ABSTRACT
Although chronic infection with various pathogens including viruses directly contributes to only approximately 25% of cancers worldwide, chronic inflammation is closely linked to the development, progression and prognosis of most human cancers. In this article the author bring forth a hypothesis termed as “Cancer Evolution-Development” (Cancer Evo-Dev), which is based on our series of studies on the molecular mechanisms of HBV infection-induced hepatocarcinogenesis, gastrointestinal and urological cancers, and world wide advances in this field. The core theory of this hypothesis is: the imbalance or dysfunction caused by the interactions of genetic predispositions and environmental exposures such as viral infection is responsible for the maintenance of chronic non-resolving inflammation. Then non-resolving inflammation promotes cancer occurrence and progression and persists throughout the cancer evolution, which is characterized by a process of “mutation-selection-adaptation”. Under the microenvironment of non-resolving inflammation, pro-inflammatory factors promote mutations in viral or host genomes by trans-activating cytidine deaminases and their analogues or by inducing oxidative stress. The majority of cells acquired somatic mutations and mutated viruses are eliminated in survival competition; only a small percentage of the mutated cells are selected and function as canceHnitiating cells; these mutated cells have altered survival signaling pathways and undergo epithelial-to-mesenchymal transition via epigenetic modification by proinflammatory molecules in an inflammatory microenvironment. The selected cells exhibit the characteristics of “sternness” such as overcoming senescence. robbing nutrition, and proliferating immortally, thus promotes carcinogenesis and invasion. Cancers generally possess the properties of “backward evolution” and “retro-differentiation”, suggesting the indispensability of stem-like signaling pathways in cancer Evo-Dev. This hypothesis of Cancer Evo
ABSTRACT
Objective Study the relationship between type A influenza virus genetic variation with survival selective pressure, help for the finding of possible vaccine conserved antigen target. Methods Select seven strains of same HA (Hemagglutinin) serotype, regional and isolation time closely related type A influenza virus with full HA gene coding sequence; use Blast2 program to calculate the parameter of nucleotide conservative, amino acid conservative, mutation ratio of codon 3rd (over) non 3rd locus, survival selective pressure indicator of these virus strains; analysis the parameters relationship with survival selective pressure indicator. Results Nucleotide conservative of HA gene is significantly lower than that of other genes; amino acid conservative of HA gene is similar with NS gene, all lower than that of other genes; genetic variation of HA gene is under survival selective pressure; selective pressure toward NS, PB1 gene is relatively lower than that toward NA, NP gene; survival selective pressure indicator is strongly correlated with mutation frequency upon codon 3rd locus. Conclusions Genetic variation of influenza virus is determined both by mechanism of relax replication model and survival selective pressure; genetic conservative of each gene is different, NA, NP gene could be selected as possible vaccine target for their relative high conservative, HA gene possesses medium genetic conservative with prospective of finding more conserved epitope region within its full sequence, NS, PB1 are not recommended as vaccine candidate for their relative low genetic conservative.