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Increasing evidence suggests that altered gene expression is associated with the induction and maintenance of malignancy in various organs including mouse lung adenocarcinomas. A competitive cDNA library screening (CCLS) was used to examine gene expression in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung adenocarcinomas from (C3H/HeJ x A/J])F1 mice. Comparisons of RNA expression in lung adenocarcinomas to those of normal surrounding lung tissue revealed altered expression in 220 clones from more than 50,000 clones screened. Fifty clones were selected for quantitative reverse transcriptase-polymerase chain reaction (PCR) analysis to verify altered expression. PCR primers were designed based on partial sequence analysis of the clones. Twenty-two clones were found to be differentially expressed in lung adenocarcinomas compared with normal lungs. GenBank database analysis showed that 14 of the 22 clones were homologous with known genes, whereas 8 clones contained novel sequences. Thirteen clones were down regulated in tumors compared to normal lung tissues, and 9 were overexpressed. The clones underexpressed or absent include adipocyte p27, carbonic anhydrase III, carbonyl reductase, cytochrome CYP2E1, skelemin, myosin, major urinary protein, and contrapsin. Overexpressed clones include Bruton's tyrosine kinase, cyclin D3, poly(A)-binding protein, alpha-fetoprotein, transferrin, and mouse B2 family repetitive sequence. Further examination of biologic implications of the differentially expressed genes in lung adenocarcinomas is necessary to understand their role(s) in mouse lung carcinogenesis.

OBJECTIVES:In cancer, treatments often aim to extend time to progression. The implications on overall survival are often inconclusive, as trials are too short and the majority of patients are still alive at the end of the trial. However, for decision making, it is important to estimate both the treatment effect on Progression Free Survival as well as the treatment effect on Overall Survival. This poster shows how the estimation of Overall Survival benefit can be improved by the use of Progression Free Survival data. METHODS: The developed Network Meta-Analysis model uses the tested hypothesis that treatments provided until progression in general do not change the length of the post-progression period. This hypothesis is tested in detail based on systematic literature reviews concerning 4 different types of cancer. A test for equal lengths of the post-progression periods is described too. RESULTS: A network meta-analysis model is described, which can be used to obtain estimates for OS from PFS data for treatments for which no OS data or insufficient OS data are available. This informs decision making in situations where otherwise no conclusion can be drawn. The methodology is applied to an indirect comparison of Chlorambucil, Fludarabine and Fludarabine Cyclophosphamide. Comparable DIC were obtained to individual fitting of OS and PFS for the situation that OS

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