[Histochemical findings in breast carcinoma].
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Biomedical subjects
Publications and source records attributed to H Schmidt-Matthiesen.
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In-vitro sensitivity to cystostatic agents was tested in 137 cases of breast carcinoma, with 125 tests being analysable. Inhibition of in-vitro incorporation of 3H-uridine or 3H-thymidine into RNA or DNA of the original tumour cells after incubation with antineoplastic substances was used as the index for the in-vivo sensitivity of the tumour. 30% of the carcinoma cells were sensitive in-vitro, 70% resistant. About 75% of sensitive cancers were sensitive against several agents. Cyclophosphamide proved to be most effective in-vitro: it was tested via 4-hydroxycyclophosphamide or 4-hydroperoxycyclophosphamide. There was a correlation between histological type and in-vitro sensitivity of the cancer, as well as between proliferative activity and in-vitro sensitivity in that proliferation-active tumours were more frequently sensitive in-vitro than proliferation-poor ones. Primary tumours and metastases of the same patient frequently showed different sensitivity. In some cases the development of resistance against cytostatic drugs was demonstrated during treatment. Testing tumours against combinations of cytostatic drugs demonstrated an additive effect of the antineoplastic substances in-vitro.
A new in vitro assay for screening the sensitivity of human tumour cells against Cyclophosphamide has been developed. While biologically activated Cyclophosphamide was unsuitable because of unpurities in the material, synthetic 4-Hydroxycyclophosphamide was shown to inhibit the incorporation of tritiated uridine and thymidine into the nucleic acids of human tumour cells in vitro. 29 tumours including 14 mammarial carcinomas, 8 ovarial carcinomas and 7 other malignant tumours were tested. While 12 tumours showed a significant and 5 only a slight inhibition of the 3H-uridine incorporation in vitro. 12 tumours showed no effect. Histologically none-differentiated tumours were more sensitive against 4-Hydroxycyclophosphamide as compared with the more differentiated ones. First observations point to 4-Hydroperoxycyclophosphamide instead of 4-Hydroxycyclophosphamide as a more suitable form of activated Cyclophosphamid for the in vitro assay of Cyclophosphamide sensitiveness because of the higher stability and better availability of this compound.
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