Original ContributionsHuman DNA topoisomerase I: An anticancer drug target present in human sarcomas*,**
Section snippets
Sources of tissue
Paraffin blocks from 55 sarcoma cases were retrieved from the surgical pathology files at the University of Utah Health Sciences Center. All cases were reviewed to confirm the diagnosis. Forty-two of the tumors were high grade, 4 were intermediate grade, and 9 were low grade. The sarcomas were graded as low, intermediate, or high according to tumor differentiation, necrosis, and mitotic count.25
Chemical and antibodies
The topo I antibody is a mouse monoclonal antibody that recognizes human topo I on Western blots and
Patient characteristics
The clinicopathologic characteristics of the sarcoma patients in our study are shown in Table 1.The age of the patients ranged from 19 to 93 years with an average age of 56.1 years. Nine neoplasms were low grade, 4 were intermediate grade, and 42 were high grade. These sarcomas all originated from the soft tissues and were represented by 20 cases of malignant fibrous histiocytoma, 20 cases of undifferentiated/spindle cell sarcoma, 8 cases of fibrosarcoma, 4 cases of leiomyosarcoma, 2 cases of
Discussion
Topo I inhibitors are showing activity against a wide range of malignancies. Several topo I–targeted drugs have been approved for the treatment of specific solid tumors. Despite these advances, many human neoplasms are resistant to current treatment regimens. Among these resistant malignancies are human sarcomas. They are difficult to treat, and the current medical treatment options are limited both in number and efficacy.4, 5
In this study, we evaluated a series of 55 human sarcomas for
Acknowledgements
The authors thank J. Chris Pitchford for his ongoing interest in the topoisomerases as anticancer drug targets.
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2012, Journal of Thoracic OncologyCitation Excerpt :In PC-9/Met cells, the mRNA and protein expression, and the activity of topo I were higher than in the PC-9 cells. The results of the topo I activity assays performed in this study are consistent with previous studies showing that the sensitivity to topo I inhibitors correlates with the topo I activity of the tumor cells.25–28 We next examined the effects of MET-specific siRNA or MET stimulation by HGF on the topo I level in these experiments.
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Supported by the ARUP Institute for Clinical and Experimental Pathology, the Biotechnological and Biological Sciences Research Council (UK), and Pharmacia Upjohn Inc.
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Address correspondence and reprint requests to Joseph A. Holden, MD, PHD, University of Utah Health Sciences Center, Salt Lake City, UT 84132.