scholarly journals The enzyme succinate dehydrogenase (SDH) and its role in hereditary pituitary adenomas

2013 ◽  
Vol 10 (4) ◽  
pp. 10-15
Author(s):  
Iu V Pankratova ◽  
E G Przhiyalkovskaya ◽  
E A Pigarova ◽  
L K Dzeranova
Keyword(s):  
Pituitary Adenomas ◽  
Multiple Endocrine Neoplasia ◽  
Germline Mutations ◽  
Genetic Defects ◽  
Hereditary Syndromes ◽  
Pituitary Tumorigenesis ◽  
Active Research ◽  
Familial Pituitary Adenomas

Despite active research involving familial pituitary adenomas and characterization of five hereditary syndromes, the genetic defects in more than 80 - 95% of patients remain not found. Besides, there is more than 25 cases of coexistence of pheochromocytomas and pituitary adenomas described in literature that up to date is not integrated in any syndrome; genetic defects of such coexistence also aren't defined. However it is supposed that in pituitary tumorigenesis, germline mutations of SDH can take part that is obviously important aspect of further investigation. Germline mutations of SDH were found in patients with different phenotypes of pituitary adenomas. Studying of mutations in genes SDHD, SDHB, SDHC, SDHA and their prevalence in patients with familial pituitary adenomas or with phenotypes of multiple endocrine neoplasia without mutations in MEN1, CDKN1B, PRKAR1A, AIP genes can provide clarity in a role of mutations in SDH in endocrine and in particular pituitary tumorigenesis.

scholarly journals Molecular Characterization of the Men1 Tumor Suppressor Gene in Sporadic Pituitary Tumors

1998 ◽  
Vol 83 (4) ◽  
pp. 1388-1391 ◽  
Author(s):  
Toni R. Prezant ◽  
Jonathan Levine ◽  
Shlomo Melmed
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Anterior Pituitary ◽  
Pituitary Tumors ◽  
Suppressor Gene ◽  
Coding Region ◽  
Men1 Gene ◽  
Pituitary Tumorigenesis

Anterior pituitary tumors arise sporadically, and also as part of the inherited multiple endocrine neoplasia type 1 (MEN 1) syndrome. To investigate the role of the recently isolated men1 gene in sporadic pituitary tumorigenesis, the complete coding sequence was screened for mutations in 45 sporadic anterior pituitary tumors, including 14 hormone-secreting tumors and 31 nonsecreting tumors, by dideoxy fingerprinting and sequence analysis. No pathogenic sequence changes were found in the men1 coding region. The men1 gene was expressed in 43 of these tumors with sufficient RNA, including one tumor with loss of heterozygosity (LOH) for several polymorphic markers on chromosomal region 11q13. Furthermore, both alleles were expressed in 19 tumors in which the constitutional DNA was heterozygous for intragenic polymorphisms. Thus, inactivation of the men1 tumor suppressor gene, by mutation or by imprinting, does not appear to play a prominent role in sporadic pituitary adenoma pathogenesis.

scholarly journals Myocarditis: Which Role for Genetics?

2021 ◽  
Vol 23 (6) ◽  
Author(s):  
Chiara Baggio ◽  
Giulia Gagno ◽  
Aldostefano Porcari ◽  
Alessia Paldino ◽  
Jessica Artico ◽  
...  
Keyword(s):  
Genetic Background ◽  
Clinical Course ◽  
Risk Profile ◽  
Myocardial Inflammation ◽  
Genetic Defects ◽  
Prognostic Role ◽  
Clinical Presentations

Abstract Purpose of Review Myocarditis is a polymorphic disease, both in its presentation and clinical course. Recent data suggests that the genetic background, interacting with environmental factors, could be diriment both in the susceptibility and evolution of myocarditis in different clinical presentations. The aim of this paper is to expose the current available evidences and the evolving concepts on this topic, in order to provide insight for improving the clinical management of those patients. In this regard, the main goal is an optimal characterization of each patient’s risk, with the purpose of individualizing the treatment and the follow-up. Recent Findings The latest research highlights the possible prognostic role of some pathogenic mutations that could create a vulnerable myocardium prone to myocardial inflammation and also to the development of a long-lasting cardiomyopathy. Summary The identification of these genetic defects and of myocarditis patients requiring genetic testing is emerging as a challenge for the future. In fact, identifying a possible genetic background responsible for a particularly high-risk profile could be of extreme importance in improving management of myocarditis. This and many other aspects in the genetics of myocarditis remain uncovered, and further studies are expected based to refine our daily clinical practice.

scholarly journals Emerging Targets in Pituitary Adenomas: Role of the CXCL12/CXCR4-R7 System

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Federica Barbieri ◽  
Stefano Thellung ◽  
Roberto Würth ◽  
Federico Gatto ◽  
Alessandro Corsaro ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Immune Surveillance ◽  
Axonal Guidance ◽  
Brain Areas ◽  
Pathological Conditions ◽  
Pituitary Tumorigenesis ◽  
Chemokine Cxcl12 ◽  
The Central Nervous System ◽  
Neuroendocrine Functions

Chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. Several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. In particular, the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, form a functional network that controls plasticity in different brain areas, influencing neurotransmission, neuromodulation, and cell migration, and the dysregulation of this chemokinergic axis is involved in several neurodegenerative, neuroinflammatory, and malignant diseases. CXCR4 primarily mediates the transduction of proliferative signals, while CXCR7 seems to be mainly responsible for scavenging CXCL12. Importantly, the multiple intracellular signalling generated by CXCL12 interaction with its receptors influences hypothalamic modulation of neuroendocrine functions, although a direct modulation of pituitary functioningviaautocrine/paracrine mechanisms was also reported. Both CXCL12 and CXCR4 are constitutively overexpressed in pituitary adenomas and their signalling induces cell survival and proliferation, as well as hormonal hypersecretion. In this review we focus on the physiological and pathological functions of immune-related cyto- and chemokines, mainly focusing on the CXCL12/CXCR4-7 axis, and their role in pituitary tumorigenesis. Accordingly, we discuss the potential targeting of CXCR4 as novel pharmacological approach for pituitary adenomas.

scholarly journals Role of the high mobility group A proteins in the regulation of pituitary cell cycle

2010 ◽  
Vol 44 (6) ◽  
pp. 309-318 ◽  
Author(s):  
Monica Fedele ◽  
Alfredo Fusco
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenomas ◽  
High Mobility ◽  
High Mobility Group ◽  
Tumor Evolution ◽  
Pituitary Cells ◽  
Pituitary Tumorigenesis ◽  
Human Pathology ◽  
Group A

Pituitary cells are particularly sensitive to alterations of the cell cycle machinery. In fact, mutations affecting expression of proteins critical for cell cycle progression, including retinoblastoma protein, cyclins D1 and D3, p16INK4A, and p27kip1, are frequent in human pituitary adenomas. Similarly, both targeted disruption and overexpression of either cell cycle inhibitors or activators, respectively, lead to the development of pituitary adenomas in mice. Recent evidence has added the high mobility group A (HMGA) proteins as a new class of cell cycle regulators that play significant roles in the pathways that lead to pituitary tumor evolution in both humans and experimental animal models. Here, we first review the role of the cell cycle in pituitary tumorigenesis, as witnessed by human pathology and transgenic mice; and then, we focus on HMGA proteins and their cell cycle-related role in pituitary tumorigenesis.

scholarly journals Pituitary adenomas in the framework of hereditary syndromes

2014 ◽  
Vol 60 (4) ◽  
pp. 51-59 ◽  
Author(s):  
E O Mamedova ◽  
E G Przhiyalkovskaya ◽  
E A Pigarova ◽  
N G Mokrysheva ◽  
L K Dzeranova ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Special Reference ◽  
Pituitary Adenomas ◽  
Present Review ◽  
Genetic Defects ◽  
Pituitary Neoplasms ◽  
Pituitary Tumours ◽  
Genetic Studies ◽  
Hereditary Syndromes

The overwhelming majority of the pituitary tumours are benign adenomas that remain a serious challenge to endocrinologists and neurosurgeons by virtue of great variety of their early manifestations, the impossibility to predict the neoplastic growth, and the influence exerted on the patients' quality of life. Most pituitary adenomas are sporadic tumours and only few of them develop in the framework of hereditary syndromes. The present review is focused on the variants of hereditary syndromes with special reference to various pituitary neoplasms. The molecular and genetic studies revealed several genetic defects that are believed to contribute to the formation of pituitary adenomas. Moreover, a few genes were identified responsible for the development of hereditary forms of pituitary tumours. Identification of such genes and pathogenetic mechanisms underlying the development of pituitary microadenomas is of paramount importance for the improvement of their diagnostics and treatment that in its turn may promote the understanding of pathogenesis of sporadic adenomas and improve their prognosis.

PIT1 upregulation by HMGA proteins has a role in pituitary tumorigenesis

2011 ◽  
Vol 19 (2) ◽  
pp. 123-135 ◽  
Author(s):  
Dario Palmieri ◽  
Teresa Valentino ◽  
Ivana De Martino ◽  
Francesco Esposito ◽  
Paolo Cappabianca ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Gene Promoter ◽  
Pituitary Tumour ◽  
Human Pituitary ◽  
Expression Levels ◽  
Pituitary Tumorigenesis ◽  
Its Gene ◽  
Gland Development

We have previously demonstrated that HMGA1B and HMGA2 overexpression in mice induces the development of GH and prolactin (PRL) pituitary adenomas mainly by increasing E2F1 transcriptional activity. Interestingly, these adenomas showed very high expression levels of PIT1, a transcriptional factor that regulates the gene expression ofGh,Prl,GhrhrandPit1itself, playing a key role in pituitary gland development and physiology. Therefore, the aim of our study was to identify the role ofPit1overexpression in pituitary tumour development induced by HMGA1B and HMGA2. First, we demonstrated that HMGA1B and HMGA2 directly interact with both PIT1 and its gene promoterin vivo, and that these proteins positively regulatePit1promoter activity, also co-operating with PIT1 itself. Subsequently, we showed, by colony-forming assays on two different pituitary adenoma cell lines, GH3 and αT3, thatPit1overexpression increases pituitary cell proliferation. Finally, the expression analysis ofHMGA1,HMGA2andPIT1in human pituitary adenomas of different histological types revealed a direct correlation betweenPIT1and HMGA expression levels. Taken together, our data indicate a role ofPit1upregulation by HMGA proteins in pituitary tumours.

Phenocopies of multiple endocrine neoplasia type 1: role of the genes, associated with the development of pituitary adenomas

2016 ◽  
Vol 62 (4) ◽  
pp. 4-10
Author(s):  
Elizaveta O. Mamedova ◽  
Natalya G. Mokrysheva ◽  
Ekaterina A. Pigarova ◽  
Elena G. Przhiyalkovskaya ◽  
Evgeny V. Vasilyev ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
New Genes ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Exon 1 ◽  
Aip Gene

Background. Absence of detectable MEN1 mutations in a patient with multiple endocrine neoplasia type 1 (MEN1) phenotype may disprove the hereditary predisposition and the necessity of a lifelong regular screening for detecting the remaining components of the syndrome, and the examination of the first-degree relatives. Nevertheless, there may be other genes involved in the co-occurrence of several MEN1-associated tumors. Aim — to determine the role of genes, associated with the development of familial pituitary adenomas (PA), and genes, presumably involved in pathogenesis of sporadic PA, in the development of MEN1 phenocopies with PA as one of components.Material and methods. 23 patients with MEN1 phenocopy were included in the study. The patients underwent next-generation sequencing (NGS) (Ion TorrentTM PGMTM, Thermo Fisher Scientific — Life Technologies, USA) using a panel of candidate genes (MEN1, CDKN1B, PRKAR1A, AIP, SDHA, SDHB, SDHC, SDHD, GNAS, PRKCA, CDKN2A, CDKN2C, POU1F1, PTTG2).Results. In 1 (4%) female patient with acromegaly and primary hyperparathyroidism (PHPT) a germline heterozygous change in exon 6 of AIP gene c.911G>A (p.R304Q) was revealed. In four female patients with acromegaly and PHPT we revealed polymorphisms whose pathological significance is not defined: heterozygous change in exon 1 of PTTG2 gene c.134G>A (p.R45H), heterozygous change in intron 1 of PRKAR1A gene (c.–10G>C), heterozygous change in exon 5 of SDHB gene c.487T>C (p.S163P), heterozygous change in 3’-UTR of CDKN1B gene g.3897G>T (c*8G>T).Conclusions. The results of our study show that mutations in the majority of the examined genes associated with the development of hereditary and sporadic PA, do not cause the development of MEN1 phenocopies. The necessity to study AIP gene in all patients with MEN1 phenocopies needs further research. It is recommended to search for new genes, mutations in which could be the cause of the development of MEN1 phenocopies.

Digital x-ray mapping of nanometer-size supported bimetallic catalysts

1988 ◽  
Vol 46 ◽  
pp. 530-531
Author(s):  
L. T. Germinario
Keyword(s):  
Background Radiation ◽  
Metal Cluster ◽  
Single Element ◽  
Beam Diameter ◽  
X Rays ◽  
X Ray ◽  
Major Interest ◽  
Induced Changes

Understanding the role of metal cluster composition in determining catalytic selectivity and activity is of major interest in heterogeneous catalysis. The electron microscope is well established as a powerful tool for ultrastructural and compositional characterization of support and catalyst. Because the spatial resolution of x-ray microanalysis is defined by the smallest beam diameter into which the required number of electrons can be focused, the dedicated STEM with FEG is the instrument of choice. The main sources of errors in energy dispersive x-ray analysis (EDS) are: (1) beam-induced changes in specimen composition, (2) specimen drift, (3) instrumental factors which produce background radiation, and (4) basic statistical limitations which result in the detection of a finite number of x-ray photons. Digital beam techniques have been described for supported single-element metal clusters with spatial resolutions of about 10 nm. However, the detection of spurious characteristic x-rays away from catalyst particles produced images requiring several image processing steps.

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