Improving bladder cancer treatment a new formulation containing an environmental mycobacterium /

• Autores: Estela Noguera Ortega
• Directores de la Tesis: Esther Julián Gómez (dir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2015
• Idioma: inglés
• Tribunal Calificador de la Tesis: Antonio Villaverde Corrales (presid.), Julià González Martín (secret.), Margarida Santos (voc.)
• Materias:
  • Ciencias de la vida
    • Inmunología
    • Microbiología
  • Ciencias médicas
    • Patología
      • Oncología
• Enlaces
  • Tesis en acceso abierto en: DDD
• Resumen

  • Bladder cancer (BC) is one of the most common cancers in Europe. Fortunately, most of the cases are diagnosed at early stages of the disease, when tumours are still confined to the mucosa. These are called non-muscle invasive bladder cancer (NMIBC). The treatment consists on resecting the tumour and, then, on the intravesical administration of the attenuated stain of Mycobacterium bovis, M. bovis BCG in its live form. The benefits of BCG in NMIBC patients are clear; BCG avoids recurrence and progression of BC which improves the survival rate of the patients. Nevertheless, the drawbacks cannot be forgotten. Most treated patients experience mild to severe side effects and many patients have to abort the BCG treatment due to its toxicity. Thus, safer alternatives are needed. It has been recently described the antitumour capacity of Mycobacterium brumae, an environmental mycobacterium. M. brumae showed in vitro a similar antitumour activity to BCG on different BC cell lines. Moreover, this species showed to be able to activate murine macrophages and to activate peripheral blood mononuclear cells¿ cytotoxicity against BC cells. Thus, the next step was to test M. brumae¿s antitumour capacity and its ability to activate an immune response in an animal model of BC. Moreover, another important issue was addressed on the way. It is known that mycobacteria, due to the high lipidic content of their cell wall, are very hydrophobic and have the tendency to aggregate in aqueous solutions. These clumps might difficult the interaction between the bacteria and the BC cells. In this thesis, different emulsions were assayed in order to diminish the size of these aggregates. In addition, the chosen emulsion had to maintain M. brumae viability, to maintain its antitumour activity and its capacity to induce an immune response in vitro. Once one emulsion was chosen, different treatments were tested in the animal model. Survival rates of the treated tumour-bearing mice were recorded and the local and systemic immune response was also studied by using different techniques. In conclusion, emulsified M. brumae showed promising results in the BC mouse model which means it could be a safer alternative to BCG for NMIBC patients.