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Cellular and vascular effects of hyperthermia

This special issue of the International Journal of Hyperthermia contains the proceedings of the Third European Society for Hyperthermic Oncology (ESHO) educational day symposium on hyperthermia entitled ‘Cellular and Vascular Effects of Hyperthermia’. The symposium was held on 13 June 2007 in the historic Bethlehem Chapel located in the Old Town of Prague in the Czech Republic. It was held in conjunction with the 24th Annual Meeting of ESHO (14–16 June 2007), in the same facility. On behalf of the ESHO Biological Committee, Valeria Milani and Michael Horsman were asked to organize an educational meeting on those hyperthermia-related topics in the field of biology relevant for understanding the results of clinical trials and of particular interest for the development of targeted therapies in combination with hyperthermia. The goal was to give new perspectives in the field of clinical and technical hyperthermia and create an environment to stimulate collaborations between basic researchers and clinicians. This educational activity was designed for academic scientists including biochemists, biophysicists, cell biologists, and medical and radiation oncologists interested in the application of hyperthermia. The symposium was divided into two sessions: the first concerned the cellular response to heat, while the second was on the vascular mediated responses to heat. As a result, this special issue contains nine articles and is designed to provide a founded knowledge on the cellular and vascular response to heat. The first article in this issue is an overview on the cellular responses to hyperthermia by Roti Roti, in which he focuses on those factors that contribute to direct cell killing by heat and those that play a role in the heat enhancement of ionizing radiation and chemotherapeutic agents. While high temperature thermal ablation treatments can induce direct DNA damage, lower hyperthermic treatments primarily affect cellular macromolecular functions. Thus he presents evidence demonstrating that both cell killing and the enhancement of conventional treatments by hyperthermia are mediated through protein-related changes that influence DNA replication, chromosomal aberrations, and DNA repair. Heat mediated effects on DNA repair is also the basis of the next article by Iliakis et al., which deals with the issue of thermal radiosensitization. They present the historical concept that the enhancement of radiation damage was originally believed to be the result of an inhibition of radiation-induced DNA double strand breaks (DSB). However, more recent studies in mutants with defective DSB repair, but still showing heat radiosensitization, led to the proposal that other mechanisms were responsible. In this review the authors revisit the issue and propose a model that still supports the role of an inhibition of DSB repair in heat radiosensitization. Another critical topic of relevance to the cellular affects of heat is stress proteins that confer resistance to physical stresses, especially heat shock (heat shock proteins, HSPs). The article by Calderwood and Ciocca gives a comprehensive review of HSPs in terms of the molecular aspects of the regulation of the stress response in cells and the diverse functions of HSPs. However, aside from discussing their role in influencing tumour growth and resistance to therapy the authors also discuss in detail the potential of targeting HSPs as a form of therapy using either pharmacological or immunological approaches. The relationship between hyperthermia and immunological affects was also the basis of the next article by Dayanc et al. These authors presented a summary of the literature regarding the role of temperature and natural killer (NK) cell anti-tumour activity. They show that while moderate thermal stress can both enhance and inhibit the cytotoxic action of NK cells against tumour cells, fever-range thermal stress only improves NK mediated tumour cell killing. After proposing several mechanisms for this enhancement they conclude that NK cells may play a significant role in enhancing the long-term efficacy of clinical hyperthermia. In the second half of this special issue the articles deal with various aspects related to the tumour vasculature. The first article by Horsman begins with a brief review of angiogenesis, the process by