1,720,988 research outputs found
Application of molecular biology of differentiated thyroid cancer for clinical prognostication
No full textAlthough cancer outcome results from the interplay between genetics and environment, researchers are making a great effort for applying molecular biology in the prognostication of differentiated thyroid cancer (DTC). Nevertheless, role of molecular characterisation in the prognostic setting of DTC is still nebulous. Among the most common and well-characterised genetic alterations related to DTC, including mutations of BRAF and RAS and RET rearrangements, BRAF(V600E) is the only mutation showing unequivocal association with clinical outcome. Unfortunately, its accuracy is strongly limited by low specificity. Recently, the introduction of next-generation sequencing techniques led to the identification of TERT promoter and TP53 mutations in DTC. These genetic abnormalities may identify a small subgroup of tumours with highly aggressive behaviour, thus improving specificity of molecular prognostication. Although knowledge of prognostic significance of TP53 mutations is still anecdotal, mutations of the TERT promoter have showed clear association with clinical outcome. Nevertheless, this genetic marker needs to be analysed according to a multigenetic model, as its prognostic effect becomes negligible when present in isolation. Given that any genetic alteration has demonstrated, taken alone, enough specificity, the co-occurrence of driving mutations is emerging as an independent genetic signature of aggressiveness, with possible future application in clinical practice. DTC prognostication may be empowered in the near future by non-tissue molecular prognosticators, including circulating BRAF(V600E) and miRNAs. Although promising, use of these markers needs to be refined by the technical sight, and the actual prognostic value is still yet to be validated
Application of molecular biology of differentiated thyroid cancer for clinical prognostication
Full text linkAlthough cancer outcome results from the interplay between genetics and environment, researchers are making a great effort for applying molecular biology in the prognostication of differentiated thyroid cancer (DTC). Nevertheless, role of molecular characterisation in the prognostic setting of DTC is still nebulous. Among the most common and well-characterised genetic alterations related to DTC, including mutations of BRAF and RAS and RET rearrangements, BRAF(V600E) is the only mutation showing unequivocal association with clinical outcome. Unfortunately, its accuracy is strongly limited by low specificity. Recently, the introduction of next-generation sequencing techniques led to the identification of TERT promoter and TP53 mutations in DTC. These genetic abnormalities may identify a small subgroup of tumours with highly aggressive behaviour, thus improving specificity of molecular prognostication. Although knowledge of prognostic significance of TP53 mutations is still anecdotal, mutations of the TERT promoter have showed clear association with clinical outcome. Nevertheless, this genetic marker needs to be analysed according to a multigenetic model, as its prognostic effect becomes negligible when present in isolation. Given that any genetic alteration has demonstrated, taken alone, enough specificity, the co-occurrence of driving mutations is emerging as an independent genetic signature of aggressiveness, with possible future application in clinical practice. DTC prognostication may be empowered in the near future by non-tissue molecular prognosticators, including circulating BRAF(V600E) and miRNAs. Although promising, use of these markers needs to be refined by the technical sight, and the actual prognostic value is still yet to be validated
Expression of p40 (∆Np63) protein in meningiomas, an unexpected finding: immunohistochemical study and evaluation of its possible prognostic role
No full textAccording to the 2007 WHO (World Health Organization) Classification, meningiomas are divided into three grades of malignancy, with different recurrence rate, based exclusively on histopathological parameters. Loss/reduction of PgR (Progesterone Receptor) expression and increased Ki67 L.I. (Labeling Index) have been proven as possible prognostic factors able to predict the relapse of the disease. However, they sometimes result unreliable, especially when discordant. p40 is the short form of the p53 homologue gene p63, also named ∆Np63, and its antibody has recently been introduced as a highly specific diagnostic marker of the squamous cell carcinoma of the lung. Nevertheless its expression has been found in many other unconventional sites (e.g. placenta, urotheluim, etc). Herein we assessed the immuno-expression of p40 protein in a series of 72 meningiomas (35 grade I and 37 grade II) and analyzed its correlation with clinicopathological parameters, overall survival and recurrence free interval. We found that a high p40 score correlated with high histological grade, presence of recurrence, increased Ki67 L.I. and loss/reduction of PgR signal. Moreover, a higher expression of p40 was shown to be a significant prognostic factor for the development of recurrences and resulted a prognostic independent variable in multivariate analysis. Overall, for the first time, we investigated the expression of p40 protein in meningiomas and explored its usefulness as prognostic marker in addition to PgR and Ki67 L.I
Ketogenic diet: a tool for the management of neuroendocrine neoplasms?
No full textNeuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms, whose incidence has rapidly increased in the last years. Nutrition plays an important role in their management; indeed, malnutrition negatively impacts on rates of complications, hospitalization, hospital stay, costs and mortality. Furthermore, it has been reported that a poor nutritional status could influence the outcome of patients with pancreatic NENs. Moreover, obesity, predisposing to insulin resistance and compensatory hyperinsulinemia, could stimulate the growth of these neoplasms. Ketogenic diet (KD), a high-fat, low-carbohydrate diet with adequate amounts of protein, has been reported to be a promising approach for the management of several types of cancer, mostly gynecological and neurological ones. Indeed, it appears to sensitize most cancers to standard treatment by exploiting the reprogramed metabolism of cancer cells and thus resulting in a promising candidate as an adjuvant cancer therapy. Thus, the aim of this review is to provide an overview on the importance of nutrition in cancer management and in particular in NENs' setting. Furthermore, we reported the current evidence on the efficacy of KD in the management of cancer and based on molecular mechanisms; we also hypothesize the potential use of this nutritional pattern in the management of NENs
Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy
Full text linkMedullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC
Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms
Full text linkThe prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs
Impact of COVID-19 and Antibiotic Treatments on Gut Microbiome: A Role for Enterococcus spp.
No full textObjective: Several studies showed the substantial use of antibiotics and increased risk of antimicrobial resistant infections in patients with COVID-19. The impact of COVID-19-related treatments and antibiotics on gut dysbiosis has not been clarified. Design: The prospective cohort study included hospitalized COVID-19 patients (April–December 2020). The gut microbiome composition was analysed by 16S sequencing. The gut diversity and changes in opportunistic bacteria (OBs) or symbionts were analysed according to clinical parameters, laboratory markers of disease progression, type of non-antibiotic COVID-19 treatments (NACT) and type, WHO AWaRe group, and duration of antibiotic therapy (AT). Results: A total of 82 patients (mean age 66 ± 13 years, 70% males) were enrolled. The relative abundance of Enterococcus was significantly correlated with duration of hospitalization, intensive care unit stay, O2 needs, and D-dimer, ferritin, and IL-6 blood levels. The presence of Enterococcus showed the highest number of correlations with NACT, AT, and AT + NACT (e.g., hydroxychloroquine ± lopinavir/ritonavir) and increased relative abundance with AWaRe Watch/Reserve antibiotics, AT duration, and combinations. Abundance of Dorea, Agathobacter, Roseburia, and Barnesiella was negatively correlated with AT and corticosteroids use. Patients with increased IL-6, D-dimer, and ferritin levels receiving AT were more likely to show dysbiosis with increased abundance of Enterococcus and Bilophila bacteria and decreased abundance of Roseburia compared with those not receiving AT. Conclusion: Microbiome diversity is affected by COVID-19 severity. In this context, antibiotic treatment may shift the gut microbiome composition towards OBs, particularly Enterococcus. The impact of treatment-driven dysbiosis on OBs infections and long-term consequences needs further study to define the role of gut homeostasis in COVID-19 recovery and inform targeted interventions
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
- …
