Oral complaints and stimulated salivary flow rate in 1188 adults.

BACKGROUND: Recently, oral sensory complaints (OSC) were proposed as a disease entity to represent idiopathic sensory disturbances of dry mouth, burning mouth, and taste disturbance, even though neither the status of OSC in the general population nor its underlying mechanism has yet been elucidated. Moreover, these three OSC-related complaints have not been assessed in combination by means of a visual analog scale (VAS) in a large-scale, community-dwelling population of a broad age range. METHODS: In a 1188-member community-dwelling adult population, comprised of 373 males and 815 females, aged 20-90 years, the three OSC-related complaints and stimulated salivary flow rate (SSFR) were assessed by means of a VAS and modified Saxon test, respectively. Association of each complaint with age, gender, SSFR, and other complaints was analyzed. RESULTS: Increases in both prevalence and intensity of subjective dry mouth and burning mouth were associated closely with decreasing SSFR. Even for taste disturbance, which may be affected less significantly by salivation status than the other two complaints, a significant association was suggested between decreasing SSFR and especially severe taste disturbance. However, these oral complaints were found in considerable prevalence even in the individuals with high SSFR. Often overlapping presentation of these complaints and a close association in intensity between the complaints to each other were also found. CONCLUSIONS: Hyposalivation may be a significant and common etiology for the three oral complaints, although the considerable prevalence of complaints without hyposalivation suggests other etiologies, including those related to the OSC.

Global DNA hypomethylation suppresses squamous carcinogenesis in the tongue and esophagus.

Genome-wide DNA hypomethylation and concomitant site-specific gene hypermethylation are among the most common molecular alterations in human neoplasia. Previous studies revealed that genetic reduction of the DNA methylation level results in opposing effects on tumor development, depending on the tumor cell type and on the different stages of the tumorigenesis. For instance, reduced levels of DNA methylation in mice strongly inhibited tumor development of the intestine, whereas they induced thymic lymphomas and liver tumors. In the present study, using DNA methyltrasferase 1 (Dnmt1) hypomorphic alleles to reduce genomic methylation, we examined the effects of DNA hypomethylation on a murine squamous carcinogenesis in the tongue and esophagus induced by 4-nitroquinoline 1-oxide. Genetic reduction of DNA methylation level led to the suppression of tumor formation in both tongue and esophagus. Histological analyses revealed that DNA hypomethylation preferentially inhibited the development of squamous cell carcinomas. The results suggest that genomic hypomethylation inhibits squamous carcinogenesis in the tongue and esophagus, and that pharmacological modification of epigenetic status might be useful for the prevention and treatment of cancers in the upper digestive tract.

Aberrant promoter hypermethylation of the CHFR gene in oral squamous cell carcinomas.

Recent studies have shown that promoter hypermethylation of tumor suppressor genes is an important factor in carcinogenesis of several human organs. The purpose of this study was to examine the methylation status of CHFR, a novel cell cycle regulatory gene, in both primary oral cancer tumors and the adjacent normal mucosa, and to clarify the relation between the methylation status and expression of the CHFR-related chromosomal passenger protein Aurora-A. The methylation status of the CHFR gene was examined by the methylation-specific PCR (MSP) in 49 primary oral squamous cell carcinomas (OSCC) and 6 OSCC cell lines. In 13 cases, the adjacent normal oral mucosal tissues were also examined. Normal oral mucosa from 18 healthy volunteers was used as the control. The mRNA level of Aurora-A and CHFR in OSCC cell lines was investigated by real-time RT PCR and the protein expression of Aurora-A in certain tumor samples was confirmed by immunohistochemistry. Aberrant promoter methylation of the CHFR gene was detected in 34.7% (17 of 49) of OSCC cases. As for the 13 OSCC cases with paired cancerous and adjacent normal tissues, promoter hypermethylation of the CHFR gene was detected in 46.1% (6 of 13) of the cancerous tissues. In contrast, promoter hypermethylation of the CHFR gene was recognized in only 7.7% (1 of 13) of the surrounding normal mucosa. No hypermethylation of the CHFR gene was detected in healthy volunteers. Only one OSCC cell line shows hypermethylation of the CHFR gene with concurrently silenced mRNA expression, however, Aurora-A was expressed abundantly in all cell lines. Furthermore, there is no significant relationship between methylation status of the CHFR gene and Aurora-A protein expression in OSCC. Hypermethylation of the CHFR gene was detected in a certain part of OSCC cases whereas it had very low frequency in adjacent normal oral tissues. Although further study is needed, Aurora-A gene expression seems to be independent from methylation status of the CHFR gene in OSCC.

Preventive effect of fermented brown rice and rice bran on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats.

A number of possible preventive agents for cancers in different organs have been reported, however, little information is available regarding the effective agents for the development of gastric cancers. The rice components are known to be effective for the prevention of the development of cancers. Our group has demonstrated that fermented brown rice by Aspergillus Orzae (FBRA) has chemopreventive potentials in several organs. In this study, we investigated the modifying effects of FBRA exposed during the initiation or post-initiation phase of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in rats. Five-week-old male ACI rats were divided into 7 groups. Groups 1-5 were given oral administration of MNNG (100 mg/l in distilled water) for 24 weeks starting at 6 weeks of age. Groups 2 and 3 were fed a diet containing 5 and 10% FBRA during the initiation phase, respectively, whereas groups 4 and 5 were fed these diets during the post-initiation phase. Group 6 was given a diet containing 10% FBRA throughout the experiment. Group 7 was kept on the basal diet alone and served as an untreated control. Rats were sacrificed at 52 weeks after the start, and the epithelium of the stomach was investigated in detail. Incidence and multiplicity of gastric proliferative lesions of group 1 (MNNG alone) were 61% and 1.67+/-1.57/rat, respectively. Those of group 5 (25%, 0.35+/-0.67) which were given FBRA at a dose of 10% during the post-initiation phase were significantly less than those of group 1. Furthermore, the same group expressed a significantly decreased Ki67-labeling index in the non-lesional gastric epithelium when compared to that of group 1. These results indicate that FBRA inhibits MNNG-induced development of gastric tumors by administration during the post-initiation phase in rats. FBRA is regarded as a promising dietary agent for the prevention of human gastric cancer.