التفاصيل البيبلوغرافية
| العنوان: |
Targeting Cyclooxygenase-2 in Pheochromocytoma and Paraganglioma: Focus on Genetic Background. |
| المؤلفون: |
Ullrich, Martin, Richter, Susan, Seifert, Verena, Hauser, Sandra, Calsina, Bruna, Martínez-Montes, Ángel M., ter Laak, Marjolein, Ziegler, Christian G., Timmers, Henri, Eisenhofer, Graeme, Robledo, Mercedes, Pietzsch, Jens |
| المصدر: |
Cancers; Jun2019, Vol. 11 Issue 6, p743, 1p |
| مصطلحات موضوعية: |
NONSTEROIDAL anti-inflammatory agents, CYCLOOXYGENASE 2, ANIMAL experimentation, HYPOXEMIA, CANCER chemotherapy, DRUG delivery systems, GENE expression, HOMOGRAFTS, MESSENGER RNA, MICE, GENETIC mutation, PHEOCHROMOCYTOMA, PARAGANGLIOMA, VON Hippel-Lindau disease, IN vivo studies, THERAPEUTICS |
| مستخلص: |
Cyclooxygenase 2 (COX-2) is a key enzyme of the tumorigenesis-inflammation interface and can be induced by hypoxia. A pseudohypoxic transcriptional signature characterizes pheochromocytomas and paragangliomas (PPGLs) of the cluster I, mainly represented by tumors with mutations in von Hippel–Lindau (VHL), endothelial PAS domain-containing protein 1 (EPAS1), or succinate dehydrogenase (SDH) subunit genes. The aim of this study was to investigate a possible association between underlying tumor driver mutations and COX-2 in PPGLs. COX-2 gene expression and immunoreactivity were examined in clinical specimens with documented mutations, as well as in spheroids and allografts derived from mouse pheochromocytoma (MPC) cells. COX-2 in vivo imaging was performed in allograft mice. We observed significantly higher COX-2 expression in cluster I, especially in VHL-mutant PPGLs, however, no specific association between COX-2 mRNA levels and a hypoxia-related transcriptional signature was found. COX-2 immunoreactivity was present in about 60% of clinical specimens as well as in MPC spheroids and allografts. A selective COX-2 tracer specifically accumulated in MPC allografts. This study demonstrates that, although pseudohypoxia is not the major determinant for high COX-2 levels in PPGLs, COX-2 is a relevant molecular target. This potentially allows for employing selective COX-2 inhibitors as targeted chemotherapeutic agents and radiosensitizers. Moreover, available models are suitable for preclinical testing of these treatments. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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