This thesis describes a number of studies that investigated several aspects of heat-induced apoptosis in human lymphoid malignancies. Cells harbour both pro- and anti-apoptotic proteins and the balance between these proteins determines whether a cell is susceptible to undergo apoptosis. In this tightly regulated process of apoptosis numerous proteins are involved which either stimulate or inhibit apoptosis, depending on intra- or intercellular signals. Most treatment strategies for cancer induce malignant cells to die by causing different types of cellular stress (e.g. DNA damage) that activate the apoptotic cell death program. In addition, cellular stress is known to induce an ancient heat-shock protein response that functions to sustain survival by limiting cellular damage and accelerating recovery. Recent evidence indicates that a coordinated interaction between these two functionally opposing pathways, apoptosis and the heat-shock response, result in an extremely complex response of which the mechanism is not yet elucidated. To get a better understanding of inducing apoptosis in cancer cells and the endogenous protection systems these cells harbour, we need to unravel the basic mechanisms that control apoptosis. Mitochondria play a critical role in the apoptotic pathway that is initiated in response to intracellular signals. Bcl-2 family members are the principal regulators of the mitochondrial pathway of apoptosis that control the release of apoptogenic factors from the mitochondria into the cytosol. However, the exact mechanisms by which Bcl-2 family proteins regulate this release are not fully understood.
|Award date||19 Sep 2008|
|Place of Publication||Enschede|
|Publication status||Published - 19 Sep 2008|