MicroRNA Role in Thyroid Cancer Development

MicroRNAs (miRNAs) are endogenous noncoding RNAs that negatively regulate gene expression by binding the 3′ noncoding region of the messenger RNA targets inducing their cleavage or blocking the protein translation. They play important roles in multiple biological and metabolic processes, including developmental timing, signal transduction, and cell maintenance and differentiation. Their deregulation can predispose to diseases and cancer. miRNA expression has been demonstrated to be deregulated in many types of human tumors, including thyroid cancers, and could be responsible for tumor initiation and progression. In this paper we reviewed the available data on miRNA deregulation in different thyroid tumors and describe the putative role of miRNA in thyroid cancer development

Multiple endocrine neoplasia type 1

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended

Model-Based Identification of Alternative Bidding Zones: Applications of Clustering Algorithms with Topology Constraints

The definition of bidding zones is a relevant question for electricity markets. The bidding zones can be identified starting from information on the nodal prices and network topology, considering the operational conditions that may lead to congestion of the transmission lines. A well-designed bidding zone configuration is a key milestone for an efficient market design and a secure power system operation, being the basis for capacity allocation and congestion management processes, as acknowledged in the relevant European regulation. Alternative bidding zone configurations can be identified in a process assisted by the application of clustering methods, which use a predefined set of features, objectives and constraints to determine the partitioning of the network nodes into groups. These groups are then analysed and validated to become candidate bidding zones. The content of the manuscript can be summarized as follows: (1) A novel probabilistic multi-scenario methodology was adopted. The approach needs the analysis of features that are computed considering a set of scenarios defined from solutions in normal operation and in planned maintenance cases. The weights of the scenarios are indicated by TSOs on the basis of the expected frequency of occurrence; (2) The relevant features considered are the Locational Marginal Prices (LMPs) and the Power Transfer Distribution Factors (PTDFs); (3) An innovative computation procedure based on clustering algorithms was developed to group nodes of the transmission electrical network into bidding zones considering topological constraints. Several settings and clustering algorithms were tested in order to evaluate the robustness of the identified solution

Safety and feasibility of outpatient surgery in benign prostatic hyperplasia: a systematic review and meta-analysis

Purpose: Most of endourological procedures along the urinary tract have been widely practiced as outpatient operations, including surgery for BPH. This systematic review and meta-analysis was conducted to assess safety and feasibility of outpatient surgery for patients suffering from symptomatic BPH candidate for endoscopic disobstruction. Materials and methods: PubMed, Web of Science, Cochrane, and Embase were searched up until March 30, 2020. MINORS tool was utilized to assess the quality of included studies and a pooled measure of failure or event rate (FR, ER) estimate was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate contribution of moderators to heterogeneity. Results: Twenty studies with a total of 1626 patients treated according to outpatient criteria for endoscopic BPH surgery were included. In total, 18 studies reporting data on immediate hospital readmission and/or inability to discharge after endoscopic procedure presented FR estimates ranging from 1.7% to 51.1%. Pooled FR estimate was 7.8% (95% confidence interval [CI]: 5.2%-10.3%); Heterogeneity: Q=76.85; d.f.=17, p<.001; I2= 75.12%. Subgroup analysis according to surgical technique revealed difference among the three approaches with pooled FR of 3% (95%CI: 1%-4.9%), 7.1% (95%CI: 3.9-10.4) and 11.8% (95%CI: 7-16.7%) for TURP, Green-light and HoLEP respectively (p<.001). At meta-regression analysis, none of the retrieved covariates were able to significantly influence the cumulative outcomes reported. ER for postoperative complications and early outpatient visit showed a pooled estimate of 18.6% (95%CI: 13.2%-23.9%) and 7.7% (95%CI: 4.3%-11%) respectively. Conclusions: Our analysis revealed how transurethral procedures for BPH on an outpatient setting are overall reliable and safe. Of note, there were significant outcome differences between groups with regard of type of surgical procedure, perioperative prostate volume and discharge protocol suggesting the need for further prospective analysis to better elucidate the best strategy in such outpatient conduct

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS 643) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and 6580% nodule volume ablation is expected (LoE = 3)

The Negative Feedback-Loop between the Oncomir Mir-24-1 and Menin Modulates the Men1 Tumorigenesis by Mimicking the “Knudson’s Second Hit”

Multiple endocrine neoplasia type 1 (MEN1) syndrome is a rare hereditary cancer disorder characterized by tumors of the parathyroids, of the neuroendocrine cells, of the gastro-entero-pancreatic tract, of the anterior pituitary, and by non-endocrine neoplasms and lesions. MEN1 gene, a tumor suppressor gene, encodes menin protein. Loss of heterozygosity at 11q13 is typical of MEN1 tumors, in agreement with the Knudson’s two-hit hypothesis. In silico analysis with Target Scan, Miranda and Pictar-Vert softwares for the prediction of miRNA targets indicated miR-24-1 as capable to bind to the 3′UTR of MEN1 mRNA. We investigated this possibility by analysis of miR-24-1 expression profiles in parathyroid adenomatous tissues from MEN1 gene mutation carriers, in their sporadic non-MEN1 counterparts, and in normal parathyroid tissue. Interestingly, the MEN1 tumorigenesis seems to be under the control of a “negative feedback loop” between miR-24-1 and menin protein, that mimics the second hit of Knudson’s hypothesis and that could buffer the effect of the stochastic factors that contribute to the onset and progression of this disease. Our data show an alternative way to MEN1 tumorigenesis and, probably, to the “two-hit dogma”. The functional significance of this regulatory mechanism in MEN1 tumorigenesis is also the basis for opening future developments of RNA antagomir(s)-based strategies in the in vivo control of tumorigenesis in MEN1 carriers