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  1. Article ; Online: Diagnostic Ability of Methods Depicting Distress of Tumor-Bearing Mice

    Wentao Xie / Marcel Kordt / Rupert Palme / Eberhard Grambow / Brigitte Vollmar / Dietmar Zechner

    Animals, Vol 11, Iss 2155, p

    2021  Volume 2155

    Abstract: Subcutaneous tumor models in mice are the most commonly used experimental animal models in cancer research. To improve animal welfare and the quality of scientific studies, the distress of experimental animals needs to be minimized. For this purpose, one ...

    Abstract Subcutaneous tumor models in mice are the most commonly used experimental animal models in cancer research. To improve animal welfare and the quality of scientific studies, the distress of experimental animals needs to be minimized. For this purpose, one must assess the diagnostic ability of readout parameters to evaluate distress. In this study, we evaluated different noninvasive readout parameters such as body weight change, adjusted body weight change, faecal corticosterone metabolites concentration, burrowing activity and a distress score by utilising receiver operating characteristic curves. Eighteen immunocompromised NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice were used for this study; half were subcutaneously injected with A-375 cells (human malignant melanoma cells) that resulted in large tumors. The remaining mice were inoculated with SCL-2 cells (cutaneous squamous cell carcinoma cells), which resulted in small tumors. The adjusted body weight and faecal corticosterone metabolites concentration had a high diagnostic ability in distinguishing between mice before cancer cell injection and mice bearing large tumors. All other readout parameters had a low diagnostic ability. These results suggest that adjusted body weight and faecal corticosterone metabolites are useful to depict the distress of mice bearing large subcutaneous tumors.
    Keywords animal model ; animal welfare ; xenograft models ; in vivo ; 3Rs ; Veterinary medicine ; SF600-1100 ; Zoology ; QL1-991
    Subject code 630
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A Sensitive LC-MS/MS Method for the Simultaneous Determination of Two Thia-Analogous Indirubin N -Glycosides and Indirubin-3′-Monoxime in Plasma and Cell Culture Medium

    Alica Fischle / Rico Schwarz / Franziska Wendt / Marcel Kordt / Robert Ramer / Lars Boeckmann / Martin Hein / Peter Langer / Steffen Emmert / Brigitte Vollmar / Burkhard Hinz

    Molecules, Vol 27, Iss 3031, p

    2022  Volume 3031

    Abstract: Indirubin was identified as an active component of Danggui Longhui Wan, an herbal mixture used in traditional Chinese medicine, and showed anticancer activity in clinical trials in patients with chronic leukemia. Investigations on the mechanisms of ... ...

    Abstract Indirubin was identified as an active component of Danggui Longhui Wan, an herbal mixture used in traditional Chinese medicine, and showed anticancer activity in clinical trials in patients with chronic leukemia. Investigations on the mechanisms of antitumor action of indirubins have mainly focused on the indirubin derivative indirubin-3′-monoxime (I3M). Meanwhile, antiproliferative and cytotoxic properties on cancer cells have also been demonstrated for several synthetic indirubin N -glycosides. In the present study, we demonstrate cytotoxic activity of the thia-analogous indirubin N -glycosides KD87 (3-[3′-oxo-benzo[ b ]thiophen-2′-( Z )-ylidene]-1-(β- d -glucopyranosyl)-oxindole) and KD85 (3-[3′-oxo-benzo[ b ]thiophen-2′-( Z )-ylidene]-1-(β- d -mannopyranosyl)-oxindole) against melanoma and squamous cell carcinoma cells as well as lung cancer and glioblastoma cells. The advanced state of preclinical studies on the effects of indirubins conducted to date underscores the need for pharmacokinetic data from cellular, animal, and human studies for which reliable quantification is required. Therefore, a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous measurement of KD87, KD85, and I3M in plasma and cell culture medium. Experimental conditions for sample preparation were optimized for human plasma protein precipitation and liquid-liquid extraction from plasma and cell culture medium. The methods were successfully validated in accordance with the U.S. Food and Drug Administration Bioanalytical Method Validation and evaluated for selectivity, sensitivity, matrix effect, recovery, carryover, calibration curve linearity, accuracy, precision, and stability. The applicability of the methods was demonstrated by the determination of KD87 in mouse plasma after prior intraperitoneal administration to mice.
    Keywords thia-analogous indirubin N -glycosides ; validation ; protein precipitation ; liquid-liquid extraction ; LC-MS/MS ; Organic chemistry ; QD241-441
    Subject code 610
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Multimodal Imaging Techniques to Evaluate the Anticancer Effect of Cold Atmospheric Pressure Plasma

    Marcel Kordt / Isabell Trautmann / Christin Schlie / Tobias Lindner / Jan Stenzel / Anna Schildt / Lars Boeckmann / Sander Bekeschus / Jens Kurth / Bernd J. Krause / Brigitte Vollmar / Eberhard Grambow

    Cancers, Vol 13, Iss 2483, p

    2021  Volume 2483

    Abstract: Background: Skin cancer is the most frequent cancer worldwide and is divided into non-melanoma skin cancer, including basal cell carcinoma, as well as squamous cell carcinoma (SCC) and malignant melanoma (MM). Methods: This study evaluates the effects of ...

    Abstract Background: Skin cancer is the most frequent cancer worldwide and is divided into non-melanoma skin cancer, including basal cell carcinoma, as well as squamous cell carcinoma (SCC) and malignant melanoma (MM). Methods: This study evaluates the effects of cold atmospheric pressure plasma (CAP) on SCC and MM in vivo, employing a comprehensive approach using multimodal imaging techniques. Longitudinal MR and PET/CT imaging were performed to determine the anatomic and metabolic tumour volume over three-weeks in vivo. Additionally, the formation of reactive species after CAP treatment was assessed by non-invasive chemiluminescence imaging of L-012. Histological analysis and immunohistochemical staining for Ki-67, ApopTag ® , F4/80, CAE, and CD31, as well as protein expression of PCNA, caspase-3 and cleaved-caspase-3, were performed to study proliferation, apoptosis, inflammation, and angiogenesis in CAP-treated tumours. Results: As the main result, multimodal in vivo imaging revealed a substantial reduction in tumour growth and an increase in reactive species after CAP treatment, in comparison to untreated tumours. In contrast, neither the markers for apoptosis, nor the metabolic activity of both tumour entities was affected by CAP. Conclusions: These findings propose CAP as a potential adjuvant therapy option to established standard therapies of skin cancer.
    Keywords kINPen™ ; malignant melanoma ; plasma medicine ; reactive oxygen and nitrogen species ; skin cancer ; squamous cell carcinoma ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Subject code 610 ; 616
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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