Refine
Has Fulltext
- yes (65)
Is part of the Bibliography
- yes (65)
Year of publication
Document Type
- Journal article (64)
- Conference Proceeding (1)
Language
- English (65)
Keywords
- adrenocortical carcinoma (9)
- obesity (5)
- metabolomics (4)
- 18F-FDG (3)
- CXCR4 (3)
- Cushing’s syndrome (3)
- FGFR (3)
- PET (3)
- adrenocortical cancer (3)
- biomarker (3)
- hypercortisolism (3)
- liraglutide (3)
- paraganglioma (3)
- pheochromocytoma (3)
- positron emission tomography (3)
- therapy (3)
- vandetanib (3)
- ACTH (2)
- C-X-C motif chemokine receptor 4 (2)
- CYP2W1 (2)
- Cushing’s disease (2)
- FGF-pathway (2)
- PPGL (2)
- Positronen-Emissions-Tomografie (2)
- TKI (2)
- [68Ga]PentixaFor (2)
- adenomas (2)
- adrenal cancer (2)
- adrenal tumours (2)
- adrenocortical tumors (2)
- cancer (2)
- carcinomas (2)
- cardiovascular events (2)
- chemokine receptor (2)
- cortisol (2)
- endoradiotherapy (2)
- gastric bypass (2)
- immune response (2)
- immunohistochemistry (2)
- immunotherapy (2)
- machine learning (2)
- medullary thyroid carcinoma (2)
- mitotane (2)
- mortality (2)
- pediatric adrenocortical cancer (2)
- pediatric adrenocortical tumor (2)
- peptide tyrosine tyrosine (PYY) (2)
- prognosis (2)
- recurrence (2)
- theranostics (2)
- treatment (2)
- tyrosine kinase inhibitor (2)
- 2- deoxy-2-(18F)fluoro-D-glucose (1)
- 2-deoxy-2-(18F)fluoro-D-glucose (1)
- ALT (1)
- ATRX (1)
- Adrenocortial carcinomas (1)
- Antigen 4 (1)
- Autoimmune-Diseases (1)
- BIRC7 (1)
- BRAF(V600E) mutation (1)
- Biochemical-Diagnosis (1)
- CCR7 (1)
- CRH stimulation test (1)
- CTNNB1 (1)
- CXCR7 (1)
- CYP2B6 (1)
- Cell lung canger (1)
- Contrast-enhanced CT (1)
- Copeptin (1)
- Cushing (1)
- Cushing's disease (1)
- Cushings syndrome (1)
- Dendritic Cells (1)
- Diagnosis (1)
- Disease prevalence (1)
- EMT (1)
- F-18-FDG PET/CT (1)
- FGF21 (1)
- FGFR-inhibitors (1)
- Fibroblast Growth Factor-21 (1)
- FoxP3 Expression (1)
- GLP-1 (1)
- Immune-System (1)
- Immunological Self-Tolerance (1)
- Klotho-related molecules (1)
- LND (1)
- LNE (1)
- MASS (1)
- MR (1)
- MTL30 (1)
- Medicine (1)
- Medizin (1)
- Medullärer Schilddrüsenkrebs (1)
- Men (1)
- Metanephrine (1)
- Methodological quality (1)
- Multiple-Sclerosis (1)
- NAFLD (1)
- NASH (1)
- NMR (1)
- NOP10 (1)
- NR3C1 (1)
- Normetanephrine (1)
- PD-L1 (1)
- PF-05231023 (1)
- PYY3-36 (1)
- Paraganglioma (1)
- Plasma (1)
- Positron-emission-tomography (1)
- RNA Expression (1)
- RNAScope (1)
- RYGB (1)
- Resistance (1)
- Roux-en-Y Gastric Bypass (1)
- Roux-en-Y gastric bypass (1)
- Roux-en-Y gastric bypass surgery (1)
- SNP (1)
- SOAT1 (1)
- Sex-Hormones (1)
- Society (1)
- Spin echo (1)
- Suppressive Function (1)
- Systemic-Lupus-Erythematosus (1)
- TERT (1)
- Test accuracy (1)
- USP8 (1)
- Utility (1)
- [11C]-Choline PET/CT (1)
- [11C]-Methionine (1)
- [177Lu]/[90Y]PentixaTher (1)
- [177Lu]PentixaTher (1)
- [18F]FDG-PET-CT (1)
- [90Y]PentixaTher (1)
- [99mTc]-Sestamibi scan (1)
- abdominal lymph node metastases (1)
- adjuvant platinum-based chemotherapy (1)
- adjuvant treatment (1)
- adrenal (1)
- adrenal cortex hormones (1)
- adrenal cortex neoplasms (1)
- adrenal glands (1)
- adrenal imaging (1)
- adrenal surgery (1)
- adrenal tumor (1)
- adrenal tumors (1)
- adrenalectomia (1)
- adrenocortical (1)
- adrenocortical adenocarcinoma (1)
- adrenocortical carcinoma (ACC) (1)
- adrenocortical development (1)
- adrenocortical tissues (1)
- aldosterone (1)
- association (1)
- autoantibodies (1)
- autonomous cortisol secretion (1)
- balance (1)
- bioinformatic clustering (1)
- biomarker prediction (1)
- biomarkers (1)
- blood pressure (1)
- branched-chain amino acids (1)
- cancer detection (1)
- cancer diagnosis (1)
- cancer treatment (1)
- cancer-testis antigens (1)
- carcinogenesis (1)
- carcinoma (1)
- carcinoma metastases to pancreas (1)
- cardiovascular risk factors (1)
- caspase-3 (1)
- catecholamines (1)
- catenin (1)
- cells (1)
- cholesterol metabolism (1)
- chromosomes (1)
- circulating microRNA (1)
- combination (1)
- comparability (1)
- comparative genomic hybridization (1)
- complication (1)
- confounders (1)
- copeptin (1)
- cortisol-producing adenoma (1)
- cytoplasmic staining (1)
- deubiquitinases (1)
- dexamethasone suppression test (1)
- diabetes insipidus (1)
- diagnosis (1)
- disease score (1)
- disease severity (1)
- dissection (1)
- distant metastases (1)
- dogs (1)
- drug therapy (1)
- early prognosis (1)
- ectopic (1)
- efficacy (1)
- endogenous hypercortisolism (1)
- epithelial markers (1)
- expression (1)
- feature selection (1)
- focused surgical approach (1)
- follow-up (1)
- genetic loci (1)
- glucocorticoid excess (1)
- guidelines (1)
- high dose dexamethasone suppression test (1)
- high-resolution analysis (1)
- hormones (1)
- hypothalamic gene expression (1)
- imaging (1)
- immune check inhibitor (1)
- immune checkpoint inhibitor (ICI) (1)
- immunity (1)
- immunohistochemistry techniques (1)
- in silico analysis (1)
- insulin resistance (1)
- intragastric balloon (1)
- isturisa (1)
- kidney disease (1)
- kinase (1)
- kinases (1)
- liquid chromatography–tandem mass spectrometry (LC–MS/MS) (1)
- livin (1)
- lymph node dissection (1)
- lymphadenectomy (1)
- lymphocytes (1)
- malignant tumors (1)
- management (1)
- mass spectrometry (1)
- mass spectronomy (1)
- medical therapy (1)
- mesenchymal markers (1)
- meta-analysis (1)
- metyrapone (1)
- miR-182-5p (1)
- miR-183 cluster (1)
- miR-483-5p (1)
- miRNA (1)
- molecular diagnostics (1)
- morbidity (1)
- multicenter (1)
- multiple myeloma (1)
- mutation (1)
- mutation triggers (1)
- neuroblastoma – diagnosis (1)
- neutral loss (1)
- normal adrenal glands (1)
- normal values (1)
- notch signaling (1)
- nuclear staining (1)
- operation (1)
- osilodrostat (1)
- osmotic stimulation (1)
- outcome (1)
- paired (1)
- papillary (1)
- papillary thyroid carcinoma (PTC) (1)
- parathyroid adenoma (1)
- parathyroid carcinoma (1)
- pathogenesis (1)
- patient survival (1)
- pediatric (1)
- pediatric adrenocortical adenoma (1)
- pediatric adrenocortical carcinoma (1)
- pembrolizumab (1)
- peptide tyrosine tyrosine 3-36 (PYY3-36) (1)
- peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) (1)
- personalized medicine (1)
- phosphatidylcholines (1)
- phosphorylation (1)
- pituitary adenomas (1)
- pituitary gland (1)
- plasma (1)
- plasma NMR (1)
- polarization (1)
- preanalytical conditions (1)
- precision medicine (1)
- predictive marker (1)
- primary hyperparathyroidism (1)
- primary polydipsia (1)
- prognostic biomarker (1)
- prognostic factors (1)
- prospective (1)
- prostate cancer (1)
- protein expression (1)
- radical resection (1)
- radioiodine (1)
- radioiodine therapy (1)
- radiotherapy (1)
- radiotherapy (RT) (1)
- recurrence free survival (1)
- recurrence-free survival (1)
- reference data (1)
- repeated surgery (1)
- review (1)
- rodent model (1)
- rygb (1)
- selpercatinib (1)
- serum (1)
- signs and symptoms (1)
- sleeve gastrectomy (1)
- somatic mutations (1)
- sphingolipids (1)
- steroid measurement (1)
- sudden cardiac death (1)
- super-obesity (1)
- surgery (1)
- surgical oncology (1)
- surgical treatment (1)
- t-lymphocytes (1)
- targeted metabolomics (1)
- targeted treatment (1)
- telomeres (1)
- thyroid carcinoma (TC) (1)
- timing (1)
- transgenic rats (1)
- tumor microenvironment (1)
- tumor-infiltrating (1)
- tumors (1)
- tyrosine kinase inhibitor (TKI) (1)
- unsupervised clustering (1)
- urine (1)
- volume (1)
Institute
- Medizinische Klinik und Poliklinik I (65) (remove)
Sonstige beteiligte Institutionen
Background:
Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(T(reg)) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs).
Objective:
We readdressed the influence of GC therapy on T(reg) cells in immunocompetent human subjects and naive mice.
Methods:
Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and T(reg) cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood T(reg) cells were analyzed prior and after a 14 day GC therapy based on different markers.
Results:
Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of T(reg) cells in blood (100 mg dexamethasone/kg body weight: 2.8 +/- 1.8 x 10(4) cells/ml vs. 33 +/- 11 x 10(4) in control mice) and spleen (dexamethasone: 2.8 +/- 1.9 x 10(5)/spleen vs. 95 +/- 22 x 10(5)/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3(+) T(reg) cells amongst the CD4(+) T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of T(reg) cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating T(reg) cells in a relevant manner, although there was some variation depending on the definition of the T(reg) cells (FOXP3(+): 4.0 +/- 1.5% vs 3.4 +/- 1.5%*; AITR(+): 0.660.4 vs 0.5 +/- 0.3%, CD127(low): 4.0 +/- 1.3 vs 5.0 +/- 3.0%* and CTLA4+: 13.8 +/- 11.5 vs 15.6 +/- 12.5%; * p < 0.05).
Conclusion:
Short-term GC therapy does not induce the hitherto supposed increase in circulating T(reg) cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating T(reg) cell numbers.
Objective:
Adrenal masses are incidentally discovered in 5% of CT scans. In 2013/2014, 81 million CT examinations were undertaken in the USA and 5 million in the UK. However, uncertainty remains around the optimal imaging approach for diagnosing malignancy. We aimed to review the evidence on the accuracy of imaging tests for differentiating malignant from benign adrenal masses. Design: A systematic review and meta-analysis was conducted.
Methods:
We searched MEDLINE, EMBASE, Cochrane CENTRAL Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index, and ZETOC (January 1990 to August 2015). We included studies evaluating the accuracy of CT, MRI, or F-18-fluoro-deoxyglucose (FDG)-PET compared with an adequate histological or imaging-based follow-up reference standard.
Results:
We identified 37 studies suitable for inclusion, after screening 5469 references and 525 full-text articles. Studies evaluated the accuracy of CT (n = 16), MRI (n = 15), and FDG-PET (n = 9) and were generally small and at high or unclear risk of bias. Only 19 studies were eligible for meta-analysis. Limited data suggest that CT density >10 HU has high sensitivity for detection of adrenal malignancy in participants with no prior indication for adrenal imaging, that is, masses with <= 10 HU are unlikely to be malignant. All other estimates of test performance are based on too small numbers.
Conclusions:
Despite their widespread use in routine assessment, there is insufficient evidence for the diagnostic value of individual imaging tests in distinguishing benign from malignant adrenal masses. Future research is urgently needed and should include prospective test validation studies for imaging and novel diagnostic approaches alongside detailed health economics analysis.
Background:
Recent decades have seen a rise in the incidence of well-differentiated (mainly papillary) thyroid carcinoma around the world. In Germany, the age-adjusted incidence of well-differentiated thyroid carcinoma in 2010 was 3.5 per 100 000 men and 8.7 per 100 000 women per year.
Method:
This review is based on randomized, controlled trials and multicenter trials on the treatment of well-differentiated thyroid carcinoma that were retrieved by a selective literature search, as well as on three updated guidelines issued in the past two years.
Results:
The recommended extent of surgical resection depends on whether the tumor is classified as low-risk or high-risk, so that papillary microcar cinomas, which carry a highly favorable prognosis, will not be overtreated. More than 90% of localized, well-differentiated thyroid carcinomas can be cured with a combination of surgery and radioactive iodine therapy. Radio active iodine therapy is also effective in the treatment of well-differentiated thyroid carcinomas with distant metastases, yielding a 10-year survival rate of 90%, as long as there is good iodine uptake and the tumor goes into remission after treatment; otherwise, the 10-year survival rate is only 10%. In the past two years, better treatment options have become available for radioactive-iodine-resistant thyroid carcinoma. Phase 3 studies of two different tyrosine kinase inhibitors have shown that either one can markedly prolong progression-free survival, but not overall survival. Their more common clinically significant side effects are hand-foot syndrome, hypertension, diarrhea, proteinuria, and weight loss.
Conclusion:
Slow tumor growth, good resectability, and susceptibility to radioactive iodine therapy lend a favorable prognosis to most cases of well-differentiated thyroid carcinoma. The treatment should be risk-adjusted and interdisciplinary, in accordance with the current treatment guidelines. Even metastatic thyroid carcinoma has a favorable prognosis as long as there is good iodine uptake. The newly available medical treatment options for radioactive-iodine-resistant disease need to be further studied.
Lack of Ubiquitin Specific Protease 8 (USP8) Mutations in Canine Corticotroph Pituitary Adenomas
(2016)
Purpose
Cushing’s disease (CD), also known as pituitary-dependent hyperadrenocorticism, is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumours. Affected humans and dogs have similar clinical manifestations, however, the incidence of the canine disease is thousand-fold higher. This makes the dog an obvious model for studying the pathogenesis of pituitary-dependent hyperadrenocorticism. Despite certain similarities identified at the molecular level, the question still remains whether the two species have a shared oncogenetic background. Recently, hotspot recurrent mutations in the gene encoding for ubiquitin specific protease 8 (USP8) have been identified as the main driver behind the formation of ACTH-secreting pituitary adenomas in humans. In this study, we aimed to verify whether USP8 mutations also play a role in the development of such tumours in dogs.
Methods
Presence of USP8 mutations was analysed by Sanger and PCR-cloning sequencing in 38 canine ACTH-secreting adenomas. Furthermore, the role of USP8 and EGFR protein expression was assessed by immunohistochemistry in a subset of 25 adenomas.
Results
None of the analysed canine ACTH-secreting adenomas presented mutations in the USP8 gene. In a subset of these adenomas, however, we observed an increased nuclear expression of USP8, a phenotype characteristic for the USP8 mutated human tumours, that correlated with smaller tumour size but elevated ACTH production in those tumours.
Conclusions
Canine ACTH-secreting pituitary adenomas lack mutations in the USP8 gene suggesting a different genetic background of pituitary tumourigenesis in dogs. However, elevated nuclear USP8 protein expression in a subset of tumours was associated with a similar phenotype as in their human counterparts, indicating a possible end-point convergence of the different genetic backgrounds in the two species. In order to establish the dog as a useful animal model for the study of CD, further comprehensive studies are needed.
Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R.
The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression.
Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform β more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability.
In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.
Background: Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(Treg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs). Objective: We readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and naı¨ve mice. Methods: Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and Treg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood Treg cells were analyzed prior and after a 14 day GC therapy based on different markers. Results: Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.861.86104 cells/ml vs. 336116104 in control mice) and spleen (dexamethasone: 2.861.96105/spleen vs. 956226105/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3+ Treg cells amongst the CD4+ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of Treg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating Treg cells in a relevant manner, although there was some variation depending on the definition of the Treg cells (FOXP3+: 4.061.5% vs 3.461.5%*; AITR+: 0.660.4 vs 0.560.3%, CD127low: 4.061.3 vs 5.063.0%* and CTLA4+: 13.8611.5 vs 15.6612.5%; * p,0.05). Conclusion: Short-term GC therapy does not induce the hitherto supposed increase in circulating Treg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating Treg cell numbers.
Background
Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin.
Case presentation
Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred.
Conclusion
Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.
Mineralocorticoid receptor (MR) inactivation in mice results in early postnatal lethality. Therefore we generated mice in which MR expression can be silenced during adulthood by administration of doxycycline (Dox). Using a lentiviral approach, we obtained two lines of transgenic mice harboring a construct that allows for regulatable MR inactivation by RNAi and concomitant expression of eGFP. MR mRNA levels in heart and kidney of inducible MR knock-down mice were unaltered in the absence of Dox, confirming the tightness of the system. In contrast, two weeks after Dox administration MR expression was significantly diminished in a variety of tissues. In the kidney, this resulted in lower mRNA levels of selected target genes, which was accompanied by strongly increased serum aldosterone and plasma renin levels as well as by elevated sodium excretion. In the healthy heart, gene expression and the amount of collagen were unchanged despite MR levels being significantly reduced. After transverse aortic constriction, however, cardiac hypertrophy and progressive heart failure were attenuated by MR silencing, fibrosis was unaffected and mRNA levels of a subset of genes reduced. Taken together, we believe that this mouse model is a useful tool to investigate the role of the MR in pathophysiological processes.
The genetic mechanisms underlying adrenocortical tumor development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays (Affymetrix SNP 6.0) to detect copy number alterations (CNAs) and copy-neutral losses of heterozygosity (cnLOH) in 15 cortisol-secreting adrenocortical adenomas with matched blood samples. We focused on microalterations aiming to discover new candidate genes involved in early tumorigenesis and/or autonomous cortisol secretion. We identified 962 CNAs with a median of 18 CNAs per sample. Half of them involved noncoding regions, 89% were less than 100 kb, and 28% were found in at least two samples. The most frequently gained regions were 5p15.33, 6q16.1, 7p22.3-22.2, 8q24.3, 9q34.2-34.3, 11p15.5, 11q11, 12q12, 16q24.3, 20p11.1-20q21.11, and Xq28 (>= 20% of cases), most of them being identified in the same three adenomas. These regions contained among others genes like NOTCH1, CYP11B2, HRAS, and IGF2. Recurrent losses were less common and smaller than gains, being mostly localized at 1p, 6q, and 11q. Pathway analysis revealed that Notch signaling was the most frequently altered. We identified 46 recurrent CNAs that each affected a single gene (31 gains and 15 losses), including genes involved in steroidogenesis (CYP11B1) or tumorigenesis (CTNNB1, EPHA7, SGK1, STIL, FHIT). Finally, 20 small cnLOH in four cases affecting 15 known genes were found. Our findings provide the first high-resolution genome-wide view of chromosomal changes in cortisol-secreting adenomas and identify novel candidate genes, such as HRAS, EPHA7, and SGK1. Furthermore, they implicate that the Notch1 signaling pathway might be involved in the molecular pathogenesis of adrenocortical tumors.