First-line therapy in HER2 positive metastatic breast cancer. Is the mosaic fully completed or are we missing additional pieces?

The discovery of human epidermal growth factor receptor 2 (HER2) and its role in the biology of breast cancer and the subsequent development of HER2-targeted therapies, have dramatically improved clinical outcomes for women with early-stage and advanced HER2-positive breast cancer (BC). HER-2 targeted therapies represent a major step forward in achieving the goal of delivering individualized targeted therapy for BC, and trastuzumab was the first anti-HER-2 strategy to be approved for treatment of HER-2 positive BC. This review discusses the treatment of metastatic HER2-positive BC and describes efficacy and safety of novel anti-HER2 target therapies in first-line metastatic settings and the future challenges include refining such treatments, reducing toxicity and simultaneously developing innovative therapies. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described. In the next future will be possible to use an ample armamentarium of combination therapies directed against HER2 and key signaling components integrated in the HER network. This approach will allow clinicians to tailor the management of the individual patient on the basis of tumor- specific biomarker profiles. There is an urgent need for prospective biomarker-driven trials to identify patients for whom targeting is cost-effective

Aggregative movement and front propagation for bi-stable population models

Front propagation for the aggregation-diffusion-reaction equation is investigated, where f is a bi-stable reaction-term and D(v) is a diffusion coefficient with changing sign, modeling aggregating-diffusing processes. We provide necessary and sufficient conditions for the existence of traveling wave solutions and classify them according to how or if they attain their equilibria at finite times. We also show that the dynamics can exhibit the phenomena of finite speed of propagation and/or finite speed of saturation

Diffusion-aggregation processes with mono-stable reaction terms

This paper analyses front propagation of the equation $u_\tau=[D(u)v_x]_x +f(v) \;\;\; \tau < 0, x \in \mathbb{R}$ where $f$ is a monostable (ie Fisher-type) nonlinear reaction term and $D(v)$ changes its sign once, from positive to negative values,in the interval $v \in[0,1]$ where the process is studied. This model equation accounts for simultaneous diffusive and aggregative behaviors of a population dynamic depending on the population density $v$ at time $\tau$ and position $x$. The existence of infinitely many travelling wave solutions is proven. These fronts are parametrized by their wave speed and monotonically connect the stationary states u = 0 and v = 1. In the degenerate case, i.e. when D(0) and/or D(1) = 0, sharp profiles appear, corresponding to the minimum wave speed. They also have new behaviors, in addition to those already observed in diffusive models, since they can be right compactly supported, left compactly supported, or both. The dynamics can exhibit, respectively, the phenomena of finite speed of propagation, finite speed of saturation, or both

Activity of eribulin mesylate in brain metastasis from breast cancer. a stone in a pond?

Background: Brain metastases develop in approximately 10-25% of patients with metastatic breast cancer (MBC) and are associated with a very poor prognosis. Case Report: We report the case of a 40-year-old woman with MBC and associated lung, bone, liver, and brain metastases, who experienced a time to progression of several months with eribulin after whole-brain radiotherapy (WBRT), 2 lines of chemotherapy, and 1 line of hormonal therapy, maintaining a good toxicity profile. Discussion: Eribulin, in association with local treatment such as WBRT, can be well tolerated and effective in achieving a long progression-free survival and a good control of brain metastases in patients with MBC who have received multiple lines of treatment. The vascular remodeling properties of eribulin, combined with brain radiotherapy, might facilitate the passage of eribulin across the blood brain barrier, improving brain response. Conclusion: Our anecdotal experience suggests that eribulin may have a potentially beneficial effect on brain metastases while maintaining a good systemic control of the disease in patients with MBC

Have we detected the most luminous ULX so far?

We report the XMM-Newton detection of a moderately bright X-ray source superimposed on the outer arms of the inactive spiral galaxy MCG-03-34-63 (z=0.0213). It is clearly offset from the nucleus (by about 19'') but well within the D25 ellipse of the galaxy, just along its bar axis. The field has also been observed with the HST enabling us to compute a lower limit of > 94 on the X-ray to optical flux ratio which, together with the X-ray spectrum of the source, argues against a background AGN. On the other hand, the detection of excess X-ray absorption and the lack of a bright optical counterpart argue against foreground contamination. Short-timescale variability is observed, ruling out the hypothesis of a particularly powerful supernova. If it is associated with the apparent host galaxy, the source is the most powerful ULX detected so far with a peak luminosity of 1.35x10^41 erg/s in the 0.5-7 keV band. If confirmed by future multi-wavelength observations, the inferred bolometric luminosity (about 3x10^41 erg/s) requires a rather extreme beaming factor (larger than 115) to accommodate accretion onto a stellar-mass black hole of 20 solar masses and the source could represent instead one of the best intermediate-mass black hole candidate so far. If beaming is excluded, the Eddington limit implies a mass of >2300 solar masses for the accreting compact object.Comment: MNRAS Letters in press; minor correction at the end of Section

GRB Observed by IBIS/PICsIT in the MeV Energy Range

We present the preliminary results of a systematic search for GRB and other transients in the publicly available data for the IBIS/PICsIT (0.2-10 MeV) detector on board INTEGRAL. Lightcurves in 2-8 energy bands with time resolution from 1 to 62.5 ms have been collected and an analysis of spectral and temporal characteristics has been performed. This is the nucleus of a forthcoming first catalog of GRB observed by PICsIT.Comment: 6 pages, 3 figures. Poster presented at COSPAR 2008. Advaces in Space Research, accepted for publicatio

Casting Light on the Hidden Bilevel Combinatorial Structure of the Capacitated Vertex Separator Problem

Given an undirected graph, we study the capacitated vertex separator problem that asks to find a subset of vertices of minimum cardinality, the removal of which induces a graph having a bounded number of pairwise disconnected shores (subsets of vertices) of limited cardinality. The problem is of great importance in the analysis and protection of communication or social networks against possible viral attacks and for matrix decomposition algorithms. In this article, we provide a new bilevel interpretation of the problem and model it as a two-player Stackelberg game in which the leader interdicts the vertices (i.e., decides on the subset of vertices to remove), and the follower solves a combinatorial optimization problem on the resulting graph. This approach allows us to develop a computational framework based on an integer programming formulation in the natural space of the variables. Thanks to this bilevel interpretation, we derive three different families of strengthening inequalities and show that they can be separated in polynomial time. We also show how to extend these results to a min-max version of the problem. Our extensive computational study conducted on available benchmark instances from the literature reveals that our new exact method is competitive against the state-of-the-art algorithms for the capacitated vertex separator problem and is able to improve the best-known results for several difficult classes of instances. The ideas exploited in our framework can also be extended to other vertex/edge deletion/ insertion problems or graph partitioning problems by modeling them as two-player Stackel- berg games and solving them through bilevel optimization

XMM-Newton observations of ULIRGs I: A Compton-thick AGN in IRAS19254-7245

We present the XMM-Newton observation of the merging system IRAS 19254-7245, also known as The Superantennae, whose southern nucleus is classified as a Seyfert 2 galaxy. The XMM-Newton data have allowed us to perform a detailed X-ray imaging and spectral analysis of this system. We clearly detect, for the first time in this system, a strong EW ~ 1.4 keV Fe emission line at 6.49+/-0.1 keV (rest-frame). The X-ray spectrum requires a soft thermal component (kT~0.9 keV; L(0.5-2) ~ 4E41 cgs), likely associated with the starburst, and a hard power-law continuum above 2 keV (observed L(2-10) ~ 4E42 cgs). We confirm the flatness of this latter component, already noted in previous ASCA data. This flatness, together with the detection of the strong Fe-Kalpha line and other broad band indicators, suggest the presence of a Compton-thick AGN with intrinsic luminosity > 1E44 cgs. We show that a Compton-thick model can perfectly reproduce the X-ray spectral properties of this object.Comment: 6 pages, 4 figures, Latex manuscript, Accepted for publication in Astronomy and Astrophysic