title: Direct chemosensitivity monitoring ex vivo on undissociated melanoma tumor tissue by impedance spectroscopy.
abstract: Stage III/IV melanoma remains incurable in most cases due to chemotherapeutic resistance. Thus, predicting and monitoring chemotherapeutic responses in this setting offer great interest. To overcome limitations of existing assays in evaluating the chemosensitivity of dissociated tumor cells, we developed a label-free monitoring system to directly analyze the chemosensitivity of undissociated tumor tissue. Using a preparation of tumor micro-fragments (TMF) established from melanoma biopsies, we characterized the tissue organization and biomarker expression by immunocytochemistry. Robust generation of TMF was established successfully and demonstrated on a broad range of primary melanoma tumors and tumor metastases. Organization and biomarker expression within the TMF were highly comparable with tumor tissue, in contrast to dissociated, cultivated tumor cells. Using isolated TMF, sensitivity to six clinically relevant chemotherapeutic drugs (dacarbazine, doxorubicin, paclitaxel, cisplatin, gemcitabine, and treosulfan) was determined by impedance spectroscopy in combination with a unique microcavity array technology we developed. In parallel, comparative analyses were performed on monolayer tumor cell cultures. Lastly, we determined the efficacy of chemotherapeutic agents on TMF by impedance spectroscopy to obtain individual chemosensitivity patterns. Our results demonstrated nonpredictable differences in the reaction of tumor cells to chemotherapy in TMF by comparison with dissociated, cultivated tumor cells. Our direct impedimetric analysis of melanoma biopsies offers a direct ex vivo system to more reliably predict patient-specific chemosensitivity patterns and to monitor antitumor efficacy.
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), Molecular Biological-Biochemical Processing Technology, Leipzig, Germany.
authors.forename: Heinz-Georg
authors.initials: HG
authors.lastname: Jahnke
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), Molecular Biological-Biochemical Processing Technology, Leipzig, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Poenick
authors.affiliation: Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Maschke
authors.affiliation: Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kendler
authors.affiliation: Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Simon
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), Molecular Biological-Biochemical Processing Technology, Leipzig, Germany. andrea.robitzki@bbz.uni-leipzig.de.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Robitzki
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D058266:Dielectric Spectroscopy / Q000379:methods*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor