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Data-Driven Identification of Biomarkers for In Situ Monitoring of Drug Treatment in Bladder Cancer Organoids.
Becker, Lucas; Fischer, Felix; Fleck, Julia L; Harland, Niklas; Herkommer, Alois; Stenzl, Arnulf; Aicher, Wilhelm K; Schenke-Layland, Katja; Marzi, Julia.
Afiliación
  • Becker L; Department for Medical Technologies and Regenerative Medicine, Institute of Biomedical Engineering, University of Tuebingen, 72076 Tuebingen, Germany.
  • Fischer F; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, 72076 Tuebingen, Germany.
  • Fleck JL; Institute of Applied Optics (ITO), University of Stuttgart, 70569 Stuttgart, Germany.
  • Harland N; Mines Saint-Etienne, CNRS, UMR 6158 LIMOS, Centre CIS, Université Clermont Auvergne, 42270 Saint Jarez-en-Priest, France.
  • Herkommer A; Department of Urology, University of Tuebingen Hospital, 72076 Tuebingen, Germany.
  • Stenzl A; Institute of Applied Optics (ITO), University of Stuttgart, 70569 Stuttgart, Germany.
  • Aicher WK; Department of Urology, University of Tuebingen Hospital, 72076 Tuebingen, Germany.
  • Schenke-Layland K; Center of Medical Research, Department of Urology at UKT, University of Tuebingen, 72076 Tuebingen, Germany.
  • Marzi J; Department for Medical Technologies and Regenerative Medicine, Institute of Biomedical Engineering, University of Tuebingen, 72076 Tuebingen, Germany.
Int J Mol Sci ; 23(13)2022 Jun 23.
Article en En | MEDLINE | ID: mdl-35805961
Three-dimensional (3D) organoid culture recapitulating patient-specific histopathological and molecular diversity offers great promise for precision medicine in cancer. In this study, we established label-free imaging procedures, including Raman microspectroscopy (RMS) and fluorescence lifetime imaging microscopy (FLIM), for in situ cellular analysis and metabolic monitoring of drug treatment efficacy. Primary tumor and urine specimens were utilized to generate bladder cancer organoids, which were further treated with various concentrations of pharmaceutical agents relevant for the treatment of bladder cancer (i.e., cisplatin, venetoclax). Direct cellular response upon drug treatment was monitored by RMS. Raman spectra of treated and untreated bladder cancer organoids were compared using multivariate data analysis to monitor the impact of drugs on subcellular structures such as nuclei and mitochondria based on shifts and intensity changes of specific molecular vibrations. The effects of different drugs on cell metabolism were assessed by the local autofluorophore environment of NADH and FAD, determined by multiexponential fitting of lifetime decays. Data-driven neural network and data validation analyses (k-means clustering) were performed to retrieve additional and non-biased biomarkers for the classification of drug-specific responsiveness. Together, FLIM and RMS allowed for non-invasive and molecular-sensitive monitoring of tumor-drug interactions, providing the potential to determine and optimize patient-specific treatment efficacy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Vejiga Urinaria / Organoides Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Vejiga Urinaria / Organoides Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza