title: Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic             and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and             microRNA/DNA interactions (Review).
abstract: In some inflammasomes tumor cells are generated. The internal environment             of the inflammasome is conducive to the induction of malignant transformation.             Epigenetic changes initiate this process. The subverted stromal connective tissue             cells act to promote and sustain the process of malignant trans-formation. In             its early stages, the premalignant cells depend on paracrine circuitries for the             reception of growth factors. The ligands are derived from the connective tissue,             and the receptors are expressed on the recipient premalignant cells. The initial             events are not a direct attack on the proto-oncogenes, and thus it may be entirely             reversible. Epigenetic processes of hypermethylation of the genes at the promoters             of tumor suppressor genes (to silence them), and deacetylation of the histones             aimed at the promoters of proto-oncogenes (to activate them) are on-going. A large             number of short RNA sequences (interfering, micro-, short hairpin, non-coding             RNAs) silence tumor suppressor genes, by neutralizing their mRNAs. In a serial             sequence oncogenes undergo amplifications, point-mutations, translocations and             fusions. In its earliest stage, the process is reversible by demethylation of             the silenced suppressor gene promoters (to reactivate them), or re-acetylation             of the histones of the oncogene promoters, thus de-activating them. The external             administration of histone deacetylase inhibitors usually leads to the restoration             of histone acetylation. In time, the uncorrected processes solidify into constitutive             and irreversible gene mutations. Some of the pathogens inducing inflammations             with consquential malignant transformation contain oncogenic gene sequences (papilloma             viruses, Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, hepatitis B             and C viruses, Merkel cell polyoma virus, Helicobacter pylori, enterotoxigenic             Bacteroides fragilis). These induced malignancies may be multifocal. Other pathogens             are devoid of any known oncogenic genomic sequences (mycoplasma vav-carcinogenesis,             chlamydia MALT-lymphoma genesis). In these cases the host's inflammatory reactions             induce the malignant transformation in serial sequences of gene alterations initiated             by hypoxia and reactive oxygen and nitrogen species generation. Carcinogenic intrinsic             inflammatory processes endogenously initiated without a pathogen are recognized.             Chronic inflammatory processes signal the RNA/DNA complex. In response, the DNA             may revert into its ancient primordial 'immortal' format, which the clinics recognize             as 'oncogenesis'. The DNA remains the ultimate master of bioengineering in order             to sustain life. A discussion on the most versatile and resistant primordial RNA/DNA             complex and the pre-, proto-, and unicellular world in which they co-existed is             included.
authors.affiliation: St. Joseph's Hospital Cancer Institute, 3001 Martin Luther King Jr. Blvd, Tampa, FL 33607-6307, USA. sinkovi.joseph@baycare.org
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Sinkovics
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000382:microbiology / Q000821:virology; D035683:MicroRNAs / Q000378:metabolism*; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D009857:Oncogenes; D018384:Oxidative Stress; D018805:Sepsis / Q000150:complications / Q000382:microbiology
chemical_list: D035683:MicroRNAs; D004247:DNA