Casola di Napoli, Italy
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Vaira V.,Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico | Elli F.,Endocrinology Unit | Elli F.,University of Milan | Forno I.,University of Milan | And 10 more authors.
Journal of Molecular Endocrinology | Year: 2012

A subset of over-expressed microRNAs (miRNAs) identified in parathyroid carcinomas (Ca) compared to normal glands belongs to C19MC, a cluster on chromosome 19q13.4 involved in stem cell biology and tumourigenesis. In this study, the expression of C19MC-MIR371-3 clusters and the molecular mechanisms presiding their modulation were investigated in a series of six normal parathyroids, 24 adenomas (Ad), 15 Ca and five matched metastases. The general expression levels of C19MC or MIR371-3 clusters in Ad lesions did not differ from normal glands, while they distinguished Ad from Ca at unsupervised hierarchical cluster analysis (P=0·0008). MIR517C showed the most significant difference in expression between Ca and Ad (P=0·0003) and it positively correlated with serum calcium, parathormone and tumour weight. In regard to the molecular mechanism determining C19MC cluster activation, we could detect C19MC copy number (CN) gain in ten Ca (67%) extending distal to the MIR371-3 cluster in almost all samples. Conversely, only four Ad (16%) showed C19MC amplification, with one case presenting distal genomic aberration to MIR371-3. Globally, CN variations of 19q13.4 loci were significantly associated with MIR517C up-regulation (P=0·006). Opposite to normal glands where C19MC promoter was methylated, hypomethylation occurred in 15 out of 30 analysed tumours. Though the epigenetic status did not correlate with C19MC miRNA expression levels, loss of C19MC promoter methylation was significantly associated with Ca and metastatic disease (P=0·01). In conclusion, C19MC cluster aberrations are a characteristic of Ca with respect to Ad. Altogether, these evidences point towards a role for 19q13.4 miRNA clusters as oncogenes in parathyroid tumourigenesis. © 2012 Society for Endocrinology.


Verdelli C.,Laboratory of Molecular Biology | Avagliano L.,University of Milan | Creo P.,Laboratory of Stem Cells for Tissue Engineering | Guarnieri V.,IRCCS Hospital Casa Sollievo Sofferenza | And 9 more authors.
Endocrine-Related Cancer | Year: 2015

Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immuno-histochemistry for alpha-smooth muscle actin (α-SMA) showed an abundant periacinar distribution of α-SMA+ cells in normal parathyroid glands (nZ3). This pattern was progressively lost in parathyroid adenomas (PAds; nZ6) where α-SMA+ cells were found to surround new microvessels, as observed in foetal parathyroid glands (nZ2). Moreover, in atypical adenomas (nZ5) and carcinomas (nZ4), α-SMA+ cells disappeared from the parenchyma and accumulated in the capsula and fibrous bands. At variance with normal glands, parathyroid tumours (nZ37) expressed high levels of fibroblast-activation protein (FAP) transcripts, a marker of tumour-associated fibroblasts. We analysed the ability of PAd-derived cells to activate fibroblasts using human bone-marrow mesenchymal stem cells (hBM-MSCs). PAd-derived cells induced a significant increase in FAP and vascular endothelial growth factor A (VEGFA) mRNA levels in co-cultured hBM-MSCs. Furthermore, the role of the calcium-sensing receptor (CASR) and of the CXCL12/CXCR4 pathway in the PAd-induced activation of hBM-MSCs was investigated. Treatment of co-cultures of hBM-MSCs and PAd-derived cells with the CXCR4 inhibitor AMD3100 reduced the stimulated VEGFA levels, while CASR activation by the R568 agonist was ineffective. PAd-derived cells co-expressing parathyroid hormone (PTH)/CXCR4 and PTH/CXCL12 were identified by FACS, suggesting a paracrine/autocrine signalling. Finally, CXCR4 blockade by AMD3100 reduced PTH gene expression levels in PAd-derived cells. In conclusion, i) PAd-derived cells activated cells of mesenchymal origin; ii) PAd-associated fibroblasts were involved in tumuor neoangiogenesis and iii) CXCL12/CXCR4 pathway was expressed and active in PAd cells, likely contributing to parathyroid tumour neoangiogenesis and PTH synthesis modulation. © 2015 Society for Endocrinology.


News Article | November 30, 2016
Site: www.eurekalert.org

A team of surgeons at Mount Sinai Beth Israel (MSBI), led by William B. Inabnet III, MD, the Eugene W. Friedman, MD, Professor of Surgery and Chair for the Department of Surgery at MSBI and Chief of Endocrine Surgery Quality for the Mount Sinai Health System, have performed the first endoscopic transoral thyroidectomy in New York, and one of the first of its kind in the nation. Their initial case, which is the first published report in the United States, was recently described in the journal Surgical Endoscopy. With the assistance of Gustavo Fernandez-Ranvier, MD, and Hyunsuk Suh, MD, both Assistant Professors in the Department of Surgery at the Icahn School of Medicine at Mount Sinai, Dr. Inabnet removed the thyroid gland by making three small incisions inside the mouth underneath the lower lip. He inserted ports through the incisions, including an endoscope - a medical device with a light and camera. Once a working space within the neck area was created, Dr. Inabnet preserved the critical structures and removed the thyroid gland through the largest of the incisions. This minimally-invasive procedure leaves a hidden scar compared to the conventional transcervical approach, which leaves a visible scar on the patient's neck. "Out of all of the approaches, this is the one type of thyroid operation where there is no sign that the patient underwent surgery," said Dr. Inabnet. "This procedure is best equipped for smaller nodules and early-stage papillary thyroid cancer. I anticipate it will evolve for other applications going forward." Dr. Inabnet and his team specialize in a group of operations known as hidden-scar endoscopic thyroid surgery, which includes the transaxillary approach where incisions are made under the armpit, and the bilateral axillary breast approach, also known as BABA, where four small incisions are made in hidden locations on the chest. "The transoral route is a natural addition to our growing program of minimally invasive techniques," said Dr. Inabnet. "We now have the ability to approach the thyroid gland from below, from the side, or from above through the mouth." Dr. Inabnet has pioneered new techniques in minimally invasive endocrine neck surgery as well as adrenal and pancreatic surgery. In 1998, he helped perform the first endoscopic thyroid resection in the United States (the second in the world) and has advanced the field of video-endoscopic neck surgery. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. , or find Mount Sinai on Facebook, Twitter and YouTube.


News Article | November 30, 2016
Site: www.prweb.com

A team of surgeons at Mount Sinai Beth Israel (MSBI), led by William B. Inabnet III, MD, the Eugene W. Friedman, MD, Professor of Surgery and Chair for the Department of Surgery at MSBI and Chief of Endocrine Surgery Quality for the Mount Sinai Health System, have performed the first endoscopic transoral thyroidectomy in New York, and one of the first of its kind in the nation. Their initial case, which is the first published report in the United States, was recently described in the journal Surgical Endoscopy. With the assistance of Gustavo Fernandez-Ranvier, MD, and Hyunsuk Suh, MD, both Assistant Professors in the Department of Surgery at the Icahn School of Medicine at Mount Sinai, Dr. Inabnet removed the thyroid gland by making three small incisions inside the mouth underneath the lower lip. He inserted ports through the incisions, including an endoscope – a medical device with a light and camera. Once a working space within the neck area was created, Dr. Inabnet preserved the critical structures and removed the thyroid gland through the largest of the incisions. This minimally-invasive procedure leaves a hidden scar compared to the conventional transcervical approach, which leaves a visible scar on the patient’s neck. “Out of all of the approaches, this is the one type of thyroid operation where there is no sign that the patient underwent surgery,” said Dr. Inabnet. “This procedure is best equipped for smaller nodules and early-stage papillary thyroid cancer. I anticipate it will evolve for other applications going forward.” Dr. Inabnet and his team specialize in a group of operations known as hidden-scar endoscopic thyroid surgery, which includes the transaxillary approach where incisions are made under the armpit, and the bilateral axillary breast approach, also known as BABA, where four small incisions are made in hidden locations on the chest. “The transoral route is a natural addition to our growing program of minimally invasive techniques,” said Dr. Inabnet. “We now have the ability to approach the thyroid gland from below, from the side, or from above through the mouth.” Dr. Inabnet has pioneered new techniques in minimally invasive endocrine neck surgery as well as adrenal and pancreatic surgery. In 1998, he helped perform the first endoscopic thyroid resection in the United States (the second in the world) and has advanced the field of video-endoscopic neck surgery. About the Mount Sinai Health System The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the “Honor Roll” of best hospitals in America, ranked No. 15 nationally in the 2016-2017 “Best Hospitals” issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation’s top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai’s Kravis Children’s Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www.mountsinai.org/, or find Mount Sinai on Facebook, Twitter and YouTube.


Corbetta S.,University of Milan | Vaira V.,University of Milan | Guarnieri V.,IRCCS Hospital Casa Sollievo Della Sofferenza | Scillitani A.,IRCCS Hospital Casa Sollievo Della Sofferenza | And 8 more authors.
Endocrine-Related Cancer | Year: 2010

Parathyroid carcinoma (PaC) is a rare cause of primary hyperparathyroidism. Though the loss of the oncosuppressor CDC73/HRPT2 gene product, parafibromin, has been involved in the hyperparathyroidism-jaw tumor syndrome and in a consistent set of sporadic PaCs, parathyroid carcinogenesis remains obscure. MicroRNAs are a new class of small, non-coding RNAs implicated in development of cancer, since their deregulation can induce aberrant expression of several target genes. The aim of the present study was to identify differentially expressed microRNAs in parathyroid cancers compared with normal tissues. We performed a TaqMan low-density array profiling of four parathyroid cancers harboring CDC73 inactivating mutations and negative for parafibromin immunostaining. Their microRNA profiling was compared with that of two normal parathyroid biopsies. Out of 362 human microRNAs assayed, 279 (77%) were successfully amplified. Fourteen and three microRNAs were significantly down- and over-expressed in parathyroid cancers respectively. Of these, miR-296 and miR-139 were down-regulated, and miR-503 and miR-222 were over-expressed with a null false discovery rate. Carcinomas could be discriminated from parathyroid adenomas by a computed score based on the expression levels of miR-296, miR-222, and miR-503 as miR-139 was similarly down-regulated in both cancers and adenomas. Finally, miR-296 and miR-222 levels negatively correlated with mRNA levels of the hepatocyte growth factor receptor-regulated tyrosine kinase substrate and p27/kip1 levels respectively. These results suggest the existence of an altered microRNA expression pattern in PaCs together with a potential role of miR-296 as novel oncosuppressor gene in these neoplasia. © 2010 Society for Endocrinology Printed in Great Britain.


Kouniavsky G.,Endocrine Surgery | Kouniavsky G.,The Surgical Center | Zeiger M.A.,Endocrine Surgery | Zeiger M.A.,Johns Hopkins University
Current Opinion in Oncology | Year: 2010

Purpose of review The purpose of this review is to provide an update on recent advances in the understanding of thyroid cancer tumorigensis and implications in clinical practice. Recent findings: Recent novel and promising findings include additional abnormalities in key pathways associated with thyroid tumorigenesis (RET-Ras-BRAF-MEK; RET-β-cateinin; TRK-PI3K-AKT; and MDM-p53-PTEN), single-nucleotide polymorphisms associated with thyroid cancer susceptibility, epigenetic silencing, alternative splicing, and gene expression abnormalities. Complex regulatory mechanisms and insights into ways in which molecular aberrancies occur are becoming better understood through this research. Summary: With ongoing research, clinical problems such as the suspicious thyroid fine needle aspiration, better treatment algorithms for well differentiated thyroid cancer, and more effective treatment for anaplastic cancer will likely be found. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Gambelunghe G.,University of Perugia | Bini V.,University of Perugia | Stefanetti E.,University of Perugia | Colella R.,University of Perugia | And 3 more authors.
International Journal of Hyperthermia | Year: 2014

Purpose: The literature reports a wide range of percentages of ablation in the treatment of thyroid nodules. The aim of this nested case-control study was to evaluate whether the different morphological (well-defined vs. agglomerate) characteristics of nodules affect the success rate.Materials and methods: We selected 20 patients with a single and /or dominant well-defined nodule (group 1) and 20 with a nodular formation resulting from the fusion of multiple nodules (group 2). All the nodules were treated by the laser method receiving the same energy.Results: At 6 months, patients in group 1 showed a greater decrease in volume than those in group 2. These differences were more evident after 12 months.Conclusions: Our study demonstrates that the efficacy of laser treatment can be predicted by nodule morphology and contributes to explaining the wide differences in the percentages of ablation reported in literature. © 2014 Informa UK Ltd.

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