1,721,024 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
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
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
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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