Since the assumed α/β value of 1.5 Gy for prostate cancer cells is clearly below the α/β values of bladder (α/β value 4.0) and rectum (α/β value 3.9), a radiation biological more effective dose could be administered due to increased single doses without increasing risks of late adverse effects.
With remaining PINCH1-dependent differences in radiosensitivity, these cells similarly survived under suspension as compared to adhesion conditions after exposure to increasing single doses of X-rays, a finding confirmed by PINCH1 reconstitution in PINCH1−/− MEF.
Phase I, a rising dose tolerance investigation, examined the acute effects of progressively increasing single doses of chlorine disinfectants to normal healthy adult male volunteers.
The individual net values of the area under the curve of plasma concentration (AUC) and cumulative urinary excretion (CUE), both obtained with the test formulation as post-dose minus baseline, were multiplied by 2, 3, 4, 5 and 6 and added to the baseline in order to simulate the administration of increasing single doses of the test, assuming dose linear kinetics.
Interestingly, this was also true when comparing MEFs irradiated with increasing single doses of X-ray 24 h after plating with MEFs irradiated 48 h after plating (Fig. 1B).
For determination of clonogenic survival following IR, cells were seeded in six-well plates and exposed to increasing single doses of IR.
The safety and efficacy of increasing single and repeated doses of intramuscular naked plasmid DNA encoding FGF type 1 administered to patients with unreconstructable end-stage PAD was first shown in a phase I study [ 11].
In both studies, the increase in dose intensity was obtained by increasing the single dose per cycle while intervals between cycles were not reduced, that is, the dose density was not increased (Thor et al, 1998; Di Leo et al, 2002).
A similar cardioprotective effect was seen when the endogenous GLP-1 plasma concentration was increased with a single dose of the DPP-4 inhibitor sitagliptin.
EL increased following a single dose of 1,200 mg/kg body weight, while PEI was significantly decreased at this dose on day 7, compared with the distilled-water control (both p < 0.05).
