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Pilocytic astrocytoma (PA) is the most common brain tumor in children. This tumor is usually benign and has a good prognosis. Total resection is the treatment of choice and will cure the majority of patients. However, often only partial resection is possible due to the location of the tumor. In that case, spontaneous regression, regrowth, or progression to a more aggressive form have been observed. The dependency between the residual tumor size and spontaneous regression is not understood yet. Therefore, the prognosis is largely unpredictable and there is controversy regarding the management of patients for whom complete resection cannot be achieved. Strategies span from pure observation (wait and see) to combinations of surgery, adjuvant chemotherapy, and radiotherapy. Here, we introduce a mathematical model to investigate the growth and progression behavior of PA. In particular, we propose a Markov chain model incorporating cell proliferation and death as well as mutations. Our model analysis shows that the tumor behavior after partial resection is essentially determined by a risk coefficient γ, which can be deduced from epidemiological data about PA. Our results quantitatively predict the regression probability of a partially resected benign PA given the residual tumor size and lead to the hypothesis that this dependency is linear, implying that removing any amount of tumor mass will improve prognosis. This finding stands in contrast to diffuse malignant glioma where an extent of resection threshold has been experimentally shown, below which no benefit for survival is expected. These results have important implications for future therapeutic studies in PA that should include residual tumor volume as a prognostic factor.

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Die Arbeit beschreibt das phänotypische Verhalten von kultivierten Langerhanszellen, antigenpräsentierenden Zellen der Epidermis, sowie die Art und Weise ihrer Elimination. Hierfür wurden Zellkulturen von Langerhanszellen durch Migration aus normaler menschlicher Haut gewonnen. Die Langerhanszellen durchlaufen dabei die gleiche funktionelle Entwicklung, wie nach Antigenpräsentation in situ. Ziel der Untersuchung war es, die funktionellen und zellulären Eigenschaften und die Elimination von Langerhanszellen in der Zellkultur zu ermitteln. Die Anzahl viabler Zellen wurde mittels Trypanblauausschluß zu verschiedenen Zeitpunkten der Kultur ermittelt. Außerdem wurden die Zellen mittels Elektronenmikroskopie und Immuncytochemie untersucht. Die Befunde zeigen, daß die Zellen in der Kultur eine Veränderung ihres Phänotyps sowie funktionelle Änderungen im Sinne einer Ausreifung zu antigenpräsentierenden, T-Zell stimulierenden Zellen erfahren. Das in-vitro-Verhalten entspricht dem von Langerhanszellen in vivo nach Kontaktsensibilisierung. Mit Hilfe von eines für Apoptose spezifischen ELISA (= Enzyme-linked immunosorbent assay: eine Nachweisreaktion für Antigene bzw. Antikörper mithilfe von Enzymen) und Elektronenmikroskopie wurde nachgewiesen, daß die Zellen in unseren Kulturen durch Apoptose starben. Es gibt keinen Anhaltspunkt dafür, daß sich die Zellen nicht auch in vivo apoptotisch eliminieren. Die Verlauf der Funktionsmarker weist darauf hin, daß vorwiegend die maturierten Zellen von Apoptose betroffen waren, und die Apoptose über das CD 95/CD 95 L- System gesteuert wurde. Die Versuche zeigten insgesamt, daß Langerhanszellen durch Apoptose aus der Kultur eliminiert werden. Da sich die Zellen nach Migration in vitro wie Langerhanszellen nach Antigenpräsentation in vivo verhalten, scheint die Apoptose ein biologisches Regulativ für die Elimination von funktionell ausgereiften Langerhanszellen darzustellen. / This work describes the phenotypic behavior of cultivated Langerhans-cells, epidermal cells presenting antigenes and how they are eliminated . Therefore cultures of Langerhans-cells won by migration from normal human skin were used. The migrated Langerhans-cells have the same phenotypic features as Langerhans-cells after presentation of antigenes in situ. The aim of this work was to show the functional and cellular features of Langerhans-cells in culture and the way of their elimination. The cells still alive were count at distinct times using the Trypan-blue-exclusion-method. Additionally the cells were examined by electron microscopy and immuncytochemical methods. The findings show, that the cells in culture have the same characteristics of the phenotype and change of their function in the direction of developing to antigen-presenting, T-cell-stimulating cells. The in vitro behaviour is the same as of Langerhans-cells in vivo after contact-sensitization. With the help of an elisa (=Enzyme-linked immunosorbent assay) specific for apoptosis ( Cell Death Detection Elisa = CDDE) and with electron microscopy was shown, that the cultivated cells died by apoptosis. There is no reference point, that the cells do not do the same in vivo. The process of the functional markers shows, that predominantly the matured cells die by apoptosis and that it was controled by the CD 95/CD 95-L -system The investigations showed, that the Langerhans-cells were eliminated by apoptosis of the culture. The cells after migration in vitro behave in the same manner as after presentation of antigen in vivo. This indicates apoptosis to be the biologic regulation for the elimination of functional matured Langerhans-cells.

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