SOS1 inhibitor BI-3406 shows in vivo antitumor activity akin to genetic ablation and synergizes with a KRAS inhibitor in KRAS LUAD.

We evaluated the in vivo therapeutic efficacy and tolerability of BI-3406-mediated pharmacological inhibition of SOS1 in comparison to genetic ablation of this universal Ras-GEF in various KRAS-dependent experimental tumor settings. Contrary to the rapid lethality caused by SOS1 genetic ablation in SOS2 mice, SOS1 pharmacological inhibition by its specific inhibitor BI-3406 did not significantly affect animal weight/viability nor cause noteworthy systemic toxicity. Allograft assays using different KRAS cell lines showed that treatment with BI-3406 impaired RAS activation and RAS downstream signaling and decreased tumor burden and disease progression as a result of both tumor-intrinsic and -extrinsic therapeutic effects of the drug.

Critical requirement of SOS1 for tumor development and microenvironment modulation in KRAS-driven lung adenocarcinoma.

The impact of genetic ablation of SOS1 or SOS2 is evaluated in a murine model of KRAS-driven lung adenocarcinoma (LUAD). SOS2 ablation shows some protection during early stages but only SOS1 ablation causes significant, specific long term increase of survival/lifespan of the KRAS mice associated to markedly reduced tumor burden and reduced populations of cancer-associated fibroblasts, macrophages and T-lymphocytes in the lung tumor microenvironment (TME). SOS1 ablation also causes specific shrinkage and regression of LUAD tumoral masses and components of the TME in pre-established KRAS LUAD tumors.

Noble gas isotopes reveal degassing-derived eruptions at Deception Island (Antarctica): implications for the current high levels of volcanic activity.

Deception Island is one of the most active volcanoes in Antarctica with more than twenty explosive eruptions in the past two centuries. Any future volcanic eruption(s) is a serious concern for scientists and tourists, will be detrimental to marine ecosystems and could have an impact to global oceanographic processes. Currently, it is not possible to carry-out low and high frequency volcanic gas monitoring at Deception Island because of the arduous climatic conditions and its remote location.

Preliminary results of customized bone graft made by robocasting hydroxyapatite and tricalcium phosphates for oral surgery.

Objective: The objective of this study was to assess the mechanical characteristics and the clinical usefulness of beta-tricalcium phosphate (β-TCP) and hydroxyapatite (HA) bioblocks grafted in edentulous jaws of 12 patients.

Methods: The scaffolds were produced by robocasting ceramic inks containing 80%/20% β-TCP and HA, respectively, with an overall porosity of 60%, with a macropore size between 300 and 500 μm. The mechanical performance of cylindrical vs conical specimens was compared using a universal testing machine.

Mesenchymal Stromal Cell Irradiation Interferes with the Adipogenic/Osteogenic Differentiation Balance and Improves Their Hematopoietic-Supporting Ability.

Bone marrow mesenchymal stromal cells (MSCs) are precursors of adipocytes and osteoblasts and key regulators of hematopoiesis. Irradiation is widely used in conditioning regimens. Although MSCs are radio-resistant, the effects of low-dose irradiation on their behavior have not been extensively explored.