Particular gene upregulation and p53 heterogeneous expression in TP53-mutated maxillary carcinoma.

It has been demonstrated that tumor protein p53 (TP53) mutation in maxillary squamous cell carcinoma, is more treatment-resistant compared with the carcinoma without TP53 mutation. However, the association between TP53 mutation and treatment resistance remains unclear. As a first step in understanding the biological differences between tumors with and without TP53 mutation, a comprehensive gene expression analysis of maxillary squamous cell carcinoma with or without TP53 mutation was performed. A total of 42 genes were identified to be differentially expressed by >4-fold. Quantification of their mRNA using quantitative polymerase chain reaction indicated 18 genes with high expression and three genes with low expression in TP53 mutated tumors vs. TP53 wild-type tumors. The 18 genes included eight cell adhesion (DSC3, GRHL1, EPPK1, PROM2, ANXA8, DSP, JUP, and KRT6B) and four cell growth inhibition (SFN, CLCA2, SAMD9 and TP63) genes. Among these genes, DSC3, SFN, and CSTA, whose expression was markedly increased, also demonstrated high protein expression in immunohistochemical staining of TP53 mutated tumors. The TP53 mutated tumors demonstrated high nuclear staining of the TP53 protein only in tumor cells at the tumor margins adjacent to the stroma, whereas the tumor interior was negative for TP53. However, all tumor cells of TP53 wild-type tumors exhibited positive nuclear staining for the TP53 protein. The combined findings suggest that TP53 mutated tumors possess a phenotype opposite to that associated with cancer progression and malignant transformation, and exhibit tumor cell heterogeneity between the tumor interior and margins.

The effect of compound nasal surgery on obstructive sleep apnea syndrome.

BACKGROUND: Nasal surgery often fails to ameliorate the symptoms of obstructive sleep apnea syndrome (OSAS). We developed a compound nasal surgery (CNS) method that consists of septoplasty combined with submucosal inferior turbinectomy and posterior nasal neurectomy to ensure low nasal resistance during sleep. OBJECTIVE: To clarify the effect of CNS on OSAS, pre- and postoperative changes in sleep-related events were studied by using polysomnography, the Epworth sleepiness scale (ESS), the visual analog scale for snoring, and health-related quality of life (QOL). METHODS: Forty-five consecutive patients with OSAS and with nasal problems underwent CNS. Three months later, the postoperative effect on OSAS was assessed by using polysomnography findings, daytime sleepiness by the ESS, nasal allergy symptoms, and health-related QOL. Snoring was assessed by the family by using a visual analog scale. RESULTS: The indices of apnea, apnea-hypopnea, oxygen desaturation, and arousal; the ESS; allergic symptom score; health-related QOL; and snoring on a visual analog scale were all significantly improved. CONCLUSIONS: CNS improves OSAS events without any pharyngeal surgical procedure in selected patients. If high nasal resistance associated with OSAS is present, then CNS should thus be considered.

p53 mutation, but not in vitro predictor genes of therapeutic efficacy of cisplatin, is clinically relevant in comparing partial and complete responder cases of maxillary squamous cell carcinoma.

To predict the efficacy of cisplatin and radiation therapy for maxillary squamous cell carcinoma, we examined the mRNA expression of 14 cisplatin-resistant genes and p53 mutation in specimens biopsied from patients prior to initiation of therapy. Five of 10 patients had mutations in the p53 gene, of whom four had residual tumors pathologically following chemoradiotherapy (p=0.0476). Of 14 genes examined, the mRNA expression of ATP7B was significantly lower in cases that were resistant to chemoradiotherapy. Six genes including multidrug resistance protein 1 (MDR-1), multidrug resistance associated protein 1 (MRP-1), Cu++ transporting, beta polypeptide (ATP7B), xeroderma pigmentosum, complementation group A (XPA), excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC-1) and B-cell CLL/lymphoma 2 (BCL2) were down-regulated in cases of recurrent cancers. These results show that the evaluation of p53 mutation provides the most useful predictor of therapeutic effects. In responder cases, the drug-resistant genes that were determined in cell lines by culture do not necessarily translate into clinical relevance.