Treatment outcomes of adjunctive teriparatide therapy for medication-related osteonecrosis of the jaw (MRONJ): A multicenter retrospective analysis in Japan.

BACKGROUND: Therapeutic strategies for patients with medication-related osteonecrosis of the jaw (MRONJ) remain controversial. The aim of the present study was to clarify the effectiveness and safety of teriparatide therapy in Japanese MRONJ patients based on a large number of case series with a multicenter retrospective analysis. PATIENTS AND METHODS: Between January 2012 and December 2016, 29 patients who were diagnosed with MRONJ at 10 hospitals were treated with teriparatide. The medical records of these patients were retrospectively reviewed to assess the efficacy and safety of teriparatide therapy for MRONJ patients. RESULTS: Adverse events occurred in 17.2% of patients (5/29). One patient developed severe arthralgia and discontinued teriparatide therapy after 12 days, while others continued the treatment. Among 29 patients, the median period of administration of teriparatide was 14.0 months (range, 0.3-26 months), and treatment outcomes were evaluated as effective in 75.9% of patients with complete resolution in 65.5%. Among patients treated with oral bisphosphonates (BPs), 83.3% were effectively treated with teriparatide and 40% with intravenous BPs. The oral administration of BPs was associated with successful treatment outcomes with teriparatide (p = 0.062). CONCLUSIONS: Teriparatide therapy has potential as an effective treatment option for MRONJ.

[A Case of Consciousness Disorder Induced by the Syndrome of Inappropriate Antidiuretic Hormone Secretion Following Cisplatin and 5-Fluorouracil Chemotherapy in a Patient with Tongue Cancer].

We herein report a case of a consciousness disorder that was induced by the syndrome of inappropriate antidiuretic hormone secretion following cisplatin (CDDP) and 5 -fluorouracil (5-FU) chemotherapy in a patient with tongue cancer. A 72- year-old woman complained of tongue pain and was admitted to our hospital for neoadjuvant chemotherapy, under a diagnosis of tongue squamous cell carcinoma (T4aN2bM0). She was treated with CDDP and 5-FU. On the second day after administration, she complained of nausea and anorexia, and on the third day, she showed impaired consciousness. Laboratory studies revealed that the patient had a serum sodium concentration 112mEq/L, and no dehydration was noted. The patient was diagnosed with SIADH, using the appropriate diagnostic criteria based on serum and urine hypoosmolality. We subsequently discontinued chemotherapy and initiated fluid restriction and sodium supplements. Two days after this treatment, her consciousness level improved, and on the fifth day of treatment, laboratory studies revealed a serum sodium level of 134mEq/ L.

A Case of Congenital Mild Hemophilia Diagnosed After Wisdom Teeth Extraction.

Hemophilia A is a recessive congenital deficiency of factor VIII that is characterized by normal bleeding time, normal prothrombin time, and prolonged activated partial thromboplastin time. In moderate and severe cases, abnormal bleeding is observed even after minor trauma, and the diagnosis is usually made by the age of 5-6 years, whereas in mild cases, abnormal bleeding is detected after major trauma or surgery. Herein, we present a case of hemophilia A that was discovered due to difficulties with hemostasis after tooth extraction.

Clinical Characteristics of the Cleft Lip and/or Palate: Association with Congenital Anomalies, Syndromes, and Chromosomal Anomalies.

Background: Cleft lip and/or palate (CL/P) can be accompanied by other congenital anomalies. We conducted a long-term evaluation of the associations between cleft patterns, sex distribution, and accompanying congenital anomalies of patients with CL/P. Methods: The medical records of 739 patients with CL/P, seen between January 1967 and December 2020, were retrospectively reviewed. Fisher's exact test was used for statistical analysis. Results: Among the 739 patients with CL/P, the male-to-female ratio was 1.1. Regarding the cleft pattern, 121 (16.4%), 104 (14.1%), 280 (37.9%), 198 (26.8%), and 36 (4.9%) patients had cleft lip (CL), cleft lip and alveolus (CLA), cleft lip and palate (CLP), cleft palate (CP), and submucous cleft palate (SMCP), respectively. Congenital anomalies were identified in 107 (14.5%) cases, of which 53 (49.5%) had congenital heart disease. The frequencies of congenital anomalies patients with in CL/P were 14/225 (6.2%), 36/280 (12.9%), 43/198 (21.7%), and 14/36 (38.9%) for a combination of CL and CLA, CLP, CP, and SMCP, respectively. Accompanying syndromes and chromosomal anomalies were identified in 40 (5.4%) cases, in which Pierre Robin sequence (16 cases of CP and 4 cases of SMCP) was the most frequent. Conclusion: No sex differences were observed in CL/P, and CLP and CP were the most common cleft patterns. Congenital anomalies associated with CL/P were dominated by congenital heart disease and were most frequently identified in CP and SMCP cases. Notably, the Pierre Robin sequence, a complex syndrome characterized by micrognathia, glossoptosis, respiratory obstruction, and a U- or V-shaped CP, was found in cases of both CP and SMCP, and accounted for the symptoms in most cases.

Development of New Formulas for Sex and Age Estimation by Assessing Maxillary Sinus Morphology on CBCT.

Background: The morphology of the maxillary sinus varies between individuals which could be used in the forensic personal identification process. Methods: In the current study, the CBCT images of the maxillary sinus in 453 patients (217 males, 236 females) aged 14 to 95 years were analyzed. In particular, each left, and right maxillary sinus of the subjects was measured for its maximum height, width, and breadth in 2-D, and volume in 3-D perspectives, and their usefulness for age and sex estimation was examined. Regarding age estimation, because the size of the maxillary sinus increases up to 20s and then decreases over time, two separate age estimation formulas were created, one for subjects in their 14-21 years and the other for those over 22 years old. For each age group, multiple regression formulas were generated using the diameters and volume as explanatory variables and the chronological age as a response variable. This study used 150 cases not included in the study as a validation set for age estimation. Results: Generally, all the diameters and volumes in both sinuses tended to increase till the mid-20s, and then gradually decreased over time. The derived formulas were tested for their accuracy on additional 150 subjects. Plausibly, the model could estimate the age between 14-21 years old with an average accuracy of ± 1.8 years for men and ± 3.2 years for women. Whereas for those over 22 years old, it was possible to estimate the age with an accuracy of ± 11.8 years for males and ± 10.3 years for females, respectively. A comparison of estimated age and chronological age did not show a statistically significant difference(P > 0.05). It was found that the left maxillary sinus had more age groups showing the most significant difference than other measurements between sexes(P < 0.05). The maxillary sinus height may be significantly affected by gender differences. Conclusion: Overall, this study showed the effectiveness of age and sex estimation using the maxillary sinus morphometric analyses.

[Successful outcome from treatment modality with low-dose S-1 for three oldest old patients with advanced oral cancer].

We herein present three oldest old patients with advanced oral cancer for whom low-dose S-1 treatment was effective and improved QOL. The first patient is a 90-year-old female with cancer of the maxilla(T4N0Mx). Because of her generally poor condition, her family did not desire radical therapy. S-1(40mg/m2)was administered for 2 weeks followed by a 1-week interval. Because of a partial response without serious side effects, we increased the dose of S-1 to 50mg/m2. The tumor currently shows a tendency toward reduction. The second patient is a 96-year-old female with cancer of the mandible(T4N0Mx). Because of her old age, her family desired palliative therapy. S-1(40mg/m2)was administered for 2 weeks followed by a 1-week interval. A complete response was obtained at the end of the second course. There has been no recurrence. The third patient is a 94-year-old female with cancer of the maxilla(T3N0M0). Her family selected palliative therapy. S-1(50mg/m2)was administered for 2 weeks followed by a 1-week interval. The tumor size decreased after administration of S-1, without serious side effects. However, the tumor increased after the end of the fifth course. Considering the patient's condition, S-1 administration was discontinued at the end of the eighth course. S-1 is considered to be an effective and safe treatment for the maintenance or improvement of the QOL of old and oldest old patients with advanced oral cancer.

Risk Factors of Free Flap Complications in Reconstruction for Head and Neck Cancer.

Background: Although head and neck reconstruction using free flaps has become a common procedure, flap complications remain a concern. This study aimed to analyze the risk factors of free flap complications and to identify the causes of these complications. Methods: We studied 97 patients with head and neck cancer with intraoral defects who underwent reconstruction using free flaps at Tottori University Hospital between 2011 and 2020. We used a retrospective cohort study design to investigate whether flap complications, including flap necrosis (total and partial) and flap dehiscence, were related to various factors, including the underlying disease condition, treatment status, and surgical factors. Results: Of the 97 patients analyzed, total flap necrosis was observed in one patient (1.0%). The incidence rate of flap complications, including flap necrosis and flap dehiscence, was 29.9%. When the time taken to perform one vascular anastomosis, including preparation of the recipient vessel and flap vessel, exceeded 30 min, the incidence rates of flap necrosis (total and partial) (odds ratio, 8.30; 95% confidence interval, 1.91-36.00; P = 0.005) and flap dehiscence (odds ratio, 3.46; 95% confidence interval, 1.05-11.36; P = 0.041) increased significantly. Conclusion: The time taken to perform one vessel anastomosis was the factor that contributed the most to the incidence of flap complications. Reconstructive surgeons should reduce the incidence of flap complications by keeping the known risk factors of the surgery in mind and by aiming to complete a vascular anastomosis time, including the time taken for the preparation of vessels, of ≤ 30 min per vessel during surgery.

Cytoplasmic-only Expression of Maspin Predicts Poor Prognosis in Patients With Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Maspin has tumor-suppressor functions; however, its prognostic value in patients with oral squamous cell carcinoma (OSCC) remains unknown. We aimed to assess the prognostic importance of the subcellular localization of maspin in patients with OSCC. PATIENTS AND METHODS: Eighty resected specimens were analyzed by immunohistochemistry. Cytoplasmic-only expression observed in >10% of the tumor was defined as maspin-positive. RESULTS: The maspin-positive status (25%) was significantly associated with a higher recurrence rate and shorter disease-free survival (DFS). Cox's multivariate analysis showed that maspin-positive status was an independent factor for shorter DFS. All OSCC cell lines (HSC2, HSC3, HSC4, Ca9-22 and SAS) showed maspin protein localization to both the cytoplasm and nucleus using western blot analysis. In HSC4 cells, cell invasion was significantly increased in response to maspin knockdown. CONCLUSION: Cytoplasmic-only expression of maspin could be an independent poor prognostic factor for patients with OSCC.

Establishment of human immortalized mesenchymal stem cells lines for the monitoring and analysis of osteogenic differentiation in living cells.

Mesenchymal stem cells (MSCs) are expected to be useful in bone regeneration treatment for various diseases and conditions, including cleft lip and palate, fracture, and bone absorption. However, to date, MSCs have failed to produce satisfactory results in clinical settings. This is primarily due to the low rate of induced osteogenic differentiation. To realize MSC potential, it is necessary to establish methods for the isolation of MSC-derived living osteoblasts. However, no osteoblast markers have been reported to date. In an attempt to develop a method for the assessment of osteoblast differentiation, we established reporter human immortalized MSC (hiMSC) lines for in vitro monitoring of bone gamma-carboxyglutamate protein (BGLAP, osteocalcin) expression. To this end, we successfully knocked-in an enhanced green fluorescent protein (EGFP) gene cassette immediately downstream of the first ATG of BGLAP via CRISPR-Cas9, and established hiMSC lines expressing EGFP to monitor osteogenic differentiation. On differentiation day 7, EGFP-positive cells were collected by flow cytometric cell sorting, and the expression of EGFP and endogenous BGLAP was analyzed. During osteogenic differentiation, EGFP upregulation was found to correlate with expression of endogenous BGLAP. Moreover, mineralization was confirmed using Alizarin red-S staining after two weeks of osteogenic differentiation of the modified hiMSC lines. The modified hiMSC lines, as well as the derived differentiated osteoblasts obtained herein, are valuable tools for the monitoring osteoblast gene and protein expression, and can be used to develop novel methods for isolating living osteoblasts.

Clinical Features of Oral Multiple Primary Carcinomas Compared with Oral Single Primary Carcinoma.

BACKGROUND: Owing to the increase in the older population and the increased life span, the number of patients with oral multiple primary carcinomas will increase. Predicting the second and third carcinoma clinically is difficult, and the presence of second or third carcinomas is a factor that determines the prognosis of oral carcinoma. In this study, we examined the clinical features of oral multiple primary carcinomas treated in our department. METHODS: We retrospectively reviewed the medical records of patients with oral squamous cell carcinoma who underwent radical treatment at and were followed by the Department of Oral and Maxillofacial Surgery, Tottori University Hospital from January 2003 to October 2017. RESULTS: This study included 261 patients: 241 patients had oral single primary carcinoma and 20 patients had oral multiple primary carcinomas. Oral multiple primary carcinomas showed female predilection and occurred more frequently in the lower gingiva and significantly less frequently in the tongue (P < 0.01). Oral multiple primary carcinomas showed a significantly higher recurrence rate (P < 0.01). The 5-year overall survival of oral single primary carcinoma patients was 88.0% compared with 95% for oral multiple primary carcinomas, with no significant difference (log rank test, P = 0.54). However, the 15-year survival rate dropped to 28.1% in oral multiple primary carcinomas. The cumulative disease incidence rates of metachronous second primary carcinoma from first carcinoma at 5 years and 10 years were 3.45% and 5.36%, respectively. CONCLUSION: Oral multiple primary carcinomas rarely occur in the tongue. The 5-year survival rate showed no difference between single and multiple carcinoma patients, but over longer observation, the prognosis of multiple carcinoma was poor owing to a high recurrence rate. Because of the high recurrence rate and risk of further metachronous carcinoma in oral multiple primary carcinomas, longer-term follow-up is required.

Bisphosphonate-induced reactive oxygen species inhibit proliferation and migration of oral fibroblasts: A pathogenesis of bisphosphonate-related osteonecrosis of the jaw.

BACKGROUND: The onset mechanism for bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been reported, with a focus on bone remodeling, biofilm formation, and epithelial cell proliferation and migration. However, the involvement of stromal cells, especially fibroblasts, in the oral cavity is unclear. Therefore, this study was focused on how bisphosphonates (BPs) affect orthotopic periodontal ligament fibroblasts from the viewpoint of oxidative stress compared with ectopically obtained fibroblasts. METHODS: Normal human periodontal ligament fibroblasts (HPdLFs) and normal human dermal fibroblasts (NHDFs) were used to gain insight into the functional differences in sensitivity and reactions to BPs. Cell growth assay, measurement of reactive oxygen species (ROS) and nitric oxide (NO) production, and wound-healing assay in vitro were performed. Maxillary first molars were extracted in C57BL/6 mice and either BP, N-acetyl-cysteine (NAC), and BP or saline were administered. RESULTS: BP-induced IC50 values were significantly lower in HPdLFs (30.6 µM) than in NHDFs (109.7 µM). BP resulted in an increase in ROS, but not NO generation in HPdLFs. BPs also inhibited proliferation and migration of HPdLFs but not NHDFs, while the addition of a ROS inhibitor, NAC, reversed those inhibitions. A BRONJ mouse model in which BP was administered and then the tooth was extracted, impaired wound healing of the socket was observed. When NAC was administered before tooth extraction, wound healing was significantly improved. CONCLUSION: These results suggest that BP causes fibroblasts obtained from the oral cavity but not from skin to generate ROS and that the subsequent ROS-mediated inhibition of fibroblast growth and migration definitely delays wound healing, thereby contributing to BRONJ pathogenesis.

Study on the Development of a New Device with Dual Cameras for Evaluating Expiratory Nasal Flow.

BACKGROUND: Use of the Glatzel mirror for measuring expiratory nasal flow in preschool children has the disadvantage of vagueness, and the mirror may induce fear and inhibition of interest in those children. In response to these limitations, we developed a new device with dual cameras for measuring expiratory nasal flow in 2 to 6 year old children. The aim of this study is to compare the Glatzel mirror and the new device, in terms of accurate assessment of expiratory nasal flow, children's feelings, and correlation to each child's profile. METHODS: This study evaluated 20 cleft lip and palate patients and 21 healthy children aged between 2 and 6 (under 7) years. After consent was granted, a 4-week screening period was undertaken followed by inspection at weeks 8, 16, 24, and 32. Each inspection was conducted while the children were asked to pronounce various sounds and comprised three stages: i) use of the Glatzel mirror, ii) subjective visual assessment using the new device, and iii) image recording by dual cameras of the new device. Questionnaires for the new device were administered at the initial and final inspections. To contrast the results between the Glatzel mirror and the new device, the numbers that indicated values of subjective visual assessment and camera assessment greater than the assessment values of the Glatzel mirror were compared. For measuring the children's responses to the new device compared with those to the Glatzel mirror, the answers to the questionnaires were compared. For the comparison of the children's profiles (age and sex) and feelings, the numbers of subjects who could use the new device were measured. RESULTS: The camera assessment of the new device indicated significantly greater values than that of the Glatzel mirror (P < 0.05). The feelings of the subjects to the new device mostly improved as the study progressed. Subjects aged 3 years and older were generally able to use the new device from the initial inspection. For both sexes, as the inspection progressed, the number occasions of successful use increased. CONCLUSION: This study demonstrated the superiority of the new device with dual cameras to the Glatzel mirror in terms of functionality and attitude of children.

Effects of oral consumption of the green tea polyphenol EGCG in a murine model for human Sjogren's syndrome, an autoimmune disease.

SIGNIFICANCE: Protection of glandular cells from autoimmune-induced damage would be of significant clinical benefit to Sjogren's syndrome (SS) patients. Epigallocatechin-3-gallate (EGCG) possesses anti-apoptotic, anti-inflammatory, and autoantigen-inhibitory properties. AIMS: To investigate if EGCG protects against certain autoimmune-induced pathological changes in the salivary glands of the non-obese diabetic (NOD) mouse model for SS. MAIN METHODS: Animals were provided with either water or water containing 0.2% EGCG. At the age of 8, 16 and 22 weeks, submandibular salivary gland tissue and serum samples were collected for pathological and serological analysis. KEY FINDINGS: Significant lymphocyte infiltration was observed in the salivary glands of the water-fed group at the age of 16 weeks, while the EGCG group showed reduced lymphocyte infiltration. By 22 weeks of age, water-fed animals demonstrated elevated levels of apoptotic activity within the lymphocytic infiltrates, and high levels of serum total anti-nuclear antibody, compared to EGCG-fed animals. Remarkably, proliferating cell nuclear antigen (PCNA) and Ki-67 levels in the salivary glands of water-fed NOD mice were significantly elevated in comparison to BALB/c control mice; in contrast, PCNA and Ki-67 levels in EGCG-fed NOD animals were similar to BALB/c mice. These results indicate that EGCG protects the NOD mouse submandibular glands from autoimmune-induced inflammation, and reduces serum autoantibody levels. Abnormal proliferation, rather than apoptosis, appears to be a characteristic of the NOD mouse gland that is normalized by EGCG. The evidence suggests that EGCG could be useful in delaying or managing SS-like autoimmune disorders.

Runt-related transcription factor 3 expression in human oral squamous cell carcinomas; implication for tumor progression and prognosis.

Runt-related transcription factor 3 (RUNX3) is a tumor suppressor factor of gastric cancer and appears to be an important component of the transforming growth factor-beta (TGF-beta)-induced tumor suppression pathway. This study aimed to analyze the expression of the RUNX3 protein in human oral normal epithelia, dysplasia and squamous cell carcinomas (SCCs), comparing it with clinicopathological profiles. Western blot analysis revealed the RUNX3 protein as a single band at 44kDa in oral non-neoplastic mucosa and SCC. The expression of RUNX3 protein was also examined in 10 normal epithelia, 51 dysplasias and 108 oral SCCs. The labeling indices (LIs) of RUNX3, Ki-67, P21, P27 and the apoptotic index (AI) were evaluated using immunohistochemistry and the TUNEL method. The LI of RUNX3 was 7.7+/-1.6 in the normal epithelia, 20.8+/-2.7 in the dysplasias and 9.0+/-1.3 in the SCCs. The LI of RUNX3 was significantly highest in the dysplasias, followed by the SCCs (p<0.05) and normal epithelia (p<0.05). The RUNX3 LI correlated with the histological differentiation of SCCs, being the highest in the well differentiated SCCs (p<0.01). In addition, RUNX3 expression was significantly related to the lower Ki-67 LI, but not to LI of P21 and P27, and AI in the SCCs. The survival rate was significantly lower in the patients with lower RUNX3 expression (<5%) than in those with higher expression (5%) (p<0.05). These results indicate that the expression of RUNX3 is correlated with histological differentiation, and inversely with cellular proliferation of the oral SCCs, and might be a new prognostic marker in the patients with oral SCC.

Palonosetron Prevents Highly Emetogenic Chemotherapy-induced Nausea and Vomiting in Oral Cancer Patients.

BACKGROUND/AIM: To evaluate the efficacy of palonosetron in preventing acute and delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC) in oral cancer patients. PATIENTS AND METHODS: Oral cancer patients receiving HEC were enrolled; among the 40 patients, 87 courses of chemotherapy were administered. On day 1, 0.75 mg palonosetron was intravenously administrated just before chemotherapy. RESULTS: The primary endpoint was the proportion of patients with a complete response (CR) and the secondary endpoint was the proportion of patients with complete control (CC) during the acute and delayed phase. During the acute phase, 86 of 87 courses (98.9%) had CR and 84 of 87 courses (96.6%) had CC. During the delayed phase, 84 of 87 courses (96.6%) had CR and 70 of 87 courses (80.5%) had CC. CONCLUSION: Palonosetron is effective at preventing HEC-induced chemotherapy-induced nausea and vomiting (CINV) in oral cancer chemotherapeutic regimens in the acute and delayed phases.

Associations between Systemic Markers of Bone Turnover or Bone Mineral Density and Anti-Resorptive Agent-Related Osteonecrosis of the Jaw in Patients Treated with Anti-Resorptive Agents.

BACKGROUND: Some previous studies have examined anti-resorptive agent-related osteonecrosis of the jaw (ARONJ) prediction using systemic markers of bone turnover as risk factors. Radiographic imaging is also effective at detecting ARONJ. In this study, computed tomography (CT)-derived bone mineral density (BMD) values and the levels of systemic markers of bone turnover were evaluated, and then each parameter was compared between patients that developed ARONJ and those who did not after treatment with systemic anti-resorptive agents. The aim of this study was to determine whether systemic markers of bone turnover and/or BMD values can be used to predict the risk of ARONJ. METHODS: The subjects' serum levels of cross-linked N-terminal telopeptide of type I collagen (NTX) and bone alkaline phosphatase (BAP) (systemic markers of bone turnover) were measured. BMD was calibrated to CT values using a medical imaging phantom. Then, the subjects' BMD were assessed using quantitative computed tomography. Fifty-six patients who had received systemic anti-resorptive agents were included in this study. Thirty-two of the patients developed ARONJ after receiving the drugs whereas the remaining 24 did not. RESULTS: No correlation was observed between the serum levels of the systemic markers of bone turnover and the incidence of ARONJ. On the other hand, the ARONJ patients exhibited higher mandibular BMD values than the control group. BMD was not associated with healing or the clinical stage of ARONJ. CONCLUSION: These results suggest that increased mandibular BMD values are associated with ARONJ. Furthermore, mandibular BMD might serve as a novel marker for predicting the risk of ARONJ in patients that are taking anti-resorptive agents and are about to undergo tooth extraction. Accordingly, mandibular BMD could be a useful tool for aiding risk assessments and guiding treatment decisions.

A novel PAX3 mutation in a Japanese boy with Waardenburg syndrome type 1.

Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant disorder characterized by hair hypopigmentation, abnormal iris pigmentation, and congenital hearing loss. WS1 is caused by mutations in paired box gene 3 (PAX3). We identified a novel PAX3 mutation (c.1107 C>G, p.Ser369Arg) in a Japanese WS1 patient showing abnormal right iris pigmentation, right-sided congenital hearing loss, synophrys, incomplete left cleft lip, and cryptorchidism.

Cyclo-oxygenase-1 and -2 expression in human oral mucosa, dysplasias and squamous cell carcinomas and their pathological significance.

Cyclo-oxygenase (COX) is a key enzyme in the conversion of arachidonic acid to prostanoids. The expression of its isoforms, COX-1 and -2 is found in many human malignancies. This study analyzed the correlation between COX expression and the pathobiological nature of human oral mucosa, dysplasias and squamous cell carcinomas (SCCs). We examined 9 specimens of normal oral epithelia, 65 lesions with dysplasias and 50 SCCs. Labeling indices (LIs) for COX-1, COX-2, Ki-67 and P53, microvessel density (MVD) and apoptotic index (AI) were evaluated using immunohistochemistry and TUNEL methods. Western blot analysis of COX-1 and -2 was performed on four human oral SCC cell lines, all of which showed expression. The LIs for COX-1 and -2 were higher for the dysplasias than the SCCs. LIs of COX-2 but not COX-1 correlated with the histological grade of dysplasia, being highest for the severe dysplasias (p < 0.05). In contrast, the COX-2 LIs as well as COX-1 were significantly (p < 0.05) inversely correlated with the histological differentiation of the SCCs. COX-2 expression was significantly correlated with LIs of COX-1 for dysplasia (p < 0.05), but not for the SCCs. In addition no significant relationship was noted between COX-2 expression and the Lis of Ki-67, P53, AI as well as MVD for the dysplasias and SCCs. The expression of COX-1 and -2 is correlated with early stage tumorigenesis and cellular differentiation of SCCs in the oral dysplasia-carcinoma sequence.

The Effect of Bamboo Leaf Extract Solution and Sodium Copper Chlorophyllin Solution on Growth and Volatile Sulfur Compounds Production of Oral Malodor Associated Some Anaerobic Periodontal Bacteria.

BACKGROUND: Bamboo leaf extract solution (BLES) and sodium copper chlorophyllin solution (SCCS) are known for their anti-oxidant activities. Oral malodor is often related with periodontal pathogens. The present study was undertaken to investigate the anti-bacterial effect of both BLES and SCCS on anaerobic periodontal bacteria producing oral malodorous volatile sulfur compounds (VSC). METHODS: Porphyromonas gingivalis W83 (PG), Prevotella intermidai TDC19B (PI), Fusobacterium nucleatum ATCC25586 (FN) and Prevotella nigrescence ATCC33563 (PN) were investigated as oral isolated bacteria. VSC production ability of the oral strains was investigated by gas chromatography. With serial dilution of BLES or SCCS, the strains PG, PI, FN or PN were cultured anaerobically with AnaeroPack at 37 ℃ for 3 days. For the determination of anti-bacterial action of BLES or SCCS, the inoculum was cultured with original concentrations of BLES 0.16% (w/v) or SCCS 0.25% (w/v). RESULTS: Gas chromatography exhibited that all strains, PG, PI, FN and PN were responsible for producing a high range of H2S and a moderate range of CH3SH. Anti-bacterial effect of BLES or SCCS on the strains was observed. Inhibition of BLES or SCCS on the strains was revealed as concentration dependent. BLES or SCCS inhibited bacterial proliferation at higher concentrations (PG; 0.04% BLES or 0.03% SCCS, PI; 0.002% BLES or 0.03% SCCS, FN; 0.005% BLES or 0.01% SCCS, PN; 0.01% BLES or 0.015% SCCS). No viable bacterial colony observed at original concentration of BLES 0.16% or SCCS 0.25%. Strain growth was eliminated from inhibition at lower concentrations (PG; 0.02% BLES or 0.015% SCCS, PI; 0.001% BLES or 0.015% SCCS, FN; 0.002% BLES or 0.007% SCCS, PN; 0.005% BLES or 0.007% SCCS). CONCLUSION: High concentrations of both BLES (0.16%) and SCCS (0.25%) show superior inhibiting capability on all four oral malodor associated periodontal anaerobes during testing, suggesting that these compounds might have a beneficial effect on oral health care.

Low prevalence of Merkel cell polyomavirus with low viral loads in oral and maxillofacial tumours or tumour-like lesions from immunocompetent patients: Absence of Merkel cell polyomavirus-associated neoplasms.

It was recently demonstrated that ~80% of Merkel cell carcinomas (MCCs) harbour a novel polyomavirus, Merkel cell polyomavirus (MCPyV). MCPyV has been detected in various human tissue samples. However, previous studies on the prevalence of MCPyV in oral tumours or tumour-like lesions are incomplete. To address this issue, we measured MCPyV DNA quantity using quantitative polymerase chain reaction (qPCR) in 327 oral tumours or tumour-like lesions and 54 jaw tumours or cyst lesions from 381 immunocompetent patients, as well as in 4 oral lesions from 4 immunosuppressed patients. qPCR revealed a low MCPyV prevalence (25/381, 6.6%) with low viral loads (0.00024-0.026 copies/cell) in oral and maxillofacial tumours and tumour-like lesions from immunocompetent patients. The prevalence was 7/176 (4.0%) in invasive squamous cell carcinomas (SCCs) [2/60 (3.33%) SCCs of the tongue, 4/52 (7.7%) SCCs of the gingiva and 1/19 (5.3%) SCCs of the floor of the mouth], 1/10 (10%) in dysplasias, 1/5 (20%) in adenocarcinomas, 2/13 (15.4%) in adenoid cystic carcinomas, 1/10 (10%) in non-Hodgkin's lymphomas, 3/10 (30%) in lipomas, 3/5 (60%) in neurofibromas, 1/3 (33.3%) in Schwannomas, 2/12 (16.7%) in Warthin's tumours, 2/11 (18.2%) in pyogenic granulomas, 1/14 (7.1%) in radicular cysts and 1/12 (8.3%) in ameloblastomas. The prevalence in lesions from immunosuppressed patients (1/4, 25%) was higher compared with that in lesions from immunocompetent patients (25/381, 6.6%), but the difference was not statistically significant. To the best of our knowledge, this study was the first to report prevalence data of MCPyV in tumours and cysts of the jaws (2/54, 3.7%). These data indicated absence of MCPyV-related tumours or tumour-like lesions in the oral cavity and jaws and suggested that the detected MCPyV DNA was derived from non-neoplastic background tissues with widespread low-level MCPyV infection.