Kai-Feng Hung

An Investigation of the Differential Expression of Her2/neu Gene Expression in Normal Oral Mucosa, Epithelial Dysplasia, and Oral Squamous Cell Carcinoma in Taiwan

Background: Her2/neu was thought to be a proto‐oncogene with sequence homology to epidermal growth factor receptor (EGFR). Its overexpression was seen in many cancers and referred to regimens of anticancer therapy. The aim of this study was to investigate whether the abnormal expression existed in oral carcinogenesis. Methods: Immunohistochemistry (IHC) was used to detect Her2/neu expression in normal oral mucosa (NOM) (n = 20), oral precancerous lesions of epithelial dysplasia (ED) (n = 20), and oral squamous cell carcinoma (OSCC) (n = 30). The association of clinicopathologic covariates of areca use, tumor size, neck lymph node metastasis, differentiation and stages of cancer with the expression of Her2/neu was examined. The significance of Neu immunoreactivity in different groups or with different covariates was investigated using Fishers exact test. Results: Her2/neu immunoreactivity was very low with Her2/neu(+) in 10% (2/20) of NOM cases and in 25% (5/20) of ED cases, respectively. The Her2/neu expression was high in OSCC cases, with 40% (12/30) of Her2/neu(+) and 10% (3/30) of Her2/neu(++). Significant difference was observed between NOM/ED and OSCC cases (p < 0.05). All clinicopathologic covariates showed no significant relation to the expression of Her2/neu in OSCC cases. Conclusion: These findings suggested a dynamic change in Her2/neu expression during the development of OSCC. The overexpression of Her2/neu can be used as a marker in distinguishing NOM/ED from OSCC.

Transpositioned flap vestibuloplasty combined with implant surgery in the severely resorbed atrophic edentulous ridge.

The use of transpositioned flap (lipswitch) vestibuloplasty combined with implant surgery in patients with severely resorbed atrophic edentulous ridges is reviewed. The cases of 17 patients with severely resorbed atrophic edentulous ridges at the mandible undergoing implant rehabilitation were reviewed. Lipswitch vestibuloplasty was followed immediately by the implant surgery. Postoperative follow-up consisted of clinical and radiographic examinations. Seventeen patients with atrophic ridges (12 class II and 5 class III) each had 2 implant fixtures placed in the mandible as abutments for a clip and bar overdenture. The average time of follow-up was 6 years. Before surgery, all patients had severely atrophic ridges with a compromised shallow vestibule of varying degrees. Satisfactory results were observed in regard to the immediate and long-term morphology of the vestibule, the health of the peri-implant tissue, the stability of implant fixtures, and the functionality of the prostheses. The lipswitch vestibuloplasty offers a safe and convenient method of surgical access for implant fixture installation, with the advantage of rebuilding the vestibule of a compromised atrophic ridge in the anterior mandible.

MicroRNA-31 upregulation predicts increased risk of progression of oral potentially malignant disorder

OBJECTIVES MicroRNAs (miRNAs, miRs) have shown diagnostic and prognostic potential for oral cancer but their role in oral potentially malignant disorder (OPMD) has been less investigated. We aimed to assess whether miR-21 and miR-31, two of the most relevant miRNAs in oral cancer, are useful as prognostic factors for OPMD progression. MATERIALS AND METHODS miR-21 and miR-31 in 20 saliva samples and 46 tissue samples from patients with OPMD (mean follow-up of 820days) were analyzed by quantitative reverse transcription PCR and in situ hybridization, respectively. The log-rank test, receiver operating characteristic curve, and Kaplan-Meier disease free survival analysis were used to assess the correlation between miRNA levels and OPMD progression. RESULTS Significantly increased salivary miR-21 and miR-31 expression (P=0.003 and P<0.001, respectively) was observed in patients with OPMD compared to control individuals. Patients with recurrent OPMD and/or malignant transformation exhibited a further augmented expression of miR-31, but not miR-21, in the epithelium. Furthermore, increased miR-31 expression as well as epithelial dysplasia is an independent risk factor for OPMD progression as demonstrated in Cox-proportional hazard model (HR: 8.43, P<0.05, 95%CI: 1.04 to 68.03). CONCLUSIONS Salivary miR-21 and miR-31 are applicable as useful OPMD screening tools. Epithelial dysplasia and miR-31 up-regulation synergistically predict the increased incidence of recurrence and/or malignant transformation in patients with OPMD. Detection of miR-31 expression is an adjuvant method for screening of high-risk OPMD.

A Method Using Vestibulo-sulcoplasty Combining a Split-thickness Skin Graft and a Palatal Keratinized Mucosa Graft for Peri-implant Tissue Secondary to Oral Cancer Surgery

Twelve patients presented with oral submucosal fibrosis and loss of keratinized gingiva in a compromised vestibule of a severely deficient mandibular edentulous ridge secondary to oral cancer surgery. They received implant rehabilitation with a total of 49 fixtures without major bone graft augmentation. To overcome vestibular compromise, soft tissue management consisting of simultaneous vestibulo-sulcoplasty, split-thickness skin graft (STSG), and palatal keratinized mucosa graft (KMG) was performed as a second stage when healing abutment was transferred to replace the cover screw of the dental implant. Postoperative follow-up of all patients consisted of clinical and radiographic examinations for an average of 4 years, revealing good stability of implant fixtures with a 91.8% success rate and generally healthy peri-implant tissue, the latter with an average sulcus depth of 2.9 +/- 0.6 mm. Satisfactory results were also demonstrated regarding improved morphology of the vestibule, cosmetics, and prosthetic functionality. Vestibulo-sulcoplasty combining STSG and palatal KMG offers a stable and convenient method for rebuilding peri-implant tissue without need for bone grafting in selected patients who have compromised atrophic ridges secondary to cancer surgery.

Asb6 upregulation by Areca nut extracts is associated with betel quid-induced oral carcinogenesis.

Betel quit (BQ) chewing is a popular habit, especially in southern and southeastern Asia. Areca nut extracts (ANE), the major components of BQ, have been documented to induce reactive oxygen species, and consequently to cause genetic damage. ANE usage is tightly linked to oral cancer; however, the details of the molecular mechanism that results in carcinogenesis remain unclear. Previously, we successfully established HaCaT cells surviving from the long-term exposure of sublethal doses of ANE (Lai KC, Lee TC. Genetic damage in cultured human keratinocytes stressed by long-term exposure to areca nut extracts. Mutat Res 2006;599:66-75). Here, we identified the upregulation of Asb6, a coupling protein to the APS adapter protein, which is involved in insulin signaling for glucose transportation, of normal keratinocytes and oral cancer cells under ANE treatment. Immunohistochemical analyses of Asb6 on oral squamous cell carcinoma (OSCC) tissues (n=57) demonstrated the positive correlation between Asb6 upregulation (cancerous tissues versus adjacent normal tissues) and clinicopathological features. We showed that the combination of ANE-enhanced Asb6 expression in vitro and Asb6 upregulation in OSCC patients leads to poor survival status. In conclusion, our results suggest that upregulated Asb6 could act as a prognostic marker for oral cancer.

Angioleiomyoma in Right Lingual Gingiva-A Case Report

Leiomyomas are benign soft tissue neoplasms that arise from smooth muscle. There are three distinct types of leiomyomas: piloleiomyomas, angioleiomyomas, and genital leiomyomas, which reflect the most origin of the smooth muscle tumor and correspond to the histologic or anatomic site. Angioleiomyomas, as we present here, originate from smooth muscle within the walls of arteries and veins. Although some cases are reported in the gastrointestinal tract, larynx, and brain, oral angioleiomyomas are infrequently found. Malignant transformation probably does not occur, and therefore, they do not affect mortality directly. However, careful histologic examination is still necessary to distinguish these benign lesions from their malignant counterparts due to different prognosis. Here, we present a case of angioleiomyoma found attached to the lower gingival. Clinical and histological presentation of angioleiomyomas with its treatment will be discussed in this article.

Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis

BackgroundTid1 is a mitochondrial co-chaperone protein and its transcript is abundantly expressed in skeletal muscle tissues. However, the physiological function of Tid1 during skeletal myogenesis remains unclear.MethodsIn vitro induced differentiation assay of mouse myoblast C2C12 cells was applied to examine the physiological role of Tid1 during skeletal myogenesis. In addition, transgenic mice with muscle specific (HSA-Cre) Tid1 deletion were established and examined to determine the physiological function of Tid1 during skeletal muscle development in vivo.ResultsExpression of Tid1 protein was upregulated in the differentiated C2C12 cells, and the HSA-Tid1f/f mice displayed muscular dystrophic phenotype. The expression of myosin heavy chain (MyHC), the protein served as the muscular development marker, was reduced in HSA-Tid1f/f mice at postnatal day (P)5 and P8. The protein levels of ATP sensor (p-AMPK) and mitochondrial biogenesis protein (PGC-1α) were also significantly reduced in HSA-Tid1f/f mice. Moreover, Tid1 deficiency induced apoptotic marker Caspase-3 in muscle tissues of HSA-Tid1f/f mice. Consistent with the in vivo finding, we observed that downregulation of Tid1 not only reduced the ATP production but also abolished the differentiation ability of C2C12 cells by impairing the mitochondrial activity.ConclusionTogether, our results suggest that Tid1 deficiency reduces ATP production and abolishes mitochondrial activity, resulting in energy imbalance and promoting apoptosis of muscle cells during myogenesis. It will be of importance to understand the function of Tid1 during human muscular dystrophy in the future.

Attenuation of cancer-initiating cells stemness properties by abrogating S100A4 calcium binding ability in head and neck cancers

S100A4 is a calcium-binding protein capable of promoting epithelial-mesenchymal transition. Previously, we have demonstrated that S100A4 is required to sustain the head and neck cancer-initiating cells (HN-CICs) subpopulation. In this study, to further investigate the molecular mechanism, we established the head and neck squamous cell carcinoma (HNSCC) cell lines stably expressing mutant S100A4 proteins with defective calcium-binding sites on either N-terminal (NM) or C-terminal (CM), or a deletion of the last 15 amino-acid residues (CD). We showed that the NM, CM and CD harboring sphere cells that were enriched with HN-CICs population exhibited impaired stemness and malignant properties in vitro, as well as reduced tumor growth ability in vivo. Mechanistically, we demonstrated that mutant S100A4 proteins decreased the promoter activity of Nanog, likely through inhibition of p53. Moreover, the biophysical analyses of purified recombinant mutant S100A4 proteins suggest that both NM and CM mutant S100A4 were very similar to the WT S100A4 with subtle difference on the secondary structure, and that the CD mutant protein displayed the unexpected monomeric form in the solution phase. Taken together, our results suggest that both the calcium-binding ability and the C-terminal region of S100A4 are important for HN-CICs to sustain its stemness property and malignancy, and that the mechanism could be mediated by repressing p53 and subsequently activating the Nanog expression.

Multimodality Treatment for Rehabilitation of Adult Orthodontic Patient with Complicated Dental Condition and Jaw Relation

A 50-year-old man with severe malocclusion requested comprehensive oral rehabilitation. He presented with retrognathic mandible, anterior deep bite and a gummy smile in the premaxilla, and tenting occlusal plane with severe buccal crossbite of the left maxillary posterior teeth. Inappropriate fixed prostheses spanned the maxilla and the mandible with a class II jaw relationship. A detailed analysis indicated the need for orthodontic treatment, orthognathic surgery, bone graft at the deficient alveolar ridge for implant surgery and a revision of all prostheses. Over a 2-year-period of management, the patient received anterior osteotomy for intrusion of lower anterior teeth, bilateral sagittal splitting osteotomy for mandible advancement and posterior osteotomy for inward upward repositioning of posterior teeth of the left maxilla to correct major jaw deformities. The deficient alveolar ridge in the premaxilla was augmented by autogenous bone graft harvested during the orthognathic surgery. He sequentially had mini-plate and dental implant as anchorage assisting teeth alignment in the mandible. Two 3-fixture-supported implant prostheses were delivered in the premaxilla and the mandible. The improvement in cosmesis, stability and function through treatment and a 2-year clinical follow-up were considered satisfactory.

Implant Rehabilitation of Severely Traumatised Anterior Alveolar Ridge

Abstract Objective: To propose a sequential treatment approach for implant rehabilitation of a traumatised and deficient maxillary or mandibular alveolar ridge. Patients and Methods: Patients with severely deficient alveolar ridge and loss of teeth due to injury underwent sequential reconstructive procedures at the maxillary or mandibular edentulous areas with autogenous symphyseal bone or allogeneic bone graft with guided bone regeneration; vestibuloplasty with or without keratinised palatal mucosal graft to rebuild the vestibule; and implant rehabilitation. Postoperative followup consisted of clinical and radiographic examinations. Results: Thirty six implant fixtures were placed in the maxilla or mandible in 12 patients. The average follow-up period after treatment was 4 years. Before surgery, all patients had severely deficient ridges with a compromised shallow vestibule. Satisfactory results were observed in regard to the long-term stability of the rehabilitation result, contour of the reconstructed ridge, morphology of the vestibule, health of the periimplant tissue, and functionality of the implant-retained prostheses. Conclusion: The proposed sequential reconstructive treatment approach for both hard and soft tissues offers a reliable method of implant rehabilitation after traumatic injury.