Hyperthermic potentiation of cisplatin toxicity in a human small cell lung carcinoma cell line and a cisplatin resistant subline

Hettinga, J. V. E.; Lemstra, Willy; Meijer, Coby; Mulder, Nanno; Konings, Awt; Vries, Elisabeth G.E. de; Kampinga, Harm H.

doi:10.3109/02656739409012372

Cited by 32 publications

(25 citation statements)

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“…We have shown that these pleiotropic effects of heat are also effective in enhancing cDDP accumulation, adduct formation and/or adduct removal in cDDP-resistant cells. This indicates why the multifactorial aspects of hyperthermia have been found to be so suitable for the (partial) reversal of cDDP resistance in a variety of cell lines with different mechanisms of resistance (Wallner et al, 1986;Herman et al, 1988;Mansouri et al, 1989;Konings et al, 1993;Hettinga et al, 1994; this study). Therefore, our data provide a scientific basis for supporting the use of combined heat and cDDP chemotherapy in cDDP-resistant tumours, and therefore this combined modality deserves further attention in the clinic.…”

Section: Discussionmentioning

confidence: 71%

“…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.…”

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confidence: 99%

“…Determination of cell survival For clonogenic survival determination, the samples were washed after treatment in complete medium, appropriately diluted to obtain about 100 colonies per plate and plated on 0.5% soft agar plates as described previously Hettinga et al, 1994). In the absence of treatment, plating efficiencies were always over 90% for the EN and ER cells and about 50-70% for the GLC4 and GLC4-cDDP cells.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 71%

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confidence: 99%

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confidence: 99%

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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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“…A hyperthermic potentiation of intracellular drug accumulation could be demonstrated for cisplatin only in cisplatin-resistant but not in-sensitive cell lines. Other mechanisms of hyperthermic potentiation such as increased DNA adduct formation and DNA damage could be demonstrated to the same extent in sensitive and resistant cells [43]. Doxorubicin is the only anthracycline which has been extensively studied in combination with HT.…”

Section: Ht and The Antineoplastic Drug Resistancementioning

confidence: 99%

Hyperthermia as an Adjunct to the Standard Treatment of Neoplastic Diseases: Few Cures but some Advances

Feyerabend¹,

Wiedemann²,

Richter³

et al. 1999

Oncol Res Treat

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Laboratory and clinical data confirm that hyperthermia may enhance the therapeutic index of ionizing radiation and specific cytotoxic drugs. As for whole-body hyperthermia (WBH), several generations of trials have been performed. Especially in refractory sarcomas, the combination of WBH and chemotherapy with ifosfamide, carboplatin, and etoposide led to a striking increase of response rates compared to chemotherapy alone. Toxicity of WBH procedures can be limited by using a radiant heat device. To evaluate the role of WBH in different tumor entities, several trials are under way. Hyperthermia, especially WBH, seems to stimulate the immune system, e. g. natural killer cell activity and number of cytotoxic T cells. Furthermore, the expression of the intracellular adhesion molecule 1 in tumors is enhanced by WBH, leading to an increased response of lymphokine-activated killer cells. As for locoregional hyperthermia, local control rates can be increased in combination with radiotherapy, e. g. in recurrent breast cancer and melanoma. Triple modality therapy (radiochemo-thermotherapy) seems to be useful especially in large lesions with poor prognosis.

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“…In preclinical trials the Cisplatin was shown to be effective [29], so the clinical studies were concentrating on this drug combination. Special case report has shown the feasibility [30] and the median survival gain (from 15 ( = 20) to 25 ( = 32) months) [31].…”

Section: Introductionmentioning

confidence: 99%

Oncothermia with Chemotherapy in the Patients with Small-Cell Lung Cancer

Lee

Haam

Kim

et al. 2013

Conference Papers in Medicine

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Small-cell lung cancer (SCLC) is one of the most aggressive and lethal forms of lung cancers. Chemotherapy and radiotherapy would be standard modality for SCLC with median survival being less than 4 months only. Complementary treatment to chemotherapy is desired. Oncothermia will be one of the candidates to this addition. We have made a study of 31 SCLC patients from April 2006 to March 2012. 23 cases were treated with combined chemotherapy and oncothermia, and 8 cases were treated with chemotherapy alone. Three patients from 14 patients (14/31) died in the study period; there were equal numbers in the two arms, including one long survival case of 28 months and one of 26 months, in the combination and chemo-group, respectively .16 patients (16/31) are alive: 4 patients with chemotherapy only, including one long survival case of 28.7 months, and 11 cases with combined therapy including three long survival cases of more than 3 years. We conclude that the combined use of chemotherapy and oncothermia has significantly enhanced the survival rate in comparison with the use of chemotherapy alone (log-rank test: P value < 0.02).

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Hyperthermic potentiation of cisplatin toxicity in a human small cell lung carcinoma cell line and a cisplatin resistant subline

Cited by 32 publications

References 8 publications

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

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

Hyperthermia as an Adjunct to the Standard Treatment of Neoplastic Diseases: Few Cures but some Advances

Oncothermia with Chemotherapy in the Patients with Small-Cell Lung Cancer

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