Theory in the Pathophysiology of Carcinogenesis

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This e-book explains the essential role of angiogenesis in the progression and spread of the neoplasm, including the mechanics of initial carcinogenesis in promoting malignant transformation. The ...
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Aberrant Cell Cycling Potentiates Genetic Instability in Astrocytoma Transformation

Pp. 35-43 (9)

Lawrence M. Agius

Abstract

Transition progression with transformation of Astrocytoma to Glioblastoma multiforme coincides with the acquisition of decontrolled cell cycling activity of the tumor cells as clonal expansions of a single common cell of origin for the neoplasm. One would operatively consider dysfunctional pathways of mutant p53 and pRb components in the light of amplification of mutant Epidermal Growth Factor Receptors and of immortalization arising from reactivation of telomerase activity. Glioblastoma as a highly heterogeneous group of lesions would implicate biologic and histologic diversity in the further development of decontrolled cell cycling due to both complete and partial deletion of genes and of splicing of coding sequences. Both loss of expression of protein products such as Glial Fibrillary Acidic Protein and the acquisition of new forms of expression such as nestin immunoreactivity might account for a transition phenomenon centrally deregulating cell division mechanics in terms of both initiation and progression of the glioma. Early stages of gliomagenesis would faithfully predict a transition mechanics aimed at reproduction of phenotypic traits indicative of transformation of both Grade and dynamics of cell cycling in the first instance.

Keywords:

transformation, astrocytoma, growth factors, receptors.

Affiliation:

Department of Pathology, University of Malta Medical School Mater Dei Hospital, MALTA EUROPE.