In prior work it was demonstrated that normal human bronchial epithelial cells (HBECs) could be immortalized with a combination of hTERT and CDK4 expression [ 18].
By recombining stroma and epithelium under different experimental conditions it was demonstrated that normal mammary epithelial cells were "instructed" to become tumor cells only when the stroma was treated with a carcinogen [ 3, 4].
It has been demonstrated that in normal cells p16ink4a localizes mainly in nuclei [ 34].
It has been demonstrated that cognitively normal adults aged >60 years can possess pathological brain levels of fibrillar Aβ (i.e. they are amyloid positive) [ 13– 13].
On the other hand, it has also been demonstrated that the normal microenvironment functions as a non-permissive barrier to block tumor initiation and/or progression [ 6].
It has been demonstrated that, in normal control subjects, breathing CO2 causes vasodilation and thereby leads to an increase of retinal and ONH blood flow [ 43– 43].
In this regard, it has been demonstrated that in normal cells D4Z4 repeats are methylated and show histone marks of repression (H3K27me3), and that both features are lost in FSHD patients [16,17,37].
Although we often use the concept of "vesicle collapse" into the plasma membrane, it is not certain that it has indeed been demonstrated that under normal circumstances the vesicle actually completely flattens onto this membrane.
It has been demonstrated that encapsulated erythrocites present normal morphology, normal metabolic and antigenic properties, and normal survival in vivo [ 16].
In further experiments, it had been demonstrated that chronic treatment of normal synovial fibroblasts with the Dnmt inhibitor 5-AZA (5-aza-2'-deoxycytidine) changed the cellular profile into an RASF-like phenotype [ 33].
