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Trends in Cancer Research   Volumes    Volume 1 
The immunological implications of gene alterations in the progression of colorecatal cancer: indications for prognosis, treatment and tumor understanding
D. Adorno, I. Contasta, P. Pellegrini, A. M. Berghella, T. Del Beato
Pages: 59 - 75
Number of pages: 17
Trends in Cancer Research
Volume 1 

Copyright © 2005 Research Trends. All rights reserved


Changes in gene structure and function have been shown to characterize the initiation, promotion, and progression of cancer in general. Point mutations, deletions, and chromosomal rearrangements involving specific oncogenes and tumor suppressor genes have all been observed during the various stages of human colon carcinogenesis. The genes most frequently altered are the c-Ki-ras and p53 genes which encode proteins involved in the establishment of a state of continuous stimulus for cell division. However, how these gene alterations influence tumoural mechanisms on an immunological level is still not clear. In a previous study we found that disregulation between TH1 and TH2 cell functions is implicated in the establishment and progression of colorectal cancer disease and hence the aim of this study was to investigate the immunological implications of p53 and c-Ki-ras gene alterations. The effect of alterations in the Bc12 gene were also studied; the Bcl-2 gene is located upstream of the regulatory genes for the apoptotic pathway that is mainly responsible for apoptotic inhibition at a physiological and pharmacological level. Therefore, the identification of agents capable of correcting the malfunctioning of this gene and bringing about the suicide elimination of tumor cells and restoring the physiological equilibrium would be a step forward in tumor treatment. Our results show that an alteration in the c-Ki-ras gene results in a switch to a suppressive type of immune response which, as we have reported in previous papers, may be a determining or concurrent cause of malignant transformation. c-Ki-ras gene mutations seem to determine an impairment of immune cell activation at both antigen presenting cell and T cell levels. Alterations in the p53 gene do not appear to impair patients’ immunological response further. Overall our data suggests that c-Ki-ras gene mutations and p53 deletions can be used as prognostic markers for the passage of normal tissue to adenoma and adenoma to carcinoma. However an evaluation of c-Ki-ras gene alterations rather than p53 alterations would seem to be more relevant for the prevention and biotherapeutic treatment of this disease.

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