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Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
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dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas . Journal of Clinical Endocrinology and Metabolism 92 3822 – 3828 . ( https://doi.org/10.1210/jc.2007-0709 ) Bechmann N Poser I Seifert V
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Endocrinology Unit, Biochemistry Unit, Institute of Clinical Chemistry and Laboratory Medicine, Istituto Toscano Tumori, Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio’, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy
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In solid tumors, neoplastic cells grow in contact with the so-called tumor microenvironment. The interaction between tumor cells and the microenvironment causes reciprocal metabolic reprogramming and favorable conditions for tumor growth and metastatic spread. To obtain an experimental model resembling the in vivo conditions of the succinate dehydrogenase B subunit (SDHB)-mutated paragangliomas (PGLs), we evaluated the effects of SDHB silencing on metabolism and proliferation in the human neuroblastoma cell line (SK-N-AS), cultured alone or in association with human fibroblasts. Silencing caused a 70% decrease in protein expression, an almost complete loss of the complex specific enzymatic activity, and a significant increase in HIF1α and HIF2α expression; it thus resembled the in vivo tumor cell phenotype. When compared with WT SK-N-AS cells, SDHB-silenced cells showed an altered metabolism characterized by an unexpected significant decrease in glucose uptake and an increase in lactate uptake. Moreover, silenced cells exhibited a significant increase in cell proliferation and metalloproteinase activity. When co-cultured with human fibroblasts, control cells displayed a significant decrease in glucose uptake and a significant increase in cell proliferation as compared with their mono-cultured counterparts. These effects were even more evident in co-cultured silenced cells, with a 70% decrease in glucose uptake and a 92% increase in cell proliferation as compared to their mono-cultured counterparts. The present data indicate for the first time, to our knowledge, that SDHB impairment causes metabolic and functional derangement of neural-crest-derived tumor cells and that the microenvironment, here represented by fibroblasts, strongly affects their tumor metabolism and growth capacity.
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-Roqueplo AP 2007 Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas . Journal of Clinical Endocrinology and Metabolism 92 3822 – 3828 . ( doi:10.1210/jc.2007-0709 ). Benn DE
Department of Endocrinology, Cambridge University NHS Foundation Trust, Cambridge, UK
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-0033) Srirangalingam U Walker L Khoo B MacDonald F Gardner D Wilkin TJ Skelly RH George E Spooner D Monson JP 2008 Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH
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Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, INSERM, Endocrinology Unit, Reproductive and Adult Endocrinology Program, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, INSERM, Endocrinology Unit, Reproductive and Adult Endocrinology Program, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
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Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas . Journal of Clinical Endocrinology and Metabolism 92 3822 – 3828 . Astrom K Cohen JE Willett-Brozick JE Aston CE Baysal
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.1210/jc.2004-1398 ). Amar L Baudin E Burnichon N Peyrard S Silvera S Bertherat J Bertagna X Schlumberger M Jeunemaitre X Gimenez-Roqueplo AP 2007 Succinate dehydrogenase B gene mutations predict survival in patients with malignant
Program in Reproductive and Adult Endocrinology, Nuclear Medicine Division, Radiology and Imaging Sciences Department, Section of Endocrinology and Metabolism, Medical Oncology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
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Program in Reproductive and Adult Endocrinology, Nuclear Medicine Division, Radiology and Imaging Sciences Department, Section of Endocrinology and Metabolism, Medical Oncology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
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for succinate dehydrogenase B, C, and D mutations. The primary tumor was found in the urinary bladder and was removed with en bloc cystectomy, prostatectomy, with lymphatic node dissection and creation of ileal neobladder in 2005. In 2009, he was
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Department of Medicine-Solna, Yale Endocrine Neoplasia Laboratory, Department of Surgery, Departments of Oncology-Pathology, Molecular Medicine and Surgery, Department of Pathology, Karolinska Institutet, Karolinska University Hospital CMM, SE-171 76 Stockholm, Sweden
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Department of Medicine-Solna, Yale Endocrine Neoplasia Laboratory, Department of Surgery, Departments of Oncology-Pathology, Molecular Medicine and Surgery, Department of Pathology, Karolinska Institutet, Karolinska University Hospital CMM, SE-171 76 Stockholm, Sweden
Department of Medicine-Solna, Yale Endocrine Neoplasia Laboratory, Department of Surgery, Departments of Oncology-Pathology, Molecular Medicine and Surgery, Department of Pathology, Karolinska Institutet, Karolinska University Hospital CMM, SE-171 76 Stockholm, Sweden
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Department of Medicine-Solna, Yale Endocrine Neoplasia Laboratory, Department of Surgery, Departments of Oncology-Pathology, Molecular Medicine and Surgery, Department of Pathology, Karolinska Institutet, Karolinska University Hospital CMM, SE-171 76 Stockholm, Sweden
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Department of Medicine-Solna, Yale Endocrine Neoplasia Laboratory, Department of Surgery, Departments of Oncology-Pathology, Molecular Medicine and Surgery, Department of Pathology, Karolinska Institutet, Karolinska University Hospital CMM, SE-171 76 Stockholm, Sweden
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Department of Medicine-Solna, Yale Endocrine Neoplasia Laboratory, Department of Surgery, Departments of Oncology-Pathology, Molecular Medicine and Surgery, Department of Pathology, Karolinska Institutet, Karolinska University Hospital CMM, SE-171 76 Stockholm, Sweden
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biological evidence of metastatic disease according to the current WHO criteria. Relationship between C228T and molecular phenotypes Mutation of the succinate dehydrogenase B gene ( SDHB ) is a frequent genetic event in PGL, especially in malignant PGL
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X Schlumberger M Jeunemaitre X Gimenez-Roqueplo AP 2007 Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas . Journal of Clinical Endocrinology and Metabolism 92 3822
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of Clinical Oncology 23 8812 – 8818 . Amar L Baudin E Burnichon N Peyrard S Silvera S Bertherat J Bertagna X Schlumberger M Jeunemaitre X Gimenez-Roqueplo AP 2007 Succinate dehydrogenase B gene mutations predict survival in