Recent gene expression and copy number profilings of glioblastoma multiforme (GBM) by The Cancer Genome Atlas (TCGA) Research Network suggest the existence of distinct subtypes of this tumor. However, these approaches might not be easily applicable in routine clinical practice. In the current study, we aimed to establish a proteomics‐based subclassification of GBM by integrating their genomic and epigenomic profiles. We subclassified 79 newly diagnosed GBM based on expression patterns determined by comprehensive immunohistochemical observation in combination with their DNA copy number and DNA methylation patterns. The clinical relevance of our classification was independently validated in TCGA datasets. Consensus clustering identified the four distinct GBM subtypes: Oligodendrocyte Precursor (OPC) type, Differentiated Oligodendrocyte (DOC) type, Astrocytic Mesenchymal (AsMes) type and Mixed type. The OPC type was characterized by highly positive scores of Olig2, PDGFRA, p16, p53 and synaptophysin. In contrast, the AsMes type was strongly associated with strong expressions of nestin, CD44 and podoplanin, with a high glial fibrillary acidic protein score. The median overall survival of OPC‐type patients was significantly longer than that of the AsMes‐type patients (19.9 vs 12.8 months). This finding was in agreement with the Oncomine analysis of TCGA datasets, which revealed that PDGFRA and Olig2 were favorable prognostic factors and podoplanin and CD44 were associated with a poor clinical outcome. This is the first study to establish a subclassification of GBM on the basis of immunohistochemical analysis. Our study will shed light on personalized therapies that might be feasible in daily neuropathological practice. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02377.x, 2012)
We present the electronic and vibrational spectra of quasi-one-dimensional 3 4 -filled ͑EDO-TTF͒ 2 X (EDO-TTF= ethylenedioxy-tetrathiafulvalene, X =PF 6 and AsF 6 ) above and below the metal-insulator phase transition (T MI = 280 K for the PF 6 salt and 268 K for the AsF 6 salt). For the low-temperature insulating phase, the pattern of both bond and charge order was identified. Almost all charge density is localized on the strongly bound central pair of 0110 tetramer giving rise to a characteristic spectrum of electronic excitations. Infrared spectra along the stacking axis show evidence of strong electron-molecular vibration coupling between the charge transfer band within the pair and some specific intramolecular vibrations. This charge order is assisted by a molecular deformation.
Expression of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene has been shown to correlate with clinical outcomes in patients with glioblastoma multiforme treated with alkylating agents. We evaluated MGMT protein expression in 53 primary glioblastomas by the immunohistochemistry (IHC) and analyzed the correlation between results of immunostaining and patient outcomes. There were 28 MGMT-immunopositive and 25 negative glioblastomas. Patients with MGMT-immunonegative glioblastomas showed significantly longer progression-free survival (PFS) (P = 0.0032), but no statistically significant benefits on overall survival (OS) (P = 0.0825) were shown. In 41 glioblastomas treated with temozolomide (TMZ) therapy (MGMT-immunopositive: n = 22, negative: n = 19), both PFS and OS were significantly better in MGMT-immunonegative glioblastomas. (PFS: P = 0.0015, OS: P = 0.0384). We conclude that MGMT expression on immunohistochemistry (IHC) correlates with outcomes in patients with primary glioblastoma receiving TMZ and suggest the use of MGMT-IHC as a surrogate marker for predicting tumor chemosensitivity.
Thin films of α-MoGe show progressively reduced Tc's as the thickness is decreased below 30 nm and the sheet resistance exceeds 100 Ω/ . We have performed far-infrared transmission and reflection measurements for a set of α-MoGe films to characterize this weakened superconducting state. Our results show the presence of an energy gap with ratio 2∆0/kBTc = 3.8 ± 0.1 in all films studied, slightly higher than the BCS value, even though the transition temperatures decrease significantly as film thickness is reduced. The material properties follow BCS-Eliashberg theory with a large residual scattering rate except that the coherence peak seen in the optical scattering rate is found to be strongly smeared out in the thinner superconducting samples. A peak in the optical mass renormalization at 2∆0 is predicted and observed for the first time.PACS numbers: 74.81.Bd, Disorder and reduced dimensionality affect the physical properties of metallic systems in a number of ways. Anomalous diffusion leads to localization of electrons and a related enhancement of the Coulomb interaction via reduced screening[1, 2], seen as an increase in µ * , the renormalized Coulomb interaction parameter. In a system of lower dimensions, the coupling to disorder increases, and pronounced effects are expected. Disorder-driven localization and the related enhancement of the Coulomb interaction inherently compete with the attractive interaction in superconducting metals [3,4], described by the electron-phonon spectral density α 2 F (ω) [5]. This competition reduces the transition temperature. Of particular interest are two-dimensional (2D) superconductors in which the degree of disorder can be adjusted by varying the appropriate parameters. In an ideal 2D system, the relevant parameter is normally considered to be the sheet resistance, R . The sheet resistance is determined by two factors: the (possibly thickness dependent) conductivity σ and the film thickness d.Amorphous MoGe (α-MoGe) thin films are thought to be a model system for studying the interplay between superconductivity and disorder. Several transport experiments have revealed a sharp reduction in the superconducting transition temperature T c with increasing R , even in the weakly localized regime [6,7,8,9]. The suppression of T c has been attributed to localization and an increase in the Coulomb interaction [3]. In this Letter, we explore the T c suppression in α-MoGe thin films with different thickness via temperature-dependent far-infrared transmittance and reflectance. A strong suppression of T c with increasing R is observed. The superconducting energy gap is also reduced, but the ratio of gap energy to transition temperature and the normal-state conductivity, both of which could be dependent on the disorderdriven Coulomb interaction, are not affected at all.Our films were prepared by co-magnetron sputtering
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