Mediastinal paragangliomas: Association with mutations in the succinate dehydrogenase genes and aggressive behavior
Department of Internal Medicine, University of Texas, Dallas, Texas 75390-8857, USA.Endocrine Related Cancer (Impact Factor: 4.81). 03/2009; 16(1):291-9. DOI: 10.1677/ERC-08-0214
Extra-adrenal pheochromocytomas, otherwise known as paragangliomas (PGLs), account for about 20% of catecholamine-producing tumors. Catecholamine excess and mutations in the genes encoding succinate dehydrogenase subunits (SDHx) are frequently found in patients with PGLs. Only 2% of PGLs are found in the mediastinum, and little is known about genetic alterations in patients with mediastinal PGLs, catecholamine production by these tumors, or their clinical behavior. We hypothesized that most mediastinal PGLs are associated with germ line SDHx mutations, norepinephrine and/or dopamine excess, and aggressive behavior. The objective of this study was to characterize genetic, biochemical, and clinical data in a series of ten patients with mediastinal PGLs. All ten primary mediastinal PGL patients had germ line SDHx mutations, six in SDHB, and four in SDHD genes. Chest or back pain were the most common presenting symptoms (five patients), and catecholamines and/or their metabolites were elevated in seven patients. Additional tumors included head and neck PGLs in four patients, pheochromocytoma in one patient, and bladder PGL in another. Metastatic disease was documented in six patients (60%), and a concurrent abdominal mass was found in one patient. We conclude that mediastinal PGLs are strongly associated with SDHB and SDHD gene mutations, noradrenergic phenotype, and aggressive behavior. The present data suggest that all patients with mediastinal PGLs should be screened for SDHx gene mutations, regardless of age.
Article: The VitreousA.M.A. archives of ophthalmology 10/1957; 58(3):455-64. DOI:10.1001/archopht.1957.00940010745012
Conference Paper: Results and status of the Alcator C-Mod tokamak[Show abstract] [Hide abstract]
ABSTRACT: Recent Alcator C-Mod experimental campaigns have focused upon the study of the Advanced Tokamak regimes, which includes characterization of the RF heating, the formation and dynamics of internal barriers, H-mode edge pedestal, and divertor and scrape-off physics. The ICRF system has been recently upgraded with the improved performance of the 4-strap antenna. Total ICRF power in excess of 5 MW has been launched successfully into the plasma during this campaign. Due to the compact nature of C-Mod, the power feeds for the antenna are vacuum strip lines. Their orientation, to the tokamak B-field, is governed by maintaining E<15 kV/cm in locations where the RF E-field is parallel to tokamak B-field. Other modifications included improved protection tile grounding and installation of protective shields for Faraday screen ceramic isolators. The antennas also make use of BN protection tiles to eliminate high Z impurities from the antennas. The present empirical power limit results from arcing in a region of the antenna strap where E∼15 kV/cm and parallel to B and injections from the metallic fasteners used to attach the BN tiles to the antenna.Fusion Engineering, 2002. 19th Symposium on; 02/2002
Article: Pheochromocytoma and Paraganglioma.[Show abstract] [Hide abstract]
ABSTRACT: Pheochromocytoma is a very special kind of tumor full of duplicity. On the one hand it represents its own microworld with unique clinical, biochemical and pathological features, while on the other it constitutes a tremendously significant part of whole body system, playing a vital role for practically every organ system. It has a very special character - sometimes like a child it can be sweet and predictable, while at times it can behave like a deadly wild beast, crashing and tearing everything on its path in a fierce rage. It also consists of the amazingly intelligent neuroendocrine cells that possess a magical ability to make miraculous substances of many kinds. But most of all, it is a system that is able to drive our curiosity and the itch of "Cogito, ergo sum" to limitless depths and year by year it still amazes us with new and unexpected discoveries that move our understanding of multiple pathways and metabolic events closer to the ultimate truth. Recent discoveries of succinate dehydrogenase (SHD) and prolyl hydroxylase (PHD) mutations, for example, propelled our understanding of neuroendocrine tumorigenesis as a whole, as well as physiology of mitochondrial respiratory chain and phenomenon of pseudohypoxia in particular. Good old discoveries make their way from dusty repositories to shine with new meaning, appropriate for the current level of knowledge. This acquired wisdom makes us better physicians - knowing the specific expression makeup of catecholamine transporters, GLUTs and SRIFs allows for better tailored imaging and therapeutic manipulations. There are still long ways to go, keeping in mind that pheochromocytoma is but so very special, and we are optimistic and expect many great things to come.Progress in brain research 01/2010; 182:343-73. DOI:10.1016/S0079-6123(10)82015-1 · 2.83 Impact Factor
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