Intra-arterial instillation of microencapsulated, Ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting
| Autor: | Reiko Wiessner, Karlheinz Hauenstein, Günter Klöppel, Kerstin von Rombs, Ilse Schwendenwein, Matthias Löhr, Robert Michael Saller, Helga Bergmeister, Peter Karle, Walter H. Günzburg, Robert Obermaier, Matthias Renner, A. Probst, Petra Müller, Udo Losert, Horst Nizze, Brian Salmons, Jens-Christian Kröger, Anne Hoffmeyer, Thomas E. Wagner, Zoltan Bago, Stefan Benz |
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| Rok vydání: | 2002 |
| Předmět: |
Pathology
medicine.medical_specialty Cell Transplantation Swine Endocrinology Diabetes and Metabolism medicine.medical_treatment Capsules Splenic artery In Vitro Techniques Cell Line In vivo medicine.artery medicine Animals Humans Ifosfamide Antineoplastic Agents Alkylating Pancreas Chemotherapy Hepatology business.industry Gastroenterology Angiography medicine.disease Microspheres Femoral Artery medicine.anatomical_structure Instillation Drug Regional Blood Flow Circulatory system Cytochrome P-450 CYP2B1 Pancreatitis Feasibility Studies business Genetic Engineering Perfusion Splenic Artery medicine.drug |
| Zdroj: | Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 3(1) |
| ISSN: | 1424-3903 |
| Popis: | Background: The therapeutic efficacy of intratumoral instillation of genetically engineered, CYP2B1-expressing, microencapsulated cells in combination with ifosfamide had been previously demonstrated in xenografted human pancreatic ductal carcinomas [Gene Ther 1998;5:1070–1078]. Prior to a clinical study, the feasibility of an intra-arterial application of microencapsulated cells to the pancreas and its consequences to the organ had to be evaluated. Material and Methods: Microencapsulated, CYP2B1-producing cells were instilled both in vivo (transfemoral angiographical access) and in vitro (perfusion model) in the splenic lobe of the pig pancreas. In vivo, animals were monitored clinically for 7 days, then treated with ifosfamide and sacrificed. In vitro, ifosfamide was administered intra-arterially. Results: In all animals, 100 microcapsules could be instilled safely via the femoral route without clinical, biochemical or histological signs of pancreatitis. Histological examination revealed partial obstruction of small arteries by the capsules, without causing any parenchymal damage. In vitro, instillation reduced blood flow by half. Ifosfamide, also in combination with the capsules, did not add any damage to the pancreas. Conclusion: Intra-arterial instillation of microencapsulated cells to the pig pancreas is feasible and safe. Neither pancreatitis, foreign body reactions nor circulatory disturbances were observed. Clinical application of this genetically enhanced chemotherapeutic method seems possible. |
| Databáze: | OpenAIRE |
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