Hyperthermia and Drugs

Engelhardt, Ralf

doi:10.1007/978-3-642-82955-0_5

Cited by 133 publications

(32 citation statements)

References 96 publications

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“…The reduction of the side effects of chemotherapy and an increase in its effectiveness is certainly a desired result. Preliminary studies of Engelhardt [110], Dahl [111], Hahn [112] Urano [113] and Issels [114] have revealed that hyperthermia showed a synergism with chemotherapy as well as with radiotherapy. We have summarized the synergism and activity of drugs and HT in various micro-environmental conditions, in The activity of drugs in presence of hyperthermia is in the majority of cases additive and increase with the increase of the temperature [112,115].…”

Section: • Mitochondria Suffer Different Alterations In Their Cristaementioning

confidence: 99%

A Brief Overview of Hyperthermia in Cancer Treatment

Baronzio¹,

Parmar²,

Ballerini³

et al. 2014

J Integr Oncol

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Despite the large economic and intellectual efforts, cancer is still not easily treatable disease by conventional therapies. This led ultimately to reconsider hyperthermia, like one of interesting treatment methods connected to immunity and tumor metabolism. Hyperthermia has also the ability to play an additional role when used together with the conventional methods of treatment: surgery, radiotherapy, chemotherapy and immunotherapy. Recent trials in Holland and Germany have demonstrated that hyperthermia can prolong life and decrease disease re-appraisal when used in combination with radiotherapy and chemotherapy. Some tumors seem more responsive than others. In this brief summary we will attempt to give a vision of hyperthermia from a physical stand point, but more importantly we will give clinical and biological aspects. The results obtained in these trials on certain types of cancers such as cervix cancer, recurrent breast cancer and head neck cancer, melanoma, sarcomas, liver, glioblastoma and pancreatic cancer support the use of this technique, although some clinical and technical problems persist and have not been completely resolved.

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Section: • Mitochondria Suffer Different Alterations In Their Cristaementioning

confidence: 99%

A Brief Overview of Hyperthermia in Cancer Treatment

Baronzio¹,

Parmar²,

Ballerini³

et al. 2014

J Integr Oncol

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“…Hyperthermia can strongly potentiate the cytotoxic action of cisdiamminedichloroplatinum (cisplatin, cDDP) both in vitro and in vivo (reviewed by Engelhardt, 1987). In addition, relatively high heat doses (above 42°C) can (partly) reverse in vitro acquired cDDP resistance (Wallner et al, 1986;Herman et al, 1988;Mansouri et al, 1989;Konings et al, 1993;Hettinga et al, 1994).…”

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confidence: 99%

Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells

Hettinga

Lemstra²,

Meijer³

et al. 1997

Br J Cancer

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Summary In this study, the mechanism(s) by which heat increases cis-diamminedichloroplatinum (cisplatin, cDDP) sensitivity in cDDPsensitive and -resistant cell lines of murine as well as human origin were investigated. Heating cells at 430C during cDDP exposure was found to increase drug accumulation significantly in the cDDP-resistant cell lines but had little effect on drug accumulation in the cDDP-sensitive cell lines. DNA adduct formation, however, was significantly increased in all cell lines studied. Furthermore, ongoing formation of platinum (Pt)-DNA adducts after the end of cDDP treatment was enhanced and/or adduct removal was decreased in heated cells, resulting in relatively more DNA damage remaining at 24 h after the end of cDDP exposure. Correlation plots with survival revealed weak correlations with cellular Pt accumulation (r2 = 0.59) and initial Pt-DNA adduct formation (r2 = 0.64). Strong correlations, however, were found with Pt-DNA adducts at 6 h (r2 = 0.97) and 24 h (r2 = 0.89) after the incubation with the drug. In conclusion, the mechanism by which heat sensitizes cells for cDDP action seems to be the sum of multiple factors, which comprise heat effects on accumulation, adduct formation and adduct processing. This mechanism did not seem to differ between cDDP-sensitive and -resistant cells, emphasizing the potential of hyperthermia to reduce cDDP resistance.Keywords: thermochemosensitization; cisplatin resistance; cisplatin accumulation; cisplatin-DNA adducts; adduct repair Hyperthermia can strongly potentiate the cytotoxic action of cisdiamminedichloroplatinum (cisplatin, cDDP) both in vitro and in vivo (reviewed by Engelhardt, 1987). In addition, relatively high heat doses (above 42°C) can (partly) reverse in vitro acquired cDDP resistance (Wallner et al, 1986;Herman et al, 1988;Mansouri et al, 1989;Konings et al, 1993;Hettinga et al, 1994). Resistance to cDDP is a major problem in the clinic and limits the success of this drug. Thus, the combined use of heat and cDDP appears to be an interesting possibility to minimize this problem. The mechanism by which cells become resistant to cDDP has been extensively studied by numerous groups and has been found to be multifactorial (reviewed by Andrews and Howell, 1990), including (combinations of) decreased drug accumulation, increased detoxification of the drug via glutathione (GSH) metabolism or metallothioneins, decreased drug-DNA adduct formation and increased repair of the drug-induced DNA damage. The mechanism(s) by which hyperthermia sensitizes cells to cDDP is (are) less clear. Altered platinum (Pt) accumulation, total Pt-DNA adduct and DNA cross-link formation and/or repair of DNA damage have been reported as a result of combined heat and cDDP treatments (Meyn et al, 1980;Wallner et al, 1986;Herman et al, 1988Herman et al, , 1989Herman et al, , 1990Mann et al, 1988;Mansouri et al, 1989;Eichholtz-Wirth and Hietel, 1990;Los et al, 1993;Takahashi et al, 1993;Ohno et al, 1994). However, the published data are rather contradictory, and in most ...

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“…Hyperthermia is a powerful tool to enhance the cell killing effects of radiation (Konings, 1987) and many anti-neoplastic agents (Engelhardt, 1987). However, heat pretreatment leads to a reduction in the toxic action of some drugs.…”

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confidence: 99%

Hyperthermia, thermotolerance and topoisomerase II inhibitors

Kampinga

1995

Br J Cancer

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Summary The cytoxicity of both intercalating (m-AMSA) and non-intercalating (VP16, VM26) topoisomerase II-targeting drugs is thought to occur via trapping DNA topoisomerase II on DNA in the form of cleavable complexes. First, analysis of cleavable complexes (detected as DNA double-strand breaks) by pulsed-field gel electrophoresis confirmed the correlation between cleavable complex formation and cytotoxicity of three topoisomerase-targeting drugs in HeLa S3 cells (the order of effects being VM26> m-AMSA>VP16). In contrast to many antineoplastic agents, hyperthermic treatments were found to protect cells against the toxicity of all three topoisomerase II drugs. Hyperthermia treatment does not alter drug accumulation but reduces the ability of the drug-topoisomerase II complex to form the cleavable complexes. Nuclear protein aggregation induced by heat at the sites of topoisomerase II-DNA interaction may explain such an effect. In thermotolerant cells, the toxic effects of VP16 but not m-AMSA were reduced. For both drugs, however, the status of thermotolerance did not affect cleavable complex formation by the drugs. Thus, protection against VP-16 toxicity seems not to be associated with heat-induced activation of the P-gp 170 pump or altered topoisomerase II-DNA interactions. Rather, a protective (heat shock protein mediated?) mechanism against non-intercalating topoisomerase II drugs seems to occur at a stage after DNA-drug interaction. Finally, heat treatment before topoisomerase II drug treatment reduced toxicity and cleavable complex formation in thermotolerant cells to about the same extent as in non-tolerant cells, consistent with the presumption of nuclear protein aggregation being responsible for this effect.

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Hyperthermia and Drugs

Cited by 133 publications

References 96 publications

A Brief Overview of Hyperthermia in Cancer Treatment

A Brief Overview of Hyperthermia in Cancer Treatment

Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells

Hyperthermia, thermotolerance and topoisomerase II inhibitors

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