Dataset Information

Phase I/II Studie zum Einsatz von Capecitabin und Oxaliplatin (XELOX) in Kombination mit Bevacizumab und Imatinib in der Erstlinientherapie von Patienten mit fortgeschrittenem kolorektalem Karzinom

ABSTRACT: Primary objectives: Primäres Studienziel der Phase IDefinition der empfohlenen Dosis von Capecitabin und Oxaliplatin bei gleichzeitiger Therapie mit Bevacizumab und Imatinib. Primäres Studienziel der Phase IIMachbarkeit und Verträglichkeit der in der Phase I ermittelten Dosis der Kombination aus XELOX mit Bevacizumab und Imatinib anhand der Bestimmung der Sicherheit und der Nebenwirkungen und Toxizitäten der Kombinationstherapie. Primary endpoints: Phase I Definition der empfohlenen Dosis von Capecitabin und Oxaliplatin bei gleichzeitiger Therapie mit Imatinib und Bevacizumab. Phase II Bestimmung der Sicherheit und der Nebenwirkungen und Toxizitäten der Kombinationstherapie mit Capecitabin, Oxaliplatin, Imatinib und Bevacizumab

DISEASE(S): Colorectal Cancer Stage Iv,Fortgeschrittenes Kolorektalen Karzinom Mit Inoperablen Metastasen

PROVIDER: 2521499 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Inhibition of deregulated protein kinases by small molecule drugs has evolved into a major therapeutic strategy for the treatment of human malignancies. Imatinib mesylate has emerged as the leading compound to treat chronic myeloid leukemia (CML), through its inhibition of Bcr- Abl tyrosine kinases, and other cancers. However, resistance to imatinib develops frequently, particularly in late-stage disease and has necessitated the development of new BCR-ABL inhibitors. The synthesis of a new series of phenylaminopyrimidines, structurally related to imatinib showed large interest since the introduction of the nilotibin. To identify the cellular pathways affected by new synthesized compounds, we applied mass spectrometry together with stable isotope labeling by amino acids in cell culture (SILAC) for the comparative study of protein expression in K562 cells that were untreated or treated with imatinib and imatinib derivates. Further, the global proteome of the K562 cells treated with imatinib were quantitatively compared with the cells treated with the new compounds. This study enriched our knowledge about direct cellular targets of kinase selective drugs. Further the results offered important new knowledge for gaining insights into the structural effects of action of the new compounds. Samples were analyzed on a longer column (30cm) and a longer gradient (180min). Raw data files were processed with Mascot distiller 2.3. The mgf files were searched with Mascot daemon 2.3. The quantification was also done by Mascot Distiller. All data was stored in ms_lims. The manual validation of false peptide ratios was done with Rover (part of ms_lims). Fixed modifications: none. Variable modifications: acetylation of peptide N-terminus, pyroglutamate formation of N-terminal glutamine, methionine oxidation. Enzyme: trypsine with one missed cleavage allowed. Precursor mass tolerance: 10 ppm. Peptide fragment mass tolerance: 0.5 Da Quantitation method: SILAC arginine and lysine +6 Da. Overview of the 17 different analyses: B SK23 vs DMSO C Y22 vs DMSO D SK20 vs DMSO E Y18 vs DMSO I SK20 vs DMSO K Y18 vs DMSO O Y22 vs DMSO R Imatinib vs Water Z Imatinib vs Water J SK20 vs Imatinib M SK23 vs Imatinib N Y22 vs Imatinib P SK23 vs Imatinib Q Y18 vs Imatinib S Y22 vs Imatinib T SK20 vs Imatinib Y Y18 vs Imatinib

Dataset Information

Phase I/II Studie zum Einsatz von Capecitabin und Oxaliplatin (XELOX) in Kombination mit Bevacizumab und Imatinib in der Erstlinientherapie von Patienten mit fortgeschrittenem kolorektalem Karzinom

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