Cell biological effects of hyperthermia alone or combined with radiation or drugs: A short introduction to newcomers in the field

Figures & data

Figure 1. Overview of some critical cell biological events induced by a hyperthermic treatment. (a) Schematical figure of the kinetics of HSP up-regulation after heating (closed squares), development of thermotolerance (TT) against a second heat treatment (closed circles), expression of cells death after the 1st heat treatment (closed diamonds), the magnitude of thermal radiosensitization expressed as thermal enhancement ratios (TER) being the ratio of doses required to kill a fixed percentage of cell with radiation alone or with heat plus radiation (closed triangles) and the amount of protein aggregation after heating (open squares) (see also (c)). (b) Schematical figure of magnitude of radiosensitization (expressed as TER) for a mild (triangles) or severe (diamonds) heat treatment given after (left), simultaneously with (grey area) or before (right) radiation. Cells made thermotolerant by prior heating (TT, squares) show reduced radiosensitization and more rapid loss of interaction for heat given before (but not after) radiation. (c) Radiosensitivity of cells when left unheated (C: open circles) or when heated just before radiation (C+heat: closed circles) and effects of thermotolerance (TT, squares). Note that TT (pre-heated long before radiation and thus without residual protein aggregates, but with high HSP levels show equal radiosensitivity (TT: open squares) as control cells, but reduced sensitization by the (2nd) test heat treatment (TT+heat: closed squares). In this schematic figure, data are corrected for cell death as induced by heat alone. Also, it is indicated how TERs are calculated. (d) Effect of hyperthermia on the sensitivity of cells to cisplatin (cDDP): comparison between a platin-responsive parental cell line (open symbols) and a cDDP-resistant variant derived from this cell line (closed symbols). After heating the cell lines have become equally cDDP responsive. Note that all figures (except (d)) are purely meant to be illustrative for educational purposes and that the axes are in arbitrary units and that the data do not represent actual data points. Data from (d) are redrawn from Hettinga et al. [21].

Table I.  Overview of the interaction between heat and some chemotherapeutic agents (derived from [19]).

Class of agents	Compounds tested	Interaction	Remarks
Alkylating agents	Melphalan; Ifosfamide; Mitomycin C	More than additive	Gradual increase with increasing temperature; Largest when simultaneous
Nitrosureas	BCNU; CCNU	More than additive	Largest when simultaneous
Platinum drugs	Cisplatin (cDDP); Carboplatin; Tetraplatin	More than additive	Gradual increase with increasing temperature; Largest when simultaneous
Antibiotics	Bleomycin	More than additive	Only >42°C; Largest when simultaneous
	Doxorubicin; Actinomycin D	Complex	Less than additive when heat precedes drug
Pyrimidine antagonists	5-FU; Ara-C	Additive
Vinca alkaloids	Vincristine; Vinblastine	Additive
Other	mAMSA; VP16	Complex	Less than additive when heat precedes drug

Hettinga JVE, Lemstra W, Meijer C, Mulder NH, Konings AWT, de EGE, Kampinga HH. Hyperthermic potentiation of cisplatin toxicity in a human small cell lung carcinoma cell line and a cisplatin resistant subline. International Journal of Hyperthermia 1994; 10: 795–806

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