title: The malignant transformation event as a clonal transformation of apoptosis to anti-apoptosis pathways and of cell cycle dynamics.
abstract: Anti-apoptosis, as a more vital aspect of a whole series of progressive steps in carcinogenesis, would appear primarily a phenomenon of variable nonresponsiveness. Programmed cell death, in addition, would appear to affect the individual cell as attributes also of an integral field phenomenon constituted by clones of tumor cells that grow, proliferate and spread. Various modes of development of anti-apoptosis subsequently involving the development of genetic abnormalities would possibly account for transformation as a neoplastic phenomenon. It is in terms of such pathways as telomeric length preservation, of anti-apoptosis as failed activation of apoptosis, and of failed DNA binding events that clonally selected tumor cells would tend to inherently progress to higher grade and stage and to spread systemically. Moreover, clonal and field events would possibly influence in their turn individual cell cyclical activity and programmed cell pathways in neoplastic transformation. Anti-apoptosis would constitute, in fact, a predicted system of pathways that switch from apoptosis as an essential pathway in malignant transformation. Angiogenesis, as a full series of cascade events of a paracrine/autocrine nature, would also participate with anti-apoptosis in a tumor cell cycle transformation that is self-amplifying. Given different modes of how apoptosis would convert to anti-apoptosis in tumorigenesis, perhaps abnormal cell cycle dynamics might also contribute to the evolving nature of such neoplastic transformation.
authors.affiliation: Department of Pathology, St. Luke's Hospital, Gwardamangia, Medical school, University of Malta, Malta. lawrence.agius@um.edu.mt
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Agius
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008962:Models, Theoretical; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D016615:Telomere / Q000648:ultrastructure; D014162:Transfection
chemical_list: D016207:Cytokines