Dokument: Experimental investigation of photodynamic diagnostic and therapy on a human chordoma cell line model in vitro
| Titel: | Experimental investigation of photodynamic diagnostic and therapy on a human chordoma cell line model in vitro | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=50917 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20191029-080855-4 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Eismann, Lennert [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. med. Cornelius, Jan Frederick [Gutachter] Priv. Doz. Dr. Wagenmann, Martin [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Summary
Chordomas are rare neoplasm of the axial skeleton with predilection for the skull base and sacral region. Patients become symptomatic at advanced tumor stages due to slow and infiltrative growth into adjacent anatomical structures. At present, standard therapy is radical resection followed by radiotherapy. However, late diagnosis and proximity to surrounding vital structures often result in subtotal excision and hence in elevated local recurrence rates. Up to date, chemotherapy has shown to be ineffective. Therefore, new adjuvant treatment modalities are needed. 5-aminolevulinic acid based photodynamic therapy revealed promising results in meningioma, glioma and puitary adenoma models and encouraged us to investigate the efficacy of ALA/PDT on a human chordoma cell line in vitro. The results indicated that PPIX accumulation was superior after 6 h 5-ALA incubation time in comparison to a standard incubation time of 4 h. Furthermore, we detected a lethal effect 24 h of laser-irradiation on chordoma cells having been incubated for 6 h with graded doses of 5-ALA beforehand. High cell density of chordomas increased toxic effect of ALA/PDT. This might be explained by high intercellular communication and suggests existence of a so-called bystander effect. These preliminary findings of PPIX accumulation after exogenous 5-ALA application in chordoma cells may be of clinical interest for fluorescence-guided surgery of chordomas. In fact, residual tumor might better be detected increasing local tumor control. Even more, unresectable tumor remnants might be destroyed by ALA/PDT as intraoperative adjuvant treatment modality. Further investigations on different chordoma cell lines and tumor cells are needed to confirm these preliminary findings.Zusammenfassung Chordome sind seltene Tumore der Schädelbasis und des Os sacrum. Charakteristisch ist ihr langsames infiltratives Wachstum, weshalb diese Tumore meist erst im fortgeschrittenen Stadium symptomatisch werden. Der Goldstandard in der Therapie ist eine möglichst radikale Resektion gefolgt von einer adjuvanten Bestrahlung. Aufgrund von später Diagnosestellung und der Nähe zu vitalen Strukturen ist eine komplette Resektion schwierig und nur selten möglich. Residuales Tumorgewebe erhöht die lokale Rezidivrate. Chemotherapeutika zeigten bisher noch keinen Erfolg, sodass neue adjuvante Therapiemöglichkeiten notwendig sind. Eine alternative Behandlungsmethode könnte die 5- Aminolävulinsäure gestützte photodynamische Therapie darstellen, die bisher vielversprechende Ergebnisse bei unterschiedlichen Hirntumoren gezeigt hat. In der vorliegenden Arbeit untersuchten wir das Potential von 5-ALA gestützter PDT an einer humanen Chordomzelllinie in einem in vitro Modell. Dabei konnten wir im Vergleich zur Standardinkubationszeit von 4 Stunden eine erhöhte dosisabhängige Fluoreszenz nach 6 stündiger Inkubationszeit beobachten. Zudem verzeichneten wir einen letalen Effekt 24 h nach Bestrahlung mittels Laserlicht der mit 5-ALA behandelten Zellen. Eine hohe Zelldichte konnte dabei als positiver Einflussfaktor für einen maximalen letalen Effekt identifiziert werden. Dies könnte Hinweis auf eine hohe interzelluläre Kommunikation und die Existenz eines sogenannten Bystander Effekts sein. Diese Ergebnisse weisen erstens auf einen möglichen klinischen Nutzen von 5-ALA zur fluoreszenz-gestützten Resektion von Chordomen hin. Weiterhin könnten inoperable Tumorreste mittels photodynamischer Therapie adjuvant im gleichen Setting mit behandelt werden. Weitere Untersuchungen an Zelllinien und Tumorgewebe sind allerdings nötig, um diese vielversprechenden ersten experimentellen Ergebnisse weiter abzusichern. | |||||||
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Comprehensive Review of Intracranial Chordoma. RadioGraphics. 2003;23(4):995-1009. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 29.10.2019 | |||||||
| Dateien geändert am: | 29.10.2019 | |||||||
| Promotionsantrag am: | 15.10.2015 | |||||||
| Datum der Promotion: | 03.09.2019 |
