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  1. Article ; Online: ABL allosteric inhibitors synergize with statins to enhance apoptosis of metastatic lung cancer cells.

    Luttman, Jillian Hattaway / Hoj, Jacob P / Lin, Kevin H / Lin, Jiaxing / Gu, Jing Jin / Rouse, Clay / Nichols, Amanda G / MacIver, Nancie J / Wood, Kris C / Pendergast, Ann Marie

    Cell reports

    2021  Volume 37, Issue 4, Page(s) 109880

    Abstract: Targeting mitochondrial metabolism has emerged as a treatment option for cancer patients. The ABL tyrosine kinases promote metastasis, and enhanced ABL signaling is associated with a poor prognosis in lung adenocarcinoma patients. Here we show that ABL ... ...

    Abstract Targeting mitochondrial metabolism has emerged as a treatment option for cancer patients. The ABL tyrosine kinases promote metastasis, and enhanced ABL signaling is associated with a poor prognosis in lung adenocarcinoma patients. Here we show that ABL kinase allosteric inhibitors impair mitochondrial integrity and decrease oxidative phosphorylation. To identify metabolic vulnerabilities that enhance this phenotype, we utilized a CRISPR/Cas9 loss-of-function screen and identified HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway and target of statin therapies, as a top-scoring sensitizer to ABL inhibition. Combination treatment with ABL allosteric inhibitors and statins decreases metastatic lung cancer cell survival in vitro in a synergistic manner. Notably, combination therapy in mouse models of lung cancer brain metastasis and therapy resistance impairs metastatic colonization with a concomitant increase in animal survival. Thus, metabolic combination therapy might be effective to decrease metastatic outgrowth, leading to increased survival for lung cancer patients with advanced disease.
    MeSH term(s) Allosteric Regulation/drug effects ; Allosteric Regulation/genetics ; Animals ; Apoptosis/drug effects ; Apoptosis/genetics ; Cell Line, Tumor ; Drug Synergism ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/enzymology ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Oncogene Proteins v-abl/antagonists & inhibitors ; Oncogene Proteins v-abl/genetics ; Oncogene Proteins v-abl/metabolism ; Protein Kinase Inhibitors/pharmacology ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Xenograft Model Antitumor Assays
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Oncogene Proteins v-abl ; Protein Kinase Inhibitors
    Language English
    Publishing date 2021-10-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.109880
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Cyclic tensile strain increases interactions between human epidermal keratinocytes and quantum dot nanoparticles.

    Rouse, Jillian G / Haslauer, Carla M / Loboa, Elizabeth G / Monteiro-Riviere, Nancy A

    Toxicology in vitro : an international journal published in association with BIBRA

    2008  Volume 22, Issue 2, Page(s) 491–497

    Abstract: The effects of quantum dots (QD) on cell viability have gained increasing interest due to many recent developments utilizing QD for pharmaceutical and biomedical applications. The potential use of QD nanoparticles as diagnostic, imaging, and drug ... ...

    Abstract The effects of quantum dots (QD) on cell viability have gained increasing interest due to many recent developments utilizing QD for pharmaceutical and biomedical applications. The potential use of QD nanoparticles as diagnostic, imaging, and drug delivery agents has raised questions about their potential for cytotoxicity. The objective of this study was to investigate the effects of applied strain on QD uptake by human epidermal keratinocytes (HEK). It was hypothesized that introduction of a 10% average strain to cell cultures would increase QD uptake. HEK were seeded at a density of 150,000 cells/mL on collagen-coated Flexcell culture plates (Flexcell Intl.). QD were introduced at a concentration of 3 nM and a 10% average strain was applied to the cells. After 4h of cyclic strain, the cells were examined for cell viability, QD uptake, and cytokine production. The results indicate that addition of strain results in an increase in cytokine production and QD uptake, resulting in irritation and a negative impact on cell viability. Application of physiological load conditions can increase cell membrane permeability, thereby increasing the concentration of QD nanoparticles in cells.
    MeSH term(s) Borates/toxicity ; Cell Membrane Permeability/drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Cytokines/analysis ; Cytokines/biosynthesis ; Epidermis/cytology ; Epidermis/drug effects ; Ethidium ; Fluoresceins ; Fluorescent Dyes ; Humans ; Keratinocytes/drug effects ; Keratinocytes/physiology ; Microscopy, Fluorescence ; Pharmaceutical Vehicles/chemistry ; Polyethylene Glycols/chemistry ; Quantum Dots ; Tensile Strength
    Chemical Substances Borates ; Cytokines ; Fluoresceins ; Fluorescent Dyes ; Pharmaceutical Vehicles ; calcein AM (148504-34-1) ; Polyethylene Glycols (30IQX730WE) ; Ethidium (EN464416SI)
    Language English
    Publishing date 2008-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 639064-x
    ISSN 1879-3177 ; 0887-2333
    ISSN (online) 1879-3177
    ISSN 0887-2333
    DOI 10.1016/j.tiv.2007.10.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2223: Show issues Location:
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  3. Article: Effects of mechanical flexion on the penetration of fullerene amino acid-derivatized peptide nanoparticles through skin.

    Rouse, Jillian G / Yang, Jianzhong / Ryman-Rasmussen, Jessica P / Barron, Andrew R / Monteiro-Riviere, Nancy A

    Nano letters

    2007  Volume 7, Issue 1, Page(s) 155–160

    Abstract: Dermatomed porcine skin was fixed to a flexing device and topically dosed with 33.5 mg.mL-1 of an aqueous solution of a fullerene-substituted phenylalanine (Baa) derivative of a nuclear localization peptide sequence (Baa-Lys(FITC)-NLS). Skin was flexed ... ...

    Abstract Dermatomed porcine skin was fixed to a flexing device and topically dosed with 33.5 mg.mL-1 of an aqueous solution of a fullerene-substituted phenylalanine (Baa) derivative of a nuclear localization peptide sequence (Baa-Lys(FITC)-NLS). Skin was flexed for 60 or 90 min or left unflexed (control). Confocal microscopy depicted dermal penetration of the nanoparticles at 8 h in skin flexed for 60 and 90 min, whereas Baa-Lys(FITC)-NLS did not penetrate into the dermis of unflexed skin until 24 h. TEM analysis revealed fullerene-peptide localization within the intercellular spaces of the stratum granulosum.
    MeSH term(s) Amino Acids/chemistry ; Fluorescein-5-isothiocyanate ; Fullerenes/chemistry ; Microscopy, Confocal ; Nanoparticles/chemistry ; Nuclear Localization Signals ; Peptides/pharmacokinetics ; Skin Absorption
    Chemical Substances Amino Acids ; Fullerenes ; Nuclear Localization Signals ; Peptides ; Fluorescein-5-isothiocyanate (I223NX31W9)
    Language English
    Publishing date 2007-01-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1530-6984
    ISSN 1530-6984
    DOI 10.1021/nl062464m
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Fullerene-based amino acid nanoparticle interactions with human epidermal keratinocytes.

    Rouse, Jillian G / Yang, Jianzhong / Barron, Andrew R / Monteiro-Riviere, Nancy A

    Toxicology in vitro : an international journal published in association with BIBRA

    2006  Volume 20, Issue 8, Page(s) 1313–1320

    Abstract: The functionalization of C(60) with such complexes as amino acids has the potential to provide greater interaction between the fullerene and the biological environment yielding potential new medical and pharmacological applications. Although scientific ... ...

    Abstract The functionalization of C(60) with such complexes as amino acids has the potential to provide greater interaction between the fullerene and the biological environment yielding potential new medical and pharmacological applications. Although scientific research in the past decade has revealed much about the chemical and physical properties of C(60), the biological activities of this compound and its derivatives are still relatively unclear. In an attempt to understand the biological activity of functionalized C(60), human epidermal keratinocytes (HEK) were exposed to fullerene-based amino acid (Baa) solutions ranging in concentrations of 0.4-0.00004 mg/mL in a humidified 5% CO(2) atmosphere at 37 degrees C. MTT cell viability after 48 h significantly decreased (p<0.05) for concentrations of 0.4 and 0.04 mg/mL. In an additional study, human cytokines IL-6, IL-8, TNF-alpha, IL-1beta, and IL-10 were assessed for concentrations ranging from 0.4-0.004 mg/mL. Media was harvested at 1, 4, 8, 12, 24 and 48 h for cytokine analysis. IL-8 concentrations for the 0.04 mg/mL treatment were significantly greater (p<0.05) than all other concentrations at 8, 12, 24, and 48 h. IL-6 and IL-1beta activities were greater at the 24h and 48 h for 0.4 and 0.04 mg/mL. No significant TNF-alpha or IL-10 activity existed at any time points for any of the concentrations. These results indicate that concentrations lower than 0.04 mg/mL initiate less cytokine activity and maintain cell viability. In HEK, Baa concentrations of 0.4 and 0.04 mg/mL decrease cell viability and initiate a pro-inflammatory response.
    MeSH term(s) Amino Acids/toxicity ; Cell Line ; Cell Survival/drug effects ; Cytokines/analysis ; Cytokines/biosynthesis ; Cytokines/metabolism ; Dose-Response Relationship, Drug ; Epidermis/cytology ; Epidermis/drug effects ; Fullerenes/toxicity ; Humans ; Keratinocytes/drug effects ; Microscopy, Electron, Transmission ; Nanoparticles/toxicity ; Tetrazolium Salts ; Thiazoles ; Vacuoles/drug effects ; Vacuoles/ultrastructure
    Chemical Substances Amino Acids ; Cytokines ; Fullerenes ; Tetrazolium Salts ; Thiazoles ; thiazolyl blue (EUY85H477I)
    Language English
    Publishing date 2006-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 639064-x
    ISSN 1879-3177 ; 0887-2333
    ISSN (online) 1879-3177
    ISSN 0887-2333
    DOI 10.1016/j.tiv.2006.04.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2223: 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)

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