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  1. Book ; Online: WW Domain Proteins in Signaling, Cancer Growth, Neural Diseases, and Metabolic Disorders

    Chang, Nan-Shan / Lin, Rongtuan / Sze, Chun-I / Aqeilan, Rami I.

    2019  

    Keywords Medicine ; Oncology ; WW domain ; WWOX ; signaling ; Hippo ; Smurf ; neurodegeneration ; Cancer
    Size 1 electronic resource (138 pages)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021230562
    ISBN 9782889631773 ; 288963177X
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Engineering organoids: a promising platform to understand biology and treat diseases.

    Aqeilan, Rami I

    Cell death and differentiation

    2020  Volume 28, Issue 1, Page(s) 1–4

    MeSH term(s) Biology/methods ; Genetic Engineering/methods ; Humans ; Medicine/methods ; Organoids/physiology
    Language English
    Publishing date 2020-12-14
    Publishing country England
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225672-9
    ISSN 1476-5403 ; 1350-9047
    ISSN (online) 1476-5403
    ISSN 1350-9047
    DOI 10.1038/s41418-020-00680-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4230: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 80: Show issues

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  3. Article ; Online: TOP1 and R-loops facilitate transcriptional DSBs at hypertranscribed cancer driver genes.

    Hidmi, Osama / Oster, Sara / Monin, Jonathan / Aqeilan, Rami I

    iScience

    2024  Volume 27, Issue 3, Page(s) 109082

    Abstract: DNA double-stranded breaks (DSBs) pose a significant threat to genomic integrity, and their generation during essential cellular processes like transcription remains poorly understood. In this study, we employ several techniques to map DSBs, R-loops, and ...

    Abstract DNA double-stranded breaks (DSBs) pose a significant threat to genomic integrity, and their generation during essential cellular processes like transcription remains poorly understood. In this study, we employ several techniques to map DSBs, R-loops, and topoisomerase 1 cleavage complex (TOP1cc) to comprehensively investigate the interplay between transcription, DSBs, topoisomerase 1 (TOP1), and R-loops. Our findings reveal the presence of DSBs at highly expressed genes enriched with TOP1 and R-loops. Remarkably, transcription-associated DSBs at these loci are significantly reduced upon depletion of R-loops and TOP1, uncovering the pivotal roles of TOP1 and R-loops in transcriptional DSB formation. By elucidating the intricate interplay between TOP1cc trapping, R-loops, and DSBs, our study provides insights into the mechanisms underlying transcription-associated genomic instability. Moreover, we establish a link between transcriptional DSBs and early molecular changes driving cancer development, highlighting the distinct etiology and molecular characteristics of driver mutations compared to passenger mutations.
    Language English
    Publishing date 2024-02-01
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2024.109082
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: WWOX-Related Neurodevelopmental Disorders: Models and Future Perspectives.

    Steinberg, Daniel J / Aqeilan, Rami I

    Cells

    2021  Volume 10, Issue 11

    Abstract: The WW domain-containing oxidoreductase ( ...

    Abstract The WW domain-containing oxidoreductase (
    MeSH term(s) Animals ; Central Nervous System/metabolism ; Disease Models, Animal ; Humans ; Loss of Function Mutation/genetics ; Neurodevelopmental Disorders/metabolism ; Translational Research, Biomedical ; WW Domain-Containing Oxidoreductase/metabolism
    Chemical Substances WW Domain-Containing Oxidoreductase (EC 1.1.1.-)
    Language English
    Publishing date 2021-11-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10113082
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Protocol for mapping physiological DSBs using in-suspension break labeling in situ and sequencing.

    Hidmi, Osama / Oster, Sara / Shatleh, Diala / Monin, Jonathan / Aqeilan, Rami I

    STAR protocols

    2024  Volume 5, Issue 2, Page(s) 103059

    Abstract: Physiological double-stranded breaks (DSBs) are a major source of genomic instability. Here, we present a protocol for mapping physiological DSBs by in-suspension break labeling in situ and sequencing (sBLISS) in a single-nucleotide resolution. We ... ...

    Abstract Physiological double-stranded breaks (DSBs) are a major source of genomic instability. Here, we present a protocol for mapping physiological DSBs by in-suspension break labeling in situ and sequencing (sBLISS) in a single-nucleotide resolution. We describe steps for cell fixation, labeling of DSBs, DNA isolation followed by in vitro transcription (IVT), reverse transcription, and library preparation. sBLISS provides a map of DSBs over the genome and can be used to study the role of different factors in DSB formation. For complete details on the use and execution of this protocol, please refer to Hidmi et al.
    Language English
    Publishing date 2024-05-07
    Publishing country United States
    Document type Journal Article
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2024.103059
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Programmed DNA Damage and Physiological DSBs: Mapping, Biological Significance and Perturbations in Disease States.

    Oster, Sara / Aqeilan, Rami I

    Cells

    2020  Volume 9, Issue 8

    Abstract: DNA double strand breaks (DSBs) are known to be the most toxic and threatening of the various types of breaks that may occur to the DNA. However, growing evidence continuously sheds light on the regulatory roles of programmed DSBs. Emerging studies ... ...

    Abstract DNA double strand breaks (DSBs) are known to be the most toxic and threatening of the various types of breaks that may occur to the DNA. However, growing evidence continuously sheds light on the regulatory roles of programmed DSBs. Emerging studies demonstrate the roles of DSBs in processes such as T and B cell development, meiosis, transcription and replication. A significant recent progress in the last few years has contributed to our advanced knowledge regarding the functions of DSBs is the development of many next generation sequencing (NGS) methods, which have considerably advanced our capabilities. Other studies have focused on the implications of programmed DSBs on chromosomal aberrations and tumorigenesis. This review aims to summarize what is known about DNA damage in its physiological context. In addition, we will examine the advancements of the past several years, which have made an impact on the study of genome landscape and its organization.
    MeSH term(s) Animals ; B-Lymphocytes/physiology ; Cell Differentiation/genetics ; DNA Breaks, Double-Stranded ; DNA Damage/physiology ; DNA Repair/genetics ; Genome ; Humans ; Meiosis/genetics ; Neoplasms/genetics ; T-Lymphocytes/physiology ; Transcription, Genetic ; Translocation, Genetic/genetics ; V(D)J Recombination
    Language English
    Publishing date 2020-08-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9081870
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Mapping the breakome reveals tight regulation on oncogenic super-enhancers.

    Oster, Sara / Aqeilan, Rami I

    Molecular & cellular oncology

    2020  Volume 7, Issue 3, Page(s) 1698933

    Abstract: DNA double-strand breaks (DSBs) could be deleterious and lead to age-related diseases, such as cancer. Recent evidence, however, associates DSBs with vital cellular processes. As discussed here, genome-wide mapping of DSBs revealed an unforeseen coupling ...

    Abstract DNA double-strand breaks (DSBs) could be deleterious and lead to age-related diseases, such as cancer. Recent evidence, however, associates DSBs with vital cellular processes. As discussed here, genome-wide mapping of DSBs revealed an unforeseen coupling mechanism between transcription and DNA repair at super-enhancers, as means of hypertranscription of oncogenic drivers.
    Language English
    Publishing date 2020-02-11
    Publishing country United States
    Document type Journal Article
    ISSN 2372-3556
    ISSN 2372-3556
    DOI 10.1080/23723556.2019.1698933
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Correction: WWOX promotes osteosarcoma development via upregulation of Myc.

    Akkawi, Rania / Hidmi, Osama / Haj-Yahia, Ameen / Monin, Jonathon / Diment, Judith / Drier, Yotam / Stein, Gary S / Aqeilan, Rami I

    Cell death & disease

    2024  Volume 15, Issue 2, Page(s) 141

    Language English
    Publishing date 2024-02-14
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-024-06518-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: WWOX promotes osteosarcoma development via upregulation of Myc.

    Akkawi, Rania / Hidmi, Osama / Haj-Yahia, Ameen / Monin, Jonathon / Diment, Judith / Drier, Yotam / Stein, Gary S / Aqeilan, Rami I

    Cell death & disease

    2024  Volume 15, Issue 1, Page(s) 13

    Abstract: Osteosarcoma is an aggressive bone tumor that primarily affects children and adolescents. This malignancy is highly aggressive, associated with poor clinical outcomes, and primarily metastasizes to the lungs. Due to its rarity and biological ... ...

    Abstract Osteosarcoma is an aggressive bone tumor that primarily affects children and adolescents. This malignancy is highly aggressive, associated with poor clinical outcomes, and primarily metastasizes to the lungs. Due to its rarity and biological heterogeneity, limited studies on its molecular basis exist, hindering the development of effective therapies. The WW domain-containing oxidoreductase (WWOX) is frequently altered in human osteosarcoma. Combined deletion of Wwox and Trp53 using Osterix1-Cre transgenic mice has been shown to accelerate osteosarcoma development. In this study, we generated a traceable osteosarcoma mouse model harboring the deletion of Trp53 alone (single-knockout) or combined deletion of Wwox/Trp53 (double-knockout) and expressing a tdTomato reporter. By tracking Tomato expression at different time points, we detected the early presence of tdTomato-positive cells in the bone marrow mesenchymal stem cells of non-osteosarcoma-bearing mice (young BM). We found that double-knockout young BM cells, but not single-knockout young BM cells, exhibited tumorigenic traits both in vitro and in vivo. Molecular and cellular characterization of these double-knockout young BM cells revealed their resemblance to osteosarcoma tumor cells. Interestingly, one of the observed significant transcriptomic changes in double-knockout young BM cells was the upregulation of Myc and its target genes compared to single-knockout young BM cells. Intriguingly, Myc-chromatin immunoprecipitation sequencing revealed its increased enrichment on Myc targets, which were upregulated in double-knockout young BM cells. Restoration of WWOX in double-knockout young BM cells reduced Myc protein levels. As a prototype target, we demonstrated the upregulation of MCM7, a known Myc target, in double-knockout young BM relative to single-knockout young BM cells. Inhibition of MCM7 expression using simvastatin resulted in reduced proliferation and tumor cell growth of double-knockout young BM cells. Our findings reveal BM mesenchymal stem cells as a platform to study osteosarcoma and Myc and its targets as WWOX effectors and early molecular events during osteosarcomagenesis.
    MeSH term(s) Animals ; Humans ; Mice ; Bone Neoplasms/genetics ; Osteosarcoma/genetics ; Tumor Suppressor Proteins/genetics ; Up-Regulation/genetics ; WW Domain-Containing Oxidoreductase/genetics ; WW Domain-Containing Oxidoreductase/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism
    Chemical Substances tdTomato ; Tumor Suppressor Proteins ; WW Domain-Containing Oxidoreductase (EC 1.1.1.-) ; WWOX protein, human (EC 1.1.1.-) ; Wwox protein, mouse (EC 1.1.1.-) ; Myc protein, mouse ; Proto-Oncogene Proteins c-myc
    Language English
    Publishing date 2024-01-05
    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/s41419-023-06378-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Unveiling the relationship between WWOX and BRCA1 in mammary tumorigenicity and in DNA repair pathway selection.

    Bidany-Mizrahi, Tirza / Shweiki, Aya / Maroun, Kian / Abu-Tair, Lina / Mali, Bella / Aqeilan, Rami I

    Cell death discovery

    2024  Volume 10, Issue 1, Page(s) 145

    Abstract: Breast cancer is the leading cause of cancer-related deaths in women worldwide, with the basal-like or triple-negative breast cancer (TNBC) subtype being particularly aggressive and challenging to treat. Understanding the molecular mechanisms driving the ...

    Abstract Breast cancer is the leading cause of cancer-related deaths in women worldwide, with the basal-like or triple-negative breast cancer (TNBC) subtype being particularly aggressive and challenging to treat. Understanding the molecular mechanisms driving the development and progression of TNBC is essential. We previously showed that WW domain-containing oxidoreductase (WWOX) is commonly inactivated in TNBC and is implicated in the DNA damage response (DDR) through ATM and ATR activation. In this study, we investigated the interplay between WWOX and BRCA1, both frequently inactivated in TNBC, on mammary tumor development and on DNA double-strand break (DSB) repair choice. We generated and characterized a transgenic mouse model (K14-Cre;Brca1
    Language English
    Publishing date 2024-03-18
    Publishing country United States
    Document type Journal Article
    ISSN 2058-7716
    ISSN 2058-7716
    DOI 10.1038/s41420-024-01878-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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