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11 results on '"Ziegler, C.G."'

1. Metastatic Pheochromocytoma and Paraganglioma: Somatostatin Receptor 2 Expression, Genetics, and Therapeutic Responses.

Author

Fischer, A., Kloos, S., Maccio, U., Friemel, J., Remde, H., Fassnacht, M., Pamporaki, C., Eisenhofer, G., Timmers, H.J.L.M., Robledo, M., Fliedner, S.M.J., Wang, K., Maurer, J., Reul, A., Zitzmann, K., Bechmann, N., Žygienė, G., Richter, S., Hantel, C., Vetter, D., Lehmann, K., Mohr, H., Pellegata, N.S., Ullrich, M., Pietzsch, J., Ziegler, C.G., Bornstein, S.R., Kroiss, M., Reincke, M., Pacak, K., Grossman, A.B., Beuschlein, F., Nölting, S., Fischer, A., Kloos, S., Maccio, U., Friemel, J., Remde, H., Fassnacht, M., Pamporaki, C., Eisenhofer, G., Timmers, H.J.L.M., Robledo, M., Fliedner, S.M.J., Wang, K., Maurer, J., Reul, A., Zitzmann, K., Bechmann, N., Žygienė, G., Richter, S., Hantel, C., Vetter, D., Lehmann, K., Mohr, H., Pellegata, N.S., Ullrich, M., Pietzsch, J., Ziegler, C.G., Bornstein, S.R., Kroiss, M., Reincke, M., Pacak, K., Grossman, A.B., Beuschlein, F., and Nölting, S.

Abstract

Contains fulltext : 296796.pdf (Publisher’s version ) (Open Access), CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)-dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface therapeutic biomarker of such tumors. OBJECTIVE: Exploration of the relationship between SSTR2 immunoreactivity and SDHB immunoreactivity, mutational status, and clinical behavior of PPGLs. Evaluation of SSTR-based therapies in metastatic PPGLs. METHODS: Retrospective analysis of a multicenter cohort of PPGLs at 6 specialized Endocrine Tumor Centers in Germany, The Netherlands, and Switzerland. Patients with PPGLs participating in the ENSAT registry were included. Clinical data were extracted from medical records, and immunohistochemistry (IHC) for SDHB and SSTR2 was performed in patients with available tumor tissue. Immunoreactivity of SSTR2 was investigated using Volante scores. The main outcome measure was the association of SSTR2 IHC positivity with genetic and clinical-pathological features of PPGLs. RESULTS: Of 202 patients with PPGLs, 50% were SSTR2 positive. SSTR2 positivity was significantly associated with SDHB- and SDHx-related PPGLs, with the strongest SSTR2 staining intensity in SDHB-related PPGLs (P = .01). Moreover, SSTR2 expression was significantly associated with metastatic disease independent of SDHB/SDHx mutation status (P < .001). In metastatic PPGLs, the disease control rate with first-line SSTR-based radionuclide therapy was 67% (n = 22, n = 11 SDHx), and with first-line "cold" somatostatin analogs 100% (n = 6, n = 3 SDHx). CONCLUSION: SSTR2 expression was independently associated with SDHB/SDHx mutations and metastatic disease. We confirm a high disease control rate of somatostatin receptor-based therapies in metastatic PPGLs.

Published
2023

3. Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: Antiproliferative effects of peptide analogues

Author

Ziegler, C.G., Brown, J.W., Schally, A.V., Erler, A., Gebauer, L., Treszl, A., Young, L., Fishman, L.M., Engel, J.B., Willenberg, H.S., Petersenn, S., Eisenhofer, G., Ehrhart-Bornstein, M., and Bornstein, S.R.

Subjects
Hormone receptors -- Health aspects, Hormone receptors -- Research, Protein microarrays -- Usage, Science and technology
Abstract

Peptide analogues targeting various neuropeptide receptors have been used effectively in cancer therapy. A hallmark of adrenocortical tumor formation is the aberrant expression of peptide receptors relating to uncontrolled cell proliferation and hormone overproduction. Our microarray results have also demonstrated a differential expression of neuropeptide hormone receptors in tumor subtypes of human pheochromocytoma. In light of these findings, we performed a comprehensive analysis of relevant receptors in both human adrenomedullary and adrenocortical tumors and tested the antiproliferative effects of peptide analogues targeting these receptors. Specifically, we examined the receptor expression of somatostatin-type-2 receptor, growth hormone-releasing hormone (GHRH) receptor or GHRH receptor splice variant-1 (SV-1) and luteinizing hormone-releasing hormone (LHRH) receptor at the mRNA and protein levels in normal human adrenal tissues, adrenocortical and adrenomedullary tumors, and cell lines. Cytotoxic derivatives of somatostatin AN-238 and, to a lesser extent, AN-162, reduced cell numbers of uninduced and NGF-induced adrenomedullary pheochromocytoma cells and adrenocortical cancer cells. Both the splice variant of GHRH receptor SV-1 and the LHRH receptor were also expressed in adrenocortical cancer cell lines but not in the pheochromocytoma cell line. The GHRH receptor antagonist MZ-4-71 and LHRH antagonist Cetrorelix both significantly reduced cell growth in the adrenocortical cancer cell line. In conclusion, the expression of receptors for somatostatin, GHRH, and LHRH in the normal human adrenal and in adrenal tumors, combined with the growth-inhibitory effects of the antitumor peptide analogues, may make possible improved treatment approaches to adrenal tumors. targeted therapy | tumor endocrinology | aberrant receptors | cytotoxic peptide derivatives

Published
2009

4. The transCampus metabolic training programme explores the link of SARS-CoV-2 virus to metabolic disease

Author

Bornstein, S.R., Guan, K., Brunßen, C., Mueller, G., Kamvissi-Lorenz, V., Lechler, R., Trembath, R., Mayr, M., Poston, L., Sancho, R., Ahmed, S., Alfar, E., Aljani, B., Alves, T.C., Amiel, S., Andoniadou, C.L., Bandral, M., Belavgeni, A., Berger, I., Birkenfeld, A.L., Bonifacio, E., Chavakis, T., Chawla, P., Choudhary, P., Cujba, A.M., Delgadillo Silva, L.F., Demcollari, T., Drotar, D.M., Duin, S., El-Agroudy, N.N., El-Armouche, A., Eugster, A., Gado, M., Gavalas, A., Gelinsky, M., Guirgus, M., Hansen, S., Hanton, E., Hasse, M., Henneicke, H., Heller, C., Hempel, H., Hogstrand, C., Hopkins, D., Jarc, L., Jones, P.M., Kamel, M., Kämmerer, S., King, A.J.F., Kurzbach, A., Lambert, C., Latunde-Dada, Y., Lieberam, I., Liers, J., Li, J.W., Linkermann, A., Locke, S., Ludwig, B., Manea, T., Maremonti, F., Marinicova, Z., McGowan, B.M., Mickunas, M., Mingrone, G., Mohanraj, K., Morawietz, H., Ninov, N., Peakman, M., Persaud, S.J., Pietzsch, J., Cachorro, E., Pullen, T.J., Pyrina, I., Rubino, F., Santambrogio, A., Schepp, F., Schlinkert, P., Scriba, L.D., Siow, R., Solimena, M., Spagnoli, F.M., Speier, S., Stavridou, A., Steenblock, C., Strano, A., Taylor, P., Tiepner, A., Tonnus, W., Tree, T., Watt, F.E., Werdermann, M., Wilson, M., Yusuf, N., and Ziegler, C.G.

Subjects
0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clinical Biochemistry, education, MEDLINE, Disease, Settore MED/17 - MALATTIE INFETTIVE, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Pandemic, Diabetes Mellitus, medicine, Humans, Obesity, Metabolic disease, Pandemics, metabolic training programme, Medical education, Communicable disease, Scope (project management), SARS-CoV-2, Biochemistry (medical), COVID-19, General Medicine, 030104 developmental biology, Infectious disease (medical specialty), transCampus, Education, Medical, Continuing, Covid-19, Metabolic Training Programme, Transcampus, 030217 neurology & neurosurgery
Abstract

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.

Published
2021

5. Targeting Cyclooxygenase-2 in Pheochromocytoma and Paraganglioma: Focus on Genetic Background

Author

Ullrich, M., Richter, S., Seifert, V., Hauser, S., Calsina, B., Martinez-Montes, A.M., Laak, M.C. ter, Ziegler, C.G., Timmers, H.J., Eisenhofer, G., Robledo, M., Pietzsch, J., Deutsche Forschungsgemeinschaft (Alemania), Paradifference Foundation, and Instituto de Salud Carlos III

Subjects
Inflammation, endocrine system diseases, Mouse pheochromocytoma cells, mouse pheochromocytoma cells, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Hypoxia-inducible factor, succinate dehydrogenase, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, lcsh:RC254-282, Article, Fluorescence imaging, Succinate dehydrogenase, fluorescence imaging, NF1, EPAS1, inflammation, VHL, immunohistochemistry, radiosensitization, neoplasms, hypoxia-inducible factor, Radiosensitization
Abstract

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&ndash, 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.

Published
2019

6. P6286Interaction between oxidized LDL, angiotensin II and oxidative stress

Author

Catar, R.A., primary, Goettsch, C., additional, Taye, A., additional, Hofmann, A., additional, Brunssen, C., additional, Muller, G., additional, Shahid, A., additional, Lehmann, S., additional, Schubert, U., additional, Ludwig, B., additional, Ziegler, C.G., additional, Bornstein, S.R., additional, Krug, A.W., additional, Walther, T., additional, and Morawietz, H., additional

Published
2017
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