Colon cancer and gene alterations: their immunological implications and suggestions for prognostic indices and improvements in biotherapy.
Studies have shown that changes occur in c-Ki-ras, p53, and Bcl2 gene structure and function during the various stages of human colon carcinogenesis. Alterations of these genes are responsible for the establishment of a state of continuous stimulus for cell division and apoptotic inhibition at physiological and pharmacological levels. This paper focuses on the results of our research aimed at investigating how these gene alterations influence tumoral mechanisms on an immunological level and how immunological parameters can be used as prognostic markers for the passage of normal tissue to adenoma and adenoma to carcinoma. Overall, our data suggest that an alteration in the c-Ki-ras gene results in a switch to a suppressive type of immune response, determining an impairment of immune cell activation at both antigen- presenting-cell and T-cell levels. c-Ki-ras gene mutations, p53 deletions, and Bc12 expression, on the other hand, can be used as prognostic markers for the passage of normal tissue to adenoma and adenoma to carcinoma. The p53 oncogene does not appear to impair patients' immunological response further. In conclusion, an evaluation of c-Ki-ras, rather than p53 gene alterations, would seem to be more relevant in colon cancer prevention programs and biotherapy improvement.
Contasta
Ida
I
CNR Institute of Organ Transplantation and Immunocytology (ITOI), L'Aquila, Italy. i.contasta@itoi.cnr.it
Pellegrini
Patrizia
P
Berghella
Anna Maria
AM
Del Beato
Tiziana
T
Adorno
Domenico
D
D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D019254:Genes, bcl-2; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D011379:Prognosis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D015847:Interleukin-4