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5-Aminolevulinic acid-induced fluorescence in bronchial tumours: dependency on the patterns of tumour invasion
Authors:Gamarra F  Lingk P  Marmarova A  Edelmann M  Hautmann H  Stepp H  Baumgartner R  Huber R M
Institution:1. Medizinische Klinik – Innenstadt, Klinikum der Ludwig-Maximilians-Universität, Ziemssenstr. 1, 80336 München, Germany;2. Laserforschungslabor an der Urologie, Klinikum der Ludwig-Maximilians-Universität, Marchioninistr. 23, 81377 München, Germany;1. Blood Transfusion Service SRC Berne, Bern, Switzerland;2. Blood Transfusion Service SRC Zurich, Zurich, Switzerland;3. Blood Transfusion Service SRC Vaud, Epalinges, Switzerland;4. Blood Transfusion Service SRC Nordost Schweiz, St. Gallen, Switzerland;5. Blood Transfusion Service SRC Innerschweiz, Luzern, Switzerland;1. Graduate School of Architecture, Planning and Preservation, Columbia University, 400 Avery Hall, 1172 Amsterdam Avenue, New York, NY 10027, USA;2. Universitat Internacional de Catalunya (UIC), Barcelona, Spain;3. The Bartlett Development Planning Unit, University College London, UK;4. Comuna 8, Medellín, Colombia;1. School of Materials Science and Engineering, Guilin University of Electronic Technology, Guilin 541004, China;2. Guangxi Key Laboratory of Information Materials, Guilin University of Electronic Technology, Guilin 541004, China
Abstract:5-ALA-induced protoporphyrin IX (PPIX) fluorescence kinetics was quantified by fluorescence microscopy in three-dimensional organ co-cultures of human bronchial epithelium, which were infiltrated by four different lung tumour cell lines (EPLC-M31, LCLC-103H, NCI-H125 and NCI-H841). Corresponding fluorescence measurements were performed in monolayer cultures of these tumour cell lines and BEAS-2B cells as a model for normal bronchial epithelium by flow cytometry. Significant differences of fluorescence intensities (FI) between the tumours were detected in organ co-cultures as well as in single cell measurements. Relative FI values in organ co-cultures (FI(EPLC-32M1)>FI(LCLC-H103)>FI(NCI-H125)>FI(NCI-H841)) did not correspond to the measurements in single cells (FI(LCLC-H103)>FI(NCI-H125)>FI(NCI-H841)>FI(EPLC-32M1)). Histology of organ co-cultures revealed different patterns of invasion and tumour cell densities depending on the tumour type. After correction of FI in the co-cultures to tumour cell density the correlation coefficient for fluorescence values between both models increased considerably. Thus, additionally to distinctive features of 5-ALA metabolism, patterns of tumour invasion may be a factor determining 5-ALA-induced fluorescence. Considering these results, a pronounced heterogeneity of 5-ALA-induced fluorescence might be expected in different bronchial tumours in vivo. This could interfere with the diagnostic reliability of 5-ALA-induced fluorescence for early tumour detection.
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