Ionizing radiation and inhibition of angiogenesis in a spontaneous mammary carcinoma and in a syngenic heterotopic allograft tumor model: a comparative study

Autor: Martin Pruschy, Angela Broggini-Tenzer, Christoph Oehler-Jänne, Wolfram Jochum, Van Vuong, Oliver Riesterer
Přispěvatelé: University of Zurich, Pruschy, M
Rok vydání: 2011
Předmět:
lcsh:Medical physics. Medical radiology. Nuclear medicine
Male
Pathology
medicine.medical_specialty
Pyridines
medicine.drug_class
Angiogenesis
lcsh:R895-920
medicine.medical_treatment
Short Report
Mice
Nude
610 Medicine & health
Angiogenesis Inhibitors
Apoptosis
Mammary Neoplasms
Animal
lcsh:RC254-282
Tyrosine-kinase inhibitor
Mice
In vivo
Radiation
Ionizing
medicine
Carcinoma
2741 Radiology
Nuclear Medicine and Imaging
Animals
Humans
Transplantation
Homologous
Radiology
Nuclear Medicine and imaging
Neovascularization
Pathologic
Tumor hypoxia
business.industry
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
10044 Clinic for Radiation Oncology
Radiation therapy
Receptors
Vascular Endothelial Growth Factor
Oncology
Radiology Nuclear Medicine and imaging
Phthalazines
Syngenic
2730 Oncology
Female
business
Tyrosine kinase
Neoplasm Transplantation
Zdroj: Radiation Oncology (London, England)
Radiation Oncology, Vol 6, Iss 1, p 66 (2011)
ISSN: 1748-717X
DOI: 10.1186/1748-717x-6-66
Popis: 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 treatment modality, and that the treatment responses in spontaneous mammary carcinomas and syngenic allografts tumor models are comparable.
Databáze: OpenAIRE
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