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  1. Article ; Online: Outcomes of Uterine Rupture in the Setting of the Unscarred Compared With the Scarred Uterus.

    McEvoy, Aoife / Corbett, Gillian A / Nolan, Ciara / Daly, Ronan / Murnane, Megan / Higgins, Shane / Malone, Fergal D / O'Connell, Michael P / Hehir, Mark P / Walsh, Jennifer M

    Obstetrics and gynecology

    2023  Volume 141, Issue 4, Page(s) 854–856

    Abstract: Uterine rupture is a rare obstetric complication that is associated with maternal and neonatal morbidity and mortality. The aim of this study was to examine uterine rupture and its outcomes in the setting of the unscarred compared with the scarred uterus. ...

    Abstract Uterine rupture is a rare obstetric complication that is associated with maternal and neonatal morbidity and mortality. The aim of this study was to examine uterine rupture and its outcomes in the setting of the unscarred compared with the scarred uterus. A retrospective observational cohort study was performed examining all cases of uterine rupture in three tertiary care hospitals in Dublin, Ireland, over a 20-year period. The primary outcome was perinatal mortality rate with uterine rupture, which was 11.02% (95% CI 6.5-17.3). There was no significant difference in perinatal mortality between cases of scarred and unscarred uterine rupture. Unscarred uterine rupture was associated with higher maternal morbidity , defined as major obstetric hemorrhage or hysterectomy.
    MeSH term(s) Pregnancy ; Infant, Newborn ; Female ; Humans ; Uterine Rupture/etiology ; Uterine Rupture/surgery ; Pregnancy Outcome ; Retrospective Studies ; Uterus ; Hysterectomy/adverse effects ; Perinatal Death
    Language English
    Publishing date 2023-03-09
    Publishing country United States
    Document type Observational Study ; Journal Article
    ZDB-ID 207330-4
    ISSN 1873-233X ; 0029-7844
    ISSN (online) 1873-233X
    ISSN 0029-7844
    DOI 10.1097/AOG.0000000000005108
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Potent Activity of an Anti-ICAM1 Antibody-Drug Conjugate against Multiple Myeloma.

    Sherbenou, Daniel W / Su, Yang / Behrens, Christopher R / Aftab, Blake T / Perez de Acha, Olivia / Murnane, Megan / Bearrows, Shelby C / Hann, Byron C / Wolf, Jeffery L / Martin, Thomas G / Liu, Bin

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2020  Volume 26, Issue 22, Page(s) 6028–6038

    Abstract: Purpose: New therapies have changed the outlook for patients with multiple myeloma, but novel agents are needed for patients who are refractory or relapsed on currently approved drug classes. Novel targets other than CD38 and BCMA are needed for new ... ...

    Abstract Purpose: New therapies have changed the outlook for patients with multiple myeloma, but novel agents are needed for patients who are refractory or relapsed on currently approved drug classes. Novel targets other than CD38 and BCMA are needed for new immunotherapy development, as resistance to daratumumab and emerging anti-BCMA approaches appears inevitable. One potential target of interest in myeloma is ICAM1. Naked anti-ICAM1 antibodies were active in preclinical models of myeloma and safe in patients, but showed limited clinical efficacy. Here, we sought to achieve improved targeting of multiple myeloma with an anti-ICAM1 antibody-drug conjugate (ADC).
    Experimental design: Our anti-ICAM1 human mAb was conjugated to an auristatin derivative, and tested against multiple myeloma cell lines
    Results: The anti-ICAM1 ADC displayed potent anti-myeloma cytotoxicity
    Conclusions: We propose that anti-ICAM1 ADC should be further studied for toxicity, and if safe, tested for clinical efficacy in patients with relapsed or refractory multiple myeloma.
    MeSH term(s) ADP-ribosyl Cyclase 1/antagonists & inhibitors ; ADP-ribosyl Cyclase 1/immunology ; Adult ; Aged ; Animals ; Antibodies, Anti-Idiotypic/immunology ; Antibodies, Anti-Idiotypic/pharmacology ; Antibodies, Monoclonal/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Female ; Flow Cytometry ; Heterografts ; Humans ; Immunoconjugates/immunology ; Immunoconjugates/pharmacology ; Intercellular Adhesion Molecule-1/genetics ; Intercellular Adhesion Molecule-1/immunology ; Male ; Mice ; Middle Aged ; Multiple Myeloma/drug therapy ; Multiple Myeloma/genetics ; Multiple Myeloma/immunology ; Multiple Myeloma/pathology
    Chemical Substances Antibodies, Anti-Idiotypic ; Antibodies, Monoclonal ; ICAM1 protein, human ; Immunoconjugates ; Intercellular Adhesion Molecule-1 (126547-89-5) ; daratumumab (4Z63YK6E0E) ; ADP-ribosyl Cyclase 1 (EC 3.2.2.6)
    Language English
    Publishing date 2020-09-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-20-0400
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment.

    Lam, Christine / Ferguson, Ian D / Mariano, Margarette C / Lin, Yu-Hsiu T / Murnane, Megan / Liu, Hui / Smith, Geoffrey A / Wong, Sandy W / Taunton, Jack / Liu, Jun O / Mitsiades, Constantine S / Hann, Byron C / Aftab, Blake T / Wiita, Arun P

    Haematologica

    2018  Volume 103, Issue 7, Page(s) 1218–1228

    Abstract: The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Activation of JAK/STAT signaling is thought to be a central component of these microenvironment-induced phenotypes. In a prior drug ... ...

    Abstract The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Activation of JAK/STAT signaling is thought to be a central component of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor Food and Drug Administration (FDA) approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Herein, we validated
    MeSH term(s) Animals ; Bone Marrow/drug effects ; Bone Marrow/pathology ; Cell Communication ; Disease Models, Animal ; Drug Repositioning ; Humans ; Janus Kinases/metabolism ; Mesenchymal Stem Cells/metabolism ; Mice ; Multiple Myeloma/drug therapy ; Multiple Myeloma/metabolism ; Multiple Myeloma/pathology ; Phosphoproteins/metabolism ; Piperidines/administration & dosage ; Piperidines/therapeutic use ; Plasma Cells/metabolism ; Plasma Cells/pathology ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/therapeutic use ; Proteome ; Proteomics/methods ; Pyrimidines/administration & dosage ; Pyrimidines/therapeutic use ; Pyrroles/administration & dosage ; Pyrroles/therapeutic use ; STAT Transcription Factors/metabolism ; Signal Transduction/drug effects ; Tumor Microenvironment/drug effects ; Xenograft Model Antitumor Assays
    Chemical Substances Phosphoproteins ; Piperidines ; Protein Kinase Inhibitors ; Proteome ; Pyrimidines ; Pyrroles ; STAT Transcription Factors ; tofacitinib (87LA6FU830) ; Janus Kinases (EC 2.7.10.2)
    Language English
    Publishing date 2018-04-05
    Publishing country Italy
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2017.174482
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Validation of the Hsp70-Bag3 protein-protein interaction as a potential therapeutic target in cancer.

    Li, Xiaokai / Colvin, Teresa / Rauch, Jennifer N / Acosta-Alvear, Diego / Kampmann, Martin / Dunyak, Bryan / Hann, Byron / Aftab, Blake T / Murnane, Megan / Cho, Min / Walter, Peter / Weissman, Jonathan S / Sherman, Michael Y / Gestwicki, Jason E

    Molecular cancer therapeutics

    2015  Volume 14, Issue 3, Page(s) 642–648

    Abstract: Hsp70 is a stress-inducible molecular chaperone that is required for cancer development at several steps. Targeting the active site of Hsp70 has proven relatively challenging, driving interest in alternative approaches. Hsp70 collaborates with the Bcl2- ... ...

    Abstract Hsp70 is a stress-inducible molecular chaperone that is required for cancer development at several steps. Targeting the active site of Hsp70 has proven relatively challenging, driving interest in alternative approaches. Hsp70 collaborates with the Bcl2-associated athanogene 3 (Bag3) to promote cell survival through multiple pathways, including FoxM1. Therefore, inhibitors of the Hsp70-Bag3 protein-protein interaction (PPI) may provide a noncanonical way to target this chaperone. We report that JG-98, an allosteric inhibitor of this PPI, indeed has antiproliferative activity (EC50 values between 0.3 and 4 μmol/L) across cancer cell lines from multiple origins. JG-98 destabilized FoxM1 and relieved suppression of downstream effectors, including p21 and p27. On the basis of these findings, JG-98 was evaluated in mice for pharmacokinetics, tolerability, and activity in two xenograft models. The results suggested that the Hsp70-Bag3 interaction may be a promising, new target for anticancer therapy.
    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Antineoplastic Agents/pharmacology ; Apoptosis Regulatory Proteins/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Forkhead Box Protein M1 ; Forkhead Transcription Factors/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; HSP70 Heat-Shock Proteins/metabolism ; HT29 Cells ; HeLa Cells ; Humans ; MCF-7 Cells ; Mice ; Proliferating Cell Nuclear Antigen/metabolism ; Protein Interaction Domains and Motifs/physiology
    Chemical Substances Adaptor Proteins, Signal Transducing ; Antineoplastic Agents ; Apoptosis Regulatory Proteins ; BAG3 protein, human ; CDKN1A protein, human ; Cyclin-Dependent Kinase Inhibitor p21 ; FOXM1 protein, human ; Forkhead Box Protein M1 ; Forkhead Transcription Factors ; HSP70 Heat-Shock Proteins ; Proliferating Cell Nuclear Antigen ; p27 antigen
    Language English
    Publishing date 2015-01-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2063563-1
    ISSN 1538-8514 ; 1535-7163
    ISSN (online) 1538-8514
    ISSN 1535-7163
    DOI 10.1158/1535-7163.MCT-14-0650
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The p97 Inhibitor CB-5083 Is a Unique Disrupter of Protein Homeostasis in Models of Multiple Myeloma.

    Le Moigne, Ronan / Aftab, Blake T / Djakovic, Stevan / Dhimolea, Eugen / Valle, Eduardo / Murnane, Megan / King, Emily M / Soriano, Ferdie / Menon, Mary-Kamala / Wu, Zhi Yong / Wong, Stephen T / Lee, Grace J / Yao, Bing / Wiita, Arun P / Lam, Christine / Rice, Julie / Wang, Jinhai / Chesi, Marta / Bergsagel, P Leif /
    Kraus, Marianne / Driessen, Christoph / Kiss von Soly, Szerenke / Yakes, F Michael / Wustrow, David / Shawver, Laura / Zhou, Han-Jie / Martin, Thomas G / Wolf, Jeffrey L / Mitsiades, Constantine S / Anderson, Daniel J / Rolfe, Mark

    Molecular cancer therapeutics

    2017  Volume 16, Issue 11, Page(s) 2375–2386

    Abstract: Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system, and CB-5083, a first-in-class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematologic and solid ... ...

    Abstract Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system, and CB-5083, a first-in-class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematologic and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma cell lines and a number of
    MeSH term(s) Adenosine Triphosphatases/antagonists & inhibitors ; Adenosine Triphosphatases/genetics ; Animals ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Indoles/administration & dosage ; Mice ; Multiple Myeloma/drug therapy ; Multiple Myeloma/genetics ; Multiple Myeloma/pathology ; Nuclear Proteins/antagonists & inhibitors ; Nuclear Proteins/genetics ; Nuclear Respiratory Factor 1/genetics ; Proteasome Endopeptidase Complex/drug effects ; Proteasome Inhibitors/administration & dosage ; Pyrimidines/administration & dosage ; Ubiquitin/genetics ; Unfolded Protein Response/drug effects ; Xenograft Model Antitumor Assays
    Chemical Substances CB-5083 ; Indoles ; NRF1 protein, human ; Nuclear Proteins ; Nuclear Respiratory Factor 1 ; Proteasome Inhibitors ; Pyrimidines ; Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Adenosine Triphosphatases (EC 3.6.1.-) ; p97 ATPase (EC 3.6.1.-)
    Language English
    Publishing date 2017-09-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2063563-1
    ISSN 1538-8514 ; 1535-7163
    ISSN (online) 1538-8514
    ISSN 1535-7163
    DOI 10.1158/1535-7163.MCT-17-0233
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery.

    Haddad, Elie / Logan, Brent R / Griffith, Linda M / Buckley, Rebecca H / Parrott, Roberta E / Prockop, Susan E / Small, Trudy N / Chaisson, Jessica / Dvorak, Christopher C / Murnane, Megan / Kapoor, Neena / Abdel-Azim, Hisham / Hanson, Imelda C / Martinez, Caridad / Bleesing, Jack J H / Chandra, Sharat / Smith, Angela R / Cavanaugh, Matthew E / Jyonouchi, Soma /
    Sullivan, Kathleen E / Burroughs, Lauri / Skoda-Smith, Suzanne / Haight, Ann E / Tumlin, Audrey G / Quigg, Troy C / Taylor, Candace / Dávila Saldaña, Blachy J / Keller, Michael D / Seroogy, Christine M / Desantes, Kenneth B / Petrovic, Aleksandra / Leiding, Jennifer W / Shyr, David C / Decaluwe, Hélène / Teira, Pierre / Gillio, Alfred P / Knutsen, Alan P / Moore, Theodore B / Kletzel, Morris / Craddock, John A / Aquino, Victor / Davis, Jeffrey H / Yu, Lolie C / Cuvelier, Geoffrey D E / Bednarski, Jeffrey J / Goldman, Frederick D / Kang, Elizabeth M / Shereck, Evan / Porteus, Matthew H / Connelly, James A / Fleisher, Thomas A / Malech, Harry L / Shearer, William T / Szabolcs, Paul / Thakar, Monica S / Vander Lugt, Mark T / Heimall, Jennifer / Yin, Ziyan / Pulsipher, Michael A / Pai, Sung-Yun / Kohn, Donald B / Puck, Jennifer M / Cowan, Morton J / O'Reilly, Richard J / Notarangelo, Luigi D

    Blood

    2018  Volume 132, Issue 17, Page(s) 1737–1749

    Abstract: The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and ... ...

    Abstract The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with
    MeSH term(s) CD4-Positive T-Lymphocytes/immunology ; Genotype ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune Reconstitution/immunology ; Lymphocyte Count ; Retrospective Studies ; Severe Combined Immunodeficiency/genetics ; Severe Combined Immunodeficiency/mortality ; Severe Combined Immunodeficiency/therapy
    Language English
    Publishing date 2018-08-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2018-03-840702
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MO 364: Show issues

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