@article{BriestGrassSeddingetal.2017,
  author    = {Briest, Franziska and Grass, Irina and Sedding, Dagmar and Moebs, Markus and Christen, Friederike and Benecke, Joana and Fuchs, Karolin and Mende, Stefanie and Kaemmerer, Daniel and S{\"a}nger, J{\"o}rg and Kunze, Almut and Geisler, Christina and Freitag, Helma and Lewens, Florentine and Worpenberg, Lina and Iwaszkiewicz, Sara and Siegmund, Britta and Walther, Wolfgang and Hummel, Michael and Grabowski, Patricia},
  title     = {Mechanisms of Targeting the MDM2-p53-FOXM1 Axis in Well-Differentiated Intestinal Neuroendocrine Tumors},
  series = {Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships},
  volume    = {107},
  journal   = {Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships},
  number    = {1},
  publisher = {Karger},
  address   = {Basel},
  issn      = {0028-3835},
  doi       = {10.1159/000481506},
  pages     = {1 -- 23},
  year      = {2017},
  abstract  = {Background/Aims: The tumor suppressor p53 is rarely mutated in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) but they frequently show a strong expression of negative regulators of p53, rendering these tumors excellent targets for a p53 recovery therapy. Therefore, we analyzed the mechanisms of a p53 recovery therapy on intestinal neuroendocrine tumors in vitro and in vivo. Methods: By Western blot and immunohistochemistry, we found that in GEP-NEN biopsy material overexpression of MDM2 was present in intestinal NEN. Therefore, we analyzed the effect of a small-molecule inhibitor, nutlin-3a, in p53 wild-type and mutant GEP-NEN cell lines by proliferation assay, flow cytometry, immunofluorescence, Western blot, and by multiplex gene expression analysis. Finally, we analyzed the antitumor effect of nutlin-3a in a xenograft mouse model in vivo. During the study, the tumor volume was determined. Results: The midgut wild-type cell line KRJ-I responded to the treatment with cell cycle arrest and apoptosis. By gene expression analysis, we could demonstrate that nutlins reactivated an antiproliferative p53 response. KRJ-I-derived xenograft tumors showed a significantly decreased tumor growth upon treatment with nutlin-3a in vivo. Furthermore, our data suggest that MDM2 also influences the expression of the oncogene FOXM1 in a p53-independent manner. Subsequently, a combined treatment of nutlin-3a and cisplatin (as chemoresistance model) resulted in synergistically enhanced antiproliferative effects. Conclusion: In summary, MDM2 overexpression is a frequent event in p53 wild-type intestinal neuroendocrine neoplasms and therefore recovery of a p53 response might be a novel personalized treatment approach in these tumors. (c) 2017 S. Karger AG, Basel},
  language  = {en}
}
@misc{deVinuesaAbdelilahSeyfriedKnausetal.2016,
  author    = {de Vinuesa, Amaya Garcia and Abdelilah-Seyfried, Salim and Knaus, Petra and Zwijsen, An and Bailly, Sabine},
  title     = {BMP signaling in vascular biology and dysfunction},
  series = {New journal of physics : the open-access journal for physics},
  volume    = {27},
  journal   = {New journal of physics : the open-access journal for physics},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {1359-6101},
  doi       = {10.1016/j.cytogfr.2015.12.005},
  pages     = {65 -- 79},
  year      = {2016},
  abstract  = {The vascular system is critical for developmental growth, tissue homeostasis and repair but also for tumor development. Bone morphogenetic protein (BMP) signaling has recently emerged as a fundamental pathway of the endothelium by regulating cardiovascular and lymphatic development and by being causative for several vascular dysfunctions. Two vascular disorders have been directly linked to impaired BMP signaling: pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia. Endothelial BMP signaling critically depends on the cellular context, which includes among others vascular heterogeneity, exposure to flow, and the intertwining with other signaling cascades (Notch, WNT, Hippo and hypoxia). The purpose of this review is to highlight the most recent findings illustrating the clear need for reconsidering the role of BMPs in vascular biology. (C) 2015 Elsevier Ltd. All rights reserved.},
  language  = {en}
}
@article{MuellerRoeberBalazadeh2014,
  author    = {M{\"u}ller-R{\"o}ber, Bernd and Balazadeh, Salma},
  title     = {Auxin and its role in plant senescence},
  series = {Journal of plant growth regulation},
  volume    = {33},
  journal   = {Journal of plant growth regulation},
  number    = {1},
  publisher = {Springer},
  address   = {New York},
  issn      = {0721-7595},
  doi       = {10.1007/s00344-013-9398-5},
  pages     = {21 -- 33},
  year      = {2014},
  abstract  = {Leaf senescence represents a key developmental process through which resources trapped in the photosynthetic organ are degraded in an organized manner and transported away to sustain the growth of other organs including newly forming leaves, roots, seeds, and fruits. The optimal timing of the initiation and progression of senescence are thus prerequisites for controlled plant growth, biomass accumulation, and evolutionary success through seed dispersal. Recent research has uncovered a multitude of regulatory factors including transcription factors, micro-RNAs, protein kinases, and others that constitute the molecular networks that regulate senescence in plants. The timing of senescence is affected by environmental conditions and abiotic or biotic stresses typically trigger a faster senescence. Various phytohormones, including for example ethylene, abscisic acid, and salicylic acid, promote senescence, whereas cytokinins delay it. Recently, several reports have indicated an involvement of auxin in the control of senescence, however, its mode of action and point of interference with senescence control mechanisms remain vaguely defined at present and contrasting observations regarding the effect of auxin on senescence have so far hindered the establishment of a coherent model. Here, we summarize recent studies on auxin-related genes that affect senescence in plants and highlight how these findings might be integrated into current molecular-regulatory models of senescence.},
  language  = {en}
}