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Genomes and Genes | Klaus StrebhardtSummaryAffiliation: Frankfurt am Main Country: Germany Publications
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Publications
Paul Ehrlich's magic bullet concept: 100 years of progressKlaus Strebhardt
Klaus Strebhardt is at the Department of Obstetrics and Gynaecology, School of Medicine, J W Goethe University, Theodour Stern Kai 7, 60590 Frankfurt, Germany
Nat Rev Cancer 8:473-80. 2008..His postulate of creating 'magic bullets' for use in the fight against human diseases inspired generations of scientists to devise powerful molecular cancer therapeutics...
The biological relevance of FHL2 in tumour cells and its role as a putative cancer targetKai Kleiber
Department of Gynecology and Obstetrics, Medical School, J W Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
Anticancer Res 27:55-61. 2007..Since transcription factors control all fundamental developmental and homeostatic processes, transcriptional cofactors like FHL2 are likely to contribute to human carcinogenesis and are of clinical importance in various forms of cancer...- Small molecules keep mitotic kinases in checkKlaus Strebhardt
Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
ACS Chem Biol 1:683-6. 2006..Compounds targeting the nucleotide binding pockets of polo-like kinases in particular provide significant new insights into the molecular mechanisms controlling cell-division phenotypes... - Multifaceted polo-like kinases: drug targets and antitargets for cancer therapyKlaus Strebhardt
Department of Obstetrics and Gynaecology, School of Medicine, J W Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
Nat Rev Drug Discov 9:643-60. 2010..In this article, recent insights into the biology of PLKs will be reviewed, with an emphasis on their role in malignant transformation, and progress in the development of small-molecule PLK1 inhibitors will be examined... - Targeting polo-like kinase 1 for cancer therapyKlaus Strebhardt
Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Theodore Stern Kai 7, 60590 Frankfurt, Germany
Nat Rev Cancer 6:321-30. 2006..We address the structural features of the kinase domain and the unique polo-box domain of PLK1 that are most suited for drug development and discuss our current understanding of the therapeutic potential of PLK1... - Effect of RNA silencing of polo-like kinase-1 (PLK1) on apoptosis and spindle formation in human cancer cellsBirgit Spänkuch-Schmitt
Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Frankfurt, Germany
J Natl Cancer Inst 94:1863-77. 2002..To investigate the role of PLK1 in neoplastic proliferation, we used the technique of RNA interference... - Down-regulation of Polo-like kinase 1 elevates drug sensitivity of breast cancer cells in vitro and in vivoBirgit Spänkuch
Department of Obstetrics and Gynecology, Medical School, J W Goethe University, Frankfurt, Germany
Cancer Res 66:5836-46. 2006.... - Long-term downregulation of Polo-like kinase 1 increases the cyclin-dependent kinase inhibitor p21(WAF1/CIP1)Nina Naomi Kreis
Department of Gynecology and Obstetrics, School of Medicine, JW Goethe University, Frankfurt, Germany
Cell Cycle 8:460-72. 2009..Importantly, HeLa cells with reduced level of Plk1, which induces an increase of p21, p73 and Bax, are more sensitive to some chemotherapeutic agents, such as cisplatin... - Iressa (ZD 1839) inhibits phosphorylation of three different downstream signal transducers in head and neck cancer (SCCHN)Markus Hambek
Department of Otorhinolaryngology, School of Medicine, J. W. Goethe University, 60590 Frankfurt, Germany
Anticancer Res 25:1871-5. 2005..We conclude that Iressa has a high potency to inhibit nuclear gene transcription responsible for cell cycle progression. Furthermore, dose reduction of Iressa in the case of toxicity may not severely influence the response to treatment... - Cancer inhibition in nude mice after systemic application of U6 promoter-driven short hairpin RNAs against PLK1Birgit Spänkuch
Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
J Natl Cancer Inst 96:862-72. 2004..We used a xenograft mouse model to determine whether an RNA interference-based strategy that used short hairpin RNAs (shRNAs) to suppress PLK1 expression could inhibit tumor growth in vivo... 
Tumor inhibition by genomically integrated inducible RNAi-cassettesSven Kappel
Department of Gynecology and Obstetrics, School of Medicine, J.W. Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany
Nucleic Acids Res 34:4527-36. 2006..Taken together, our data revealed that genomically integrated RNAi-elements are suitable to hamper tumor growth by conditional expression of shRNA...- FHL2 regulates cell cycle-dependent and doxorubicin-induced p21Cip1/Waf1 expression in breast cancer cellsBernd T Martin
Department of Gynecology and Obstetrics, Medical School, J W Goethe University, Frankfurt, Germany
Cell Cycle 6:1779-88. 2007.... - Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxolIlija Androic
Department of Obstetrics and Gynecology, School of Medicine, J, W, Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
BMC Cancer 8:391. 2008..Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers... - Biological impact of freezing Plk1 in its inactive conformation in cancer cellsSarah Keppner
Department of Obstetrics and Gynecology, Medical School, Goethe University, Frankfurt, Germany
Cell Cycle 9:761-73. 2010..This study suggests that Plk1 kinase inhibitors targeting the inactive conformation of Plk1 may be considered for the development of cancer therapeutics... - Polo-like kinase 1-mediated phosphorylation stabilizes Pin1 by inhibiting its ubiquitination in human cellsFrank Eckerdt
Department of Gynecology and Obstetrics, J W Goethe University, Theodor Stern Kai 7, Frankfurt D 60590, Germany
J Biol Chem 280:36575-83. 2005..Since previous reports suggested that Plk1 is a substrate of Pin1, our work adds a new dimension to this interaction of two important mitotic regulators... - Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cellsMonika Raab
Department of Obstetrics and Gynecology, School of Medicine, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
Nat Commun 2:395. 2011..Responses to Plk1-depletion, both in cultured primary cells and in our iKD-mouse model, correspond well and thus provide the basis for using validated iKD mice in predicting responses to therapeutic interventions... - Silencing of the HER2/neu gene by siRNA inhibits proliferation and induces apoptosis in HER2/neu-overexpressing breast cancer cellsTimo Faltus
Department of Obstetrics and Gynecology, Medical School, J. W. Goethe University, Theodor-Stern-Kai 7, Frankfurt 60590, Germany
Neoplasia 6:786-95. 2004..Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as antiproliferative agents that display activity against neoplastic cells at very low doses... - Conditional inhibition of cancer cell proliferation by tetracycline-responsive, H1 promoter-driven silencing of PLK1Yves Matthess
Department of Gynecology and Obstetrics, School of Medicine, JW Goethe-University, Theodor-Stern-Kai 7, Haus 15, Frankfurt 60590, Germany
Oncogene 24:2973-80. 2005..Our data indicate that an inducible transcription system for shRNAs based on the human H1 promoter could be a versatile tool for controlled gene silencing in vitro... - Polo-box domain inhibitor poloxin activates the spindle assembly checkpoint and inhibits tumor growth in vivoJuping Yuan
Department of Gynecology and Obstetrics, School of Medicine, J W Goethe University, Frankfurt, Germany
Am J Pathol 179:2091-9. 2011..The data highlight that targeting the PBD by Poloxin is a powerful approach for selectively inhibiting Plk1 function in vitro and in vivo... - Reduction of cisplatin dosage by ZD 1839Markus Hambek
Department of Otorhonolaryngology, School of Medicine, J. W. Goethe University, 60590 Frankfurt, Germany
Anticancer Res 25:3985-8. 2005..Adding ZD 1839 to CDDP may therefore enable CDDP treatment at a lower dose without compromising antiproliferative effects... - Cooperative phosphorylation including the activity of polo-like kinase 1 regulates the subcellular localization of cyclin B1Juping Yuan
Department of Obstetrics and Gynecology, JW Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
Oncogene 21:8282-92. 2002..Still, multiple serine mutations are required to prevent nuclear translocation completely indicating that orchestrated phosphorylation within the CRS triggers rapid import of cyclin B1... - Efficient internalization of the polo-box of polo-like kinase 1 fused to an Antennapedia peptide results in inhibition of cancer cell proliferationJuping Yuan
Department of Obstetrics and Gynecology, Medical School, J.W. Goethe-University, 60590 Frankfurt, Germany
Cancer Res 62:4186-90. 2002..The treatment caused mitotic arrest, misaligned chromosomes, and multiple centrosomes. Taken together, membrane-permeable polo-box peptides inhibit cancer cell proliferation efficiently... - Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8 activityYves Matthess
Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Frankfurt, Germany
Mol Cell Biol 30:5726-40. 2010..Finally, this new mechanism may also contribute to tumorigenesis... - Silencing of mammalian genes by tetracycline-inducible shRNA expressionSven Kappel
Department of Gynaecology and Obstetrics, School of Medicine, J W Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt Main, Germany
Nat Protoc 2:3257-69. 2007..The entire protocol (preparation of constructs, generation of stable cell lines and functional analysis) can be completed in 3 months... - Functional and spatial regulation of mitotic centromere-associated kinesin by cyclin-dependent kinase 1Mourad Sanhaji
Department of Gynecology and Obstetrics, School of Medicine, J W Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
Mol Cell Biol 30:2594-607. 2010..This is the first study demonstrating that Cdk1 regulates the localization and activity of MCAK in mitosis by directly phosphorylating the catalytic core domain of MCAK... - Downregulation of human polo-like kinase activity by antisense oligonucleotides induces growth inhibition in cancer cellsBirgit Spänkuch-Schmitt
Department of Obstetrics and Gynecology, School of Medicine, JW Goethe University, Theodor Stern Kai 7, 60596 Frankfurt, Germany
Oncogene 21:3162-71. 2002..Considerable antitumor activity was observed in vivo against A549 cells. This study suggests that antisense inhibitors targeted against PLK1 at well tolerated doses may be considered as a cancer therapeutic agent... - Polo-like kinases and oncogenesisFrank Eckerdt
Department of Gynecology and Obstetrics, Medical School, JW Goethe University, Theodor Stern Kai 7, Frankfurt D 60590, Germany
Oncogene 24:267-76. 2005..In this review, we shall discuss the roles of Plks in oncogenesis and Plk1 as a target for therapeutic intervention against cancer... - STAT 3 activation in head and neck squamous cell carcinomas is controlled by the EGFRMarkus Hambek
Department of Otorhinolaryngology, School of Medicine, J W Goethe University, 60590 Frankfurt, Germany
Anticancer Res 24:3881-6. 2004..These findings provide evidence that STAT 3 signal activity in head and neck carcinomas, which is partially responsible for proliferative activity, can be controlled via the EGFR... - Expression of polo-like kinase (PLK1) in thin melanomas: a novel marker of metastatic diseaseLucas Kneisel
Department of Dermatology, Johann Wolfgang Goethe-University, School of Medicine, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
J Cutan Pathol 29:354-8. 2002..35% vs. 4.53%; p = 0.150473). CONCLUSIONS: Our results suggest that PLK1 expression in thin melanomas is a reliable marker to identify patients at high risk for metastases... - Demands on caring relatives of head and neck cancer patientsMehran Baghi
Department of Otorhinolaryngology, School of Medicine, J W Goethe University, Frankfurt, Germany
Laryngoscope 117:712-6. 2007.... - The role of early expression of inducible nitric oxide synthase in human breast cancerSibylle Loibl
Department of Gynaecology and Obstetrics, J W Goethe University of Frankfurt, Theodor Stern Kai 7 9, 60590 Frankfurt am Main, Germany
Eur J Cancer 41:265-71. 2005..8% versus 67.1%; P=0.049; log-rank test). To date, this is the largest analysis of i-NOS expression in breast cancer patients and the only study to assess survival... - Investigations on the inducible and endothelial nitric oxide synthases in human breast cancer cell line MCF-7 - estrogen has an influence on e-NOS, but not on i-NOSSibylle Loibl
Department of Gynecology and Obstetrics, University of Frankfurt, Theodor Stern Kai 7 9, 60590 Frankfurt am Main, Germany
Pathol Res Pract 202:1-7. 2006..In conclusion, e-NOS and i-NOS are weakly expressed in the MCF-7 cell line, but are stimulated differently. The MCF-7 cell may contain both a constitutive NOS and an inducible NOS... - Expression of endothelial and inducible nitric oxide synthase in benign and malignant lesions of the breast and measurement of nitric oxide using electron paramagnetic resonance spectroscopySibylle Loibl
Department of Gynecology and Obstetrics, University of Frankfurt, Frankfurt am Main, Germany
Cancer 95:1191-8. 2002..An increased NO concentration catalyzed by NO synthase (NOS) is cytotoxic and can promote apoptosis. The expression of endothelial NOS (e-NOS) and induced NOS (i-NOS) was examined in various breast tumors... - RNA interference-based gene silencing in mice: the development of a novel therapeutical strategyBirgit Spänkuch
Department of Obstetrics and Gynecology, Medical School, J W Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
Curr Pharm Des 11:3405-19. 2005..In summary, multiple lines of evidence indicate that RNAi seems to become a powerful tool for the fight against undesirable gene expression in human diseases... - Another look at imatinib mesylateKlaus Strebhardt
Department of Obstetrics and Gynecology, School of Medicine, J.W. Goethe University, Frankfurt, Germany
N Engl J Med 355:2481-2. 2006 - Identification of high risk breast-cancer patients by gene expression profilingAndre Ahr
Lancet 359:131-2. 2002..Our analysis identifies breast-cancer patients with a high risk of disease recurrence, and could act as a first step towards improved patient-adapted therapy... - Trastuzumab-modified nanoparticles: optimisation of preparation and uptake in cancer cellsIsabel Steinhauser
Institute for Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe-University, Max-von-Laue-Strasse 9, D-60438 Frankfurt, Germany
Biomaterials 27:4975-83. 2006..These data provide the basis for the development of stable and biological active carrier systems for directed targeting of tumour cells using trastuzumab-conjugated HSA nanoparticles... - Inhibition of polo-like kinase 1 by blocking polo-box domain-dependent protein-protein interactionsWolfgang Reindl
Department of Molecular Biology, Max Planck Institute of Biochemistry and Munich Center for Integrated Protein Science CiPS M, Martinsried, Germany
Chem Biol 15:459-66. 2008..Our data validate the Plk1 PBD as an anticancer target and provide a rationale for developing thymoquinone derivatives as anticancer drugs... - Highly specific HER2-mediated cellular uptake of antibody-modified nanoparticles in tumour cellsHeidrun Wartlick
Institute for Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe-University, Marie-Curie-Strasse 9, D-60439 Frankfurt, Germany
J Drug Target 12:461-71. 2004..To our knowledge, this is the first study that demonstrates the effective and specific targeting of protein-based nanoparticles as drug delivery systems... - Polo-like kinase 1: target and regulator of anaphase-promoting complex/cyclosome-dependent proteolysisFrank Eckerdt
Department of Pharmacology, University of Colorado School of Medicine, Denver, Colorado 80262, USA
Cancer Res 66:6895-8. 2006..The mechanisms underlying the control of genomic stability by Plk1 are discussed in this review... - Polo-like kinase 1: target and regulator of transcriptional controlBernd T Martin
Department of Gynecology and Obstetric, Medical School, J.W. Goethe-University, Frankfurt, Germany
Cell Cycle 5:2881-5. 2006..Furthermore, transcription factors regulated by Plk1 will also be subject of discussion... - Antiproliferative activity of bortezomib alone and in combination with cisplatin or docetaxel in head and neck squamous cell carcinoma cell linesJens Wagenblast
ENT Department, Medical School, Goethe University, Frankfurt am Main, Germany
J Cancer Res Clin Oncol 134:323-30. 2008.... - Tumour cell delivery of antisense oligonuclceotides by human serum albumin nanoparticlesHeidrun Wartlick
Institute for Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe-University, Marie-Curie-Strasse 9, D-60439 Frankfurt, Germany
J Control Release 96:483-95. 2004.... - Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cellsJuping Yuan
Department of Gynaecology and Obstetrics, Medical School, JW Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany
Oncogene 23:5843-52. 2004..These results indicate that siRNAs against cyclin B1 could become a powerful antiproliferative tool in future antitumor therapy...