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Báo cáo khoa học: "Ionizing radiation and inhibition of angiogenesis in a spontaneous mammary carcinoma and in a syngenic heterotopic allograft tumor model: a comparative study."

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: Ionizing radiation and inhibition of angiogenesis in a spontaneous mammary carcinoma and in a syngenic heterotopic allograft tumor model: a comparative study. | Riesterer et al. Radiation Oncology 2011 6 66 http www.ro-journal.eom content 6 1 66 RADIATION ONCOLOGY SHORT REPORT Open Access Ionizing radiation and inhibition of angiogenesis in a spontaneous mammary carcinoma and in a syngenic heterotopic allograft tumor model a comparative study 11 11 2.3 1 1 Oliver Riesterer Christoph Oehler-Janne Wolfram Jochum Angela Broggini-Tenzer Van Vuong and Martin Pruschy1 Abstract Background The combined treatment modality of ionizing radiation IR with inhibitors of angiogenesis IoA is a promising treatment modality based on preclinical in vivo studies using heterotopic xeno- and allograft tumor models. Nevertheless reservations still exist to translate this combined treatment modality into clinical trials and more advanced spontaneous orthotopic tumor models are required for validation to study the efficacy and safety of this treatment modality. Findings We therefore investigated the combined treatment modality of IR in combination with the clinically relevant VEGF receptor VEGFR tyrosine kinase inhibitor PTK787 in the MMTV c-neu induced mammary carcinoma model and a syngenic allograft tumor model using athymic nude mice. Mice were treated with fractionated IR the VEGFR-inhibitor PTK787 ZK222584 PTK787 or in combination and efficacy and mechanistic-related endpoints were probed in both tumor models. Overall the treatment response to the IoA was comparable in both tumor models demonstrating minimal tumor growth delay in response to PTK787 and PTK787-induced tumor hypoxia. Interestingly spontaneously growing tumors were more radiosensitive than the allograft tumors. More important combined treatment of irradiation with PTK787 resulted in a supraadditive tumor response in both tumor models with a comparable enhancement factor namely 1.5 and 1.4 in the allograft and in the spontaneous tumor model respectively. Conclusions These results demonstrate that IR in combination with VEGF-receptor tyrosine kinase inhibitors is a valid promising