Inhibition of Ras GTPases prevents Collagen-Induced Arthritis by Reducing the Generation of Pathogenic CD4 T Cells and the Hyposialylation of Autoantibodies.

Objective: RasGTPases are master regulators of multiple intracellular signaling cascades. Perturbation of this pathway has been implicated in the pathogenesis of rheumatoid arthritis (RA). In this study we aimed to define the therapeutic potential of a novel RasGTPases inhibitor, farnesylthiosalicylate (FTS), in the preclinical mouse model of collagen-induced arthritis (CIA) and better delineate its immunomodulatory effects both ex vivo and in the mouse.

NCAM1/FGF module serves as a putative pleuropulmonary blastoma therapeutic target.

Pleuropulmonary blastoma (PPB) is a rare pediatric lung neoplasm that recapitulates developmental pathways of early embryonic lungs. As lung development proceeds with highly regulated mesenchymal-epithelial interactions, a DICER1 mutation in PPB generates a faulty lung differentiation program with resultant biphasic tumors composed of a primitive epithelial and mesenchymal stroma with early progenitor blastomatous cells. Deciphering of PPB progression has been hampered by the difficulty of culturing PPB cells, and specifically progenitor blastomatous cells.

In Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example.

Cancer stem cell (CSC) identification relies on transplantation assays of cell subpopulations sorted from fresh tumor samples. Here, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in vivo propagating patient-derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of epithelial to mesenchymal transition, invasion/motility, metastasis, and self-renewal, pinpointing putative MRT CSC markers.

Peroxisome proliferator-activated receptor gamma (PPARγ) is central to the initiation and propagation of human angiomyolipoma, suggesting its potential as a therapeutic target.

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Ras Signaling Inhibitors Attenuate Disease in Adjuvant-Induced Arthritis Targeting Pathogenic Antigen-Specific Th17-Type Cells.

The Ras family of GTPases plays an important role in signaling nodes downstream to T cell receptor and CD28 activation, potentially lowering the threshold for T-cell receptor activation by autoantigens. Somatic mutation in or may cause a rare autoimmune disorder coupled with abnormal expansion of lymphocytes. T cells from rheumatoid arthritis (RA) patients show excessive activation of Ras/MEK/ERK pathway.