Introduction 2000 2003 2007 2003 For a better understanding of the functioning of scalp cooling, it is important to quantify the contribution of reduced drug uptake and drug damage, if any, on the hair preservative effect of scalp cooling. To this end, we investigated experimentally the relationship between doxorubicin exposure and cell damage at different temperatures using normal human epidermal keratinocytes. 2001 The goal of the experiments was to assess the effects of temperature and chemotherapy on keratinocyte survival. Materials and Methods 2 2 6 −1 T L T M T H 1983 1988 1990 1983 −1 2 S 1 \documentclass[12pt]{minimal}
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\begin{document}$$S_{T,C}  = \mu  + \alpha T + \beta C + \gamma (T \cdot C) + \varepsilon $$\end{document} p Results 1 −1 −1 −1 2003 2 −1 −1 −1 T H T L T M −1 Figure 1. −1 −1 −1 −1 −1  Figure 2. Delta T L filled square T M open circle T H 1  F p F p \documentclass[12pt]{minimal}
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\begin{document}$$\eta _{\text{p}}^2 $$\end{document} 1 T L T H −1 −1 p T M T H −1 −1 T L T M −1 −1 Table 1. Results of an ANOVA analysis for determining the significance between different temperature groups at a specific doxorubicin concentration −1 F p T L T H T M T H T L T M 0.01 F 0.733       0.04 F 0.166       0.1 F <0.001 p   p 0.5 F <0.001 p p   1 F <0.05 p     3 F <0.001 p p   10 F <0.001 p p p p p asterisk Discussion We examined the role reduced metabolism has on the hair preservative effect of scalp cooling. For this, a controlled in vitro experiment was conducted to assess the damage exerted by doxorubicin on human epidermal keratinocytes for a range of chemotherapy concentrations and exposure temperatures. The effects of temperature and doxorubicin on cell damage were determined from cell viability measurements (MTT assay). −1 −1 The results of the experiment are in line with the hypothesis of scalp cooling. In this hypothesis, the reduced temperature caused by scalp cooling will result in lower perfusion and a lower cellular metabolism. With this, the supply, uptake and damage of a chemotherapeutic agent will be diminished. −1 Another remarkable result is that there is no significant difference between the medium and low temperature group. Thus, it seems that there is a limit in effect of reduced temperature. In a pilot study to determine optimal doxorubicin exposure temperature, we found that an exposure temperature of 26° C also showed increased cell viability (data not shown), and this increase did not differ from other temperature groups. During scalp cooling, a skin temperature of approximately 20° C is reached. Based on the results of our experiment, one might expect that the limit in effect of reduced temperature during scalp cooling may be reached for a temperature as high as 26° C. This means that during scalp cooling, the effect of reduced metabolism is already at its maximum. However, care has to be taken when the results of an in vitro experiment are generalized. Therefore, further studies on the effect of reduced temperature on cell damage are needed to exactly define this limit. Ideally, an in vitro hair follicle model is used in these studies. Our current study confines the boundary conditions in doxorubicin concentration and exposure temperature that can be used in these further studies. 2007