Events occurring during and after TNF-based ILP. Events in the tumour compartment (bottom) are listed in parallel to those taking place in peripheral tissues (top) over time. During the 90 minutes ILP, TNF activates angiogenic endothelial cells in the tumour tissue, resulting in increased permeability and improved melphalan penetration within the tumour tissue. After ILP, suppression of αvβ3 integrin occurs and endothelial cells undergo progressive apoptosis that parallels the apoptosis of tumour cells induced by melphalan. After ILP, a systemic inflammatory response develops in the peripheral tissues, with the secretion of inflammatory cytokines, soluble TNF receptors and an extracellular matrix degradation product that appear in the plasma.