Internalization and mechanisms of toxicity of lipid nanocapsules in HepG2 and HepaRG hepatoma cells upon acute and chronic exposures.

Lipid nanocapsules (LNCs) used as nanomedicine have been developed to enhance pharmacokinetics and decrease side effects of drugs, particularly for cancer therapies. After intravenous administration, LNCs possess an important hepatic tropism however, few data exist about their toxicity and even less after repeated exposure. This study aimed to assess the in vitro toxicity and internalization of unloaded LNCs, of 50 and 100 nm size, on HepG2 and HepaRG liver cell lines.

Fusion-negative rhabdomyosarcoma 3D organoids to predict effective drug combinations: A proof-of-concept on cell death inducers.

Rhabdomyosarcoma (RMS) is the main form of pediatric soft-tissue sarcoma. Its cure rate has not notably improved in the last 20 years following relapse, and the lack of reliable preclinical models has hampered the design of new therapies. This is particularly true for highly heterogeneous fusion-negative RMS (FNRMS).

3D multi-cell-type liver organoids: A new model of non-alcoholic fatty liver disease for drug safety assessments.

The development of in vitro models that recapitulate critical liver functions is essential for accurate assessments of drug toxicity. Although liver organoids can be used for drug discovery and toxicology, they are limited by (i) the lack of expression and activity of xenobiotic-metabolizing enzymes, and (ii) the difficulty of mimicking non-alcoholic fatty liver disease (NAFLD, which influences the expression of these enzymes) in vitro. Here, we generated three-dimensional multi-cell-type liver organoids (hereafter "HML organoids") from HepaRG cells, primary human macrophages, and hepatic-stellate-cell-derived LX-2 cells.

SMAD2/3 mediate oncogenic effects of TGF-β in the absence of SMAD4.

TGF-β signaling is involved in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis, representing one of the four major pathways genetically altered in 100% of PDAC cases. TGF-β exerts complex and pleiotropic effects in cancers, notably via the activation of SMAD pathways, predominantly SMAD2/3/4. Though SMAD2 and 3 are rarely mutated in cancers, SMAD4 is lost in about 50% of PDAC, and the role of SMAD2/3 in a SMAD4-null context remains understudied.

Complex Elucidation of Cells-of-Origin in Pediatric Soft Tissue Sarcoma: From Concepts to Real Life, Hide-and-Seek through Epigenetic and Transcriptional Reprogramming.

Soft tissue sarcoma (STS) comprise a large group of mesenchymal malignant tumors with heterogeneous cellular morphology, proliferative index, genetic lesions and, more importantly, clinical features. Full elucidation of this wide diversity remains a central question to improve their therapeutic management and the identity of cell(s)-of-origin from which these tumors arise is part of this enigma. Cellular reprogramming allows transitions of a mature cell between phenotypes, or identities, and represents one key driver of tumoral heterogeneity.