The combination of retinoic acid or tumor necrosis factor alpha (TNF-alpha) with interferon gamma (IFN-gamma) resulted in a synergistic amplification of the anti-proliferative effect of IFN-gamma on cultured breast cancer cells. Retinoic acid could be replaced by other biologically active retinoids. This synergism was also observed for the induction of 2'-5'-oligoadenylate-synthetase, an enzyme which is not expressed constitutively on BT-20 human breast cancer cells and not inducible by retinoic acid or TNF-alpha alone. However, both substances augmented the IFN-gamma-mediated expression. On the other hand, only TNF-alpha and not retinoic acid was able to increase the IFN-gamma induced expression of HLA-DR on the cell surface. Both cytokines antagonized the IFN-gamma effect on detachability of cultured BT-20 cells. The combinations of retinoic acid with IFN-gamma increased the down-regulation of specific binding sites for 125I-IFN-gamma. On the other hand, IFN-gamma exerted no effect on the concentration of the cytoplasmic binding protein for retinoic acid. Data obtained in this study demonstrate a different pattern of action between retinoic acid and TNF-alpha regarding their synergism in combination with IFN-gamma.
Specimens of saliva were obtained from 106 women with normal pregnancies and from 42 women, whose children turned out to small for dates (birthweight below the 10th centile). Saliva estriol was highly significantly (P less than 0.0001) decreased in the group with a newborn with a birthweight below the 10th centile (500 +/- 340 ng/ml, mean +/- SD) when compared with the group with infants whose birthweight was over the 10th centile (813 +/- 449 ng/ml). Estriol determination in saliva seems to be a simple, non invasive method of aiding the detection of fetal growth retardation.
The human breast cancer cells BT-20 were treated for 18 months in the continuous presence of interferon-gamma (HuIFN-gamma; 500 U/ml). These cells have become completely resistant to HuIFN-gamma and interestingly also to IFN-alpha 2. However, the expression of HLA-DR and the regulation of cell adhesion to tissue culture plastic remained partially under the domain of HuIFN-gamma. A reduced number of IFN-gamma binding sites in comparison to the wild-type cells were observed on the IFN-resistant BT-20 cells.
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