Estudio preclínico de la acriflavina en la progresión tumoral del carcinoma epidermoide nasal

  1. Macia Colón, Germán
Supervised by:
  1. Fernando Noguerales Fraguas Director
  2. Pedro Cuevas Sánchez Co-director

Defence university: Universidad de Alcalá

Fecha de defensa: 13 April 2012

Committee:
  1. J. A. Rodríguez Montes Chair
  2. Miguel Angel Dapena Crespo Secretary
  3. Javier Angulo Frutos Committee member
  4. Julio Jesús Acero Sanz Committee member
  5. Guillermo Giménez Gallego Committee member
Department:
  1. Cirugía, Ciencias Médicas y Sociales

Type: Thesis

Abstract

Cancer is the second leading cause of death in developed countries. The head and neck tumors are common in Spain, and represent the fourth or fifth neoplasia among men and the tenth or eleventh among women. Most are squamous cell carcinomas and account for 5-10 per cent of all malignant tumors. In Spain, those tumors cause about 5 per cent of cancer deaths, representing about 4000 deaths annually, and it is estimated that by 2015 there will be about 12,000 new cases per year. Tumors of the nasal region are encompassed within the head and neck tumors. Its biological behavior and clinical study and diagnosis are similar in different locations and, therefore, the treatment is applicable to similar concepts and principles. The tumor growth, both primary and secondary, from a certain diameter (of only 2-3 mm3), requires vascularization. Without it, the tumor cells die from lack of nutrients and oxygen, and lack of disposal of waste substances. Angiogenesis is therefore essential for tumor progression. In this work, we study the anti-angiogenic effect and apoptogenic properties of a compound called Acriflavine against tumor cells of rat nasal squamous-cell carcinoma or FAT-7. The Acriflavine, tested in vitro studies, has antiproliferative effects against this cell line that are directly proportional to the administered dose. In the in vivo test, we subcutaneously implanted tumor cells in the abdominal region of 19 Fisher rats, 13 males and 6 females. The rats developed macroscopic tumor after four days and progressive tumor growth on subsequent days. The Acriflavine, daily injected intraperitoneally and after one week of the implantation of FAT-7 cells, was safe for the experimental animals and is capable of inhibiting tumor progression, reaching complete tumor remission after two weeks treatment. In addition, the Acriflavine inhibits angiogenesis of this cell line implanted in Fisher rats, as the histological sections of these tumors shows a decrease in the number of blood vessels and apoptogenic properties by TUNEL tecnic.