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Martins R.,University of Algarve | Bugalho M.J.,Instituto Portugues Of Oncologia Of Lisbon Francisco Gentil Epe | Bugalho M.J.,New University of Lisbon
International Journal of Endocrinology | Year: 2014

Paragangliomas are rare neuroendocrine tumors that arise in the sympathetic or parasympathetic nervous system. Sympathetic paragangliomas are mainly found in the adrenal medulla (designated pheochromocytomas) but may also have a thoracic, abdominal, or pelvic localization. Parasympathetic paragangliomas are generally located at the head or neck. Knowledge concerning the familial forms of paragangliomas has greatly improved in recent years. Additionally to the genes involved in the classical syndromic forms: VHL gene (von Hippel-Lindau), RET gene (Multiple Endocrine Neoplasia type 2), and NF1 gene (Neurofibromatosis type 1), 10 novel genes have so far been implicated in the occurrence of paragangliomas/pheochromocytomas: SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, EGLN1, HIF2A, and KIF1B. It is currently accepted that about 35% of the paragangliomas cases are due to germline mutations in one of these genes. Furthermore, somatic mutations of RET, VHL, NF1, MAX, HIF2A, and H-RAS can also be detected. The identification of the mutation responsible for the paraganglioma/pheochromocytoma phenotype in a patient may be crucial in determining the treatment and allowing specific follow-up guidelines, ultimately leading to a better prognosis. Herein, we summarize the most relevant aspects regarding the genetics and clinical aspects of the syndromic and nonsyndromic forms of pheochromocytoma/paraganglioma aiming to provide an algorithm for genetic testing. © 2014 Rute Martins and Maria João Bugalho.

Santos M.J.,Instituto Portugues Of Oncologia Of Lisbon Francisco Gentil Epe | Bugalho M.J.,Instituto Portugues Of Oncologia Of Lisbon Francisco Gentil Epe | Bugalho M.J.,New University of Lisbon
Endocrine | Year: 2016

pT3 papillary thyroid carcinoma (PTC) can be divided into three subgroups according to the largest diameter >4 cm or evidence of minimal extrathyroidal extension (ETE): A >4 cm, no ETE; B ≤4 cm, with ETE; and C >4 cm, with ETE. The aim of this study was to analyze whether these subgroups are clinically different. A retrospective analysis of clinicopathological data of patients with pT3 PTC, with a minimum follow-up of 2 years, at a referral center was conducted. Outcome was evaluated after primary treatment and after 2 and 5 years of follow-up. Patients were classified as no evidence of disease (NED), biochemical evidence of disease (BED), and structural evidence of disease (SED) either locoregional (SED-L) or at distance (SED-D). The study patients were classified into three groups as follows: Group A (n = 91), Group B (n = 101), and Group C (n = 23). Most patients were female (80.0 %); mean age at diagnosis was 49.9 ± 16.5 years. 214 patients underwent total thyroidectomy; 208 patients were treated with 131I. Median follow-up was 6.0 years. After primary treatment, the condition of NED was significantly different between the groups (A—87.9 %, B—68.3 %, C—43.5 %; p < 0.001). Recurrence rate, either biochemical or structural, was 8.8, 7.2, and 30.0 % in groups A, B, and C, respectively. Clinical status after 2 years anticipated clinical status after 5 years, except for Group B. ETE and tumor size were found to be predictors of disease status after primary treatment and after 2 years. ETE appeared as the strongest predictor of persistence of disease after primary treatment as well as of evidence of disease, either biochemical or structural, after 2 years of follow-up. © 2016 Springer Science+Business Media New York

Bugalho M.J.,Instituto Portugues Of Oncologia Of Lisbon Francisco Gentil Epe | Domingues R.,Instituto Portugues Of Oncologia Of Lisbon Francisco Gentil Epe
BMJ Case Reports | Year: 2016

Multiple endocrine neoplasia type 4 (MEN 4) is a novel form of multiple endocrine neoplasia caused by mutations in the CDKN1B gene. Its clinical presentation includes MEN 1-related tumours such as parathyroid and anterior pituitary tumours in possible association with gonadal, adrenal, renal and thyroid tumours as well as facial angiofibromas, colagenomas and meningiomas. We describe the case of a patient with meningioma, papillary thyroid carcinoma, parathyroid adenoma and, additionally, Hürthle cell adenoma, cholesteatoma and uterine leiomyomas. Considering that this association could represent a MEN 4-like phenotype, we looked for germline mutations in the CDKN1B gene. A rare heterozygous single nucleotide substitution c.397C>A was identified. Its role as a susceptibility factor remains to be established. Copyright 2016 BMJ Publishing Group. All rights reserved.

Lado-Abeal J.,University of Santiago de Compostela | Lado-Abeal J.,Health Science University | Celestino R.,University of Porto | Bravo S.B.,University of Santiago de Compostela | And 10 more authors.
Endocrine-Related Cancer | Year: 2010

Our main objective was to search for mutations in candidate genes and for paired box gene 8-peroxisome proliferator-activated receptor gamma (PAX8-PPARγ) rearrangement in a well-differentiated angioinvasive follicular thyroid carcinoma (FTC) causing hyperthyroidism. DNA and RNA were extracted from the patient's thyroid tumor, as well as 'normal' thyroid tissue, and from peripheral blood lymphocytes (PBLs) of the patient, her daughter, and two siblings. Nuclear isolation was extracted from the patient's tumor, 'normal' thyroid tissue, PBLs, and uterine leiomyoma tissue. TSH receptor (TSHR), RAS, and BRAF genes were sequenced. We searched for PAX8-PPARγ in thyroid, PBL, and uterine leiomyoma samples from the patient and family members. Proliferative effects of detected mutants on non-transformed human thyrocytes cultures. An activating TSHR mutation, M453T, was detected in the tumor. PAX8 (exons 1-8+ 10 )-PPARγ was found in all tested patient's tissues. A second rearrangement, PAX8 (exons 1-8)-PPARγ, was detected in the patient's normal thyroid tissue. Under deprived medium condition, co-transfection of PAX8-PPARγ and TSHR-M453T dramatically increased the number of thyrocytes, an effect that it was not observed with TSHR wild-type (WT); under complete medium conditions, co-transfection of PAX8-PPARγ with either TSHR-M453T or TSHR-WT inhibited cell proliferation. We report a patient with hyperthyroidism due to a FTC bearing an activating TSHR mutation and PAX8-PPARγ rearrangements. PAX8-PPARγ was present as a mosaicism affecting tissues from endodermal and mesodermal origin. PAX8-PPARγ and TSHR-M453T inhibited or promoted thyrocyte proliferation depending on medium conditions. The activating TSHR mutation could promote in vivo FTC development in PAX8-PPARγ-positive thyrocytes under poor blood supply with deprivation of growth factors but restraint the tumor growth when growth factors are supplied. © 2010 Society for Endocrinology.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.2.1 | Award Amount: 4.43M | Year: 2013

MOnarCH targets (i) the development of a novel framework to model mixed human-robot societies, and (ii) its demonstration using a network of heterogeneous robots and sensors, in the pediatric area of an oncological hospital. It will handle uncertainties introduced by people and robots, generate natural interactions, and engage in edutainment activities.\nThe expected outcomes are (i) an operational system able to interact with people in a natural way, (ii) novel results on key properties of networked robot systems, and (iii) guidelines to translate the system to applications in hospital environments, and further scenarios sharing similarities with them, e.g., kindergarten, and personal assistance to elderly at home.\nInnovation is expected mainly in (i) the modeling and analysis of the dynamics of social organizations, and social individuals, (ii) the mapping between such models and implementable systems, (iii) the integration between models related to social and asocial behaviors, (iv) the introduction of creative methods of interaction between people and robots, based on models of the dynamics of social organizations and individuals, and (v) the adaptation of robots to individuals and groups of people. This framework will map concepts in social sciences into social skills, group behaviors, and human-robot interaction, using learning methodologies and decision-theoretic principles.\nFunctional tests will be executed using the networked robotics environment at IST and other partners. Technologies such as a network of fixed cameras, RFID tags, teleoperation devices, voice generation, both isolated and combined as augmented reality interfaces, will be used. Specific tests will be carried out in a real hospital, at IPOL.\nThe Consortium is formed by research institutions, SMEs, and one hospital, and has the competences to (i) ensure that the deployed system fully complies with the hospital requirements, and (iii) enable the transition to market of the obtained solutions.

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