Katherine De Azambuja1, Provabati Barman1, Joy Toyama1, David Elashoff2, Gregory W Lawson3, Lisa K Williams3, Kristofer Chua1, Deborah Lee1, Joseph J Kehoe4, Andre Brodkorb4, Rebecca Schwiebert5, Scott Kitchen6, Aamir Bhimani1, Dorothy J Wiley7. 1. Division of Translational Sciences, School of Nursing, University of California at Los Angeles (UCLA), Los Angeles, CA, U.S.A. 2. Division of General Internal Medicine and Health Services Research and David Geffen School of Medicine at UCLA, Los Angeles, CA, U.S.A. 3. Department of Laboratory Animal Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, U.S.A. 4. Teagasc Food Research Centre, Moorepark, Fermoy, Ireland. 5. Center of Comparative Medicine, Baylor College of Medicine, Houston, TX, U.S.A. 6. UCLA Department of Medicine, Hematology/Oncology, Los Angeles, CA, U.S.A. 7. Division of Translational Sciences, School of Nursing, University of California at Los Angeles (UCLA), Los Angeles, CA, U.S.A. dwiley@ucla.edu.
Abstract
BACKGROUND/AIM: Human papillomavirus Type 16 (HPV16) infection is a necessary but alone insufficient cause of invasive cervical cancer (ICC) and likely causes other genital cancers. Individual genetic variability influences the natural history of the neoplasm. Developing a variety of animal models to investigate HPV16-mediated carcinogenesis is important to Phase 1 trials for human cancer treatments. MATERIALS AND METHODS: C57BL/6 mice expressing the HPV16-E7 transgene were treated with 100 nmoles of 7,12-dimethylbenz(a)anthracene (DMBA) on dorsal-thoracolumbar skin for ≤20 weeks. RESULTS: Transgenic-HPV16E7 mice showed more tumors (14.11±1.49 vs. 7.2±0.73) that more quickly reached maximal size (17.53±0.53 vs. 28.75±0.67 weeks) than syngeneic controls. CONCLUSION: DMBA topically-treated C57BL/6-HPV16E7 mice developed chronic inflammation as well as benign and malignant lesions, many of which ulcerated. Histology showed that the HPV16-E7 transgene more than doubled the effect of complete carcinogenesis against a C57BL/6 background alone, strongly influencing the number, size, and time-to-maximal tumor burden for DMBA-exposed transgenic-C57BL/6 mice.
BACKGROUND/AIM: Human papillomavirus Type 16 (HPV16) infection is a necessary but alone insufficient cause of invasive cervical cancer (ICC) and likely causes other genital cancers. Individual genetic variability influences the natural history of the neoplasm. Developing a variety of animal models to investigate HPV16-mediated carcinogenesis is important to Phase 1 trials for humancancer treatments. MATERIALS AND METHODS: C57BL/6 mice expressing the HPV16-E7 transgene were treated with 100 nmoles of 7,12-dimethylbenz(a)anthracene (DMBA) on dorsal-thoracolumbar skin for ≤20 weeks. RESULTS:Transgenic-HPV16E7 mice showed more tumors (14.11±1.49 vs. 7.2±0.73) that more quickly reached maximal size (17.53±0.53 vs. 28.75±0.67 weeks) than syngeneic controls. CONCLUSION:DMBA topically-treated C57BL/6-HPV16E7 mice developed chronic inflammation as well as benign and malignant lesions, many of which ulcerated. Histology showed that the HPV16-E7 transgene more than doubled the effect of complete carcinogenesis against a C57BL/6 background alone, strongly influencing the number, size, and time-to-maximal tumor burden for DMBA-exposed transgenic-C57BL/6 mice.
Authors: Sharmal Narayan; Allison Choyce; Richard Linedale; Nicholas A Saunders; Alison Dahler; Emily Chan; Germain J Fernando; Ian H Frazer; Graham R Leggatt Journal: Eur J Immunol Date: 2009-02 Impact factor: 5.532
Authors: Rebeccah R Riley; Stefan Duensing; Tiffany Brake; Karl Münger; Paul F Lambert; Jeffrey M Arbeit Journal: Cancer Res Date: 2003-08-15 Impact factor: 12.701