Project description:Primary Objective:
Correlation of the skin and/or eye toxicity grade secondary to Cetuximab or Panitumumab and the SNP profile of the Epidermal Growth Factor Receptor (EGFR) domain III region.
Secondary Objectives:
Correlation of SNP profile with indicators of tumour response parameters, such as radiological response, duration of response, time to progression (TTP), overall survival (OS) time, incidence of non-dermatological adverse events.
Project description:During inflammation, neutrophils are rapidly mobilized from the bone marrow storage pool into peripheral blood to subsequently enter lesional sites where most of them rapidly undergo apoptosis. Monocytes constitute a second wave of inflammatory immigrates giving rise to long-lived macrophages and dendritic cell subsets. According to descriptive immunophenotypic and cell culture studies, neutrophils may directly M-bM-^@M-^\transdifferentiateM-bM-^@M-^] into monocytes/macrophages. We here provide mechanistic data in human supporting the existence of this cellular pathway. Global transcriptional profiling of neutrophil-dervived monocytic cells revealed close resemblance of gene expression with monocytes and a clear separation of these cells from neutrophils. G-CSF mobilized neutrophils from peripheral blood were isolated and in vitro stimulated with GM-CSF, TNFa, and Il-1b for 5 days to generate monocytic cells. RNA were isolated from these cells and freshly isolated blood neutrophils and monocytes.
Project description:Monocytes and neutrophils are both myeloid cells that have the same progenitor, the granulocyte macrophage precursor (GMP). Neutrophils are mature innate cells that are phagocytes and can degranulate to mount an immune response, whereas monocytes are immature pluripotent cells that can differentiate into macrophages and dendritic cells that can phagocytose and present antigen. To compare the expression pattern and validate samples purity by comparing expression data with previously generated data for monocytes and neutrophils, we isolated monocytes (CD45+ CD64+ CD14+ CD16-) and neutrophils (CD66b+ CD16+) from eight healthy volunteers.