Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial

Background Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM. Methods Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response. Results The lapatinib-temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09-20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82-3.37]. Conclusions The lapatinib-temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesion

Paraphrastic Reformulations in Spoken Corpora

International audienceOur work addresses the automatic detection of paraphrastic reformulation in French spoken corpora. The proposed approach is syn-tagmatic. It is based on specific markers and the specificities of the spoken language. Manual multi-dimensional annotation performed by two annotators provides fine-grained reference data. An automatic method is proposed in order to decide whether sentences contain or not paraphras-tic relations. The obtained results show up to 66.4% precision. Analysis of the manual annotations indicates that few paraphrastic segments show morphological modifications (inflection, derivation or compounding) and that the syntactic equivalence between the segments is seldom respected, as these usually belong to different syntactic categories

Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions

Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies. © 2014 The Author(s)

Etico, Sostenibile, Tecnologico, Territoriale, Internazionale, Multiculturale…| Ethical, Susatinable, Technological, National, International, Multicultural…

La selezione dei progetti e dei prodotti di eccellenza del 2018, attraverso le sue 13 sezioni, conferma pienamente l’attitudine multiforme del design italiano, capace di muoversi sia su registri produttivi da industria avanzata (Industria 4.0), sia su soluzioni sperimentali limitate ed estreme, sia infine sulle numerose piccole e grandi problematiche del quotidiano alle quali cerca di dare risposte intelligenti e sostenibili

Washback in language assessment

This paper reviews the progress made in washback studies over the quarter century since Hughes (1989) placed it at the centre of his textbook Testing for Language Teachers. Research into washback and the development of models of washback are described and an agenda is suggested for test developers wishing to build washback into their programmes. It is recommended that future projects should pay greater attention to test design features and to the outcomes of learning as well as continuing to explore learner motivation and cultural factors that might encourage participants to react to tests in certain ways, but not in others. Washback research itself is seen to be a potentially valuable tool in persuading participants to adopt new practices

Event coreference and discourse relations

Event coreference is largely ignored in works on coreference as well as in works on temporal order in discourses, in which temporal relations between two eventualities e1 and e2 always suppose that e1 6=e2. However, event coreference is not an uncommon phenomenon. We show that it is the keystone on which at least four types of discourses are based: on the one hand, particularizing and generalizing discourses, which can be viewed as special cases of elaboration andreformulation discourses respectively, on the other hand causal discourses in which the effect is expressed by means of a causative verb, which are generally analyzed as explanation or result discourses. Descriptionsand linguistic analyses of these discourses allow us to present unusual linguistic phenomena (e.g., coreference between existentially quantified elements, or assymetrical behavior of explanation or resultdiscourses). The discourse relations involved are examined. This leads us to introduce and define new discourse relations . It also sheds a new light on the discourse relations Explanation and Result

Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial.

info:eu-repo/semantics/publishe