Yang Wenjun

Shikonin inhibits tumor invasion via down-regulation of NF-κB-mediated MMP-9 expression in human ACC-M cells

OBJECTIVE The aim of this study was to examine the anti-invasion effect of Shikonin on human high-metastatic adenoid cystic carcinoma (ACC-M) cells and to explain the possible molecular mechanism involved. METHODS The ACC-M cells were treated with Shikonin (0, 2.5, 5, 10 μM) for 24 h. The protein levels and gelatinolytic activities of MMP-2 and MMP-9 were analyzed using Western blot and Gelatin zymography test, respectively. Matrigel invasion assays were used to investigate tumor invasive potential and electromobility shift assays were used to determine the activity of NF-κB. RESULTS The invasiveness of ACC-M cells was reduced in a dose dependent manner following 24-h treatment of up to 10 μM of the Shikonin at which concentration no cytotoxicity occurred. The protein levels and gelatinolytic activities of MMP-9 were significantly suppressed by increasing Shikonin concentrations. The down-regulation of MMP-9 appeared to be via the inactivation of NF-κB as the treatment with Shikonin suppressed the protein level of phosphate-IkBa, which was accompanied by a decrease in DNA-binding level of the factor. CONCLUSIONS Shikonin inhibits tumor invasion via downregulation of MMP-9 expression in ACC-M cells. Pharmacologic inhibition of the NF-κB-mediated MMP-9 expression by Shikonin might be a powerful treatment option for ACC patients in future.

Toll‐like receptor‐9 agonists increase cyclin D1 expression partly through activation of activator protein‐1 in human oral squamous cell carcinoma cells

Increasing evidence suggests that malignant transformation can result from chronic infection, and Toll‐like receptors (TLRs) may play an important role in this process. We have previously reported that the increased expression of TLR‐9 is associated with tumor cell proliferation in oral cancer. However, the mechanisms involved have not been elucidated. The aim of this study was to investigate whether CpG‐oligodeoxynucleotides (CpG‐ODN), a special TLR‐9 agonist, is able to exert the proliferation‐promoting effect in human oral squamous cell carcinoma (OSCC), and to explore the possible underlying molecular mechanism. Flow cytometry, MTT, and colony formation assay were used to evaluate cell proliferation and cell cycle distribution. The mRNA and protein levels were analyzed by quantitative RT‐PCR and Western blot assay. Luciferase reporter gene, EMSA, and ChIP assays were used to detect the activity of activator protein‐1 (AP‐1) and nuclear factor‐κB (NF‐κB) in HB cells. Results showed that CpG‐ODN could stimulate proliferation of HB cells in a dose‐ and time‐dependent manner with a promoted G1/S cell cycle progression. Increased cyclin D1 expression was detected in the nuclear region after CpG‐ODN treatment. Moreover, CpG‐ODN promoted nuclear translocation and activation of AP‐1, which appeared to be required for TLR‐9‐mediated cyclin D1 expression and subsequently cell proliferation, but seemed to have little impact on NF‐κB activity. Our results indicate that CpG‐ODN stimulates tumor cell proliferation through TLR‐9‐mediated AP‐1‐activated cyclin D1 expression in OSCC HB cells. Pharmacologic inhibition of the TLR‐9/AP‐1/cyclin D1 pathway may be a new therapeutic approach for prevention as well as treatment of OSCC.

Increased expression of MUC-1 has close relation with patient survivor in high-grade salivary gland mucoepidermoid carcinoma.

PURPOSE High-grade mucoepidermoid carcinoma (MEC) is an infrequent malignant neoplasm originates most commonly in the salivary glands with poor prognosis. Thus far, there is little knowledge on MUC-1 expression in high-grade MEC or how it may relate to patient survival. The aim of this study was to determine the extent of MUC-1 expression in high-grade MEC and correlate expression with clinic outcome. METHODS Surgical specimens from 62 cases of primary high-grade MEC and 10 cases of normal salivary gland tissue were examined by immunohistochemistry. The relationship between MUC-1 expression and the clinicopathological data and patient survival was analyzed. RESULTS The disease-free survival rates were 54.6% (3 years) and 37.7% (5 years) for high-grade MEC patients. Patient who with primary location at submandibular gland have the worst prognosis (P = 0.042) in comparing with other sites. High expression of MUC-1 in high-grade MEC was significantly correlated with lymphatic/regional metastasis (P = 0.003) and clinic stage (P = 0.02), and high expression of MUC-1 (>75%) was confirmed to be significant independent prognostic factors in high-grade MEC patients [HR 2.929 (95% CI 1.246-6.881); P < 0.0137]. CONCLUSIONS The findings suggest that high levels of MUC-1 expression may be a potential marker for worse outcome in high-grade MEC and could be used as a new molecule target to improve outcomes for these patients in the future.

Dental implant distractor combined with free fibular flap: a new design for simultaneous functional mandibular reconstruction.

PURPOSE The purpose of the present study was to present a new method that combines the use of the fibular flap and a custom-made vertical distractor/dental implant device into 1 surgical procedure for simultaneous functional mandibular reconstruction. PATIENTS AND METHODS The present retrospective case series included 10 patients who were treated using the fibular flap and dental implant distractor (DID) in a single-stage procedure. These 10 patients were treated within a 3-year period (from 2005 to 2007). RESULTS Of the 10 patients included in the study, 5 were males and 5 were females. The mean age of the sample was 33.8 years (range 17 to 48). The cumulative survival rate of the fibular flaps was 100%. The mean vertical bone height attained with the DID device was 11.4 mm. The mean period from the first operation to the start of dental implant loading was 6.3 months. The cumulative survival rate of the dental implants was 93.75%. CONCLUSIONS The use of the DID in the fibular flap for mandibular reconstruction is advantageous because it combines vertical distraction osteogenesis of the fibular flap and dental implantation into a single procedure. Implants placed in the reconstructed areas were found to integrate normally, with survival rates comparable to those with 2-stage operations. As such, this novel DID technique can be used for single-stage reconstruction and rehabilitation of segmental mandibular defects in selected patients.

Oral and maxillofacial desmoid-type fibromatoses in an eastern Chinese population: a report of 20 cases

OBJECTIVE Primary desmoid-type fibromatoses arising from the oral and maxillofacial region are uncommon and hold the character of local invasion and regional recurrence. The purpose of this study was to analyze the clinicoepidemiologic characteristics of this rare disease in an eastern Chinese population. STUDY DESIGN Epidemiological and clinicopathological data on 20 patients were reviewed from the hospital records and analyzed accordingly. RESULTS Twelve males and 8 females with a ratio of 3:2 were involved. The mandible was the most common site of presentation. Suspected malignant change was found in 6 cases and an extremely high recurrence rate was also found in up to 53%. Abnormally high blood levels of alkaline phosphatase were found in 65% of patients, which had a close relation with tumor malignant change. CONCLUSION Chinese people are more susceptible to desmoid-type fibromatoses and are at an extremely high risk of regional malignant change. Elevated serum alkaline phosphatase levels may be taken as an indicator for malignant transformation.

An investigation of stage-based parallel programming model for stateful network services on COTS platforms

Stateful network services are a growing population of applications in the Internet, whose architecture relies more and more on COTS components. A good parallel programming model is the key to the success of network services. We argue that stage-based parallel programming model is the most suitable candidate, which takes the whole service logic as a set of stages interconnected by event queues, and in each stage, one or multiple threads reside to service messages. And we also reveal several key design principles for this model. 1) The number of stages should not be over 10 for a single CPU system. 2) For stages with blocking calls, a good estimation of the number of threads for that stage can be gotten by (call arrival rate blocking time) and moreover excessive threads give minor performance degradation. 3) To deliver message quickly, it is much better to locate this part of service in a separate nonblocking stage.