Topoisomerase I activity in squamous cell carcinoma of the head and neck

Abstract

In recent preclinical and clinical trials, topoisomerase I inhibitors have shown great promise as antitumor agents. These agents are most effective against tumors with high topoisomerase I activity. Therefore, determining topoisomerase I activity in advance may predict response to topoisomerase I inhibitors. Squamous cell carcinoma of the head and neck and normal tissue samples were obtained from 12 patients. Cellular extracts were prepared, and topoisomerase I activity assays were performed. The results suggest that topoisomerase I activity in squamous cell carcinoma of the head and neck is increased approximately sixtyfold compared to normal tissue. Increased activity often correlates with clinical responsiveness; these results predict that topoisomerase I inhibitors should be effective and selective against squamous cell carcinoma of the head and neck.

Correlation between topoisomerase I and tyrosyl-DNA phosphodiesterase 1 activities in non-small cell lung cancer tissue

“…Comparing the activity of TOP1 between the tumor and non-tumor samples we found TOP1 to be 2.9-fold upregulated (p = 0.0038) in the tumor samples compared to the non-tumor samples (Fig. 4A) as also reported in several other types of cancer (Guichard et al, 1999;Husain et al, 1994;Masin et al, 1995). When comparing the TOP1 activity in individual tumor samples to the non-tumor samples we found TOP1 to be upregulated in 78% (14/ 18) and 82% (14/17) if disregarding the sample without tumor cells (Fig.…”

Bevacizumab enhances the therapeutic efficacy of Irinotecan against human head and neck squamous cell carcinoma xenografts

“…The formation of this complex induces replication fork arrest and chromatid breaks by preventing relaxation of DNA supercoiling during replication 26 . Since HNSCCs have been associated with high topoisomerase-1 activity 27 , we examined the antitumor activity of Irinotecan against FaDu HNSCC xenografts alone and in combination with Bevacizumab. While the activity of Irinotecan has been demonstrated against a variety of experimental tumors and human tumor xenografts, only a few reports have investigated its activity in head and neck cancer 13,28 .…”

Immunohistochemical study of DNA topoisomerase I, DNA topoisomerase IIα, p53, and Ki-67 in oral preneoplastic lesions and oral squamous cell carcinomas

“…Topo I inhibitors topotecan and irinotecan have been tested in head and neck SCC patients. [17][18][19] Topo I activity 20 and expression of corresponding drug resistance-related genes 21 have been evaluated. However, there are very few data on the use of this group of anticancer drugs in the therapy for oral SCCs.…”