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Advances in Brief

Chemoprevention of Spontaneous Intestinal Adenomas in the Apc Min Mouse Model by the Nonsteroidal Anti-inflammatory Drug Piroxicam

Russell F. Jacoby, David J. Marshall, Michael A. Newton, Kristian Novakovic, Kendra Tutsch, Carolyn E. Cole, Ronald A. Lubet, Gary J. Kelloff, Ajit Verma, Amy R. Moser and William F. Dove
Russell F. Jacoby
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David J. Marshall
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Michael A. Newton
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Kristian Novakovic
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Kendra Tutsch
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Carolyn E. Cole
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Ronald A. Lubet
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Gary J. Kelloff
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Ajit Verma
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Amy R. Moser
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William F. Dove
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DOI:  Published February 1996
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Abstract

C57BL/6J-Min/+ mice (n = 56), heterozygous for a nonsense mutation in the Apc gene, were randomized at weaning to seven groups, including groups treated with piroxicam at 0, 50, 100, and 200 ppm in the AIN93G diet. After only 6 weeks of treatment, intestinal adenomas and aberrant crypt foci were counted, and serum levels of piroxicam and thromboxane B2 were quantitated. Tumor multiplicity was decreased in a dose-dependent manner from 17.3 ± 2.7 in the control to 2.1 ± 1.1 (12%) in the high-dose piroxicam group (P < 0.001). Thromboxane B2 levels in plasma also decreased monotonically in parallel to the decrease in tumor multiplicity, consistent with the prostaglandin inhibitory effect of piroxicam. The Min mouse model demonstrates that the nonsteroidal anti-inflammatory drug piroxicam has strong biological and therapeutic effects, potentially useful for prevention of the early adenoma stage of tumor development.

Footnotes

  • ↵1 This study was funded in part by NIH Grants CA14520, CA59352, CA50585, and CA64677; NIH Contract NCI/CN45591-72; and a Merit Review grant from the Department of Veteran's Affairs.

  • ↵2 To whom requests for reprints should be addressed, at H6/516 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792. Phone: (608) 262-7056; Fax: (608) 262-7641; E-mail: jacoby@facstaff.wisc.edu.

  • Received November 20, 1995.
  • Accepted January 2, 1996.
  • ©1996 American Association for Cancer Research.
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February 1996
Volume 56, Issue 4
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Chemoprevention of Spontaneous Intestinal Adenomas in the Apc Min Mouse Model by the Nonsteroidal Anti-inflammatory Drug Piroxicam
Russell F. Jacoby, David J. Marshall, Michael A. Newton, Kristian Novakovic, Kendra Tutsch, Carolyn E. Cole, Ronald A. Lubet, Gary J. Kelloff, Ajit Verma, Amy R. Moser and William F. Dove
Cancer Res February 15 1996 (56) (4) 710-714;

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Chemoprevention of Spontaneous Intestinal Adenomas in the Apc Min Mouse Model by the Nonsteroidal Anti-inflammatory Drug Piroxicam
Russell F. Jacoby, David J. Marshall, Michael A. Newton, Kristian Novakovic, Kendra Tutsch, Carolyn E. Cole, Ronald A. Lubet, Gary J. Kelloff, Ajit Verma, Amy R. Moser and William F. Dove
Cancer Res February 15 1996 (56) (4) 710-714;
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