Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy

Our plain-English summary of Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy, by Y. Wang, X. Wang, M.A. Le Bitoux, et al (Lasers in Surgery and Medicine, 2015).

The study

• Authors: Y. Wang, X. Wang, M.A. Le Bitoux, G. Wagnieres, H. Vandenbergh, M. Gonzalez, H.B. Ris, J.Y. Perentes, T. Krueger
• Journal: Lasers in Surgery and Medicine
• Published: 2015;47(4):323-30
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response.

Methods: Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group).

Results: Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls.

Conclusions: Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics.

© 2015 Wiley Periodicals, Inc.

In plain English

This was a mouse experiment, not a study of asbestos exposure. The authors grew a human mesothelioma cell line (H-Meso1) in nude mice and tested low-dose photodynamic therapy (L-PDT). In this treatment a light-activated drug, Visudyne, is followed by laser light, here at a fluence rate of 100 mW/cm2 and total light doses of 5, 10, 30 or 50 J/cm2. Using microscopy (5 animals per group), they tracked how a large fluorescent tracer, FITC-Dextran, entered tumor and normal tissue. The article reports that tumor uptake rose significantly, by 10-fold compared with controls, at 10 J/cm2 but not at the other doses. At 30 and 50 J/cm2, tumor blood vessels closed while normal tissue took up more tracer. In a second experiment, L-PDT at 10 J/cm2 alone and liposomal cisplatin (Lipoplatin) alone each slowed tumor growth slightly, but not significantly, compared with untreated controls. The two combined slowed growth significantly for up to 28 days. The authors concluded that the right light dose could raise drug uptake specifically in tumors. They said further work is needed to show the combination is synergistic.

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 in mice (xenografts), with live microscopy of tracer uptake and a tumor growth experiment comparing treatment groups
• Who was studied: Nude mice implanted with a human mesothelioma cell line (H-Meso1). Tracer uptake was measured in 5 animals per group. A luciferase-labelled version of the cells (H-Meso1-Luc) was used for the tumor growth experiment.
• Exposure: No asbestos exposure was studied. The treatment tested was Visudyne-mediated low-dose photodynamic therapy at a fluence rate of 100 mW/cm2 and total fluences of 5, 10, 30 and 50 J/cm2. The 10 J/cm2 dose was then combined with a single dose of liposomal cisplatin (Lipoplatin) and compared with L-PDT alone, Lipoplatin alone and untreated controls.
• Main results:
  • Tumor uptake of the tracer FITC-Dextran was significantly increased, by 10-fold, after L-PDT at 10 J/cm2, but not at 5, 30 or 50 J/cm2. This statement and the 10-fold figure appear in the article's abstract, where the comparison is with controls.
  • At 30 and 50 J/cm2, the tumor blood vessels were blocked (vascular shutdown), while normal surrounding tissue showed increased tracer uptake.
  • Based on the ratio of tumor to normal tissue uptake, 10 J/cm2 was the best light dose for tumor uptake with little normal tissue leakage.
  • L-PDT (10 J/cm2) alone and Lipoplatin alone each caused a slight decrease in tumor growth compared with untreated controls, which was not statistically significant.
  • L-PDT at 10 J/cm2 combined with Lipoplatin significantly reduced tumor growth (measured by bioluminescence) for up to 28 days.
  • Tumor volume measured with calipers was significantly lower over time in the combined treatment group than in controls.
• The authors' conclusion: The authors concluded that photodynamic drug delivery with the appropriate fluence and fluence rate has the potential to increase tumor uptake of drugs given through the bloodstream, specifically in tumors.
• Limitations the authors state:
  • The authors said the combined treatment seemed synergistic but that further work is required to prove this.
  • The authors said further studies are needed to better define how long the window of enhanced drug delivery lasts.
  • The authors noted that the procedure remains complex and invasive for use in patients.

Topics

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

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

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