title: A mouse model for oral squamous cell carcinoma.
abstract: Despite recent advances, the prognosis of oral squamous cell carcinoma is still poor. Therapeutic options such as radiotherapy, chemotherapy, surgery and the novel treatment option gene therapy are being investigated in animal models. Diverse models have been studied to induce oral squamous cell carcinomas. The carcinogenic 4-nitroquinoline-1-oxide (4NQO) model has proven to be successful although until now it is unknown at what time point the established tumor is a representative squamous cell carcinoma and has a suitable volume for scientific treatment. For this end we applied 4NQO 3 times a week during 16 weeks and measured the volume of tumor tissue each week until the end of the experiment at 40 weeks. Concurrent histopathology at different time points up to the end of the experiment revealed that all mice bearing oral tumors were diagnosed with squamous cell carcinoma. Immunohistochemistry with markers cyclin D1 and E-cadherin revealed that the generated mouse oral tumors showed strong similarities with the described immunopathology in human oral tumors. The 4NQO model is a suitable alternative for preclinical gene therapy experiments with primary oral tumors. Future survey of therapeutic options in the carcinogenic 4NQO model should be conducted around 40 weeks after the start of the treatment.
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands. r.a.l.schoop@lumc.nl
authors.forename: Remilio A L
authors.initials: RA
authors.lastname: Schoop
authors.forename: Mathieu H M
authors.initials: MH
authors.lastname: Noteborn
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Baatenburg de Jong
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000737:chemistry; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D014059:Tongue / Q000473:pathology; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D019938:Cyclin D1; D015112:4-Nitroquinoline-1-oxide
references.citation: Nature. 1998 Mar 12;392(6672):190-3
references.pmid: 9515965
references.citation: Cancer Biol Ther. 2008 Sep;7(9):1368-73
references.pmid: 18708764
references.citation: Cancer Lett. 2005 Apr 18;221(1):29-39
references.pmid: 15797624
references.citation: Int J Oral Maxillofac Surg. 1995 Feb;24(1 Pt 1):53-8
references.pmid: 7782642
references.citation: Gene Ther. 2003 Jul;10(14):1135-41
references.pmid: 12833122
references.citation: Lancet Oncol. 2006 Feb;7(2):149-56
references.pmid: 16455479
references.citation: Oral Oncol. 2001 Oct;37(7):579-85
references.pmid: 11564579
references.citation: Cancer Gene Ther. 2002 Jan;9(1):53-61
references.pmid: 11924525
references.citation: Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):301-13
references.pmid: 14734483
references.citation: J Oral Pathol Med. 1998 Aug;27(7):308-17
references.pmid: 9725568
references.citation: Clin Cancer Res. 1999 Oct;5(10):2810-9
references.pmid: 10537346
references.citation: Cancer Gene Ther. 2009 May;16(5):383-92
references.pmid: 19011598
references.citation: Head Neck. 1996 Sep-Oct;18(5):441-9
references.pmid: 8864735
references.citation: Carcinogenesis. 2006 Mar;27(3):619-30
references.pmid: 16219633
references.citation: Expert Opin Investig Drugs. 2008 Oct;17(10):1517-31
references.pmid: 18808311
references.citation: Ann Oncol. 2002 Jul;13(7):995-1006
references.pmid: 12176777
references.citation: J Oral Pathol. 1981 Jun;10(3):186-91
references.pmid: 6798180
references.citation: Oral Oncol. 2004 Aug;40(7):656-67
references.pmid: 15172634
references.citation: Int J Cancer. 2004 Mar;109(1):38-42
references.pmid: 14735465
references.citation: Ned Tijdschr Geneeskd. 1972 May 20;116(21):903-4
references.pmid: 5026100
references.citation: Odontol Revy. 1973;24(1):39-48
references.pmid: 4514062
references.citation: Head Neck. 1994 Sep-Oct;16(5):424-32
references.pmid: 7960739
references.citation: Oral Oncol. 2006 Aug;42(7):655-67
references.pmid: 16448841
references.citation: J Clin Oncol. 2003 Apr 15;21(8):1544-9
references.pmid: 12697879
references.citation: CA Cancer J Clin. 2005 May-Jun;55(3):178-94
references.pmid: 15890640
references.citation: CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
references.pmid: 15761078
references.citation: N Engl J Med. 2004 May 6;350(19):1937-44
references.pmid: 15128893