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  1. Article ; Online: The Roles of Secreted Wnt Ligands in Cancer

    Johannes Werner / Kim E. Boonekamp / Tianzuo Zhan / Michael Boutros

    International Journal of Molecular Sciences, Vol 24, Iss 5349, p

    2023  Volume 5349

    Abstract: Wnt ligands are secreted signaling proteins that display a wide range of biological effects. They play key roles in stimulating Wnt signaling pathways to facilitate processes such as tissue homeostasis and regeneration. Dysregulation of Wnt signaling is ... ...

    Abstract Wnt ligands are secreted signaling proteins that display a wide range of biological effects. They play key roles in stimulating Wnt signaling pathways to facilitate processes such as tissue homeostasis and regeneration. Dysregulation of Wnt signaling is a hallmark of many cancers and genetic alterations in various Wnt signaling components, which result in ligand-independent or ligand-dependent hyperactivation of the pathway that have been identified. Recently, research is focusing on the impact of Wnt signaling on the interaction between tumor cells and their micro-environment. This Wnt-mediated crosstalk can act either in a tumor promoting or suppressing fashion. In this review, we comprehensively outline the function of Wnt ligands in different tumor entities and their impact on key phenotypes, including cancer stemness, drug resistance, metastasis, and immune evasion. Lastly, we elaborate approaches to target Wnt ligands in cancer therapy.
    Keywords Wnt signaling ; Wnt ligands ; cancer ; non-canonical Wnt signaling ; tumor microenvironment ; metastasis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures

    Annie S. P. Yang / Devanjali Dutta / Kai Kretzschmar / Delilah Hendriks / Jens Puschhof / Huili Hu / Kim E. Boonekamp / Youri van Waardenburg / Susana M. Chuva de Sousa Lopes / Geert-Jan van Gemert / Johannes H. W. de Wilt / Teun Bousema / Hans Clevers / Robert W. Sauerwein

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 12

    Abstract: Abstract Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-infected mosquito bite. While an attractive stage for life-cycle interruption, understanding of parasite- ... ...

    Abstract Abstract Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-infected mosquito bite. While an attractive stage for life-cycle interruption, understanding of parasite-hepatocyte interaction is inadequate due to limitations of existing in vitro models. We explore the suitability of hepatocyte organoids (HepOrgs) for Pf-development and show that these cells permitted parasite invasion, differentiation and maturation of different Pf strains. Single-cell messenger RNA sequencing (scRNAseq) of Pf-infected HepOrg cells has identified 80 Pf-transcripts upregulated on day 5 post-infection. Transcriptional profile changes are found involving distinct metabolic pathways in hepatocytes with Scavenger Receptor B1 (SR-B1) transcripts highly upregulated. A novel functional involvement in schizont maturation is confirmed in fresh primary hepatocytes. Thus, HepOrgs provide a strong foundation for a versatile in vitro model for Pf liver-stages accommodating basic biological studies and accelerated clinical development of novel tools for malaria control.
    Keywords Science ; Q
    Subject code 572
    Language English
    Publishing date 2023-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Establishment and characterization of a canine keratinocyte organoid culture system

    Wiener, Dominique J / Angelos Papaspyropoulos / Hans Clevers / Kai Kretzschmar / Kim E. Boonekamp / Onur Basak / Priyanca Asra

    Veterinary dermatology. 2018 Oct., v. 29, no. 5

    2018  

    Abstract: BACKGROUND: Perturbations of epidermal and follicular homeostasis have been attributed to a variety of skin diseases affecting dogs. The availability of an in vitro system to investigate these diseases is important to understand underlying ... ...

    Abstract BACKGROUND: Perturbations of epidermal and follicular homeostasis have been attributed to a variety of skin diseases affecting dogs. The availability of an in vitro system to investigate these diseases is important to understand underlying pathomechanisms. OBJECTIVES: To establish an accurate and reliable in vitro 3D system of canine keratinocyte organoids to lay the basis for studying functional defects in interfollicular epidermis (IFE) and hair follicle (HF) morphogenesis, reconstitution and differentiation that lead to alopecic and epidermal diseases. ANIMALS: Skin biopsies were obtained from freshly euthanized dogs of different breeds with no skin abnormalities. METHODS: Cells derived from microdissected IFE and HFs were seeded in Matrigel and keratinocyte organoids were grown and characterized using immunohistochemistry, RT‐qPCR and RNA sequencing. RESULTS: Both organoid lines develop into a basal IFE‐like cell type. Gene and protein expression analysis revealed high mRNA and protein levels of keratins 5 and 14, IFE differentiation markers and intercellular molecules. Key markers of HF stem cells were lacking. Withdrawal of growth factors resulted in upregulation of markers such as KRT16, Involucrin, KRT17 and SOX9, showing the potential of the organoids to develop towards more differentiated tissue. CONCLUSION AND CLINICAL IMPORTANCE: Our 3D in vitro culture system provides the basis to explore epidermal function, to investigate the culture conditions necessary for the development of organoids with a HF signature and to address cutaneous disorders in dogs. However, for induction of HF signatures or hair growth, addition of different growth factors or co‐culture with dermal papilla will be required.
    Keywords biopsy ; breeds ; coculture ; dogs ; genes ; growth factors ; hair follicles ; homeostasis ; immunohistochemistry ; keratinocytes ; messenger RNA ; morphogenesis ; protein content ; protein synthesis ; quantitative polymerase chain reaction ; reverse transcriptase polymerase chain reaction ; sequence analysis ; skin diseases ; stem cells ; veterinary medicine
    Language English
    Dates of publication 2018-10
    Size p. 375-e126.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 2011122-8
    ISSN 1365-3164 ; 0959-4493
    ISSN (online) 1365-3164
    ISSN 0959-4493
    DOI 10.1111/vde.12541
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: The drug-induced phenotypic landscape of colorectal cancer organoids

    Johannes Betge / Niklas Rindtorff / Jan Sauer / Benedikt Rauscher / Clara Dingert / Haristi Gaitantzi / Frank Herweck / Kauthar Srour-Mhanna / Thilo Miersch / Erica Valentini / Kim E. Boonekamp / Veronika Hauber / Tobias Gutting / Larissa Frank / Sebastian Belle / Timo Gaiser / Inga Buchholz / Ralf Jesenofsky / Nicolai Härtel /
    Tianzuo Zhan / Bernd Fischer / Katja Breitkopf-Heinlein / Elke Burgermeister / Matthias P. Ebert / Michael Boutros

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 15

    Abstract: The heterogeneity underlying cancer organoid phenotypes is not yet well understood. Here, the authors develop an imaging analysis assay for high throughput phenotypic screening of colorectal organoids that allows to define specific morphological changes ... ...

    Abstract The heterogeneity underlying cancer organoid phenotypes is not yet well understood. Here, the authors develop an imaging analysis assay for high throughput phenotypic screening of colorectal organoids that allows to define specific morphological changes that occur following different drug treatments.
    Keywords Science ; Q
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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