[Show abstract][Hide abstract] ABSTRACT: Oral squamous cell carcinoma (OSCC) is a type of head and neck malignancy with a high mortality rate. Oral submucous fibrosis (OSF) is the pre-cancerous lesion of OSCC, whose molecular mechanisms in OSCC tumorigenesis remain largely unclear. Activation of the Wnt/β-catenin signaling pathway plays an important role in oral mucous carcinogenesis, although rare mutations of Wnt signaling molecules are found in OSCC, suggesting an epigenetic mechanism mediating aberrant Wnt/β‑catenin signaling in OSCC. Wnt inhibitory factor-1 (WIF1) is an Wnt antagonist, and its downregulation and methylation have been reported in a number of malignancies. However, the expression and methylation of WIF1 in the development of OSF have yet to be reported. In the present study, we investigated the WIF1 expression level by immuno-histochemical staining and semi‑quantitative RT-PCR in normal oral, OSF and OSCC tissues, as well as the methylation status by methylation-specific PCR and bisulfite genomic sequencing. The results showed that WIF1 was readily expressed in normal oral mucous tissues, but decreased gradually in OSF early, moderately advanced and advanced tissues, and was less expressed in OSCC tissues. Moreover, WIF1 was able to translocate from the nuclear to cytoplasm in OSF and OSCC tissues. Furthermore, WIF1 was frequently methylated in OSCC cases with betel quid chewing habit, but not in normal oral mucous and different stages of OSF tissues, suggesting WIF1 methylation is tumor-specific in the development of OSF. Thus, the results demonstrated that WIF1 is frequently downregulated or silenced by promoter methylation in the carcinogenesis of OSF, which serves as a potential epigenetic biomarker for the early detection of OSCC.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the performance of dental implant-supported telescopic crown (TC)-retained overdentures to restore the oral function of patients who have insufficient jawbone volume resulting from tumor resection or trauma.
From January 2004 to December 2008, implant-supported TC-retained overdentures were used to restore the oral function of patients with severe bony defects resulting from tumor resection or trauma. Clinical data, including implant success and survival rates, biologic and mechanical complications, prosthodontic maintenance efforts, and patient satisfaction, were analyzed annually after delivery of the final prostheses.
Twenty-four patients were treated, and a total of 88 implants were inserted to support TC-retained overdentures. The mean modified plaque index of implants remained low (<20%), and the majority of implants (>76.3%) in the study showed the absence of bleeding on probing at follow-up visits. Peri-implant marginal bone loss (MBL) ranged from 0.8 to 1.2 mm. There was no statistically significant difference in the MBL between maxillary and mandibular implants (P = .43). The implant success rate was 100% after 5 years, and the prosthodontic maintenance and complication rate was 0.22 times per year. More than 90% of patients were satisfied with the restoration of their oral function using TCs.
Based on our study of 24 patients treated with TC-retained overdentures, it appears that this treatment may be a viable option for patients with insufficient jawbone volume.
The International journal of oral & maxillofacial implants 07/2015; 30(4):937-44. DOI:10.11607/jomi.3697 · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objectives of this study were to analyze the regional characteristics of the cervical lymph node metastasis and to investigate the factors associated with the risk of lymph node involvement. One hundred seventy-one patients suffering from early primary squamous cell carcinoma (SCC) of the tongue (cT1-2N0) were enrolled. Gender, age, growth site, T stage, histological grade, and neurovascular invasion were statistically analyzed by K-M survival analysis and Cox multivariate analysis to evaluate the relationship between the factors and the neck lymph node metastasis. Of the 171 cases divided into the neck dissection group and observation group, 40 ended up with lymph node metastasis, of which 17 were metastasized to level I, 27 to level II, 10 to level III, 2 to level IV, and 1 to level V. Histological grade and neurovascular invasion were significantly associated with lymph node involvement in univariate and multivariate analyses. Age distribution was found to be significantly associated with the lymph node metastasis in multivariate analysis. The metastasis of early tongue SCC has a certain regularity at different sites. Age was not a critical risk factor for cervical lymph node metastasis after surgery. Tumor size was suspected to exert a negative effect on metastasis by influencing tumor invasion. Histological grade and neurovascular invasion were significantly associated with the risk of cervical lymph node metastasis of early tongue SCC.
[Show abstract][Hide abstract] ABSTRACT: The use of vascularized nerve graft models has been limited because of the complexity of the operation. The authors sought to develop a simple and effective rabbit model for facial nerve repair and evaluated its advantages over conventional nerve grafts.
Rabbits were divided into three groups consisting of six rabbits each. The central auricular nerve and its nutrient vessels were used as a vascularized graft. Rabbits were grafted with a vascularized facial nerve graft (vascularized nerve graft group), with a free nerve graft (free nerve graft group), or with a vascularized nerve graft and a free nerve graft on each side of the face (vascularized nerve graft/free nerve graft group). Four months after surgery, facial performance and electrophysiologic monitoring were evaluated. The rabbits were then killed to prepare the nerve specimens for histologic, immunohistochemical, and transmission electron microscope study.
At 4 months after the facial nerve repair, the functional recovery of the facial nerve was observed and analyzed. The side grafted with vascularized nerve graft was superior to the side grafted with free nerve graft. Regenerated nerve fibers were observed in all groups, and rabbits grafted with vascularized nerve grafts had more regenerated axons than those that underwent free nerve grafting, although the regenerated nerves were not as good as the natural nerves.
This study demonstrates that it is feasible to establish a vascularized nerve graft model in rabbits. The model offers the obvious advantages of operability and reliability. The vascularized nerve graft is demonstrated to have a superior value for facial nerve repair.
[Show abstract][Hide abstract] ABSTRACT: Purposes
The continuity and integrity of the enveloping nutritive periosteum may be compromised during the installation of the dental implant distractor (DID) device. This novel animal experiment aims to study the influence of the periosteum on the bony regenerate in 3 scenarios of periosteal coverage: whole periosteum (WP), half periosteum (HP) and no periosteum (NP).
Materials and methods
Twelve goat tibias were vertically osteotomised into two segments each and divided into the three groups of WP, HP and NP. A DID device was surgically installed onto each segment, followed by 10 days of distraction at a rate of 0.35mm twice daily. Fluorescence-labeling and trabeculae count per high powered field (TBC/HPF) measurements were performed and statistically compared across the various groups. Implant stability quotients (ISQ) of all fixtures were also done.
New bone formation of WP and HP groups were found to be faster than the NP group under fluoroscopy. The TBC/HPF values had no statistically significant differences across all three groups. All WP groups showed significantly higher ISQ values (0.93) compared to the HP (0.85) and NP (0.84) groups.
Vertical distraction osteogenesis can be successfully performed with the dental implant distractor to obtain bone of adequate stock and density. However, the enveloping periosteum should be preserved as much as possible during the installation of the DID device.
Journal of Oral and Maxillofacial Surgery 10/2014; 72(10). DOI:10.1016/j.joms.2014.06.440 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
Reconstruction of lower lip defect with Karapandzic flap often leads to greater rounding of commissure. The aim of this study was to provide a new design of bilateral Karapandzic flap, which is useful in large lower lip defect reconstruction.
In this retrospective study of case series, a modification of the Karapandzic lip reconstruction technique was used with an additional incision to recruit more tissue. The esthetic outcome of the reconstruction was assessed in a 4 point scale with regard to the shape of commissure, lip symmetry, appearance of the scar and lip projection. The functional outcome were assessed in terms of speech, preservation of oral competence, lip sensory, facial expression, diet and denture usage.
Seventeen lower lip squamous cell carcinoma patients underwent single-stage lip reconstruction (13 males, 4 females) with an age range of 52 to 82 years. The lip defects post tumor resection ranged from 50 to 90% of the lower lips. All patients achieved oral competence, without leading to greater rounding of the commissure. The esthetic outcome was considered excellent/good in 88% of cases and the reconstruction did not lead to functional impairments of speech, oral competence, lip sensory, facial expression, diet or denture usage.
Modified bilateral Karapandzic flap is a reliable technique to reconstruct large lip defects without leading to rounding of the commissure. With this technique, good esthetic and functional outcomes could be achieved.
Journal of Oral and Maxillofacial Surgery 10/2014; 72(10). DOI:10.1016/j.joms.2014.04.014 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
To evaluate the use of the buccal fat pad (BFP) in theimmediate reconstruction of oncological palate defects and the influence of postoperative radiotherapy on reconstruction.
Patients who were diagnosed with moderate- to high- grade malignancies of palate underwent partial maxillectomy. BFP was used as a pedicled flap to reconstruct the defects. All patients received postoperative radiotherapy 4-5 weeks after surgery.
Eighteen patients (9 males, 9 females) with an age range of 37 to 81 years underwent surgery and subsequent radiotherapy. The size of all defects ranged from 7.5-19.2cm2. Adequate closure of the defects was achieved during surgery and all the flaps were epithelialized within 3 weeks after operation with no complications of dehiscence or flap failure. Furthermore, there were no complications derived from the postoperative radiotherapy.
Our study suggests that the BFP is an effective and reliable method for the reconstruction of small to medium sized palate defects. Furthermore, postoperative radiotherapy doesn’t influence the success of the reconstruction.
Journal of Oral and Maxillofacial Surgery 07/2014; 72(12). DOI:10.1016/j.joms.2014.06.459 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
The aim of the study is to estimate the impact of different defect size and used flaps on post-operative soft palate functional outcomes.
The study included 45 consecutive patients who were treated by three different reconstructive flaps for their soft palate defect. Post-operative speech and swallowing functions were assessed to measure the relationships between the defect size and postoperative function of soft palate, the different flap reconstructed and postoperative function. The one-way ANOVA test was computed. P <.05 was considered significant.
Postoperative evaluation revealed that both speech and swallowing functions were normal or near normal in patients with type II defects but poor in the patients of type III and IV defects. No significant changes in postoperative soft palate functions using different flap sizes for the same defect type.
The study confirms that the size of defect, rather than the type of the flap, has the most critical influence on the soft palate post-operative functions. Defect size of 50% or less has a better outcomes than those with a defect of more than 50%.
Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 07/2014; 72(7). DOI:10.1016/j.joms.2014.01.012 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Kallmann syndrome 1 sequence gene (KAL1) protein is an extracellular matrix associated protein which plays vital roles in neurons development and cell migration. However, its biological functions and clinical implications have yet not been revealed in oral carcinogenesis. The objective of the study was to evaluate the role of KAL1 in oral cancer and determine clinical significance of KAL1 in oral squamous cell carcinomas (OSCCs).Methods
The expression pattern of KAL1 was examined in a testing cohort including OSCCs (n = 42) and paired adjacent tissues (PATs) (n = 14) by real-time PCR. The result was further validated in a validating cohort of OSCCs (n = 32). Correlation between clinicopathological parameters and KAL1 mRNA levels was analyzed by Kruskal–Wallis test. In vitro, the effects of KAL1 ablation through siRNA-mediated knockdown on the proliferation of OSCC cells were determined by CCK-8, BrdU, and colonies formation assays, respectively. In addition, cell cycle distribution was further evaluated by cytometry.ResultsWe observed that remarkably decreased expression of KAL1 mRNA in two independent cohorts (P = 0.0002 and P = 0.033, respectively). Furthermore, downregulated KAL1 mRNA was significantly associated with worse pathological grade (P = 0.013 and P = 0.035, respectively). Upon KAL1 silencing, the proliferation and colonies formation potentials of OSCC cells were notably promoted by accelerating G1 to M phase transition.Conclusion
These data indicated that KAL1 plays a potential suppressive role on OSCC initiation and progression, and KAL1 gene may serve as an adjuvant biomarker for the identification of pathological grade.
Journal of Oral Pathology and Medicine 07/2014; 44(2). DOI:10.1111/jop.12206 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To present the clinical, imaging, pathological and immunohistochemical features of giant cell angiofibroma (GCA).
In this paper we report an atypical case of a GCA extending from the parotid to the parapharyngeal space. The lesion was being treated as a vascular malformation for one year prior to surgical removal. We summarize the clinical manifestations, imaging, pathological and molecular features of this rare disease.After complete surgical removal of the tumor, immunohistochemical analysis revealed strong positivity for the mesenchymal markers vimentin, CD34, CD31 and CD99 in neoplastic cells. Tumor proliferation antigen marker Ki67 was partly positive (<5% of cells). Tumor cells were negative for muscle-specific actin, epithelial membrane antigen, smooth muscle actin, cytokeratin pan, S100, desmin, glial fibrillary acidic protein, myogenin, MyoD1 and F8. The morphological and immunohistochemical profile was consistent with the diagnosis of GCA.
GCA is a rare soft tissue tumor that can easily be misdiagnosed in the clinical preoperative setting. In view of the clinical, pathological and molecular features of the tumor, complete surgical removal is the current optimal treatment option, providing accurate diagnosis and low to minimal recurrence rate.
World Journal of Surgical Oncology 04/2014; 12(1):117. DOI:10.1186/1477-7819-12-117 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Toll-like receptor 4 (TLR4) is expressed in head and neck squamous cell carcinoma (HNSCC) cells and is associated with HNSCC cancer progression. Rapamycin has been proven to be efficient for the treatment of HNSCC in vivo, yet the mechanism is not understood and rapamycin demonstrates little effect in vitro. In the present study, the HNSCC cell lines CAL27 and SCC4 were pre-treated with rapamycin then stimulated with a TLR4 ligand lipopolysaccharide (LPS). Cell proliferation, migration, invasion, resistance to TRAIL-induced apoptosis, cytokine production, NF-κB and p65 activation were determined. The results indicated that LPS significantly stimulated HNSCC cell proliferation, cytokine production, migration, invasion and resistance to apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Pretreatment with rapamycin significantly attenuated LPS-induced pro-oncogenic effects by inhibiting the activation of NF-κB by LPS. siRNA knockdown of TLR4 in HNSCC cells demonstrated that rapamycin attenuated LPS-induced pro-oncogenic effects via TLR4. Hence, this study suggests rapamycin may be efficient for the treatment of HNSCC by attenuating TLR4-induced pro-oncogenic effects.
[Show abstract][Hide abstract] ABSTRACT: Increasing evidence suggests that communication between tumor and immune cells can alter the tumor microenvironment in ways that promote tumor development. The purpose of this study was to characterize the immune response elicited by TLR-9-activated OSCC cells, to identify the cytokines involved in the signaling pathway and to elucidate the molecular mechanism of this pathway in OSCC cells. MTS, flow cytometry and ELISA assay were used to evaluate T-cell immune responses, cancer cell proliferation and pro-inflammatory cytokine secretion, respectively. Western blot analysis, EMSA and ChIP assay were employed to detect the activity of the NF-κB and AP-1 signaling pathways. A marked response was observed when T-cells were co-cultured with supernatants from CpG-ODN-treated OSCC cells. This response was characterized by increased CD4+ and CD8+ T-cell proliferation and an increase in IFN-γ production by the CD4+ T-cell population. Treatment of OSCC cells with CpG-ODN resulted in an increase in IL-6 secretion as well as an increase in AP-1 binding activity to the IL-6 promoter. Moreover, blockage of the TLR-9/AP-1 pathway significantly decreased IL-6 expression and T-cell immune response. In human OSCC, the TLR-9 pathway, when stimulated by CpG-ODNs, promotes a T-cell immune response mediated by AP-1-activated IL-6 secretion. Although the complete molecular mechanism has yet to be understood, these findings provide evidence linking tumor cell activities to immune system responses. In addition, the TLR-9/AP-1/IL-6 pathway provides new therapeutic targets for the prevention and treatment of OSCC.
International Journal of Oncology 03/2014; 44(6). DOI:10.3892/ijo.2014.2356 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Activation of Toll like receptors (TLRs) signaling has been implicated in promoting malignant cell invasion and metastatic potential. Previously we demonstrated that increased TLR-9 expression predicted poor survival in oral cancer patients. The objective of this study is to further investigate the roles and potential molecular mechanisms of TLR-9 signaling in human oral cancer cell invasion.
Cell migration, invasion and protein expression were detected by wound healing assay, Transwell chambers model and western blot. The secretion and activity levels of metalloproteinases-2/9 were quantified by ELISA and Gelatin zymography. EMSA and ChIP assays were employed to detect the activity of AP-1signal pathway. TLR-9 siRNA transfection was used to regulate the expression and activity of TLR-9 in oral cancer cell line HB cells.
The results of both wound healing assay and in vitro Transwell assay revealed that activation of TLR-9 induced dose- and time- dependent migration and invasion of HB cells. An increased expression, secretion and activity of MMP-2 were observed upon the treatment of CpG-ODN. The TLR-9 signaling-mediated MMP-2 expression appeared to be a consequence of AP-1 activation, because that their DNA binding activity was enhanced by CpG-ODN treatment. All these influences were efficiently repressed by the knockdown of TLR-9 through siRNA or pretreatment of an AP-1 inhibitor.
Activation of TLR-9 signaling could promote human oral cancer HB cells invasion with the induction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel anti-metastatic application for TLR-9 targeted therapy in oral cancer in the future.
PLoS ONE 03/2014; 9(3):e92748. DOI:10.1371/journal.pone.0092748 · 3.23 Impact Factor