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6. Knorpeldefektbehandlung

Author

Meenen, N. M., Rischke, B., Adamietz, P., Dauner, M., Fink, J., Göpfert, C., Rueger, J. M., Hartel, W., editor, and Herfarth, Ch.

Published
1998
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23. 18F-RB390: Innovative ligand for imaging the T877A androgen receptor mutant in prostate cancer via positron emissiontomography (PET)

Author

Bertolini, R, Goepfert, C, Andrieu, T, Nichols, S, Walter, MA, Frey, FJ, McCammon, JA, and Frey, BM

Abstract

© 2014 Wiley Periodicals, Inc. BACKGROUND. Detecting prostate cancer before spreading or predicting a favorable therapy are challenging issues for impacting patient's survival. Presently, 2-[18F]-fluoro-2- deoxy-D-glucose (18F-FDG) and/or18F-fluorocholine (18F-FCH) are the generally used PET-tracers in oncology yet do not emphasize the T877A androgen receptor (AR) mutation being exclusively present in cancerous tissue and escaping androgen deprivation treatment. METHODS. We designed and synthesized fluorinated 5α-dihydrotestosterone (DHT) derivatives to target T877A-AR. We performed binding assays to select suitable candidates using COS-7 cells transfected with wild-type or T877A AR (WT-AR, T877A-AR) expressing plasmids and investigated cellular uptake of candidate18F-RB390. Stability, biodistribution analyses and PET-Imaging were assessed by injecting18F-RB390 (10MBq), with and without co-injection of an excess of unlabeled DHT in C4-2 and PC-3 tumor bearing male SCID mice (n = 12). RESULTS. RB390 presented a higher relative binding affinity (RBA) (28.1%, IC50 = 32 nM) for T877A-AR than for WT-AR (1.7%, IC50= 357 nM) related to DHT (RBA = 100%). A small fraction of18F-RB390 was metabolized when incubated with murine liver homogenate or human blood for 3 hr. The metabolite of RB390, 3-hydroxysteroid RB448, presented similar binding characteristics as RB390.18F-RB390 but not18F-FDG or18F-FCH accumulated 2.5x more in COS-7 cells transfected with pSG5AR-T877A than with control plasmid. Accumulation was reduced with an excess of DHT. PET/CT imaging and biodistribution studies revealed a significantly higher uptake of18F-RB390 in T877A mutation positive xenografts compared to PC-3 control tumors. This effect was blunted with DHT. CONCLUSION. Given the differential binding capacity and the favorable radioactivity pattern,18F-RB390 represents the portrayal of the first imaging ligand with predictive potential for mutant T877A-AR in prostate cancer for guiding therapy.

Published
2015

33. Disordered cellular migration and angiogenesis in cd39-null mice

Author

Goepfert, C, Sundberg, Christian, Sevigny, J, Enjyoji, K, Hoshi, T, Csizmadia, E, Robson, S, Goepfert, C, Sundberg, Christian, Sevigny, J, Enjyoji, K, Hoshi, T, Csizmadia, E, and Robson, S

Abstract

BACKGROUND: Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39 is the major ectonucleotidase of endothelial cells and monocytes and catalyzes phosphohydrolysis of extracellular nucleoside diphosphates (NDP) and triphosphates (NTP, eg, ATP and UTP). Deletion of cd39 causes perturbations in the hydrolysis of NTP and NDP in the vasculature. Activation of P2 receptors appears to influence endothelial cell chemotactic and mitogenic responses in vitro. Therefore, aberrant regulation of nucleotide P2 receptors may influence angiogenesis in cd39-null mice. Methods and Results- In control mice, implanted Matrigel plugs containing growth factors were rapidly populated by monocyte/macrophages, endothelial cells, and pericytes, with the development of new vessels over days. In cd39-null mice, migrating cells were completely confined to the tissue-Matrigel interface in a clearly stratified manner. Absolute failure of new vessel ingrowth was consistently observed in the mutant mice. Linked to these findings, chemotaxis of cd39-null monocyte/macrophages to nucleotides was impaired in vitro. This abnormality was associated with desensitization of nucleotide receptor P2Y-mediated signaling pathways. CONCLUSIONS: Our findings demonstrate a role for NTPDase1 and phosphohydrolysis of extracellular nucleotides in the regulation of the cellular infiltration and new vessel growth in a model of angiogenesis.

Published
2001
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43. COAGULATION AND THROMBOTIC DISORDERS ASSOCIATED WITH PIG ORGAN AND HEMATOPOIETIC CELL TRANSPLANTATION IN NONHUMAN PRIMATES

Author

B??hler, L., primary, Basker, M., additional, Alwayn, I. P. J., additional, Goepfert, C., additional, Kitamura, H., additional, Kawai, T., additional, Gojo, S., additional, Kozlowski, T., additional, Ierino, F. L., additional, Awwad, M., additional, Sachs, D. H., additional, Sackstein, R., additional, Robson, S. C., additional, and Cooper, D. K. C., additional

Published
2000
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45. PORCINE PERIPHERAL BLOOD STEM CELL TRANSPLANTATION IN BABOONS IS COMPLICATED BY THROMBOTIC THROMBOCYTOPENIC PURPURA

Author

Buhler, L., primary, Goepfert, C., additional, Basker, M., additional, Gojo, S., additional, Guckelberger, O., additional, Chang, Q., additional, Nash, K., additional, Watts, A., additional, Treter, S., additional, Oravec, G., additional, Awwad, M., additional, Shimizu, A., additional, Andrews, D., additional, White-Scharf, M., additional, Sachs, D. H., additional, Robson, S. C., additional, Sackstein, R., additional, and Cooper, D. K.C., additional

Published
1999
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46. Postoperatives Erbrechen

Author

Apfel, C. C., primary, Greim, C.-A., additional, Goepfert, C., additional, Grundt, D., additional, Usadel, J., additional, Sefrin, P., additional, and Roewer, N., additional

Published
1998
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