The SIGnaling Network Open Resource (SIGNOR 3.0, https://signor.uniroma2.it) is a public repository that captures causal information and represents it according to an ‘activity-flow’ model. SIGNOR provides freely-accessible static maps of causal interactions that can be tailored, pruned and refined to build dynamic and predictive models. Each signaling relationship is annotated with an effect (up/down-regulation) and with the mechanism (e.g. binding, phosphorylation, transcriptional activation, etc.) causing the regulation of the target entity. Since its latest release, SIGNOR has undergone a significant upgrade including: (i) a new website that offers an improved user experience and novel advanced search and graph tools; (ii) a significant content growth adding up to a total of approx. 33,000 manually-annotated causal relationships between more than 8900 biological entities; (iii) an increase in the number of manually annotated pathways, currently including pathways deregulated by SARS-CoV-2 infection or involved in neurodevelopment synaptic transmission and metabolism, among others; (iv) additional features such as new model to represent metabolic reactions and a new confidence score assigned to each interaction.
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlighted the relevance of the TME in GISTs, with possible implications for clinical practice in the near future. Moreover, the expression of immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and their relationship to the clinical phenotype in GIST are emerging as potential prognostic biomarkers. Looking forward, these variables related to the underlying tumoral microenvironment in GIST, though limited to still-ongoing trials, might lead to the potential use of immunotherapy, alone or in combination with targeted therapy, in advanced TKI-refractory GISTs. This review aims to deepen understanding of the potential link between mutational status and the immune microenvironment in GIST.
Intraoperative parathyroid hormone dosage allows real-time monitoring of the decrease in PTH levels during parathyroidectomy and verify procedure’s efficacy. Currently, none of the interpretative criteria used has absolute accuracy. The aim of this study is to evaluate diagnostic accuracy of the Rome criterion verifying diagnostic significance of the individual assays. A total of 205 patients with primary hyperparathyroidism from a single adenoma were retrospectively evaluated and monitored with baseline PTH, PTH at 10 min and PTH at 20 min after adenoma excision. The accuracy of the latter two assays compared with baseline was compared by ROC curves. In addition, was evaluated the influence on these data of localization diagnostics (ultrasounds and scintigraphy), definitive histology, and type of surgery performed. The ratio of 20-min sampling to baseline in the Rome criterion showed highest diagnostic significance. This finding was not influenced by the type of surgery performed, definitive histologic examination, or intraoperative localization of the adenoma. The Rome criterion has shown its high reliability in detecting persistence. The ratio of sampling at 20 min to baseline is by far the best performing. Further studies are needed to evaluate whether sampling at 10 min after adenoma excision can be considered not mandatory.
Anaplastic thyroid carcinoma (ATC) is a very rare and extremely aggressive disease with a very poor prognosis. Several risk factors have been hypothesized, but there is no clear-cut literature data on it. We reviewed the literature concerning risk factors for ATC and analyzed the institutional database from 2005 to 2022. In total, 15 papers were suitable for review, while the retrospective data collection search, conducted on our institutional database, provided 13 results. In our experience, in agreement with literature data, ATC seems to be a neoplasm peculiar to old age (in our database, mean age is 72 years), with a higher prevalence in subjects with a low level of education and a long history of multinodular goiter (MNG). The role of cigarette smoking and blood group, hypothesized on some literature data, was more uncertain, although the small sample size evaluated probably had a great influence on these results. The higher incidence of the disease in individuals with a history of MNG could suggest more aggressive choices in the treatment of a benign disease, in contrast to current practice. However, this may be a highly questionable point considering that ATC accounts for no more than 2% of all thyroid neoplasms in surgical departments, even those dedicated to endocrine neck surgery. Further studies are therefore necessary for a step forward in this direction.
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