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  1. Article ; Online: Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy.

    Hsieh, Yao-Te / Gang, Eun Ji / Geng, Huimin / Park, Eugene / Huantes, Sandra / Chudziak, Doreen / Dauber, Katrin / Schaefer, Paul / Scharman, Carlton / Shimada, Hiroyuki / Shojaee, Seyedmehdi / Klemm, Lars / Parameswaran, Reshmi / Loh, Mignon / Kang, Eun-Suk / Koo, Hong Hoe / Hofmann, Wolf-Karsten / Andrade, Jacob / Crooks, Gay M /
    Willman, Cheryl L / Müschen, Markus / Papayannopoulou, Thalia / Heisterkamp, Nora / Bönig, Halvard / Kim, Yong-Mi

    Blood

    2013  Volume 121, Issue 10, Page(s) 1814–1818

    Abstract: Bone marrow (BM) provides chemoprotection for acute lymphoblastic leukemia (ALL) cells, contributing to lack of efficacy of current therapies. Integrin alpha4 (alpha4) mediates stromal adhesion of normal and malignant B-cell precursors, and according to ... ...

    Abstract Bone marrow (BM) provides chemoprotection for acute lymphoblastic leukemia (ALL) cells, contributing to lack of efficacy of current therapies. Integrin alpha4 (alpha4) mediates stromal adhesion of normal and malignant B-cell precursors, and according to gene expression analyses from 207 children with minimal residual disease, is highly associated with poorest outcome. We tested whether interference with alpha4-mediated stromal adhesion might be a new ALL treatment. Two models of leukemia were used, one genetic (conditional alpha4 ablation of BCR-ABL1 [p210(+)] leukemia) and one pharmacological (anti-functional alpha4 antibody treatment of primary ALL). Conditional deletion of alpha4 sensitized leukemia cell to nilotinib. Adhesion of primary pre-B ALL cells was alpha4-dependent; alpha4 blockade sensitized primary ALL cells toward chemotherapy. Chemotherapy combined with Natalizumab prolonged survival of NOD/SCID recipients of primary ALL, suggesting adjuvant alpha4 inhibition as a novel strategy for pre-B ALL.
    MeSH term(s) Animals ; Antibodies, Monoclonal, Humanized/pharmacology ; Bone Marrow/drug effects ; Bone Marrow/metabolism ; Bone Marrow/pathology ; Cell Adhesion ; Child ; Drug Resistance, Neoplasm ; Flow Cytometry ; Fusion Proteins, bcr-abl/physiology ; Humans ; Integrases/metabolism ; Integrin alpha4/chemistry ; Integrin alpha4/genetics ; Integrin alpha4/metabolism ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Natalizumab ; Neoplasm, Residual/drug therapy ; Neoplasm, Residual/metabolism ; Neoplasm, Residual/mortality ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Stromal Cells/drug effects ; Stromal Cells/metabolism ; Stromal Cells/pathology
    Chemical Substances Antibodies, Monoclonal, Humanized ; Natalizumab ; RNA, Messenger ; Integrin alpha4 (143198-26-9) ; Fusion Proteins, bcr-abl (EC 2.7.10.2) ; Cre recombinase (EC 2.7.7.-) ; Integrases (EC 2.7.7.-)
    Language English
    Publishing date 2013-01-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2012-01-406272
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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    Zs.MO 364: Show issues

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  2. Article ; Online: Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia.

    Park, Eugene / Gang, Eun Ji / Hsieh, Yao-Te / Schaefer, Paul / Chae, Sanna / Klemm, Lars / Huantes, Sandra / Loh, Mignon / Conway, Edward M / Kang, Eun-Suk / Hoe Koo, Hong / Hofmann, Wolf-Karsten / Heisterkamp, Nora / Pelus, Louis / Keerthivasan, Ganesan / Crispino, John / Kahn, Michael / Müschen, Markus / Kim, Yong-Mi

    Blood

    2011  Volume 118, Issue 8, Page(s) 2191–2199

    Abstract: Relapse of drug-resistant acute lymphoblastic leukemia (ALL) has been associated with increased expression of survivin/BIRC5, an inhibitor of apoptosis protein, suggesting a survival advantage for ALL cells. In the present study, we report that ... ...

    Abstract Relapse of drug-resistant acute lymphoblastic leukemia (ALL) has been associated with increased expression of survivin/BIRC5, an inhibitor of apoptosis protein, suggesting a survival advantage for ALL cells. In the present study, we report that inhibition of survivin in patient-derived ALL can eradicate leukemia. Targeting survivin with shRNA in combination with chemotherapy resulted in no detectable minimal residual disease in a xenograft model of primary ALL. Similarly, pharmacologic knock-down of survivin using EZN-3042, a novel locked nucleic acid antisense oligonucleotide, in combination with chemotherapy eliminated drug-resistant ALL cells. These findings show the importance of survivin expression in drug resistance and demonstrate that survivin inhibition may represent a powerful approach to overcoming drug resistance and preventing relapse in patients with ALL.
    MeSH term(s) Animals ; Combined Modality Therapy ; Drug Resistance, Neoplasm/genetics ; Gene Expression ; Gene Targeting ; Humans ; Inhibitor of Apoptosis Proteins/antagonists & inhibitors ; Inhibitor of Apoptosis Proteins/deficiency ; Inhibitor of Apoptosis Proteins/genetics ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Neoplasm, Residual ; Oligonucleotides/genetics ; Oligonucleotides/therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; RNA, Small Interfering/genetics ; Repressor Proteins/deficiency ; Repressor Proteins/genetics ; Survivin ; Tumor Stem Cell Assay ; Xenograft Model Antitumor Assays
    Chemical Substances BIRC5 protein, human ; Birc5 protein, mouse ; EZN 3042 ; Inhibitor of Apoptosis Proteins ; Oligonucleotides ; RNA, Small Interfering ; Repressor Proteins ; Survivin
    Language English
    Publishing date 2011-06-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2011-04-351239
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.140: 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.MO 364: 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.

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