Theory in the Pathophysiology of Carcinogenesis

Pathways of induced realization constitute strictly regional conglomeration of antiapoptosis effect in terms of the injury to the cell genome and of the preselectivity of further characterized biology of systemic projection as metastatic spread. One might consider it significant in terms of the genotoxicity of malignant transformation as it is a step-wise recharacterization of the metastatic cascade. It is particularly significant to consider injury as an agonist effect of unique and far-reaching effect and in terms of sequential amplification and reconstitution, beyond simple dimensions of the given individual neoplastic cell. One might therefore consider the impact of biologic agonists beyond simple developmental origin of stem cells or as etiologic dissemination of potential local and systemic spread effect arising as genomic toxicity. Carcinogenesis hence constitutes a mirrored model in the constitutive re-characterization of unique features in genomic serial transformations beyond simple enumeration of toxic agents or of pathogenesis of the individuality of the malignant cell in transformation.

Dimensions of further incremental progression in infiltration of the central nervous system by high grade glioma are symptomatic of the overall implications of the individual astrocyte that undergoes a malignant change in the first instance. Such malignant transformation is faithfully incorporated within dimensional context of an infiltrative tumor front that encompasses further malignant transformation in its own right. It is the significant role of several aggregates of neoplastic astrocytes that allows for the amplification of the injury beyond the development of infiltrative attributes and as a consequential contrast of attributes between genotype and phenotype characterization. The individual malignant astrocyte is indeed a specific form of malignancy that incorporates the dimensions of an infiltrative front evidenced by whole aggregates of such individual malignant astrocytes. It is in terms of ongoing amplification that the developmental dimensions of injury are translated into onset and progression of the malignant transformation process, and as further evidenced by field effect in carcinogenesis.

Hence, infiltrativeness by neoplastic astrocytes is both individually manifested and also an aggregate phenomenon in subsequent reconstitution of the injury at cellular and tissue level of operative contrasting influence.

Contrasting influence exerted by a chronicity of the acute inflammatory reactivity affecting the colorectal mucosa in ulcerative colitis induces a progression in dysplasia as permissive conditioning of the cellular microenvironment. Inducible representative models would allow the emergence of a series of consequential pathways as identifiable profiles that project as carcinogenesis. It is in terms of relatively simple dimensional increase in proliferative cellular activity that epithelial cell dysplasia further promotes malignant transformation in the relative absence of corrective or reparative gene expression systems. The increased potentiality for malignant change is symptomatic of the progressiveness towards definable loss of fidelity of constitutive pathways that both specifically and non-specifically contribute to pathobiology of carcinogenetic pathways as overlapping incomplete profiles of preneoplastic and paraneoplastic integrative systems of reproducibility.

Interventional reconstitution of events in carcinogenesis resembles the conceptual hierarchical organization of events leading to perceptible aggregation of the neoplastic cells around foci of tumor necrosis, individual neurons and also perivascularly. The dimensions of such aggregation constitute a real reference point in the further elucidation of genesis in terms of events that project as propagation and as anti-apoptosis of these same neoplastic cells. In terms, therefore, that permit the emergence of abnormal homeostatic control mechanisms in cellular constitutional events there might further develop an overall permissive environment based on further constitutional change. Transfer of unitary elements such as genetic material would implicate a revolutionary change in bearing with such elements as the developmental status and maintenance of events that promote and further amplify infiltration of stroma and metastatic spread via vascular involvement in a systemic fashion.

A series of models as consequential steps in evolution in tumorigenesis is representative indices of the developmental history in establishment of the metastasizing potentiality of osteosarcoma. One might allow for the integral representations of further pathway generation in the evolution of the malignant lesion both in terms of the production of the malignant osteoid and also the proliferation of the malignant osteoblasts in the first instance. Only in recognition of such sequential series of hierarchal stages in development of the osteosarcoma, as both an evolved and de-evolved lesion complex, one can further realize the complexity of the consequences of spread of the tumor. It is to be further recognized the representation of stages in tumorigenesis as essential primary zones of consequence in that the osteosarcoma both evolves and de-evolves in its own right beyond simple dimensions of histogenetic principles as applicable to normal related tissues or organs.

In this sense, an integration of compound factors in pathogenesis is constitutive of the metastasizing potential for spread of a lesion that both microscopically and macroscopically involves the tumor origin and the consequence of steps in tumorigenesis as components of interaction and amplification of the malignant process.

Within overlapping systems of consequence, the pathogenesis of the osteosarcoma is constituted by the determining roles of establishment of a metastasizing potentiality beyond simple dynamics of a carcinogenic series of agents or agonists in tumorigenesis.

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.

Aberrant, convergent pathways of sequential and non-sequential nature characterize the malignant transformation process as integral to the primary spread of metastatic lesions in cases such as ovarian carcinoma. One might further demonstrate a series of influential consequences that arises as phenomenal attributes of such integral neogenesis of the primary carcinomatous focus on the ovary with the development of focally specific susceptibility of peritoneal foci for implant evolution. Hence, it is the further formulation of events as dynamics of such focal peritoneal susceptibility that contrasts with a traditionally recognized system of metastatic implantation in the genesis of peritoneal lesions in cases of malignant ovarian carcinoma. It is, in fact, the biology of neogenesis of the primary ovarian neoplasm that participates in the formulation of final non-sequential systems of susceptibility implicating peritoneal attributes in terms of the pathobiology of primary carcinogenesis of the ovarian germinal epithelium and of developmental systems of infiltration of the underlying ovarian stroma and parenchyma.

Transition dynamics conclusively determines the malignant transformation steps that chiefly characterize the objective development of invasive tumor attributes within foci of pre-existing carcinoma in situ, as seen particularly with primary breast neoplasia. The conceptual definition of in situ neoplasia is linked with the developmental dynamics of a field effect in carcinogenesis. It is significant that there is no direct relative involvement in frequency of invasive attributes as considered in terms of the quantification of the in situ change initially present.

Aberrant recognition of receptivity events in the vascular endothelial growth factor cascade involves an excessive response in terms of vascular endothelial cell proliferation beyond the simple dynamics of a purely angiogeneic adaptive response. The implicit development of malignancy as a term of reference with regard to the pathogenesis of malignancy is a further documented or registered imprint towards the evolution of systems to spread based on such angiogenesis.

Relative dimensions of malignant lymphoma incidence in cases of congenital or acquired immunodeficiency constitute a critical reappraisal of the status of the susceptibility traits for occurrence and progression of monoclonal groups of malignant lymphocytes. The constitutive relative incidence of Epstein-Barr virus and even of Burkitt’s lymphoma in patients with AIDS contrasts and also compares with incidences in the various subtypes of organ transplant patients and of patients with ataxia telangiectasia and Wiskott Aldrich syndrome.

The complex dimensionality of the tumor microenvironment is symptomatic of a constantly ongoing progression centered on metastatic spread. In this sense, it is significant that the reactive responses of the host systems towards the evolutionary course of the neoplastic lesion are terms of reference in contextual concord with the pathology of the metastatic lesion.

Simple delineation of the evolutionary dynamics of neoplastic growth in contrast with a host of associated biologic events in neoplastic infiltration of stroma and adjacent tissues or the metastatic spread of the tumor cells, bring into prominent profile the diversity of architectural reconstitutive identity of neoplasms in a manner constant with a great diversity of genetic mutability. In this sense, the further progression of injury as genotoxicity proves an underlying demonstrative step in its own right in formulating the characterizations of the carcinogenetic steps in malignant transformation of cells and tissues.

An interface phenomenon appears to operate in a phasic fashion with regard to interactivity between processes of hyperplasia and neoplastic transformation. It is significant that such a process is not simply one of continuum, but would implicate a realization of systems of operability inbuilt within network pathways of generation of cellular proliferative activity per se. In this sense, the breast fibroadenoma is an adaptive lesion to such operative proliferation of epithelial and stromal cell elements both within the context of other lesions such as fibrocystic disease or as a purely hyperplastic phenomenon in its own right.