- Global DNA Methylation Analysis Identifies Two Discrete clusters of Pheochromocytoma with Distinct Genomic and Genetic Alterations. [Journal Article]
- SRSci Rep 2017 Mar 22; 7:44943
- Pheochromocytomas and paragangliomas (PPGLs) are rare and frequently heritable neural-crest derived tumours arising from the adrenal medulla or extra-adrenal chromaffin cells respectively. The majori...
Pheochromocytomas and paragangliomas (PPGLs) are rare and frequently heritable neural-crest derived tumours arising from the adrenal medulla or extra-adrenal chromaffin cells respectively. The majority of PPGL tumours are benign and do not recur with distant metastases. However, a sizeable fraction of these tumours secrete vasoactive catecholamines into the circulation causing a variety of symptoms including hypertension, palpitations and diaphoresis. The genetic landscape of PPGL has been well characterized and more than a dozen genes have been described as recurrently mutated. Recent studies of DNA-methylation have revealed distinct clusters of PPGL that share DNA methylation patterns and driver mutations, as well as identified potential biomarkers for malignancy. However, these findings have not been adequately validated in independent cohorts. In this study we use an array-based genome-wide approach to study the methylome of 39 PPGL and 4 normal adrenal medullae. We identified two distinct clusters of tumours characterized by different methylation patterns and different driver mutations. Moreover, we identify genes that are differentially methylated between tumour subcategories, and between tumours and normal tissue.
- Planar Diamond-Based Multiarrays to Monitor Neurotransmitter Release and Action Potential Firing: New Perspectives in Cellular Neuroscience. [Journal Article]
- ACACS Chem Neurosci 2017 Feb 15; 8(2):252-264
- High biocompatibility, outstanding electrochemical responsiveness, inertness, and transparency make diamond-based multiarrays (DBMs) first-rate biosensors for in vitro detection of electrochemical an...
High biocompatibility, outstanding electrochemical responsiveness, inertness, and transparency make diamond-based multiarrays (DBMs) first-rate biosensors for in vitro detection of electrochemical and electrical signals from excitable cells together, with potential for in vivo applications as neural interfaces and prostheses. Here, we will review the electrochemical and physical properties of various DBMs and how these devices have been employed for recording released neurotransmitter molecules and all-or-none action potentials from living cells. Specifically, we will overview how DBMs can resolve localized exocytotic events from subcellular compartments using high-density microelectrode arrays (MEAs), or monitoring oxidizable neurotransmitter release from populations of cells in culture and tissue slices using low-density MEAs. Interfacing DBMs with excitable cells is currently leading to the promising opportunity of recording electrical signals as well as creating neuronal interfaces through the same device. Given the recent increasingly growing development of newly available DBMs of various geometries to monitor electrical activity and neurotransmitter release in a variety of excitable and neuronal tissues, the discussion will be limited to planar DBMs.
- Novel sulfoglycolipid IG20 causes neuroprotection by activating the phase II antioxidant response in rat hippocampal slices. [Journal Article]
- NNeuropharmacology 2017; 116:110-121
- Compound IG20 is a newly synthesised sulphated glycolipid that promotes neuritic outgrowth and myelinisation, at the time it causes the inhibition of glial proliferation and facilitates exocytosis in...
Compound IG20 is a newly synthesised sulphated glycolipid that promotes neuritic outgrowth and myelinisation, at the time it causes the inhibition of glial proliferation and facilitates exocytosis in chromaffin cells. Here we have shown that IG20 at 0.3-10 μM afforded neuroprotection in rat hippocampal slices stressed with veratridine, glutamate or with oxygen plus glucose deprivation followed by reoxygenation (OGD/reox). Excess production of reactive oxygen species (ROS) elicited by glutamate or ODG/reox was prevented by IG20 that also restored the depressed tissue levels of GSH and ATP in hippocampal slices subjected to OGD/reox. Furthermore, the augmented iNOS expression produced upon OGD/reox exposure was also counteracted by IG20. Additionally, the IG20 elicited neuroprotection was prevented by the presence of inhibitors of the signalling pathways Jak2/STAT3, MEK/ERK1/2, and PI3K/Akt, consistent with the ability of the compound to increase the phosphorylation of Jak2, ERK1/2, and Akt. Thus, the activation of phase II response and the Nrf2/ARE pathway could explain the antioxidant and anti-inflammatory effects and the ensuing neuroprotective actions of IG20.
- Metastatic carotid body paraganglioma of lungs and lymph nodes: Unsuspected diagnosis on EBUS-TBNA. [Case Reports]
- DCDiagn Cytopathol 2017; 45(4):327-332
- Paragangliomas are tumors that originate from the extra-adrenal chromaffin and nonchromaffin cells of neural crest origin. Lymph node metastases are common, while distant metastases to lung, liver, a...
Paragangliomas are tumors that originate from the extra-adrenal chromaffin and nonchromaffin cells of neural crest origin. Lymph node metastases are common, while distant metastases to lung, liver, and bone are rare events and usually occur in the presence of a long standing clinically evident primary tumor. Primary diagnosis of paraganglioma at a metastatic site without a known primary is a diagnostic challenge. We report a case of an adult woman with incidentally detected metastasis to bilateral lungs from an occult carotid body paraganglioma, which presented a cytopathological diagnostic dilemma on EBUS-TBNA from paratracheal lymph nodes. Diagn. Cytopathol. 2017;45:327-332. © 2016 Wiley Periodicals, Inc.
- Adrenal cortical and chromaffin stem cells: Is there a common progeny related to stress adaptation? [Review]
- MCMol Cell Endocrinol 2017 Feb 05; 441:156-163
- The adrenal gland is a highly plastic organ with the capacity to adapt the body homeostasis to different physiological needs. The existence of stem-like cells in the adrenal cortex has been revealed ...
The adrenal gland is a highly plastic organ with the capacity to adapt the body homeostasis to different physiological needs. The existence of stem-like cells in the adrenal cortex has been revealed in many studies. Recently, we identified and characterized in mice a pool of glia-like multipotent Nestin-expressing progenitor cells, which contributes to the plasticity of the adrenal medulla. In addition, we found that these Nestin progenitors are actively involved in the stress response by giving rise to chromaffin cells. Interestingly, we also observed a Nestin-GFP-positive cell population located under the adrenal capsule and scattered through the cortex. In this article, we discuss the possibility of a common progenitor giving rise to subpopulations of cells both in the adrenal cortex and medulla, the isolation and characterization of this progenitor as well as its clinical potential in transplantation therapies and in pathophysiology.
- Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions. [Review]
- FEFront Endocrinol (Lausanne) 2016; 7:98
- In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, ...
In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions.
- Microelectrode Arrays of Diamond-Insulated Graphitic Channels for Real-Time Detection of Exocytotic Events from Cultured Chromaffin Cells and Slices of Adrenal Glands. [Journal Article]
- ACAnal Chem 2016 Aug 02; 88(15):7493-9
- A microstructured graphitic 4 × 4 multielectrode array was embedded in a single-crystal diamond substrate (4 × 4 μG-SCD MEA) for real-time monitoring of exocytotic events from cultured chromaffin cel...
A microstructured graphitic 4 × 4 multielectrode array was embedded in a single-crystal diamond substrate (4 × 4 μG-SCD MEA) for real-time monitoring of exocytotic events from cultured chromaffin cells and adrenal slices. The current approach relies on the development of a parallel ion beam lithographic technique, which assures the time-effective fabrication of extended arrays with reproducible electrode dimensions. The reported device is suitable for performing amperometric and voltammetric recordings with high sensitivity and temporal resolution, by simultaneously acquiring data from 16 rectangularly shaped microelectrodes (20 × 3.5 μm(2)) separated by 200 μm gaps. Taking advantage of the array geometry we addressed the following specific issues: (i) detect both the spontaneous and KCl-evoked secretion simultaneously from several chromaffin cells directly cultured on the device surface, (ii) resolve the waveform of different subsets of exocytotic events, and (iii) monitoring quantal secretory events from thin slices of the adrenal gland. The frequency of spontaneous release was low (0.12 and 0.3 Hz, respectively, for adrenal slices and cultured cells) and increased up to 0.9 Hz after stimulation with 30 mM KCl in cultured cells. The spike amplitude as well as rise and decay time were comparable with those measured by carbon fiber microelectrodes and allowed to identify three different subsets of secretory events associated with "full fusion" events, "kiss-and-run" and "kiss-and-stay" exocytosis, confirming that the device has adequate sensitivity and time resolution for real-time recordings. The device offers the significant advantage of shortening the time to collect data by allowing simultaneous recordings from cell populations either in primary cell cultures or in intact tissues.
- Mediastinal paraganglioma fed by the left circumflex artery. [Journal Article]
- ICInteract Cardiovasc Thorac Surg 2016; 23(5):835-836
- A 60-year-old male patient who previously underwent carotid and jugular paraganglioma resections was referred because of a mediastinal recurrence at the root of the great vessels. Coronary angiograph...
A 60-year-old male patient who previously underwent carotid and jugular paraganglioma resections was referred because of a mediastinal recurrence at the root of the great vessels. Coronary angiography confirmed the circumflex artery of the left coronary artery as the feeding artery of the tumour. The patient underwent surgery due to the tumour's location and malignant potential. Upon mass resection, histopathological examination characterized the tumour as a secondary paraganglioma. Neuroendocrine tumours arising from chromaffin tissues at the extra-adrenal paraganglions of the autonomic nervous system are termed paragangliomas. Clinically, they are divided into functional and non-functional types, depending on their catecholamine secretion. The mediastinal location is exceptional and its treatment is challenging.
- Studying the peripheral sympathetic nervous system and neuroblastoma in zebrafish. [Journal Article]
- MCMethods Cell Biol 2016; 134:97-138
- The zebrafish serves as an excellent model to study vertebrate development and disease. Optically clear embryos, combined with tissue-specific fluorescent reporters, permit direct visualization and m...
The zebrafish serves as an excellent model to study vertebrate development and disease. Optically clear embryos, combined with tissue-specific fluorescent reporters, permit direct visualization and measurement of peripheral nervous system formation in real time. Additionally, the model is amenable to rapid cellular, molecular, and genetic approaches to determine how developmental mechanisms contribute to disease states, such as cancer. In this chapter, we describe the development of the peripheral sympathetic nervous system (PSNS) in general, and our current understanding of genetic pathways important in zebrafish PSNS development specifically. We also illustrate how zebrafish genetics is used to identify new mechanisms controlling PSNS development and methods for interrogating the potential role of PSNS developmental pathways in neuroblastoma pathogenesis in vivo using the zebrafish MYCN-driven neuroblastoma model.
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- [Pheochromocytoma and pregnancy. A case report]. [Case Reports]
- GOGinecol Obstet Mex 2015; 83(11):735-42
- CONCLUSIONS: Thus, it is important that obstetrician knows this disease and its management during pregnancy; so we present this case report.