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Lucia Festino*, Alessio Fabozzi*, Anna Manzo, Valentina Gambardella, Erika Martinelli, Teresa Troiani, Ferdinando De Vita, Michele Orditura, Fortunato Ciardiello, Floriana Morgillo Division of Medical Oncology, Department of clinical and experimental medicine and surgery "F. Magrassi e A. Lanzara", Second University of Naples, Napoli, Italy*These authors contributed equally to this work Abstract: The lack of valid clinical management options for patients affected by metastatic colorectal cancer, which has progressed after all approved standard treatments, has lead to research into new active molecules. Regorafenib is an oral small-molecule multi kinase inhibitor, binding to several intracellular kinases, with powerful inhibitory activity against vascular endothelial growth factor receptors (VEGFR-1,VEGFR-2, and VEGFR-3), platelet-derived growth factor receptor, fibroblast growth factor receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF. The antitumor activity of regorafenib has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in several cancer models, particularly colorectal cancer and gastrointestinal stromal tumors. The most frequent adverse events of grade 3 or higher related to regorafenib were hand-foot skin reaction, fatigue, diarrhea, hypertension, and rash or desquamation. Only a few Phase I–II trials, and most recently a Phase III trial in pretreated colorectal cancer, have been carried out to date. Several ongoing trials are testing the efficacy of regorafenib in combination with chemotherapy. At this point in time, regorafenib is the first small-molecule tyrosine kinase inhibitor to gain approval by the US Food and Drug Administration for pretreated metastatic colorectal cancer patients. Keywords: colorectal cancer, angiogenesis, regorafenib

This paper investigates the behaviour of FRP strips glued to concrete subjected to the cyclic loads often induced on structures by dynamic actions, such as the ones induced by traffic loads or earthquake events. The study moves from a theoretical model recently formulated by the Authors and capable to simulate the mechanical response of the aforementioned FRP-to-concrete joints. The model formulation, shortly summarised in this paper, is consistent with the general assumptions of fracture mechanics and closed-form expressions are obtained for determining the key fracture-related quantities. Then, a parametric analysis is carried out for investigating the influence of both the cyclic load protocol and the bond length on the resulting cyclic response of the system under consideration. The obtained results unveil that debonding failure under cyclic actions can be described by means of general conceptual tools derived by the theory of fatigue.

The European Society for Medical Oncology (ESMO) is one of the leading societies of oncology professionals in the world. Approximately 30% of the 13 000 ESMO members are below the age of 40 and thus meet the society's definition of young oncologists (YOs). ESMO has identified the training and development of YOs as a priority and has therefore established a comprehensive career development programme. This includes a leadership development programme to help identify and develop the future leaders in oncology. Well-trained and highly motivated future generations of multidisciplinary oncologists are essential to ensure the optimal evolution of the field of oncology with the ultimate goal of providing the best possible care to patients with cancer. ESMO's career development portfolio is managed and continuously optimised by several dedicated committees composed of ESMO officers and is directly supervised by the ESMO Executive Board and the ESMO President. It offers unique resources for YOs at all stages of training and includes a broad variety of fellowship opportunities, educational courses, scientific meetings, publications and resources. In this article, we provide an overview of the activities and career development opportunities provided by ESMO to the next generation of oncologists.

Objectives: Biodegradable implants can be used in patients with bone fractures and make a second surgery to remove them unnecessary. In the last years bioresorbable Magnesium implants are under investigation due to the high biocompatibility and low stress shielding which means similar mechanical properties[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2015)

BACKGROUND: The mitogen-activated protein kinase (MAPK) pathway has been implicated in the molecular pathogenesis of human cancers, including metastatic colorectal cancer (mCRC). This provides a rationale for the development of MAPK-targeted agents such as pimasertib. METHODS: Patients with KRAS mutant mCRC were treated in the second-line setting with FOLFIRI (5-fluorouracil/folinic acid/irinotecan) plus pimasertib. The primary objective of the safety run-in phase was to determine the maximum-tolerated dose (MTD) and the recommended phase II dose of pimasertib combined with FOLFIRI. RESULTS: Sixteen patients were enrolled in the trial. Ten and six patients were treated daily with 45 and 60 mg of pimasertib plus FOLFIRI, respectively. The MTD was considered to be 45 mg per day. The most common treatment-emergent adverse events were diarrhoea, nausea, vomiting, asthenia and skin/rash event. Of the 15 patients in the efficacy analysis group, two patients had partial response, nine patients had stable disease, three patients had progressive disease as their best overall response and one patient could not be evaluated. CONCLUSIONS: Dose escalation of pimasertib in combination with FOLFIRI was limited by toxicity. At the MTD of 45 mg per day, pimasertib was adequately tolerated in patients with mCRC and no unexpected or new safety signals or concerns were identified. ispartof: British Journal of Cancer vol:112 issue:12 pages:1874-1881 ispartof: location:England status: published

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High sensitivity and cross-selectivity are mandatory properties for sensor arrays. Although metalloporphyrins and pH indicators are among the most common and appropriate choices for the preparation of optical sensor arrays, the sensitivity spectrum of these dyes is limited to those analytes able to induce an optical response. To extend the receptive field of optical sensors, we explore the design of composite materials, where the molecular interaction among the subunits enriches their sensing working mechanisms. We demonstrate that blends of single metalloporphyrins and pH indicators, tested with a transduction apparatus based on ubiquitous and easily available hardware, can be endowed with sensing properties wider than those of single constituents, enabling the recognition of a broad range of volatiles.

Medulloblastoma is the most frequent malignant pediatric brain tumor with a dismal prognosis in 30% of cases. We examined the activity of AEE788, a dual inhibitor of human epidermal receptor (HER) 1/2 and vascular endothelial growth factor receptor (VEGFR) 1/2, in medulloblastoma preclinical models. Established lines (Daoy and D283), chemoresistant (DaoyPt), and ectopically HER2-overexpressing (DaoyHER2) cells expressed diverse levels of total and activated AEE788 target receptors. In vitro, AEE788 inhibited cell proliferation (IC50 from 1.7 to 3.8 μM) and prevented epidermal growth factor- and neuregulin-induced HER1, HER2, and HER3 activation. Inhibition of Akt paralleled that of HER receptors. In vivo, AEE788 growth inhibited Daoy, DaoyPt, and DaoyHER2 xenografts by 51%, 45%, and 72%, respectively. Immunohistochemical analysis of mock- and HER2-transfected xenografts revealed that the latter showed, along with high HER2 expression, high VEGFR2 staining in tumor and endothelial cells and increased expression of the endothelial marker CD31. AEE788 reduced the activation of target receptors and angiogenesis. In 21 primary medulloblastoma, HER2 expression significantly correlated (P