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Phulpin B.,Head and Neck Surgery and Dental Units | Phulpin B.,University of Lorraine | Dolivet G.,Head and Neck Surgery and Dental Units | Dolivet G.,University of Lorraine | And 6 more authors.
Journal of Biomedicine and Biotechnology | Year: 2011

Background. We aimed to explore (i) the short-term retention of intramedullary implanted mesenchymal stem cells BMSCs and (ii) their impact on the bone blood flow and metabolism in a rat model of hindlimb irradiation. Methods. Three months after 30 Gy irradiation, fourteen animals were referred into 2 groups: a sham-operated group (n = 6) and a treated group (n = 8) in which 111In-labelled BMSCs (2 × 10 6 cells) were injected in irradiated tibias. Bone blood flow and metabolism were assessed by serial 99mTc-HDP scintigraphy and 1-wk cell retention by recordings of 99mTc/ 111In activities. Results. The amount of intramedullary implanted BMSCs was of 70% at 2H, 40% at 48H, and 38% at 168 H. Bone blood flow and bone metabolism were significantly increased during the first week after cell transplantation, but these effects were found to reduce at 2-mo followup. Conclusion. Short-term cell retention produced concomitant enhancement in irradiated bone blood flow and metabolism. Copyright © 2011 Bérengre Phulpin et al. Source

Phulpin B.,Head and Neck Surgery and Dental Units | Phulpin B.,University of Lorraine | Tran N.,University of Lorraine | Leroux A.,University of Lorraine | And 14 more authors.
Journal of Radiation Research | Year: 2012

Radiotherapy is an integral part of overall cancer therapy. One of the most serious adverse effects of irradiation concern, for long-term survivors, the development of post-radiation sarcoma (PRS) in healthy tissues located within the irradiated area. PRS have bad prognosis and are often detected at a late stage. Therefore, it is obvious that the early detection PRS is a key-point and the development of preclinical models is worthy to evaluate innovative diagnostic and therapeutic procedures. The aim of this study was to develop a spontaneous murin model of PRS and to evaluate the potency of Positron Emission Tomography (PET) for early detection. Fifteen Wistars rats were irradiated unilateraly on the hindlimb with a single dose of 30 Gy. Sequential analysis was based on observational staging recordings, Computerized Tomography (CT) scanning and PET. Tumors were removed and, histopathological and immunochemistry analyses were performed. Among the irradiated rats, 12 sarcomas (80%) were detected. All tumors occurred naturallty within the irradiated hindlimb and were highly aggressive since most tumors (75%) were successfully transplanted and maintained by serial transplantation into nude mice. Upon serial staging recordings, using PET, was found to enable the detection of PRS earlier after irradiation than with the other methods (i.e. 11.9 ±1.8 vs 12.9 ± 2.6 months). These results confirmed the interest of experimental models of PRS for the preclinical evaluation of innovative diagnostic strategies and confirmed the potency of PET for early detection of PRS. This preclinical model of PRS can also be proposed for the evaluation of therapeutic strategies. Source

Gallet P.,University of Lorraine | Phulpin B.,University of Lorraine | Phulpin B.,Head and Neck Surgery and Dental Units | Merlin J.-L.,University of Lorraine | And 8 more authors.
PLoS ONE | Year: 2011

Purpose: Beside its efficacy in cancer treatment, radiotherapy induces degeneration of healthy tissues within the irradiated area. The aim of this study was to analyze the variations of proinflammatory (IL-1α, IL-2, IL-6, TNF-α, IFN-γ), profibrotic (TGF-β1), proangiogneic (VEGF) and stem cell mobilizing (GM-CSF) cytokines and growth factors in an animal model of radiation-induced tissue degeneration. Materials and Methods: 24 rats were irradiated unilaterally on the hindlimb at a monodose of 30 Gy. Six weeks (n = 8), 6 months (n = 8) and 1 year (n = 8) after irradiation the mediators expression in skin and muscle were analyzed using Western blot and the Bio-Plex® protein array (BPA) technology. Additional histological severity for fibrosis, inflammation, vascularity and cellularity alterations scoring was defined from histology and immnunohistochemistry analyses. Results: A significant increase of histological severity scoring was found in irradiated tissue. Skin tissues were more radio-sensitive than muscle. A high level of TGF-β1 expression was found throughout the study and a significant relation was evidenced between TGF-β1 expression and fibrosis scoring. Irradiated tissue showed a chronic inflammation (IL-2 and TNF-α significantly increased). Moreover a persistent expression of GM-CSF and VEGF was found in all irradiated tissues. The vascular score was related to TGF-β1 expression and the cellular alterations score was significantly related with the level of IL-2, VEGF and GM-CSF. Conclusion: The results achieved in the present study underline the complexity and multiplicity of radio-induced alterations of cytokine network. It offers many perspectives of development, for the comprehension of the mechanisms of late injuries or for the histological and molecular evaluation of the mode of action and the efficacy of rehabilitation techniques. © 2011 Gallet et al. Source

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