title: Model examination of chemoprevention with retinoids in squamous cell carcinomas of the head and neck region and suitable biomarkers for chemoprevention.
abstract: The prognosis for patients with head and neck tumors (HNSCC) is poor, due among other things to the high-risk factor for locoregional recurrence and/or second primary tumors. Extensive studies on chemoprevention of oral pre-cancers to stop carcinogenesis and to prevent recurrence and/or second primary tumors have failed to reach the desired effects. The toxicity of retinoids (RA) for example limits their dosage. Biomarkers are used to evaluate the duration of therapy. In this study, cell culture models are used to demonstrate immunocytochemical expression of RA receptors (RAR, RXR), Ki-67 and p53 before and after all-trans retinoic acid (ATRA) treatment. Telomerase activity in PCR is used to assess the effectiveness of ATRA. Along with an RA-sensitive HNSCC cell line UM-SCC-35 we employed cell lines UM-SCC-14C and HaCaT. Our immunocytochemical examination produced no proof of a statistically significant change in expression of RARα, RARβ or RXRγ receptors after ATRA treatment, either in the cells of the sensitive UM-SCC-35 line or in HaCaT cells. The RARβ and RXRγ receptors showed increased expression after brief cell treatment of UM-SCC-14C. The reduced telomerase activity after prolonged treatment of the UM-SCC-35-cells with ATRA (as well as the reduced p53 expression) proved to be a biomarker for evaluating the success of therapy. Although XTT and MTT tests demonstrated that cell proliferation in UM-SCC-35 cells was inhibited after brief and extended RA influence, the immunocytological Ki-67 scores failed to confirm the inhibition. No reduction of p53 expression, of telomerase activity or of cell proliferation in the XTT and MTT test was detected in the RA-insensitive cell line UM-SCC-14C or in HaCaT cells. We also demonstrated the parameters used in examining the models in sections of carcinoma tissue and in control tissues from the head and neck region, so they can be examined in clinical chemopreventive studies on biopsy tissue.
authors.affiliation: Clinic for Oral and Maxillofacial Surgery, Campus Virchow Hospital, Charité - Universitätsmedizin, Berlin, Germany. eva-maria.fabricius@charite.de
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Fabricius
authors.forename: Ute
authors.initials: U
authors.lastname: Kruse-Boitschenko
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schneeweiss
authors.forename: Gustav-Paul
authors.initials: GP
authors.lastname: Wildner
authors.forename: Bodo
authors.initials: B
authors.lastname: Hoffmeister
authors.forename: Jan-Dirk
authors.initials: JD
authors.lastname: Raguse
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D019098:Telomerase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D016159:Tumor Suppressor Protein p53; D019098:Telomerase