These results give insight into the enhanced normal-tissues-sparing capacity of IMRT.
On contrast-enhanced MR imaging prostate cancer shows a typical early and rapidly accelerating enhancement compared with normal tissues[ 38– 40] which can be used to detect the tumour, and to evaluate ECE or SVI.
However, it is now widely accepted that the toxicity was due to formation of highly oligomerized aggregates of this tagged version of TRAIL, which are toxic to normal tissues through enhanced multimerization of TRAIL receptors [20].
Our findings showed that the mammary tumours from each transgenic strain rapidly and selectively converted 5-ALA to PpIX, and showed five- to seven-fold enhanced fluorescence compared with surrounding normal tissues under blue light excitation.
It must be borne in mind that iniparib may act via a different mechanism to the PARP inhibitors discussed above, and does not appear to have the limitation of enhanced toxicity in normal tissue [ 39, 41, 42].
Ninety years ago, Otto Warburg [ 39] discovered that enhanced aerobic glycolysis distinguishes cancer from normal tissues (also known as the Warburg effect).
Millano et al have reported enhanced lytic response against some of the studied normal tissues in esophageal adenocarcinoma suggesting the possibility of adverse effects against normal tissues in esophageal cancer [ 30].
These insights now provide us with approaches to attempt to manipulate these responses for patient benefit, such as enhanced tumor cell kill with therapy, protection of normal tissues from toxic effects of therapy, and even prevention of cancer development.
In line with the Western blot data, extracts from breast tumours showed largely enhanced levels of ADP-ribosylation as compared with the normal tissues, which displayed only very faint amounts of ADP-ribosylated Rho proteins.
Secondly, owing to enhanced permeability and retention (EPR) effects, nanospheres loaded with drugs can release drugs slowly and deposit them in the target organ so that their toxicity would be enhanced in tumor tissues while reduced in normal tissues [8 10].
This approach exploits the preferred accumulation of nanoparticles, within a certain size range and surface charge, on cancer tissue as compared to normal tissues, a unique biological mechanism ascribed to an enhanced permeability and retention (EPR) effect such as micropinocytosis.
