TRAIL Receptor Signaling Regulation of Chemosensitivity In Vivo but Not In Vitro

Background: Signaling by Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) and Fas ligand (FasL) has been proposed to contribute to the chemosensitivity of tumor cells treated with various other anti-cancer agents. However, the importance of these effects and whether there are differences in vitro and in vivo is unclear. Methodology/Principal Findings: To assess the relative contribution of death receptor pathways to this sensitivity and to determine whether these effects are intrinsic to the tumor cells, we compared the chemosensitivity of isogenic BJAB human lymphoma cells where Fas and TRAIL receptors or just TRAIL receptors were inhibited using mutants of the adaptor protein FADD or by altering the expression of the homeobox transcription factor Six1. Inhibition of TRAIL receptors did not affect in vitro tumor cell killing by various anti-cancer agents indicating that chemosensitivity is not significantly affected by the tumor cell-intrinsic activation of death receptor signaling. However, selective inhibition of TRAIL receptor signaling caused reduced tumor regression and clearance in vivo when tested in a NOD/SCID mouse model. Conclusions: These data show that TRAIL receptor signaling in tumor cells can determine chemosensitivity in vivo but not in vitro and thus imply that TRAIL resistance makes tumors less susceptible to conventional cytotoxic anti-cancer drugs a

Cross-shell excited configurations in the structure of Si34

The cross-shell excited states of Si34 have been investigated via β decays of the 4- ground state and the 1+ isomeric state of Al34. Since the valence protons and valence neutrons occupy different major shells in the ground state as well as the intruder 1+ isomeric state of Al34, intruder levels of Si34 are populated via allowed β decays. Spin assignments to such intruder levels of Si34 were established through γ-γ angular correlation analysis for the negative-parity states with dominant configurations (νd3/2)-1⊗ - (νf7/2)1 as well as the positive-parity states with dominant configurations (νsd)-2⊗ - (νf7/2p3/2)2. The configurations of such intruder states play crucial roles in our understanding of the N=20 shell gap evolution. A configuration interaction model derived from the FSU Hamiltonian was utilized in order to interpret the intruder states in Si34. Shell model interaction derived from a more fundamental theory with the valence space in medium similarity renormalization group method was also employed to interpret the structure of Si34