Alterations in uptake and distribution of adriamycin in single cells and spheroids by shock wave exposure as analyzed by cytometric methods

Worle, K and Steinbach, P and Hofstadter, F (1995) Alterations in uptake and distribution of adriamycin in single cells and spheroids by shock wave exposure as analyzed by cytometric methods. PHYSICA MEDICA, 11 (4). pp. 135-145. ISSN 1120-1797,

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Abstract

Lithotripter shock waves have the potential to expose a spatially limited region of the body to high amounts of acoustic energy, providing the possibility for a local intensification of a systemic therapy. For this reason we examined the effects of high-energy shock waves (HESW) generated by an experimental Siemens lithotripter on uptake and distribution of adriamycin (ADR) in single cells and multicell spheroids of several bladder cancer cell lines in vitro. Due to the inherent fluorescence, ADR can easily be detected by fluorometric methods. Flow cytometry was employed to characterize cellular drug uptake. Confocal laser scanning microscopy (CLSM) revealed subcellular distribution of ADR. Combined with interactive morphometric analysis, nuclear and cytoplasmic fluorescence intensities were evaluated separately and NIC ratios were calculated. Drug diffusion into multicell spheroids was examined by fluorescence microscopy. Scanning electron microscopy (SEM) of spheroids provided further insight into HESW action. It was found that HESW enhance cellular ADR accumulation and induce a shift towards nuclear localization of ADR. Cell aggregates of spheroids were loosened up by HESW, thus providing better drug diffusion into deeper regions of spheroids. All findings were paralleled with a markedly reduced proliferative capacity of cells treated simultaneously with ADR and HESW. These results suggest that HESW can cause a regionally enhanced drug efficiency in tissue.

Item Type: Article
Uncontrolled Keywords: INTRACELLULAR DOXORUBICIN DISTRIBUTION; BONE-MARROW CELLS; FLOW-CYTOMETRY; MULTIDRUG-RESISTANCE; CYTO-TOXICITY; INVITRO; GROWTH; LINES; ANTHRACYCLINES; ULTRASTRUCTURE; shock waves; adriamycin; combination therapy; fluorescence methods
Depositing User: Dr. Gernot Deinzer
Last Modified: 19 Oct 2022 08:37
URI: https://pred.uni-regensburg.de/id/eprint/52298

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