Establishment of mouse lung tumor models and development of new therapeutic approaches
Lade...
Datum
Autor:innen
Betreuer/Gutachter
Weitere Beteiligte
Beteiligte Institutionen
Herausgeber
Zeitschriftentitel
ISSN der Zeitschrift
Bandtitel
Verlag
Lizenz
Zitierlink
Zusammenfassung
Two mouse models of lung cancer were used to investigate cancer progression, cancer treatment, and cancer imaging. One model was established by subcutaneous injection of human adenocarcinoma A549 cells and lewis lung carcinoma (LLC1) cells, the other by intratracheal instillation of LLC1 cells. In the first study, the role of HIF-1 in tumor progression was investigated. Overexpression of HIF-1alpha by genetic alteration of adenocarcinoma cells decreased tumor size, due to decreased proliferation and increased apoptosis, despite an augmented vascularization observed in these tumors. In a further study, tumor regression by immunological approaches was attempted. Hybrids were generated by fusing dendritic cells and syngeneic poorly immunogenic LLC1 cells of C57/BL6 origin. Hybrid immunization induced the expression of a variety of cytokines and the partial host protective immunity against LLC1 tumor challenge. Moreover, hybrid vaccination and adoptive immunotherapy resulted in notable tumor regression. For establishing small animal tumor imaging in our study, three different imaging modalities, micro computed tomography (müCT), multi slice computed tomography (MSCT), and flat panel volumetric computed tomography (fpvCT) were investigated. The müCT images of intrapulmonary tumors suggested that µCT is a reliable and non-destructive method for quantifying the volume of intrapulmonary tumors in the mouse model. In addition, müCT can be used to evaluate tumor angiogenesis. We exploited MSCT and fpvCT for the in vivo imaging and detection of lung nodules in a mouse LLC1 lung tumor model. FpvCT allowed easy monitoring of a lung tumor model with high resolution, facilitating follow-up investigations in cancer research. In addition, the superiority of fpvCT over MSCT was clearly demonstrated. Furthermore, both imaging modalities (müCT and fpvCT), along with fluorescent microspheres, were applied to delineate the relative contribution of blood supply via the pulmonary and the systemic arteries to LLC1 lung tumors. All three methods revealed the pulmonary artery to be the primary functional source for feeding vessels to the lung tumors. Moreover, both modalities demonstrated the microanatomy of the vessels and blood-supplying tissue. The development of experimental mouse lung tumor models is essential to the understanding of tumor pathophysiology and vascular microanatomy. Our findings can be used to identify novel targets for anticancer treatment and for site specific drug targeting. Additionally, the successful employment of various computed tomography systems for lung cancer imaging in rodents offers in vivo evaluation of such strategies.Verknüpfung zu Publikationen oder weiteren Datensätzen
Beschreibung
Anmerkungen
Erstpublikation in
Giessen : VVB Laufersweiler 2006