche in tissue pattern formation.
This study reveals that miR-483-5p is upregulated by cisplatin treatment and exacerbates cisplatin-induced acute kidney injury via negative regulation of GPX3 and contributes to tubular cell apoptosis. The authors demonstrate that miR-483-5p is a key upstream mediator regulating acute kidney injury induced by cisplatin and may serve as a new target for diagnosis and therapy.
Silencing of LINC01963 enhances the chemosensitivity of prostate cancer cells to docetaxel by targeting the miR-216b-5p/TrkB axis
The authors show that LINC01963 is overexpressed in the PC3-DR cells and that LINC01963 silencing enhances the chemosensitivity of PC3-DR to docetaxel and inhibits tumorigenicity and lung metastasis. Silencing of LINC01963 ireduces TrkB protein levels to enhance the chemosensitivity of cells to docetaxel by competitively binding to miR-216b-5p.
The E3 ubiquitin ligase SOCS-7 reverses immunosuppression via Shc1 signaling in hepatocellular carcinoma
The authors demonstrate that the expression of SOCS-7 is decreased in (HCC) cells, as well as in patients, and overexpression of SOCS-7 significantly decreases the proliferation and migration of HCC cells and increases apoptosis in cultured HCC cells. An animal xenogeneic model shows that overexpression of SOCS-7 inhibits tumors, and knockout of SOCS-7 results in tumor growth.
High-fat diet-induced nonalcoholic steatohepatitis is accelerated by low carnitine and impaired glucose tolerance in novel murine models
The authors successfully developed two novel murine models for high-fat diet-induced nonalcoholic steatohepatitis that progresses to hepatic tumors with proliferative changes similar to those seen in humans. The jvs/+ mice with low carnitine as well as wild-type mice with early-stage impaired glucose tolerance induction by alloxan treatment developed obesity, insulin resistance, steatohepatitis and fibrosis, and eventually enhanced tumorigenesis. These results indicate that low carnitine and impaired glucose tolerance are important factors for the progression of nonalcoholic steatohepatitis.
SLUG is expressed in the myoepithelial cells of normal salivary glands and is highly upregulated in the neoplastic myoepithelial cells and stromal cells of pleomorphic adenoma (PA). SLUG is less likely to be affected by PLAG1. SLUG is involved in the regulation of epithelial-mesenchymal transition (EMT) marker expression in primary cultured PA cells, indicating that SLUG might be a key transcription factor controlling EMT in PA.
Interpretable tumor differentiation grade and microsatellite instability recognition in gastric cancer using deep learning
Gastric cancer possesses great histological and molecular diversity, which creates obstacles for rapid and efficient diagnoses. To overcome the limitations of the classic diagnostic procedure in gastric cancer, the authors established a deep learning system to achieve intelligent tumor differentiation grading and microsatellite instability status recognition using hematoxylin-eosin stained whole slide images from 467 patients. They used the convolutional neural network visualization to demonstrate the key pathological features learned by the system to increase system interpretability.
Semi-automated validation and quantification of CTLA-4 in 90 different tumor entities using multiple antibodies and artificial intelligence
A convolutional neural network (U-Net) for the assessment of aberrant CTLA-4 antibody staining using two independent antibody clones (MSVA-152R and CAL49) was trained and validated on 4582 tumor samples in this study. The deep learning-based framework facilitated automated CTLA-4 quantification in more than 90 different tumor entities via compensating for individual antibody shortcomings.
Experimental models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor
Soft tissue sarcomas are rare and aggressive neoplasms with limited models for laboratory-based studies. This study established eight models of soft tissue sarcomas, three malignant peripheral nerve sheath tumors, four undifferentiated pleomorphic sarcomas, and one unclassified spindle cell sarcoma. The new sarcoma cell lines are tools to elucidate molecular aberrations and improve treatment options for these difficult-to-treat sarcomas.