Mechanisms that link the oncogenic epithelial–mesenchymal transition to suppression of anoikis

The oncogenic epithelial–mesenchymal transition (EMT) contributes to tumor progression in various context-dependent ways, including increased metastatic potential, expansion of cancer stem cell subpopulations, chemo-resistance and disease recurrence. One of the hallmarks of EMT is resistance of tumor cells to anoikis. This resistance contributes to metastasis and is a defining property not only of EMT but also of cancer stem cells. Here, we review the mechanistic coupling between EMT and resistance to anoikis. The discussion focuses on several key aspects. First, we provide an update on new pathways that lead from the loss of E-cadherin to anoikis resistance. We then discuss the relevance of transcription factors that are crucial in wound healing in the context of oncogenic EMT. Next, we explore the consequences of the breakdown of cell-polarity complexes upon anoikis sensitivity, through the Hippo, Wnt and transforming growth factor β (TGF-β) pathways, emphasizing points of crossregulation. Finally, we summarize the direct regulation of cell survival genes through EMT-inducing transcription factors, and the roles of the tyrosine kinases focal adhesion kinase (FAK) and TrkB neurotrophin receptor in EMT-related regulation of anoikis. Emerging from these studies are unifying principles that will lead to improvements in cancer therapy by reprogramming sensitivity of anoikis

Personalized High-Dose-Rate Brachytherapy with Non-Sealed Rhenium-188 in Non-Melanoma Skin Cancer

Objectives: Most non-melanoma skin tumors are treated with conventional methods, being the most common surgery. However, satisfactory surgical treatment can be very challenging for patients with large or multiple lesions. In cases where the tumor is located on the face, hands or genital areas, the results may be suboptimal in terms of aesthetics and/or function. A high dose-rate brachytherapy using non-sealed Rhenium-188 was developed to offer a personalized solution for these cases as well as cases where a surgical approach was not preferred. Here we show a retrospective analysis of 43 patients treated with this technique.Methods: The technique, called dermatological high-dose-rate beta-brachytherapy (DBBR), is a brachytherapy based on a non-sealed beta-emitter embedded in a complex specially-designed acrylic matrix. We use Rhenium-188 as the beta-emitter. This matrix is applied over the tumor, which is protected by a special thin plastic foil avoiding any direct physical contact of the radioisotope with the skin. After the calculated required amount of time, the protective foil with the applied radioactive acrylic matrix is removed. 43 patients (basal/squamous cell carcinomas, BCCs and SCCs) were treated with this technique after histological confirmation of the non-melanoma skin tumor. Patients were then followed up, to evaluate wound healing as well as potential side-effects and recurrences.Results: 29 BCC and 14 SCC patients were treated with DBBR. 36/42 achieved complete clinical remission with only 1 application (24 BCC, 12 SCC) and 6/42 with 2 applications (4 BCC, 2 SCC); 1 BCC patient was lost to follow-up before wound closing. In 4 of the 6 patients (3 BCC, 1 SCC) treated twice the second treatment was planned due to the thickness of the tumor; in the remaining 2 patients (1 BCC, 1 SCC) the second treatment was needed to treat a recurrence at the border of the previously treated area. No side effects were reported. Wound healing was complete in 34-180 days (average 65 days, median 53) for all 42 patients that were followed-up. An average follow-up of 288 days (after one or two treatments) showed no single recurrence (42 patients).Conclusions: DBBR is a very promising alternative for treatment of BCCs and SCCs for all cases in which a surgical approach is not recommended or accepted by the patient

Development of an anthropomorphic breast phantom for combined PET, B-mode ultrasound and elastographic imaging

International audienceCombining the advantages of different imaging modalities leads to improved clinical results. For example, ultrasound provides good real-time structural information without any radiation and PET provides sensitive functional information. For the ongoing ClearPEM-Sonic project combining ultrasound and PET for breast imaging, we developed a dual-modality PET/Ultrasound (US) phantom. The phantom reproduces the acoustic and elastic properties of human breast tissue and allows labeling the different tissues in the phantom with different concentrations of FDG. The phantom was imaged with a whole-body PET/CT and with the Supersonic Imagine Aixplorer system. This system allows both B-mode US and shear wave elastographic imaging. US elastography is a new imaging method for displaying the tissue elasticity distribution. It was shown to be useful in breast imaging. We also tested the phantom with static elastography. A 6D magnetic positioning system allows fusing the images obtained with the two modalities. ClearPEM-Sonic is a project of the Crystal Clear Collaboration and the European Centre for Research on Medical Imaging (CERIMED)

Beelines: Joyce’s apian aesthetics

This article examines the presence of apian life in James Joyce’s body of work in light of Maurice Maeterlinck’s discovery at the turn of the twentieth-century that honeybees communicate using a complex system of language. In December 1903, Joyce offered to translate Maeterlinck’s book-length study La Vie Des Abeille (The Life of the Bee) (1901) for the Irish Bee-Keeper, and the pages of the journal later resurface on a book-cart in Ulysses. Beginning with a discussion of the ‘economy of bee life’ in Stephen Hero, this article explores Joyce’s career-long fascination with nonhuman modes of communication, tracing his fascination with apian intelligence through close readings of Bloom’s bee-sting in Ulysses, as well as through the swarm of references that appear in Finnegans Wake. Finally, it argues that bees offer new ways of reading Joyce’s work, opening up new lines of connection between the fields of literary criticism and apiculture, and drawing the reader’s attention to the peripheral hum or murmur at the edges of human speech

Intersection types for unbind and rebind

We define a type system with intersection types for an extension of lambda-calculus with unbind and rebind operators. In this calculus, a term with free variables, representing open code, can be packed into an "unbound" term, and passed around as a value. In order to execute inside code, an unbound term should be explicitly rebound at the point where it is used. Unbinding and rebinding are hierarchical, that is, the term can contain arbitrarily nested unbound terms, whose inside code can only be executed after a sequence of rebinds has been applied. Correspondingly, types are decorated with levels, and a term has type decorated with k if it needs k rebinds in order to reduce to a value. With intersection types we model the fact that a term can be used differently in contexts providing different numbers of unbinds. In particular, top-level terms, that is, terms not requiring unbinds to reduce to values, should have a value type, that is, an intersection type where at least one element has level 0. With the proposed intersection type system we get soundness under the call-by-value strategy, an issue which was not resolved by previous type systems.Comment: In Proceedings ITRS 2010, arXiv:1101.410

Bayesian physical reconstruction of initial conditions from large scale structure surveys

We present a fully probabilistic, physical model of the non-linearly evolved density field, as probed by realistic galaxy surveys. Our model is valid in the linear and mildly non-linear regimes and uses second order Lagrangian perturbation theory to connect the initial conditions with the final density field. Our parameter space consists of the 3D initial density field and our method allows a fully Bayesian exploration of the sets of initial conditions that are consistent with the galaxy distribution sampling the final density field. A natural byproduct of this technique is an optimal non-linear reconstruction of the present density and velocity fields, including a full propagation of the observational uncertainties. A test of these methods on simulated data mimicking the survey mask, selection function and galaxy number of the SDSS DR7 main sample shows that this physical model gives accurate reconstructions of the underlying present-day density and velocity fields on scales larger than ~6 Mpc/h. Our method naturally and accurately reconstructs non-linear features corresponding to three-point and higher order correlation functions such as walls and filaments. Simple tests of the reconstructed initial conditions show statistical consistency with the Gaussian simulation inputs. Our test demonstrates that statistical approaches based on physical models of the large scale structure distribution are now becoming feasible for realistic current and future surveys.Comment: 20 pages, 8 figure

Ionization potentials of crystalline organic thin films: Position dependence due to molecular shape and charge redistribution

In addition to electronic polarization or charge redistribution, the shape of neutral conjugated molecules yields position-dependent ionization potentials and electron affinities in organic thin films. Self-consistent I(n) and A(n) are computed in each layer n of 10-layer films of prototypical organics on a metal. The depth dependence of I(n) is discussed at surfaces of anthracene, C60 and PTCDA. The shape contribution can be substantial, up to 0.5 eV, and comes primarily from charge-quadrupole interactions.Comment: 13 pages, 4 figures, Accepted in Chem. Phys. Letter