Hyperthermia and mafosfamide in a human-derived malignant pleural mesothelioma cell line

Our plain-English summary of Hyperthermia and mafosfamide in a human-derived malignant pleural mesothelioma cell line, by E.M. Ehlers, W. Kühnel, G.J. Wiedemann (Journal of Cancer Research and Clinical Oncology, 2002).

The study

• Authors: E.M. Ehlers, W. Kühnel, G.J. Wiedemann
• Journal: Journal of Cancer Research and Clinical Oncology
• Published: 2002;128(2):65-72
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: Diffuse malignant pleural mesothelioma is the most common primary pleural malignancy. At the beginning of the last century, this tumor was of minor incidence. Meanwhile, the use of asbestos has led to and is still leading to a rise in pleural mesothelioma incidence. There is no standard therapy for this highly aggressive disease and the development of new therapeutic strategies is imperative.

Methods: We, therefore, investigated the morphological and pharmakokinetic effects of a combined thermochemotherapy consisting of the administration of different dosages of mafosfamide with and without the application of a 1-h hyperthermia at 41.7 degrees C on the human biphasic malignant pleural mesothelioma cell line MSTO-211H. After therapy, cells were prepared for light and electron microscopy. BrdU-incorporation for the S-phase fraction, TUNEL-labeling for detection of apoptosis, and quantitative assessments using the MTT assay were performed.

Results: Our results demonstrate that the combination of mafosfamide with hyperthermia leads to qualitatively and quantitatively enhanced cellular damage compared to monotherapy. During combined thermochemotherapy, cell damage and death is already induced at lower mafosfamide concentrations than without hyperthermia which suggests an additive effect from hyperthermia to the action of the alkylating drug mafosfamide. Cell death thereby mostly occurs as necrotic cell death rather than as apoptosis, although in a combined thermochemotherapy apoptosis is induced temperature-dependently, when comparing temperatures from 37 degrees C to 43 degrees C.

Conclusions: We suggest that the effect of substances such as ifosfamide and cyclophosfamide which are in clinical use, might be enhanced by the combination of local or regional hyperthermia in order to improve the therapeutical index of these substances in the treatment of pleural mesothelioma.

In plain English

This was a laboratory study of cancer cells grown in dishes, not of patients. It did not examine asbestos exposure. The authors used a cell line called MSTO-211H, derived from a human biphasic malignant pleural mesothelioma and obtained from the American Type Culture Collection. They treated the cells for one hour with the chemotherapy drug mafosfamide, with heat (hyperthermia at 41.7 degrees C for one hour), or with both. They then examined the cells by microscopy and laboratory tests. Adding heat to the drug killed an average of 14% more cells than the drug alone. At a drug concentration of 10 micromolar, about 50% of cells were killed by the drug alone and approximately 72% by the combination. Most cell death under the combined treatment appeared to be necrosis rather than apoptosis (programmed cell death). The authors suggested that the effect of drugs in clinical use, such as ifosfamide and cyclophosphamide, might be enhanced by local or regional hyperthermia in treating pleural mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: in vitro laboratory experiment on a human cancer cell line
• Who was studied: The human biphasic malignant pleural mesothelioma cell line MSTO-211H, obtained from the American Type Culture Collection; no patients were studied
• Exposure: No asbestos exposure was studied. Cells were treated for 1 hour with mafosfamide (concentrations from 0 to 30 micromolar), with hyperthermia (41.7 degrees C for 1 hour; 37, 39, 41.7 and 43 degrees C were compared in some tests), or with both combined
• Main results:
  • With mafosfamide alone, cell killing rose with dose up to about 15 micromolar, where 70% of cells were killed; raising the dose to 20 or 30 micromolar added only 3% to 4% more killing
  • Adding hyperthermia to mafosfamide killed an average of 14% more cells than mafosfamide alone
  • At 10 micromolar mafosfamide, 50% of cells were killed by the drug alone and approximately 72% by the drug combined with hyperthermia
  • When combined with mafosfamide, hyperthermia lowered the fraction of cells copying their DNA (S-phase fraction) by approximately 25%
  • Hyperthermia alone at 41.7 and 43 degrees C killed significantly more cells than 37 degrees C (p less than 0.05 and p less than 0.01), while 39 degrees C did not differ from 37 degrees C
  • At 43 degrees C, viable cells were reduced to one third; with mafosfamide added at that temperature, hardly any cells were detectable
  • At 37 degrees C, 10 micromolar mafosfamide produced twice as many apoptotic cells as in the control group
  • Adding hyperthermia to 10 micromolar mafosfamide lowered the percentage of apoptotic cells by more than 50% compared with the drug alone. Hyperthermia alone did not differ significantly from control in apoptosis
  • With mafosfamide plus 41.7 degrees C, cell killing was more than 70% but only 5% of cells were apoptotic; the authors interpreted this as cell death occurring mostly by necrosis
• The authors' conclusion: The authors suggested that the effect of drugs in clinical use, such as ifosfamide and cyclophosphamide, might be enhanced by local or regional hyperthermia to improve their therapeutic index in treating pleural mesothelioma

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biphasic Mesothelioma, Apoptosis.

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