Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

Ryu, Samuel; Brown, Stephen L.; Kim, Sang Hie; Khil, Mark S.; Kim, Jae Ho

doi:10.1016/0360-3016(95)02017-9

Cited by 50 publications

(27 citation statements)

References 15 publications

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“…30 Comparably hyperthermia treatment significantly increased cell lethality in the 3-dimensional tumor spheroid model used in our study. Interestingly, large tumor spheroids were slightly more susceptible towards hyperthermia treatment, which may be due to the more acidic tissue microenvironment in large as compared to small tumor spheroids.…”

Section: Discussionmentioning

confidence: 55%

“…29 To assess hyperthermiainduced cell lethality in tumor spheroids of different size, i.e., small, drug sensitive, tumor spheroids (50 -100 m) vs. large, drug resistant tumor spheroids (300 -400 m) the tissues were treated for different times with a temperature of 42°C, which has been previously shown to affect cell viability of DU-145 prostate cancer cells. 30 Subsequently, cell lethality was determined by staining of nonviable cells using the fluorescence dye Sytox green, and clonogenic capacity was assessed by outgrowth experiments (Fig. 1a,b).…”

Section: Cell Lethality Upon Hyperthermia Treatment Of Multicellular mentioning

confidence: 99%

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Regulation of the multidrug resistance transporter P‐glycoprotein in multicellular prostate tumor spheroids by hyperthermia and reactive oxygen species

Wartenberg

Gronczynska

Bekhite

et al. 2004

Intl Journal of Cancer

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Hyperthermia is an important component of many cancer treatment protocols. In our study the regulation of the multidrug resistance (MDR) transporter P-glycoprotein by hyperthermia was studied in multicellular prostate tumor spheroids. Hyperthermia treatment of small (50 -100 m) tumor spheroids significantly increased P-glycoprotein and mdr-1 mRNA expression with a maximum effect at 42°C, whereas only moderate elevation of P-glycoprotein was found in large (350 -450 m) tumor spheroids. Hyperthermia caused an elevation of intracellular reactive oxygen species (ROS). Inhibition of ROS generation with NADPH-oxidase inhibitors diphenylen iodonium (DPI) and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF) abolished P-glycoprotein expression but did not affect its transcript levels following heat treatment. This indicates that P-glycoprotein levels are controlled by regulating its translation rate or stability. Hyperthermia incubation resulted in a differential activation of p38 mitogen-activated protein kinase (MAPK), extracellular regulated kinase 1,2 (ERK1,2), and c-jun N-terminal kinase (JNK) immediately, 4 hr and 24 hr after treatment. Furthermore, upregulation of hypoxia-inducible factor 1␣ (HIF-1␣) was observed. Elevation of HIF-1␣ and Pglycoprotein expression following hyperthermia treatment were abolished upon coadministration of the p38 inhibitor SB203580. In contrast the JNK inhibitor SP600125 and the ERK1,2 inhibitor UO126 resulted in increase of HIF-1␣ and P-glycoprotein in the control as well as the hyperthermia-treated samples, indicating negative regulation of intrinsic HIF-1␣ and P-glycoprotein expression by ERK1,2 and JNK signaling cascades. In summary our data demonstrate that hyperthermia-induced upregulation of P-glycoprotein and HIF-1␣ is mediated by activation of p38, whereas ERK1,2 and JNK are involved in repression of P-glycoprotein and HIF-1␣ under control conditions. Key words: multidrug resistance; P-glycoprotein; hyperthermia; hypoxia-inducible factor 1-␣ Hyperthermia in combination with chemotherapy and radiotherapy has been previously successfully used in anti-cancer strategies. [1][2][3][4][5] The efficiency of chemotherapeutic as well as radiotherapeutic cancer treatment is generally restricted by the expression of MDR transporters that confer resistance to a variety of structurally unrelated, clinically important antineoplastic agents. 6 -8 The most clinically significant MDR transporter P-glycoprotein, a 170 kDa ATP-dependent membrane-bound transporter, has been recently demonstrated to be upregulated by hyperthermia. 9,10 The promotor of the mdr-1 gene, which encodes for P-glycoprotein, harbors different responsive elements that are inducible by various stress factors including hyperthermia. 11 In this respect, it has been previously demonstrated in colon cancer cells that hyperthermia resulted in nuclear translocation of the Y-box transcription factor YB-1 and enhanced expression of mdr-1. 12 Binding of hyperthermia factors to defined heat shock element (HSE) motifs of the mdr-1 pr...

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Section: Discussionmentioning

confidence: 55%

Section: Cell Lethality Upon Hyperthermia Treatment Of Multicellular mentioning

confidence: 99%

Regulation of the multidrug resistance transporter P‐glycoprotein in multicellular prostate tumor spheroids by hyperthermia and reactive oxygen species

Wartenberg

Gronczynska

Bekhite

et al. 2004

Intl Journal of Cancer

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“…In spite of the lack of evidence, in many centres patients affected by advanced prostate cancer have been treated with hyperthermia combined with radiotherapy, achieving positive results in terms of feasibility and very low toxicity [11,13,14]. In human prostatic cancer cells, the combination of fractionated irradiation with continuous heating at 40 C or a single acute dose radiation following heat treatment at 41 C, achieves a thermal enhancement ratio (TER) in the range of 1.4 to 2.0 even if a mild hyperthermia is given [15]. In prostate cancer LHT does not increase late effects when added to conventional radiotherapy and it seems to enhance efficacy of combined treatment [11,13].…”

Section: Discussionmentioning

confidence: 99%

Conformal radiotherapy plus local hyperthermia in patients affected by locally advanced high risk prostate cancer: Preliminary results of a prospective phase II study

Maluta

Dall’Oglio

Romano

et al. 2007

International Journal of Hyperthermia

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“…(40-42˚C) to increase radiosensitivity of human tumour cells has been shown to be cell line-dependent (8,26,(100)(101)(102)(103)(104)(105). In a study by Xu et al, pre-treatment of cells at 41.1˚C for 1 h did not induce radiosensitisation, whereas treatment for 2 h or more resulted in radiosensitisation in the HT-resistant but not in the HT-sensitive cell line (106).…”

Section: Discussionmentioning

confidence: 99%

Cell survival and radiosensitisation: Modulation of the linear and quadratic parameters of the LQ model

Franken

Oei

Kok

et al. 2013

International Journal of Oncology

100

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Abstract.The linear-quadratic model (LQ model) provides a biologically plausible and experimentally established method to quantitatively describe the dose-response to irradiation in terms of clonogenic survival. In the basic LQ formula, the clonogenic surviving fraction S d ̸S 0 following a radiation dose d (Gy) is described by an inverse exponential approximation:, wherein α and β are experimentally derived parameters for the linear and quadratic terms, respectively. Radiation is often combined with other agents to achieve radiosensitisation. In this study, we reviewed radiation enhancement ratios of hyperthermia (HT), halogenated pyrimidines (HPs), various cytostatic drugs and poly(ADP-ribose) polymerase-1 (PARP1) inhibitors expressed in the parameters α and β derived from cell survival curves of various mammalian cell cultures. A significant change in the α/β ratio is of direct clinical interest for the selection of optimal fractionation schedules in radiation oncology, influencing the dose per fraction, dose fractionation and dose rate in combined treatments. The α/β ratio may increase by a mutually independent increase of α or decrease of β. The results demonstrated that the different agents increased the values of both α and β. However, depending on culture conditions, both parameters can also be separately influenced. Moreover, it appeared that radiosensitisation was more effective in radioresistant cell lines than in radiosensitive cell lines. Furthermore, radiosensitisation is also dependent on the cell cycle stage, such as the plateau or exponentially growing phase, as well as on post-treatment plating conditions. The LQ model provides a useful tool in the quantification of the effects of radiosensitising agents. These insights will help optimize fractionation schedules in multimodality treatments.

show abstract

Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

Cited by 50 publications

References 15 publications

Regulation of the multidrug resistance transporter P‐glycoprotein in multicellular prostate tumor spheroids by hyperthermia and reactive oxygen species

Regulation of the multidrug resistance transporter P‐glycoprotein in multicellular prostate tumor spheroids by hyperthermia and reactive oxygen species

Conformal radiotherapy plus local hyperthermia in patients affected by locally advanced high risk prostate cancer: Preliminary results of a prospective phase II study

Cell survival and radiosensitisation: Modulation of the linear and quadratic parameters of the LQ model

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