LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 3 of total 3

Search options

  1. Article ; Online: ORAOV1, CCND1, and MIR548K Are the Driver Oncogenes of the 11q13 Amplicon in Squamous Cell Carcinoma.

    Mahieu, Céline I / Mancini, Andrew G / Vikram, Ellee P / Planells-Palop, Vicente / Joseph, Nancy M / Tward, Aaron D

    Molecular cancer research : MCR

    2023  Volume 22, Issue 2, Page(s) 152–168

    Abstract: 11q13 amplification is a frequent event in human cancer and in particular in squamous cell carcinomas (SCC). Despite almost invariably spanning 10 genes, it is unclear which genetic components of the amplicon are the key driver events in SCC. A ... ...

    Abstract 11q13 amplification is a frequent event in human cancer and in particular in squamous cell carcinomas (SCC). Despite almost invariably spanning 10 genes, it is unclear which genetic components of the amplicon are the key driver events in SCC. A combination of computational, in vitro, ex vivo, and in vivo models leveraging efficient primary human keratinocyte genome editing by Cas9-RNP electroporation, identified ORAOV1, CCND1, and MIR548K as the critical drivers of the amplicon in head and neck SCC. CCND1 amplification drives the cell cycle in a CDK4/6/RB1-independent fashion and may confer a novel dependency on RRM2. MIR548K contributes to epithelial-mesenchymal transition. Finally, we identify ORAOV1 as an oncogene that acts likely via its ability to modulate reactive oxygen species. Thus, the 11q13 amplicon drives SCC through at least three independent genetic elements and suggests therapeutic targets for this morbid and lethal disease.
    Implications: This work demonstrates novel mechanisms and ways to target these mechanisms underlying the most common amplification in squamous cell carcinoma, one of the most prevalent and deadly forms of human cancer.
    MeSH term(s) Humans ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Cell Cycle ; Cell Line, Tumor ; Cyclin D1/genetics ; Gene Amplification ; Oncogenes/genetics
    Chemical Substances CCND1 protein, human ; Cyclin D1 (136601-57-5) ; MIRN548 microRNA, human ; LTO1 protein, human
    Language English
    Publishing date 2023-11-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2098788-2
    ISSN 1557-3125 ; 1541-7786
    ISSN (online) 1557-3125
    ISSN 1541-7786
    DOI 10.1158/1541-7786.MCR-23-0746
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5744: 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)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing.

    Balke-Want, Hyatt / Keerthi, Vimal / Gkitsas, Nikolaos / Mancini, Andrew G / Kurgan, Gavin L / Fowler, Carley / Xu, Peng / Liu, Xikun / Asano, Kyle / Patel, Sunny / Fisher, Christopher J / Brown, Annie K / Tunuguntla, Ramya H / Patel, Shabnum / Sotillo, Elena / Mackall, Crystal L / Feldman, Steven A

    Molecular cancer

    2023  Volume 22, Issue 1, Page(s) 100

    Abstract: Background: Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma cell malignancies and could disrupt the therapeutic landscape of solid tumors. However, access to CAR-T cells is not adequate to ... ...

    Abstract Background: Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma cell malignancies and could disrupt the therapeutic landscape of solid tumors. However, access to CAR-T cells is not adequate to meet clinical needs, in part due to high cost and long lead times for manufacturing clinical grade virus. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 and double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) via homology-directed repair (HDR), however yields with this approach have been limiting for clinical application (dsDNA) or access to large yields sufficient to meet the manufacturing demands outside early phase clinical trials is limited (ssDNA).
    Methods: We applied homology-independent targeted insertion (HITI) or HDR using CRISPR/Cas9 and nanoplasmid DNA to insert an anti-GD2 CAR into the T cell receptor alpha constant (TRAC) locus and compared both targeted insertion strategies in our system. Next, we optimized post-HITI CRISPR EnrichMENT (CEMENT) to seamlessly integrate it into a 14-day process and compared our knock-in with viral transduced anti-GD2 CAR-T cells. Finally, we explored the off-target genomic toxicity of our genomic engineering approach.
    Results: Here, we show that site directed CAR integration utilizing nanoplasmid DNA delivered via HITI provides high cell yields and highly functional cells. CEMENT enriched CAR T cells to approximately 80% purity, resulting in therapeutically relevant dose ranges of 5.5 × 10
    Conclusions: Our work provides a novel platform to perform guided CAR insertion into primary human T-cells using nanoplasmid DNA and holds the potential to increase access to CAR-T cell therapies.
    MeSH term(s) Humans ; T-Lymphocytes ; DNA ; Recombinational DNA Repair ; Immunotherapy, Adoptive
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2023-06-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2091373-4
    ISSN 1476-4598 ; 1476-4598
    ISSN (online) 1476-4598
    ISSN 1476-4598
    DOI 10.1186/s12943-023-01799-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Antibody targeting of E3 ubiquitin ligases for receptor degradation.

    Marei, Hadir / Tsai, Wen-Ting K / Kee, Yee-Seir / Ruiz, Karen / He, Jieyan / Cox, Chris / Sun, Tao / Penikalapati, Sai / Dwivedi, Pankaj / Choi, Meena / Kan, David / Saenz-Lopez, Pablo / Dorighi, Kristel / Zhang, Pamela / Kschonsak, Yvonne T / Kljavin, Noelyn / Amin, Dhara / Kim, Ingrid / Mancini, Andrew G /
    Nguyen, Thao / Wang, Chunling / Janezic, Eric / Doan, Alexander / Mai, Elaine / Xi, Hongkang / Gu, Chen / Heinlein, Melanie / Biehs, Brian / Wu, Jia / Lehoux, Isabelle / Harris, Seth / Comps-Agrar, Laetitia / Seshasayee, Dhaya / de Sauvage, Frederic J / Grimmer, Matthew / Li, Jing / Agard, Nicholas J / de Sousa E Melo, Felipe

    Nature

    2022  Volume 610, Issue 7930, Page(s) 182–189

    Abstract: Most current therapies that target plasma membrane receptors function by antagonizing ligand binding or enzymatic activities. However, typical mammalian proteins comprise multiple domains that execute discrete but coordinated activities. Thus, inhibition ...

    Abstract Most current therapies that target plasma membrane receptors function by antagonizing ligand binding or enzymatic activities. However, typical mammalian proteins comprise multiple domains that execute discrete but coordinated activities. Thus, inhibition of one domain often incompletely suppresses the function of a protein. Indeed, targeted protein degradation technologies, including proteolysis-targeting chimeras
    MeSH term(s) Animals ; Antibodies/immunology ; Antibodies/metabolism ; Antibody Specificity ; Colorectal Neoplasms/metabolism ; Ligands ; Membrane Proteins/immunology ; Membrane Proteins/metabolism ; Proteolysis ; Receptors, Cell Surface/immunology ; Receptors, Cell Surface/metabolism ; Substrate Specificity ; Ubiquitin-Protein Ligases/immunology ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances Antibodies ; Ligands ; Membrane Proteins ; Receptors, Cell Surface ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
    Language English
    Publishing date 2022-09-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-022-05235-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 26: 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)
    Zs.MG 9: Show issues
    Zs.MO 244: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top