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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: Targeting growth hormone in cancer: future perspectives.

    Wang, Yue / Jamieson, Stephen M F / Perry, Jo K

    Endocrine-related cancer

    2023  Volume 30, Issue 9

    Abstract: Decades of published research support a role for growth hormone (GH) in cancer. Accordingly, there is increasing interest in targeting GH in oncology, with GH antagonists exhibiting efficacy in xenograft studies as single agents and in combination with ... ...

    Abstract Decades of published research support a role for growth hormone (GH) in cancer. Accordingly, there is increasing interest in targeting GH in oncology, with GH antagonists exhibiting efficacy in xenograft studies as single agents and in combination with anticancer therapy or radiation. Here we discuss challenges associated with using growth hormone receptor (GHR) antagonists in preclinical models and considerations for translation, such as the identification of predictive biomarkers for selecting patients and for monitoring drug efficacy. Ongoing research will determine whether suppressing GH signalling pharmacologically will also reduce the risk of developing cancer. An increase in GH-targeted drugs in preclinical development will ultimately provide new tools to test anticancer efficacy of blocking the GH signalling pathway.
    MeSH term(s) Humans ; Growth Hormone/therapeutic use ; Growth Hormone/metabolism ; Receptors, Somatotropin/metabolism ; Human Growth Hormone/metabolism ; Neoplasms/drug therapy ; Signal Transduction
    Chemical Substances Growth Hormone (9002-72-6) ; Receptors, Somatotropin ; Human Growth Hormone (12629-01-5)
    Language English
    Publishing date 2023-07-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 1218450-0
    ISSN 1479-6821 ; 1351-0088
    ISSN (online) 1479-6821
    ISSN 1351-0088
    DOI 10.1530/ERC-23-0033
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4192: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  3. Article ; Online: Design, Synthesis and Anticancer Evaluation of Nitroimidazole Radiosensitisers.

    Liew, Lydia P / Shome, Avik / Wong, Way W / Hong, Cho R / Hicks, Kevin O / Jamieson, Stephen M F / Hay, Michael P

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 11

    Abstract: The role of hypoxic tumour cells in resistance to radiotherapy, and in suppression of immune response, continues to endorse tumour hypoxia as a bona fide, yet largely untapped, drug target. Radiotherapy innovations such as stereotactic body radiotherapy ... ...

    Abstract The role of hypoxic tumour cells in resistance to radiotherapy, and in suppression of immune response, continues to endorse tumour hypoxia as a bona fide, yet largely untapped, drug target. Radiotherapy innovations such as stereotactic body radiotherapy herald new opportunities for classical oxygen-mimetic radiosensitisers. Only nimorazole is used clinically as a radiosensitiser, and there is a dearth of new radiosensitisers in development. In this report, we augment previous work to present new nitroimidazole alkylsulfonamides and we document their cytotoxicity and ability to radiosensitise anoxic tumour cells in vitro. We compare radiosensitisation with etanidazole and earlier nitroimidazole sulfonamide analogues and we identify 2-nitroimidazole and 5-nitroimidazole analogues with marked tumour radiosensitisation in ex vivo assays of surviving clonogens and with in vivo tumour growth inhibition.
    MeSH term(s) Humans ; Cell Hypoxia ; Nitroimidazoles/pharmacology ; Radiation-Sensitizing Agents/pharmacology ; Hypoxia ; Neoplasms/drug therapy ; Neoplasms/radiotherapy
    Chemical Substances Nitroimidazoles ; Radiation-Sensitizing Agents
    Language English
    Publishing date 2023-05-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28114457
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    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

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  4. 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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  5. 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
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  6. Article ; Online: Clonal dynamics limits detection of selection in tumour xenograft CRISPR/Cas9 screens.

    Lee, Tet Woo / Hunter, Francis W / Tsai, Peter / Print, Cristin G / Wilson, William R / Jamieson, Stephen M F

    Cancer gene therapy

    2023  Volume 30, Issue 12, Page(s) 1610–1623

    Abstract: Transplantable in vivo CRISPR/Cas9 knockout screens, in which cells are edited in vitro and inoculated into mice to form tumours, allow evaluation of gene function in a cancer model that incorporates the multicellular interactions of the tumour ... ...

    Abstract Transplantable in vivo CRISPR/Cas9 knockout screens, in which cells are edited in vitro and inoculated into mice to form tumours, allow evaluation of gene function in a cancer model that incorporates the multicellular interactions of the tumour microenvironment. To improve our understanding of the key parameters for success with this method, we investigated the choice of cell line, mouse host, tumour harvesting timepoint and guide RNA (gRNA) library size. We found that high gRNA (80-95%) representation was maintained in a HCT116 subline transduced with the GeCKOv2 whole-genome gRNA library and transplanted into NSG mice when tumours were harvested at early (14 d) but not late time points (38-43 d). The decreased representation in older tumours was accompanied by large increases in variance in gRNA read counts, with notable expansion of a small number of random clones in each sample. The variable clonal dynamics resulted in a high level of 'noise' that limited the detection of gRNA-based selection. Using simulated datasets derived from our experimental data, we show that considerable reductions in count variance would be achieved with smaller library sizes. Based on our findings, we suggest a pathway to rationally design adequately powered in vivo CRISPR screens for successful evaluation of gene function.
    MeSH term(s) Humans ; Mice ; Animals ; Aged ; CRISPR-Cas Systems ; Gene Editing/methods ; Heterografts ; RNA, Guide, CRISPR-Cas Systems ; Clone Cells
    Chemical Substances RNA, Guide, CRISPR-Cas Systems
    Language English
    Publishing date 2023-09-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1212513-1
    ISSN 1476-5500 ; 0929-1903
    ISSN (online) 1476-5500
    ISSN 0929-1903
    DOI 10.1038/s41417-023-00664-5
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4125: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Clinical relevance and therapeutic predictive ability of hypoxia biomarkers in head and neck cancer tumour models.

    Lee, Tet Woo / Singleton, Dean C / Harms, Julia K / Lu, Man / McManaway, Sarah P / Lai, Amy / Tercel, Moana / Pruijn, Frederik B / Macann, Andrew M J / Hunter, Francis W / Wilson, William R / Jamieson, Stephen M F

    Molecular oncology

    2024  

    Abstract: Tumour hypoxia promotes poor patient outcomes, with particularly strong evidence for head and neck squamous cell carcinoma (HNSCC). To effectively target hypoxia, therapies require selection biomarkers and preclinical models that can accurately model ... ...

    Abstract Tumour hypoxia promotes poor patient outcomes, with particularly strong evidence for head and neck squamous cell carcinoma (HNSCC). To effectively target hypoxia, therapies require selection biomarkers and preclinical models that can accurately model tumour hypoxia. We established 20 patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) models of HNSCC that we characterised for their fidelity to represent clinical HNSCC in gene expression, hypoxia status and proliferation and that were evaluated for their sensitivity to hypoxia-activated prodrugs (HAPs). PDX models showed greater fidelity in gene expression to clinical HNSCC than cell lines, as did CDX models relative to their paired cell lines. PDX models were significantly more hypoxic than CDX models, as assessed by hypoxia gene signatures and pimonidazole immunohistochemistry, and showed similar hypoxia gene expression to clinical HNSCC tumours. Hypoxia or proliferation status alone could not determine HAP sensitivity across our 20 HNSCC and two non-HNSCC tumour models by either tumour growth inhibition or killing of hypoxia cells in an ex vivo clonogenic assay. In summary, our tumour models provide clinically relevant HNSCC models that are suitable for evaluating hypoxia-targeting therapies; however, additional biomarkers to hypoxia are required to accurately predict drug sensitivity.
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13620
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6637: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
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  8. 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
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  9. 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
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  10. Article ; Online: Calcium Enabled Remote Loading of a Weak Acid Into pH-sensitive Liposomes and Augmented Cytosolic Delivery to Cancer Cells via the Proton Sponge Effect.

    Yang, Mimi M / Yarragudi, Sasi Bhushan / Jamieson, Stephen M F / Tang, Mingtan / Wilson, William R / Wu, Zimei

    Pharmaceutical research

    2022  Volume 39, Issue 6, Page(s) 1181–1195

    Abstract: While delivery of chemotherapeutics to cancer cells by nanomedicines can improve therapeutic outcomes, many fail due to the low drug loading (DL), poor cellular uptake and endosomal entrapment. This study investigated the potential to overcome these ... ...

    Abstract While delivery of chemotherapeutics to cancer cells by nanomedicines can improve therapeutic outcomes, many fail due to the low drug loading (DL), poor cellular uptake and endosomal entrapment. This study investigated the potential to overcome these limitations using pH-sensitive liposomes (PSL) empowered by the use of calcium acetate. An acidic dinitrobenzamide mustard prodrug SN25860 was used as a model drug, with non pH-sensitive liposomes (NPSL) as a reference. Calcium acetate as a remote loading agent allowed to engineer PSL- and NPSL-SN25860 with DL of > 31.1% (w/w). The IC
    MeSH term(s) Animals ; Calcium ; Cell Line, Tumor ; Drug Delivery Systems ; Endosomes ; Hydrogen-Ion Concentration ; Liposomes/pharmacology ; Mice ; Neoplasms ; Protons
    Chemical Substances Liposomes ; Protons ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2022-02-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 843063-9
    ISSN 1573-904X ; 0724-8741 ; 0739-0742
    ISSN (online) 1573-904X
    ISSN 0724-8741 ; 0739-0742
    DOI 10.1007/s11095-022-03206-0
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1937: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
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