ABSTRACT
<p><b>OBJECTIVE</b>To investigate the enhancive effect of N,N'-dinitrosopiperazine (DNP) on induced carcinogenesis in nasal and/or nasopharyngeal epithelia among TgN(p53mt-LMP1)/HT transgenic mice to examine the underlying mechanism for the development of nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>TgN(p53mt-LMP1)/HT transgenic mice and the same strain of C(57)BL/6J wild-type mice both at the age of 5 months were randomly divided into 2 groups in parallel, respectively, i.e., TgN(p53mt-LMP1)/HT cancerous lesion-inducing group (TI), TgN(p53mt-LMP1)/HT control group (TC), C57BL/6J cancerous lesion-inducing group (CI), and C57BL/6J control group (CC). TI and CI mice were treated only with DNP for 16 weeks, twice each week, while TC and CC mice were given the same volume of saline as controls. At the end of treatment, animals were sacrificed to collect epithelial tissue samples from nasal cavity and nasopharynx for pathohistological evaluation by haematoxylin and eosin (HE) staining and for determination on the expression of TRAF2, c-Jun, and p16 by immunohistochemistry.</p><p><b>RESULTS</b>Atypical hyperplasia was more significant in the samples of TI than in those of TC, CI, and CC, with the rates of lesions being 90%, 10%, 0, and 0 (P<0.01) respectively, though DNP was used alone in a much shortened inducing period at less dosage and without the use of carcinogenic promoter 12-O-tetradecanoylphorbol-13-acetate as usual. The expressions of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and c-Jun in these samples were significantly up-regulated in TI (P<0.01), while the expression of p16 was significantly lower in TI than in the other groups (P<0.01).</p><p><b>CONCLUSION</b>TgN(p53mt-LMP1)/HT mice hold inherited constitutional defect in immune surveillance function, which can be aggravated by environmental carcinogens, such as DNP used even though in a much less strength. The enhanced carcinogenesis-inducing effect of DNP on TgN(p53mt-LMP1)/HT mice should be closely associated with abnormal signaling of activator protein-1 (AP-1) pathway, especially up-regulated expressions of TRAF2 and c-Jun, and down-regulated expression of p16.</p>
Subject(s)
Animals , Mice , Epithelial Cells , Metabolism , Pathology , JNK Mitogen-Activated Protein Kinases , Metabolism , Mice, Transgenic , Mutation , Genetics , Nasopharyngeal Neoplasms , Genetics , Metabolism , Pathology , Nitrosamines , Pharmacology , Nose Neoplasms , Genetics , Metabolism , Pathology , Precancerous Conditions , Genetics , Pathology , TNF Receptor-Associated Factor 2 , Metabolism , Tumor Suppressor Protein p53 , Genetics , Metabolism , Viral Matrix Proteins , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the correlation between TCM syndrome type and intracranial aggressive potentiality of untreated nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>Sixty untreated NPC patients of different syndrome types were treated conventionally and followed up for over one year. Correlation between the TCM syndrome type differentiated at the first consultation and the intracranial aggressive potentiality of the primary focus of NPC were analyzed.</p><p><b>RESULTS</b>The incidence of intracranial aggression was significantly higher in patients with Qi-Yin deficiency type than that in those with other two syndrome types during the follow-up period (P < 0.01).</p><p><b>CONCLUSION</b>The intracranial aggessive rate in the untreated NPC patients of Qi-Yin deficiency type was higher than in those of either Qi and blood coagulation type or fire-toxin stagnation type.</p>