An experimental model for treatment of mesothelioma

Our plain-English summary of An experimental model for treatment of mesothelioma, by W.E. Smith, D.D. Hubert, S.M. Holiat, et al (Cancer, 1981).

The study

• Authors: W.E. Smith, D.D. Hubert, S.M. Holiat, H.J. Sobel, S. Davis
• Journal: Cancer
• Published: 1981;47(4):658-63
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy.

Abstract

A peritoneal mesothelioma was induced by asbestos in a hamster, and was established in serial transfer to new hosts by injection of peritoneal effusion containing tumor cells. Biologically and histopathologically, this tumor is similar to its human counterpart. Three drugs were tested for efficacy using this model. Survival time was used as the only parameter of response and was compared with survival time of controls. Survival time increased 25 to 50% after short regimens of doxorubicin or 5-fluorouracil. Survival time increased up to 308% after long-continued treatments with cyclophosphamide. No cures were achieved.

In plain English

This was an animal experiment in male golden Syrian hamsters. One hamster given an attempted injection of tremolite asbestos ore into the right chest (pleural) cavity was killed 184 days later and found to have a peritoneal mesothelioma, in the abdominal lining. The authors judged that the needle had passed through the diaphragm, depositing most of the asbestos in the abdominal cavity. Fluid from its abdomen was used to pass the tumor on to new hamsters through 39 transplant generations. In later generations, untreated hamsters with the transplanted tumor died within 21 to 38 days. The authors tested three cancer drugs, mostly in groups of six hamsters, and compared average survival with untreated controls. Short courses increased average survival by 25% with doxorubicin, 32% and 50% with 5-fluorouracil, and 53% with cyclophosphamide. The most intensive cyclophosphamide treatment increased average survival by 308%, but these animals had the most extensive cancer spread. No cures were achieved: all animals died with peritoneal mesothelioma. The authors concluded that the tumor resembles human mesothelioma and should prove useful for screening candidate drugs.

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: an asbestos-induced peritoneal mesothelioma in a hamster was transplanted serially to new hamsters and used to test three chemotherapy drugs, with survival time as the only measure of response
• Who was studied: Male Lak:LVG golden Syrian hamsters. The original tumor was found in one hamster and was carried through 39 transplant generations. In chemotherapy trials (transplant generations 20 to 36), each treatment group generally had six hamsters, compared with six untreated controls of the same generation. Treated groups in Generation 31 had three hamsters each.
• Exposure: The original tumor followed an attempted right intrapleural injection of an ore sample (72N) of asbestiform tremolite. The authors concluded that most of this inoculum was deposited in the peritoneal cavity. Transplanted animals received tumor-containing peritoneal fluid and were treated with doxorubicin, 5-fluorouracil or cyclophosphamide, or given saline as a sham control.
• Main results:
  • The original hamster, killed 184 days after the injection, had a peritoneal mesothelioma confirmed by histopathology. No tumor was found in its lungs.
  • There were few fibers in the pleural lesions and many in the peritoneal lesions. From this, the authors concluded that the needle used for the attempted pleural injection had penetrated the diaphragm and deposited most of the inoculum in the peritoneal cavity.
  • The tumor was carried through 39 serial transplant generations by intraperitoneal injection of peritoneal fluid. No tumors developed in the three hamsters given minced tumor tissue into the thigh muscle.
  • In transplant generations after Generation 2, untreated hamsters died within 21 to 38 days, with average survival of 28 to 32 days.
  • Average survival of sham-operated hamsters given saline differed from that of untreated controls by -9 to +4%. The difference was not statistically significant.
  • With drugs injected into the abdomen starting on day 1, average survival increased by: 53% after four weekly doses of 25 mg/kg cyclophosphamide; 32% after four weekly doses and 50% after six weekly doses of 50 mg/kg 5-fluorouracil; and 25% after four weekly doses of 1 mg/kg doxorubicin.
  • The most intensive cyclophosphamide regimen (100 mg/kg into the muscle, to a total of 1500 mg/kg) increased average survival by 308%. These animals died between 113 and 123 days, with more extensive metastatic disease than any other group.
  • No cures were achieved. All animals in the trials died with diffuse peritoneal mesotheliomas, often with spread to the lungs.
  • One cyclophosphamide group (average survival +26%) was not significantly different from its control. The doxorubicin group (+25%) was significantly different from its control (p less than 0.001).
  • Hamsters treated with doxorubicin had severe (26%) weight loss within 34 days.
• The authors' conclusion: The authors concluded that no cures were achieved, that the tumor resembles its human counterpart in histopathology and growth behavior, and that it should prove useful for screening candidate drugs.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Peritoneal Mesothelioma, Doxorubicin, Fluorouracil (5-FU).

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• The value of adriamycin in the treatment of diffuse malignant pleural mesothelioma — B.S. Yap, R.S. Benjamin, et al. (1978)
• Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development — S. Sun, F. Frontini, et al. (2021)

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