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Necrotising sialometaplasia (NSM) is a non‐neoplastic lesion mainly arising in the minor salivary glands of the oral cavity. In the clinical features, NSM shows swelling with or without ulceration, and can mimic a malignant disease such as squamous cell carcinoma. Histopathologically, NSM usually shows the lobular architecture that is observed in the salivary glands. Additionally, acinar infarction and squamous metaplasia of salivary ducts and acini are observable. The aetiology of this lesion remains unknown, although it has a characteristic feature that sometimes requires clinical and histopathological differentiation from malignancy. In this study, we investigated upregulated genes in NSM compared with normal salivary glands, and focused on the TGF‐β3 (TGFB3) gene. The results of the histopathological studies clarified that fibroblasts surrounding the lesion express TGF‐β3. Moreover, in vitro studies using mouse salivary gland organoids revealed that TGF‐β3 suppressed salivary gland cell proliferation and induced squamous metaplasia. We demonstrated a possible aetiology of NSM by concluding that increased TGF‐β3 expression during wound healing or tissue regeneration played a critical role in cell proliferation and metaplasia. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Ganglioneuroma is a benign neoplasm of neuroblastic origin and can arise from any sympathetic nervous system tissue throughout the body. The most commonly affected sites are the posterior mediastinum, retroperitoneum, and adrenal gland; ganglioneuroma rarely presents in the cervical region. We note that ganglioneuroma is slow-growing, presents without noticeable pain clinically, and is normally asymptomatic while the tumor is small. Therefore, the tumor is often discovered incidentally or at a more advanced stage when pressure symptoms appear in surrounding tissues. In this report, we present a rare case of a 47-year-old woman with ganglioneuroma of the cervical nerve that was discovered incidentally during neck dissection for oral cancer surgery. No mass lesion was palpable on clinical examination, and contrast-enhanced computed tomography, contrast-enhanced magnetic resonance imaging, ultrasonography of the head and neck, and fluorodeoxyglucose-positron emission tomography failed to detect a mass lesion; therefore, preoperative diagnosis revealed no evidence of a cervical mass lesion. More specifically, we performed hemiglossectomy with supraomohyoid neck dissection and reconstruction of the tongue using a free vascularized forearm flap. On neck dissection, we found a mass lesion contiguous with the third cervical nerve, and this mass was excised. The histopathological diagnosis was ganglioneuroma. Surgical excision is regarded as the most effective treatment for ganglioneuroma. Although the prognosis for this tumor type is good, long-term postoperative follow-up is necessary due to rare cases of recurrence. [ABSTRACT FROM AUTHOR]

Bone invasion is a critical factor in determining the prognosis of oral squamous cell carcinoma (OSCC) patients. Transforming growth factor β (TGF-β) is abundantly expressed in the bone matrix and is involved in the acquisition of aggressiveness by tumors. TGF-β is also important to cytoskeletal changes during tumor progression. In this study, we examined the relationship between TGF-β signaling and cytoskeletal changes during bone invasion by OSCC. Immunohistochemical staining of OSCC samples from five patients showed the expression of p130Cas (Crk-associated substrate) in the cytoplasm and phosphorylated Smad3 expression in the nucleus in OSCC cells. TGF-β1 induced the phosphorylation of Smad3 and p130Cas, as well as epithelial–mesenchymal transition (EMT) accompanied by the downregulation of the expression of E-cadherin, a marker of epithelial cells, and the upregulation of the expression of N-cadherin, or Snail, a marker of mesenchymal cells, in human HSC-2 cells and mouse squamous cell carcinome VII (SCCVII) cells. SB431542, a specific inhibitor of Smad2/3 signaling, abrogated the TGF-β1-induced phosphorylation of p130Cas and morphological changes. Silencing p130Cas using an short hairpin RNA (shRNA) or small interfering RNA in SCCVII cells suppressed TGF-β1-induced cell migration, invasion, EMT and matrix metalloproteinase-9 (MMP-9) production. Compared with control SCCVII cells, SCCVII cells with silenced p130Cas strongly suppressed zygomatic and mandibular destruction in vivo by reducing the number of osteoclasts, cell proliferation and MMP-9 production. Taken together, these results showed that the expression of TGF-β/p130Cas might be a new target for the treatment of OSCC bone invasion. [ABSTRACT FROM AUTHOR]

Nanoparticles are used in industry and medicine, because of their physiochemical properties, such as size, charge, large surface area and surface reactivity. Recently, metal nanoparticles were reported to show cell toxicity on cancer cells. In this study, we focused novel platinum nanoparticles‐conjugated latex beads (P2VPs), platinum nanocomposite (PtNCP) beads, and investigated the possibility to incorporate novel anti‐cancer effect of these combined nanoparticles. Oral squamous cell carcinoma cell lines, HSC‐3‐M3 cells were injected subcutaneously into the back of nude mice to produce a xenograft model. PtNCP beads were injected locally and examined by measuring tumor volume and comparing pathological histology. PtNCP beads treatment suppressed tumor growth and identified increasing pathological necrotic areas, in vivo. PtNCP beads inhibited the cell viability of HSC‐3‐M3 cells in dose‐dependent manner and induced the cytotoxicity with extracellular LDH value, in vitro. Furthermore, SEM images were morphologically observed in PtNCP beads‐treated HSC‐3‐M3 cells. The aggregation of the PtNCP beads on the cell membrane, the destructions of the cell membrane and globular structures were observed in the SEM image. Our results indicated that a potential anti‐cancer effect of the PtNCP beads, suggesting the possibility as a therapeutic tool for cancer cell‐targeted therapy. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2281–2287, 2019. [ABSTRACT FROM AUTHOR]

Direct pulp capping is an important procedure for preserving pulp viability. The pulp capping agent must possess several properties, including usability, biocompatibility, and the ability to induce reparative dentin formation. In this study, a novel bioactive glass‐based cement was examined to determine whether the cement has the necessary properties to act as a direct pulp capping agent. Physicochemical properties of the bioactive glass‐based cement and in vitro effects of the cement on odontoblast‐like cells, as well as in vivo effects on the exposed dental pulp, were analyzed. The cement immersed in water stabilized at pH10, and hydroxyapatite‐like precipitation was induced on the surface of the cement in simulate body fluid. There were no cytotoxic effects on the viability, alkaline phosphatase activity, or calcium deposition ability of odontoblast‐like cells. In the in vivo rat study of an exposed dental pulp model, the cement induced a sufficient level of reparative dentin formation by odontoblast‐like cells expressing odontoblastic markers at the exposed area of the dental pulp. These results suggest that the newly developed bioactive glass‐based cement provides favorable biocompatibility with the dental pulp and may be useful as a direct pulp capping agent. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 161–168, 2019. [ABSTRACT FROM AUTHOR]

We aimed to determine the significance and usefulness of imaging characteristics of gubernaculum tracts (GT) for the diagnosis of odontogenic tumors or cysts. This was a retrospective analysis of relationships between odontogenic or non-odontogenic tumors or cysts and the GT that were visualized using multi-detector computed tomography (MDCT). The relationship between the size of a mass and expansion of the GT in all odontogenic tumors or cysts to which GTs were contiguous on MDCT, was statistically analyzed. Intact or expanded GTs were detected in MDCT images on the top of almost all odontogenic tumors or cysts, but not on non-odontogenic tumors or cysts. Characteristic image findings regarding the relationship between the GT and the odontogenic mass were detected for the respective odontogenic tumors or cysts in which the GTs were contiguous to the mass on MDCT. In ameloblastomas, expansion of the GTs significantly and very strongly correlated with tumor size (r = 0.741, p = 0.0001), but this correlation was very weak in dentigerous cysts (r = 0.167, p = 0.028) and there was no correlation between these parameters in odontogenic keratocysts (r = -0.089, p = 0.557). The imaging characteristics of GTs at the top of masses should be very useful for both the differential diagnosis of the pathological diagnosis of odontogenic masses and for differentiation between odontogenic and non-odontogenic masses. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: This study aimed to evaluate the effects of thymosin β4 (TB4) on bone formation. Methods: A 5mm diameter bone defect was created in the skulls of Wistar rats. Two types of experimental models were prepared: one with atelocollagen sponges used to fill the bone defect and one without. In each experimental model, bone formation in calvarial defects was compared between the group receiving synthetic partial peptides of TB4 intraperitoneally (TB group) and the control group, which received an equivalent amount of phosphate-buffered saline. Calvarial defect sections collected on postoperative days 5, 10, and 20 were analyzed, and the area of newly formed bone was measured. Furthermore, the sections on postoprerative day 5 were immunostained with anti-osterix antibody and the osterix-positive cells were counted. The total RNA extracted from granulation tissue obtained on postoperative day 10 was analyzed using reverse transcriptase–polymerase chain reaction (RT–PCR). Results: In both models, with or without atelocollagen sponges, new bone formation was significantly greater in the TB4 group than in the control group. In some TB4 group individuals, the entire bone defect region of diameter 5mm was almost covered with newly formed bone by postoperative day 20. Immunostaining revealed a significant number of osterix-positive cells in the TB4 group. On postoperative day 10, the expression levels of bone-related genes were analyzed by RT–PCR, which showed no statistically significant differences between the two groups. Conclusion: The osteogenesis-promoting effects of TB4 observed in critical-sized defects could be of practical use in bone regeneration therapy. [Copyright &y& Elsevier]

Background: Methylation of CpG islands of genome DNA and lysine residues of histone H3 and H4 tails regulates gene transcription. Inhibition of polyamine synthesis by ornithine decarboxylase antizyme-1 (OAZ) in human oral cancer cell line resulted in accumulation of decarboxylated S-adenosylmethionine (dcSAM), which acts as a competitive inhibitor of methylation reactions. We anticipated that accumulation of dcSAM impaired methylation reactions and resulted in hypomethylation of genome DNA and histone tails. Methodology/Principal Findings: Global methylation state of genome DNA and lysine residues of histone H3 and H4 tails were assayed by Methylation by Isoschizomers (MIAMI) method and western blotting, respectively, in the presence or absence of OAZ expression. Ectopic expression of OAZ mediated hypomethylation of CpG islands of genome DNA and histone H3 lysine 9 dimethylation (H3K9me2). Protein level of DNA methyltransferase 3B (DNMT3B) and histone H3K9me specific methyltransferase G9a were down-regulated in OAZ transfectant. Conclusions/Significance: OAZ induced hypomethylation of CpG islands of global genome DNA and H3K9me2 by down-regulating DNMT3B and G9a protein level. Hypomethylation of CpG islands of genome DNA and histone H3K9me2 is a potent mechanism of induction of the genes related to tumor suppression and DNA double strand break repair. [ABSTRACT FROM AUTHOR]

It is important to develop a suitable three‐dimensional scaffold for the regeneration therapy of dental pulp. In the present study, the effects of hyaluronic acid (HA) sponge on responses of the odontoblastic cell line (KN‐3 cells) in vitro, as well as responses of amputated dental pulp of rat molar in vivo, were examined. In vitro, KN‐3 cells adhered to the stable structure of HA sponge and that of collagen sponge. In vivo, dental pulp proliferation and vessel invasion were observed in both sponges implanted at dentin defect area above amputated dental pulp, and the cell‐rich reorganizing tissue was observed in the dentin defect when HA sponge was implanted as compared with collagen sponge. Expression levels of IL‐6 and TNF‐α in KN‐3 cells seeded in HA sponge were nearly the same with those in the cells seeded in collagen sponge, while the numbers (0.67 × 103 at 1 week and 0.7 × 103 at 3 weeks) of granulated leukocytes that invaded into HA sponge from amputated dental pulp was significantly lower than those (1.22 × 103 at 1 week and 1.1 × 103 at 3 weeks) of collagen sponge (p < 0.01 at 1 week and p < 0.05 at 3 weeks). These results suggest that HA sponge has an appropriate structure, biocompatibility, and biodegradation for use as a scaffold for dental pulp regeneration. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2010 [ABSTRACT FROM AUTHOR]

This study examined the effect of squamous cell carcinoma antigen 1 (SCCA1) and SCCA2 on TNF-α-induced cell death in human oral squamous cell carcinoma cell lines. The viability of MISK81-5 and sMISK cells treated with TNF-α dose-dependently decreased. The sMISK cells which stably overexpressed SCCA1 and SCCA2 cDNA showed a greater resistance against the cell death induced by TNF-α than the controls. Immunocytochemical staining for cytochrome c showed a punctate pattern in the cytoplasm of the TNF-α-untreated cells. After treatment with TNF-α, the punctate staining pattern was preserved in the transfectants, while this pattern disappeared in the controls. In the transfectants, the release of cytochrome c from the mitochondria to cytosol after TNF-α treatment was lower than in the controls. A decreased level of active caspase-9 was also observed in the transfectants. These results suggest that both SCCA1 and SCCA2 play a role in the prevention of TNF-α-induced cell death in vitro, by inhibiting the release of mitochondrial cytochrome c to some degree. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Methylation of CpG islands of genome DNA and lysine residues of histone H3 and H4 tails regulates gene transcription. Inhibition of polyamine synthesis by ornithine decarboxylase antizyme-1 (OAZ) in human oral cancer cell line resulted in accumulation of decarboxylated S-adenosylmethionine (dcSAM), which acts as a competitive inhibitor of methylation reactions. We anticipated that accumulation of dcSAM impaired methylation reactions and resulted in hypomethylation of genome DNA and histone tails. Methodology/Principal Findings: Global methylation state of genome DNA and lysine residues of histone H3 and H4 tails were assayed by Methylation by Isoschizomers (MIAMI) method and western blotting, respectively, in the presence or absence of OAZ expression. Ectopic expression of OAZ mediated hypomethylation of CpG islands of genome DNA and histone H3 lysine 9 dimethylation (H3K9me2). Protein level of DNA methyltransferase 3B (DNMT3B) and histone H3K9me specific methyltransferase G9a were down-regulated in OAZ transfectant. Conclusions/Significance: OAZ induced hypomethylation of CpG islands of global genome DNA and H3K9me2 by down-regulating DNMT3B and G9a protein level. Hypomethylation of CpG islands of genome DNA and histone H3K9me2 is a potent mechanism of induction of the genes related to tumor suppression and DNA double strand break repair.

Abstract: This is the first reported case of an osteolipoma affecting the left lower lip of a 68-year-old Japanese man. It is important to be aware of lipomas, such in the present rare case, to avoid their misdiagnosis. [Copyright &y& Elsevier]

Objectives: To elucidate whether fluorine-18-labeled (18F) fluoro-2-deoxy-d-glucose (FDG) accumulation can reflect the extent of periodontal inflammation, periapical inflammation, or dental caries. Study Design: 18F-FDG accumulations on positron emission tomography (PET)-computed tomography (CT) were retrospectively compared with the size of the bone resorption areas caused by periodontal inflammation, periapical inflammation, or dental caries on panoramic radiographs, CT, and magnetic resonance imaging (MRI) in 44 subjects. Results: A significant correlation was found between the size of the bone resorption area caused by periodontal (r = 0.595, P < .01) or periapical (r = 0.560, P < .01) inflammation and the highest standardized uptake value (SUVmax) of 18F-FDG accumulation. A significant correlation was found between the periodontal (r = 0.622, P < .01) or periapical (r = 0.394, P < .01) inflammatory findings on MRI and the SUVmax of 18F-FDG accumulation. The SUVmax of 18F-FDG around most teeth with caries was under 1.5. Conclusions: 18F-FDG accumulation reflects the extent of dental inflammation, not dental caries. [ABSTRACT FROM AUTHOR]