Nobiletin inhibits cell growth through restraining aerobic glycolysis via PKA-CREB pathway in oral squamous cell carcinoma.

BACKGROUND/AIM: Nobiletin is a polymethoxylated flavone enriched in Citrus and is used as an important drug in traditional Chinese medicine for various kinds of diseases. Among its multiple functions, it has shown that nobiletin inhibits proliferation of various cancer cells. However, it is unclear whether nobiletin inhibits the growth of oral squamous cell carcinoma (OSCC) cells. MATERIALS AND METHODS: We explored the antitumor effects of nobiletin in TCA-8113 and CAL-27 oral squamous cells. The Cell Counting Kit-8 (CCK8) assay was used to measure cell vitality. Flow cytometry was performed to measure the number of cells in the various phases of the cell cycle. PCR and Western blot were applied to determine mRNA and protein expression, respectively. RESULTS: Nobiletin inhibited proliferation of TCA-8113 and CAL-27 cells via inducing cell cycle arrest at the G1 phase. In addition, the levels of phosphorylated-PKA and phosphorylated-CREB were reduced in nobiletin-treated TCA-8113 and CAL-27 cells. Importantly, our results showed that nobiletin treatment resulted in impaired mitochondrial function and altered glucose consumption, and pyruvate and lactate production. Lastly, nobiletin was found to inhibit the generation of xenografts in vivo. Interestingly, administration of 50 µmol/L Sp-cAMP, a potent PKA activator, rescued all phenotypes caused by nobiletin. CONCLUSIONS: Nobiletin inhibits OSCC cell proliferation in a mitochondria-dependent manner, indicating that it may have a promising role in cancer treatment and attenuation of drug resistance.

[Infections of the head and neck leading to descending necrotizing mediastinitis: management of 9 cases].

OBJECTIVE: To report nine cases of descending necrotizing mediastinitis (DNM) and to summarize the management experience. METHODS: Between December 2005 and December 2008, nine patients (mean age, 55.7 years; age range, 38 to 78 years) with DNM were treated. Eight patients underwent surgical drainage of the involved cervical region and mediastinum (4 with cervical drainage alone; 4 with cervical drainage and right thoracotomy). RESULTS: Two patients died, one of them refused surgical therapy and the other one died of multiorgan failure related to postoperative septic shock. Seven patients recovered. The mortality rate was 22%. CONCLUSIONS: Delayed diagnosis and inadequate drainage are the main causes of high mortality rate of DNM. Aggressive surgical drainage and debridement of the neck and mediastinum by a multidisciplinary team of surgeons are very important in the treatment of DNM.

[Experimental study on the reconstruction of mandibular symphyseal defects by internal tri-focal distractor].

OBJECTIVE: To introduce the internal tri-focal distractor developed by the authors and evaluate its primary application and feasibility in animal experiment. METHODS: Four hybrid dogs were selected and segmental resection at the mandibular symphysis was performed. Two transfer disks, 10 mm in width, were respectively fixed at the two ends of bone defect and the internal tri-focal distractor was installed. The force was applied one week after the operation, with a tractive speed of 0.5 mm/12 h. After 13 - 16 days, the traction was completed when the two transfer disks were combined. The occlusal films were taken at the 1st day, 4th, 8th and 12th week after traction. The animals were killed at the 12th week, samples of the traction area taken and histological examination performed. Finally, the new bone formation was observed. RESULTS: All the animals survived in the experiment, abruption and rust-eaten was not found in distractor. In the 12th week after installation, new bones in traction gap were mature and bony union between the two transfer dishes was accomplished. CONCLUSIONS: The internal tri-focal distractor used in this study may become a potential device in reconstruction of mandibular symphyseal defects.

[Distraction osteogenesis for treatment of unilateral temporomandibular joint ankylosis and secondary OSAHS in children: report of 4 cases].

PURPOSE: To evaluate the efficiency of distraction osteogenensis for treatment of unilateral temporomandibular joint ankylosis and secondary OSAHS in children. METHODS: 4 children with temporomandibular joint ankylosis and secondary OSAHS were retrospectively reviewed for their treatment. There were 2 males and 2 females, ranging from 5 to 13 years in age with the median of 6.5 years. Based on the history of the disease, the clinical manifestations, CT scan and PSG findings, the diagnosis was confirmed to be unilateral temporomandibular joint ankylosis and secondary OSAHS. All the patients were treated by gap arthroplasty to restore mouth opening, combined with mandibular body distraction osteogenesis for treatment of OSAHS. One-stage operation was performed on 3 patients, and two-stage operation on 1 patient. Unilateral and bilateral mandibular distraction osteogenesis was undergone on 2 patients individually. At the end of consolidation period of 3 months, the PSG examination was performed again and the distractor was removed. RESULTS: OSAHS was cured, the average AHI was lowered from 42.7 to 4.9, the average lowest saturation of blood oxygen rose from 74.3% to 89.8%, the average incisor distance reached 25.5mm compared to 6.5mm before surgery and facial deformity was corrected satisfactorily. Following up 38.1 months (13-58 months), no relapse appeared. CONCLUSION: Mandibular body distraction osteogenesis, combined with gap arthroplasty, could be the potential treatment modality for children with unilateral temporomandibular joint ankylosis, secondary OSAHS and facial asymmetry; it is recommended that both procedures be performed at the same time.