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  1. Article: ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1.

    Rincon-Torroella, Jordina / Molin, Marco Dal / Mog, Brian / Han, Gyuri / Watson, Evangeline / Wyhs, Nicolas / Ishiyama, Shun / Ahmedna, Taha / Minn, Il / Azad, Nilofer S / Bettegowda, Chetan / Papadopoulos, Nickolas / Kinzler, Kenneth W / Zhou, Shibin / Vogelstein, Bert / Gabrielson, Kathleen / Sur, Surojit

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s exhibit a marked overexpression of Monocarboxylate Transporter 1 (MCT1) offering a unique opportunity for therapy. However, biochemical inhibitors of MCT1 have proven unsuccessful in clinical trials. ...

    Abstract Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s exhibit a marked overexpression of Monocarboxylate Transporter 1 (MCT1) offering a unique opportunity for therapy. However, biochemical inhibitors of MCT1 have proven unsuccessful in clinical trials. In this study we present an alternative approach using 3-Bromopyruvate (3BP) to target MCT1 overexpressing PDACs. 3BP is a cytotoxic agent that is known to be transported into cells via MCT1, but its clinical usefulness has been hampered by difficulties in delivering the drug systemically. We describe here a novel microencapsulated formulation of 3BP (ME3BP-7), that is effective against a variety of PDAC cells in vitro and remains stable in serum. Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity. ME3BP-7 is, therefore, a prototype of a promising new drug, in which the targeting moiety and the cytotoxic moiety are both contained within the same single small molecule.
    One sentence summary: ME3BP-7 is a novel formulation of 3BP that resists serum degradation and rapidly kills pancreatic cancer cells expressing high levels of MCT1 with tolerable toxicity in mice.
    Language English
    Publishing date 2023-07-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.23.550207
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape.

    Cook, Ashley L / Sur, Surojit / Dobbyn, Laura / Watson, Evangeline / Cohen, Joshua D / Ptak, Blair / Lee, Bum Seok / Paul, Suman / Hsiue, Emily / Popoli, Maria / Vogelstein, Bert / Papadopoulos, Nickolas / Bettegowda, Chetan / Gabrielson, Kathy / Zhou, Shibin / Kinzler, Kenneth W / Wyhs, Nicolas

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Despite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on the tumor cell surface. As an intrinsic cellular pathway, nonsense- mediated decay (NMD) conceals neoantigens through the ... ...

    Abstract Despite exciting developments in cancer immunotherapy, its broad application is limited by the paucity of targetable antigens on the tumor cell surface. As an intrinsic cellular pathway, nonsense- mediated decay (NMD) conceals neoantigens through the destruction of the RNA products from genes harboring truncating mutations. We developed and conducted a high throughput screen, based on the ratiometric analysis of transcripts, to identify critical mediators of NMD. This screen revealed disruption of kinase SMG1's phosphorylation of UPF1 as a potent disruptor of NMD. This led us to design a novel SMG1 inhibitor, KVS0001, that elevates the expression of transcripts and proteins resulting from truncating mutations
    One sentence summary: Disruption of the nonsense-mediated decay pathway with a newly developed SMG1 inhibitor with
    Language English
    Publishing date 2023-12-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.28.573594
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: TRBC1-targeting antibody-drug conjugates for the treatment of T cell cancers.

    Nichakawade, Tushar D / Ge, Jiaxin / Mog, Brian J / Lee, Bum Seok / Pearlman, Alexander H / Hwang, Michael S / DiNapoli, Sarah R / Wyhs, Nicolas / Marcou, Nikita / Glavaris, Stephanie / Konig, Maximilian F / Gabelli, Sandra B / Watson, Evangeline / Sterling, Cole / Wagner-Johnston, Nina / Rozati, Sima / Swinnen, Lode / Fuchs, Ephraim / Pardoll, Drew M /
    Gabrielson, Kathy / Papadopoulos, Nickolas / Bettegowda, Chetan / Kinzler, Kenneth W / Zhou, Shibin / Sur, Surojit / Vogelstein, Bert / Paul, Suman

    Nature

    2024  Volume 628, Issue 8007, Page(s) 416–423

    Abstract: Antibody and chimeric antigen receptor (CAR) T cell-mediated targeted therapies have improved survival in patients with solid and haematologic ... ...

    Abstract Antibody and chimeric antigen receptor (CAR) T cell-mediated targeted therapies have improved survival in patients with solid and haematologic malignancies
    MeSH term(s) Animals ; Female ; Humans ; Mice ; Immunoconjugates/immunology ; Immunoconjugates/therapeutic use ; Immunotherapy, Adoptive ; Leukemia, T-Cell/drug therapy ; Leukemia, T-Cell/immunology ; Lymphoma, T-Cell/drug therapy ; Lymphoma, T-Cell/immunology ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; Xenograft Model Antitumor Assays
    Chemical Substances Immunoconjugates ; Receptors, Antigen, T-Cell, alpha-beta ; Receptors, Chimeric Antigen ; TRBC1 protein, human
    Language English
    Publishing date 2024-03-27
    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/s41586-024-07233-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    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

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  4. Article ; Online: Bispecific antibodies targeting mutant

    Douglass, Jacqueline / Hsiue, Emily Han-Chung / Mog, Brian J / Hwang, Michael S / DiNapoli, Sarah R / Pearlman, Alexander H / Miller, Michelle S / Wright, Katharine M / Azurmendi, P Aitana / Wang, Qing / Paul, Suman / Schaefer, Annika / Skora, Andrew D / Molin, Marco Dal / Konig, Maximilian F / Liu, Qiang / Watson, Evangeline / Li, Yana / Murphy, Michael B /
    Pardoll, Drew M / Bettegowda, Chetan / Papadopoulos, Nickolas / Gabelli, Sandra B / Kinzler, Kenneth W / Vogelstein, Bert / Zhou, Shibin

    Science immunology

    2021  Volume 6, Issue 57

    Abstract: Mutations in ... ...

    Abstract Mutations in the
    MeSH term(s) Amino Acid Sequence ; Animals ; Antibodies, Bispecific/immunology ; Antibodies, Bispecific/pharmacology ; Antigens, Neoplasm/chemistry ; Antigens, Neoplasm/immunology ; Biomarkers, Tumor/antagonists & inhibitors ; Biomarkers, Tumor/chemistry ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/immunology ; Cell Line ; Cross Reactions ; HLA Antigens/immunology ; Humans ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Mutant Proteins/antagonists & inhibitors ; Mutant Proteins/chemistry ; Mutant Proteins/immunology ; Mutation ; Peptide Fragments ; Protein Binding/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; ras Proteins/antagonists & inhibitors ; ras Proteins/chemistry ; ras Proteins/genetics ; ras Proteins/immunology
    Chemical Substances Antibodies, Bispecific ; Antigens, Neoplasm ; Biomarkers, Tumor ; HLA Antigens ; Mutant Proteins ; Peptide Fragments ; ras Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2021-03-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.abd5515
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Targeting a neoantigen derived from a common

    Hsiue, Emily Han-Chung / Wright, Katharine M / Douglass, Jacqueline / Hwang, Michael S / Mog, Brian J / Pearlman, Alexander H / Paul, Suman / DiNapoli, Sarah R / Konig, Maximilian F / Wang, Qing / Schaefer, Annika / Miller, Michelle S / Skora, Andrew D / Azurmendi, P Aitana / Murphy, Michael B / Liu, Qiang / Watson, Evangeline / Li, Yana / Pardoll, Drew M /
    Bettegowda, Chetan / Papadopoulos, Nickolas / Kinzler, Kenneth W / Vogelstein, Bert / Gabelli, Sandra B / Zhou, Shibin

    Science (New York, N.Y.)

    2021  Volume 371, Issue 6533

    Abstract: ... ...

    Abstract TP53
    MeSH term(s) Alleles ; Animals ; Antibodies, Bispecific/chemistry ; Antibodies, Bispecific/immunology ; Antibodies, Bispecific/therapeutic use ; Antibodies, Neoplasm/chemistry ; Antibodies, Neoplasm/immunology ; Antibodies, Neoplasm/therapeutic use ; Antigens, Neoplasm/immunology ; Arginine/genetics ; COS Cells ; Chlorocebus aethiops ; Female ; HEK293 Cells ; HLA-A2 Antigen/chemistry ; HLA-A2 Antigen/genetics ; HLA-A2 Antigen/immunology ; Histidine/genetics ; Humans ; Immunization, Passive ; Jurkat Cells ; Lymphocyte Activation ; Mice, Inbred NOD ; Mutation ; Neoplasms/therapy ; T-Lymphocytes/immunology ; Tumor Suppressor Protein p53/chemistry ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/immunology ; Xenograft Model Antitumor Assays ; Mice
    Chemical Substances Antibodies, Bispecific ; Antibodies, Neoplasm ; Antigens, Neoplasm ; HLA-A*02:01 antigen ; HLA-A2 Antigen ; TP53 protein, human ; Tumor Suppressor Protein p53 ; Histidine (4QD397987E) ; Arginine (94ZLA3W45F)
    Language English
    Publishing date 2021-03-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abc8697
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 27: 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 77: Show issues

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