DNA demethylating agent decitabine increases AQP5 expression and restores salivary function.

Xerostomia is the symptom of oral dryness resulting most frequently, but not exclusively, from salivary gland hypofunction. Because the prevalence of xerostomia may increase with age, it has multiple oral health consequences in aging populations. In the present study, we demonstrate that the in vivo administration of 5-aza-2'-deoxycytidine (5-Aza-CdR; decitabine), a DNA demethylating agent, to the murine aging model C57BL/6CrSlc mice (24 wks old) increased the volumes of salivary flow compared with those of control mice. Western blot analysis and immunohistochemical staining demonstrated the augmented expression of AQP5 protein in the salivary glands of 5-Aza-CdR-treated mice compared with those of control mice. In addition, AQP5 protein expression levels in 5-Aza-CdR-treated old mice (27 wks old) were much higher than those in untreated and young mice (6 wks old). Global methylation levels in the salivary glands were significantly lower in the 5-Aza-CdR-treated mice than in the untreated mice. Moreover, the induction of demethylation in the AQP5 promoter of 5-Aza-CdR-treated mice was stronger than in the control mice. Analysis of our data therefore suggests that a DNA demethylating agent may be a useful drug for restoring hyposalivation in elderly individuals, thereby leading to the resolution of xerostomia.

[Brain metastases from esophageal cancers: clinical features and treatment results].

Metastatic brain tumors from esophageal cancer are relatively rare. We analyzed the clinical features and results of treatment in 14 cases of brain metastases from esophageal carcinoma. The average time to diagnosis of brain metastases in the 11 patients with metachronous lesions was 13 months. The average age of patients at the diagnosis of brain metastasis was 65 years. Most patients had T4 or N1 disease at the time of diagnosis of esophageal cancer. Performance status of grade 3 was most frequent at the time of diagnosis of brain metastasis. Treatment for brain metastases was surgery followed by radiation in five cases, radiotherapy alone in seven cases, and conservative treatment in two cases. The median survival time of all patients from the treatment of brain metastases was 2 months, with only one patient alive after more than one year. Improvement in neurological symptoms was demonstrated in 42% of cases. These extremely poor treatment results reflect the fact that most patients at the time of diagnosis of brain metastasis had poor performance status and the presence of extracerebral metastases. Therefore, a short-course, high-dose-per-fraction treatment for brain metastases from esophageal cancer should be selected from the viewpoint of quality of life.

Treatment of roentgenographically occult endobronchial carcinoma with external beam radiotherapy and intraluminal low-dose-rate brachytherapy: second report.

PURPOSE: To evaluate the efficacy and toxicity of treatment with external beam radiotherapy and intraluminal low-dose-rate brachytherapy for roentgenographically occult endobronchial carcinoma (ROEC). METHOD AND MATERIALS: A total of 79 lesions (71 cases) of ROEC were treated with external beam radiotherapy and intraluminal low-dose-rate brachytherapy from July 1991 to December 1998. Of these lesions, 68 (64 cases) were treated with our standard dose (external beam radiotherapy of 40 Gy and intraluminal low-dose-rate brachytherapy of 25 Gy) and are the subject of this report. All 64 patients were males, and their ages ranged from 55 to 80 (median, 68) years. The histologic diagnosis was squamous cell carcinoma in all patients. RESULTS: In all cases, the scheduled treatment was carried out within 2 months. Follow-up period ranged from 4 to 91 (median, 44) months from the beginning of this treatment. Acute toxicity was tolerable. Grade 2 radiation pneumonitis was observed in 4 cases, and there was no case of greater than Grade 2 radiation fibrosis. Nineteen cases of bronchial stenosis and 23 cases of bronchial obstruction were observed on follow-up bronchoscopy. However, no Grade 2 or greater deterioration of respiratory function due to radiotherapy, prolonged symptoms, or fatal toxicity was observed. Nine patients suffered recurrence, 5 of whom were rescued by surgery and external beam radiotherapy, and 4 of whom died of disease. The 5-year cause-specific survival, overall-survival, and disease-free rate were 96.1%, 72.3%, and 87.3%, respectively. CONCLUSION: Combined treatment with external beam radiotherapy and intraluminal low-dose-rate brachytherapy is effective and results in acceptable complications for ROEC.

Radiographic findings of degeneration in cervical spines of middle-aged soccer players.

Twelve amateur veteran soccer players (average age 40.1 +/- 5.4 years), who began playing in their teens and who were admitted with symptoms most likely to be related to cervical spondylosis, were examined by cervical radiography. Abnormal radiographic findings included: calcification of anterior longitudinal ligament (25%), anterior (75%) and posterior vertebral spurs (75%), ossicle between spinous processes (75%), calcification of nuchal ligament (Barsony) (58%), ossicle on spinous process (25%), and bony spur of Luschka's joints (83%). It was shown in the stress distribution by finite element method analysis that the stress in heading the ball was applied mainly to the lower parts of the cervical spine. The results of this analysis also corresponded well with some of the radiographic findings.