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Immuno-chemotherapy reduces recurrence of malignant pleural mesothelioma : an experimental setting

Ampollini, Luca and Soltermann, Alex and Felley-Bosco, Emanuela and Lardinois, Didier and Arni, Stephan and Speck, Roberto F. and Weder, Walter and Opitz, Isabelle. (2009) Immuno-chemotherapy reduces recurrence of malignant pleural mesothelioma : an experimental setting. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, Vol. 35. pp. 457-462.

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Official URL: http://edoc.unibas.ch/dok/A6005102

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Abstract

OBJECTIVE: To assess the effect of immuno-chemotherapy on the extent of local tumour recurrence in an established rat model of malignant pleural mesothelioma (MPM). METHODS: Six days after subpleural inoculation of a syngeneic MPM cell line Interleukin-45 (IL-45), left-sided pneumonectomy and resection of the tumour nodule was performed. Animals were randomised into four treatment groups for intrapleural therapy: control (n=6), 500 microg cytosine phosphate guanosine oligodeoxynucleotide (CpG-ODN) (n=6), cisplatin-fibrin (n=6), cisplatin-fibrin+500 microg CpG (n=6). Six days later the volume of tumour recurrence was assessed, which was the primary endpoint. Secondary endpoints were quantification of the ratio host/tumour cells in the local recurrence and cytokine expression profile in the tumour tissue by real time quantitative PCR (qPCR). T lymphocyte subpopulations in the tumour recurrence tissue were evaluated by immunohistochemistry. Treatment-related toxicity was monitored by measuring blood chemistry and complete blood count. RESULTS: The volume of tumour recurrence was significantly reduced from 610 mm(3) in the control group to 11.7 mm(3) in the cisplatin-fibrin group (p=0.004) and to 21.8mm(3) in the cisplatin-fibrin+CpG group (p=0.004). Pro-inflammatory cytokines (Interferon-gamma (IFN-gamma), Interleukin-6 (IL-6), Interleukin-12 (IL-12)) were increased after treatment with cisplatin-fibrin+CpG in comparison to cisplatin-fibrin alone but differences were not statistically significant. We found a higher ratio of host/tumour cells in the cisplatin-fibrin+CpG group (45/55%) compared to the cisplatin-fibrin group (27/73%). In comparison to the control group, animals treated with cisplatin-fibrin+CpG showed a higher number of CD8+ T-cells in the tumour tissue. No significant treatment-related toxicity was observed. CONCLUSIONS: Adjuvant treatment with chemotherapy or immuno-chemotherapy leads to significant reduction of mesothelioma recurrence after surg in this rat MPM model. Immuno-chemotherapy resulted in an increased recruitment of inflammatory cells to the site of tumourigenesis and elicited higher level of tumour growth inhibiting cytokines.
Faculties and Departments:03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe > Thoraxchirurgie (Lardinois)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Innere Organe > Thoraxchirurgie (Lardinois)
UniBasel Contributors:Lardinois, Didier
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Oxford Univ. Press
ISSN:1010-7940
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Apr 2013 07:02
Deposited On:26 Apr 2013 06:53

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