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  1. Book: Wissenschaftliches Publizieren in der Medizin

    Mylonas, Ioannis / Brüning, Ansgar

    ein Leitfaden

    2013  

    Author's details Ioannis Mylonas ; Ansgar Brüning
    Keywords Medizin ; Wissenschaftliches Manuskript
    Subject Wissenschaftliche Abhandlung ; Wissenschaftliche Arbeit ; Humanmedizin ; Heilkunst ; Medicine
    Language German
    Size XV, 152 S. : Ill., graph. Darst.
    Publisher Springer
    Publishing place Berlin u.a.
    Publishing country Germany
    Document type Book
    HBZ-ID HT017719249
    ISBN 978-3-642-37177-6 ; 3-642-37177-9 ; 9783642371783 ; 3642371787
    Database Catalogue ZB MED Medicine, Health

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  2. Article ; Online: Targeting the off-targets: a computational bioinformatics approach to understanding the polypharmacology of nelfinavir.

    Brüning, Ansgar

    Expert review of clinical pharmacology

    2011  Volume 4, Issue 5, Page(s) 571–573

    Abstract: In recent years, the identification of new pharmacological effects of already established or abandoned drugs has become a valuable tool for drug repositioning purposes. The HIV drug nelfinavir belongs to those drugs for which empirical data indicate ... ...

    Abstract In recent years, the identification of new pharmacological effects of already established or abandoned drugs has become a valuable tool for drug repositioning purposes. The HIV drug nelfinavir belongs to those drugs for which empirical data indicate additional pharmacological applications for various diseases, including cancer. To identify and confirm binding partners of nelfinavir other than HIV-1 protease, Xie et al. performed a systematic computational analysis to identify possible structural similarities between the nelfinavir-binding pocket of HIV-1 protease and 5985 protein database entries. Of 126 possible binding partners to nelfinavir, a remarkably high percentage of protein kinases were identified. Further in-depth computational ligand-binding studies indicated the EGF receptor and cytosolic protein kinase B as the most likely off-targets of nelfinavir. Astonishingly, these in silico data are in accordance with previous data obtained by experimental in vitro analysis, indicating a high predictive value of the computer-based approach developed and applied by Xie et al. The computational approach and the authors' results, with respect to their integration in systems biology, are presented and discussed.
    Language English
    Publishing date 2011-09
    Publishing country England
    Document type Comment ; Journal Article
    ISSN 1751-2441
    ISSN (online) 1751-2441
    DOI 10.1586/ecp.11.37
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Analysis of nelfinavir-induced endoplasmic reticulum stress.

    Brüning, Ansgar

    Methods in enzymology

    2011  Volume 491, Page(s) 127–142

    Abstract: Nelfinavir (Viracept®) is an HIV protease inhibitor that has been shown to induce the endoplasmic reticulum (ER) stress reaction in human cancer cells. Although the presumed drug doses needed for an efficient ER stress reaction and ensuing apoptosis in ... ...

    Abstract Nelfinavir (Viracept®) is an HIV protease inhibitor that has been shown to induce the endoplasmic reticulum (ER) stress reaction in human cancer cells. Although the presumed drug doses needed for an efficient ER stress reaction and ensuing apoptosis in cancer cells is somewhat higher than those prescribed for HIV-infected persons, nelfinavir represents one of the few clinically applicable ER stress-inducing agents, and is currently being tested in clinical studies on cancer patients. Therefore, this chapter describes how to obtain and use nelfinavir for in vitro and in vivo studies. In addition, methods are described that might facilitate the analysis and monitoring of the nelfinavir-induced ER stress response either in cancer cells in cell culture or in cancer tissue biopsies. These methods include various fluorescence-based ER staining techniques and the expression analysis of primary and secondary ER stress markers by immunoblotting and RT-PCR analysis. Among the several methods presented, the analysis of an unconventional XBP1 splicing, caused by the ER stress sensor IRE1, is shown to present the most sensitive and most specific marker for nelfinavir-induced ER stress. Primers and PCR conditions suitable for XBP1 PCR and splicing analysis are presented. Such a PCR-based XBP1 splicing analysis might not only be suitable to monitor nelfinavir-induced ER stress, but could also be applied in drug screening programs to test for other ER stress-inducing agents with similar activities or synergistic activities with nelfinavir.
    MeSH term(s) Animals ; Cell Line, Tumor ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/metabolism ; HIV Protease Inhibitors/pharmacology ; Humans ; Immunoblotting/methods ; Microscopy, Fluorescence/methods ; Microscopy, Phase-Contrast/methods ; Nelfinavir/pharmacology ; Neoplasms/drug therapy ; Reverse Transcriptase Polymerase Chain Reaction/methods
    Chemical Substances HIV Protease Inhibitors ; Nelfinavir (HO3OGH5D7I)
    Language English
    Publishing date 2011
    Publishing country United States
    Document type Journal Article
    ISSN 1557-7988 ; 0076-6879
    ISSN (online) 1557-7988
    ISSN 0076-6879
    DOI 10.1016/B978-0-12-385928-0.00008-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Inhibition of mTOR signaling by quercetin in cancer treatment and prevention.

    Bruning, Ansgar

    Anti-cancer agents in medicinal chemistry

    2012  Volume 13, Issue 7, Page(s) 1025–1031

    Abstract: Quercetin is an abundant micronutrient in our daily diet. Several beneficial health effects are associated with the dietary uptake of this bioflavonoid, including alleviating effects on chronic inflammation and atherosclerosis. A variety of in vitro data ...

    Abstract Quercetin is an abundant micronutrient in our daily diet. Several beneficial health effects are associated with the dietary uptake of this bioflavonoid, including alleviating effects on chronic inflammation and atherosclerosis. A variety of in vitro data indicate a possible use of quercetin for cancer treatment purposes through its interaction with multiple cancer-related pathways. Among these, recent data reveal that quercetin can inhibit mTOR activity in cancer cells. Inhibition of the mTOR signaling pathway by quercetin has directly been described and can further be deduced from its interference with PI3K-dependent Akt stimulation, AMP-dependent protein kinase activation and hamartin upregulation. The ability of quercetin to interfere with both mTOR activity and activation of the PI3K/Akt signaling pathway gives quercetin the advantage to function as a dual-specific mTOR/PI3K inhibitor. The mTOR complex, often hyperactivated in cancer, is a crucial regulator of homeostasis controlling essential pathways leading to cell growth, protein biosynthesis and autophagy. The ability of quercetin to inhibit mTOR activity by multiple pathways makes this otherwise safe bioflavonoid an interesting tool for the treatment of cancers and other diseases associated with mTOR deregulation.
    MeSH term(s) Animals ; Antioxidants/pharmacology ; Humans ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/prevention & control ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors ; Proto-Oncogene Proteins c-akt/metabolism ; Quercetin/pharmacology ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/metabolism
    Chemical Substances Antioxidants ; Protein Kinase Inhibitors ; Quercetin (9IKM0I5T1E) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2012-09-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2217610-X
    ISSN 1875-5992 ; 1871-5206
    ISSN (online) 1875-5992
    ISSN 1871-5206
    DOI 10.2174/18715206113139990114
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Oxidizing to death: disulfiram for cancer cell killing.

    Brüning, Ansgar / Kast, Richard E

    Cell cycle (Georgetown, Tex.)

    2014  Volume 13, Issue 10, Page(s) 1513–1514

    Language English
    Publishing date 2014-04-22
    Publishing country United States
    Document type Comment ; Editorial
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.4161/cc.28959
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Misfolded proteins: from little villains to little helpers in the fight against cancer.

    Brüning, Ansgar / Jückstock, Julia

    Frontiers in oncology

    2015  Volume 5, Page(s) 47

    Abstract: The application of cytostatic drugs targeting the high proliferation rates of cancer cells is currently the most commonly used treatment option in cancer chemotherapy. However, severe side effects and resistance mechanisms may occur as a result of such ... ...

    Abstract The application of cytostatic drugs targeting the high proliferation rates of cancer cells is currently the most commonly used treatment option in cancer chemotherapy. However, severe side effects and resistance mechanisms may occur as a result of such treatment, possibly limiting the therapeutic efficacy of these agents. In recent years, several therapeutic strategies have been developed that aim at targeting not the genomic integrity and replication machinery of cancer cells but instead their protein homeostasis. During malignant transformation, the cancer cell proteome develops vast aberrations in the expression of mutated proteins, oncoproteins, drug- and apoptosis-resistance proteins, etc. A complex network of protein quality-control mechanisms, including chaperoning by heat shock proteins (HSPs), not only is essential for maintaining the extravagant proteomic lifestyle of cancer cells but also represents an ideal cancer-specific target to be tackled. Furthermore, the high rate of protein synthesis and turnover in certain types of cancer cells can be specifically directed by interfering with the proteasomal and autophagosomal protein recycling and degradation machinery, as evidenced by the clinical application of proteasome inhibitors. Since proteins with loss of their native conformation are prone to unspecific aggregations and have proved to be detrimental to normal cellular function, specific induction of misfolded proteins by HSP inhibitors, proteasome inhibitors, hyperthermia, or inducers of endoplasmic reticulum stress represents a new method of cancer cell killing exploitable for therapeutic purposes. This review describes drugs - approved, repurposed, or under investigation - that can be used to accumulate misfolded proteins in cancer cells, and particularly focuses on the molecular aspects that lead to the cytotoxicity of misfolded proteins in cancer cells.
    Language English
    Publishing date 2015-02-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2015.00047
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cbfa1/Runx2-transduced adult adipose stem cells on biodegradable scaffolds for segmental bone defect repair.

    Brüning, Ansgar / Mylonas, Ioannis

    The Journal of surgical research

    2013  Volume 185, Issue 1, Page(s) e67–8

    MeSH term(s) Adipose Tissue/metabolism ; Animals ; Bone Diseases/therapy ; Core Binding Factor Alpha 1 Subunit/metabolism ; Periosteum/surgery ; Stem Cell Transplantation ; Stem Cells/metabolism ; Surgical Flaps
    Chemical Substances Core Binding Factor Alpha 1 Subunit
    Language English
    Publishing date 2013-11
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 80170-7
    ISSN 1095-8673 ; 0022-4804
    ISSN (online) 1095-8673
    ISSN 0022-4804
    DOI 10.1016/j.jss.2012.06.055
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Selective occlusion of the portal vein while maintaining hepatic artery blood flow during partial hepatectomy: a new method for preventing ischemia-reperfusion injury?

    Brüning, Ansgar / Mylonas, Ioannis

    The Journal of surgical research

    2013  Volume 185, Issue 1, Page(s) e45–8

    MeSH term(s) Animals ; Female ; Hepatectomy/methods ; Hepatic Artery/physiology ; Liver/blood supply ; Liver Circulation/physiology ; Liver Regeneration/physiology ; Male ; Portal System/surgery ; Portal Vein/physiology ; Reperfusion Injury/prevention & control
    Language English
    Publishing date 2013-11
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 80170-7
    ISSN 1095-8673 ; 0022-4804
    ISSN (online) 1095-8673
    ISSN 0022-4804
    DOI 10.1016/j.jss.2012.09.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Induction of apoptosis in cervical cancer cells by the duplex drug 5-FdU-ECyd, coupling 2'-deoxy-5-fluorouridine and 3'-C-ethinylcytidine.

    Schott, Sarah / Brüning, Ansgar

    Gynecologic oncology

    2014  Volume 135, Issue 2, Page(s) 342–348

    Abstract: Objective: Therapeutic options are limited for patients with advanced cervical cancer, and more effective drugs with favorable side-effect profiles are needed. We developed a nucleoside analogue duplex drug (5-FdU-ECyd), in which the DNA synthesis ... ...

    Abstract Objective: Therapeutic options are limited for patients with advanced cervical cancer, and more effective drugs with favorable side-effect profiles are needed. We developed a nucleoside analogue duplex drug (5-FdU-ECyd), in which the DNA synthesis inhibitor 5-fluorodeoxyuridine is coupled to the RNA synthesis inhibitor 3'-C-ethinylcytidine. We therefore aimed to test its efficacy in cervical carcinoma cells in vitro and to establish its mechanism of action.
    Methods: The cytotoxic effects of 5-FdU-ECyd on cervical cancer cells were assessed using the MTT assay, clonality assays, FACScan analysis, and its effect on cancer cell spheroids. Mechanisms of cell death were analyzed by Western blotting for apoptosis and autophagy pathways and mitochondrial membrane potential.
    Results: HeLa, CaSki, SiHa, and Me180 cervical cancer cells were highly sensitive to 5-FdU-ECyd in both 2- and 3-dimensional cancer models. The cell death induced by 5-FdU-ECyd was associated with characteristic morphological and biochemical signs of apoptosis, including nuclear chromatin condensation and fragmentation, PARP cleavage, and a breakdown in mitochondrial membrane potential. 5-FdU-ECyd treatment led to an early S-phase arrest and drastically reduced expression of the anti-apoptosis protein Mcl-1 and increased signaling via the JNK and p38 MAPK pathways.
    Conclusions: 5-FdU-ECyd is highly cytotoxic in cervical cancer cells and exploits apoptosis pathways that might be specific to cancer, but not normal cells. 5-FdU-ECyd might represent a new chemotherapeutic option for patients with advanced or treatment refractory cervical cancer.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Carcinoma, Squamous Cell ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Female ; HeLa Cells ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Oligonucleotides/pharmacology ; Uterine Cervical Neoplasms
    Chemical Substances 2'-deoxy-5-fluorouridylyl-(3'-5')-3'-C-ethynylcytidine ; Antineoplastic Agents ; Oligonucleotides
    Language English
    Publishing date 2014-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 801461-9
    ISSN 1095-6859 ; 0090-8258
    ISSN (online) 1095-6859
    ISSN 0090-8258
    DOI 10.1016/j.ygyno.2014.08.034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The metastasis-associated gene MTA3 is an independent prognostic parameter in uterine non-endometrioid carcinomas.

    Mylonas, Ioannis / Brüning, Ansgar

    Histopathology

    2012  Volume 60, Issue 4, Page(s) 665–670

    MeSH term(s) Aged ; Carcinoma/metabolism ; Carcinoma/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Proteins/metabolism ; Prognosis ; Uterine Neoplasms/metabolism ; Uterine Neoplasms/pathology ; Uterus/pathology
    Chemical Substances MTA3 protein, human ; Neoplasm Proteins
    Language English
    Publishing date 2012-03
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 131914-0
    ISSN 1365-2559 ; 0309-0167
    ISSN (online) 1365-2559
    ISSN 0309-0167
    DOI 10.1111/j.1365-2559.2011.04103.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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