Shanghai Key Laboratory of Stomatology

Shanghai, China

Shanghai Key Laboratory of Stomatology

Shanghai, China
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Zhang L.,Shanghai JiaoTong University | Zhang L.,Shanghai Key Laboratory of Stomatology | Zheng J.W.,Shanghai JiaoTong University | Zheng J.W.,Shanghai Key Laboratory of Stomatology | And 2 more authors.
Drug Design, Development and Therapy | Year: 2015

Objective: To evaluate the efficacy and adverse effects of interferon-α2a in the treatment of alarming infantile hemangiomas in the head and neck region. Patients and methods: From January 2009-December 2010, a subcutaneous injection of interferon-α2a was applied to eleven infants with giant multifocal or segmental hemangiomas at a dose of 3 million units/m² per day. All patients did not respond to propranolol or corticosteroids. The age at initiation of interferon-α2a therapy ranged from 3 days to 8 months (median: 4 months). The duration of therapy ranged from 2-4.5 months (median: 3 months). Eight patients received medication for 3 months, one patient for 4.5 months, and two patients for 2 months. Results: Nine patients had a reduction in tumor mass of 95%; two patients’ tumors decreased in size by 75%. The overall response rate was 100%. The main adverse effects included fever, diarrhea, and anorexia, which resolved after stopping the medication. No serious adverse effect was observed. Conclusion: Short-term treatment with interferon-α2a can be used as a safe and effective treatment for alarming infantile hemangiomas that are resistant to propranolol or corticosteroids, and that endanger the proper functioning of the affected organ or the patient’s life. © 2015 Zhang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License.


Wang X.,Shanghai JiaoTong University | Wang X.,Shanghai Key Laboratory of Stomatology | Deng R.,Shanghai JiaoTong University | Deng R.,Shanghai Key Laboratory of Stomatology | And 10 more authors.
Basic and Clinical Pharmacology and Toxicology | Year: 2013

Gambogic acid (GA) is known for its anti-cancer activity in a phase II clinical trial. However, the detailed molecular mechanisms of its anti-multidrug resistance remain unclear. The present study was designed to study the relationship between GA and multidrug-resistant protein ATP-binding cassette transporter B1 (ABCB1). GA dose dependently inhibited ABCB1 activity levels in the in vitro Pgp-Glo assay system and increased the cellular accumulation of ABCB1 substrate adriamycin. Although GA had no significant influence on ABCB1 mRNA in the real-time PCR assay, Western blot detection indicated the compound reduced ABCB1 protein levels. Further study showed the proteasome inhibitor MG-132 reversed the GA-decreased ABCB1 level and prolonged half-life of ABCB1. It was also found that GA coordinated with other anti-cancer drugs (such as adriamycin, docetaxel, verapamil and protopanaxadiol) to enhance cellular cytotoxicity on human epithelial cancer cell lines with higher ABCB1 expression levels. These data suggest that GA functions as a non-competitive inhibitor of ABCB1 by directly inhibiting and reducing its expression levels by promoting protein degradation through post-translational proteasome pathway. The results of this study will aid in the understanding of the synergistic effects of combining GA with other drugs as a new anti-multidrug-resistant agent. © 2012 The Authors. Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.


Cui Z.,Shanghai JiaoTong University | Cui Z.,Shanghai Key Laboratory of Stomatology | Cao W.,Shanghai JiaoTong University | Cao W.,Shanghai Key Laboratory of Stomatology | And 7 more authors.
PLoS ONE | Year: 2013

Tripartite motif-containing 24 (TRIM24), a member of the transcriptional intermediary factor 1 family, functions as a co-regulator that positively or negatively modulates the transcriptional activities of several nuclear receptors. The aim of this study was to investigate TRIM24 expression and its clinical significance in head and neck squamous cell carcinoma. The expression levels of TRIM24 variants were examined in head and neck squamous cell carcinoma (HNSCC) samples and cell lines by real-time PCR and WB. The expression levels of TRIM24 measured in 91 locally advanced HNSCC tumors were measured by immunohistochemistry and correlated with clinical and pathological parameters. The functional role of TRIM24 in HNSCC was further investigated by silencing its expression in HNSCC cell lines. TRIM24 variants were up-regulated in 56 HNSCC samples (P<.001) and 9 HNSCC cell lines (P<.05). TRIM24 protein was overexpressed in 6 of 8 HNSCC cell lines and in 2 of 3 HNSCC samples. Furthermore, 54.95% (50/91) of HNSCC samples exhibited remarkably elevated expression of TRIM24 by immunohistochemistry. Univariate analysis revealed that high TRIM24 expression was associated with worse overall survival (P =. 020). In multivariate analysis, TRIM24 expression was identified as an independent predictor of overall survival (P =. 030), after adjusting for other clinicopathological parameters. Upon TRIM24 silencing, the proliferation of HNSCC cells was notably inhibited due to the induction of apoptosis. These results suggest that aberrant TRIM24 expression may play an important role in the development of HNSCC and is a promising prognostic indicator for patients with locally advanced HNSCC. © 2013 Cui et al.


Song Z.C.,Shanghai JiaoTong University | Shu R.,Shanghai JiaoTong University | Zhang X.L.,Shanghai Key Laboratory of Stomatology
Cell Proliferation | Year: 2010

Objectives: The aim of this study was to investigate biological effects and gene expression profiles of enamel matrix proteins (EMPs), on human bone marrow stromal cells (HBMSCs), for preliminary understanding of mechanisms involved in promoting periodontal regeneration by EMPs. Materials and methods: EMPs were extracted using the acetic acid method, and HBMSCs from human bone marrow aspirates were cultured. Attachment levels, level of cells morphologically attenuated, cell proliferation, alkaline phosphatase (ALP) activity and staining of HBMSCs were measured in the absence and in the presence of EMPs. Microarray analysis was performed to detect gene profiles of HBMSCs by treatment with 200 μg/ml EMPs, for 5 days. Four differential genes were selected for validation of the microarray data using real-time PCR. Results: EMPs promoted proliferation and ALP activity of HBMSCs in a time- and dose-dependent manner, and at a concentration of 200 μg/ml significantly enhanced proliferation and ALP expression. However, there were no significant changes between EMP-treated groups and the control group in cell attachment and cell process attenuation levels. Twenty-seven genes were differentially expressed by HBMSCs in the presence of EMPs. Expressions of 18 genes were upregulated and expressions of nine genes were found to be downregulated. There was good consistency between data obtained from the validation group and microarray results. Conclusions: EMPs promoted cell proliferation and differentiation and gene expression profiles of HBMSCs were affected. This may help elucidation of mechanisms involved in promoting regeneration of periodontal tissues by EMPs. © 2009 Blackwell Publishing Ltd.


Zhang J.,Shanghai JiaoTong University | Zhang J.,Shanghai Key Laboratory of Stomatology | Sun Q.,Shanghai JiaoTong University | Zhang Z.,Shanghai JiaoTong University | And 6 more authors.
Oncogene | Year: 2013

Dysregulated microRNAs (miRNAs) have an important role in many malignant tumors. However, elucidating the roles of miRNAs in cancer biology, especially in epithelial cancers, remains an ongoing process. In this study, we show that both miR-143 and miR-145, which belong to the same miRNA cluster, can negatively modulate expression of their target gene, MDM2. The miR-143 and miR-145 is posttranscriptionally activated by upregulated p53, thereby generating a short miRNAs-MDM2-p53 feedback loop. Re-expression of these miRNAs suppresses cellular growth and triggers the apoptosis of epithelial cancer, in vitro and in vivo, by enhancing p53 activity via MDM2 turnover. Moreover, the miRNA-dependent MDM2 turnover contributes to the equilibrium of repeated p53 pulses in response to DNA damage stress. These findings suggest that MDM2 dysregulation caused by downregulation of miR-143 and miR-145 contributes to epithelial cancer development and has a key role in regulating cellular proliferation and apoptosis. Re-expression of miR-143 and miR-145 may be a reasonable strategy for treatment of epithelial cancers. © 2013 Macmillan Publishers Limited.


Cao W.,Shanghai JiaoTong University | Cao W.,Shanghai Key Laboratory of Stomatology | Feng Z.,Shanghai JiaoTong University | Feng Z.,Shanghai Key Laboratory of Stomatology | And 9 more authors.
Cancer | Year: 2012

BACKGROUND: The authors previously observed that enhancer of zeste homolog 2 (EZH2) overexpression was associated significantly with the development of oral cancer. In the current study, they investigated whether EZH2 can function as a prognostic predictor for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Expression levels of EZH2 in HNSCC cells were detected using reverse transcriptase-polymerase chain reaction (PCR) and Western blot analyses. In addition, the effects of EZH2 ablation on the proliferation and invasion of HNSCC cells were investigated through small interfering RNA (siRNA)-mediated knockdown. Real-time PCR and immunohistochemistry were used to evaluate EZH2 and cyclin D1 expression in 46 HNSCC samples, and the expression levels also were re-evaluated in 124 independent samples by immunohistochemistry. RESULTS: EZH2 expression was elevated remarkably in HNSCC specimens and cell lines. Upon EZH2 silencing, the proliferation and invasion of HNSCC cells were remarkably suppressed. EZH2 expression frequently was correlated with cyclin D1 expression (P =.034) and tumor differentiation (P =.020). In addition, both EZH2 messenger RNA levels and EZH2 protein levels were strongly associated with signs of histologic severity (P =.012 and P =.032, respectively). Univariate analysis revealed that high EZH2 expression was associated with worse overall survival (P =.001) and disease-free survival (P =.002). The combined expression of EZH2 and cyclin D1 had superior prognostic ability for patients with HNSCC than the expression of either marker alone. In multivariate analysis, EZH2 expression was identified as an independent predictor of overall and disease-free survival. CONCLUSIONS: The current results indicated that EZH2 is an independent prognostic indicator for patients with HNSCC. In addition, an analysis of the combined expression of EZH2 and cyclin D1 can serve as a more powerful prognostic predictor for patients with HNSCC. Copyright © 2011 American Cancer Society.


Sun S.,Shanghai Key Laboratory of Stomatology | Sun S.,Shanghai JiaoTong University | Liu S.,Anhui University of Science and Technology | Duan S.Z.,Chinese Academy of Sciences | And 12 more authors.
Cancer Research | Year: 2014

Cancer stem-like cells (CSC) thought to contribute to head and neck squamous carcinomas (HNSCC) may offer attractive therapeutic targets if a tractable approach can be developed. In this study, we report that silencing c-Met is sufficient to suppress sphere formation, tumor initiation, and metastatic properties of HNCSC. Pharmacologic inhibition of c-Met with the selective inhibitor PF-2341066 preferentially targeted CSC and synergized with conventional chemotherapy to improve efficacy in a mouse xenograft model of HNSCC, impeding tumor growth and reducing metastasis. Mechanistic investigations showed that CSC elimination was due to downregulation of Wnt/β-catenin signaling in HN-CSC and that the Wnt pathway receptor FZD8 was essential for interactions of c-Met and Wnt/β-catenin signaling in HN-CSC. Notably, ectopic expression of FZD8 rescued the impaired phenotype of HN-CSC where c-Met was inhibited. Furthermore, c-Met upregulated FZD8 through the ERK/c-Fos cascade in HN-CSC. Taken together, our results offer a preclinical proof-of-concept for targeting the c-Met/FZD8 signaling axis as a CSC-directed therapy to improve HNSCC treatment. ©2014 AACR.


Song X.,Shanghai JiaoTong University | Song X.,Shanghai Key Laboratory of Stomatology | Song X.,University of Maryland, Baltimore | Xia R.,Shanghai JiaoTong University | And 8 more authors.
Clinical Cancer Research | Year: 2014

Purpose: To determine Notch1 mutation status in oral squamous cell carcinoma (OSCC) from Chinese population and its potential clinical implications. Experimental Design: Surgically resected OSCC tissues from 51 Chinese patients and 13 head and neck squamous cell carcinoma (HNSCC) cell lines were sequenced for mutations in the entire coding regions of Notch1 and TP53 using a next-generation sequencing platform. Sequences of the genes were also determined in corresponding normal tissues from 46 of the 51 patients. Mutations and their association with clinical parameters were analyzed. Results: Six mutations in Notch1 and 11 mutations in TP53 coding regions were detected in 4 (31%) and 10 (77%) of the 13 HNSCC cell lines, respectively. Forty-two somatic Notch1 mutations, including 7 nonsense mutations and 11 mutations within the domain commonly harboring potential activating mutations in acute lymphoblastic leukemia, were detected in 22 (43%) of the 51 Chinese OSCC tumors. In comparison, 25 somatic TP53 mutations were observed in 21 (41%) of the 51 tumors. Patients whose tumors carried Notch1 mutation had significantly shorter overall and diseasefree survivals (P = 0.004 and P = 0.001, respectively, by log-rank test) compared with those whose tumors carried no Notch1 mutation. Multivariate analysis showed that both Notch1 mutation and lymph node metastasis are independent prognostic factors in the patient population (P = 0.001). All 15 patients with both Notch1 mutation and nodal metastasis recurred or metastasized within 2 years after surgery. Conclusions: Notch1 mutation is common in Chinese OSCC and associates with clinical outcomes. The complexity of the mutation spectrum warrants further investigation of Notch1 in Chinese patients with OSCC. © 2014 American Association for Cancer Research.


Yan M.,Shanghai JiaoTong University | Yan M.,Shanghai Key Laboratory of Stomatology | Xu Q.,Shanghai JiaoTong University | Xu Q.,Shanghai Key Laboratory of Stomatology | And 7 more authors.
BMC Cancer | Year: 2010

Background: Nuclear factor-kappa B (NF-κB) signaling constitutes a key event in the multistep process of carcinogenesis, progression and treatment in many cancer types. However, the significance of NF-κB pathway for complex and tissue-specific aspects of head and neck cancer progression, such as invasion and metastasis, is less understood.Methods: The expression of NF-κB p65 in squamous cell carcinoma of the head and neck (SCCHN) clinical specimens by immunohistochemistry. The role of NF-κB activity in head and neck squamous cell carcinoma was determined by western blot, reporter assay and EMSA analysis in vitro and metastasis assays in vivo in different metastatic potential tumor cells. Furthermore, the apoptosis rate and expression of metastasis-related protein such as MMP9 and VEGF were examined by Annexin V/PI staining and Western blot, respectively.Results: A higher level of active nuclear-localized NF-κB was observed in the metastatic SCCHN specimens group (p < 0.01). The NF-κB activities of SCCHN cell lines with different metastatic potentials were then determined and in excellent agreement with results found in SCCHN specimens, highly metastatic SCCHN cell lines expressed high level of NF-κB activity. The treatment of highly metastatic SCCHN cells with NF-κB inhibitors reduced the in vitro cell invasion capacity of the cells without affecting the apoptotic rate. Additionally, the NF-κB inhibitors significantly inhibited the experimental lung metastasis of Tb cells and lymph node metastasis of TL cells in nude mice. Furthermore, the expression of metastasis-related proteins, such as matrix metalloproteinase 9 and vascular endothelial growth factor, was inhibited by pyrrolidine dithiocarbonate.Conclusions: This study suggests that NF-κB activity significantly contributes to tumor hematologic and lymphatic metastases and may aid in the development of early detection methods or therapies targeting non-conventional molecular targets. © 2010 Yan et al; licensee BioMed Central Ltd.


Xu Z.,Shanghai Biomaterials Research and Testing Center | Xu Z.,Shanghai JiaoTong University | Xu Z.,Shanghai Key Laboratory of Stomatology | Chou L.,Boston University | And 3 more authors.
Journal of Applied Toxicology | Year: 2012

Silicon dioxide nanoparticles (SiO 2 NPs) have attracted increasing interest as nanovehicles for delivering drugs, genes and bio-active molecules into cells. However, it is still unknown whether SiO 2 NPs could cause side-effects to normal cells. In the present study, human lung fibroblasts (HFL-Is) were directly exposed to two different sizes of SiO 2 NPs. The effect of size and concentration on cell response was studied by analyzing the cell viability, the ratio of apoptosis and the pathway of cell injury. The results demonstrated that a size-associated and a dose-dependent toxicity of HFL-Is was induced by SiO 2 NPs. Meanwhile, the expression of reactive oxygen species in HFL-I was significantly increased. This activation effect was accompanied by upregulation of p53 expression, release of cytochrome C from chondriosomes, inhibition of Bcl2, and activation of Bax and caspase 9. These findings implied that SiO 2 NPs might induce apoptosis of HFL-Is by stimulating reactive oxygen species release and subsequently causing the activation of p53 pathway in vitro. © 2011 John Wiley & Sons, Ltd.

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