Effects of photodynamic therapy on xenografts of human mesothelioma and rat mammary carcinoma in nude mice

Our plain-English summary of Effects of photodynamic therapy on xenografts of human mesothelioma and rat mammary carcinoma in nude mice, by S.L. Gibson, T.H. Foster, R.H. Feins, et al (British Journal of Cancer, 1994).

The study

• Authors: S.L. Gibson, T.H. Foster, R.H. Feins, R.F. Raubertas, M.A. Fallon, R. Hilf
• Journal: British Journal of Cancer
• Published: 1994;69(3):473-81
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

We have examined the effectiveness of photodynamic therapy against R3230AC rat mammary adenocarcinoma and human mesothelioma as xenografts in the same host. The results demonstrate that the xenografted human tumour is significantly more responsive to photodynamic treatment than the rodent mammary tumour. Studies also showed that the mesothelioma xenograft was fluence rate- and fluence-dependent while the rat tumour exposed to the same conditions demonstrated neither of these dependencies. This disparity in response was not attributable to a difference in either whole-tumour uptake or subcellular distribution of the porphyrin photosensitiser. Analysis of the effects of visible irradiation on cytochrome c oxidase activity, measured in mitochondria prepared from tumours borne on hosts injected with photosensitiser, demonstrated that photoradiation-induced enzyme inhibition was significantly greater in mesothelioma than in R3230AC mammary tumour preparations. However, in parallel studies conducted in vitro, when photosensitiser and light were delivered to previously unperturbed mitochondria, rates of enzyme inhibition were not significantly different. Both tumours were established in long-term cell culture. While the uptake of porphyrin photosensitiser was equivalent in both cell lines, the R3230AC cells displayed a significantly greater photosensitivity than the mesothelioma cells. The data presented here demonstrate that the mechanisms that govern response to photodynamic therapy are complex, but in the case of these two xenografted tumours host response to therapy is not likely to play a significant role.

In plain English

This animal and laboratory experiment on a treatment did not study asbestos exposure. The authors tested photodynamic therapy (the drug Photofrin Porfimer Sodium plus laser light) on human H-MESO-1 mesothelioma and rat R3230AC mammary carcinoma tumours grown under the skin of nude mice. Every light treatment significantly delayed growth of both tumour types compared with untreated controls (P less than 0.004). At 50 mW/cm2, mesothelioma growth delay rose significantly from 90 to 180 J/cm2 of total light. The rise to 270 J/cm2 was not significant (P = 0.053), and 270 and 360 J/cm2 did not differ. With fractionated (on-off) light, 5 of 7 mice showed no tumour volume doubling over 208 to 371 days. No dependence on light dose or intensity was detected for the rat tumours. Mesothelioma was controlled significantly better than the rat tumour at most doses. Both tumours took up similar amounts of a radiolabelled preparation described as similar to the drug. Cultured rat tumour cells, however, were significantly more sensitive at higher drug doses. The authors concluded that the difference could not be attributed directly to photosensitiser uptake or its location inside cells.

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 (tumour xenografts in nude mice) with accompanying laboratory studies on isolated mitochondria and cultured tumour cells
• Who was studied: Athymic nude mice (Ncr-nu) bearing either human H-MESO-1 mesothelioma tumours or R3230AC rat mammary carcinoma tumours implanted under the skin of the flank, at the University of Rochester, USA. Treatment groups ranged from 5 to 21 mesothelioma tumours and from 6 to 13 R3230AC tumours (Tables I and II).
• Exposure: No asbestos exposure was studied. The exposure was photodynamic therapy: 5 mg/kg Photofrin Porfimer Sodium (PPS) given into the abdomen, then 630 nm laser light through the skin 24 hours later. Light was given in three ways: at 200 mW/cm2 (360 J/cm2 total); at 50 mW/cm2 (90, 180, 270 or 360 J/cm2 total); or fractionated at 100 mW/cm2 (30 s on, 30 s off, for 2 h).
• Main results:
  • In both tumour types, all light treatments significantly delayed tumour volume doubling time compared with untreated controls (P less than 0.004).
  • For mesothelioma xenografts treated at 50 mW/cm2, tumour volume doubling time increased significantly from 90 to 180 J/cm2 total fluence.
  • For mesothelioma xenografts at 50 mW/cm2, the increase from 180 to 270 J/cm2 was nearly significant (P = 0.053), and no difference was observed between 270 and 360 J/cm2.
  • For the R3230AC rat tumour xenografts, no dependence of response on fluence rate or total fluence was detected.
  • Mesothelioma xenografts were controlled significantly better than R3230AC xenografts at all total fluences except 180 J/cm2 at 50 mW/cm2.
  • With the fractionated light regimen, 5 of 7 mice with mesothelioma xenografts showed no tumour volume doubling during observation periods of 208 to 371 days after treatment.
  • Uptake was measured with carbon-14-labelled polyhaematoporphyrin (PII), which the supplier described as similar to PPS. Mesothelioma and R3230AC xenografts accumulated and/or retained similar amounts of it.
  • The two tumour types did not differ significantly in labelled porphyrin content in any subcellular fraction.
  • Mitochondria were taken from tumours of mice given PPS and then exposed to light. Light inhibited the enzyme cytochrome c oxidase significantly more in the mesothelioma preparations. The initial rate of inhibition was 0.12% per unit of light dose for mesothelioma and 0.08% for R3230AC.
  • Mitochondria from untreated tumours were also exposed to the drug and light in the laboratory. Under these conditions, the enzyme showed no apparent difference in photosensitivity between the two tumour types.
  • In cultured cells, uptake of the labelled porphyrin was equivalent in both cell lines. Even so, R3230AC cells were significantly more sensitive (P less than 0.05) than mesothelioma cells to the higher PPS doses (5 or 10 micrograms per ml).
• The authors' conclusion: The authors concluded that the human mesothelioma xenograft's sensitivity to photodynamic therapy depended on total fluence and was inversely dependent on fluence rate. They found it significantly more responsive than the rat R3230AC xenograft in the same host. They could not attribute this difference directly to photosensitiser uptake or its location inside cells, and they identified no obvious host feature responsible.
• Limitations the authors state:
  • The uptake and biochemical measurements were averages over the whole tumour, so they could not detect differences in how the photosensitiser was distributed within tumours.
  • The authors stated it was not yet known whether the structural (histological) differences between the two tumours explain their different responses.

Topics

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

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

Related studies

• Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts — H.B. Ris, T. Krueger, et al. (1999)
• Response of Photofrin-sensitised mesothelioma xenografts to photodynamic therapy with 514 nm light — T.H. Foster, S.L. Gibson, et al. (1996)
• In vitro killing of human malignant mesothelioma by photodynamic therapy — S.M. Keller, D.D. Taylor, et al. (1990)
• Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy — Y. Wang, X. Wang, et al. (2015)
• Effects of natural interferon alpha, natural tumor necrosis factor alpha and their combination on human mesothelioma xenografts in nude mice — T. Ohnuma, L. Szrajer, et al. (1993)
• Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma — H.B. Ris, A. Giger, et al. (1997)

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