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Werner F Blum University Children’s Hospital, Giessen, Germany

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Abdullah Alherbish Al Habib Medical Group, Riyadh, Saudi Arabia

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Afaf Alsagheir King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Ahmed El Awwa Department of Pediatric Endocrinology & Diabetes, Hamad Medical Center, Doha, Qatar

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Walid Kaplan Tawam Hospital, Al Ain, UAE

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Ekaterina Koledova Global Medical Affairs Endocrinology, Merck KGaA, Darmstadt, Germany

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Martin O Savage William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, London, UK

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specific receptor or to importin-beta at the cell surface. It is then translocated to the cell nucleus where it interacts with the retinoid X receptor and nuclear receptor 77 to form a complex that can regulate transcription and can induce apoptosis ( 12

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Konstantin Yakimchuk Department of Biosciences and Nutrition Karolinska Institutet, Neo, Huddinge, Sweden

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Chandrashekar Bangalore Revanna Department of Biosciences and Nutrition Karolinska Institutet, Neo, Huddinge, Sweden

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Dan Huang Department of Biosciences and Nutrition Karolinska Institutet, Neo, Huddinge, Sweden

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Jose Inzunza Department of Biosciences and Nutrition Karolinska Institutet, Neo, Huddinge, Sweden

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Sam Okret Department of Biosciences and Nutrition Karolinska Institutet, Neo, Huddinge, Sweden

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affect apoptosis To investigate the mechanism of the reduced TV by the treatment with BPA or genistein, cell proliferation and apoptosis were analyzed in the above lymphoma samples by Ki67 staining and TUNEL assay, respectively. Treatment with either 50

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Elham Barazeghi Department of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, Uppsala, Sweden

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Per Hellman Department of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, Uppsala, Sweden

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Gunnar Westin Department of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, Uppsala, Sweden

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Peter Stålberg Department of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, Uppsala, Sweden

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many processes, such as cell differentiation and proliferation, apoptosis, adhesion and motility, through dephosphorylation of multiple proteins in signaling pathways. PTPRM is a homophilic cell-adhesion molecule, involved in cell–cell adhesion and

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Eric Seidel Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nephrology and Medical Intensive Care, BCRT – Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany
Berlin Institute of Health (BIH), Berlin, Germany
Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

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Gudrun Walenda Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

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Clemens Messerschmidt Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany

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Benedikt Obermayer Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany

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Mirko Peitzsch Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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Paal Wallace Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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Rohini Bahethi Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

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Taekyeong Yoo Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea

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Murim Choi Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea

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Petra Schrade Charité – Universitaetsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Vegetative Anatomie, Berlin, Germany

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Sebastian Bachmann Charité – Universitaetsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Vegetative Anatomie, Berlin, Germany

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Gerhard Liebisch Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

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Graeme Eisenhofer Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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Dieter Beule Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany
Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany

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Ute I Scholl Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nephrology and Medical Intensive Care, BCRT – Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany
Berlin Institute of Health (BIH), Berlin, Germany
Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

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mitotane concentrations (30–50 µM), and mitochondrial disruption appears to activate apoptosis through caspase 3/7, accounting for cytotoxicity ( 11 ). Effects also include a decrease in the expression of mitochondrial genes involved in steroidogenesis

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Zhengrong Jiang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Linghong Huang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Lijun Chen Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Jingxiong Zhou Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Bo Liang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Xuefeng Bai Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Lizhen Wu Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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Huibin Huang Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China

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time points (24, 48, 72, and 96 h), 10 μL of CCK-8 reagent was added to each well. After incubation at 37°C for 2 h, a microplate reader was applied to measure the absorbance at 450 nm. Flow cytometry Apoptosis was detected using the AnnexinV

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Anne H van der Spek Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

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Olga V Surovtseva Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

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Saskia Aan Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

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Anton T J Tool Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands

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Annemarie van de Geer Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands

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Korcan Demir Division of Pediatric Endocrinology, Dokuz Eylül University, Izmir, Turkey

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Anja L M van Gucht Department of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands

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A S Paul van Trotsenburg Department of Pediatric Endocrinology, Academic Medical Center, Amsterdam, The Netherlands

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Timo K van den Berg Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands

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Eric Fliers Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

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Anita Boelen Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

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), interleukin 8 (IL-8) and PAF. Results were compared to a day control, and to the normal range of historical controls ( n  = 132). Neutrophil apoptosis Spontaneous apoptosis was assessed in freshly isolated unstimulated neutrophils. Cells were incubated

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Mai Morsi Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Braunschweig, Germany

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Torben Schulze Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Braunschweig, Germany

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Eike Früh Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Braunschweig, Germany

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Dennis Brüning Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Braunschweig, Germany

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Uwe Panten Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Braunschweig, Germany

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Ingo Rustenbeck Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Braunschweig, Germany

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) Freshly isolated (upper row) or 22-h-cultured (middle row) islets were loaded with annexinV-Andy Fluor 488 to indicate incipient apoptosis and ethidium homodimer III to indicate necrotic nuclei. Beginning apoptosis is only visible in the outermost cell

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Satoshi Inoue Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA
James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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Taichi Mizushima Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA
James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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Hiroki Ide Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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Guiyang Jiang Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA
James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA

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Takuro Goto Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA
James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA

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Yujiro Nagata Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA
James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA

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George J Netto Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA

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Hiroshi Miyamoto Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA
James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Department of Urology, University of Rochester Medical Center, Rochester, New York, USA

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fixed with methanol and stained with 0.1% crystal violet. The number of colonies in photographed pictures was quantitated, using ImageJ software (National Institutes of Health). Apoptosis and cell cycle analysis The TUNEL assay was performed on

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Felix Haglund Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Gustaf Rosin Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Inga-Lena Nilsson Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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C Christofer Juhlin Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Ylva Pernow Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Sophie Norenstedt Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Andrii Dinets Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Catharina Larsson Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Johan Hartman Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Anders Höög Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden
Department of Oncology–Pathology, Cancer Centre Karolinska, Department of Biosciences and Nutrition, Department of Molecular Medicine and Surgery, Department of Surgery #4, Karolinska Institutet, Stockholm, Sweden

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Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness.

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Hathairat Rueangdetnarong Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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Rattanaporn Sekararithi Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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Thidarat Jaiwongkam Cardiac Electrophysiology Research and Training Center (CERT), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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Sirinart Kumfu Cardiac Electrophysiology Research and Training Center (CERT), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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Nipon Chattipakorn Cardiac Electrophysiology Research and Training Center (CERT), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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Theera Tongsong Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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Phudit Jatavan Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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Objective

The primary objective of this study was to compare the levels of oxidative stress biomarkers between pregnancies with gestational diabetes mellitus (GDM) and normoglycemic pregnancies.

Materials and methods

A prospective study was conducted on pregnant women at average risk for GDM. The participants were screened for GDM with glucose challenge test and confirmed by 100 g, 3-h oral glucose tolerance test and categorized into the control (non-GDM) and GDM groups. Maternal blood was collected from all participants at gestational age (GA) 24–28 weeks and early labor and fetal cord blood was collected for measurements of 8 Isoprostane (8Isop) (oxidative stress marker), TNF-α (inflammatory marker) and IL-10 (anti-inflammatory marker) and were followed up for maternal and neonatal outcomes.

Result

A total of 62 women, 30 in GDM and 32 in control group, met the inclusion criteria. At 24–28 weeks of gestation, maternal serum 8Isop and TNF-α levels were significantly higher in GDM group (P = 0.032 and P = 0.047), in spite of good glycemic control. At early labor, maternal 8Isop levels were significantly higher in GDM (P = 0.001). The biomarkers in the cord blood as well as maternal and neonatal outcomes in both groups were not significantly different.

Conclusion

GDM is significantly associated with inflammatory process when compared to normal pregnancy, as indicated by higher oxidative stress and apoptosis markers. However, such levels were not correlated with the pregnancy outcomes. An increase in oxidative stress could not be prevented by good glycemic control. Cord blood biomarker levels in pregnancy with GDM were not changed, suggesting that the placenta could be the barrier for the oxidative stress and cytokines.

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