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

Evolution of magnetic fields and energetics of flares in active region 8210

To better understand eruptive events in the solar corona, we combine sequences of multi-wavelength observations and modelling of the coronal magnetic field of NOAA AR 8210, a highly flare-productive active region. From the photosphere to the corona, the observations give us information about the motion of magnetic elements (photospheric magnetograms), the location of flares (e.g., H$\alpha$, EUV or soft X-ray brightenings), and the type of events (H$\alpha$ blueshift events). Assuming that the evolution of the coronal magnetic field above an active region can be described by successive equilibria, we follow in time the magnetic changes of the 3D nonlinear force-free (nlff) fields reconstructed from a time series of photospheric vector magnetograms. We apply this method to AR 8210 observed on May 1, 1998 between 17:00 UT and 21:40 UT. We identify two types of horizontal photospheric motions that can drive an eruption: a clockwise rotation of the sunspot, and a fast motion of an emerging polarity. The reconstructed nlff coronal fields give us a scenario of the confined flares observed in AR 8210: the slow sunspot rotation enables the occurence of flare by a reconnection process close to a separatrix surface whereas the fast motion is associated with small-scale reconnections but no detectable flaring activity. We also study the injection rates of magnetic energy, Poynting flux and relative magnetic helicity through the photosphere and into the corona. The injection of magnetic energy by transverse photospheric motions is found to be correlated with the storage of energy in the corona and then the release by flaring activity. The magnetic helicity derived from the magnetic field and the vector potential of the nlff configuration is computed in the coronal volume. The magnetic helicity evolution shows that AR 8210 is dominated by the mutual helicity between the closed and potential fields and not by the self helicity of the closed field which characterizes the twist of confined flux bundles. We conclude that for AR 8210 the complex topology is a more important factor than the twist in the eruption process

What memory binding functions is the hippocampus responsible for?

The role of the hippocampus in binding information in working memory (WM) is little understood. When complex experiences comprise associations between different pieces of information such as objects and locations (relational binding), the function of the hippocampus is required to hold them in WM (Mitchell et al., 2000; 2006; Piekema, 2006). However, recent evidence suggests that if the to-be-associated information leads to the formation of integrated objects such as coloured shapes (conjunctive binding), the hippocampus is less involved in holding temporary representations of these complex events in WM (Baddeley et al., 2010; Piekema, 2006). We investigated the relational and conjunctive binding hypotheses of the hippocampal functions in a patient with right hippocampal damage. The patient and controls were asked to study visual arrays of stimuli which consisted of shape-colour relations (shape-colour pairs) or shape-colour conjunctions (coloured shapes). After the study array, they were presented with a new screen consisting of one set of shapes (line drawings) and one set of colours. They were asked to reconstruct the bindings by selecting the shapes and their corresponding colours. As compared to healthy controls, the patient was impaired in holding relations of shapes and colours in WM whereas he could retain the conjunctions similarly to controls. These results lend support to the role of the hippocampus in supporting memory for inter-item associations but not memory for conjunctions of features which define objects' identity

Microgravity research at the University of Mexico: Experiments in payload G-006

The experiments contained in the G-006 payload related to thin film vapor deposition, vacuum variations in a chamber vented to space, solidification of a Zn-Al-Cu alloy, and multiple location temperature monitoring for thermal model validation are described in detail. A discussion of the expected results is presented, together with the methods selected to conduct the postflight analysis, and finally, a overview of the future activities in this field

The course of cancer related fatigue up to ten years in early breast cancer patients. What impact in clinical practice?

Little is known about the cancer related fatigue (CRF) along cancer course and risk factors that could predict CRF development and persistence in breast cancer (BC) survivors. This prospective study detected incidence, timing of onset, duration of CRF, impact on QoL and psychological distress. Seventy-eight early BC patients, undergoing chemotherapy (CT) followed or not by hormonal therapy were assessed for QoL and psychological distress by EORTC QLQC30 and HADs questionnaires. Fatigue was investigated with mix methods, structured interview and psychometric measures. A qualitative analysis was added to assess the behavioral pattern of CRF. Low fatigue levels were identified after surgery (9%), increasing during (49%) and at the end of CT (47%), maintaining after 1 year (31%) and declining up to ten years of follow-up. Prevalence of CRF was higher at the end of CT and lower at follow-up. At the end and after 1 and 2 years from CT, persistence of CRF was associated to anxiety in 20%, 11% and 5% and to depression in 15%, 10% and 5% respectively. A relationship between CRF and psychological distress was observed; patients presenting depression and anxiety before CT were at higher risk for fatigue onset at a later period. A relationship between fatigue and QoL was noted at the end of CT. Our study shows the fatigue timely trend in early BC patients from surgery, CT and follow-up. Identification of biological, psychological, social predictor factors related to fatigue could be helpful for early interventions in patients at higher risk of developing fatigue

Lactante de 9 meses con convulsiones

- Datos Clínicos. - Antecedentes personales. - Enfermedad actual. - Aciduria Glutárica tipo I

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