Dissociation mechanism for solid-phase epitaxy of silicon in the Si <100>/Pd2Si/Si (amorphous) system

Solid-phase epitaxial growth (SPEG) of silicon was investigated by a tracer technique using radioactive 31Si formed by neutron activation in a nuclear reactor. After depositing Pd and Si onto activated single-crystal silicon substrates, Pd2Si was formed with about equal amounts of radioactive and nonradioactive Si during heating at 400 °C for 5 min. After an 1-sec annealing stage (450-->500 °C in 1 h) this silicide layer, which moves to the top of the sample during SPEG, is etched off with aqua regia. From the absence of radioactive 31Si in the etch, it is concluded that SPEG takes place by a dissociation mechanism rather than by diffusion

Heterostructure by solid‐phase epitaxy in the Si〈111〉/Pd/Si (amorphous) system

When a thin film of Pd reacts with a 〈111〉 Si substrate, a layer of epitaxial Pd_2Si is formed. It is shown that Si can grow epitaxially on such a layer by solid‐phase reaction

Depth dependence of atomic mixing by ion beams

Ion backscattering spectrometry has been used to investigate the depth dependence of atomic mixing induced by ion beams. Samples consisting of a thin Pt (or Si) marker a few tens of angstroms thick buried at different depths in a deposited Si (or Pt) layer were bombarded with Xe+ of 300 keV at 2×10^16 cm^–2 dose and Ar+ of 150 keV at 5×10^15cm^–2 dose. Significant spreading of the marker was observed as a result of ion irradiation. The amount of spreading was measured as a function of depth of the marker, which was then compared with the deposited energy distribution. Measurements of this kind promise new insight into the nature of the interaction between ion beams and solids

Growth mechanism for solid-phase epitaxy of Si in the Si <100>/Pd2Si/Si(amorphous) system studied by a radioactive tracer technique

A tracer technique using radioactive 31Si (T1/2=2.62 h) was used to study solid-phase epitaxial growth (SPEG) of silicon. After depositing Pd and Si onto single-crystal substrates which had been activated in a nuclear reactor, Pd2Si was formed with about equal amounts of radioactive and nonradioactive silicon during heating at 400 °C for 5 min. After a second annealing stage (450 °C-->500 °C in 1 h) the silicide layer which moves to the top of the sample during SPEG was etched off with aqua regia. From the absence of radioactive 31Si in the etchant solution it is concluded that SPEG takes place by dissociation of the Pd2Si layer at the single-crystal interface to provide free Si for epitaxial growth, while new silicide is formed at the interface with the amorphous Si. These results were confirmed by evaporating radioactive silicon onto nonactivated silicon substrates before evaporation of Pd and stable amorphous Si and by measuring the activity in the SPEG sample before and after etching off the silicide layer

Antimony doping of Si layers grown by solid-phase epitaxy

We report here that layers of Si formed by solid-phase epitaxial growth (SPEG) can be doped intentionally. The sample consists initially of an upper layer of amorphous Si (~1 µm thick), a very thin intermediate layer of Sb (nominally 5 Å), and a thin lower layer of Pd (~500 Å), all electron-gun deposited on top of a single-crystal substrate (1–10 Ω cm, p type, orientation). After a heating cycle which induces epitaxial growth, electrically active Sb atoms are incorporated into the SPEG layer, as shown by the following facts: (a) the SPEG layer forms a p-n junction against the p-type substrate, (b) the Hall effect indicates strong n-type conduction of the layer, and (c) Auger electron spectra reveal the presence of Sb in the layer

Validation of vessel size imaging (VSI) in high-grade human gliomas using magnetic resonance imaging, image-guided biopsies, and quantitative immunohistochemistry.

To evaluate the association between a vessel size index (VSIMRI) derived from dynamic susceptibility contrast (DSC) perfusion imaging using a custom spin-and-gradient echo echoplanar imaging (SAGE-EPI) sequence and quantitative estimates of vessel morphometry based on immunohistochemistry from image-guided biopsy samples. The current study evaluated both relative cerebral blood volume (rCBV) and VSIMRI in eleven patients with high-grade glioma (7 WHO grade III and 4 WHO grade IV). Following 26 MRI-guided glioma biopsies in these 11 patients, we evaluated tissue morphometry, including vessel density and average radius, using an automated procedure based on the endothelial cell marker CD31 to highlight tumor vasculature. Measures of rCBV and VSIMRI were then compared to histological measures. We demonstrate good agreement between VSI measured by MRI and histology; VSIMRI = 13.67 μm and VSIHistology = 12.60 μm, with slight overestimation of VSIMRI in grade III patients compared to histology. rCBV showed a moderate but significant correlation with vessel density (r = 0.42, p = 0.03), and a correlation was also observed between VSIMRI and VSIHistology (r = 0.49, p = 0.01). The current study supports the hypothesis that vessel size measures using MRI accurately reflect vessel caliber within high-grade gliomas, while traditional measures of rCBV are correlated with vessel density and not vessel caliber

Ribosomal Proteins RPS11 and RPS20, Two Stress-Response Markers of Glioblastoma Stem Cells, Are Novel Predictors of Poor Prognosis in Glioblastoma Patients.

Glioblastoma stem cells (GSC) co-exhibiting a tumor-initiating capacity and a radio-chemoresistant phenotype, are a compelling cell model for explaining tumor recurrence. We have previously characterized patient-derived, treatment-resistant GSC clones (TRGC) that survived radiochemotherapy. Compared to glucose-dependent, treatment-sensitive GSC clones (TSGC), TRGC exhibited reduced glucose dependence that favor the fatty acid oxidation pathway as their energy source. Using comparative genome-wide transcriptome analysis, a series of defense signatures associated with TRGC survival were identified and verified by siRNA-based gene knockdown experiments that led to loss of cell integrity. In this study, we investigate the prognostic value of defense signatures in glioblastoma (GBM) patients using gene expression analysis with Probeset Analyzer (131 GBM) and The Cancer Genome Atlas (TCGA) data, and protein expression with a tissue microarray (50 GBM), yielding the first TRGC-derived prognostic biomarkers for GBM patients. Ribosomal protein S11 (RPS11), RPS20, individually and together, consistently predicted poor survival of newly diagnosed primary GBM tumors when overexpressed at the RNA or protein level [RPS11: Hazard Ratio (HR) = 11.5, p&lt;0.001; RPS20: HR = 4.5, p = 0.03; RPS11+RPS20: HR = 17.99, p = 0.001]. The prognostic significance of RPS11 and RPS20 was further supported by whole tissue section RPS11 immunostaining (27 GBM; HR = 4.05, p = 0.01) and TCGA gene expression data (578 primary GBM; RPS11: HR = 1.19, p = 0.06; RPS20: HR = 1.25, p = 0.02; RPS11+RPS20: HR = 1.43, p = 0.01). Moreover, tumors that exhibited unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) or wild-type isocitrate dehydrogenase 1 (IDH1) were associated with higher RPS11 expression levels [corr (IDH1, RPS11) = 0.64, p = 0.03); [corr (MGMT, RPS11) = 0.52, p = 0.04]. These data indicate that increased expression of RPS11 and RPS20 predicts shorter patient survival. The study also suggests that TRGC are clinically relevant cells that represent resistant tumorigenic clones from patient tumors and that their properties, at least in part, are reflected in poor-prognosis GBM. The screening of TRGC signatures may represent a novel alternative strategy for identifying new prognostic biomarkers

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

© 2018 The Author(s). Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section

Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide.

BackgroundTemozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35&nbsp;μM).MethodsMGMT-expressing GSC cultures are resistant to TMZ, and IC50 (half maximal inhibitory concentration) is estimated at around 500&nbsp;μM. Clonogenic GSC surviving 500&nbsp;μM TMZ (GSC-500&nbsp;μM TMZ), were isolated. Molecular signatures were identified via comparative analysis of expression microarray against parental GSC (GSC-parental). The recombinant protein of top downregulated signature was used as a single agent or in combination with TMZ, for evaluating therapeutic effects of treatment of GSC.ResultsThe molecular signatures characterized an activation of protective stress responses in GSC-500&nbsp;μM TMZ, mainly including biotransformation/detoxification of xenobiotics, blocked endoplasmic reticulum stress-mediated apoptosis, epithelial-to-mesenchymal transition (EMT), and inhibited growth/differentiation. Bone morphogenetic protein 7 (BMP7) was identified as the top down-regulated gene in GSC-500&nbsp;μM TMZ. Although augmenting BMP7 signaling in GSC by exogenous BMP7 treatment did not effectively stop GSC growth, it markedly sensitized both GSC-500&nbsp;μM TMZ and GSC-parental to 35&nbsp;μM TMZ treatment, leading to loss of self-renewal and migration capacity. BMP7 treatment induced senescence of GSC cultures and suppressed mRNA expression of CD133, MGMT, and ATP-binding cassette drug efflux transporters (ABCB1, ABCG2), as well as reconfigured transcriptional profiles in GSC by downregulating genes associated with EMT/migration/invasion, stemness, inflammation/immune response, and cell proliferation/tumorigenesis. BMP7 treatment significantly prolonged survival time of animals intracranially inoculated with GSC when compared to those untreated or treated with TMZ alone (p = 0.0017), whereas combination of two agents further extended animal survival compared to BMP7 alone (p = 0.0489).ConclusionsThese data support the view that reduced endogenous BMP7 expression/signaling in GSC may contribute to maintained stemness, EMT, and chemoresistant phenotype, suggesting that BMP7 treatment may provide a novel strategy in combination with TMZ for an effective treatment of glioblastoma exhibiting unmethylated MGMT