199 research outputs found
L’eterogeneità perfusionale: un biomarker prognostico per il cancro del polmone non a piccole cellule (NSCLC)
No full textL’introduzione in oncologia di nuove terapie, in particolare quelle a bersaglio molecolare, ha condotto a notevoli progressi terapeutici, determinando miglior controllo del tumore, selettività terapeutica, ridotta tossicità. Tuttavia la prognosi per i pazienti affetti da tumore polmonare non a piccole cellule (NSCLC) in stadio avanzato risulta tuttora molto severa. Sebbene il più importante fattore prognostico sia attualmente costituito dallo stadio del tumore, la sopravvivenza di pazienti affetti da NSCLC e appartenenti allo stesso stadio risulta ampiamente variabile. Per queste ragioni, è necessario identificare marcatori prognostici più efficaci che siano in grado di stabilire quali tumori saranno sensibili o resistenti alle terapie. Questo condurrebbe ad una migliore gestione e stratificazione dei pazienti affetti da NSCLC, con notevoli implicazioni nella scelta dei trattamenti. L’analisi dell’eterogeneità neoplastica nei pazienti NSCLC, caratterizzata attraverso l’analisi strutturale mediante Tomografia Computerizzata (TC), ha mostrato notevoli potenzialità nel predire l’aggressività di un tumore. Anche più promettente è l’analisi dell’eterogeneità funzionale in grado di mettere in luce non solo le anomalie strutturali ma anche le disomogeneità funzionali presenti all’interno di un tumore. Tra le tecniche di imaging funzionale, particolare rilievo sta assumendo la TC perfusionale (TCp), che permette l’identificazione di pattern vascolari anomali, consentendo una valutazione precoce della risposta alle terapie citostatiche. In questo lavoro retrospettivo, valutiamo se alcuni indicatori, calcolabili a partire dalle mappe di valori perfusionali ottenute tramite TCp, possano essere utilizzati come marcatori prognostici. I risultati rilevano una coppia di indicatori in grado di separare pazienti affetti da NSCLC con diversa aspettativa di sopravvivenza. Viene confermata la comune aspettativa che una maggiore eterogeneità correli con una maggiore aggressività, riflettendosi gravemente sulla sopravvivenza dei pazienti. Si può quindi concludere che la misura emodinamica dell’eterogeneità tumorale rappresenti un significativo e oggettivo fattore prognostico, con possibili ricadute cliniche della TCp
A Computational Approach to Poetic Structure, Rhythm and Rhyme
No full textIn this paper we present SPARSAR, a system for the automatic analysis of English and Italian poetry. The system can work on any type of poem and produces a set of parameters that are then used to compare poems with one another, of the same author or of different authors. In this paper, we will concentrate on the second module, which is a rule-based system to represent and analyze poetic devices. Evaluation of the system on the basis of a manually created dataset - including poets from Shakespeare's time down to T.S.Eliot and Sylvia Plath - has shown its high precision and accuracy approximating 90%
Exploring Speech Technologies for Language Learning
No full textThe teaching of the pronunciation of any foreign language must encompass both segmental and suprasegmental aspects
of speech. In computational terms, the two levels of language learning activities can be decomposed at least into
phonemic aspects, which include the correct pronunciation of single phonemes and the co-articulation of phonemes into
higher phonological units; as well as prosodic aspects which include
the correct position of stress at word level;
the alternation of stress and unstressed syllables in terms of compensation and vowel reduction;
the correct position of sentence accent;
the generation of the adequate rhymth from the interleaving of stress, accent, and phonological rules;
the generation of adequate intonational pattern for each utterance related to communicative functions;
As appears from above, for a student to communicate intelligibly and as close as possible to native-speaker's
pronunciation, prosody is very important [3]. We also assume that an incorrect prosody may hamper communication
from taking place and this may be regarded a strong motivation for having the teaching of Prosody as an integral part of
any language course. From our point of view it is much more important to stress the achievement of successful
communication as the main objective of a second language learner rather than the overcoming of what has been termed
“foreign accent”, which can be deemed as a secondary goal. In any case, the two goals are certainly not coincident even
though they may be overlapping in some cases. We will discuss about these matter in the following sections.
All prosodic questions related to “rhythm” will be discussed in the first section of this chapter. In [4] the author argues
in favour of prosodic aids, in particular because a strong placement of word stress may impair understanding from the
listener’s point of view of the word being pronounced. He also argues in favour of acquiring correct timing of
phonological units to overcome the impression of “foreign accent” which may ensue from an incorrect distribution of
stressed vs. unstressed stretches of linguistic units such as syllables or metric feet. Timing is not to be confused with
speaking rate which need not be increased forcefully to give the impression of a good fluency: trying to increase
speaking rate may result in lower intelligibility. The question of “foreign accent” is also discussed at length in (Jilka M.,
1999). This work is particularly relevant as far as intonational features of a learner of a second language which we will
address in the second section of this chapter. Correcting the Intonational Foreign Accent (hence IFA) is an important
component of a Prosodic Module for self-learning activities, as categorical aspects of the intonation of the two languages
in contact, L1 and L2 are far apart and thus neatly distinguishable. Choice of the two languages in contact is determined
mainly by the fact that the distance in prosodic terms between English and Italian is maximal, according to (Ramus, F.
and J. Mehler, 1999; Ramus F., et al., 1999)
Targeting RET-rearranged non-small-cell lung cancer: future prospects
No full textGiuseppe Bronte, Paola Ulivi, Alberto Verlicchi, Paola Cravero, Angelo Delmonte, Lucio Crinò Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy Abstract: Non-small-cell lung cancer (NSCLC) patients with mutated or rearranged oncogene drivers can be treated with upfront selective inhibitors achieving higher response rates and longer survival than chemotherapy. The RET gene can undergo chromosomal rearrangements in 1%–2% of all NSCLC patients, involving various upstream fusion partners such as KIF5B, CCDC6, NCOA4, and TRIM33. Many multikinase inhibitors are active against rearranged RET. Cabozantinib, vandetanib, sunitinib, lenvatinib, and nintedanib achieved tumor responses in about 30% of these patients in retrospective studies. Prospective phase II trials investigated the activity and toxicity of cabozantinib, vandetanib, sorafenib, and lenvatinib, and did not reach significantly higher response rates. VEGFR and EGFR inhibition represented the main ways of developing off-target toxicity. An intrinsic resistance emerged according to the type of RET fusion partners, as KIF5B-RET fusion is the most resistant. Also acquired mutations in rearranged RET oncogene developed as resistance to these multikinase inhibitors. Interestingly, RET fusions have been found as a resistance mechanism to EGFR-TKIs in EGFR-mutant NSCLC patients. The combination of EGFR and RET inhibition can overcome this resistance. The limitations in terms of activity and tolerability of the various multikinase inhibitors prompted the investigation of new highly selective RET inhibitors, such as RXDX-105, BLU-667, and LOXO-292. Some data emerged about intracranial antitumor activity of BLU-667 and LOXO-292. If these novel drugs will achieve high activity in RET rearranged NSCLC, also these oncogene-addicted tumors can undergo a significant survival improvement. Keywords: RET, non-small-cell lung cancer, multi-kinase inhibitors, gene rearrangemen
Targeting Chromatin-Mediated Transcriptional Control of Gene Expression in Non-Small Cell Lung Cancer Therapy: Preclinical Rationale and Clinical Results
No full textTargeting chromatin-mediated transcriptional control of gene expression is nowadays considered a promising new strategy, transcending conventional anticancer therapy. As a result, molecules acting as DNA demethylating agents or histone deacetylase inhibitors (HDACi) have entered the clinical arena in the last decade. Given the evidence suggesting that epigenetic regulation is significantly involved in lung cancer development and progression, the potential of epigenetically active compounds to modulate gene expression and reprogram cancer cells to a less aggressive phenotype is, at present, a promising strategy. Accordingly, a large number of compounds that interact with the epigenetic machinery of gene expression regulation are now being developed and tested as potential antitumor agents, either alone or in combination with standard therapy. The preclinical rationale and clinical data concerning the pharmacological modulation of chromatin organization in non-small cell lung cancer (NSCLC) is described in this review. Although preclinical data suggest that a pharmacological treatment targeting the epigenetic machinery has relevant activity over the neoplastic phenotype of NSCLC cells, clinical results are disappointing, leading only to short periods of disease stabilization in NSCLC patients. This evidence calls for a significant rethinking of strategies for an effective epigenetic therapy of NSCLC. The synergistic effect of concurrent epigenetic therapies, use at low doses, the priming of current treatments with previous epigenetic drugs, and the selection of clinical trial populations based on epigenetic biomarkers/signatures appear to be the cornerstones of a mature therapeutic strategy aiming to establish new regimens for reprogramming malignant cells and improving the clinical history of affected patients
Spontaneous Upbeat Nystagmus and Selective Anterior Semicircular Canal Hypofunction on Video Head Impulse Test: A New Variant of Canalith Jam?
No full text: We describe a rare case of spontaneous upbeat nystagmus (UBN) attributable to a canalith jam involving the anterior semicircular canal (ASC) in a patient in whom comprehensive vestibular assessment was useful to identify the underlying pathomechanism. A 56-year-old woman with unsteadiness following repositioning procedures for left-sided benign paroxysmal positional vertigo (BPPV) presented with spontaneous UBN that showed slight right torsional components. A vestibular test battery detected isolated left ASC hypofunction on a video-head impulse test (Video-HIT). We postulated a persistent utriculopetal deflection of the left ASC cupula, which was attributable to entrapment of debris in a narrow canal tract, with consequent sustained inhibition of the ampullary afferents. Although spontaneous UBN receded after impulsive physical therapy, unsteadiness deteriorated into positional vertigo secondary to canalolithiasis involving the ipsilateral posterior canal. In our view, physical therapy possibly fragmented the canalith jam and released free-floating otoconia that eventually settled into the ipsilateral posterior canal. Video HIT revealed normalization of ASC hypofunction, and leftsided posterior canal canalolithiasis was successfully treated using appropriate repositioning procedures. We propose that a canalith jam involving the ASC should be considered in the differential diagnosis of spontaneous UBN, particularly in patients with a history of BPPV and isolated ASC hypofunction detected on video HIT
Role of liquid biopsy in oncogene-addicted non-small cell lung cancer
No full textThe discovery of actionable oncogene in non-small cell lung cancer (NSCLC) allowed the identification of a subgroup of patients who benefit from targeted tyrosine kinase inhibitors more than others. Mutations in the epidermal growth factor receptor (EGFR), translocations in the anaplastic lymphoma kinase (ALK) and rearrangements in the ROS proto-oncogene 1 (ROS1) must be identified in tumor tissue to guide the proper treatment choice. Liquid biopsy is based on the analysis of tumor materials released in the circulation. Liquid biopsy can be complementary to tissue biopsy, both at baseline and at progression, especially in the detection of somatic gene alterations emerging during the treatment with tyrosine kinase inhibitors (TKIs). Particularly, circulating DNA is used to find mutations in driver oncogenes, while circulating tumor cells, extracellular vesicles (EVs) and cell-free microRNAs (cfmiRNAs) are still under investigation. To help the unbiased use of liquid biopsy in the choice of the appropriate therapy, some recommendations were delivered by expert panels. Currently, analysis of EGFR mutations in cell-free DNA (cfDNA) is recommended at baseline when tissue biopsy harbors scarce tumor cells, and at progression before performing tissue biopsy; liquid biopsy analysis for other oncogenic drivers is not indicated in the clinical practice
Targeting RET-rearranged non-small-cell lung cancer: future prospects
No full textNon-small-cell lung cancer (NSCLC) patients with mutated or rearranged oncogene drivers can be treated with upfront selective inhibitors achieving higher response rates and longer survival than chemotherapy. The RET gene can undergo chromosomal rearrangements in 1%–2% of all NSCLC patients, involving various upstream fusion partners such as KIF5B, CCDC6, NCOA4, and TRIM33. Many multikinase inhibitors are active against rearranged RET. Cabozantinib, vandetanib, sunitinib, lenvatinib, and nintedanib achieved tumor responses in about 30% of these patients in retrospective studies. Prospective phase II trials investigated the activity and toxicity of cabozantinib, vandetanib, sorafenib, and lenvatinib, and did not reach significantly higher response rates. VEGFR and EGFR inhibition represented the main ways of developing off-target toxicity. An intrinsic resistance emerged according to the type of RET fusion partners, as KIF5B-RET fusion is the most resistant. Also acquired mutations in rearranged RET oncogene developed as resistance to these multikinase inhibitors. Interestingly, RET fusions have been found as a resistance mechanism to EGFR-TKIs in EGFR-mutant NSCLC patients. The combination of EGFR and RET inhibition can overcome this resistance. The limitations in terms of activity and tolerability of the various multikinase inhibitors prompted the investigation of new highly selective RET inhibitors, such as RXDX-105, BLU-667, and LOXO-292. Some data emerged about intracranial antitumor activity of BLU-667 and LOXO-292. If these novel drugs will achieve high activity in RET rearranged NSCLC, also these oncogene-addicted tumors can undergo a significant survival improvement
Bordetella bronchiseptica pneumonia in a patient with lung cancer; a case report of a rare infection
No full textAbstract Background Bordetella bronchiseptica (B.bronchiseptica) is a frequent cause of respiratory infections in animals but rarely causes serious infection in humans. We present a rare case of B. bronchiseptica pneumonia in a patient with lung cancer. Case presentation A 52-year-old white male with non small cell lung cancer developed fever during treatment with nivolumab. A persistent productive cough and a deterioration in his clinical condition led to his hospitalization for evaluation. Bronchoscopy was performed and a diagnosis of B. bronchiseptica pneumonia was made. The infection was successfully managed by antiobiotic therapy. Conclusions B. bronchiseptica is a pathogen that can cause serious infection in humans, especially in immunocompromised or immunoincompetent individuals. In our patient it showed unusual resistance to cephalosporins and poor sensitivity to amikacin. To our knowledge this is the first case of such an infection in a lung cancer patient undergoing treatment with nivolumab. When B. bronchiseptica is identified, the possibility of a nosocomial transmission must be considered
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