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[Vascular thickness and cytostatic-resistant bronchial carcinoma]
M Volm1, R Koomägi, G van Kaick
1Deutsches Krebsforschungszentrum, Heidelberg.
Background And Objective:
A new way of treatment of malignant tumours was suggested by blocking angiogenesis and thus creating subpopulations of cells which, due to their decreased oxygen content, react differently to treatment. The relationship between angiogenesis (vessel density) and resistance to cytostatic drugs was investigated.
Patients And Methods:
Results were analysed retrospectively for 83 untreated patients (73 men, 10 women; mean age 60 [37-75] years) with non-small cell bronchial carcinoma. Vessel density and resistance proteins were determined immunohistochemically. Radioactive incorporation of nucleic acid precursors with and without doxorubicin was measured with the in vitro short-term test.
Results:
There were significant differences between vessel density and various resistance proteins. With low vessel density (less than mean value) glutathione-S-transferase pi (P < 0.01), thymidylate synthase (P < 0.05) and metallothioneine (P < 0.05) were significantly increased. P-glycoprotein showed a corresponding relationship, but it was not statistically significant, while there was no relationship with topoisomerase II. Bronchial carcinoma with low vessel density was more frequently resistant in vitro to doxorubicin than carcinomas with higher vessel density (P < 0.05).
Conclusions:
Non-small cell bronchial carcinoma with low vessel density more frequently expresses resistance proteins and is more commonly resistant to doxorubicin. Blocking angiogenesis to improve the results of treatment is therefore problematic.