Kurzfassung

Pancreatic cancer falls within the top ten causes of cancer related deaths worldwide. Overall 5 year survival following diagnosis ranges between 0.4% and 4%. To date the only marginally successful treatment is surgical resection, which increases the 5 year survival to 17-24%. Unfortunately, only 10-15% of pancreatic patients qualify for surgery. For the remaining patients, treatment is mostly palliative. Adjuvant therapy following resection includes chemotherapy with 5-fluorouracil/folinic...Pancreatic cancer falls within the top ten causes of cancer related deaths worldwide. Overall 5 year survival following diagnosis ranges between 0.4% and 4%. To date the only marginally successful treatment is surgical resection, which increases the 5 year survival to 17-24%. Unfortunately, only 10-15% of pancreatic patients qualify for surgery. For the remaining patients, treatment is mostly palliative. Adjuvant therapy following resection includes chemotherapy with 5-fluorouracil/folinic acid (5-FU/FA) and/or radiotherapy.

Interferons (IFNs) are cytokines. There are two groups of IFNs: Type I and type II. IFN-α and -β belong to the first group while IFN-γ belong to the latter. Type I IFNs bind to the same IFN-receptor, which leads to the activation of the Jak-STAT signal transduction pathway and activated gene expression. IFNs cause cytotoxicity in cells and for pancreatic cancer this cytotoxicity has been ascribed to the induction of caspase dependant apoptosis. Type I IFNs are used in the treatment of malignant melanoma.

The combination therapy of pancreatic cancer with CDDP, 5-FU, ionizing radiation and IFN-α lead to a dramatically increase in the 5 year survival of patients. As the increase in survival was attributed to the inclusion of IFNs, we determined the effect of IFNs on survival of a panel of pancreatic cancer cell lines. The effectiveness of IFN-α vs. IFN-β was also assayed for. Finally, the question of whether IFNs have an enhancement effect on ionizing radiation in pancreatic cancer cell lines was determined. Cytotoxicity in 8 out of 10 pancreatic cancer cell lines were observed when treating with IFN-β compared to 5 out of 10 for IFN-α. Collectively, the data show that IFN-β is more active in pancreatic cancer cell lines than IFN-α. IFN-β caused radio-sensitization of 2 out of 10 pancreatic cancer cell lines and radioprotection in 1. IFN-α caused radio-sensitization in 1 out of 10 pancreatic cell lines and radioprotection in 2. The data show that type I IFNs is not effective radio-sensitizers of pancreatic cancer cell lines.


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