Slug-based epithelial-mesenchymal transition gene signature is associated with prolonged time to recurrence in glioblastoma

Background
We previously identified a precise stage-associated gene expression signature of coordinately expressed genes, including the transcription factor Slug (SNAI2) and other epithelial mesenchymal transition (EMT) markers, present in samples from publicly available gene expression datasets in multiple cancer types. The expression levels of the co-expressed genes vary in a continuous and coordinate manner across the samples, ranging from absence of expression to strong co-expression of all genes. These data suggest that tumor cells may pass through an EMT like process of mesenchymal transition to varying degrees. 

Findings
Here we show that this signature in glioblastoma multiforme (GBM) is associated with time to recurrence following initial treatment. By analyzing data from The Cancer Genome Atlas (TCGA), we found that GBM patients who responded to therapy and had long time to recurrence had low levels of the signature in their tumor samples (P = 3x10^-7^). We also found that the signature is strongly correlated in gliomas with the putative stem cell marker CD44, and is highly enriched among the differentially expressed genes in glioblastomas vs. lower grade gliomas. 

Conclusions 
Our results suggest that long delay before tumor recurrence is associated with absence of the mesenchymal transition signature, raising the possibility that inhibiting this transition might improve the durability of therapy in glioma patients

Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes

Adhesion molecules of the integrin beta1 family are thought to be involved in the malignant progression renal cell carcinoma (RCC). Still, it is not clear how they contribute to this process. Since the hematogenous phase of tumour dissemination is the rate-limiting step in the metastatic process, we explored beta1 integrin alterations on several RCC cell lines (A498, Caki1, KTC26) before and after contacting vascular endothelium in a tumour-endothelium (HUVEC) co-culture assay. Notably, alpha2, alpha3 and alpha5 integrins became down-regulated immediately after the tumour cells attached to HUVEC, followed by re-expression shortly thereafter. Integrin down-regulation on RCC cells was caused by direct contact with endothelial cells, since the isolated endothelial membrane fragments but not the cell culture supernatant contributed to the observed effects. Integrin loss was accompanied by a reduced focal adhesion kinase (FAK) expression, FAK activity and diminished binding of tumour cells to matrix proteins. Furthermore, intracellular signalling proteins RCC cells were altered in the presence of HUVEC membrane fragments, in particular 14-3-3 epsilon, ERK2, PKCdelta, PKCepsilon and RACK1, which are involved in regulating tumour cell motility. We, therefore, speculate that contact of RCC cells with the vascular endothelium converts integrin-dependent adhesion to integrin-independent cell movement. The process of dynamic integrin regulation may be an important part in tumour cell migration strategy, switching the cells from being adhesive to becoming motile and invasive

Opial type L

This paper presents a class of Lp-type Opial inequalities for generalized fractional derivatives for integrable functions based on the results obtained earlier by the first author for continuous functions (1998). The novelty of our approach is the use of the index law for fractional derivatives in lieu of Taylor's formula, which enables us to relax restrictions on the orders of fractional derivatives

Computational analysis of the synergy among multiple interacting genes

Diseases such as cancer are often related to collaborative effects involving interactions of multiple genes within complex pathways, or to combinations of multiple SNPs. To understand the structure of such mechanisms, it is helpful to analyze genes in terms of the purely cooperative, as opposed to independent, nature of their contributions towards a phenotype. Here, we present an information-theoretic analysis that provides a quantitative measure of the multivariate synergy and decomposes sets of genes into submodules each of which contains synergistically interacting genes. When the resulting computational tools are used for the analysis of gene expression or SNP data, this systems-based methodology provides insight into the biological mechanisms responsible for disease

New features of modulational instability of partially coherent light; importance of the incoherence spectrum

It is shown that the properties of the modulational instability of partially coherent waves propagating in a nonlinear Kerr medium depend crucially on the profile of the incoherent field spectrum. Under certain conditions, the incoherence may even enhance, rather than suppress, the instability. In particular, it is found that the range of modulationally unstable wave numbers does not necessarily decrease monotonously with increasing degree of incoherence and that the modulational instability may still exist even when long wavelength perturbations are stable.Comment: 4 pages, 2 figures, submitted to Phys. Rev. Let

Partially incoherent optical vortices in self-focusing nonlinear media

We observe stable propagation of spatially localized single- and double-charge optical vortices in a self-focusing nonlinear medium. The vortices are created by self-trapping of partially incoherent light carrying a phase dislocation, and they are stabilized when the spatial incoherence of light exceeds a certain threshold. We confirm the vortex stabilization effect by numerical simulations and also show that the similar mechanism of stabilization applies to higher-order vortices.Comment: 4 pages and 6 figures (including 3 experimental figures

Exact soliton solutions, shape changing collisions and partially coherent solitons in coupled nonlinear Schroedinger equations

We present the exact bright one-soliton and two-soliton solutions of the integrable three coupled nonlinear Schroedinger equations (3-CNLS) by using the Hirota method, and then obtain them for the general $N$-coupled nonlinear Schroedinger equations (N-CNLS). It is pointed out that the underlying solitons undergo inelastic (shape changing) collisions due to intensity redistribution among the modes. We also analyse the various possibilities and conditions for such collisions to occur. Further, we report the significant fact that the various partial coherent solitons (PCS) discussed in the literature are special cases of the higher order bright soliton solutions of the N-CNLS equations.Comment: 4 pages, RevTex, 1 EPS figure To appear in Physical Review Letter

Stable vortex and dipole vector solitons in a saturable nonlinear medium

We study both analytically and numerically the existence, uniqueness, and stability of vortex and dipole vector solitons in a saturable nonlinear medium in (2+1) dimensions. We construct perturbation series expansions for the vortex and dipole vector solitons near the bifurcation point where the vortex and dipole components are small. We show that both solutions uniquely bifurcate from the same bifurcation point. We also prove that both vortex and dipole vector solitons are linearly stable in the neighborhood of the bifurcation point. Far from the bifurcation point, the family of vortex solitons becomes linearly unstable via oscillatory instabilities, while the family of dipole solitons remains stable in the entire domain of existence. In addition, we show that an unstable vortex soliton breaks up either into a rotating dipole soliton or into two rotating fundamental solitons.Comment: To appear in Phys. Rev.

Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease

Copyright @ 2010 Cancer Research UK. This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.Background: α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy. However, there is little information on the pattern of CD4 (Th1) and CD8 (Tc1) T-cell response to AFP in patients with HCC and their association with the clinical characteristics of patients. Methods: We therefore analysed CD4 and CD8 T-cell responses to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-γ. Results: Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly elevated serum AFP concentrations (P=0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child–Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child–Pugh A score and in 46% with a B or C score. Conclusion: These results suggest that anti-AFP Th1 responses are more likely to be present in patients who are in an early stage of disease (for both tumour stage and liver cirrhosis), whereas anti-AFP Tc1 responses are more likely to be present in patients with late-stage liver cirrhosis. Therefore, these data provide valuable information for the design of vaccination strategies against HCC.Association for International Cancer Research and Polkemmet Fund, London Clinic

Statistical Effects in the Multistream Model for Quantum Plasmas

A statistical multistream description of quantum plasmas is formulated, using the Wigner-Poisson system as dynamical equations. A linear stability analysis of this system is carried out, and it is shown that a Landau-like damping of plane wave perturbations occurs due to the broadening of the background Wigner function that arises as a consequence of statistical variations of the wave function phase. The Landau-like damping is shown to suppress instabilities of the one- and two-stream type.Comment: 5 page