Detection and Screening of Oral Cancer and Pre-cancerous Lesions

Oral cancer is a fatal disease, accounting for the fourth highest incidence of malignancy in males and the seventh in females in Taiwan. The relatively high prevalence of oral cancer in Taiwan is mainly because there is a high-risk group of 2.5 million people with the habit of smoking and betel nut chewing. Unfortunately, 50% of new cases in our medical center who present with TNM stage III or IV lesions have a shorter than 5-year survival after treatment. This highlights the need for: (1) early treatment of fresh oral cancer cases; (2) screening of the high-risk population to detect new lesions; (3) careful follow-up of cases after treatment; and (4) detection of occult early neck nodal adenopathy in surgical cases. It is generally accepted that prevention and screening of oral cancer are equally important to treatment due to its location. In this review article, we describe the nature of oral cancer and highlight the various conventional and novel methods of screening for this disease and ongoing important related research. Related literature is reviewed and future work that needs to be done is detailed

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

BackgroundHer2/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.MethodsImmunohistochemistry (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 Fisher's exact test.ResultsHer2/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.ConclusionThese 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

Lateral trap-door window approach with maxillary sinus membrane lifting for dental implant placement in atrophied edentulous alveolar ridge

Abstract One of the most challenging and technically sensitive surgical procedures in conjunction with dental implant rehabilitation is sinus membrane lifting to increase the bone height or volume from the maxillary sinus floor. This important preprosthetic surgical technique has been available for &gt;15 years, making possible the creation of bone volume in the edentulous posterior maxilla for the placement of dental implants in surgically compromised cases. Substantial literature exists regarding the most efficacious way to increase the predictability of this surgical procedure, and reduce its associated complications. In this article, we describe the regional anatomy of the maxillary sinus, the evolution of the sinus membrane lifting procedure, the current surgical technique, its survival rate and associated complications, the need for bone graft or bone substitutes, and current advances in the lateral approach through a trap-door window for sinus membrane lifting for dental implants

Bmi-1 Regulates Snail Expression and Promotes Metastasis Ability in Head and Neck Squamous Cancer-Derived ALDH1 Positive Cells

Recent studies suggest that ALDH1 is a putative marker for HNSCC-derived cancer stem cells. However, the regulation mechanisms that maintain the stemness and metastatic capability of HNSCC-ALDH1+ cells remain unclear. Initially, HNSCC-ALDH1+ cells from HNSCC patient showed cancer stemness properties, and high expression of Bmi1 and Snail. Functionally, tumorigenic properties of HNSCC-ALDH1+ cells could be downregulated by knockdown of Bmi-1. Overexpression of Bmi-1 altered in expression property ALDH1− cells to that of ALDH1+ cells. Furthermore, knockdown of Bmi-1 enhanced the radiosensitivity of radiation-treated HNSCC-ALDH1+ cells. Moreover, overexpression of Bmi-1 in HNSCC-ALDH1− cells increased tumor volume and number of pulmonary metastatic lesions by xenotransplant assay. Importantly, knock-down of Bmi1 in HNSCC-ALDH1+ cells significantly decreased distant metastases in the lungs. Clinically, coexpression of Bmi-1/Snail/ALDH1 predicted the worst prognosis in HNSCC patients. Collectively, our data suggested that Bmi-1 plays a key role in regulating Snail expression and cancer stemness properties of HNSCC-ALDH1+ cells

A Combined DNA-Affinic Molecule and N-Mustard Alkylating Agent Has an Anti-Cancer Effect and Induces Autophagy in Oral Cancer Cells

Although surgery or the combination of chemotherapy and radiation are reported to improve the quality of life and reduce symptoms in patients with oral cancer, the prognosis of oral cancer remains generally poor. DNA alkylating agents, such as N-mustard, play an important role in cancer drug development. BO-1051 is a new 9-anilinoacridine N-mustard-derivative anti-cancer drug that can effectively target a variety of cancer cell lines and inhibit tumorigenesis in vivo. However, the underlying mechanism of BO-1051-mediated tumor suppression remains undetermined. In the present study, BO-1051 suppressed cell viability with a low IC50 in oral cancer cells, but not in normal gingival fibroblasts. Cell cycle analysis revealed that the tumor suppression by BO-1051 was accompanied by cell cycle arrest and downregulation of stemness genes. The enhanced conversion of LC3-I to LC3-II and the formation of acidic vesicular organelles indicated that BO-1501 induced autophagy. The expression of checkpoint kinases was upregulated as demonstrated with Western blot analysis, showing that BO-1051 could induce DNA damage and participate in DNA repair mechanisms. Furthermore, BO-1051 treatment alone exhibited a moderate tumor suppressive effect against xenograft tumor growth in immunocompromised mice. Importantly, the combination of BO-1051 and radiation led to a potent inhibition on xenograft tumorigenesis. Collectively, our findings demonstrated that BO-1051 exhibited a cytotoxic effect via cell cycle arrest and the induction of autophagy. Thus, the combination of BO-1051 and radiotherapy may be a feasible therapeutic strategy against oral cancer in the future

Lateral trap-door window approach with maxillary sinus membrane lifting for dental implant placement in atrophied edentulous alveolar ridge

One of the most challenging and technically sensitive surgical procedures in conjunction with dental implant rehabilitation is sinus membrane lifting to increase the bone height or volume from the maxillary sinus floor. This important preprosthetic surgical technique has been available for >15 years, making possible the creation of bone volume in the edentulous posterior maxilla for the placement of dental implants in surgically compromised cases. Substantial literature exists regarding the most efficacious way to increase the predictability of this surgical procedure, and reduce its associated complications. In this article, we describe the regional anatomy of the maxillary sinus, the evolution of the sinus membrane lifting procedure, the current surgical technique, its survival rate and associated complications, the need for bone graft or bone substitutes, and current advances in the lateral approach through a trap-door window for sinus membrane lifting for dental implants

RB Maintains Quiescence and Prevents Premature Senescence through Upregulation of DNMT1 in Mesenchymal Stromal Cells

Many cell therapies currently being tested are based on mesenchymal stromal cells (MSCs). However, MSCs start to enter the senescent state upon long-term expansion. The role of retinoblastoma (RB) protein in regulating MSC properties is not well studied. Here, we show that RB levels are higher in early-passage MSCs compared with late-passage MSCs. RB knockdown induces premature senescence and reduced differentiation potentials in early-passage MSCs. RB overexpression inhibits senescence and increases differentiation potentials in late-passage MSCs. Expression of DNMT1, but not DNMT3A or DNMT3B, is also higher in early-passage MSCs than in late-passage MSCs. Furthermore, DNMT1 knockdown in early-passage MSCs induces senescence and reduces differentiation potentials, whereas DNMT1 overexpression in late-passage MSCs has the opposite effect. These results demonstrate that RB expressed in early-passage MSCs upregulates DNMT1 expression and inhibits senescence in MSCs. Therefore, genetic modification of RB could be a way to improve the efficiency of MSCs in clinical use

Increased Plasma Circulating Cell-Free DNA Could Be a Potential Marker for Oral Cancer

Background: Oral squamous cell carcinoma (OSCC) is a disease that affects patients worldwide. DNA of dead cells is released into the blood stream and may be isolated from plasma or serum samples. This DNA is termed cell-free DNA (cfDNA). cfDNA is increased in several types of malignancies. We investigated if there was a correlation between cfDNA levels and the progression of OSCC. Methods: Using quantitative spectrometry, we measured plasma cfDNA in 121 patients with OSCC and 50 matched controls. Mann Whitney and Wilcoxon tests were used to compare differences among various clinical variants. Receiver operating characteristic (ROC) analysis was used to obtain levels suitable for the separation of the clinical subsets. Kaplan-Meier analysis was used to assess correlation with survival. Results: Plasma cfDNA was significantly elevated in patients with OSCC relative to controls. Plasma cfDNA levels correlated with larger tumor size, cervical lymph node metastasis and late stage. Higher plasma cfDNA levels were associated with a poor prognosis of OSCC, which is a new finding. Conclusion: Plasma cfDNA could serve as a novel and easily accessible biomarker in OSCC, providing diagnostic and prognostic value

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