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  1. AU="Saini, Avneesh K"
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  1. Article ; Online: Multimeric Anti-DR5 IgM Agonist Antibody IGM-8444 Is a Potent Inducer of Cancer Cell Apoptosis and Synergizes with Chemotherapy and BCL-2 Inhibitor ABT-199.

    Wang, Beatrice T / Kothambawala, Tasnim / Wang, Ling / Matthew, Thomas J / Calhoun, Susan E / Saini, Avneesh K / Kotturi, Maya F / Hernandez, Genevive / Humke, Eric W / Peterson, Marvin S / Sinclair, Angus M / Keyt, Bruce A

    Molecular cancer therapeutics

    2021  Volume 20, Issue 12, Page(s) 2483–2494

    Abstract: Death receptor 5 (DR5) is an attractive target for cancer therapy due to its broad upregulated expression in multiple cancers and ability to directly induce apoptosis. Though anti-DR5 IgG antibodies have been evaluated in clinical trials, limited ... ...

    Abstract Death receptor 5 (DR5) is an attractive target for cancer therapy due to its broad upregulated expression in multiple cancers and ability to directly induce apoptosis. Though anti-DR5 IgG antibodies have been evaluated in clinical trials, limited efficacy has been attributed to insufficient receptor crosslinking. IGM-8444 is an engineered, multivalent agonistic IgM antibody with 10 binding sites to DR5 that induces cancer cell apoptosis through efficient DR5 multimerization. IGM-8444 bound to DR5 with high avidity and was substantially more potent than an IgG with the same binding domains. IGM-8444 induced cytotoxicity in a broad panel of solid and hematologic cancer cell lines but did not kill primary human hepatocytes
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Genes, bcl-2/genetics ; Humans ; Immunoglobulin M/pharmacology ; Immunoglobulin M/therapeutic use ; Mice ; Mice, Nude ; Receptors, TNF-Related Apoptosis-Inducing Ligand/antagonists & inhibitors ; Sulfonamides/pharmacology ; Sulfonamides/therapeutic use
    Chemical Substances Antineoplastic Agents ; Bridged Bicyclo Compounds, Heterocyclic ; Immunoglobulin M ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; Sulfonamides ; venetoclax (N54AIC43PW)
    Language English
    Publishing date 2021-10-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2063563-1
    ISSN 1538-8514 ; 1535-7163
    ISSN (online) 1538-8514
    ISSN 1535-7163
    DOI 10.1158/1535-7163.MCT-20-1132
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5750: 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)

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  2. Article ; Online: Discovery of enzymes for toluene synthesis from anoxic microbial communities.

    Beller, Harry R / Rodrigues, Andria V / Zargar, Kamrun / Wu, Yu-Wei / Saini, Avneesh K / Saville, Renee M / Pereira, Jose H / Adams, Paul D / Tringe, Susannah G / Petzold, Christopher J / Keasling, Jay D

    Nature chemical biology

    2018  Volume 14, Issue 5, Page(s) 451–457

    Abstract: Microbial toluene biosynthesis was reported in anoxic lake sediments more than three decades ago, but the enzyme catalyzing this biochemically challenging reaction has never been identified. Here we report the toluene-producing enzyme PhdB, a glycyl ... ...

    Abstract Microbial toluene biosynthesis was reported in anoxic lake sediments more than three decades ago, but the enzyme catalyzing this biochemically challenging reaction has never been identified. Here we report the toluene-producing enzyme PhdB, a glycyl radical enzyme of bacterial origin that catalyzes phenylacetate decarboxylation, and its cognate activating enzyme PhdA, a radical S-adenosylmethionine enzyme, discovered in two distinct anoxic microbial communities that produce toluene. The unconventional process of enzyme discovery from a complex microbial community (>300,000 genes), rather than from a microbial isolate, involved metagenomics- and metaproteomics-enabled biochemistry, as well as in vitro confirmation of activity with recombinant enzymes. This work expands the known catalytic range of glycyl radical enzymes (only seven reaction types had been characterized previously) and aromatic-hydrocarbon-producing enzymes, and will enable first-time biochemical synthesis of an aromatic fuel hydrocarbon from renewable resources, such as lignocellulosic biomass, rather than from petroleum.
    MeSH term(s) Acidobacteria/enzymology ; Acidobacteria/genetics ; Acidobacteria/isolation & purification ; Anaerobiosis ; Bacteria/enzymology ; Bacteria/genetics ; Biomass ; Carboxy-Lyases/metabolism ; Catalysis ; Genes, Bacterial ; Geologic Sediments/microbiology ; Lakes/microbiology ; Lignin/chemistry ; Likelihood Functions ; Metagenomics ; Microbiota ; Phenylacetates/chemistry ; Phylogeny ; Proteomics ; Recombinant Proteins/metabolism ; Sewage/microbiology ; Toluene/metabolism
    Chemical Substances Phenylacetates ; Recombinant Proteins ; Sewage ; lignocellulose (11132-73-3) ; Toluene (3FPU23BG52) ; Lignin (9005-53-2) ; Carboxy-Lyases (EC 4.1.1.-) ; phenylacetic acid (ER5I1W795A)
    Language English
    Publishing date 2018-03-19
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2202962-X
    ISSN 1552-4469 ; 1552-4450
    ISSN (online) 1552-4469
    ISSN 1552-4450
    DOI 10.1038/s41589-018-0017-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6251: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 90: Show issues

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