@article{LoehrHaertigSchulzeetal.2022,
  author    = {L{\"o}hr, Mario and H{\"a}rtig, Wolfgang and Schulze, Almut and Kroiß, Matthias and Sbiera, Silviu and Lapa, Constantin and Mages, Bianca and Strobel, Sabrina and Hundt, Jennifer Elisabeth and Bohnert, Simone and Kircher, Stefan and Janaki-Raman, Sudha and Monoranu, Camelia-Maria},
  title     = {SOAT1: A suitable target for therapy in high-grade astrocytic glioma?},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {7},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23073726},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284178},
  year      = {2022},
  abstract  = {Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.},
  language  = {en}
}
@article{EckhardtSbieraKrebsetal.2022,
  author    = {Eckhardt, Carolin and Sbiera, Iuliu and Krebs, Markus and Sbiera, Silviu and Spahn, Martin and Kneitz, Burkhard and Joniau, Steven and Fassnacht, Martin and K{\"u}bler, Hubert and Weigand, Isabel and Kroiss, Matthias},
  title     = {High expression of Sterol-O-Acyl transferase 1 (SOAT1), an enzyme involved in cholesterol metabolism, is associated with earlier biochemical recurrence in high risk prostate cancer},
  series = {Prostate Cancer and Prostatic Diseases},
  volume    = {25},
  journal   = {Prostate Cancer and Prostatic Diseases},
  number    = {3},
  issn      = {1476-5608},
  doi       = {10.1038/s41391-021-00431-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271819},
  pages     = {484-490},
  year      = {2022},
  abstract  = {Background Prostate cancer (PCa) is the most frequent cancer in men. The prognosis of PCa is heterogeneous with many clinically indolent tumors and rare highly aggressive cases. Reliable tissue markers of prognosis are lacking. Active cholesteryl ester synthesis has been associated with prostate cancer aggressiveness. Sterol-O-Acyl transferases (SOAT) 1 and 2 catalyze cholesterol esterification in humans. Objective To investigate the value of SOAT1 and SOAT2 tissue expression as prognostic markers in high risk PCa. Patients and Methods Formalin-fixed paraffin-embedded tissue samples from 305 high risk PCa cases treated with radical prostatectomy were analyzed for SOAT1 and SOAT2 protein expression by semi-quantitative immunohistochemistry. The Kaplan-Meier method and Cox proportional hazards modeling were used to compare outcome. Main Outcome Measure Biochemical recurrence (BCR) free survival. Results SOAT1 expression was high in 73 (25\%) and low in 219 (75\%; not evaluable: 13) tumors. SOAT2 was highly expressed in 40 (14\%) and at low levels in 249 (86\%) samples (not evaluable: 16). By Kaplan-Meier analysis, we found significantly shorter median BCR free survival of 93 months (95\% confidence interval 23.6-123.1) in patients with high SOAT1 vs. 134 months (112.6-220.2, Log-rank p < 0.001) with low SOAT1. SOAT2 expression was not significantly associated with BCR. After adjustment for age, preoperative PSA, tumor stage, Gleason score, resection status, lymph node involvement and year of surgery, high SOAT1 but not SOAT2 expression was associated with shorter BCR free survival with a hazard ratio of 2.40 (95\% CI 1.57-3.68, p < 0.001). Time to clinical recurrence and overall survival were not significantly associated with SOAT1 and SOAT2 expression CONCLUSIONS: SOAT1 expression is strongly associated with BCR free survival alone and after multivariable adjustment in high risk PCa. SOAT1 may serve as a histologic marker of prognosis and holds promise as a future treatment target.},
  language  = {en}
}
@article{VetrivelZhangEngeletal.2022,
  author    = {Vetrivel, Sharmilee and Zhang, Ru and Engel, Mareen and Oßwald, Andrea and Watts, Deepika and Chen, Alon and Wielockx, Ben and Sbiera, Silviu and Reincke, Martin and Riester, Anna},
  title     = {Characterization of adrenal miRNA-based dysregulations in Cushing's syndrome},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {14},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23147676},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284394},
  year      = {2022},
  abstract  = {MiRNAs are important epigenetic players with tissue- and disease-specific effects. In this study, our aim was to investigate the putative differential expression of miRNAs in adrenal tissues from different forms of Cushing's syndrome (CS). For this, miRNA-based next-generation sequencing was performed in adrenal tissues taken from patients with ACTH-independent cortisol-producing adrenocortical adenomas (CPA), from patients with ACTH-dependent pituitary Cushing's disease (CD) after bilateral adrenalectomy, and from control subjects. A confirmatory QPCR was also performed in adrenals from patients with other CS subtypes, such as primary bilateral macronodular hyperplasia and ectopic CS. Sequencing revealed significant differences in the miRNA profiles of CD and CPA. QPCR revealed the upregulated expression of miR-1247-5p in CPA and PBMAH (log2 fold change > 2.5, p < 0.05). MiR-379-5p was found to be upregulated in PBMAH and CD (log2 fold change > 1.8, p < 0.05). Analyses of miR-1247-5p and miR-379-5p expression in the adrenals of mice which had been exposed to short-term ACTH stimulation showed no influence on the adrenal miRNA expression profiles. For miRNA-specific target prediction, RNA-seq data from the adrenals of CPA, PBMAH, and control samples were analyzed with different bioinformatic platforms. The analyses revealed that both miR-1247-5p and miR-379-5p target specific genes in the WNT signaling pathway. In conclusion, this study identified distinct adrenal miRNAs as being associated with CS subtypes.},
  language  = {en}
}
@article{DetomasPivonelloPellegrinietal.2022,
  author    = {Detomas, Mario and Pivonello, Claudia and Pellegrini, Bianca and Landwehr, Laura-Sophie and Sbiera, Silviu and Pivonello, Rosario and Ronchi, Cristina L. and Colao, Annamaria and Altieri, Barbara and De Martino, Maria Cristina},
  title     = {MicroRNAs and long non-coding RNAs in adrenocortical carcinoma},
  series = {Cells},
  volume    = {11},
  journal   = {Cells},
  number    = {14},
  issn      = {2073-4409},
  doi       = {10.3390/cells11142234},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281795},
  year      = {2022},
  abstract  = {Non-coding RNAs (ncRNAs) are a type of genetic material that do not encode proteins but regulate the gene expression at an epigenetic level, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The role played by ncRNAs in many physiological and pathological processes has gained attention during the last few decades, as they might be useful in the diagnosis, treatment and management of several human disorders, including endocrine and oncological diseases. Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine cancer, still characterized by high mortality and morbidity due to both endocrine and oncological complications. Despite the rarity of this disease, recently, the role of ncRNA has been quite extensively evaluated in ACC. In order to better explore the role of the ncRNA in human ACC, this review summarizes the current knowledge on ncRNA dysregulation in ACC and its potential role in the diagnosis, treatment, and management of this tumor.},
  language  = {en}
}
@article{TamburelloAltieriSbieraetal.2022,
  author    = {Tamburello, Mariangela and Altieri, Barbara and Sbiera, Iuliu and Sigala, Sandra and Berruti, Alfredo and Fassnacht, Martin and Sbiera, Silviu},
  title     = {FGF/FGFR signaling in adrenocortical development and tumorigenesis: novel potential therapeutic targets in adrenocortical carcinoma},
  series = {Endocrine},
  volume    = {77},
  journal   = {Endocrine},
  number    = {3},
  doi       = {10.1007/s12020-022-03074-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324420},
  pages     = {411-418},
  year      = {2022},
  abstract  = {FGF/FGFR signaling regulates embryogenesis, angiogenesis, tissue homeostasis and wound repair by modulating proliferation, differentiation, survival, migration and metabolism of target cells. Understandably, compelling evidence for deregulated FGF signaling in the development and progression of different types of tumors continue to emerge and FGFR inhibitors arise as potential targeted therapeutic agents, particularly in tumors harboring aberrant FGFR signaling. There is first evidence of a dual role of the FGF/FGFR system in both organogenesis and tumorigenesis, of which this review aims to provide an overview. FGF-1 and FGF-2 are expressed in the adrenal cortex and are the most powerful mitogens for adrenocortical cells. Physiologically, they are involved in development and maintenance of the adrenal gland and bind to a family of four tyrosine kinase receptors, among which FGFR1 and FGFR4 are the most strongly expressed in the adrenal cortex. The repeatedly proven overexpression of these two FGFRs also in adrenocortical cancer is thus likely a sign of their participation in proliferation and vascularization, though the exact downstream mechanisms are not yet elucidated. Thus, FGFRs potentially offer novel therapeutic targets also for adrenocortical carcinoma, a type of cancer resistant to conventional antimitotic agents.},
  language  = {en}
}