Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hämatologie und Onkologie OSHO-53 phase II study

Background We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. Patients and methods From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. Results Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. Conclusions Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of lif

The Distinct Metabolic Phenotype of Lung Squamous Cell Carcinoma Defines Selective Vulnerability to Glycolytic Inhibition

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high 18F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient

Synaptic Proteins Linked to HIV-1 Infection and Immunoproteasome Induction: Proteomic Analysis of Human Synaptosomes

Infection of the central nervous system with human immunodeficiency virus type 1 (HIV-1) can produce morphological changes in the neocortical synaptodendritic arbor that are correlated with neurocognitive impairment. To determine whether HIV-1 infection influences the protein composition of human synapses, a proteomic study of isolated nerve endings was undertaken. Synaptosomes from frontal neocortex were isolated using isopyknic centrifugation from 19 human brain specimens. Purity and enrichment were assessed by measuring pre- and postsynaptic protein markers. Two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to screen for proteins differentially expressed in HIV/AIDS. The concentrations of 31 candidate protein spots were potentially abnormal in HIV-infected decedents with HIV encephalitis and/or increased expression of immunoproteasome subunits. Immunoblots showed that the concentration of some of them was related to HIV-1 infection of the brain and immunoproteasome (IPS) induction. Synapsin 1b and stathmin were inversely related to brain HIV-1 load; 14-3-3ζ and 14-4-4ε proteins were higher in subjects with HIV-1 loads. Perturbed synaptosome proteins were linked with IPS subunit composition, and 14-3-3ζ was histologically colocalized with IPS subunits in stained neocortical neurons. Proteomics illustrates that certain human proteins within the synaptic compartment are involved with changes in the synaptodendritic arbor and neurocognitive impairment in HIV-1-infected people

VIS Fabry-Pérot Interferometer with structured (TiO2/PE-SiO2)3 Bragg-reflectors on 5mm large LP-Si3N4 membranes

Miniaturized spectrometry systems are achievable e.g. by the use of MEMS based tunable Fabry-Perot Interferometers (FPI) as wavelength selective filter elements. Main part of a FPI is the reflector which is usually realized as a stack of alternating dielectric layers with high and low refractive index. To achieve high reflectance layer stacks with larger number of layers and/or layers with a higher refractive index contrast are needed. Both have to be integrated within the manufacturing processes chain which in practice proves to be a difficult process. We present a FPI with a (TiO2/SiO2)(3) reflector stack with a reflectance of 97 % and TiO2 as high refractive index layer for the use in the VIS-range of 555 nm to 585 nm. Main achievements of TiO2 instead of Si3N4 are a higher reflectance and a minimized reflector complexity. Furthermore, we introduce a dry etch process which is compatible and integrated in the manufacturing process chain of the MEMS FPI. Manufacturing of the 7.5 mm x 7.5 mm chip size FPI is done on 6" wafers consisting of a moveable reflector on a 210 nm thin and 5 mm in diameter LP-Si3N4 membrane and a fixed reflector with an aperture of 2 mm in diameter. The measured peak transmittance is between 28 % and 37 % with a FWHM bandwidth between 1.5 nm and 1.8 nm. It could be shown that the FPIs are tunable over the spectral range from 555 nm to 585 nm with a maximum control voltage of 45 V using the 18th interference order

VIS Fabry-Pérot-Interferometer with (HL)4 PE-Si3N4/PE-SiO2 reflectors on freestanding LP-Si3N4 membranes for surface enhanced Raman spectroscopy

Profound developments of miniaturized spectrometry systems enable new breakthrough applications such as online monitoring systems for specific molecules by Surface Enhanced Raman Spectroscopy (SERS). The spectrometry system is based on SERS active surfaces in-situ generating nanoparticles and miniaturized detectors with tunable Fabry-Pérot- Interferometers (FPI) with very sharp transmission peaks and a FWHM bandwidth below 2 nm. The key part of this online monitoring system is a tunable FPI, which is fabricated with MEMS technology. This contribution presents a 7.5 x 7.5 mm² chip size FPI, consisting of a moveable reflector on a 210 nm thin and up to 5.5 mm in diameter Si3N4 membrane on a silicon carrier, and a fixed reflector on glass. The optical resonator with an aperture of 2 mm diameter is designed for the central wavelength of 570 nm and realized by adhesive SU-8 bonding of the silicon on glass substrate. The moveable Si3N4 membrane is fabricated by combined wet and dry etching of silicon. The dielectric (HL)4 Si3N4/ SiO2 reflector stack with a reflectance of 93 % is deposited by PE-CVD on the LP-CVD-Si3N4 and structured by dry etching on the membrane and the glass. The measured peak transmittance is between 52 % and 74 % with a FWHM bandwidth between 1.3 nm and 2.0 nm. It was shown, that the FPIs are tunable over the spectral range from 555 nm to 585 nm which is relevant for this SERS application with a tuning voltage of 25 V