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Frankfurt am Main, Germany

The Goethe University Frankfurt is a university which was founded in 1914 as a Citizens' University, which means that, while it was a State university of Prussia, it had been founded and financed by the wealthy and active liberal citizenry of Frankfurt am Main, a unique feature in German university history. It was named in 1932 after one of the most famous natives of Frankfurt, the poet and writer Johann Wolfgang von Goethe. Today, the university has 46,000 students, on 4 major campuses within the city.Several Nobel Prize winners have been affiliated with the university, such as Max von Laue. The university is also affiliated with 11 winners of the Gottfried Wilhelm Leibniz Prize. Wikipedia.

Fulda S.,Goethe University Frankfurt
Seminars in Cancer Biology | Year: 2015

Programmed cell death via apoptosis is characteristically disturbed in human cancers. This facilitates not only tumor formation and progression, but also treatment resistance. Since many currently applied anticancer treatment strategies rely on intact cell death signaling pathways for their therapeutic efficacy, a better understanding of the regulatory mechanisms that control cell death signaling pathways is critical to bypass resistance. Thus, reactivation of cell death programs in cancer cells may open new perspectives for more effective and more tumor-selective, yet less toxic anticancer therapies. © 2014 Elsevier Ltd.

Inhibitor of apoptosis (IAP) proteins play a critical role in the control of survival and cell death by regulating key signaling events such as caspase activation and NF-&kgreenB signaling. Because aberrantly high expression of IAP proteins represents a frequent oncogenic event in human cancers, therapeutic targeting of IAP proteins is considered as a promising approach. Several small-molecule pharmacologic inhibitors of IAP proteins that mimic the binding domain of the endogenous IAP antagonist second mitochondrial activator of caspases (Smac) to IAP proteins have been developed over the past few years. IAP antagonists have been shown in various preclinical cancer models to either directly initiate cell death or, alternatively, to prime cancer cells for cytotoxic therapies by lowering the threshold for cell death induction. IAP antagonists (i.e., GDC-0917/CUDC-427, LCL161, AT-406, HGS1029, and TL32711) are currently under evaluation in early clinical trials alone or in combination regimens. Thus, the concept to therapeutically target IAP proteins in human cancer has in principle been successfully transferred into a clinical setting and warrants further evaluation as a treatment approach. Clin Cancer Res; 20(2); 289-95. © 2013 AACR.

Over the last 20 years, it has become clear that cytochrome P450 (P450) enzymes generate a spectrum of bioactive lipid mediators from endogenous substrates. However, studies focused on the determining biologic activity of the P450 system have focused largely on the metabolites generated by one substrate (i.e., arachidonic acid). However, epoxides and diols derived from other endogenous substrates, such as linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid, may be generated in higher concentrations and may potentially be of more physiologic relevance. Recent studies that used a combination of phenotyping and lipid array analyses revealed that rather than being inactive products, fatty acid diols play important roles in a number of biologic processes including inflammation, angiogenesis, and metabolic regulation. Moreover, inhibitors of the soluble epoxide hydrolase that increase epoxide but decrease diol levels have potential for the treatment of the metabolic syndrome. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Kreuter J.,Goethe University Frankfurt
Advanced Drug Delivery Reviews | Year: 2014

Nanoparticles enable the delivery of a great variety of drugs including anticancer drugs, analgesics, anti-Alzheimer's drugs, cardiovascular drugs, protease inhibitors, and several macromolecules into the brain after intravenous injection of animals. The mechanism of the nanoparticle-mediated drug transport across the BBB appears to be receptor-mediated endocytosis followed by transcytosis into the brain or by drug release within the endothelial cells. Modification of the nanoparticle surface with covalently attached targeting ligands or by coating with certain surfactants that lead to the adsorption of specific plasma proteins after injection is necessary for this receptor-mediated uptake. A very critical and important requirement for nanoparticulate brain delivery is that the employed nanoparticles are biocompatible and, moreover, rapidly biodegradable, i.e. over a time frame of a few days. In addition to enabling drug delivery to the brain, nanoparticles, as with doxorubicin, may importantly reduce the drug's toxicity and adverse effects due to an alteration of the body distribution. Because of the possibility to treat severe CNS diseases such as brain tumours and to even transport proteins and other macromolecules across the blood-brain barrier, this technology holds great promise for a non-invasive therapy of these diseases. © 2013 Elsevier B.V.

Gokbuget N.,Goethe University Frankfurt
Blood | Year: 2013

The treatment of older patients with acute lymphoblastic leukemia (ALL) is an unmet medical need. In Western countries, the population is aging, which means there will be an increasing number of older patients. However, in the past few decades, there has been little improvement in treating them, and few clinical trials specifically designed for older patients with ALL have been reported. Older patients with ALL have a significantly lower complete response rate, higher early mortality, higher relapse rate, and poorer survival compared with younger patients. This is partly explained by a higher incidence of poor prognostic factors. Most importantly, intensive chemotherapy with or without stem cell transplantation, both of which are successful in younger patients, is less well tolerated in older patients. For the future, the most promising approaches are optimized supportive care, targeted therapies, moderately intensified consolidation, and reduced-intensity stem cell transplantation. One of the most important challenges for physicians is to differentiate between fit and unfit older patients in order to offer both groups optimal treatment regarding toxicity and mortality risks, quality of life, and long-term outcome. Prospective trials for older patients with ALL are urgently needed. © 2013 by The American Society of Hematology.

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