654 research outputs found
A narrative review of genetic alterations in primary thyroid epithelial cancer
No full textThyroid carcinoma is the most frequent endocrine neoplasia. Different types of thyroid carcinoma are described: well-differentiated papillary thyroid carcinoma (PTC), poorly differentiated thyroid carcinoma (PDTC), follicular thyroid carcinoma (FTC), anaplastic thyroid carcinoma (ATC), and medullary thyroid carcinoma (MTC). MTC is inherited as an autosomal dominant trait in 25% of cases. The genetic landscape of thyroid carcinoma has been largely deciphered. In PTC, genetic alterations have been found in about 95% of tumors: BRAF mutations and RET rearrangements are the main genetic alterations. BRAF and RAS mutations have been confirmed to play an important role also in PDTC and ATC, together with TP53 mutations that are fundamental in tumor progression. It has also been clearly demonstrated that telomerase reverse transcriptase (TERT) promoter mutations and TP53 mutations are present with a high-frequency in more advanced tumors, frequently associated with other mutations, and their presence, especially if simultaneous, is a signature of aggressiveness. In MTC, next-generation sequencing confirmed that mutations in the RET gene are the most common molecular events followed by H-RAS and K-RAS mutations. The comprehensive knowledge of the genetic events responsible for thyroid tumorigenesis is important to better predict the biological behavior and better plan the therapeutic strategy for specific treatment of the malignancy based on its molecular profile
Expression of thyrotropin receptor (TSH-R), thyroglobulin, thyroperoxidase, and calcitonin messenger ribonucleic acids in thyroid carcinomas: evidence of TSH-R gene transcript in medullary histotype.
No full textWe studied the expression of the TSH receptor (TSH-R), thyroglobulin (Tg), thyroperoxidase (TPO), and calcitonin (CT) genes in a total of 53 tissues from 30 patients with thyroid carcinoma and from 9 patients with benign thyroid diseases. By Northern blot analysis of total RNA preparations, CT mRNA was expressed in all cases (n = 6) of medullary thyroid carcinoma (MTC). Surprisingly, 3 of them expressed the TSH-R mRNA, in association with the Tg and TPO mRNAs in 1. The presence of the TSH-R transcript in the neoplastic C-cells was confirmed in 1 MTC by in situ hybridization using a mixture of 3 oligonucleotide probes derived from dog TSH-R cDNA. With various degrees of expression, all differentiated thyroid carcinomas (20 papillary and 2 follicular) expressed TSH-R, Tg, and TPO, but not CT mRNAs. On the contrary, samples from 2 patients with anaplastic carcinoma did not express TSH-R, Tg, or TPO mRNA, but 1 of them expressed CT mRNA. All of the transcripts obtained from thyroid carcinomas (both primary and metastatic) were of the same size as the transcripts from normal or benign thyroid tissues, with the exception of 2 cases of differentiated thyroid cancer, in which TSH-R mRNA of lower mol wt (approximately 4.0 kilobases) was found in the absence of alteration in cDNA size and restriction map. The main conclusions of our study are that 1) the TSH-R gene is expressed in some MTC, which supports, at molecular level, the hypothesis of the existence of mixed follicular-medullary thyroid tumors; and 2) the expression of TSH-R, Tg, and TPO in undifferentiated thyroid cancer is lost.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jSCOPUS: ar.jinfo:eu-repo/semantics/publishe
Power supply noise and immunity
No full textAn electronic transformer used to supply
low-voltage halogen lamps, was designed
by means of an HSPICE simulator.
The same simulator was used to predict
conducted emission and susceptibility
in order to verify the compliance with
VDE 0875 and IEC 801-5 regulations.
With respect to the other method based
on the equivalent noise generator, the
proposed technique allows a more accurate
prediction. This method also allows a
real-time checking of the effects that the
inserted filtering and protection
devices produce on the functional
behavior of the SMPS
Targeted therapies for thyroid cancer.
No full textThyroid cancer is the most common endocrine malignancy. In the majority of cases the disease is curable by means of surgery and, when appropriate, by radioiodine treatment. However, some thyroid tumors became radioiodine-refractory (RAI-R) or they are RAI-R from the beginning because of the lack of differentiation or because they originate from parafollicular C cells (medullary thyroid cancer). Until 2011 no effective therapeutic options were available for these tumors. Moreover anaplastic thyroid cancer that is by definition RAI-R is, despite the multidisciplinary approach which includes surgery, external beam radiotherapy and chemotherapy, almost invariably lethal.
Currently, novel therapeutic agents targeting the critical oncogenes (e.g. BRAFV600E and RET) and pathways (e.g. MAPK and PI3K/AKT-mTOR) involved in thyroid cancer pathogenesis and tumor progression have been developed. These drugs known as tyrosine kinase inhibitors (TKI) bind to membrane receptors and determine a growth arrest by blocking tumoral cell proliferation.
This review offers an overview of the state of the art on the use of targeted therapies in any type of advanced, progressive and RAI-R thyroid tumors
Papillary thyroid microcarcinoma: Toward an active surveillance strategy
No full textIn the last decades, the incidence of thyroid cancer (TC) has m ore than doubled, but the disease-specific mortality rate was stable. To date, 30-40% of all TC is represented by papilla ry microcarcinomas (mPTC), an indolent tumor, that probably remained undiagnosed before routine ultrasound use. In 1993, Miyauchi was the first who hypothesized a conservative approach for low-risk mPTC and introduced the co ncept of active surveillance (AS) in its clinical management. The progression rate of mPTC during AS was low and delaying surgery did not impact the efficacy of treatment or outcome. Since then, several authors from all over the world have reported their experience of AS in mPTCs. As suggested by current guidelines, AS can be considered as an alternative to immediate surgery to avoid overtreatment in low-risk mPTC and may be the strategy to avoid complications from unnecessary surgery. In the last years, AS inclusion criteria have been extended to both bigger tumors and to younger/healthier patients. The adoption of AS should take into consideration not only tumor characteris tics but also patient psychological profiles and medical team expertise. Its safety and efficacy have been demonstrated in long-term outcome studies and in other types of tumors; however, skepticism in patients, families and physician s should be overcome by strong recommendations coming from scientific guidelines. This review analyses the seve ral and different experiences of AS and the potential obstacles in implementing it as a routine approach in mPTC pati ents
2019 European Thyroid Association Guidelines for the Treatment and Follow-Up of Advanced Radioiodine-Refractory Thyroid Cancer
No full textThe vast majority of thyroid cancers of follicular origin (TC) have a very favourable outcome, but 5-10% of cases will develop metastatic disease. Around 60-70% of this subset, hence less than 5% of all patients with TC, will become radioiodine refractory (RAI-R), with a significant negative impact on prognosis and a mean life expectancy of 3-5 years. Since no European expert consensus or guidance for this challenging condition is currently available, a task force of TC experts was nominated by the European Thyroid Association (ETA) to prepare this document based on the principles of clinical evidence. The task force started to work in September 2018 and after several revision rounds, prepared a list of recommendations to support the treatment and follow-up of patients with advanced TC. Criteria for advanced RAI-R TC were proposed, and the most appropriate diagnostic tools and the local, systemic and palliative treatments are described. Systemic therapy with multikinase inhibitors is fully discussed, including recommendations on how to start it and at which dosage, on the duration of treatment, and on the management of side effects. The appropriate relationship between the specialist and the patient/family as well as ethical issues are covered. Based on the available studies and on personal experience, the experts provided 39 recommendations aimed to improve the management of advanced RAI-R TCs. Above all of them is the indication to treat and follow these patients in a specialized setting which allows the interaction between several specialists in a multidisciplinary team
Studies with recombinant autoepitopes of thyroid peroxidase: evidence suggesting an epitope shared between the thyroid and the gastric parietal cell
No full textIn a previous work we characterized a major epitope of thyroid peroxidase (TPO), which was recognised by 66% of 157 patients with autoimmune thyroid disease (AITD) and 9 out of 50 patients with non-thyroidal autoimmune disease (NTAID) 6 of whom had antibodies to the gastric parietal cell antigen (PCA). In the present study we have affinity purified C2 antibodies and demonstrated that they bind to the native TPO enzyme in a radioimmunoassay (RIA). We have measured antibodies to the C2 peptide and a second TPO peptide, C21, in enzyme-linked immunosorbent assays (ELISA) in 30 patients with NTAID all of whom have antibodies to the gastric PCA, having first determined the incidence of antibodies to C21 in 98 patients with AITD who do not have antibodies to the gastric PCA. 58% of patients with AITD have antibodies to C21, a peptide of TPO which overlaps C2 by 21 amino acids in the region containing an 11 residue fragment which is very similar to a fragment of the H+ K+ ATPase, which has recently been shown to be a major component of the gastric PCA. In patients having NTAID and antibodies to the gastric PCA, 60% are positive for C2 Ab and 100% for C21 Ab, which is suggestive of an epitope shared by TPO and H+ K+ ATPase, corresponding to TPO 659----669 and H+ K+ ATPase 177----187. We conclude that C2 antibodies are heterogenous and comprise activities which bind to the intact enzyme and activities binding to an epitope which may be common to TPO and H+ K+ ATPase
Measurement of cAMP accumulation in Chinese hamster ovary cells transfected with the recombinant human TSH receptor (CHO-R): a new bioassay for human thyrotropin.
No full textCirculating TSH bioactivity may vary in several clinical and experimental conditions. Since the reliability of the current methods for the measurement of TSH bioactivity is limited, a new bioassay based on cAMP accumulation in Chinese Hamster Ovary cells transfected with recombinant human TSH receptor (CHO-R) was set up. The sensitivity was 0.3 +/- 0.1, 0.4 +/- 0.1 and 0.01 +/- 0.01 micrograms/L for TSH IRP 80/558, recombinant human TSH and bovine TSH, respectively. Standard curves were parallel, and the intra- and inter-assay coefficients of variation were 13 +/- 1.1% and 22 +/- 1.9%, respectively. LH, FSH, CG and TSH subunits did not stimulate cAMP accumulation up to high concentrations. Circulating TSH was partially purified by immunoaffinity separation and concentrated before being bioassayed. However, plain sera with high TSH levels, such as those from primary hypothyroid patients (PH), could be directly tested in CHO-R bioassay, provided that sera were added at concentrations lower than 10%. TSH from 6 normal subjects had biological to immunological ratio (B/I) ranging from 0.6 to 2.1 (mean +/- SD = 1.4 +/- 0.5). TSH from 6 patients with PH showed bioactivity significantly lower than in normals (B/I = 0.6 +/- 0.3; p < 0.001; range = 0.3-1.1). TSH from 5 patients with central hypothyroidism of hypothalamic origin (CH) had undetectable basal bioactivity (B/I < 0.2), which normalized in only one patient after acute TRH and in all patients after chronic TRH administration. In conclusion, CHO-R cells provide an excellent tool for evaluating TSH bioactivity, owing to high sensitivity, specificity, reproducibility and feasibility of the assay.(ABSTRACT TRUNCATED AT 250 WORDS)Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe
Characterization of three winding transformers for the reduction of switching mode power supply conducted emission
No full textThe paper focuses the attention on the modelling of transformers for the prediction of conducted emissions from SMPS. The transformer equivalent circuit component values are extracted by impedance measurements with proper load conditions. Beside a traditional two-winding transformer, also a three winding version is analysed: the third winding is used to realize a shield, in order to reduce the conducted emission. This is a quick and cheap way to realise the shield, without appreciably increase the production time. Finally, the simulation of a flyback SMPS, allows to evaluate the benefits obtained in using the shielded transformer. All simulations are experimentally validated showing a satisfactory agreement
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