Anti-LMNA monoclonal antibody, clone 242D4

Mesenchymal tumors driven byNTRKfusions are clinically and morphologically heterogeneous. With an increasing number of clinicopathological entities being associated withNTRKfusions, the diagnostic and predictive value of the identification ofNTRKfusions is uncertain. Recently, mesenchymal tumors in the gastrointestinal tract withNTRKfusions were described as gastrointestinal stromal tumors (GIST), but the nosology of such neoplasms remains controversial. We report eight mesenchymal tumors involving the gastrointestinal tract withNTRK1orNTRK3rearrangements. The tumors occurred in six children and two adults, five males and three females (age range 2 months-55 years; median 3.5 years), and involved the small intestine (n = 4), stomach (n = 2), rectum (n = 1), and mesentery (n = 1). Clinical outcomes were variable, ranging from relatively indolent (n = 2) to aggressive diseases (n = 2). Morphologically, the tumors were heterogeneous and could be classified in the following three groups: (1) infantile fibrosarcoma involving the gastrointestinal tract (n = 4), enriched forNTRK3fusions; (2) low-grade CD34-positive, S100 protein-positive spindle-cell tumors, associated withNTRK1fusions (n = 2); and (3) unclassified high-grade spindle-cell sarcomas, withNTRK1fusions (n = 2). By immunohistochemistry, the tumors demonstrated diffuse pan-TRK expression, of variable intensity, and lacked a specific line of differentiation. Four cases expressed CD34, which was coexpressed with S100 protein in three cases. Expression of SOX10, KIT, and DOG1 was consistently absent. Molecular genetic testing identifiedTPM3-NTRK1(n = 3),TPR-NTRK1,LMNA-NTRK1, andETV6-NTRK3(n = 2), andSPECC1L-NTRK3in-frame gene fusions. We conclude that the evaluation of mesenchymal spindle-cell neoplasms of the gastrointestinal tract without a definitive line of differentiation should include interrogation ofNTRKalterations, particularly in pediatric patients. Mesenchymal tumors of the gastrointestinal tract withNTRKrearrangements are clinically and morphologically heterogeneous, and few, if any, seem related to GIST.

Lead is a heavy metal pollutant that is widely present in the environment and can seriously harm human health, especially the nervous system. Long noncoding RNAs (lncRNAs) play important roles in many physiological and pathological processes; however, there remains a lack of in-depth studies on the molecular mechanisms associated with lead neurotoxicity. Here, our results showed that lead exposure inhibited cell proliferation and promoted cell apoptosis. We observed that lncRNAL20992 was significantly upregulated in a lead-induced neuronal-injury cell model according to quantitative reverse transcription polymerase chain reaction. Silencing lncRNAL20992 revealed its significant functions involved in promoting cell apoptosis and inhibiting cell proliferation according to cell-counting kit-8, EdU assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and western blot. To elucidate the molecular mechanisms of lncRNAL20992, we used RNA pulldown mass spectrometry combined with bioinformatics analysis to discover 4 proteins (AIFM1, HSP7C, GRP78, and LMNA) that interacted with lncRNAL20992. Western blot analysis indicated that lncRNAL20992 involved in lead-induced neuronal injury was mediated by the 4 proteins. Our study constitutes the first investigation of the functions and related mechanisms of lncRNAL20992 and offered valuable insight into understanding the roles of lncRNA in lead-induced neurotoxicity.