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  1. Article ; Online: Reductions and pronounced regional differences in morphine distribution in the United States.

    Dowd, Megan E / Tang, E Jessica / Yan, Kurlya T / McCall, Kenneth L / Piper, Brian J

    Research in social & administrative pharmacy : RSAP

    2023  Volume 19, Issue 6, Page(s) 926–930

    Abstract: Objectives: The purpose of this longitudinal study was to describe the temporal pattern of morphine distribution nationally and between states.: Methods: Drug weight was obtained from Report 5 of the US Drug Enforcement Administration's Automation of ...

    Abstract Objectives: The purpose of this longitudinal study was to describe the temporal pattern of morphine distribution nationally and between states.
    Methods: Drug weight was obtained from Report 5 of the US Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (ARCOS) to characterize patterns in the distribution of morphine from 2012 to 2021. Morphine distribution amounts were separated by state and business type and corrected for population. States outside a 95% confidence interval relative to the national average were considered statistically significant.
    Key findings: In 2012, there was a 4.6-fold difference in morphine distribution between the highest-prescribing state, Tennessee (180.2 mg/person), and the lowest-prescribing state, Texas (39.4 mg/person). By the end of 2021, national distribution of morphine had decreased by 59.9% when compared to the peak year 2012. In 2021, Tennessee (51.1 mg/person) remained the highest-prescribing state with a 3.0-fold difference relative to Texas (17.2 mg/person). The average hospital decrease (-73.9%) from 2012 to 2021 was larger than that of pharmacies (-58.2%).
    Conclusions: The national 59.9% decline in morphine in the last decade may be attributable to prioritization of the US opioid crisis as a public concern. Further research is necessary to understand the persistent regional difference between states.
    MeSH term(s) United States ; Humans ; Morphine/therapeutic use ; Analgesics, Opioid/therapeutic use ; Longitudinal Studies ; Practice Patterns, Physicians' ; Tennessee ; Drug Prescriptions
    Chemical Substances Morphine (76I7G6D29C) ; Analgesics, Opioid
    Language English
    Publishing date 2023-03-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2192059-X
    ISSN 1934-8150 ; 1551-7411
    ISSN (online) 1934-8150
    ISSN 1551-7411
    DOI 10.1016/j.sapharm.2023.03.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A B7-H4-Targeting Antibody-Drug Conjugate Shows Antitumor Activity in PARPi and Platinum-Resistant Cancers with B7-H4 Expression.

    Gitto, Sarah B / Whicker, Margaret / Davies, Gareth / Kumar, Sushil / Kinneer, Krista / Xu, Haineng / Lewis, Arthur / Mamidi, Srinivas / Medvedev, Sergey / Kim, Hyoung / Anderton, Judith / Tang, E Jessica / Ferman, Benjamin / Coats, Steven / Wilkinson, Robert W / Brown, Eric / Powell, Daniel J / Simpkins, Fiona

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

    2023  Volume 30, Issue 8, Page(s) 1567–1581

    Abstract: Purpose: Platinum and PARP inhibitors (PARPi) demonstrate activity in breast and ovarian cancers, but drug resistance ultimately emerges. Here, we examine B7-H4 expression in primary and recurrent high-grade serous ovarian carcinoma (HGSOC) and the ... ...

    Abstract Purpose: Platinum and PARP inhibitors (PARPi) demonstrate activity in breast and ovarian cancers, but drug resistance ultimately emerges. Here, we examine B7-H4 expression in primary and recurrent high-grade serous ovarian carcinoma (HGSOC) and the activity of a B7-H4-directed antibody-drug conjugate (B7-H4-ADC), using a pyrrolobenzodiazepine-dimer payload, in PARPi- and platinum-resistant HGSOC patient-derived xenograft (PDX) models.
    Experimental design: B7-H4 expression was quantified by flow cytometry and IHC. B7-H4-ADC efficacy was tested against multiple cell lines in vitro and PDX in vivo. The effect of B7-H4-ADC on cell cycle, DNA damage, and apoptosis was measured using flow cytometry.
    Results: B7-H4 is overexpressed in 92% of HGSOC tumors at diagnosis (n = 12), persisted in recurrent matched samples after platinum treatment, and was expressed at similar levels across metastatic sites after acquired multi-drug resistance (n = 4). Treatment with B7-H4-ADC resulted in target-specific growth inhibition of multiple ovarian and breast cancer cell lines. In platinum- or PARPi-resistant ovarian cancer cells, B7-H4-ADC significantly decreased viability and colony formation while increasing cell-cycle arrest and DNA damage, ultimately leading to apoptosis. Single-dose B7-H4-ADC led to tumor regression in 65.5% of breast and ovarian PDX models (n = 29), with reduced activity in B7-H4 low or negative models. In PARPi and platinum-resistant HGSOC PDX models, scheduled B7-H4-ADC dosing led to sustained tumor regression and increased survival.
    Conclusions: These data support B7-H4 as an attractive ADC target for treatment of drug-resistant HGSOC and provide evidence for activity of an ADC with a DNA-damaging payload in this population. See related commentary by Veneziani et al., p. 1434.
    MeSH term(s) Female ; Humans ; Apoptosis ; Carcinoma, Ovarian Epithelial/drug therapy ; Cell Line, Tumor ; Immunoconjugates/pharmacology ; Immunoconjugates/therapeutic use ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Platinum/pharmacology ; Platinum/therapeutic use ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; V-Set Domain-Containing T-Cell Activation Inhibitor 1/antagonists & inhibitors ; V-Set Domain-Containing T-Cell Activation Inhibitor 1/immunology ; Organoplatinum Compounds/pharmacology ; Organoplatinum Compounds/therapeutic use
    Chemical Substances Immunoconjugates ; Platinum (49DFR088MY) ; Poly(ADP-ribose) Polymerase Inhibitors ; VTCN1 protein, human ; V-Set Domain-Containing T-Cell Activation Inhibitor 1 ; Organoplatinum Compounds
    Language English
    Publishing date 2023-10-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-1079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Induction of

    Small, Sara H / Tang, E Jessica / Ragland, Ryan L / Ruzankina, Yaroslava / Schoppy, David W / Mandal, Rahul S / Glineburg, M Rebecca / Ustelenca, Zgjim / Powell, Daniel J / Simpkins, Fiona / Johnson, F Bradley / Brown, Eric J

    Science signaling

    2021  Volume 14, Issue 714, Page(s) eaba2611

    Abstract: Cytokine production is a critical component of cell-extrinsic responses to DNA damage and cellular senescence. Here, we demonstrated that expression of the gene encoding interleukin-19 (IL-19) was enhanced by DNA damage through pathways mediated by c-Jun ...

    Abstract Cytokine production is a critical component of cell-extrinsic responses to DNA damage and cellular senescence. Here, we demonstrated that expression of the gene encoding interleukin-19 (IL-19) was enhanced by DNA damage through pathways mediated by c-Jun amino-terminal kinase (JNK) and cGAS-STING and that
    MeSH term(s) Animals ; Cytokines/genetics ; DNA Damage ; Interleukins/metabolism ; MAP Kinase Signaling System ; Membrane Proteins/genetics ; Mice ; Nucleotidyltransferases/genetics ; Nucleotidyltransferases/metabolism ; Signal Transduction
    Chemical Substances Cytokines ; Il19 protein, mouse ; Interleukins ; Membrane Proteins ; Sting1 protein, mouse ; Nucleotidyltransferases (EC 2.7.7.-)
    Language English
    Publishing date 2021-12-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2417226-1
    ISSN 1937-9145 ; 1945-0877
    ISSN (online) 1937-9145
    ISSN 1945-0877
    DOI 10.1126/scisignal.aba2611
    Database MEDical Literature Analysis and Retrieval System OnLINE

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