Tesis doctoral de Francisco Javier Freire Salinas
Lung cancer is the first cause of cancer deaths over the world. There is a growing body of evidence that inflammation plays a central role in lung carcinogenesis many aspects of the epidemiologic association between lung chronic inflammatory conditions such as chronic obstructive pulmonary disease have not been adequately investigated due to lack of appropriate animal models. In the present thesis we have generated a new model of lung carcinogenesis initiated by a tobacco carcinogen, dimethylnitrosamine (dmna), and promoted by a chronic inflammatory process caused by crystalline silica. a single oropharingeal instillation of silica crystals significantly increased the incidence and multiplicity of tumor lesions caused by dmna. This combined model showed type-2 pneumocyte and neuroendocrine cell hyperplasia. Plasma levels of tnf-á, mip-1á and ip10 were elevated at 2,4,6, 9 and 12 months after treatment, except for tnf-á levels which were normal at 12 months, a microarray gene expression study showed that the main differences found between the both treatments were observed in adenomas rather than in adenocarcinomas. We also showed that the pattern of kras mutations was associated with the type of treatment received: g12d in the combined protocol and q61r in the group which was treated with dmna only. In addition, in order to validate the data generated by this new model, we isolated and characterized two adenocarcinoma cell lines. our data clearly support that chronic inflammation promotes lung carcinogenesis in a balb/c mouse model and that the chronic inflammation promoted tumors show specific molecular features.
Datos académicos de la tesis doctoral «Desarrollo y caracterización de un nuevo modelo de carcinogénesis pulmonar en ratón mediado por dimetilnitrosamina e inflamación crónica«
- Título de la tesis: Desarrollo y caracterización de un nuevo modelo de carcinogénesis pulmonar en ratón mediado por dimetilnitrosamina e inflamación crónica
- Autor: Francisco Javier Freire Salinas
- Universidad: Navarra
- Fecha de lectura de la tesis: 02/07/2010
Dirección y tribunal
- Director de la tesis
- Luis Montuenga Badia
- Tribunal
- Presidente del tribunal: Francisco jose Saez crespo
- alfredo Martínez ramírez (vocal)
- José Javier Gomez roman (vocal)
- José María Hermida santos (vocal)