1,720,973 research outputs found
POTENZIALE APPLICAZIONE DELL'ANALISI DEL DNA TUMORALE CIRCOLANTE IN UNA COORTE REAL-WORLD DI PAZIENTI CON ADENOCARCINOMA DEL DUTTALE PANCREATICO: LO STUDIO “PANTA REI”.
No full textBackground,Studi hanno suggerito la fattibilità e la potenziale utilità clinica dell'analisi del DNA tumorale circolante (ct) come marcatore prognostico per identificare i pazienti con adenocarcinoma duttale pancreatico (PDAC) che trarrebbero beneficio dall'intensificazione del trattamento pre e/o post-operatorio e per guidare il processo decisionale tra le diverse combinazioni disponibili per il PDAC metastatico. Il gene KRAS è mutato in oltre il 90% dei PDAC e l'eterogeneità delle mutazioni KRAS tra tumore primario e metastasi nei singoli pazienti è rara, suggerendo che il KRAS mutante circolante è un buon biomarcatore per rilevare la presenza di cellule tumorali. Tuttavia, il significato clinico del ct-DNA mutato con KRAS nel PDAC è stato poco utile in clinica perché sono stati utilizzati pochi timepoints, senza un monitoraggio longitudinale durante il trattamento. Abbiamo mirato a esplorare la fattibilità e l'utilità clinica dell'analisi del ct-DNA per informare il processo decisionale concentrandosi sulla prognosi e ruolo predittivo dei geni KRAS mutanti circolanti nel sangue e nelle urine dei pazienti con PDAC, in qualsiasi stadio e con una valutazione longitudinale in più timepoints. Abbiamo presentato i dati preliminari di una serie di casi di pazienti con PDAC in fase iniziale e avanzata. Materiale e metodi. I campioni di tumore, sangue e urina sono stati raccolti in modo prospettico alla diagnosi e nei seguenti timepoints: nei pazienti con PDAC resecabile (coorte 1), i campioni di plasma e urina sono stati raccolti ad ogni TC durante il trattamento neoadiuvante, a 4 settimane prima dell'intervento chirurgico , a 4-8 settimane dopo l'intervento, ad ogni TC. Campioni di plasma e urina sono stati analizzati per mutazioni negli esoni 2, 3, 4 di KRAS mediante ddPCR. Abbiamo utilizzato il sistema QX200 ddPCR (Bio-Rad, Berkeley, California). L'indice semi-quantitativo dell'abbondanza frazionaria dell'allele mutato è stato utilizzato e correlato all'esito clinico eseguendo il test di Pearson. La PFS e l'OS mediane sono state stimate con il metodo Kaplan-Meier. Risultati. Da gennaio 2020 a maggio 2023, sono stati arruolati prospetticamente 152 pazienti: 45 e 107 sono stati inclusi rispettivamente nella coorte 1 e nella coorte 2. Nella coorte 1 l'età media è risultata di 58,4 anni con 24 maschi, nella coorte 2 l'età media è stata di 64,6 anni con 64 maschi. Tra tutti i pazienti reclutati, 20 pazienti con PDAC KRAS-mutato hanno presentato dei risultati definitivi dall'analisi ddPCR basata su plasma e sono stati inclusi nella presente serie di casi: 11 (55%) uomini, con un'età media di 65,9 anni; 4 (20%) arruolati nella coorte 1. Nella casistica, la PFS mediana era di 4,05 mesi e la OS mediana dall'inizio della terapia era di 11,18 mesi. La sensibilità totale del rilevamento della mutazione KRAS nel plasma al basale era del 55%: nella coorte 1 risultava del 25% e nella coorte 2 del 62,5%. La correlazione tra la percentuale di incremento dell'abbondanza frazionaria e la PFS è stata fortemente negativa eseguendo il test di Pearson (indice di correlazione: -0,85).
Conclusioni. Lo studio è stato pianificato per dimostrare per la prima volta che il rilevamento del ct-DNA nel PDAC in qualsiasi fase e la sua dinamica del livello di espressione mediante valutazione longitudinale potrebbero essere utilizzati rispettivamente per la determinazione della prognosi e il monitoraggio della malattia. La presente serie di casi ha fatto luce sulle numerose sfide da superare per rendere il ct-DNA un biomarcatore fattibile e accurato sulla gestione dei pazienti con PDAC. I nostri risultati definitivi dall'ampia popolazione di studio potrebbero confermare le intuizioni tratte dalla presente serie di casi riguardo al ruolo prognostico e predittivo dell'analisi del ct-DNA.Background. Several studies suggested the feasibility and potential clinical utility of circulating tumoral (ct) DNA analysis as a prognostic marker to identify pancreatic ductal adenocarcinoma (PDAC) patients most likely to benefit from intensification of treatment pre- and/or post-operatively, and to guide decision-making among the different combinations available to metastatic PDAC. The KRAS gene is mutated in over 90% of PDAC and the heterogeneity of KRAS mutations between primary tumor and metastasis in individual patients is rare, suggesting that circulating mutant KRAS is a good biomarker for detecting the presence of cancer cells. However, the clinical significance of KRAS-mutated ct-DNA in PDAC has been inconsistent with respect to decision-making because limited points of detection of circulating mutant KRAS genes have been used, without a longitudinal monitoring throughout the treatment. We aimed to explore the feasibility and clinical utility of ct-DNA analysis to inform decision-making focusing on the prognostic
and predictive role of circulating mutant KRAS genes in the blood and urine of PDAC patients, at any stage and with a longitudinal evaluation at several time-points. We presented preliminary data of a case series of patients with early- and late-stage PDAC.
Material and Methods. Matched tumor, blood and urine samples were prospectively collected at diagnosis and at the following time-points: in patients with resectable PDAC (cohort 1), plasma and urine samples were collected at each CT imaging during the neoadjuvant treatment, at 4 weeks before surgery, at 4-8 weeks after surgery, at each CT
evaluation during the adjuvant treatment and at each follow-up visit; in patients with advanced PDAC (cohort 2), samples were collected at each CT evaluation during the first-line treatment. Formalin-fixed paraffin-embedded specimens were evaluated for KRAS mutations in exons 2, 3, 4, using MassArray. Plasma and urine samples were analyzed for mutations in KRAS exons 2, 3, 4 by droplet digital polymerase chain reaction (ddPCR). We employed QX200 ddPCR system (Bio-Rad, Berkeley, California). Semi-quantitative index of fractional abundance of mutated allele was used and correlated to clinical outcome performing the Pearson’s test. Median PFS and OS were estimated by the Kaplan-Meier method.
Results. From January 2020 to May 2023, 152 patients were prospectively enrolled: 45 and 107 were included in cohort 1 and in cohort 2, respectively. In cohort 1, the median age resulted 58.4 years with 24 males, in cohort 2 the median age was 64.6 years with 64 males. Among all the recruited patients, 20 patients with KRAS-mutated PDAC presented definitive results from plasma-based ddPCR analysis and were included in the present case series: 11 (55%) men, with a median age of 65.9 years; 4 (20%) enrolled in cohort 1. In the case series, median PFS was 4.05 months and median OS from the therapy start was 11.18 months. The total sensitivity of KRAS mutation detection in plasma at baseline was 55%: in cohort 1 it resulted 25% and in cohort 2 62.5%. Correlation between the percentage of increment of fractional abundance and PFS was strongly negative performing the Pearson’s test (correlation index: -0.85).
Conclusions This study was planned to demonstrate for the first time that ct-DNA detection in PDAC at any stage and its expression level dynamics by longitudinal evaluation could be used for prognosis determination and disease monitoring, respectively. The present case series casted light on the several challenges to be overcome in order to make ct-DNA a feasible and accurate biomarker on the management of PDAC patients. Our definitive results from the large study population could confirm the insights drawn from the present case series regarding the prognostic and predictive role of ct-DNA analysis
Microsatellite Instable Colorectal Adenocarcinoma Diagnostics: The Advent of Liquid Biopsy Approaches
Full text linkThe introduction of immunotherapy has revolutionized the oncological targeted therapy paradigm. Microsatellite instability (MSI) identifies a subgroup of colorectal cancers (CRCs) which respond to treatment with immune checkpoint inhibitors. Tissue biopsy is currently the gold standard for the assessment of MSI/Mismatch Repair deficiency (MMRd) by means immunohistochemistry or molecular assays. However, the application of liquid biopsy in the clinic may help to overcome several limitations of tissue analysis and may provide great benefit to the diagnostic scenario and therapeutic decision-making process. In the context of MSI/MMRd CRC, the use of liquid biopsy may allow to establish MSI/MMR status if tissue sampling cannot be performed or in case of discordant tissue biopsies. Liquid biopsy may also become a powerful tool to monitor treatment response and the onset resistance to immunotherapy over time and to stratify of MSI/MMRd patients according to their risk of relapse and metastases. The aim of this review is to summarize the main technical aspects and clinical applications, the benefits, and limitations of the use of liquid biopsy in MSI/MMRd colorectal cancer patients
An overview on clinical, pathological and molecular features of lung metastases from colorectal cancer
No full textIntroduction: Lung metastases occur in 10-20% of patients with colorectal cancer (CRC). Most of them are treated with palliative intent and have a poor prognosis. Pulmonary metastasectomy may be a curative option for carefully selected patients with 5-year survival rates ranging from 25% to 60%. However, up to 70% of patients develop recurrence after pulmonary metastasectomy. Therefore, the identification of prognostic factors is essential in CRC patients with resectable lung metastases. Areas covered: This review aims at summarizing the actual body of knowledge available on lung metastases from CRC focusing on their clinical, pathological and molecular profile. Moreover, we provide an update on experts' attitudes towards lung metastasectomy, adjuvant or perioperative chemotherapy. Expert opinion: Traditional clinical prognosticators such as the total number of pulmonary metastases, carcinoembryonic antigen (CEA) serum levels before surgery, and presence of lymph node metastases cannot provide reliable criteria to predict survival after lung metastasectomy. Indeed, research efforts have been directed in recent years toward studying the biological characteristics of lung lesions to better define prognosis and response to treatment, and ultimately shed new light on their proper local and systemic management
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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