Recirculating chemohyperthermia as a treatment for non-muscle invasive bladder cancer: Current and future perspectives

Table 1 Mechanisms of action of hyperthermia

	39-41	41-43	43-45
Direct Cytotoxic Effects	Slight growth arrest	Reversible growth arrest Mainly in phase M and S Brief RNA synthesis impaired Prolonged DNA synthesis impaired	Irreversible growth arrest Permanent protein denaturalization DNA repair impaired Activation of both ways of apoptosis
Immune effects	Initial increase of intracellular HSP followed by increase of extracellular HSP Signals to immune cells Cross-priming of CD8+ T cells Dendritic cell activation Natural Killer activation Increase cytosine release (IL-6, IL-10)	As above	Altered cytosine production Inactivation of immune cells Reduced expression of extracellular HSP
Vascular effects	Vasodilatation which means: Improved tumor blood flow Improve tissue O2 Reduce acidosis Improve drug absorption	Improved tumor blood flow: Improve tumor oxygenation Improve drug delivery	Reduced tumor blood flow due to vascular collapse Microthrombosis Endothelial cell damage Vessel permeation Increased acidosis and reduce tissue O2

Adapted from Rampersaud et al[11]. IL: Interleukin.