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  1. AU="Riisom, Mie"
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  1. Article ; Online: Critical evaluation of cell lysis methods for metallodrug studies in cancer cells.

    Riisom, Mie / Jamieson, Stephen M F / Hartinger, Christian G

    Metallomics : integrated biometal science

    2023  Volume 15, Issue 9

    Abstract: Intracellular accumulation studies are a key step in metallodrug development but often variable results are obtained. Therefore, we aimed here to investigate different protocols for efficient and reproducible lysis of cancer cells in terms of protein ... ...

    Abstract Intracellular accumulation studies are a key step in metallodrug development but often variable results are obtained. Therefore, we aimed here to investigate different protocols for efficient and reproducible lysis of cancer cells in terms of protein content in lysates and in cell uptake studies of the Ru anticancer complex [chlorido(8-oxyquinolinato)(η6-p-cymene)ruthenium(II)] ([Ru(cym)(HQ)Cl]). The physical lysis methods osmosis and sonication were chosen for comparison with chemical lysis with the radioimmunoprecipitation assay (RIPA) buffer. Based on the protein content and the total Ru accumulated in the lysates, the latter determined using inductively coupled plasma-mass spectrometry, RIPA buffer was the most efficient lysis method. Measurements of plastic adsorption blanks revealed that the higher Ru content determined in the RIPA buffer lysis samples may be due a higher amount of Ru extracted from the plastic incubation plates compared with osmosis and sonication. Overall, we found that the choice of lysis method needs to be matched to the information sought and we suggest the least disruptive osmosis method might be the best choice for labile drug-biomolecule adducts. Minimal differences were found for experiments aimed at measuring the overall cell uptake of the Ru complex.
    MeSH term(s) Adsorption ; Biological Transport ; Cell Death ; Cymenes ; Plastics ; Neoplasms
    Chemical Substances Cymenes ; Plastics
    Language English
    Publishing date 2023-08-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2474317-3
    ISSN 1756-591X ; 1756-5901
    ISSN (online) 1756-591X
    ISSN 1756-5901
    DOI 10.1093/mtomcs/mfad048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The aqueous stability and interactions of organoruthenium compounds with serum proteins, cell culture medium, and human serum.

    Riisom, Mie / Eade, Liam / Tremlett, William D J / Hartinger, Christian G

    Metallomics : integrated biometal science

    2022  Volume 14, Issue 7

    Abstract: Metal complexes bind to a wide variety of biomolecules and the control of the reactivity is essential when designing anticancer metallodrugs with a specific mode of action in mind. In this study, we used the highly cytotoxic compound [RuII(cym)(8-HQ)Cl] ( ...

    Abstract Metal complexes bind to a wide variety of biomolecules and the control of the reactivity is essential when designing anticancer metallodrugs with a specific mode of action in mind. In this study, we used the highly cytotoxic compound [RuII(cym)(8-HQ)Cl] (cym = η6-p-cymene, 8-HQ = 8-hydroxyquinoline), the more inert derivative [RuII(cym)(8-HQ)(PTA)](SO3CF3) (PTA = 1,3,5-triaza-7-phosphaadamantane), and [RuII(cym)(PCA)Cl]Cl (PCA = pyridinecarbothioamide) as a complex with a different coordination environment about the Ru center and investigated their stability, interactions with proteins, and behavior in medium (αMEM) and human serum by capillary zone electrophoresis. The developed method was found to be robust and provides a quick and low-cost technique to monitor the interactions of such complexes with biomolecules. Each complex was found to behave very differently, emphasizing the importance of the choice of ligands and demonstrating the applicability of the developed method. Additionally, the human serum albumin binding site preference of [RuII(cym)(8-HQ)Cl] was investigated through displacement studies, revealing that the compound was able to bind to both sites I and site II, and the type of adducts formed with transferrin was determined by mass spectrometry.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Blood Proteins ; Cell Culture Techniques ; Coordination Complexes/chemistry ; Cymenes ; Humans ; Ruthenium/chemistry ; Water/chemistry
    Chemical Substances Antineoplastic Agents ; Blood Proteins ; Coordination Complexes ; Cymenes ; Water (059QF0KO0R) ; Ruthenium (7UI0TKC3U5)
    Language English
    Publishing date 2022-08-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2474317-3
    ISSN 1756-591X ; 1756-5901
    ISSN (online) 1756-591X
    ISSN 1756-5901
    DOI 10.1093/mtomcs/mfac043
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: On-Resin Conjugation of the Ruthenium Anticancer Agent Plecstatin-1 to Peptide Vectors.

    Kumar, Saawan / Riisom, Mie / Jamieson, Stephen M F / Kavianinia, Iman / Harris, Paul W R / Metzler-Nolte, Nils / Brimble, Margaret A / Hartinger, Christian G

    Inorganic chemistry

    2023  Volume 62, Issue 35, Page(s) 14310–14317

    Abstract: Ruthenium piano-stool complexes have been explored for their anticancer activity and some promising compounds have been reported. Herein, we conjugated a derivative of plecstatin-1 to peptides in order to increase their cancer cell targeting ability. For ...

    Abstract Ruthenium piano-stool complexes have been explored for their anticancer activity and some promising compounds have been reported. Herein, we conjugated a derivative of plecstatin-1 to peptides in order to increase their cancer cell targeting ability. For this purpose, plecstatin-1 was modified at the arene ligand to introduce a functional amine handle (
    MeSH term(s) Ruthenium/pharmacology ; Coordination Complexes ; Antineoplastic Agents/pharmacology ; Peptides ; Amines
    Chemical Substances Ruthenium (7UI0TKC3U5) ; Coordination Complexes ; Antineoplastic Agents ; Peptides ; Amines
    Language English
    Publishing date 2023-08-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1484438-2
    ISSN 1520-510X ; 0020-1669
    ISSN (online) 1520-510X
    ISSN 0020-1669
    DOI 10.1021/acs.inorgchem.3c01718
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: In vitro and in vivo accumulation of the anticancer Ru complexes [Ru

    Riisom, Mie / Morrow, Stuart J / Herbert, Caitlin D / Tremlett, William D J / Astin, Jonathan W / Jamieson, Stephen M F / Hartinger, Christian G

    Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry

    2023  Volume 28, Issue 8, Page(s) 767–775

    Abstract: The cellular accumulation and the underlying mechanisms for the two ruthenium-based anticancer complexes [ ... ...

    Abstract The cellular accumulation and the underlying mechanisms for the two ruthenium-based anticancer complexes [Ru
    MeSH term(s) Animals ; Humans ; Zebrafish ; Cisplatin ; Ruthenium/chemistry ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Coordination Complexes/pharmacology ; Coordination Complexes/chemistry ; Cell Line, Tumor
    Chemical Substances Cisplatin (Q20Q21Q62J) ; Ruthenium (7UI0TKC3U5) ; Antineoplastic Agents ; Coordination Complexes
    Language English
    Publishing date 2023-11-14
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1464026-0
    ISSN 1432-1327 ; 0949-8257
    ISSN (online) 1432-1327
    ISSN 0949-8257
    DOI 10.1007/s00775-023-02026-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Tracing the anticancer compound [Ru

    Yano, Ena / Riisom, Mie / Tong, Kelvin K H / Hanif, Muhammad / Leung, Euphemia / Hartinger, Christian G

    Analytical methods : advancing methods and applications

    2021  Volume 13, Issue 12, Page(s) 1463–1469

    Abstract: Ruthenium-based complexes have attracted attention as promising anticancer candidates due to their lower general toxicity than the widely used platinum drugs. The complex [ ... ...

    Abstract Ruthenium-based complexes have attracted attention as promising anticancer candidates due to their lower general toxicity than the widely used platinum drugs. The complex [Ru
    MeSH term(s) Coordination Complexes ; Cymenes ; Humans ; Mass Spectrometry ; Ruthenium
    Chemical Substances Coordination Complexes ; Cymenes ; 4-cymene (1G1C8T1N7Q) ; Ruthenium (7UI0TKC3U5)
    Language English
    Publishing date 2021-03-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2515210-5
    ISSN 1759-9679 ; 1759-9660
    ISSN (online) 1759-9679
    ISSN 1759-9660
    DOI 10.1039/d0ay02311f
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Tracing the anticancer compound [Ruᴵᴵ(η⁶-p-cymene)(8-oxyquinolinato)Cl] in a biological environment by mass spectrometric methods

    Yano, Ena / Riisom, Mie / Tong, Kelvin K. H / Hanif, Muhammad / Leung, Euphemia / Hartinger, Christian G

    Analytical methods. 2021 Apr. 1, v. 13, no. 12

    2021  

    Abstract: Ruthenium-based complexes have attracted attention as promising anticancer candidates due to their lower general toxicity than the widely used platinum drugs. The complex [Ruᴵᴵ(η⁶-p-cymene)(8-oxyquinolinato)Cl] 1 has shown significant cytotoxic activity ... ...

    Abstract Ruthenium-based complexes have attracted attention as promising anticancer candidates due to their lower general toxicity than the widely used platinum drugs. The complex [Ruᴵᴵ(η⁶-p-cymene)(8-oxyquinolinato)Cl] 1 has shown significant cytotoxic activity in cancer cells, independent of the cellular uptake. In an attempt to rationalize this finding, we investigated the fate of 1 in cells as well as developed an analysis method for 1 and its derivatives based on molecular mass spectrometry. The methods were applied for the analysis of cell medium and HCT116 human colorectal cancer cell lysate samples. The amount of Ru detected in cell lysate after treatment with 1 by ICP-MS was virtually time-independent, while the Ru content in the cell pellet increased significantly over the course of 24 h. The compound was still detectable by LC-ESI-TOF-MS after 24 h in cell lysate as its [1 − Cl]⁺ ion that may be formed directly from 1 or after a chlorido-aqua ligand exchange reaction facilitated in the cytosol.
    Keywords antineoplastic agents ; colorectal neoplasms ; cytosol ; cytotoxicity ; humans ; ligands ; mass spectrometry ; molecular weight ; neoplasm cells ; platinum
    Language English
    Dates of publication 2021-0401
    Size p. 1463-1469.
    Publishing place The Royal Society of Chemistry
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 2515210-5
    ISSN 1759-9679 ; 1759-9660
    ISSN (online) 1759-9679
    ISSN 1759-9660
    DOI 10.1039/d0ay02311f
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Impact of Coordination Mode and Ferrocene Functionalization on the Anticancer Activity of N-Heterocyclic Carbene Half-Sandwich Complexes.

    Tong, Kelvin K H / Riisom, Mie / Leung, Euphemia / Hanif, Muhammad / Söhnel, Tilo / Jamieson, Stephen M F / Hartinger, Christian G

    Inorganic chemistry

    2022  Volume 61, Issue 43, Page(s) 17226–17241

    Abstract: The substitution of phenyl rings in established drugs with ferrocenyl moieties has been reported to yield compounds with improved biological activity and alternative modes of action, often involving the formation of reactive oxygen species (ROS). ... ...

    Abstract The substitution of phenyl rings in established drugs with ferrocenyl moieties has been reported to yield compounds with improved biological activity and alternative modes of action, often involving the formation of reactive oxygen species (ROS). Translating this concept to N-heterocyclic carbene (NHC) complexes, we report here organometallics with a piano-stool structure that feature di- or tridentate ligand systems. The ligands impacted the cytotoxic activity of the NHC complexes, but the coordination modes seemed to have a limited influence, which may be related to the propensity of forming the same species in solution. In general, the stability of the complexes in an aqueous environment and their reactivity to selected biomolecules were largely dominated by the nature of the metal center. While the complexes promoted the formation of ROS, the levels did not correlate with their cytotoxic activity. However, the introduction of ferrocenyl moieties had a significant impact on the antiproliferative potency of the complexes and, in particular, some of the ferrocenyl-functionalized compounds yielded IC
    MeSH term(s) Metallocenes/pharmacology ; Coordination Complexes/pharmacology ; Reactive Oxygen Species ; Methane/pharmacology ; Antineoplastic Agents/pharmacology ; Ligands
    Chemical Substances ferrocene (U96PKG90JQ) ; Metallocenes ; carbene (2465-56-7) ; Coordination Complexes ; Reactive Oxygen Species ; Methane (OP0UW79H66) ; Antineoplastic Agents ; Ligands
    Language English
    Publishing date 2022-10-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1484438-2
    ISSN 1520-510X ; 0020-1669
    ISSN (online) 1520-510X
    ISSN 0020-1669
    DOI 10.1021/acs.inorgchem.2c02832
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Hydrazone- and imine-containing [PdPtL

    Lisboa, Lynn S / Riisom, Mie / Dunne, Henry J / Preston, Dan / Jamieson, Stephen M F / Wright, L James / Hartinger, Christian G / Crowley, James D

    Dalton transactions (Cambridge, England : 2003)

    2022  

    Abstract: ... A new [ ... ...

    Abstract A new [PdPtL
    Language English
    Publishing date 2022-11-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 1472887-4
    ISSN 1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
    ISSN (online) 1477-9234 ; 1364-5447
    ISSN 0300-9246 ; 1477-9226
    DOI 10.1039/d2dt02720h
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Platinum(terpyridine) complexes with N-heterocyclic carbene co-ligands: high antiproliferative activity and low toxicity

    Sullivan, Matthew P / Adams, Muneebah / Riisom, Mie / Herbert, Caitlin D / Tong, Kelvin K H / Astin, Jonathan W / Jamieson, Stephen M F / Hanif, Muhammad / Goldstone, David C / Hartinger, Christian G

    Dalton transactions (Cambridge, England : 2003)

    2023  Volume 52, Issue 5, Page(s) 1388–1392

    Abstract: Pt(terpyridine) complexes are well-known DNA intercalators. The introduction of an NHC co-ligand rendered such a complex highly antiproliferative in cancer cells compared to its chlorido derivative. Despite the high potency, zebrafish embryos tolerated ... ...

    Abstract Pt(terpyridine) complexes are well-known DNA intercalators. The introduction of an NHC co-ligand rendered such a complex highly antiproliferative in cancer cells compared to its chlorido derivative. Despite the high potency, zebrafish embryos tolerated the compound well, especially compared to cisplatin. DNA interaction studies support a mode of action related to intercalation.
    MeSH term(s) Animals ; Platinum ; Antineoplastic Agents/pharmacology ; Ligands ; Zebrafish ; Cell Line, Tumor ; DNA
    Chemical Substances Platinum (49DFR088MY) ; Antineoplastic Agents ; Ligands ; carbene (2465-56-7) ; DNA (9007-49-2)
    Language English
    Publishing date 2023-01-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 1472887-4
    ISSN 1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
    ISSN (online) 1477-9234 ; 1364-5447
    ISSN 0300-9246 ; 1477-9226
    DOI 10.1039/d2dt02539f
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Development and validation of an ICP-MS method for quantification of total carbon and platinum in cell samples and comparison of open-vessel and microwave-assisted acid digestion methods.

    Riisom, Mie / Gammelgaard, Bente / Lambert, Ian H / Stürup, Stefan

    Journal of pharmaceutical and biomedical analysis

    2018  Volume 158, Page(s) 144–150

    Abstract: Cisplatin is a widely used chemotherapeutic drug. Due to severe side effects and intrinsic or acquired resistance, there is a great interest in developing new platinum-based anticancer agents and a need for robust and validated analytical methods for ... ...

    Abstract Cisplatin is a widely used chemotherapeutic drug. Due to severe side effects and intrinsic or acquired resistance, there is a great interest in developing new platinum-based anticancer agents and a need for robust and validated analytical methods for determination of platinum accumulation in biological samples. A validated ICP-MS method for quantification of total carbon and platinum in cell samples is presented, applicable for cellular drug accumulation studies of platinum-based drugs, enabling estimation of drug accumulation while simultaneously determining carbon to monitor the sample digestion efficiency. Adequate precision (RSD <6%), accuracy and sensitivity were achieved for carbon and platinum determinations. Limits of detection were 0.9-3.0 mg/L for carbon and 0.11-0.50 μg/L for platinum. Determination of platinum by ICP-MS in cell samples digested applying either open-vessel or microwave-assisted acid digestion produced similar concentrations, although the residual carbon content in the sample solutions were significantly higher following open-vessel acid digestion compared to microwave-assisted acid digestion. Experiments showed that the residual carbon content after acid digestion did not have an influence on determination of total platinum by ICP-MS.
    MeSH term(s) A549 Cells ; Acids/chemistry ; Calibration ; Carbon/analysis ; Humans ; Mass Spectrometry/instrumentation ; Mass Spectrometry/methods ; Microwaves ; Platinum/analysis ; Sensitivity and Specificity
    Chemical Substances Acids ; Platinum (49DFR088MY) ; Carbon (7440-44-0)
    Language English
    Publishing date 2018-05-24
    Publishing country England
    Document type Comparative Study ; Journal Article ; Validation Studies
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2018.05.038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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