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We investigated whether or not nitric oxide synthase 3 (NOS3) rs2070744 genotypes can affect the response for lenvatinib treatment in patients with hepatocellular carcinoma (HCC). We evaluated the relation of the NOS3 rs2070744 genotypes to the tumor response, progression-free survival (PFS), and overall survival (OS) as the response for lenvatinib. We also examined the association between fibroblast growth factor receptor (FGFR) gene polymorphisms, a potential feature of lenvatinib, and the response. There were no significant differences between the studies for either PFS or OS, even though patients with the TT genotype had a longer mean PFS (hazard ratio [HR] 0.60; p = 0.069) and mean OS (HR 0.46; p = 0.075) than those with the TC/CC genotypes. However, patients with a single-nucleotide polymorphism (SNP) combination pattern of the NOS3 rs2070744 TC/CC and FGFR4 rs351855 CT/TT genotypes had a significantly shorter mean PFS (HR 2.56; p = 0.006) and mean OS (HR 3.36; p = 0.013) than those with the other genotypes. The NOS3 rs2070744 genotypes did not influence the clinical response. However, the SNP combination pattern of the NOS3 rs2070744 and FGFR4 rs351855 genotypes may be helpful as treatment effect predictors and prognostic factors for HCC patients treated with lenvatinib.

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Plate tectonics is largely responsible for material and heat circulation in Earth, but for unknown reasons it does not exist on Venus. The strength of planetary materials is a key control on plate tectonics because physical properties, such as temperature, pressure, stress and chemical composition, result in strong rheological layering and convection in planetary interiors. Our deformation experiments show that crustal plagioclase is much weaker than mantle olivine at conditions corresponding to the Moho in Venus. Consequently, this strength contrast may produce a mechanical decoupling between the Venusian crust and interior mantle convection. One-dimensional numerical modeling using our experimental data confirms that this large strength contrast at the Moho impedes the surface motion of the Venusian crust and, as such, is an important factor in explaining the absence of plate tectonics on Venus.