25 mg L−1 MET, 5 mg L−1 CIP, 5 mg L−1 APAP, 10 L h−1 ozone flow rate and a 15 min of reaction time were found to be the ideal conditions at which the degradation of these pharmaceuticals could be simultaneously maximized (Y1 = 64.60%, Y2 = 80.58% and Y3 = 50.12%).
This suggests that the association between cytoplasmic p21 WAF 1/ CIP 1 and HER-2 positivity is stronger than for nuclear p21 WAF 1/ CIP 1.
Through an alternative anti-apoptotic pathway, HER-2 induces cytoplasmic p21 WAF 1/ CIP [ 21].
The Strept ABC Duet kit (DAKO, Denmark) was used for p21 WAF 1/ CIP detection [ 17].
The relationship between HER-2 and the subcellular localisation of p21 WAF 1/ CIP 1 was analysed using the Mann Witney U test, with the p21 WAF 1/ CIP 1 IDS used as a continuous variable.
Multivariate analysis demonstrated the independent prognostic significance of cytoplasmic p21 WAF 1/ CIP and HER-2 in relation to OS and RFS, while nuclear p21 WAF 1/ CIP was not a prognosticator in this study.
These results suggest that HER-2-positive tumours showed an increase in cytoplasmic p21 WAF 1/ CIP 1 of 50 IDS units, compared with a decrease of 5 IDS units for nuclear p21 WAF 1/ CIP 1.
In vitro, active phosphorylated Akt binds p21 WAF 1/ CIP 1 and phosphorylates threonine 145 in the nuclear localisation signal to produce cytoplasmic p21 WAF 1/ CIP 1[ 21[.
This implies that the relationship between HER-2 and the subcellular localisation of p21 WAF 1/ CIP 1 is not exclusive in vitro and in vivo, but reflects a preferential cytoplasmic localisation of p21 WAF 1/ CIP 1.
Subcellular localisation of p21 WAF 1/ CIP 1 may have relevance underlying mechanisms of HER-2 drug resistance, with the potential for cytoplasmic p21 WAF 1/ CIP 1-expressing breast tumours to have increased chemoresistance or hormone resistance.
Predominant cytoplasmic p21 WAF 1/ CIP 1 has been detected immunohistochemically in breast tumours and in ovarian tumours [ 15, 17].
