Immunoexpression of SIRT1, 6, and 7 in oral leukoplakia and oral squamous cell carcinoma.

Sirtuins (SIRTs) are a family of proteins involved in the metabolic process responsible for extending the lifespan. The role of SIRT1, 6, and 7 in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OLP), one of its precursors, is still elusive. In this study, 82 OLP and 77 OSCC were immunohistochemically examined for SIRT1, 6, and 7. Stained sections were thoroughly scanned and evaluated using a digital image analysis program. The SIRT1, 6, and 7 expressions were detected in the nuclei of epithelial and carcinoma cells in various degrees. Afterward, any correlations among SIRTs, including associations with clinicopathological features and the Kaplan-Meier curves were analyzed. OSCC demonstrated significantly higher SIRT1 expression than OLP, while non-dysplastic lesions showed significantly higher SIRT6 expression than other lesions. A strong correlation was observed between SIRT6 and 7 in OLP, SIRT1 and 6 in in OSCC and in SIRT6 and 7 when all lesion types were considered. There were no significant differences between SIRTs reactivity and the clinical features in OLP. For OSCC, SIRT1 and 6 was found to be directly associated with site of the lesion, while SIRT7 showed a direct relationship between gender, stromal lymphocytic infiltration, and depth of the invasion. OSCC with high SIRT7 expression revealed a slightly lower survival probability, although not statistically significant (p = 0.1019). Our findings suggest that SIRT1, 6, and 7 may play correlated and diverse roles in the development and advancement of OSCC.

Myeloid-derived suppressor cells and plasmacytoid dendritic cells are associated with oncogenesis of oral squamous cell carcinoma.

Myeloid-derived suppressor cells (MDSCs) help establish the tumor microenvironment by suppressing T-cell response in tumor-bearing hosts. Plasmacytoid dendritic cells (pDCs) activate antigen-specific T cells, thereby, maximizing their antitumor effects. IDO1 is associated with both MDSCs and pDCs and plays a major role in the formation of the tumor-mediated immunosuppressive environment. We utilized immunohistochemistry to examine the involvement of IDO1 in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs, precancerous lesions). We examined the expression of MDSC markers, CD11b and CD33, as well as pDC markers, CD303 and IDO1, in 60 OSCC and 45 precancerous lesion specimens and analyzed their association with clinicopathological parameters. Expression of these biomarkers identifying MDSCs and pDCs was high in precancerous lesions in patients with severe dysplasia and OSCC. While detecting pDCs, high CD303 and IDO1 expression levels were frequently observed in moderately or poorly differentiated OSCCs. CD11b, CD33, and CD303 levels were significantly correlated with the mode of invasion; CD33 was correlated with OSCC invasion depth while the other three markers tended to be highly expressed in superficial cancer cases showing microinvasion. Expression levels of all four biomarkers were significantly associated with the cancerization of OPMDs to OSCCs. We show, for the first time, that the infiltration of MDSCs and pDCs is significantly associated with progression of premalignant lesions to OSCC. This suggests that these cells may act as prognostic biomarkers for premalignant lesion progression and that immunotherapeutic approaches that control each of these immunosuppressive cells may protect against progression to malignancy.

Effect of Octacalcium Phosphate Crystals on the Osteogenic Differentiation of Tendon Stem/Progenitor Cells In Vitro.

Synthetic octacalcium phosphate (OCP) activates bone tissue-related cells, such as osteoblasts, osteoclasts, and vascular endothelial cells. However, the effect of OCP on tendon-related cell activation remains unknown. This study examined the response of rat tendon stem/progenitor cells (TSPCs) to OCP and related calcium phosphate crystals in vitro. TSPCs were cultured with OCP and Ca-deficient hydroxyapatite (CDHA) obtained from the original OCP hydrolysis to assess the activity of alkaline phosphatase (ALP) and the expression of osteogenesis-related genes. Compared with CDHA, the effect of OCP on promoting the osteogenic differentiation of TSPCs was apparent: the ALP activity and mRNA expression of RUNX2, Col1a1, OCN, and OPN were higher in OCP than in CDHA. To estimate the changes in the chemical environment caused by OCP and CDHA, we measured the calcium ion (Ca2+) and inorganic phosphate (Pi) ion concentrations and pH values of the TSPCs medium. The results suggest that the difference in the osteogenic differentiation of the TSPCs is related to the ionic environment induced by OCP and CDHA, which could be related to the progress of OCP hydrolysis into CDHA. These results support the previous in vivo observation that OCP has the healing function of rabbit rotator cuff tendon in vivo.

14 Years On: A Clinical Case Report of an 86-Year-Old Patient With Full Arch Implant-Supported Restorations With Auro Galvano Crown Attachments.

Oral reconstruction in fully edentulous patients can be challenging at times. Hence, it is important to offer the most suitable treatment option after a detailed clinical examination and treatment plan. This 14-year long-term follow-up report is the clinical case of a 71-year-old nonsmoker who visited the clinic in 2006 and opted for full-mouth reconstruction using Auro Galvano crown (AGC) attachments. Maintenance was performed twice a year for the past 14 years, and the clinical results were satisfactory, with no signs of inflammation or lack of retention of the superstructures. This was associated with a high level of patient satisfaction, as indicated by the Oral Health Impact Profile. Compared to the screw-retained implants over dentures, AGC attachments can be a viable and effective treatment option when restoring fully edentulous arches.

A case of synchronous double cancers consisting of maxillary gingival carcinoma and intraductal papillary mucinous carcinoma, invasive: case report.

BACKGROUND: The development of synchronous multiple primary cancers is one of the major causes of death in patients with head and neck cancer. Herein, we report a case of synchronous intraductal papillary mucinous carcinoma (IPMC), invasive in a patient with maxillary gingival carcinoma. CASE PRESENTATION: A 73-year-old female visited our hospital complaining of a mass on the left side of the maxillary gingiva. Intraorally, an exophytic tumor, 50 × 25 mm in size, was found on the gingiva of the left maxillary posterior, and a diagnosis of squamous cell carcinoma was revealed by cytology. Emission tomography/ computed tomography with 18 Fluorodeoxyglucose-Positron (18FDG- PET/ CT) showed increased accumulation in the left maxillary gingiva, the left side of cervical lymph nodes, and the main pancreatic duct. The pancreatic ductal tumor was performed the biopsy at esophagogastroduodenoscopy (EGD) and resulted in a pathological diagnosis of IPMC, invasive. The patient was diagnosed as synchronous double primary cancers consisting of maxillary gingival carcinoma cT4aN2bM0 and IPMC, invasive cT3N0M0. She refused radical treatment, and died 11 months later. CONCLUSION: 18FDG- PET/ CT, EGD and multidisciplinary approach is required for the detection and determining the treatment strategy of synchronous double primary cancers.

Histamine acts via H4-receptor stimulation to cause augmented inflammation when lipopolysaccharide is co-administered with a nitrogen-containing bisphosphonate.

OBJECTIVE AND METHODS: Nitrogen-containing bisphosphonates (NBPs, anti-bone-resorptive agents) have inflammatory side-effects. Alendronate (Ale, an NBP) intradermally injected into mouse ear-pinnae together with LPS (bacterial cell-wall component) induces augmented ear-swelling that depends on IL-1 and neutrophils. Using this model, we examined histamine's involvement in Ale + LPS-induced inflammation. RESULTS: Ale increased histamine in ear-pinnae by inducing histidine decarboxylase (HDC). This induction was augmented by LPS. In HDC-deficient mice, such augmented ear-swelling was not induced. At peak-swelling, 74.5% of HDC-expressing cells were neutrophils and only 0.2% were mast cells (MCs). The augmented swelling was markedly reduced by a histamine H4-receptor (H4R) antagonist, but not by an H1R antagonist. In MC-deficient mice, unexpectedly, Ale + LPS induced prolonged ear-swelling that was augmented and more persistent than in normal mice. MCs highly expressed H4Rs and produced MCP-1(inflammatory cytokine that recruits macrophages) and IL-10 (anti-inflammatory cytokine) in response to an H4R agonist. CONCLUSION: Histamine produced by HDC-induction mainly in infiltrated neutrophils stimulates H4Rs, leading to augmented Ale + LPS-induced ear-swelling via MCP-1 production by MCs. Since MCP-1 is produced by other cells, too, the contribution of MCs and their H4Rs to augmented ear-swelling is partial. In the later phase of the swelling, MCs may be anti-inflammatory via IL-10 production.

Radiologic Risk Factors for Persistent Mandibular Nerve Neurosensory Disturbance Following Sagittal Split Osteotomy.

PURPOSE: Neurosensory disturbance (NSD) occurring in the lower lips and chin is a major postoperative complication related to bilateral sagittal split osteotomy (SSO). The purpose of this study is to identify preoperative radiographic findings following SSO procedure associated with persistent NSD. METHODS: This retrospective cohort study analyzed data for consecutive patients who underwent SSO. Primary predictor variables, including ramus width, mandibular body height, mandibular angle length, gonial angle, distance from mental foramen to distal aspect of mandibular second molar (MFD), and measurement of bone marrow space (BMS), were examined in a series of radiographic images. The primary outcome variable was NSD. Patients with NSD were divided into 2 groups based on findings obtained 1 year postoperatively: persistent, for those with NSD remaining after 1 year, and transient, when NSD occurred for less than 1 year. Covariates included sex and age. Comparisons were analyzed by use of Mann-Whitney U test or χ2 test. Multivariate analysis was performed using step-wise logistic regression to determine significant factors related to persistent NSD. A P value .005 or less was considered statistically significant. RESULTS: Of the 349 sides investigated, the persistent NSD group consisted of 59 sides (16.9%), while the transient NSD group consisted of 290 sides (83.1%). The occurrence of persistent NSD was correlated with age (P < .05), MFD (P < .001), mandibular body height (P < .05), and BMS (P < .001). Multivariate logistic analysis also showed a significant association of MFD (P < .001) and BMS (P < .001). CONCLUSIONS: Preoperative MFD and BMS are radiographic findings that are associated with an increased risk for persistent NSD following SSO procedure.

Medical-Dental Collaboration and Interprofessional Training for Maxillofacial Diseases at Tohoku University Hospital.

The Tohoku University Hospital has been a clinical and research facility for all the related departments of Tohoku University. Medical-dental and interprofessional collaboration has resulted in special treatment teams, made up of members of departments such as the center for head and neck cancer, the center for dysphagia, and the cleft lip and palate center. Those treatment teams held conferences, case study meetings, reading sessions, and in-hospital seminars. The purpose of this study was to evaluate the outcomes of various medical-dental and the interprofessional collaboration at Tohoku University Hospital and training program to equip hospital dentists in higher medical institutions. The attainment targets are the acquisition of basic medical skills and knowledge under the guidance of supervising doctors. As a result, the hospital dentists could acquire their own specialized knowledge and skills certificated by each academic society. The smooth team treatment has been achieved, and the number of cases discussed by cancer boards and center for dysphagia has increased year by year due to the efficiency of their clinical pathways. On the dental care side as well, the wearing rates of maxillofacial prosthetic devices such as maxillofacial prostheses and palatal augmentation prostheses (PAP) have improved, which have contributed to improving patient's stomatognathic function. Tohoku University Hospital has been practicing collaboration between medical and dental professionals and it has produced mutual benefits. Our interprofessional training system based on the medical-dental collaboration could develop professionals who have acquired cross-disciplinary knowledge and skills from experienced doctors.

Angio-osteogenic capacity of octacalcium phosphate co-precipitated with copper gluconate in rat calvaria critical-sized defect.

The objective of this study is to investigate the effects of octacalcium phosphate (OCP)-induced bone regeneration on angiogenesis regulated by the inclusion of copper ions in OCP in vitro and in vivo. Calcium (Ca)-deficient Cu-OCPs, containing 0.01 wt% Cu (low-Cu-OCP) and 0.12 wt% Cu (high-Cu-OCP), were synthesized with co7pper gluconate salt. The lattice parameters of Cu-OCPs tended to decrease slightly with Cu inclusion, as estimated by Rietveld analysis. Cu ions were released in OCP when the materials were incubated in the medium for human umbilical vein endothelial cells (HUVECs). The solubility of Cu-OCPs, estimated by the degree of supersaturation, was slightly higher than that of the original OCP. Cu-OCP tended to hydrolyze to an apatite structure while maintaining the crystal plate-like morphology when incubated with mesenchymal stem D1 cells in osteogenic media for 14 days. The specimens were characterized by selected area electron diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy. Low-Cu-OCP significantly enhanced the HUVEC capillary cross-linking density. D1 cell differentiation was inhibited with the inclusion of Cu, even at low concentrations. The composite of low-Cu-OCP with a gelatin sponge (low-Cu-OCP/Gel) significantly enhanced angiogenesis coupled with bone regeneration when implanted in a rat calvarial critical-sized defect for 4 weeks, compared with the corresponding amount of Cu-containing Gel (Cu/Gel) or OCP/Gel materials through angiography and tissue histomorphometry. These results support the proposition that angiogenesis stimulated by low-Cu-OCP is closely related with enhanced bone regeneration.

Wound healing effect of autologous fibrin glue and polyglycolic acid sheets in a rat back skin defect model.

Fibrin glue from autologous plasma may prevent viral infection and allergic reaction. Moreover, this biomaterial contains growth factors such as TGF-ß and VEGF that promote reconstruction of the mucous membrane by stimulating fibroblast proliferation and angiogenesis. Thus, autologous fibrin glue is predicted to improve healing better than commercial fibrin glue. Here, we evaluated the effects of autologous fibrin glue on the crucial early phase of wound healing. Epithelial defects were introduced in rats and covered with polyglycolic acid (PGA) sheets with or without commercial or autologous fibrin glue. Wound healing was assessed for six weeks by histology and immunohistochemistry. Our results demonstrate that wounds covered with PGA sheets and autologous fibrin glue achieved efficient wound healing without complications such as local infection or incomplete healing. The rate of recovery of the regenerating epithelium in this group was superior to that in wounds covered with PGA sheets and commercial fibrin glue. Immunohistochemistry of laminin, cytokeratin, and VEGF confirmed fine and rapid epithelial neogenesis. Collectively, our results indicate that covering surgical wounds with autologous fibrin glue promotes wound healing and epithelialization, improves safety, and reduces the risks of viral infection and allergic reaction associated with conventional techniques.

Release of Nitrogen-Containing Bisphosphonates (NBPs) from Hydroxyapatite by Non-NBPs and by Pyrophosphate.

Bisphosphonates (BPs) are major anti-bone-resorptive drugs. Among them, the nitrogen-containing BPs (NBPs) exhibit much stronger anti-bone-resorptive activities than non-nitrogen-containing BPs (non-NBPs). However, BP-related osteonecrosis of the jaw (BRONJ) has been increasing without effective strategies for its prevention or treatment. The release of NBPs (but not non-NBPs) from NBP-accumulated jawbones has been supposed to cause BRONJ, even though non-NBPs (such as etidronate (Eti) and clodronate (Clo)) are given at very high doses because of their low anti-bone-resorptive activities. Our murine experiments have demonstrated that NBPs cause inflammation/necrosis at the injection site, and that Eti and Clo can reduce or prevent the inflammatory/necrotic effects of NBPs by inhibiting their entry into soft-tissue cells. In addition, our preliminary clinical studies suggest that Eti may be useful for treating BRONJ. Notably, Eti, when administered together with an NBP, reduces the latter's anti-bone-resorptive effect. Here, on the basis of the above background, we examined and compared in vitro interactions of NBPs, non-NBPs, and related substances with hydroxyapatite (HA), and obtained the following results. (i) NBPs bind rapidly to HA under pH-neutral conditions. (ii) At high concentrations, Eti and Clo inhibit NBP-binding to HA and rapidly expel HA-bound NBPs (potency Eti>>Clo). (iii) Pyrophosphate also inhibits NBP-binding to HA and expels HA-bound NBPs. Based on these results and those reported previously, we discuss (i) possible anti-BRONJ strategies involving the use of Eti and/or Clo to reduce jawbone-accumulated NBPs, and (ii) a possible involvement of pyrophosphate-mediated release of NBPs as a cause of BRONJ.

A Follow-Up Study on the Clinical Outcomes of Alveolar Reconstruction Using Octacalcium Phosphate Granules and Atelocollagen Complex.

PURPOSE: To observe the long-term postoperative bone formation and eruption of adjacent teeth after octacalcium phosphate granule and atelocollagen complex (OCP/Col) grafting in the treatment of alveolar cleft of patients with unilateral cleft lip with or without cleft palate (UCL ± P). METHODS: Four patients with UCL ± P who underwent OCP/Col grafting (OCP group), and 55 patients with UCL ± P who underwent autologous bone grafting (AB group) were enrolled in this study. OCP/Col or autologous bone grafting was performed before the eruption of canines or lateral incisors in mixed dentition, followed by orthodontic management. Patients in the OCP group underwent radiography before and after surgery at 1, 2, 3, 6, and over 30 months postoperatively. The volume and area of the bony defect in the alveolar cleft area were compared between the OCP and AB groups before and after 6 months of surgery. RESULTS: The bone bridge in all patients in the OCP/Col group was successfully formed, and by 6 months postoperatively, the permanent teeth adjacent to the alveolar cleft had erupted at the site of the OCP/Col complex graft. Comparison of the pre- and postoperative bone defects between the 2 groups revealed almost the same extent of bone bridge formation. CONCLUSIONS: OCP/Col grafting could be considered as an alternative to autologous bone grafting as it yielded successful bone bridge formation and facilitated permanent tooth eruption.

Bone Tissue Response to Different Grown Crystal Batches of Octacalcium Phosphate in Rat Long Bone Intramedullary Canal Area.

The microstructure of biomaterials influences the cellular and biological responses in the bone. Octacalcium phosphate (OCP) exhibits higher biodegradability and osteoconductivity than hydroxyapatite (HA) during the conversion process from OCP to HA. However, the effect of the microstructure of OCP crystals on long tubular bones has not been clarified. In this study, two types of OCPs with different microstructures, fine-OCP (F-OCP) and coarse-OCP (C-OCP), were implanted in rat tibia for 4 weeks. F-OCP promoted cortical bone regeneration compared with C-OCP. The osteoclasts appearance was significantly higher in the C-OCP group than in the control group (defect only) at 1-week post-implantation. To investigate whether the solubility equilibrium depends on the different particle sizes of OCPs, Nano-OCP, which consisted of nanometer-sized OCPs, was prepared. The degree of supersaturation (DS) tended to decrease modestly in the order of C-OCP, F-OCP, and Nano-OCP with respect to HA and OCP in Tris-HCl buffer. F-OCP showed a higher phosphate ion concentration and lower calcium ion concentration after immersion in the buffer than C-OCP. The crystal structures of both OCPs tended to be converted to HA by rat abdominal implantation. These results suggest that differences in the microstructure of OCPs may affect osteoclastogenesis and result in osteoconductivity of this material in long tubular bone by altering dissolution behavior.

Mandible fractures and dental injuries related to road traffic accidents over a 12-year period-Retrospective multicentre study.

BACKGROUND/AIM: Road traffic accidents (RTAs) are a common cause of maxillofacial injuries. The aim of this retrospective multicentre study was to investigate the characteristics of maxillofacial fractures and dental injuries that occurred in RTAs in Miyagi, Japan. MATERIALS AND METHODS: The records of 404 patients with maxillofacial injuries treated at the Oral and Maxillofacial Surgery Departments of four different institutions over a period of 12 years were analysed. Ninety-nine of these patients had suffered these injuries in an RTA. RTA-related cases were divided according to age, gender, presentation month, presentation day of the week, transportation mode, time of accident, fracture sites and fracture mechanism. RESULTS: There were 72 males and 27 females who suffered injuries as the result of an RTA, for a male-to-female ratio of 2.7:1.0, with a mean age of 35.3 years (range, 1-86 years old). Most of the accidents occurred in June and on a Wednesday, and most of the affected patients were riding a bicycle at the time. The number of patients with maxillofacial injuries related to bicycle riding showed an increasing trend in recent years. Mandible fractures were the most prevalent, followed by dental injuries and maxilla fractures. In cases with a single fracture of the mandible, the symphysis was the most frequent site, while in those with multiple fractures, the association of symphysis and bi-lateral condyle fractures was the greatest. For bicycle-related accidents, a single fracture in the mandible occurred more often than multiple fractures. CONCLUSIONS: The number of RTA-related injuries while bicycle riding showed an increasing trend with mandible fractures commonly seen in those cases. Efforts to reduce maxillofacial injuries related to bicycle accidents are needed.

Influence of oestrogen deficiency and excessive mechanical stress on condylar head of mandible.

OBJECTIVE: We assessed the aetiology of idiopathic condylar resorption by examining the effects of oestrogen and compressive mechanical stress under a low systemic oestrogen condition in temporomandibular joints (TMJ) caused by an ovariectomy. MATERIALS AND METHODS: Female rabbits were divided into non-ovariectomy (non-OVX) and ovariectomy (OVX) groups. A cortical osteotomy was performed with a custom device that was increased in length by 0.25 mm every 12 hr for 1 week after the operation, during which the TMJs in the rabbits received compressive mechanical stress. Samples from both groups were examined with micro-computed tomography and histological staining. RESULTS: Area and depth of bone resorption were both greater in the OVX group. Furthermore, a significantly earlier and greater prevalence of sub-condylar bone resorption was noted in that group, while cells positive for tartrate-resistant acid phosphatase were increased in the OVX group. CONCLUSIONS: The present findings suggest that oestrogen induced a much greater amount of bone resorption on the anterior surface of the condylar head at an earlier stage in the TMJs of the present model rabbits. Thereafter, restoration of TMJ function appeared to occur in a normal manner.

The Accuracy of Maxillary Position Using a Computer-Aided Design/Computer-Aided Manufacturing Intermediate Splint Derived Via Surgical Simulation in Bimaxillary Orthognathic Surgery.

PURPOSE: The purpose of this study was to assess the clinical interventions and the accuracy of maxillary reposition using a computer-aided design/computer-aided manufacturing (CAD/CAM) splint derived via surgical simulation. MATERIALS AND METHODS: The retrospective study comprised 24 patients who underwent bimaxillary surgery. The patients were assigned to 1 of 2 groups by a way of maxillary repositioning. One group received conventional intermediate wafers and the other CAD/CAM wafers during Le Fort I osteotomy. We recorded operation time, blood loss, the operative accuracy. Accuracy was analyzed by 3-dimensional computed tomography images before and immediately after the operation. The evaluation points were the right maxillary first incisor (U1), the right maxillary second molar (M2-right), and the left maxillary second molar (M2-left). RESULTS: The 2 groups did not differ significantly in operation time and blood losses. The vertical axis of U1 data differed significantly between the 2 groups (P = 0.008). None of the horizontal, vertical, or anteroposterior axis of M2-right data differed significantly, and anteroposterior axis of M2-left data differed significantly (P = 0.0296). The CAD/CAM group 3-dimensional distance errors were less than those of the conventional group for all points. CONCLUSION: Placement of CAD/CAM splint allowed highly accurate repositioning; the accuracy exceeded that afforded by conventional model surgery using a facebow and articulator.

Immunohistochemical assessment of growth factor signaling molecules: MAPK, Akt, and STAT3 pathways in oral epithelial precursor lesions and squamous cell carcinoma.

Several growth factors and their receptors, such as epidermal growth factor receptor, have been studied as prognostic biomarkers for many epithelial malignancies. The signal transduction cascade of those receptors includes RAS/RAF/ERK, PI3K/Akt/mTOR, and STAT3 pathways. The aim of this study was to investigate the expression levels of several key proteins of those pathways in patients with oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPLs), and to correlate the expressions of these proteins with clinicopathologic features and prognosis. Fifteen leukoplakia (LP), 15 low-grade epithelial dysplasia, 15 high-grade epithelial dysplasia (HD), and 132 OSCC specimens were immunohistochemically examined for KRAS, HRAS, NRAS, BRAF, pERK1/2, pAkt, pmTOR, and pSTAT3 expression. Immunoreactivity for these molecules predominantly occurred in regions OEPL basal to prickle layers and in most OSCC cells. KRAS and NRAS expression was significantly lower in OSCC than in OEPLs, while pAkt and pmTOR showed higher expression in OSCC than in OEPLs. pERK1/2 expression was significantly higher in HD than in LP. In OSCC, KRAS and NRAS immunoreactivity was significantly higher in advanced age and male gender. In addition, higher immunoreactivity was shown in pERK1/2 in female gender and advanced TNM stage, pAkt in advanced T classification and cases without postoperative metastasis, pmTOR in advanced mode of invasion, and pSTAT3 in invasion depth. Correlations between these markers and clinicopathological variables were also noted. MAPK, Akt, and STAT3 pathways might play diverse roles in oral carcinogenesis.

Immunohistochemical assessment of Eph/ephrin expression in oral squamous cell carcinoma and precursor lesions.

To evaluate erythropoietin-producing hepatocellular carcinoma (Eph)/Eph receptor-interaction protein (ephrin) expression in oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPLs), EphA2, EphB4, and ephrinB2 were examined and compared with microvessel density (MVD) and lymphatic vessel density (LVD). Samples from 73 OSCC and 43 OEPLs patients were immunohistochemically analyzed with antibodies against EphA2, EphB4, ephrinB2, CD34, and D2-40. Results were compared with clinicopathological findings. Immunohistochemical reactivity for EphA2, EphB4, and ephrinB2 was detected in epithelial cells and some stromal vascular cells in OEPLs and OSCC, proportionately with the level of malignancy. The number of blood vessel endothelial cells stained with CD34 and lymphatic vessel endothelial cells stained with D2-40 was increased in OEPLs and OSCC. In OSCC, ephrinB2 and EphB4 exhibited significant correlation with recurrence and invasion depth, respectively. MVD was significantly lower in slight lymphocytic reaction than in prominent stromal reaction. Association was found between LVD and T classification, postoperative metastasis, survival, mode of invasion, and invasion depth. Expression of EphA2, EphB4, ephrinB2, MVD, and LVD might be associated with malignant potential of the oral epithelium. Angiogenesis and lymphangiogenesis appear to be related to progression of potentially malignant oral lesions.

Mandibular fractures and dental injuries sustained during baseball and softball over 14 years in a Japanese population: A retrospective multicentre study.

BACKGROUND/AIM: Active participation in sports is a risk factor for maxillofacial fractures. The aim of this retrospective multicentre study was to survey and evaluate the characteristics of mandibular fractures, and dental injuries that occurred during the practice of baseball and softball in Sendai, Japan. MATERIAL AND METHODS: The records of 454 patients with maxillofacial fractures from three departments of Oral and Maxillofacial Surgery across a period 14 years were analysed. Fifty-one patients with 56 mandible fractures and dental injuries that occurred playing baseball or softball were included in this multicenter retrospective study. Patients were divided according to age, gender, sites of fractures, mechanism of fractures and treatment methods. RESULTS: There were 42 males and nine females, with a male-to-female ratio of 4.7:1.0. The mean age was 19.9 years old (range: 13-47 years old). As for the site, body of the mandible fractures prevailed, followed by the condyle, symphysis and angle. Fractures were mostly caused by the impact of a ball (42; 82.4%), followed by collisions with another player (5; 9.8%) and direct strike of a bat (4; 7.8%). All patients with mandibular fractures were treated with open reduction and internal fixation, except for six patients with condylar head fractures who were managed conservatively. CONCLUSIONS: The impact of a thrown ball against the batter's mandible can cause a condylar fracture when playing baseball and softball.

Lymph node resection induces the activation of tumor cells in the lungs.

Lymph node (LN) dissection is a crucial procedure for cancer staging, diagnosis and treatment, and for predicting patient survival. Activation of lung metastatic lesions after LN dissection has been described for head and neck cancer and breast cancer. Preclinical studies have reported that dissection of a tumor-bearing LN is involved in the activation and rapid growth of latent tumor metastases in distant organs, but it is also important to understand how normal (non-tumor-bearing) LN resection influences secondary cancer formation. Here, we describe how the resection of tumor-bearing and non-tumor-bearing LN affects distant metastases in MXH10/Mo-lpr/lpr mice. Tumor cells were administered intravenously and/or intranodally into the right subiliac lymph node (SiLN) to create a mouse model of lung metastasis. Luciferase imaging revealed that tumor cells in the lung were activated after resection of the SiLN, irrespective of whether it contained tumor cells. No luciferase activity was detected in the lungs of mice that did not undergo LN resection (excluding the intravenous inoculation group). Our results indicate that resection of an LN can activate distant metastases regardless of whether the LN contains tumor cells. Hence, lung metastatic lesions are suppressed while metastatic LN are present but activated after LN resection. If this phenomenon occurs in patients with cancer, it is likely that lung metastatic lesions may be activated by elective LN dissection in clinical N0 cases. The development of minimally invasive cancer therapy without surgery would help to minimize the risk of activation of distant metastatic lesions by LN resection.