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  1. Article ; Online: The role of histone H3 lysine demethylases in glioblastoma.

    Young, Dejauwne / Guha, Chandan / Sidoli, Simone

    Cancer metastasis reviews

    2023  Volume 42, Issue 2, Page(s) 445–454

    Abstract: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults with an average survival of 15-18 months. Part of its malignancy derives from epigenetic regulation that occurs as the tumor develops and after therapeutic treatment. Specifically, ... ...

    Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor in adults with an average survival of 15-18 months. Part of its malignancy derives from epigenetic regulation that occurs as the tumor develops and after therapeutic treatment. Specifically, enzymes involved in removing methylations from histone proteins on chromatin, i.e., lysine demethylases (KDMs), have a significant impact on GBM biology and reoccurrence. This knowledge has paved the way to considering KDMs as potential targets for GBM treatment. For example, increases in trimethylation of histone H3 on the lysine 9 residue (H3K9me3) via inhibition of KDM4C and KDM7A has been shown to lead to cell death in Glioblastoma initiating cells. KDM6 has been shown to drive Glioma resistance to receptor tyrosine kinase inhibitors and its inhibition decreases tumor resistance. In addition, increased expression of the histone methyltransferase MLL4 and UTX histone demethylase are associated with prolonged survival in a subset of GBM patients, potentially by regulating histone methylation on the promoter of the mgmt gene. Thus, the complexity of how histone modifiers contribute to glioblastoma pathology and disease progression is yet to be fully understood. To date, most of the current work on histone modifying enzymes in GBM are centered upon histone H3 demethylase enzymes. In this mini-review, we summarize the current knowledge on the role of histone H3 demethylase enzymes in Glioblastoma tumor biology and therapy resistance. The objective of this work is to highlight the current and future potential areas of research for GBM epigenetics therapy.
    MeSH term(s) Humans ; Histones/genetics ; Histones/metabolism ; Histone Demethylases/genetics ; Histone Demethylases/metabolism ; Glioblastoma/genetics ; Glioblastoma/pathology ; Lysine/genetics ; Lysine/metabolism ; Epigenesis, Genetic ; Jumonji Domain-Containing Histone Demethylases/genetics ; Jumonji Domain-Containing Histone Demethylases/metabolism
    Chemical Substances Histones ; Histone Demethylases (EC 1.14.11.-) ; Lysine (K3Z4F929H6) ; KDM4C protein, human ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-) ; KDM7A protein, human (EC 1.14.11.-)
    Language English
    Publishing date 2023-06-08
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 604857-2
    ISSN 1573-7233 ; 0167-7659
    ISSN (online) 1573-7233
    ISSN 0167-7659
    DOI 10.1007/s10555-023-10114-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1812: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  2. Article ; Online: Semi-Automated Phenotypic Analysis of Functional 3D Spheroid Cell Cultures.

    Stransky, Stephanie / Young, Dejauwne / Mikkelsen, Karoline / Thulesen, Annemette Præstegaard / Frandsen, Helle Sedighi / Sidoli, Simone

    Journal of visualized experiments : JoVE

    2023  , Issue 198

    Abstract: We present a protocol that describes the properties and advantages of using a standalone clinostat incubator for growing, treating, and monitoring 3D cell cultures. The clinostat mimics an environment where cells can assemble as highly reproducible ... ...

    Abstract We present a protocol that describes the properties and advantages of using a standalone clinostat incubator for growing, treating, and monitoring 3D cell cultures. The clinostat mimics an environment where cells can assemble as highly reproducible spheroids with low shear forces and active nutrient diffusion. We demonstrate that both cancer and non-cancer hepatocytes (HepG2/C3A and THLE-3 cell lines) require 3 weeks of growth prior to achieving functionalities comparable to liver cells. This protocol highlights the convenience of utilizing incubators for 3D cells with cameras monitoring the cell growth, as snapshots can be taken to count and measure spheroids upon treatment. We describe the comparison of THLE-3 and HepG2/C3A cell lines, showing how non-cancerous cell lines can be grown as well as immortalized cancer cells. We demonstrate and illustrate how proteomics experiments can be conducted from a few spheroids, which can be collected without perturbing cell signaling, i.e., no trypsinization required. We show that proteomics analysis can be used to monitor the typical liver phenotype of respiratory chain metabolism and the production of proteins involved in metal detoxification and describe a semi-automated system to count and measure the spheroid's area. Altogether, the protocol presents a toolbox that comprises a phenotypic characterization via image capture and a proteomics pipeline to experiment on 3D cell culture models.
    MeSH term(s) Cell Culture Techniques, Three Dimensional ; Cell Cycle ; Cell Line ; Cell Proliferation ; Diffusion
    Language English
    Publishing date 2023-08-18
    Publishing country United States
    Document type Journal Article ; Video-Audio Media ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/65086
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Volumetric segmentation in the context of posterior fossa-related pathologies: a systematic review.

    Kobets, Andrew J / Alavi, Seyed Ahmad Naseri / Ahmad, Samuel Jack / Castillo, Ashley / Young, Dejauwne / Minuti, Aurelia / Altschul, David J / Zhu, Michael / Abbott, Rick

    Neurosurgical review

    2024  Volume 47, Issue 1, Page(s) 170

    Abstract: Background: Segmentation tools continue to advance, evolving from manual contouring to deep learning. Researchers have utilized segmentation to study a myriad of posterior fossa-related conditions, such as Chiari malformation, trigeminal neuralgia, post- ...

    Abstract Background: Segmentation tools continue to advance, evolving from manual contouring to deep learning. Researchers have utilized segmentation to study a myriad of posterior fossa-related conditions, such as Chiari malformation, trigeminal neuralgia, post-operative pediatric cerebellar mutism syndrome, and Crouzon syndrome. Herein, we present a summary of the current literature on segmentation of the posterior fossa. The review highlights the various segmentation techniques, and their respective strengths and weaknesses, employed along with objectives and outcomes of the various studies reported in the literature.
    Methods: A literature search was conducted in PubMed, Embase, Cochrane, and Web of Science up to November 2023 for articles on segmentation techniques of posterior fossa. The two senior authors searched through databases based on the keywords of the article separately and then enrolled joint articles that met the inclusion and exclusion criteria.
    Results: The initial search identified 2205 articles. After applying inclusion and exclusion criteria, 77 articles were selected for full-text review after screening of titles/abstracts. 52 articles were ultimately included in the review. Segmentation techniques included manual, semi-automated, and fully automated (atlas-based, convolutional neural networks). The most common pathology investigated was Chiari malformation.
    Conclusions: Various forms of segmentation techniques have been used to assess posterior fossa volumes/pathologies and each has its advantages and disadvantages. We discuss these nuances and summarize the current state of literature in the context of posterior fossa-associated pathologies.
    MeSH term(s) Humans ; Arnold-Chiari Malformation/diagnostic imaging ; Arnold-Chiari Malformation/surgery ; Cranial Fossa, Posterior/diagnostic imaging ; Cranial Fossa, Posterior/surgery ; Cranial Fossa, Posterior/pathology ; Magnetic Resonance Imaging/methods
    Language English
    Publishing date 2024-04-19
    Publishing country Germany
    Document type Systematic Review ; Journal Article
    ZDB-ID 6907-3
    ISSN 1437-2320 ; 0344-5607
    ISSN (online) 1437-2320
    ISSN 0344-5607
    DOI 10.1007/s10143-024-02366-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1445: 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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  4. Article: Global level quantification of histone post-translational modifications in a 3d cell culture model of hepatic tissue

    Joseph-Chowdhury, Jazmine-Saskya N. / Stransky, Stephanie / Graff, Sarah / Cutler, Ronald / Young, Dejauwne / Kim, Julie S. / Madrid-Aliste, Carlos / Aguilan, Jennifer T. / Nieves, Edward / Sun, Yan / Yoo, Edwin J. / Sidoli, Simone

    Journal of visualized experiments. 2022 May 05, , no. 183

    2022  

    Abstract: Flat cultures of mammalian cells are a widely used in vitro approach for understanding cell physiology, but this system is limited in modeling solid tissues due to unnaturally rapid cell replication. This is particularly challenging when modeling mature ... ...

    Abstract Flat cultures of mammalian cells are a widely used in vitro approach for understanding cell physiology, but this system is limited in modeling solid tissues due to unnaturally rapid cell replication. This is particularly challenging when modeling mature chromatin, as fast replicating cells are frequently involved in DNA replication and have a heterogeneous polyploid population. Presented below is a workflow for modeling, treating, and analyzing quiescent chromatin modifications using a three-dimensional (3D) cell culture system. Using this protocol, hepatocellular carcinoma cell lines are grown as reproducible 3D spheroids in an incubator providing active nutrient diffusion and low shearing forces. Treatment with sodium butyrate and sodium succinate induced an increase in histone acetylation and succinylation, respectively. Increases in levels of histone acetylation and succinylation are associated with a more open chromatin state. Spheroids are then collected for isolation of cell nuclei, from which histone proteins are extracted for the analysis of their post-translational modifications. Histone analysis is performed via liquid chromatography coupled online with tandem mass spectrometry, followed by an in-house computational pipeline. Finally, examples of data representation to investigate the frequency and occurrence of combinatorial histone marks are shown.
    Keywords DNA replication ; acetylation ; cell culture ; cell physiology ; chromatin ; hepatoma ; histones ; liquid chromatography ; mammals ; models ; neoplasm cells ; polyploidy ; sodium ; sodium butyrate ; succinic acid ; tandem mass spectrometry
    Language English
    Dates of publication 2022-0505
    Size p. e63606.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/63606
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue.

    Joseph-Chowdhury, Jazmine-Saskya N / Stransky, Stephanie / Graff, Sarah / Cutler, Ronald / Young, Dejauwne / Kim, Julie S / Madrid-Aliste, Carlos / Aguilan, Jennifer T / Nieves, Edward / Sun, Yan / Yoo, Edwin J / Sidoli, Simone

    Journal of visualized experiments : JoVE

    2022  , Issue 183

    Abstract: Flat cultures of mammalian cells are a widely used in vitro approach for understanding cell physiology, but this system is limited in modeling solid tissues due to unnaturally rapid cell replication. This is particularly challenging when modeling mature ... ...

    Abstract Flat cultures of mammalian cells are a widely used in vitro approach for understanding cell physiology, but this system is limited in modeling solid tissues due to unnaturally rapid cell replication. This is particularly challenging when modeling mature chromatin, as fast replicating cells are frequently involved in DNA replication and have a heterogeneous polyploid population. Presented below is a workflow for modeling, treating, and analyzing quiescent chromatin modifications using a three-dimensional (3D) cell culture system. Using this protocol, hepatocellular carcinoma cell lines are grown as reproducible 3D spheroids in an incubator providing active nutrient diffusion and low shearing forces. Treatment with sodium butyrate and sodium succinate induced an increase in histone acetylation and succinylation, respectively. Increases in levels of histone acetylation and succinylation are associated with a more open chromatin state. Spheroids are then collected for isolation of cell nuclei, from which histone proteins are extracted for the analysis of their post-translational modifications. Histone analysis is performed via liquid chromatography coupled online with tandem mass spectrometry, followed by an in-house computational pipeline. Finally, examples of data representation to investigate the frequency and occurrence of combinatorial histone marks are shown.
    MeSH term(s) Acetylation ; Animals ; Cell Culture Techniques, Three Dimensional/methods ; Chromatin/physiology ; Chromatography, Liquid ; Histones/analysis ; Histones/metabolism ; Liver/metabolism ; Mammals/metabolism ; Protein Processing, Post-Translational/physiology ; Spheroids, Cellular/metabolism
    Chemical Substances Chromatin ; Histones
    Language English
    Publishing date 2022-05-05
    Publishing country United States
    Document type Journal Article ; Video-Audio Media ; Research Support, N.I.H., Extramural
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/63606
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Radiation Drives the Evolution of Orthotopic Xenografts Initiated from Glioblastoma Stem-like Cells.

    McAbee, Joseph H / Rath, Barbara H / Valdez, Kristin / Young, Dejauwne L / Wu, Xiaolin / Shankavaram, Uma T / Camphausen, Kevin / Tofilon, Philip J

    Cancer research

    2019  Volume 79, Issue 23, Page(s) 6032–6043

    Abstract: A consequence of the intratumor heterogeneity (ITH) of glioblastoma (GBM) is the susceptibility to treatment-driven evolution. To determine the potential of radiotherapy to influence GBM evolution, we used orthotopic xenografts initiated from ... ...

    Abstract A consequence of the intratumor heterogeneity (ITH) of glioblastoma (GBM) is the susceptibility to treatment-driven evolution. To determine the potential of radiotherapy to influence GBM evolution, we used orthotopic xenografts initiated from CD133
    MeSH term(s) Animals ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Brain Neoplasms/radiotherapy ; Cell Line, Tumor ; DNA Mutational Analysis ; Evolution, Molecular ; Female ; Genetic Heterogeneity/radiation effects ; Glioblastoma/genetics ; Glioblastoma/pathology ; Glioblastoma/radiotherapy ; Humans ; Mice ; Mutation/radiation effects ; Neoplastic Stem Cells/pathology ; Neoplastic Stem Cells/radiation effects ; Radiation Tolerance/genetics ; Tumor Microenvironment/genetics ; Tumor Microenvironment/radiation effects ; Exome Sequencing ; Xenograft Model Antitumor Assays
    Language English
    Publishing date 2019-10-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-19-2452
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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