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Artigo Acesso aberto Revisado por pares

Felix Hoppe‐Seyler, Karin Butz, Claudia Rittmüller, Magnus von Knebel Doeberitz,

... and enzymatically active luciferase extracts Get access Felix Hoppe-Seyler, Felix Hoppe-Seyler Institut für Virusforschung/ATV, Deutsches KrebsforschungszentrumIm Neuenheimer Feld ...

Tópico(s): Bacteriophages and microbial interactions

1991 - Oxford University Press | Nucleic Acids Research

Artigo Acesso aberto Revisado por pares

Bettina Fussbroich, Nina Wagener, Stephan Macher‐Goeppinger, Axel Benner, Maria Fälth, Holger Sültmann, Angela Holzer, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler,

The Enhancer of Zeste 2 (EZH2) protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi)-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection ...

Tópico(s): Cancer-related gene regulation

2011 - Public Library of Science | PLoS ONE

Artigo Acesso aberto Revisado por pares

Demissew Shenegelegn Mern, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler, Jens Hasskarl, Barbara Burwinkel,

Inhibitors of differentiation or DNA binding (Id) proteins have been shown to be involved in tumor growth, invasiveness, metastasis, and angiogenesis. Overexpression of Id proteins, especially Id1, correlates with unfavorable clinical prognosis. Thus, they are attractive molecular targets for anticancer therapy. Overexpression of Id proteins mediates breast cancer metastasis to lung. Targeting Id1 and Id3 expression in breast cancer cells reduces breast cancer metastasis in animal models. Different ...

Tópico(s): Ubiquitin and proteasome pathways

2010 - Springer Science+Business Media | Breast Cancer Research and Treatment

Artigo Acesso aberto Revisado por pares

Jenny Leitz, Miriam Reuschenbach, Claudia Lohrey, Anja Honegger, Rosita Accardi, Massimo Tommasino, Manuel Llano, Magnus von Knebel Doeberitz, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler,

The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently ...

Tópico(s): Cancer-related Molecular Pathways

2014 - Public Library of Science | PLoS Pathogens

Artigo Acesso aberto Revisado por pares

Anja Honegger, Jenny Leitz, Julia Bulkescher, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler,

The human papillomavirus (HPV) E6/E7 oncogenes play a crucial role in the HPV-induced carcinogenesis. In this study, the authors investigated whether silencing of endogenous HPV E6/E7 expression may influence the contents or amounts of extracellular microvesicles (eMVs) released from HPV-positive cancer cells. It was found that eMVs secreted from HeLa cells are enriched for Survivin protein. RNA interference studies revealed that maintenance of both intracellular and microvesicular Survivin amounts ...

Tópico(s): Genital Health and Disease

2013 - Wiley | International Journal of Cancer

Artigo Acesso aberto Revisado por pares

Anja Honegger, Daniela Schilling, Sandra Bastian, Jasmin Sponagel, Vladimir Kuryshev, Holger Sültmann, Martin Scheffner, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler,

Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome-wide analyses, we investigate whether the intracellular and exosomal miRNA compositions of HPV-positive cancer cells are dependent on endogenous E6/E7 oncogene expression. Deep sequencing studies combined with qRT-PCR analyses show that E6/E7 silencing significantly affects ten of the 52 most abundant intracellular miRNAs in HPV18-positive ...

Tópico(s): Circular RNAs in diseases

2015 - Public Library of Science | PLoS Pathogens

Artigo Acesso aberto Revisado por pares

Christina Stutz, Eileen Reinz, Anja Honegger, Julia Bulkescher, Johannes Schweizer, Katia Zanier, Gilles Travé, Claudia Lohrey, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler,

Oncogenic types of human papillomaviruses (HPVs) cause cervical cancer and other malignancies in humans. The HPV E6 oncoprotein is considered to be an attractive therapeutic target since its inhibition can lead to the apoptotic cell death of HPV-positive cancer cells. The HPV type 16 (HPV16) E6-binding peptide pep11, and variants thereof, induce cell death specifically in HPV16-positive cancer cells. Although they do not encompass the LxxLL binding motif found in cellular HPV16 E6 interaction partners, ...

Tópico(s): Hepatitis B Virus Studies

2015 - Public Library of Science | PLoS ONE

Artigo Acesso aberto Revisado por pares

Julia A. Braun, Anja L. Herrmann, Johanna I. Blase, Kristin Frensemeier, Julia Bulkescher, Martin Scheffner, Bruno Galy, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler,

The malignant growth of human papillomavirus (HPV)‐positive cancer cells is dependent on the continuous expression of the viral E6/E7 oncogenes. Here, we examined the effects of iron deprivation on the phenotype of HPV‐positive cervical cancer cells. We found that iron chelators, such as the topical antifungal agent ciclopirox (CPX), strongly repress HPV E6/E7 oncogene expression, both at the transcript and protein level. CPX efficiently blocks the proliferation of HPV‐positive cancer cells by inducing ...

Tópico(s): Genomics, phytochemicals, and oxidative stress

2019 - Wiley | International Journal of Cancer

Artigo Acesso aberto Revisado por pares

Felicitas Bossler, Bianca J. Kuhn, Thomas Günther, Stephen Kraemer, Prajakta Khalkar, Svenja Adrian, Claudia Lohrey, Angela Holzer, Mitsugu Shimobayashi, Matthias Dürst, Arnulf Mayer, Frank Rösl, Adam Grundhoff, Jeroen Krijgsveld, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler,

Oncogenic HPV types are major human carcinogens. Under hypoxia, HPV-positive cancer cells can repress the viral E6/E7 oncogenes and induce a reversible growth arrest. This response could contribute to therapy resistance, immune evasion, and tumor recurrence upon reoxygenation. Here, we uncover evidence that HPV oncogene repression is mediated by hypoxia-induced activation of canonical PI3K/mTORC2/AKT signaling. AKT-dependent downregulation of E6/E7 is only observed under hypoxia and occurs, at least ...

Tópico(s): Histone Deacetylase Inhibitors Research

2019 - American Society for Microbiology | mBio

Revisão Acesso aberto Revisado por pares

Felicitas Bossler, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler,

Human papillomavirus (HPV)-induced cancers will remain a significant clinical challenge for decades. Thus, the development of novel treatment strategies is urgently required, which should benefit from improving our understanding of the mechanisms of HPV-induced cell transformation. This should also include analyses of hypoxic tumor cells, which represent a major problem for cancer therapy. Recent evidence indicates that the PI3K/AKT/mTOR network plays a key role for the virus/host cell crosstalk ...

Tópico(s): PI3K/AKT/mTOR signaling in cancer

2019 - Multidisciplinary Digital Publishing Institute | International Journal of Molecular Sciences

Artigo Acesso aberto

Karin Hoppe‐Seyler, Anja Honegger, Felicitas Bossler, Jasmin Sponagel, Julia Bulkescher, Claudia Lohrey, Felix Hoppe‐Seyler,

... 1 , Julia Bulkescher 1 , Claudia Lohrey 1 and Felix Hoppe-Seyler 1 1 Molecular Therapy of Virus-Associated Cancers ( ... Research Center (DKFZ), 69120 Heidelberg, Germany Correspondence to: Felix Hoppe-Seyler, email: hoppe-seyler@dkfz.de Keywords: human papillomavirus; ...

Tópico(s): Virus-based gene therapy research

2017 - Impact Journals LLC | Oncotarget

Artigo

Anja Honegger, Daniela Schilling, Holger Sültmann, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler,

Oncogenic types of human papillomaviruses (HPVs) are closely linked to the development of anogenital and head and neck cancerscancers . The expression of the viral E6 and E7 genes is crucial for the transforming activities of HPVs. There is accumulating evidence that the HPV E6/E7 oncogenes can profoundly affect the cellular microRNA (miRNA) composition. Since alterations of miRNA expression levels can contribute to cancer development and maintenance, it will be important to understand in depth the ...

Tópico(s): RNA Interference and Gene Delivery

2017 - Springer Science+Business Media | Methods in molecular biology

Artigo Revisado por pares

Sophie Laurenson, Mark R. Pett, Karin Hoppe‐Seyler, Claudia Denk, Felix Hoppe‐Seyler, Nick Coleman, Paul Ko Ferrigno,

Protein microarrays represent an emerging technology that promises to facilitate high-throughput proteomics. The major goal of this technology is to employ peptides, full-length proteins, antibodies, and small molecules to simultaneously screen thousands of targets for potential protein-protein interactions or modifications of the proteome. This article describes the performance of a set of peptide aptamers specific for the human papillomavirus (HPV) type 16 oncoproteins E6 and E7 in a microarray ...

Tópico(s): Bacteriophages and microbial interactions

2010 - Elsevier BV | Analytical Biochemistry

Artigo Acesso aberto Revisado por pares

Katia Zanier, Christina Stutz, Susanne Kintscher, Eileen Reinz, Peter Sehr, Julia Bulkescher, Karin Hoppe‐Seyler, Gilles Travé, Felix Hoppe‐Seyler,

The HPV E6 oncoprotein maintains the malignant phenotype of HPV-positive cancer cells and represents an attractive therapeutic target. E6 forms a complex with the cellular E6AP ubiquitin ligase, ultimately leading to p53 degradation. The recently elucidated x-ray structure of a HPV16 E6/E6AP complex showed that HPV16 E6 forms a distinct binding pocket for E6AP. This discovery raises the question whether the E6AP binding pocket is druggable, i. e. whether it provides a docking site for functional ...

Tópico(s): Virus-based gene therapy research

2014 - Public Library of Science | PLoS ONE

Artigo Acesso aberto

E. Baumann, A. Kossel,

... GesellschaftVolume 28, Issue 4 p. 1147-1192 Nekrolog Felix Hoppe-Seyler E. Baumann, E. Baumann Physiologische Chemie (in 4 ...

Tópico(s): Chemistry and Chemical Engineering

1895 - Wiley | Berichte der deutschen chemischen Gesellschaft

Artigo Revisado por pares

Axel Haferkamp, Jens Bedke, Caroline Vetter, Maria Pritsch, Nina Wagener, Stephan Buse, Irena Crnković‐Mertens, Karin Hoppe‐Seyler, Stephan Macher‐Goeppinger, Felix Hoppe‐Seyler, Frank Autschbach, Markus Hohenfellner,

To assess the protein expression of Livin, an apoptosis inhibitor, in renal cell carcinoma (RCC) and to determine its prognostic relevance.Immunohistochemical staining for Livin was performed in tissue microarrays (TMAs), including tumour tissue cores, from patients with RCC who had undergone renal surgery. In 682 TMAs cytoplasmatic staining intensity and nuclear staining quantity were evaluated, and the association of Livin expression with progression-free survival (PFS) and cancer-specific survival ( ...

Tópico(s): Pancreatic and Hepatic Oncology Research

2008 - Wiley | BJU International

Artigo Acesso aberto Revisado por pares

Karin Hoppe‐Seyler, Peter Sauer, Claudia Lohrey, Felix Hoppe‐Seyler,

The inhibitors of pyrimidine synthesis, leflunomide and FK778, have been reported to exert broad antiviral effects, in addition to their immunosuppressive activities. Their possible therapeutic benefit for transplantation medicine is currently discussed, because they also block the replication of human cytomegalovirus and human polyomavirus BK, which both cause important complications in transplant recipients. Here, we show that leflunomide and FK778 strongly enhance hepatitis B virus (HBV) replication ...

Tópico(s): Polyomavirus and related diseases

2012 - Lippincott Williams & Wilkins | Hepatology

Artigo Acesso aberto Revisado por pares

Anja L. Herrmann, Bianca J. Kuhn, Angela Holzer, Jeroen Krijgsveld, Karin Hoppe‐Seyler, Felix Hoppe‐Seyler,

The iron-chelating drug ciclopirox (CPX) may possess therapeutic potential for cancer treatment, including cervical cancer. As is observed for other chemotherapeutic drugs, CPX can induce senescence or apoptosis in cervical cancer cells which could differently affect their therapy response. The present study aims to gain insights into the determinants which govern the switch between senescence and apoptosis in cervical cancer cells. We performed proteome analyses, proliferation studies by live-cell ...

Tópico(s): MicroRNA in disease regulation

2021 - Multidisciplinary Digital Publishing Institute | Cancers

Artigo Acesso aberto Revisado por pares

Nina Wagener, Stephan Macher‐Goeppinger, Maria Pritsch, Johannes Hüsing, Karin Hoppe‐Seyler, Peter Schirmacher, Jesco Pfitzenmaier, Axel Haferkamp, Felix Hoppe‐Seyler, Markus Hohenfellner,

Abstract Background The enhancer of zeste homolog 2 ( EZH2 ) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). Methods EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical ...

Tópico(s): Epigenetics and DNA Methylation

2010 - BioMed Central | BMC Cancer

Revisão Revisado por pares

Karin Hoppe‐Seyler, Felicitas Bossler, Julia A. Braun, Anja L. Herrmann, Felix Hoppe‐Seyler,

Human papillomavirus (HPV)-induced cancers are expected to remain a major health problem worldwide for decades. The growth of HPV-positive cancer cells depends on the sustained expression of the viral E6 and E7 oncogenes which act in concert with still poorly defined cellular alterations. E6/E7 constitute attractive therapeutic targets since E6/E7 inhibition rapidly induces senescence in HPV-positive cancer cells. This cellular response is linked to the reconstitution of the antiproliferative p53 ...

Tópico(s): Cancer-related Molecular Pathways

2017 - Elsevier BV | Trends in Microbiology

Artigo Acesso aberto Revisado por pares

Nina Wagener, Irena Crnković‐Mertens, Caroline Vetter, Stephan Macher-Göppinger, Jens Bedke, Elisabeth Gröne, H. Zentgraf, Maria Pritsch, Karin Hoppe‐Seyler, Stephan Buse, Axel Haferkamp, Frank Autschbach, Markus Hohenfellner, Felix Hoppe‐Seyler,

The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, ...

Tópico(s): RNA Interference and Gene Delivery

2007 - Springer Nature | British Journal of Cancer

Artigo Acesso aberto Revisado por pares

Daniela Holland, Karin Hoppe‐Seyler, Bettina Schuller, Claudia Lohrey, Julia Maroldt, Matthias Dürst, Felix Hoppe‐Seyler,

Abstract The malignant phenotype of human papillomavirus (HPV)-positive cancer cells is maintained by the activity of the viral E6 and E7 genes. Here, we identified the polycomb group gene enhancer of zeste homologue 2 (EZH2) as a novel downstream target for the viral oncogenes in HPV-transformed cells. EZH2 expression was activated by HPV16 E7 at the transcriptional level via E7-mediated release of E2F from pocket proteins. RNA interference analyses showed that continuous EZH2 expression is required ...

Tópico(s): Cervical Cancer and HPV Research

2008 - American Association for Cancer Research | Cancer Research

Artigo Revisado por pares

Nina Wagener, Daniela Holland, Julia Bulkescher, Irena Crnković‐Mertens, Karin Hoppe‐Seyler, Hanswalter Zentgraf, Maria Pritsch, Stephan Buse, Jesco Pfitzenmaier, Axel Haferkamp, Markus Hohenfellner, Felix Hoppe‐Seyler,

Abstract The enhancer of zeste homolog 2 ( EZH2 ) gene has been recently linked to human malignancies where it may serve as a new target for cancer therapy. Here, we analyzed EZH2 expression in primary renal cell carcinoma (RCC) specimens and in nontumorous tissue samples from adult kidney. EZH2 transcripts were detectable in all RCC specimens examined. Expression levels were significantly higher in tumor tissue ( p ≤ 0.0001) than in samples from normal adult kidney. Moreover, inhibition of endogenous EZH2 ...

Tópico(s): RNA modifications and cancer

2008 - Wiley | International Journal of Cancer

Artigo Revisado por pares

Nina Wagener, Daniela Holland, Irena Crnković‐Mertens, Karin Hoppe‐Seyler, Hanswalter Zentgraf, Maria Pritsch, Stephan Buse, Jesco Pfitzenmaier, Axel Haferkamp, Markus Hohenfellner, Felix Hoppe‐Seyler,

... Buse, Jesco Pfitzenmaier, Axel Haferkamp, Markus Hohenfellner, and Felix Hoppe-Seyler Nina WagenerNina Wagener More articles by this author , ... author Markus Hohenfellner More articles by this author Felix Hoppe-Seyler More articles by this author Expand All Advertisement ...

Tópico(s): Epigenetics and DNA Methylation

2008 - Lippincott Williams & Wilkins | The Journal of Urology

Artigo Acesso aberto Revisado por pares

Karin Hoppe‐Seyler, Felicitas Bossler, Claudia Lohrey, Julia Bulkescher, Frank Rösl, Lars Jansen, Arnulf Mayer, Peter Vaupel, Matthias Dürst, Felix Hoppe‐Seyler,

Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and ...

Tópico(s): Cancer Research and Treatments

2017 - National Academy of Sciences | Proceedings of the National Academy of Sciences

Artigo Acesso aberto Revisado por pares

Karin Hoppe‐Seyler, Anja L. Herrmann, Antonia Däschle, Bianca J. Kuhn, Tobias D. Strobel, Claudia Lohrey, Julia Bulkescher, Jeroen Krijgsveld, Felix Hoppe‐Seyler,

Abstract Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. The viral E6/E7 oncogenes maintain the malignant growth of HPV‐positive cancer cells. Targeted E6/E7 inhibition results in efficient induction of cellular senescence, which could be exploited for therapeutic purposes. Here we show that viral E6/E7 expression is strongly downregulated by Metformin in HPV‐positive cervical cancer and head and neck cancer cells, both at the transcript and protein level. Metformin‐ ...

Tópico(s): Virus-based gene therapy research

2021 - Wiley | International Journal of Cancer

Revisão Revisado por pares

Felix Hoppe‐Seyler, Karin Butz,

Abstract Specific types of human papillomaviruses (HPVs) are closely associated with the development of cervical cancer. The transforming ability of these high‐risk HPV types depends on the expression of the viral E6 and E7 oncogenes. It is therefore of particular interest to elucidate the molecular mechanisms that result in the activation of E6/E7 expression during HPV‐associated tumorigenesis. Recently, much progress has been made in characterizing the proteins involved in the regulation of HPV ...

Tópico(s): Cancer-related Molecular Pathways

1994 - Wiley | Molecular Carcinogenesis

Artigo Acesso aberto Revisado por pares

Felix Hoppe‐Seyler, Karin Butz,

Somatic mutations in the p53 tumor suppressor gene represent the single most common genetic alteration observed in human cancers. Interestingly, the great majority of malignant tumors of the cervix uteri contain wild-type p53 alleles together with the DNA of specific types of human papillomaviruses (HPVs), while the small portion of HPV-negative cervical carcinomas often carry alterations in the p53 tumor suppressor gene. Transcriptional activation of yet-undefined cellular regulatory genes has been ...

Tópico(s): Molecular Biology Techniques and Applications

1993 - American Society for Microbiology | Journal of Virology

Artigo Acesso aberto Revisado por pares

Felix Hoppe‐Seyler, Karin Butz,

Gene expression of the cancer-associated human papillomavirus (HPV) type 18 is modulated by cis-regulatory elements located within the viral upstream regulatory region (URR). All cellular factors identified so far involved in viral gene control bind to the 3′ portion of the HPV-18 URR. In contrast, very little is known about regulatory elements within the 5′ portion of the URR. We therefore analysed this region of unknown function to delineate potential cis-regulatory elements contained therein. By ...

Tópico(s): RNA Research and Splicing

1993 - Microbiology Society | Journal of General Virology

Artigo Acesso aberto Revisado por pares

Karin Butz, Felix Hoppe‐Seyler,

The malignant transformation potential of high-risk human papillomaviruses (HPVs) is closely linked to the expression of the viral E6 and E7 genes. To elucidate the molecular mechanisms resulting in HPV oncogene expression, a systematic analysis of the cis-regulatory elements within the HPV type 18 (HPV18) upstream regulatory region (URR) which regulate the activity of the E6/E7 promoter was performed. As the functional behavior of a given cis-regulatory element can be strongly influenced by the overall ...

Tópico(s): Hepatitis B Virus Studies

1993 - American Society for Microbiology | Journal of Virology