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  1. Article ; Online: ELF3, ELF5, EHF and SPDEF Transcription Factors in Tissue Homeostasis and Cancer.

    Luk, Ian Y / Reehorst, Camilla M / Mariadason, John M

    Molecules (Basel, Switzerland)

    2018  Volume 23, Issue 9

    Abstract: The epithelium-specific ETS (ESE) transcription factors (ELF3, ELF5, EHF and SPDEF) are defined by their highly conserved ETS DNA binding domain and predominant epithelial-specific expression profile. ESE transcription factors maintain normal cell ... ...

    Abstract The epithelium-specific ETS (ESE) transcription factors (ELF3, ELF5, EHF and SPDEF) are defined by their highly conserved ETS DNA binding domain and predominant epithelial-specific expression profile. ESE transcription factors maintain normal cell homeostasis and differentiation of a number of epithelial tissues, and their genetic alteration and deregulated expression has been linked to the progression of several epithelial cancers. Herein we review the normal function of the ESE transcription factors, the mechanisms by which they are dysregulated in cancers, and the current evidence for their role in cancer progression. Finally, we discuss potential therapeutic strategies for targeting or reactivating these factors as a novel means of cancer treatment.
    MeSH term(s) Animals ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation, Neoplastic ; Homeostasis ; Humans ; Molecular Targeted Therapy ; Mutation ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Organ Specificity/genetics ; Proto-Oncogene Proteins c-ets/genetics ; Proto-Oncogene Proteins c-ets/metabolism ; Signal Transduction ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances DNA-Binding Proteins ; EHF protein, human ; ELF3 protein, human ; ELF5 protein, human ; Proto-Oncogene Proteins c-ets ; SPDEF protein, human ; Transcription Factors
    Language English
    Publishing date 2018-08-30
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules23092191
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    Zs.MO 81: Show issues

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  2. Article ; Online: Cell Line Models of Molecular Subtypes of Colorectal Cancer.

    Mooi, Jennifer K / Luk, Ian Y / Mariadason, John M

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1765, Page(s) 3–26

    Abstract: Colorectal cancer (CRC) is a genetically diverse disease necessitating the need for well-characterized and reproducible models to enable its accurate investigation. Recent genomic analyses have confirmed that CRC cell lines accurately retain the key ... ...

    Abstract Colorectal cancer (CRC) is a genetically diverse disease necessitating the need for well-characterized and reproducible models to enable its accurate investigation. Recent genomic analyses have confirmed that CRC cell lines accurately retain the key genetic alterations and represent the major molecular subtypes of primary CRC, underscoring their value as powerful preclinical models. In this chapter we detail the important issues to consider when using CRC cell lines, the techniques used for their appropriate molecular classification, and the methods by which they are cultured in vitro and as subcutaneous xenografts in immune-compromised mice. A panel of commonly available CRC cell lines that have been characterized for key molecular subtypes is also provided as a resource for investigators to select appropriate models to address specific research questions.
    MeSH term(s) Animals ; Biomarkers, Tumor/genetics ; Cell Culture Techniques/instrumentation ; Cell Culture Techniques/methods ; Cell Line, Tumor ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microsatellite Instability ; Microsatellite Repeats/genetics ; Mutation ; Xenograft Model Antitumor Assays/methods
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2018-03-27
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-7765-9_1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Intestinal-specific

    Ng, Irvin / Luk, Ian Y / Nightingale, Rebecca / Reehorst, Camilla M / Dávalos-Salas, Mercedes / Jenkins, Laura J / Fong, Chun / Williams, David S / Watt, Matthew J / Dhillon, Amardeep S / Mariadason, John M

    American journal of physiology. Gastrointestinal and liver physiology

    2023  Volume 325, Issue 6, Page(s) G508–G517

    Abstract: High-fat (HF) diets (HFDs) and inflammation are risk factors for colon cancer; however, the underlying mechanisms remain to be fully elucidated. The transcriptional corepressor HDAC3 has recently emerged as a key regulator of intestinal epithelial ... ...

    Abstract High-fat (HF) diets (HFDs) and inflammation are risk factors for colon cancer; however, the underlying mechanisms remain to be fully elucidated. The transcriptional corepressor HDAC3 has recently emerged as a key regulator of intestinal epithelial responses to diet and inflammation with intestinal-specific
    MeSH term(s) Animals ; Mice ; Carcinogenesis/metabolism ; Co-Repressor Proteins/metabolism ; Colitis/metabolism ; Diet, High-Fat ; Fatty Acids/metabolism ; Inflammation/metabolism ; Intestinal Mucosa/metabolism ; Intestinal Neoplasms/metabolism ; Mice, Inbred C57BL
    Chemical Substances Co-Repressor Proteins ; Fatty Acids ; histone deacetylase 3 (EC 3.5.1.98)
    Language English
    Publishing date 2023-10-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603840-2
    ISSN 1522-1547 ; 0193-1857
    ISSN (online) 1522-1547
    ISSN 0193-1857
    DOI 10.1152/ajpgi.00160.2023
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    Uc I Zs.89: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Potentiating effect of reovirus on immune checkpoint inhibition in microsatellite stable colorectal cancer.

    Augustine, Titto / John, Peter / Friedman, Tyler / Jiffry, Jeeshan / Guzik, Hillary / Mannan, Rifat / Gupta, Riya / Delano, Catherine / Mariadason, John M / Zang, Xingxing / Maitra, Radhashree / Goel, Sanjay

    Frontiers in oncology

    2022  Volume 12, Page(s) 1018767

    Abstract: The majority of colorectal cancers (CRCs) are microsatellite stable (MSS) and resistant to immunotherapy. The current study explores the possibility of using oncolytic reovirus to sensitize MSS CRC to immune checkpoint inhibition. While reovirus reduced ... ...

    Abstract The majority of colorectal cancers (CRCs) are microsatellite stable (MSS) and resistant to immunotherapy. The current study explores the possibility of using oncolytic reovirus to sensitize MSS CRC to immune checkpoint inhibition. While reovirus reduced metabolic activity among
    Language English
    Publishing date 2022-10-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.1018767
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Induction of endoplasmic reticulum stress is associated with the anti-tumor activity of monepantel across cancer types.

    Harris, Tiffany J / Liao, Yang / Shi, Wei / Evangelista, Marco / Pal, Bhupinder / Puthalakath, Hamsa / Aston, Roger / Mollard, Richard / Mariadason, John M / Lee, Erinna F / Fairlie, Walter D

    Cancer medicine

    2023  Volume 12, Issue 12, Page(s) 13522–13537

    Abstract: Background: Monepantel is an anti-helminthic drug that also has anti-cancer properties. Despite several studies over the years, the molecular target of monepantel in mammalian cells is still unknown, and its mechanism-of-action is not fully understood, ... ...

    Abstract Background: Monepantel is an anti-helminthic drug that also has anti-cancer properties. Despite several studies over the years, the molecular target of monepantel in mammalian cells is still unknown, and its mechanism-of-action is not fully understood, though effects on cell cycle, mTOR signalling and autophagy have been implicated.
    Methods: Viability assays were performed on >20 solid cancer cell cells, and apoptosis assays were performed on a subset of these, including 3D cultures. Genetic deletion of BAX/BAK and ATG were used to establish roles of apoptosis and autophagy in killing activity. RNA-sequencing was performed on four cell lines after monepantel treatment, and differentially regulated genes were confirmed by Western blotting.
    Results: We showed that monepantel has anti-proliferative activity on a broad range of cancer cell lines. In some, this was associated with induction of apoptosis which was confirmed using a BAX/BAK-deficient cell line. However, proliferation is still inhibited in these cells following monepantel treatment, indicating cell-cycle disruption as the major anti-cancer effect. Previous studies have also indicated autophagic cell death occurs following monepantel treatment. We showed autophagy induction in multiple cell lines; however, deletion of a key autophagy regulator ATG7 had minimal impact on monepantel's anti-proliferative activity, suggesting autophagy is associated with, but not required for its anti-tumour effects. Transcriptomic analysis of four cell lines treated with monepantel revealed downregulation of many genes involved in the cell cycle, and upregulation of genes linked to ATF4-mediated ER stress responses, especially those involved in amino-acid metabolism and protein synthesis.
    Conclusions: As these outcomes are all associated with mTOR signalling, cell cycle and autophagy, we now provide a likely triggering mechanism for the anti-cancer activity of monepantel.
    MeSH term(s) Animals ; Humans ; bcl-2-Associated X Protein ; Endoplasmic Reticulum Stress ; Neoplasms/drug therapy ; Neoplasms/genetics ; Apoptosis ; TOR Serine-Threonine Kinases/metabolism ; Autophagy ; Cell Line, Tumor ; Mammals/metabolism
    Chemical Substances monepantel (82MA79VJ33) ; bcl-2-Associated X Protein ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2023-05-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2659751-2
    ISSN 2045-7634 ; 2045-7634
    ISSN (online) 2045-7634
    ISSN 2045-7634
    DOI 10.1002/cam4.6021
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  6. Article ; Online: Experimental and spontaneous metastasis assays can result in divergence in clonal architecture.

    Serrano, Antonin / Weber, Tom / Berthelet, Jean / El-Saafin, Farrah / Gadipally, Sreeja / Charafe-Jauffret, Emmanuelle / Ginestier, Christophe / Mariadason, John M / Oakes, Samantha R / Britt, Kara / Naik, Shalin H / Merino, Delphine

    Communications biology

    2023  Volume 6, Issue 1, Page(s) 821

    Abstract: Intratumoural heterogeneity is associated with poor outcomes in breast cancer. To understand how malignant clones survive and grow in metastatic niches, in vivo models using cell lines and patient-derived xenografts (PDX) have become the gold standard. ... ...

    Abstract Intratumoural heterogeneity is associated with poor outcomes in breast cancer. To understand how malignant clones survive and grow in metastatic niches, in vivo models using cell lines and patient-derived xenografts (PDX) have become the gold standard. Injections of cancer cells in orthotopic sites (spontaneous metastasis assays) or into the vasculature (experimental metastasis assays) have been used interchangeably to study the metastatic cascade from early events or post-intravasation, respectively. However, less is known about how these different routes of injection impact heterogeneity. Herein we directly compared the clonality of spontaneous and experimental metastatic assays using the human cell line MDA-MB-231 and a PDX model. Genetic barcoding was used to study the fitness of the subclones in primary and metastatic sites. Using spontaneous assays, we found that intraductal injections resulted in less diverse tumours compared to other routes of injections. Using experimental metastasis assays via tail vein injection of barcoded MDA-MB-231 cells, we also observed an asymmetry in metastatic heterogeneity between lung and liver that was not observed using spontaneous metastasis assays. These results demonstrate that these assays can result in divergent clonal outputs in terms of metastatic heterogeneity and provide a better understanding of the biases inherent to each technique.
    MeSH term(s) Humans ; Female ; Lung Neoplasms/pathology ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Lung/pathology ; Liver/pathology ; Clone Cells/pathology
    Language English
    Publishing date 2023-08-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-05167-5
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  7. Article ; Online: Molecular regulators of lipid metabolism in the intestine - Underestimated therapeutic targets for obesity?

    Dávalos-Salas, Mercedes / Mariadason, John M / Watt, Matthew J / Montgomery, Magdalene K

    Biochemical pharmacology

    2020  Volume 178, Page(s) 114091

    Abstract: The incidence of obesity and type 2 diabetes continues to rise across the globe necessitating the need to identify new therapeutic approaches to manage these diseases. In this review, we explore the potential for therapeutic interventions focussed on the ...

    Abstract The incidence of obesity and type 2 diabetes continues to rise across the globe necessitating the need to identify new therapeutic approaches to manage these diseases. In this review, we explore the potential for therapeutic interventions focussed on the intestinal epithelium, by targeting the role of this tissue in lipid uptake, lipid-mediated cross talk and lipid oxidation. We focus initially on ongoing strategies to manage obesity by targeting the essential role of the intestinal epithelium in lipid uptake, and in mediating tissue cross talk to regulate food intake. Subsequently, we explore a previously underestimated capacity of intestinal epithelial cells to oxidize fatty acids. In this context, we describe recent findings which have unveiled a key role for the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors and histone deacetylases (HDACs) in the regulation of lipid oxidation genes in enterocytes and how targeted genetic manipulation of these factors in enterocytes reduces weight gain, identifying intestinal PPARs and HDACs as potential therapeutic targets in the management of obesity.
    MeSH term(s) Animals ; Anti-Obesity Agents/administration & dosage ; Anti-Obesity Agents/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Drug Delivery Systems/methods ; Humans ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Intestines/drug effects ; Intestines/physiology ; Lipid Metabolism/drug effects ; Lipid Metabolism/physiology ; Obesity/drug therapy ; Obesity/metabolism
    Chemical Substances Anti-Obesity Agents
    Language English
    Publishing date 2020-06-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2020.114091
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    Zs.A 19: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  8. Article ; Online: Author Correction: DUSP5 is methylated in CIMP-high colorectal cancer but is not a major regulator of intestinal cell proliferation and tumorigenesis.

    Tögel, Lars / Nightingale, Rebecca / Wu, Rui / Chüeh, Anderly C / Al-Obaidi, Sheren / Luk, Ian / Dávalos-Salas, Mercedes / Chionh, Fiona / Murone, Carmel / Buchanan, Daniel D / Chatterton, Zac / Sieber, Oliver M / Arango, Diego / Tebbutt, Niall C / Williams, David / Dhillon, Amardeep S / Mariadason, John M

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 2422

    Language English
    Publishing date 2023-02-10
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-29328-y
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  9. Article ; Online: Making sense of HDAC2 mutations in colon cancer.

    Mariadason, John M

    Gastroenterology

    2008  Volume 135, Issue 5, Page(s) 1457–1459

    MeSH term(s) Apoptosis ; Cell Line, Tumor ; Colonic Neoplasms/genetics ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; DNA, Neoplasm/genetics ; Gene Expression Regulation, Neoplastic ; Histone Deacetylase 2 ; Histone Deacetylases/biosynthesis ; Histone Deacetylases/genetics ; Humans ; Mutation ; Repressor Proteins/biosynthesis ; Repressor Proteins/genetics
    Chemical Substances DNA, Neoplasm ; Repressor Proteins ; Histone Deacetylase 2 (EC 3.5.1.98) ; Histone Deacetylases (EC 3.5.1.98)
    Language English
    Publishing date 2008-11
    Publishing country United States
    Document type Comment ; Editorial
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2008.09.039
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    Ui V Zs.44: Show issues Location:
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    Zs.MO 572: Show issues

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  10. Article ; Online: Dissecting HDAC3-mediated tumor progression.

    Mariadason, John M

    Cancer biology & therapy

    2008  Volume 7, Issue 10, Page(s) 1581–1583

    MeSH term(s) Animals ; Disease Progression ; Enzyme Inhibitors/pharmacology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Histone Deacetylases/metabolism ; Histone Deacetylases/physiology ; Humans ; Lymphoma, T-Cell/therapy ; Medical Oncology/methods ; Mice ; Models, Biological ; Neoplasms/drug therapy ; Neoplasms/enzymology ; Transcription Factors/metabolism
    Chemical Substances Enzyme Inhibitors ; Transcription Factors ; Histone Deacetylases (EC 3.5.1.98) ; histone deacetylase 3 (EC 3.5.1.98)
    Language English
    Publishing date 2008-10-26
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 2146305-0
    ISSN 1555-8576 ; 1538-4047
    ISSN (online) 1555-8576
    ISSN 1538-4047
    DOI 10.4161/cbt.7.10.6863
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