Similar activity was observed in the assessment of pharmacodynamic biomarkers of erlotinib activity that showed a high dose response relationship because of the inhibition of pEGFR, cell proliferation measured by inhibition of BrdU uptake, and apoptosis (annexin V labeling).
To evaluate the possibility of non-specific inhibition by the drug at high concentrations, we observed the dose response of PDTC and LY294002 for the inhibition of IL-17 production in PBMC.
Manning, G., Kabacik, S., Finnon, P., Bouffler, S. & Badie, C. High and low dose responses of transcriptional biomarkers in ex vivo X-irradiated human blood.
When we looked at the plasma concentration of genistein for the CD-1 mouse and F344 and S-D rats, we found a much higher dose-related response of genistein concentration in the plasma of S-D rats compared with CD-1 mice and F344 rats.
Following suggestions that these agents may have a dose response relationship (O'Bryan et al, 1973; Le Cesne et al, 1995; Cerny et al, 1999), various phase-I and -II trials were performed in which they were administered at high doses, yielding response rates of 40 66% (Frustaci et al, 1997; Patel et al, 1998; Reichardt et al, 1998; Maurel et al, 2004a).
73 Another animal model showed that a low dose of LPS exposure to mice induced Th2 response, while a high dose of LPS exposure promoted Th1 response.
Surprisingly, we found that BRCA1, a key protein in DNA damage response, was degraded in response to relatively high dose of γ irradiation (20 Gy) but not in response to low dose (5 Gy, Figure S1).
While WT mice generate a protective Th2-biased immune response to a high dose of Trichuris, a low dose (30 eggs) of Trichuris induces a Th1 cell response resulting in chronic infection [21].
At high doses, induced antioxidant response of hepatocytes to arsenic leads to increased production of GSH and MRPs in the cells, leading to higher production of MADG, which can be readily effluxed via membrane-associated proteins.
When examined across trials, the controls failed to display any significant within-session variation in the HR-OR; in contrast all of the prenatal cocaine treated groups displayed either sensitization (low and high dose) or habituation of the response (middle dose).
