March 24, 2009 |
Pancreatic cancer is a devastating disease with a very poor prognosis. This warrants the development of novel therapies including gene therapy. Several of these treatments were found to be effective in pre-clinical (animal) models. However, in the subsequent clinical studies in patients the results were disappointing. The discrepancy between pre-clinical models and results seen in patients underscores the need for pre-clinical models that more reliable predict the clinical efficacy.
A research article to be published on March 21,2009 of the World Journal of Gastroenterology addresses this problem and presents a novel model system more comparable to the in vivo situation in patients. Dr. van Geer and his colleagues in the University of Amsterdam have developed a system to culture normal and cancerous pancreatic tissue isolated from resection specimens obtained from patients. They used an automatic slicing system to provide a sufficient number of slices from the minimal amounts of tissue obtained from patients. In contrast to the existing pre-clinical models such as mouse models, this new model does assess the cellular heterogeneity of solid tumors and the accumulation of extracellular matrix that occurs in human tumors.
Although ex-vivo culture of pancreatic tissue has been reported, all existing methods performed poorly with respect to reproducibility and viability. We developed a system to generate slices uniform in size, shape and viability using an automatic precision cutter. These slices can cultured for at least 6 days while retaining viability and functionality. Based on this our model system allows reproducible testing of novel treatment options for pancreatic cancer, including studies to determine the efficacy of gene therapy vectors.
The authors have developed an ex-vivo system that allows processing of minimal amounts of pancreatic tissue from resection specimens. With this method, authors provide thin and viable tissue slices in a sufficient number to compare the efficiency of different gene therapy vectors. In addition, this system can be used to test novel molecular approaches to treat pancreatic cancer. Finally, these slices seem suitable for testing the susceptibility of the cultured cancer to available cytotoxic drugs which will allow to select optimal treatment to prevent re-occurrence .
Pancreatic cancer is a devastating disease and in the last decades only minimal progress has been made and the prognosis of patients suffering from pancreatic cancer remains poor. Lack of reliable pre-clinical model systems impairs the development of novel treatments. In this paper we present an in vitro system using patient material that not only helps to test novel drugs but also seems suitable for tailoring the therapy to provide optimal treatment for patients after resection.
The Academic Medical Center of the University of Amsterdam is one of the major referral centers in The Netherlands for Gastrointestinal Diseases and Cancer. At the department of surgery up to 50 pancreaticoduodenectomies are performed each year.