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  1. Book ; Thesis: Regulation of PD-L1 by PPARg for immunotherapy in gastrointestinal cancers

    Li, Beifang / Burgermeister, Elke

    2021  

    Institution Universität Heidelberg
    Author's details vorgelegt von Beifang Li ; Referentin: Frau Priv.-Doz. Dr. rer. nat. Elke Burgermeister
    Language English
    Size 61 Blätter, Illustrationen, Diagramme, 30 cm
    Publishing place Heidelberg
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Dissertation, Ruprecht-Karls-Universität Heidelberg, 2021
    HBZ-ID HT021304833
    Database Catalogue ZB MED Medicine, Health

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  2. Book ; Thesis: Die Beeinflussung zentraler Signalkaskaden von Inflammation und kolorektaler Karzinogenese durch die Lipidphosphatase Myotubularin-Related Protein-7

    Schroeder, Torsten / Burgermeister, Elke

    2022  

    Institution Universität Heidelberg
    Author's details vorgelegt von Torsten Christian Schroeder ; Referentin: PD Dr. rer. nat. Elke Burgermeister
    Language German
    Size 81 Blätter, Diagramme, Illustrationen
    Publishing place Heidelberg
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Dissertation, Ruprecht-Karls-Universität Heidelberg, 2023
    HBZ-ID HT030654138
    Database Catalogue ZB MED Medicine, Health

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  3. Article ; Online: Mitogen-Activated Protein Kinase and Nuclear Hormone Receptor Crosstalk in Cancer Immunotherapy.

    Burgermeister, Elke

    International journal of molecular sciences

    2023  Volume 24, Issue 17

    Abstract: The three major MAP-kinase (MAPK) pathways, ERK1/2, p38 and JNK/SAPK, are upstream regulators of the nuclear "hormone" receptor superfamily (NHRSF), with a prime example given by the estrogen receptor in breast cancer. These ligand-activated ... ...

    Abstract The three major MAP-kinase (MAPK) pathways, ERK1/2, p38 and JNK/SAPK, are upstream regulators of the nuclear "hormone" receptor superfamily (NHRSF), with a prime example given by the estrogen receptor in breast cancer. These ligand-activated transcription factors exert non-genomic and genomic functions, where they are either post-translationally modified by phosphorylation or directly interact with components of the MAPK pathways, events that govern their transcriptional activity towards target genes involved in cell differentiation, proliferation, metabolism and host immunity. This molecular crosstalk takes place not only in normal epithelial or tumor cells, but also in a plethora of immune cells from the adaptive and innate immune system in the tumor-stroma tissue microenvironment. Thus, the drugability of both the MAPK and the NHRSF pathways suggests potential for intervention therapies, especially for cancer immunotherapy. This review summarizes the existing literature covering the expression and function of NHRSF subclasses in human tumors, both solid and leukemias, and their effects in combination with current clinically approved therapeutics against immune checkpoint molecules (e.g., PD1).
    MeSH term(s) Humans ; Mitogen-Activated Protein Kinases ; Immunotherapy ; Receptors, Cytoplasmic and Nuclear ; Phosphorylation ; Cell Differentiation ; Neoplasms/therapy
    Chemical Substances Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Receptors, Cytoplasmic and Nuclear
    Language English
    Publishing date 2023-09-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241713661
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Mitogen-Activated Protein Kinase and Exploratory Nuclear Receptor Crosstalk in Cancer Immunotherapy.

    Burgermeister, Elke

    International journal of molecular sciences

    2023  Volume 24, Issue 19

    Abstract: The three major mitogen-activated protein kinase (MAPK) pathways (ERK1/2, p38, and JNK/SAPK) are upstream regulators of the nuclear receptor superfamily (NRSF). These ligand-activated transcription factors are divided into subclasses comprising receptors ...

    Abstract The three major mitogen-activated protein kinase (MAPK) pathways (ERK1/2, p38, and JNK/SAPK) are upstream regulators of the nuclear receptor superfamily (NRSF). These ligand-activated transcription factors are divided into subclasses comprising receptors for endocrine hormones, metabolic compounds (e.g., vitamins, diet), xenobiotics, and mediators released from host immune reactions such as tissue injury and inflammation. These internal and external cues place the NRSF at the frontline as sensors and translators of information from the environment towards the genome. For most of the former "orphan" receptors, physiological and synthetic ligands have been identified, opening intriguing opportunities for combination therapies with existing cancer medications. Hitherto, only preclinical data are available, warranting further validation in clinical trials in patients. The current review summarized the existing literature covering the expression and function of NRSF subclasses in human solid tumors and hematopoietic malignancies and their modulatory effects on innate (e.g., macrophages, dendritic cells) and adaptive (i.e., T cell subsets) immune cells, encouraging mechanistic and pharmacological studies in combination with current clinically approved therapeutics against immune checkpoint molecules (e.g., PD1).
    MeSH term(s) Humans ; Mitogen-Activated Protein Kinases/metabolism ; p38 Mitogen-Activated Protein Kinases ; JNK Mitogen-Activated Protein Kinases ; Receptors, Cytoplasmic and Nuclear ; Immunotherapy ; Neoplasms/therapy
    Chemical Substances Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Receptors, Cytoplasmic and Nuclear
    Language English
    Publishing date 2023-09-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241914546
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Book ; Online ; Thesis: Die Beeinflussung zentraler Signalkaskaden von Inflammation und kolorektaler Karzinogenese durch die Lipidphosphatase Myotubularin-Related Protein-7

    Schroeder, Torsten [Verfasser] / Burgermeister, Elke [Akademischer Betreuer]

    2023  

    Author's details Torsten Christian Schroeder ; Betreuer: Elke Burgermeister
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language German
    Publisher Universitätsbibliothek Heidelberg
    Publishing place Heidelberg
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  6. Article ; Online: The gut virome: A new microbiome component in health and disease.

    Cao, Zhirui / Sugimura, Naoki / Burgermeister, Elke / Ebert, Matthias P / Zuo, Tao / Lan, Ping

    EBioMedicine

    2022  Volume 81, Page(s) 104113

    Abstract: The human gastrointestinal tract harbours an abundance of viruses, collectively known as the gut virome. The gut virome is highly heterogeneous across populations and is linked to geography, ethnicity, diet, lifestyle, and urbanisation. The currently ... ...

    Abstract The human gastrointestinal tract harbours an abundance of viruses, collectively known as the gut virome. The gut virome is highly heterogeneous across populations and is linked to geography, ethnicity, diet, lifestyle, and urbanisation. The currently known function of the gut virome varies greatly across human populations, and much remains unknown. We review current literature on the human gut virome, and the intricate trans-kingdom interplay among gut viruses, bacteria, and the mammalian host underlying health and diseases. We summarise evidence on the use of the gut virome as diagnostic markers and a therapeutic target. We shed light on novel avenues of microbiome-inspired diagnosis and therapies. We also review pre-clinical and clinical studies on gut virome-rectification-based therapies, including faecal microbiota transplantation, faecal virome transplantation, and refined phage therapy. Our review suggests that future research effort should focus on unravelling the mechanisms exerted by gut viruses/phages in human pathophysiology, and on developing phage-prompted precision therapies.
    MeSH term(s) Animals ; Bacteria ; Bacteriophages ; Humans ; Mammals ; Microbiota ; Virome ; Viruses
    Language English
    Publishing date 2022-06-23
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2022.104113
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Nuclear pore protein POM121 regulates subcellular localization and transcriptional activity of PPARγ.

    Yu, Yanxiong / Farooq, Mohammad S / Eberhart Meessen, Sabine / Jiang, Yidan / Kato, Dominik / Zhan, Tianzuo / Weiss, Christel / Seger, Rony / Kang, Wei / Zhang, Xiang / Yu, Jun / Ebert, Matthias P A / Burgermeister, Elke

    Cell death & disease

    2024  Volume 15, Issue 1, Page(s) 7

    Abstract: Manipulation of the subcellular localization of transcription factors by preventing their shuttling via the nuclear pore complex (NPC) emerges as a novel therapeutic strategy against cancer. One transmembrane component of the NPC is POM121, encoded by a ... ...

    Abstract Manipulation of the subcellular localization of transcription factors by preventing their shuttling via the nuclear pore complex (NPC) emerges as a novel therapeutic strategy against cancer. One transmembrane component of the NPC is POM121, encoded by a tandem gene locus POM121A/C on chromosome 7. Overexpression of POM121 is associated with metabolic diseases (e.g., diabetes) and unfavorable clinical outcome in patients with colorectal cancer (CRC). Peroxisome proliferator-activated receptor-gamma (PPARγ) is a transcription factor with anti-diabetic and anti-tumoral efficacy. It is inhibited by export from the nucleus to the cytosol via the RAS-RAF-MEK1/2-ERK1/2 signaling pathway, a major oncogenic driver of CRC. We therefore hypothesized that POM121 participates in the transport of PPARγ across the NPC to regulate its transcriptional activity on genes involved in metabolic and tumor control. We found that POM121A/C mRNA was enriched and POM121 protein co-expressed with PPARγ in tissues from CRC patients conferring poor prognosis. Its interactome was predicted to include proteins responsible for tumor metabolism and immunity, and in-silico modeling provided insights into potential 3D structures of POM121. A peptide region downstream of the nuclear localization sequence (NLS) of POM121 was identified as a cytoplasmic interactor of PPARγ. POM121 positivity correlated with the cytoplasmic localization of PPARγ in patients with KRAS mutant CRC. In contrast, POM121A/C silencing by CRISPR/Cas9 sgRNA or siRNA enforced nuclear accumulation of PPARγ and activated PPARγ target genes promoting lipid metabolism and cell cycle arrest resulting in reduced proliferation of human CRC cells. Our data suggest the POM121-PPARγ axis as a potential drugable target in CRC.
    MeSH term(s) Humans ; Nuclear Pore/metabolism ; PPAR gamma/genetics ; PPAR gamma/metabolism ; RNA, Guide, CRISPR-Cas Systems ; Nuclear Pore Complex Proteins/metabolism ; Transcription Factors/metabolism ; Neoplasms/metabolism ; Membrane Glycoproteins/metabolism
    Chemical Substances PPAR gamma ; RNA, Guide, CRISPR-Cas Systems ; Nuclear Pore Complex Proteins ; Transcription Factors ; POM121 protein, human ; Membrane Glycoproteins
    Language English
    Publishing date 2024-01-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-023-06371-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The gut virome

    Zhirui Cao / Naoki Sugimura / Elke Burgermeister / Matthias P. Ebert / Tao Zuo / Ping Lan

    EBioMedicine, Vol 81, Iss , Pp 104113- (2022)

    A new microbiome component in health and disease

    2022  

    Abstract: Summary: The human gastrointestinal tract harbours an abundance of viruses, collectively known as the gut virome. The gut virome is highly heterogeneous across populations and is linked to geography, ethnicity, diet, lifestyle, and urbanisation. The ... ...

    Abstract Summary: The human gastrointestinal tract harbours an abundance of viruses, collectively known as the gut virome. The gut virome is highly heterogeneous across populations and is linked to geography, ethnicity, diet, lifestyle, and urbanisation. The currently known function of the gut virome varies greatly across human populations, and much remains unknown. We review current literature on the human gut virome, and the intricate trans-kingdom interplay among gut viruses, bacteria, and the mammalian host underlying health and diseases. We summarise evidence on the use of the gut virome as diagnostic markers and a therapeutic target. We shed light on novel avenues of microbiome-inspired diagnosis and therapies. We also review pre-clinical and clinical studies on gut virome-rectification-based therapies, including faecal microbiota transplantation, faecal virome transplantation, and refined phage therapy. Our review suggests that future research effort should focus on unravelling the mechanisms exerted by gut viruses/phages in human pathophysiology, and on developing phage-prompted precision therapies.
    Keywords Gut virome ; Microbiome ; Virus ; Phage ; Faecal virome transplantation ; Phage therapy ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Myotubularin-related-protein-7 inhibits mutant (G12V) K-RAS by direct interaction.

    Weidner, Philip / Saar, Daniel / Söhn, Michaela / Schroeder, Torsten / Yu, Yanxiong / Zöllner, Frank G / Ponelies, Norbert / Zhou, Xiaobo / Zwicky, André / Rohrbacher, Florian N / Pattabiraman, Vijaya R / Tanriver, Matthias / Bauer, Alexander / Ahmed, Hazem / Ametamey, Simon M / Riffel, Philipp / Seger, Rony / Bode, Jeffrey W / Wade, Rebecca C /
    Ebert, Matthias P A / Kragelund, Birthe B / Burgermeister, Elke

    Cancer letters

    2024  Volume 588, Page(s) 216783

    Abstract: Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 ... ...

    Abstract Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes. Overexpression of MTMR7 reduced RAS GTPase activities and protein levels, ERK1/2 phosphorylation, c-FOS transcription and cancer cell proliferation in vitro. We located the RAS-inhibitory activity of MTMR7 to its charged coiled coil (CC) region and demonstrate direct interaction with the gastrointestinal cancer-relevant K-RAS
    MeSH term(s) Animals ; Humans ; Mice ; Neoplasms ; Peptides ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Tyrosine Phosphatases, Non-Receptor/genetics ; Protein Tyrosine Phosphatases, Non-Receptor/metabolism ; Signal Transduction
    Chemical Substances myotubularin (EC 3.1.3.48) ; Peptides ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Protein Tyrosine Phosphatases, Non-Receptor (EC 3.1.3.48) ; Mtmr7 protein, mouse (EC 3.1.3.48) ; Hras protein, mouse (EC 3.6.5.2)
    Language English
    Publishing date 2024-03-09
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2024.216783
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1177: Show issues Location:
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  10. Article ; Online: Checkpoints and beyond - Immunotherapy in colorectal cancer.

    Gutting, Tobias / Burgermeister, Elke / Härtel, Nicolai / Ebert, Matthias P

    Seminars in cancer biology

    2018  Volume 55, Page(s) 78–89

    Abstract: Immunotherapy is the latest revolution in cancer therapy. It continues to show impressive results in malignancies like melanoma and others. At least so far, effects are modest in colorectal cancer (CRC) and only a subset of patients benefits from already ...

    Abstract Immunotherapy is the latest revolution in cancer therapy. It continues to show impressive results in malignancies like melanoma and others. At least so far, effects are modest in colorectal cancer (CRC) and only a subset of patients benefits from already approved checkpoint inhibitors. In this review, we discuss major hurdles of immunotherapy like the immunosuppressive niche and low immunogenicity of CRC next to current achievements of checkpoint inhibitors, interleukin treatment and adoptive cell transfer (dendritic cells/cytokine induced killer cells, tumor infiltrating lymphocytes, chimeric antigen receptor cells, T cell receptor transfer) in pre-clinical models and clinical trials. We intensively examine approaches to overcome low immunogenicity by combination of different therapies and address future strategies of therapy as well as the need of predictive factors in this emerging field of precision medicine.
    MeSH term(s) Cell Cycle Checkpoints/genetics ; Cell Cycle Checkpoints/immunology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/therapy ; Combined Modality Therapy ; Dendritic Cells/immunology ; Humans ; Immunotherapy/trends ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/pathology ; Precision Medicine
    Language English
    Publishing date 2018-04-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1033980-2
    ISSN 1096-3650 ; 1044-579X
    ISSN (online) 1096-3650
    ISSN 1044-579X
    DOI 10.1016/j.semcancer.2018.04.003
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