Effects of natural interferon alpha, natural tumor necrosis factor alpha and their combination on human mesothelioma xenografts in nude mice

Our plain-English summary of Effects of natural interferon alpha, natural tumor necrosis factor alpha and their combination on human mesothelioma xenografts in nude mice, by T. Ohnuma, L. Szrajer, J.F. Holland, et al (Cancer Immunology, Immunotherapy, 1993).

The study

• Authors: T. Ohnuma, L. Szrajer, J.F. Holland, M. Kurimoto, J. Minowada
• Journal: Cancer Immunology, Immunotherapy
• Published: 1993;36(1):31-6
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Effects of human natural interferon alpha (nIFN) alone, human natural tumor necrosis factor alpha (nTNF) alone and their combination (OH-1) were tested on three human mesothelioma lines implanted in nude mice. Tumors were transplanted subcutaneously by trocar on treatment day -12. nIFN was given intraperitoneally (i.p.) at a dose of 2 x 10(7) or 2 x 10(8) IU kg-1 day-1, 5 days a week for 3 weeks. nTNF was given i.p. at a dose of 2 x 10(7) or 2 x 10(8) U kg-1 day-1 in the same schedule as that of nIFN. Tumor diameters were serially measured and tumor volumes were calculated. Antitumor effects were assessed by two methods: comparison of final tumor volumes in treated and control groups (T/C), and changes in median average total tumor volume. The treatment produced no clinically discernible toxicities. nIFN had strong inhibitory activity against all three human mesothelioma lines. nTNF alone had modest activity only at the high dose used. The combination of the two produced activity essentially similar to that produced by nIFN alone. High-dose nIFN may have a role as an active agent in the treatment of patients with mesothelioma.

In plain English

This was an animal experiment that did not study asbestos exposure. The authors implanted tumors from three human mesothelioma lines (ES, BG and VS) under the skin of nude mice. They treated the mice with natural interferon alpha (nIFN), natural tumor necrosis factor alpha (nTNF), or OH-1, a mixture of both. Injections were given five days a week for three weeks at a low dose (2 × 10^7 units per kg per day) or a high dose (2 × 10^8). A treated-to-control tumor volume ratio of 0.42 or less counted as activity. Near the end of treatment, high-dose nIFN gave ratios of 0.14, 0.026 and 0.29 in the three lines, and high-dose OH-1 gave 0.06, 0.035 and 0.25. nTNF alone met the cut-off only once (0.36, VS line, high dose). Adding nTNF appeared to boost nIFN in two of six experiment sets. No mice died during treatment. The authors concluded that nIFN was the main active component and that cautious clinical trials of high-dose nIFN in mesothelioma patients appear warranted.

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: Animal experiment: human mesothelioma tumors grown as xenografts in nude mice and treated with cytokines, compared with untreated controls
• Who was studied: Female nude (nu/nu) mice, four weeks old on arrival, carrying three human mesothelioma lines (ES, BG, VS) established at Mount Sinai Medical Center, New York. BG and VS were epithelial and ES was biphasic. There were three to five mice per group. The article does not say whether the tumors came from pleural or peritoneal mesothelioma.
• Exposure: No asbestos exposure was studied. The treatments were natural interferon alpha (nIFN) at 2 × 10^7 or 2 × 10^8 IU per kg per day, natural tumor necrosis factor alpha (nTNF) at 2 × 10^7 or 2 × 10^8 U per kg per day, or both combined (OH-1). All were injected into the abdominal cavity daily, 5 days a week for 3 weeks.
• Main results:
  • High-dose nIFN versus control, final tumor volume ratios: 0.14 for ES (day 17), 0.026 for BG (day 21), and 0.29 for VS (day 22) and 0.19 for VS (day 40). All met the activity cut-off.
  • High-dose OH-1 versus control ratios: 0.06 for ES, 0.035 for BG, and 0.25 for VS (day 22) and 0.14 for VS (day 40). All met the activity cut-off.
  • The high dose of nIFN or OH-1 was more active than the low dose. At the low dose, the ratios for nIFN and OH-1 were 0.50 for ES (not active) and 0.35 and 0.14 for BG (active). For VS, the ratios did not reach the activity cut-off.
  • nTNF alone met the activity cut-off only for the VS line at the high dose on day 22 (ratio 0.36). On day 40 that ratio was 0.52, not active. In the ES line, the low dose of nTNF appeared to stimulate tumor growth (ratio 1.37).
  • Across six sets of data from three cell lines, nTNF appeared to potentiate nIFN on two occasions. In the rest, the effects of OH-1 overlapped those of nIFN alone.
  • No mice died during the 3-week treatment period, and the authors saw no clinically discernible toxicities compared with untreated mice.
• The authors' conclusion: The authors concluded that high doses of OH-1 were extremely active against human mesotheliomas in nude mice and that nIFN was the major active component. They wrote that their observations appear to warrant re-evaluation of the maximum tolerated dose of nIFN and cautious clinical trials of high-dose nIFN in patients with mesothelioma.
• Limitations the authors state:
  • In two sets of data the first experiments failed because of laboratory errors and were repeated. The repeated experiments used fewer mice per group because of a shortage of the cytokines.
  • For some comparisons, the sample size was too small for the Wilcoxon rank-sum test.
  • The authors note that there are no side-by-side data comparing the toxicity of natural and recombinant interferon.

Topics

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

Medical terms in this study, explained in our Lexicon: Necrosis, Mesothelioma.

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