Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma—a long-term follow-up study

Background High-dose chemotherapy followed by autologous stem-cell transplantation (HCT-ASCT) is a promising approach in eligible patients with primary central nervous system lymphoma (PCNSL). We report long-term data of patients who were treated according to HCT-ASCT containing protocols. Patients and methods We analyzed survival and relapse rates in 43 (<67 years) immunocompetent patients with newly diagnosed PCNSL being treated according to two different high-dose methotrexate-based protocols followed by high-dose carmustine/thiotepa (BCNU/TT) plus ASCT (±whole brain irradiation). Analysis was conducted for all patients (intention-to-treat) and those patients who actually received HCT-ASCT (per-protocol). Results Thirty-four patients achieved complete remission, of those 12 relapsed (35%), while 6 of them relapsed 5 years after diagnosis. After a median follow-up of 120 months, median overall survival (OS) was reached after 104 months. Two- and 5-year OS was 81% and 70% and 2- and 5-year event-free survival (EFS) was 81% and 67%, respectively. In per-protocol analysis (N=34), 5-year OS and EFS was 82% and 79%, respectively. HCT-ASCT associated related mortality was not observed. Conclusions Sequential high-dose MTX containing chemotherapy followed by high-dose carmustine/thiotepa plus ASCT (±whole brain irradiation) is safe and leads to high survival rates in eligible patients with newly diagnosed PCNS

Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope

The nuclear pore complex (NPC) mediates nucleocytoplasmic transport through the nuclear envelope. How the NPC assembles into this double membrane boundary has remained enigmatic. Here, we captured temporally staged assembly intermediates by correlating live cell imaging with high-resolution electron tomography and super-resolution microscopy. Intermediates were dome-shaped evaginations of the inner nuclear membrane (INM), that grew in diameter and depth until they fused with the flat outer nuclear membrane. Live and super-resolved fluorescence microscopy revealed the molecular maturation of the intermediates, which initially contained the nuclear and cytoplasmic ring component Nup107, and only later the cytoplasmic filament component Nup358. EM particle averaging showed that the evagination base was surrounded by an 8-fold rotationally symmetric ring structure from the beginning and that a growing mushroomshaped density was continuously associated with the deforming membrane. Quantitative structural analysis revealed that interphase NPC assembly proceeds by an asymmetric inside-out extrusion of the INM

Imaging Molecular Structure through Femtosecond Photoelectron Diffraction on Aligned and Oriented Gas-Phase Molecules

This paper gives an account of our progress towards performing femtosecond time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe setup combining optical lasers and an X-ray Free-Electron Laser. We present results of two experiments aimed at measuring photoelectron angular distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) and dissociating, laseraligned 1,4-dibromobenzene (C6H4Br2) molecules and discuss them in the larger context of photoelectron diffraction on gas-phase molecules. We also show how the strong nanosecond laser pulse used for adiabatically laser-aligning the molecules influences the measured electron and ion spectra and angular distributions, and discuss how this may affect the outcome of future time-resolved photoelectron diffraction experiments.Comment: 24 pages, 10 figures, Faraday Discussions 17

Coulomb explosion imaging of small organic molecules at LCLS.

Fragmentation of small organic molecules by intense few-femtosecond X-ray free-electron laser pulses has been studied using Coulomb explosion imaging. By measuring kinetic energies and emission angles of the ionic fragments in coincidence, we disentangle different fragmentation pathways, for certain cases can reconstruct molecular geometry at the moment of explosion, and show how it depends on LCLS pulse duration