9 research outputs found
Mitochondrial dynamics protein drp1 is overexpressed in oncocytic thyroid tumors and regulates cancer cell migration.
No full textOncocytic cell tumors are characterized by the accumulation of morphologically abnormal mitochondria in their cells, suggesting a role for abnormal mitochondrial biogenesis in oncocytic cell transformation. Little is known about the reason for the dysmorphology of accumulated mitochondria. The proteins regulating the morphology of mitochondria, the "mitochondria-shaping" proteins, can modulate their size and number; however, nothing is known hitherto about a possible involvement of mitochondrial dynamics in oncocytic cell transformation in tumors. Our aim was to assess the status of the mitochondria morphology and its role in oncocytic cell transformation. We therefore evaluated the expression pattern of the main mitochondrial fusion and fission proteins in a series of thyroid cell tumor samples, as well as in thyroid tumor cell lines, with and without oncocytic cell features. The expression of mitochondrial fusion (Opa1, Mfn1 and Mfn2) and fission (Drp1 and Fis1) proteins were evaluated by immunohistochemistry (IHC) in a series of 88 human thyroid tumors. In vitro studies, for comparative purposes and to deepen the study, were performed using TPC1--a papillary thyroid carcinoma derived cell line--and XTC.UC1, an oncocytic follicular thyroid carcinoma-derived cell line. Both IHC and in vitro protein analyses showed an overall increase in the levels of "mitochondrial-shaping" proteins in oncocytic thyroid tumors. Furthermore, overexpression of the pro-fission protein Drp1 was found to be associated with malignant oncocytic thyroid tumors. Interestingly, genetic and pharmacological blockage of Drp1 activity was able to influence thyroid cancer cells' migration/invasion ability, a feature of tumor malignancy. In this study we show that unbalanced mitochondrial dynamics characterize the malignant features of thyroid oncocytic cell tumors, and participate in the acquisition of the migrating phenotype
Conservation of goat populations from southwestern Europe based on molecular diversity criteria
No full textGoat farming plays a key role in agricultural activity and in maintaining forest lands in Southwestern Europe. Remarkably, the Iberian Peninsula represents nearly 25% of the European goat census. Goat husbandry is often associated with low input production systems and uses selective breeding programs, which are less advanced than those employed in other livestock. Native goat breeds are very well adapted to produce in marginal areas under extensive conditions. Loss of their genetic diversity could have important economic, ecological and scientific implications as well as social consequences. Several methodologies have been developed to preserve the genetic diversity of single populations, but additional problems arise when a group of breeds, i.e., subpopulations, is considered in conservation programs. The conservation priority of a breed depends on its contribution to the overall genetic diversity of the species, in terms of the intrinsic genetic variation that it harbors and also of its relationship with other breeds. However, the estimation of the contributions of each of these two components to overall genetic diversity cannot be easily assessed. Besides, conservation goals in the short-term (avoidance of inbreeding) and long-term (adaptation to future environmental changes) should be considered when taking conservative decisions. A comprehensive analysis of Iberian goat breeds has been carried out to evaluate conservation priorities based on methodologies that account for within- or between-breed genetic diversity, or combinations of both. Based on genetic distinctiveness, breeds such as Palmera, Formentera, and Blanca Celtibérica were prioritized, whereas the maximum priority was assigned to Florida, Pirenaica, Retinta, and Moncaína breeds when focusing on within-breed diversity. Overall, combined approaches showed very little variation among breeds reflecting a history of extensive gene flow, partly due to transhumance and recent divergence. The main conclusion of our study is that these statistical analyses are useful, but conservation decisions must take into account other factors in addition to strict genetic diversity classification
Overview of the 2022 WHO Classification of Thyroid Neoplasms
No full textThis review summarizes the changes in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors that relate to the thyroid gland. The new classification has divided thyroid tumors into several new categories that allow for a clearer understanding of the cell of origin, pathologic features (cytopathology and histopathology), molecular classification, and biological behavior. Follicular cell-derived tumors constitute the majority of thyroid neoplasms. In this new classification, they are divided into benign, low-risk, and malignant neoplasms. Benign tumors include not only follicular adenoma but also variants of adenoma that are of diagnostic and clinical significance, including the ones with papillary architecture, which are often hyperfunctional and oncocytic adenomas. For the first time, there is a detailed account of the multifocal hyperplastic/neoplastic lesions that commonly occur in the clinical setting of multinodular goiter; the term thyroid follicular nodular disease (FND) achieved consensus as the best to describe this enigmatic entity. Low-risk follicular cell-derived neoplasms include non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), thyroid tumors of uncertain malignant potential, and hyalinizing trabecular tumor. Malignant follicular cell-derived neoplasms are stratified based on molecular profiles and aggressiveness. Papillary thyroid carcinomas (PTCs), with many morphological subtypes, represent the BRAF-like malignancies, whereas invasive encapsulated follicular variant PTC and follicular thyroid carcinoma represent the RAS-like malignancies. This new classification requires detailed subtyping of papillary microcarcinomas similar to their counterparts that exceed 1.0 cm and recommends not designating them as a subtype of PTC. The criteria of the tall cell subtype of PTC have been revisited. Cribriform-morular thyroid carcinoma is no longer classified as a subtype of PTC. The term "Hurthle cell" is discouraged, since it is a misnomer. Oncocytic carcinoma is discussed as a distinct entity with the clear recognition that it refers to oncocytic follicular cell-derived neoplasms (composed of > 75% oncocytic cells) that lack characteristic nuclear features of PTC (those would be oncocytic PTCs) and high-grade features (necrosis and >= 5 mitoses per 2 mm(2)). High-grade follicular cell-derived malignancies now include both the traditional poorly differentiated carcinoma as well as high-grade differentiated thyroid carcinomas, since both are characterized by increased mitotic activity and tumor necrosis without anaplastic histology and clinically behave in a similar manner. Anaplastic thyroid carcinoma remains the most undifferentiated form; squamous cell carcinoma of the thyroid is now considered as a subtype of anaplastic carcinoma. Medullary thyroid carcinomas derived from thyroid C cells retain their distinct section, and there is a separate section for mixed tumors composed of both C cells and any follicular cell-derived malignancy. A grading system for medullary thyroid carcinomas is also introduced based on mitotic count, tumor necrosis, and Ki67 labeling index. A number of unusual neoplasms that occur in the thyroid have been placed into new sections based on their cytogenesis. Mucoepidermoid carcinoma and secretory carcinoma of the salivary gland type are now included in one section classified as "salivary gland-type carcinomas of the thyroid." Thymomas, thymic carcinomas and spindle epithelial tumor with thymus-like elements are classified as "thymic tumors within the thyroid." There remain several tumors whose cell lineage is unclear, and they are listed as such; these include sclerosing mucoepidermoid carcinoma with eosinophilia and cribriform-morular thyroid carcinoma. Another important addition is thyroblastoma, an unusual embryonal tumor associated with DICER1 mutations. As in all the WHO books in the 5th edition, mesenchymal and stromal tumors, hematolymphoid neoplasms, germ cell tumors, and metastatic malignancies are discussed separately. The current classification also emphasizes the value of biomarkers that may aid diagnosis and provide prognostic information
Role of Guanidyl Moiety in the Insertion of Arginine and Nα-Benzoyl-l-argininate Ethyl Ester Chloride in Lipid Membranes
No full textRole of Guanidyl Moiety in the Insertion of Arginine and Nα-Benzoyl-l-argininate Ethyl Ester Chloride in Lipid Membranes
AbstractFull Text HTMLHi-Res PDF[1247 KB]PDF w/ Links[216 KB]FiguresReferencesA. C. Fonseca‡, M. A. Frías†, A. M. Bouchet†, S. Jarmelo‡§, P. N. Simões‡, R. Fausto§, M. H. Gil‡, F. Lairion† and E. A. Disalvo*†
Laboratory of Physical Chemistry of Lipid Membranes, Department of Analytical Chemistry and Physical Chemistry, Pharmacy and Biochemistry, University of Buenos Aires Junín 956 2° piso (1113), Buenos Aires, Argentina, Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-790 Coimbra, Portugal, and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal
J. Phys. Chem. B, 2010, 114 (17), pp 5946–5952
DOI: 10.1021/jp101007b
Publication Date (Web): April 13, 2010
Copyright © 2010 American Chemical Society
* Corresponding author. Phone: 54 11 39648249. Fax: 54 11 45083645. E-mail: [email protected]., † Department of Analytical Chemistry and Physical Chemistry, Pharmacy and Biochemistry, University of Buenos Aires Junín 956 2° piso (1113).
, ‡ Department of Chemical Engineering, University of Coimbra.
, § Department of Chemistry, University of Coimbra.
AbstractGuanidyl moieties of both arginine (Arg) and Nα-benzoyl-l-argininate ethyl ester chloride (BAEE) are protonated in all environments studied, i.e., dry solid state, D2O solutions, and dry and hydrated lipids as suggested by DFT(B3LYP)/6-31+G(d,p) calculations. Arg and BAEE are able to insert in the lipid interphase of both DMPC and DOPC monolayers as revealed by the observed decrease in the membrane dipole potential they induce. The larger decrease in the dipole potential induced by BAEE, compared to Arg, can be explained partially by the higher affinity of the hydrophobic benzoyl and ethyl groups for the membrane phase, which allows an easier insertion of this molecule. FTIR studies indicate that the guanidyl moiety of Arg is with all probability facing the hydrophobic part of the lipids, whereas in BAEE this group is facing the water phase. Zeta potential measurements provide a direct evidence that Arg orients in the lipid interphase of phosphatidylcholine (PC) bilayers with the negative charged carboxylate group (−COO−) toward the aqueous phase
Differential clinicopathological risk and prognosis of major papillary thyroid cancer variants
No full textContext: Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is conceivably a useful treatment strategy for PTC, which awaits comprehensive data demonstrating differential risks of PTC variants to support. Objective: This study sought to establish the differential clinicopathological risk of major PTC variants: conventional PTC (CPTC), follicular-variant PTC (FVPTC), and tall-cell PTC (TCPTC). Methods: Thiswasa retrospective study of clinicopathological outcomes of 6282 PTC patients (4799 females and 1483 males) from 26 centers and The Cancer Genome Atlas in 14 countries with a median age of 44 years (interquartile range, 33â€"56 y) and median follow-up time of 37 months (interquartile range, 15â€"82 mo). Results: The cohort consisted of 4702 (74.8%) patients with CPTC, 1126 (17.9%) with FVPTC, and 239 (3.8%) with TCPTC. The prevalence of high-risk parameters was significantly different among the three variants, including extrathyroidal invasion, lymph node metastasis, stages III/IV, disease recurrence, mortality, and the use (need) of radioiodine treatment (all P > .001), being highest in TCPTC, lowest in FVPTC, and intermediate in CPTC, following an order of TCPTC>CPTC蠑FVPTC. Recurrence and mortality in TCPTC, CPTC, and FVPTC were 27.3 and 6.7%, 16.1 and 2.5%, and 9.1 and 0.6%, corresponding to events per 1000 person-years (95% confidence interval [CI]) of 92.47 (64.66â€"132.26) and 24.61 (12.31â€" 49.21), 34.46 (30.71â€"38.66), and 5.87 (4.37â€"7.88), and 24.73 (18.34 â€"33.35) and 1.68 (0.54 â€"5.21), respectively. Mortality hazard ratios of CPTC and TCPTC over FVPTC were 3.44 (95% CI, 1.07â€"11.11) and 14.96 (95% CI, 3.93â€"56.89), respectively. Kaplan-Meier survival analyses showed the best prognosis in FVPTC, worst in TCPTC, and intermediate in CPTC in disease recurrence-free probability and disease-specific patient survival. This was particularly the case in patients at least 45 years old. Conclusion: This large multicenter study demonstrates differential prognostic risks of the three major PTC variants and establishes a unique risk order of TCPTC > CPTC 蠑 FVPTC, providing important clinical implications for specific variant-based management of PTC
Development of a pediatric differentiated thyroid carcinoma registry within the EuRRECa project: rationale and protocol
No full textBackground:
Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the disease, current treatment guidelines are predominantly based on the results of small observational retrospective studies and extrapolations from results in adult patients. In order to develop more personalized treatment and follow-up strategies (aiming to reduce complication rates), there is an unmet need for uniform international prospective data collection and clinical trials.
Methods and analysis:
The European pediatric thyroid carcinoma registry aims to collect clinical data for all patients ≤18 years of age with a confirmed diagnosis of DTC who have been diagnosed, assessed, or treated at a participating site. This registry will be a component of the wider European Registries for Rare Endocrine Conditions project which has close links to Endo-ERN, the European Reference Network for Rare Endocrine Conditions. A multidisciplinary expert working group was formed to develop a minimal dataset comprising information regarding demographic data, diagnosis, treatment, and outcome. We constructed an umbrella-type registry, with a detailed basic dataset. In the future, this may provide the opportunity for research teams to integrate clinical research questions.
Ethics and dissemination:
Written informed consent will be obtained from all participants and/or their parents/guardians. Summaries and descriptive analyses of the registry will be disseminated via conference presentations and peer-reviewed publications
Development of a pediatric differentiated thyroid carcinoma registry within the EuRRECa project: rationale and protocol
No full textNeurodevelopmental effects of genetic frontotemporal dementia in young adult mutation carriers
No full text© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have neurodevelopmental consequences, we examined the youngest adults in the GENFI cohort of pre-symptomatic frontotemporal dementia mutation carriers who are between 19 and 30 years of age. Structural brain differences and improved performance on some cognitive tests were found for MAPT and GRN mutation carriers relative to familial non-carriers, while smaller volumes were observed in C9orf72 repeat expansion carriers at a mean age of 26 years. The detection of such early differences supports potential advantageous neurodevelopmental consequences of some frontotemporal dementia-causing genetic mutations. These results have implications for the design of therapeutic interventions for frontotemporal dementia. Future studies at younger ages are needed to identify specific early pathophysiologic or compensatory processes that occur during the neurodevelopmental period.This project was supported by Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, and by Canadian Institutes of Health Research operating grants (327387; 452843; 70797). The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the National Institute for Health Research (NIHR) Queen Square Dementia Biomedical Research Unit and the University College London Hospitals Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC), and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Italian Ministry of Health (CoEN015 and Ricerca Corrente), the Alzheimer’s Society grant (AS-PG-16-007), the Bluefield Project and the EU Joint Programme – Neurodegenerative Disease Research (GENFI-PROX grant 2019-02248). M.B. is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a- 004-517). M.B.’s work was also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. J.D.R. is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). J.B.R. is funded by the Wellcome Trust (103838) and the National Institute for Health Research Cambridge Biomedical Research Centre. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). It is also funded by the Ministry of Health, Italy (S.S.). R.V.’s work is supported by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie. R.S.-V.’s work is supported by Instituto de Salud Carlos III (grant number 20/00448), cofunded by the EU. ANR-PRTS PrevdemALS study funding (I.L.B.). Several authors of this publication (J.C.vS., M.S., A.D., M.O., R.V., I.L.B., J.D.R.) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) - Project ID No 739510.info:eu-repo/semantics/publishedVersio
