Topographical analysis of proliferation ([3H]thymidine labelling index and mitotic index) as compared with tumour growth and tumour weight in xenotransplanted melanoma. Changes due to local and systemic application of azelaic acid.
Xenotransplanted human melanoma was investigated by measuring the increase in tumour volume and in final tumour weight (macroscopical parameters) and histomorphological parameters of cell proliferation: Mitotic index (MI) and autoradiographic [3H]thymidine labelling index (LI). A total of 87 tumours, derived from a human melanoma metastasis and a primary nodular melanoma respectively, were analysed by these methods in two series. Topical treatment of the tumours with azelaic acid cream resulted in a statistically significant reduction in the increase in tumour volume and, in the first series, in a clear decrease in final tumour weight and in the MI, as compared with controls. The LI was decreased only in the superficial region of the tumours, i.e. at the site of treatment. Subtumoral injection of azelaic acid (disodium salt solution) was the second route of local therapy. It was followed by a significant reduction in the increase in tumour volume, of final tumour weight (first series) and in the MI. The average LI was clearly smaller than in the controls, especially at the tumour base, which was the site of injection (local effect). Systemic (intravenous) injection of azelaic acid (same concentration of the disodium salt solution) had no negative effect on the increase in tumour volume or final tumour weight, but was followed by a clear reduction of the MI. The average LI of this group was significantly smaller than in the controls as well. This effect was most impressive in the perivascular regions of large and small vessels, which fact can be interpreted as a sort of local effect via the blood stream after systemic application of azelaic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Institute of Pathology, University of Hamburg, F.R.G.
A I
AI
Nüssgen
U
U
Fritz
K
K
Graupe
E W
EW
Breitbart
P
P
Schmiegelow
D000818:Animals; D000970:Antineoplastic Agents; D002455:Cell Division / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008940:Mitotic Index; D009368:Neoplasm Transplantation; D013936:Thymidine / Q000378:metabolism; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D003998:Dicarboxylic Acids; C010038:azelaic acid; D013936:Thymidine