Reevaluation of Neptunium-Nitric Acid Radiation Chemistry by Multiscale Modeling.

Multiscale modeling has been used to quantitatively reevaluate the radiation chemistry of neptunium in a range of aerated nitric acid solutions (0.1-6.0 mol dm-3). Exact calculation of initial radiolytic yields accounting for changes in radiation track chemistry was found to be crucial for reproducing experimental data. The γ irradiation induces changes in the Np(VI)/Np(V) oxidation-state distribution, predominantly driven by reactions involving HNO2, H2O2, NO2•, and NO3• from the radiolysis of aqueous nitric acid. Oxidation of Np(V) by NO3• (k = 8.1 × 108 dm3 mol-1 s-1) provides the initial increase in Np(VI) concentration, while also delaying net reduction of Np(VI) by consuming HNO2. Reduction of Np(VI) is dominated by thermal reactions with HNO2 (k = 0.7-73 dm3 mol-1 s-1) and H2O2 (k = 1.9 dm3 mol-1 s-1). A steady state is eventually established once the concentration of Np(V) is sufficiently high to be oxidized by NO2• (k = 2.4 × 102-3.1 × 104 dm3 mol-1 s-1). An additional thermal oxidation reaction between Np(V) and HNO3 (k = 2.0 × 103 dm3 mol-1 s-1) is required for nitric acid concentrations >4.0 mol dm-3. For 0.1 mol dm-3 HNO3, the rate of Np(VI) reduction is in excess of that which can be accounted for by radiolytic product mass balance, suggesting the existence of a catalytic-acid-dependent reduction process.

Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells.

Detailed studies of tumor cell-associated procoagulants and fibrinolytic factors have implied that local thrombin generation and fibrin deposition and dissolution may be important in tumor growth and dissemination. To directly determine whether fibrin(ogen) or plasmin(ogen) are determinants of the metastatic potential of circulating tumor cells, this study examined the impact of genetic deficits in each of these key hemostatic factors on the hematogenous pulmonary metastasis of 2 established murine tumors, Lewis lung carcinoma and the B16-BL6 melanoma. In both tumor models, fibrinogen deficiency strongly diminished, but did not prevent, the development of lung metastasis. The quantitative reduction in metastasis in fibrinogen-deficient mice was not due to any appreciable difference in tumor stroma formation or tumor growth. Rather, tumor cell fate studies indicated an important role for fibrin(ogen) in sustained adhesion and survival of tumor cells within the lung. The specific thrombin inhibitor, hirudin, further diminished the metastatic potential of circulating tumor cells in fibrinogen-deficient mice, although the inhibitor had no apparent effect on tumor cell proliferation in vitro. The absence of plasminogen and plasmin-mediated fibrinolysis had no significant impact on hematogenous metastasis. The authors concluded that fibrin(ogen) is a critical determinant of the metastatic potential of circulating tumor cells. Furthermore, thrombin appears to facilitate tumor dissemination through at least one fibrin(ogen)-independent mechanism. These findings suggest that therapeutic strategies focusing on multiple distinct hemostatic factors might be beneficial in the containment of tumor metastasis.