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Ferreira L.B.,University of Porto | Eloy C.,University of Porto | Pestana A.,University of Porto | Lyra J.,University of Porto | And 8 more authors.
European Journal of Endocrinology | Year: 2016

Background: Osteopontin (OPN) or secreted phosphoprotein 1 (SPP1) is a matricellular glycoprotein whose expression is elevated in various types of cancer and has been shown to be involved in tumourigenesis and metastasis in many malignancies, incluDing follicular cell-derived thyroid carcinomas. Its role in C-cell-derived thyroid lesions and tumours remains to be established. Objective: The objective of this study is to clarify the role of OPN expression in the development of medullary thyroid carcinoma (MTC). Methods: OPN expression was analysed in a series of 116 MTCs by immunohistochemistry and by qPCR mRNA quantification of the 3 OPN isoforms (OPNa, OPNb and OPNc) in six cases from which fresh frozen tissue was available. Statistical tests were used to evaluate the relationship of OPN expression and the clinicopathological and molecular characteristics of patients and tumours. Results: OPN expression was detected in 91 of 116 (78.4%) of the MTC. We also observed high OPN expression in C-cell hyperplasia as well as in C-cells scattered in the thyroid parenchyma adjacent to the tumours. OPN expression was significantly associated with smaller tumour size, PTEN nuclear expression and RAS status, and suggestively associated with non-invasive tumours. OPNa isoform was expressed significantly at higher levels in tumours than in non-tumour samples. OPNb and OPNc presented similar levels of expression in all samples. Furthermore, OPNa isoform overexpression was significantly associated with reduced growth and viability in the MTC-derived cell line (TT). Conclusion: The expression of OPN in normal C-cells and C-cell hyperplasia suggests that OPN is a differentiation marker of C-cells, rather than a marker of biological aggressiveness in this setting. At variance with other cancers, OPN expression is associated with good prognostic features in MTC. © 2016 European Society of Endocrinology Printed in Great Britain. Source

Maio P.,Centro Hospitalar Of Lisbon Central Chlc | Fernandes C.,Centro Hospitalar Of Lisbon Central Chlc | Afonso A.,Centro Hospitalar Of Lisbon Central Chlc | Sachse F.,Instituto Portugues Of Oncologia Of Lisbon Francisco Gentil | And 2 more authors.
Anais Brasileiros de Dermatologia | Year: 2013

Blastic plasmacytoid dendritic cell tumor is a rare, highly aggressive systemic neoplasm for which effective therapies have not yet been established. We describe a 73-year-old man with multiple nodules and patches emerging on the trunk and limbs. Lesional skin biopsy revealed a plasmacytoid dendritic cell tumor with dense dermal infiltrate of tumor cells with blastoid features. No apparent systemic involvement was identified in the initial stage. The patient was treated with prednisone daily, with notorious improvement of the skin lesions, although no complete remission was obtained. During the six-month follow-up period, no disease progression was documented, but fatal systemic progression occurred after that period of time. © 2013 by Anais Brasileiros de Dermatologia. Source

Silva L.S.,New University of Lisbon | Silva L.S.,Instituto Portugues Of Oncologia Of Lisbon Francisco Gentil Ipolfg | Goncalves L.G.,Xavier University | Silva F.,New University of Lisbon | And 11 more authors.
Tumor Biology | Year: 2015

Uterine cervix cancer is the second most common malignancy in women worldwide with human papillomavirus (HPV) as the etiologic factor. The two main histological variants, squamous cell carcinomas (SCC) and adenocarcinomas (AC), resemble the cell morphology of exocervix and endocervix, respectively. Cancer metabolism is a cancer hallmark conditioned by the microenvironment. As uterine cervix homeostasis is dependent on lactate, we hypothesized lactate plays a role in uterine cervix cancer progression. Using in vitro (SiHa-SCC and HeLa-AC) and BALB-c/SCID models, we demonstrated that lactate metabolism is linked to histological types, with SCC predominantly consuming and AC producing lactate. MCT1 is a key factor, allowing lactate consumption and being regulated in vitro by lactate through the FOXM1:STAT3 pathway. In vivo models showed that SCC (SiHa) expresses MCT1 and is dependent on lactate to grow, whereas AC (HeLa) expresses MCT1 and MCT4, with higher growth capacities. Immunohistochemical analysis of tissue microarrays (TMA) from human cervical tumors showed that MCT1 expression associates with the SCC type and metastatic behavior of AC, whereas MCT4 expression concomitantly increases from in situ SCC to invasive SCC and is significantly associated with the AC type. Consistently, FOXM1 expression is statistically associated with MCT1 positivity in SCC, whereas the expression of FOXO3a, a FOXM1 functional antagonist, is linked to MCT1 negativity in AC. Our study reinforces the role of the microenvironment in the metabolic adaptation of cancer cells, showing that cells that retain metabolic features of their normal counterparts are positively selected by the organ’s microenvironment and will survive. In particular, MCT1 was shown to be a key element in uterine cervix cancer development; however, further studies are needed to validate MCT1 as a suitable therapeutic target in uterine cervix cancer. © 2015 International Society of Oncology and BioMarkers (ISOBM) Source

Serrano M.,Instituto Portugues Of Oncologia Of Lisbon Francisco Gentil Ipolfg | Mao-de-Ferro S.,Instituto Portugues Of Oncologia Of Lisbon Francisco Gentil Ipolfg | Pinho R.,Manoph Laboratorio Of Endoscopia E Motilidade Digestiva | Pinho R.,ManopH Instituto CUF | And 11 more authors.
Revista Espanola de Enfermedades Digestivas | Year: 2013

Background and objective: Little is known about the clinical impact of double-balloon enteroscopy (DBE) in patients with Peutz-Jeghers syndrome (PJS). The aim of this study was to assess the efficacy and safety of DBE in the management of small-bowel polyps in PJS patients. Patients and methods: We conducted a multicentre, retrospective cohort study, which included all consecutive patients diagnosed with PJS who underwent DBE for polypectomy between January 2006 and August 2012. In all cases, previous videocapsule enteroscopy had shown at least one polyp ≥ 10 mm in size. Results: Twenty-five patients (13 men; median age 36 years; 14 with prior laparotomy) underwent 46 DBE procedures (1 to 5 per patient, 44 via oral route). Polypectomy was performed in 39/46 DBEs. A total of 214 polyps were removed (median-size 30 mm), with a median number of polypectomies per procedure of 5.0 (range 1-18). The estimated maximum-sizes of resected polyps significantly decreased at each session: 30.0, 25.0, 20.0, 15.0, and 17.5 mm (p = 0.02). In 7 DBEs no polypectomy was performed (4-only minor polyps detected; 3-endoscopic irresecability). Complications occurred in 3/39 of therapeutic procedures (2-minor delayed bleeding; 1-mucosal tear), all of them dealt with conservative or endoscopic therapy. Six patients underwent elective surgery post DBE due to polyps not amenable for endoscopic resection. There were no small-bowel polyp related complications during a median follow-up of 56.5 months. Conclusion: DBE showed to be a safe and effective technique in the management of small-bowel polyps in PJS patients, allowing a presymptomatic and non-surgical approach. Source

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