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  1. AU="Karimi, Leena"
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  1. Article ; Online: Triple combination targeting PI3K, ER, and CDK4/6 inhibits growth of ER-positive breast cancer resistant to fulvestrant and CDK4/6 or PI3K inhibitor.

    Karimi, Leena / Alves, Carla L / Terp, Mikkel G / Tuttolomondo, Martina / Portman, Neil / Ehmsen, Sidse / Johansen, Lene E / Bak, Martin / Lim, Elgene / Ditzel, Henrik J

    Cancer communications (London, England)

    2023  Volume 43, Issue 6, Page(s) 720–725

    MeSH term(s) Humans ; Female ; Breast Neoplasms ; Fulvestrant ; Phosphatidylinositol 3-Kinases ; Cell Line, Tumor ; Signal Transduction ; Cyclin-Dependent Kinase 4
    Chemical Substances Fulvestrant (22X328QOC4) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; CDK4 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22)
    Language English
    Publishing date 2023-04-26
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ISSN 2523-3548
    ISSN (online) 2523-3548
    DOI 10.1002/cac2.12425
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Bottom up design of nanoparticles for anti-cancer diapeutics: "put the drug in the cancer's food".

    Needham, David / Arslanagic, Amina / Glud, Kasper / Hervella, Pablo / Karimi, Leena / Høeilund-Carlsen, Poul-Flemming / Kinoshita, Koji / Mollenhauer, Jan / Parra, Elisa / Utoft, Anders / Walke, Prasad

    Journal of drug targeting

    2016  Volume 24, Issue 9, Page(s) 836–856

    Abstract: The story starts in Basel at CLINAM in 2013, when I asked Pieter about making nanoparticles and he advised me to "try this solvent-exchange method we have developed for making limit sized particles". We are particularly interested in what are "limit size ...

    Abstract The story starts in Basel at CLINAM in 2013, when I asked Pieter about making nanoparticles and he advised me to "try this solvent-exchange method we have developed for making limit sized particles". We are particularly interested in what are "limit size materials" because we want to test the feasibility of an idea: could we design, make, develop, and test the concept for treating metastatic cancer by, "Putting the Drug in the Cancer's Food? "Limit size" is the size of the cancer's food, ? the common Low Density Lipoprotein, (LDL) ~20 nm diameter. In this contribution to Pieter's LTAA we focus on the "bottom" (nucleation) and the "up" (growth) of "bottom-up design" as it applies to homogeneous nucleation of especially, hydrophobic drugs and the 8 physico-chemical stages and associated parameters that determine the initial size, and any subsequent coarsening, of a nanoparticle suspension. We show that, when made by the rapid solvent-exchange method, the same sized particles can be obtained without phospholipid. Furthermore, the obtained size follows the predictions of classic nucleation theory when the appropriate values for the parameters (surface tension and supersaturation) at nucleation are included. Calculations on dissolution time for nanoparticles reveal that a typical fewmicromolar-solubility, hydrophobic, anti-cancer drug (like Lapatinib, Niclosamide, Abiraterone, and Fulvestrant) of 500 nm diameter would take between 3?7 s to dissolve in an infinite sink like the blood stream; and a 50 nm particle would dissolve in less than a second! And so the nanoparticle design requires a highly water-insoluble drug, and a tight, encapsulating, impermeable lipid:cholesterol monolayer. While the "Y" junction can be used to mix an ethanolic solution with anti-solvent, we find that a "no-junction" can give equally good results. A series of nanoparticles (DiI-fluorescently labeled Triolein-cored and drug-cored nanoparticles of Orlistat) were then tested in well-characterized cell lines for uptake and efficacy as well as a PET-imageable nanoparticle in initial PET-imaging studies in animals for EPR uptake and tumor detection. We show that, while free-drug cannot be optimally administered in vivo, a nanoparticle formulation of orlistat could in principle represent a stable parenteral delivery system. The article ends with a brief discussion of what we see as the way forward in Individualized Medicine from the Diagnostic-Therapeutic ("Diapeutic") side, requiring
    MeSH term(s) Animals ; Antineoplastic Agents/administration & dosage ; Chemistry, Pharmaceutical ; Drug Delivery Systems ; Humans ; Hydrophobic and Hydrophilic Interactions ; Lipids/chemistry ; Nanoparticles ; Neoplasms/drug therapy
    Chemical Substances Antineoplastic Agents ; Lipids
    Language English
    Publishing date 2016-10-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1187110-6
    ISSN 1029-2330 ; 1061-186X
    ISSN (online) 1029-2330
    ISSN 1061-186X
    DOI 10.1080/1061186X.2016.1238092
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Systemically administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia.

    Clausen, Bettina Hjelm / Degn, Matilda / Martin, Nellie Anne / Couch, Yvonne / Karimi, Leena / Ormhøj, Maria / Mortensen, Maria-Louise Bergholdt / Gredal, Hanne Birgit / Gardiner, Chris / Sargent, Ian I L / Szymkowski, David E / Petit, Géraldine H / Deierborg, Tomas / Finsen, Bente / Anthony, Daniel Clive / Lambertsen, Kate Lykke

    Journal of neuroinflammation

    2014  Volume 11, Page(s) 203

    Abstract: Background: The innate immune system contributes to the outcome after stroke, where neuroinflammation and post-stroke systemic immune depression are central features. Tumor necrosis factor (TNF), which exists in both a transmembrane (tm) and soluble ( ... ...

    Abstract Background: The innate immune system contributes to the outcome after stroke, where neuroinflammation and post-stroke systemic immune depression are central features. Tumor necrosis factor (TNF), which exists in both a transmembrane (tm) and soluble (sol) form, is known to sustain complex inflammatory responses associated with stroke. We tested the effect of systemically blocking only solTNF versus blocking both tmTNF and solTNF on infarct volume, functional outcome and inflammation in focal cerebral ischemia.
    Methods: We used XPro1595 (a dominant-negative inhibitor of solTNF) and etanercept (which blocks both solTNF and tmTNF) to test the effect of systemic administration on infarct volume, functional recovery and inflammation after focal cerebral ischemia in mice. Functional recovery was evaluated after one, three and five days, and infarct volumes at six hours, 24 hours and five days after ischemia. Brain inflammation, liver acute phase response (APR), spleen and blood leukocyte profiles, along with plasma microvesicle analysis, were evaluated.
    Results: We found that both XPro1595 and etanercept significantly improved functional outcomes, altered microglial responses, and modified APR, spleen T cell and microvesicle numbers, but without affecting infarct volumes.
    Conclusions: Our data suggest that XPro1595 and etanercept improve functional outcome after focal cerebral ischemia by altering the peripheral immune response, changing blood and spleen cell populations and decreasing granulocyte infiltration into the brain. Blocking solTNF, using XPro1595, was just as efficient as blocking both solTNF and tmTNF using etanercept. Our findings may have implications for future treatments with anti-TNF drugs in TNF-dependent diseases.
    MeSH term(s) Animals ; Brain Ischemia/drug therapy ; Brain Ischemia/metabolism ; Injections, Intravenous ; Male ; Mice ; Mice, Inbred C57BL ; Random Allocation ; Recovery of Function/drug effects ; Treatment Outcome ; Tumor Necrosis Factor-alpha/administration & dosage ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Tumor Necrosis Factor-alpha ; XENP 1595
    Language English
    Publishing date 2014-12-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2156455-3
    ISSN 1742-2094 ; 1742-2094
    ISSN (online) 1742-2094
    ISSN 1742-2094
    DOI 10.1186/s12974-014-0203-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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