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adrenocortical adenoma

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https://www.readbyqxmd.com/read/27886397/telomerase-and-n-cadherin-differential-importance-in-adrenocortical-cancers-and-adenomas
#1
Sofia S Pereira, Valdemar Máximo, Ricardo Coelho, Rui Batista, Paula Soares, Susana G Guerreiro, Manuel Sobrinho-Simões, Mariana P Monteiro, Duarte Pignatelli
Adrenocortical carcinomas (ACC) are most frequently highly aggressive tumors. We assessed the telomerase reverse transcriptase (TERT) and N-cadherin role in the biology of ACC and their potential utility as molecular biomarkers, in different types of tumoral adrenocortical tissue. A total of 48 adrenal cortex samples (39 tumoral and 9 normal adrenal glands) were studied. TERT promoter mutations were searched by PCR and Sanger sequencing in two hotspots positions (-124 and -146). Also, telomerase and N-cadherin expression were evaluated by immunohistochemistry...
November 25, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27875378/cushing-syndrome-in-carney-complex-clinical-pathologic-and-molecular-genetic-findings-in-the-17-affected-mayo-clinic-patients
#2
Kathleen M Lowe, William F Young, Charalampos Lyssikatos, Constantine A Stratakis, J Aidan Carney
Carney complex (CNC) is a rare dominantly inherited multiorgan tumoral disorder that includes Cushing syndrome (CS). To establish the Mayo Clinic experience with the CS component, including its clinical, laboratory, and pathologic findings, we performed a retrospective search of the patient and pathologic databases of Mayo Clinic in Rochester, MN, for patients with CNC and clinical or laboratory findings of CS. Thirty-seven patients with CNC were identified. Twenty-nine had clinical, pathologic, or laboratory evidence of an adrenocortical disorder...
November 21, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27865598/suppression-of-cytochrome-p450-4b1-an-early-event-in-adrenocortical-tumorigenesis
#3
Timothy D Murtha, Reju Korah, Tobias Carling
BACKGROUND: Adrenocortical carcinoma is a rare neoplasm with a poor prognosis. Conversely, adrenocortical adenomas are common and benign. Despite their shared histologic origin, little evidence exists to suggest that adrenocortical adenoma arises from adrenocortical carcinoma. Recent genetic analyses of adrenocortical carcinoma have shown recurrent gene copy deletion of CYP4B1, a cytochrome P450 isozyme. This study investigates a potential role for CYP4B1 in modulating adrenocortical tumorigenesis and/or conferring chemoresistance to adrenocortical carcinomas...
November 16, 2016: Surgery
https://www.readbyqxmd.com/read/27864864/genetics-of-adrenocortical-tumours
#4
T Åkerström, T Carling, F Beuschlein, P Hellman
The recently available genomic sequencing techniques have led to breakthroughs in understanding of the underlying genetic mechanisms in adrenocortical tumours. Disease-causing mutations have been described for aldosterone-producing adenomas, cortisol-producing adenomas and adrenocortical carcinomas. Further, knowledge gained from transcriptome analyses and methylation arrays has provided new insights into the development of these tumours. Elucidation of the genomic landscape of adrenocortical tumours and improved techniques may in the future be useful for early diagnosis through the detection of mutated DNA in the circulation...
December 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27862984/of-channels-and-pumps-different-ways-to-boost-the-aldosterone
#5
REVIEW
Sascha Bandulik
The mineralocorticoid aldosterone is a major factor controlling the salt and water balance and thereby also the arterial blood pressure. Accordingly, primary aldosteronism characterized by an inappropiately high aldosterone secretion is the most common form of secondary hypertension. The physiological stimulation of aldosterone synthesis in adrenocortical glomerulosa cells by angiotensin II and an increased plasma K(+) concentration depends on a membrane depolarization and an increase of the cytosolic Ca(2+) activity...
November 15, 2016: Acta Physiologica
https://www.readbyqxmd.com/read/27853054/expression-of-cyp11b2-in-aldosterone-producing-adrenocortical-adenoma-regulatory-mechanisms-and-clinical-significance
#6
Yasuhiro Nakamura, Yuto Yamazaki, Yuta Tezuka, Fumitoshi Satoh, Hironobu Sasano
Aldosterone-producing adrenocortical adenoma (APA) is responsible for the majority of cases clinically diagnosed as primary aldosteronism. Aldosterone synthase (CYP11B2) is one of the enzymes that play essential roles in aldosterone synthesis and is involved in the pathogenesis of APA. Recent studies have demonstrated that various factors and regulators influence the expression and function of CYP11B2 in APA. In particular, somatic mutations, such as gain-of-function and loss-of-function mutations, have been identified in several genes, each of which encodes a pivotal protein that affects the calcium signaling pathway, the expression of CYP11B2, and aldosterone production...
2016: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27813054/mechanisms-of-aberrant-pka-activation-by-c%C3%AE-subunit-mutations
#7
D Calebiro, K Bathon, I Weigand
Somatic mutations in PRKACA, coding for the catalytic α subunit of protein kinase A (PKA), have been recently identified as the most frequent genetic alteration in cortisol-secreting adrenocortical adenomas, which are responsible for adrenal Cushing's syndrome. The mutations identified so far lie at the interface between the catalytic (C) and regulatory (R) subunit of PKA. Detailed functional studies of the most frequent of these mutations (L206R) as well as of another one in the same region of the C subunit (199_200insW) have revealed that these mutations cause constitutive activation of PKA and lack of regulation by cAMP...
November 3, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27754862/hypomethylation-of-cyp11b2-in-aldosterone-producing-adenoma
#8
Yoko Yoshii, Kenji Oki, Celso E Gomez-Sanchez, Haruya Ohno, Kiyotaka Itcho, Kazuhiro Kobuke, Masayasu Yoneda
The purpose of this study was to evaluate the DNA methylation levels of steroidogenic enzyme genes in aldosterone-producing adenoma (APA) and the effects of gene mutations in APA on the DNA methylation levels. DNA methylation array analysis was conducted using nonfunctioning adrenocortical adenoma (n=12) and APA (n=35) samples, including some with a KCNJ5 mutation (n=21), an ATP1A1 mutation (n=5), and without the known mutations (n=9). The quantitative polymerase chain reaction assay was performed for the detection of CYP11B2 and CYP11B1 expression levels in nonfunctioning adrenocortical adenoma and APA...
October 17, 2016: Hypertension
https://www.readbyqxmd.com/read/27753830/sy-03-3-overview-of-somatic-mutations-and-epigenetic-regulation-of-aldosterone-producing-adenoma-apa
#9
Satoshi Umemura
Primary aldosteronism (PA) is a heterogeneous group of disorders including both sporadic and familial forms (familial hyperaldosteronism type I, II and III). PA is the most frequent endocrine cause of secondary hypertension and associated with a higher rate of cardiovascular complications, compared with essential hypertension.Here I review the recent progress in understanding of the genetic and molecular mechanisms leading to autonomous aldosterone production in PA.Systematic screening detects primary aldosteronism in 5 to 10% of all patients with hypertension and in approximately 20% of patients with resistant hypertension...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27751767/immunohistochemistry-of-aldosterone-synthase-leads-the-way-to-the-pathogenesis-of-primary-aldosteronism
#10
Koshiro Nishimoto, Minae Koga, Tsugio Seki, Kenji Oki, Elise P Gomez-Sanchez, Celso E Gomez-Sanchez, Mitsuhide Naruse, Tomokazu Sakaguchi, Shinya Morita, Takeo Kosaka, Mototsugu Oya, Tadashi Ogishima, Masanori Yasuda, Makoto Suematsu, Yasuaki Kabe, Masao Omura, Tetsuo Nishikawa, Kuniaki Mukai
Our group previously purified human and rat aldosterone synthase (CYP11B2 and Cyp11b2, respectively) from their adrenals and verified that it is distinct from steroid 11β-hydroxylase (CYP11B1 or Cyp11b1), the cortisol- or corticosterone-synthesizing enzyme. We now describe their distributions immunohistochemically with specific antibodies. In rats, there is layered functional zonation with the Cyp11b2-positive zona glomerulosa (ZG), Cyp11b1-positive zona fasciculata (ZF), and Cyp11b2/Cyp11b1-negative undifferentiated zone between the ZG and ZF...
October 14, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27725909/cell-cycle-dependent-rrm2-may-serve-as-proliferation-marker-and-pharmaceutical-target-in-adrenocortical-cancer
#11
Vince Kornél Grolmusz, Katalin Karászi, Tamás Micsik, Eszter Angéla Tóth, Katalin Mészáros, Gellért Karvaly, Gábor Barna, Péter Márton Szabó, Kornélia Baghy, János Matkó, Ilona Kovalszky, Miklós Tóth, Károly Rácz, Péter Igaz, Attila Patócs
Adrenocortical cancer (ACC) is a rare, but agressive malignancy with poor prognosis. Histopathological diagnosis is challenging and pharmacological options for treatment are limited. By the comparative reanalysis of the transcriptional malignancy signature with the cell cycle dependent transcriptional program of ACC, we aimed to identify novel biomarkers which may be used in the histopathological diagnosis and for the prediction of therapeutical response of ACC. Comparative reanalysis of publicly available microarray datasets included three earlier studies comparing transcriptional differences between ACC and benign adrenocortical adenoma (ACA) and one study presenting the cell cycle dependent gene expressional program of human ACC cell line NCI-H295R...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27714481/tp53-and-cdkn1a-mutation-analysis-in-families-with-li-fraumeni-and-li-fraumeni-like-syndromes
#12
Raissa Coelho Andrade, Anna Claudia Evangelista Dos Santos, Joaquim Caetano de Aguirre Neto, Julián Nevado, Pablo Lapunzina, Fernando Regla Vargas
Li-Fraumeni and Li-Fraumeni like syndromes (LFS/LFL) represent rare cancer-prone conditions associated mostly with sarcomas, breast cancer, brain tumors, and adrenocortical carcinomas. TP53 germline mutations are present in up to 80 % of families with classic Li-Fraumeni syndrome, and in 20-60 % of families with Li-Fraumeni like phenotypes. The frequency of LFS/LFL families with no TP53 mutations detected suggests the involvement of other genes in the syndrome. In this study, we searched for mutations in TP53 in 39 probands from families with criteria for LFS/LFL...
October 6, 2016: Familial Cancer
https://www.readbyqxmd.com/read/27643448/diurnal-plasma-cortisol-measurements-utility-in-differentiating-various-etiologies-of-endogenous-cushing-syndrome
#13
A Tirosh, M B Lodish, G Z Papadakis, C Lyssikatos, E Belyavskaya, C A Stratakis
Cortisol diurnal variation may be abnormal among patients with endogenous Cushing syndrome (CS). The study objective was to compare the plasma cortisol AM/PM ratios between different etiologies of CS. This is a retrospective cohort study, conducted at a clinical research center. Adult patients with CS that underwent adrenalectomy or trans-sphenoidal surgery (n=105) were divided to those with a pathologically confirmed diagnosis of Cushing disease (n=21) and those with primary adrenal CS, including unilateral adrenal adenoma (n=28), adrenocortical hyperplasia (n=45), and primary pigmented nodular adrenocortical disease (PPNAD, n=11)...
September 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27642883/sy-03-3-overview-of-somatic-mutations-and-epigenetic-regulation-of-aldosterone-producing-adenoma-apa
#14
Satoshi Umemura
Primary aldosteronism (PA) is a heterogeneous group of disorders including both sporadic and familial forms (familial hyperaldosteronism type I, II and III). PA is the most frequent endocrine cause of secondary hypertension and associated with a higher rate of cardiovascular complications, compared with essential hypertension.Here I review the recent progress in understanding of the genetic and molecular mechanisms leading to autonomous aldosterone production in PA.Systematic screening detects primary aldosteronism in 5 to 10% of all patients with hypertension and in approximately 20% of patients with resistant hypertension...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27625633/alterations-of-phosphodiesterases-in-adrenocortical-tumors
#15
REVIEW
Fady Hannah-Shmouni, Fabio R Faucz, Constantine A Stratakis
Alterations in the cyclic (c)AMP-dependent signaling pathway have been implicated in the majority of benign adrenocortical tumors (ACTs) causing Cushing syndrome (CS). Phosphodiesterases (PDEs) are enzymes that regulate cyclic nucleotide levels, including cyclic adenosine monophosphate (cAMP). Inactivating mutations and other functional variants in PDE11A and PDE8B, two cAMP-binding PDEs, predispose to ACTs. The involvement of these two genes in ACTs was initially revealed by a genome-wide association study in patients with micronodular bilateral adrenocortical hyperplasia...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27616151/contralateral-adrenal-suppression-on-adrenocortical-scintigraphy-provides-good-evidence-showing-subclinical-cortisol-overproduction-from-unilateral-adenomas
#16
Takuyuki Katabami, Satoshi Ishii, Ryusei Obi, Shiko Asai, Yasushi Tanaka
Unilateral and/or predominant uptake on adrenocortical scintigraphy (ACS) may be related to autonomous cortisol overproduction in patients with subclinical Cushing's syndrome (SCS). However, there is no information regarding whether increased tracer uptake on the tumor side or decreased uptake on the contralateral side on ACS is more greatly associated with inappropriate cortisol production. Therefore, we evaluated the relationship between quantitative (131)I-6β-iodomethyl-norcholesterol ((131)I-NP-59) uptake in both adrenal glands and parameters of autonomic cortisol secretion and attempted to set a cut off for SCS detection...
September 10, 2016: Endocrine Journal
https://www.readbyqxmd.com/read/27606678/steroidogenic-acute-regulatory-protein-overexpression-correlates-with-protein-kinase-a-activation-in-adrenocortical-adenoma
#17
Weiwei Zhou, Luming Wu, Jing Xie, Tingwei Su, Lei Jiang, Yiran Jiang, Yanan Cao, Jianmin Liu, Guang Ning, Weiqing Wang
The association of pathological features of cortisol-producing adrenocortical adenomas (ACAs) with somatic driver mutations and their molecular classification remain unclear. In this study, we explored the association between steroidogenic acute regulatory protein (StAR) expression and the driver mutations activating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling to identify the pathological markers of ACAs. Immunohistochemical staining for StAR and mutations in the protein kinase cAMP-activated catalytic subunit alpha (PRKACA), protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) and guanine nucleotide binding protein, alpha stimulating (GNAS) genes were examined in 97 ACAs...
2016: PloS One
https://www.readbyqxmd.com/read/27603910/inhibition-of-human-adrenocortical-cancer-cell-growth-by-temozolomide-in-vitro-and-the-role-of-the-mgmt-gene
#18
S G Creemers, P M van Koetsveld, E S R van den Dungen, E Korpershoek, F J van Kemenade, G J H Franssen, W W de Herder, R A Feelders, L J Hofland
CONTEXT: Treatment of patients with adrenocortical carcinomas (ACC) with mitotane and/or chemotherapy is often associated with toxicity and poor tumor response. New therapeutic options are urgently needed. OBJECTIVE: To evaluate the therapeutic possibilities of temozolomide (TMZ) in ACC cells and to assess the potential predictive role of the DNA repair gene O6-Methylguanine-DNA methyltransferase (MGMT) in adrenocortical tumors. METHODS: 3 human ACC cell lines and 8 primary ACC cultures were used to assess effects of TMZ in vitro...
September 7, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27579413/intrarenal-adrenocortical-adenoma-treated-by-robotic-partial-nephrectomy-with-adrenalectomy
#19
Samay Sappal, Jay Sulek, Steven C Smith, Lance J Hampton
BACKGROUND: We present an intrarenal adrenocortical adenoma discovered incidentally after robot-assisted partial nephrectomy and total adrenalectomy for a suspicious renal mass. Current literature describes the rare occurrence of an adrenocortical adenoma arising from a renal-adrenal fusion. This case represents an uncommon, benign pathology that should be considered in the differential diagnosis of an enhancing renal mass. CASE PRESENTATION: The patient is a 62-year-old female found to have an enhancing mass at the anterolateral aspect of the upper pole of the right kidney concerning for renal-cell carcinoma...
2016: Journal of Endourology Case Reports
https://www.readbyqxmd.com/read/27575944/adipocyte-browning-and-higher-mitochondrial-function-in-periadrenal-but-not-sc-fat-in-pheochromocytoma
#20
Laurent Vergnes, Graeme R Davies, Jason Y Lin, Michael W Yeh, Masha J Livhits, Avital Harari, Michael E Symonds, Harold S Sacks, Karen Reue
CONTEXT: Patients with pheochromocytoma (pheo) show presence of multilocular adipocytes that express uncoupling protein 1 within periadrenal (pADR) and omental (OME) fat depots. It has been hypothesized that this is due to adrenergic stimulation by catecholamines produced by the pheo tumors. OBJECTIVE: To characterize the prevalence and respiratory activity of brown-like adipocytes within pADR, OME, and SC fat depots in human adult pheo patients. DESIGN: This was an observational cohort study...
November 2016: Journal of Clinical Endocrinology and Metabolism
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