A Bilocular Radicular Cyst in the Mandible with Tooth Structure Components Inside

Background. A radicular cyst is the most common odontogenic cyst of inflammatory origin. Radiographically, it commonly demonstrates clear unilocular radiolucency; radicular cysts with multilocular radiolucency are quite rare. Case Presentation. A 64-year-old Japanese man who presented with a bilocular radiolucent lesion in his left mandible was referred by a dental clinic to our oral and maxillofacial surgery department. He had no particular subjective symptoms. Orthopantomography and computed tomography (CT) revealed an 18 mm×15 mm lesion with well-defined bilocular radiolucency in the left mandible expanding from the distal side of a canine tooth to the bottom of the 2nd premolar. The lesion included the roots of the 1st and 2nd premolars. The root of the 2nd premolar showed knife-edge resorption. Although the 1st premolar was nonvital, the 2nd premolar was a vital tooth. As differential diagnoses, a radicular cyst, ameloblastoma, odontogenic keratocyst, pseudocyst, and others might be considered. We performed a total resection of the bilocular lesion and diagnosed the lesion as a radicular cyst with tooth structure components inside. The tooth structure components represented lamellar structures of cementum; they were located only in the proximal part (under the 1st premolar) of the lesion. The distal part of the lesion presented distinctive inflammation without tooth structure components. Conclusion. We encountered a rare case of a bilocular radicular cyst with tooth structure components inside

A Novel, Tumor-Induced Osteoclastogenesis Pathway Insensitive to Denosumab but Interfered by Cannabidiol

Bone metabolism is strictly regulated, and impaired regulation caused by hormonal imbalances induces systemic bone loss. Local bone loss caused by tumor invasion into bone is suggested to be induced by the generation of cytokines, which affect bone metabolism, by tumor cells. The major cause of systemic and local bone losses is excess bone resorption by osteoclasts, which differentiate from macrophages by receptor activator of nuclear factor kappa-B ligand (RANKL) or tumor necrosis factor-alpha (TNF-alpha). We previously found a novel pathway for tumor-induced osteoclastogenesis targeting osteoclast precursor cells (OPCs). Tumor-induced osteoclastogenesis was resistant to RANKL and TNF-alpha inhibitors. In the present study, we confirmed that exosomes derived from oral squamous cell carcinoma (OSCC) cells induced osteoclasts from OPCs. We also showed that the depletion of exosomes from culture supernatants of OSCC cells partially interfered with osteoclastogenesis, and cannabidiol, an innoxious cannabinoid without psychotropic effects, almost completely suppressed tumor-induced osteoclastogenesis. Osteoclastogenesis and its interference by cannabidiol were independent of the expression of nuclear factor of T cell c1 (NFATc1). These results show that osteoclastogenesis induced by OSCC cells targeting OPCs is a novel osteoclastogenic pathway independent of NFATc1 expression that is partially caused by tumor-derived exosomes and suppressed by cannabidiol

A Case of Odontogenic Infection by Streptococcus constellatus Leading to Systemic Infection in a Cogan’s Syndrome Patient

Odontogenic infection in immunocompromised patients tends to extend systemically beyond the oral cavity. Our case report presents a patient with sepsis due to a Streptococcus constellatus (S. constellatus) odontogenic infection in a 64-year-old-immunocompromised woman with Cogan’s syndrome. She had been suffering from chronic mandibular osteomyelitis which was thought to have been caused by dental caries and/or chronic periodontitis with furcation involvement of the left mandibular first molar. We suspect that the acute symptoms of the chronic osteomyelitis due to S. constellatus led to the systemic infection. This infection could be accelerated by the use of a corticosteroid and an alendronate. This is the first report which represents the potential association between odontogenic infection and Cogan’s syndrome

Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma

<div><p>The interaction between cancer cells and the cancer stroma plays a crucial role in tumor progression and metastasis in diverse malignancies, including oral cancer. However, the mechanism underlying this interaction remains incompletely elucidated. Here, to investigate the interaction between oral cancer cells and fibroblasts, which are major cellular components of the tumor stroma, we conducted an <i>in vitro</i> study by using human oral squamous cell carcinoma (OSCC) cell lines and normal human dermal fibroblasts (NHDFs). The results of transwell assays revealed that the migration and invasion of 2 OSCC cell lines, HO1-N-1 and HSC3, were markedly stimulated upon coculturing with NHDFs. To investigate the factors that promote tumor invasion, we isolated NHDFs from cocultures prepared with HO1-N-1 cells and performed microarray analysis. Among the various genes that were upregulated, we identified the gene encoding leukemia inhibitory factor (LIF), and we focused on LIF in further analyses. We confirmed that all OSCC-derived conditioned media potently upregulated LIF expression in NHDFs, and the results of our transwell analysis demonstrated that NHDF-induced OSCC migration and invasion were inhibited by LIF-neutralizing antibodies. Furthermore, immunohistochemical analysis of patient samples revealed that in 44 out of 112 OSCC cases, LIF was expressed in the tumor stroma, particularly in cancer-associated fibroblasts (CAFs), and, notably, clinicopathological analyses confirmed that LIF expression in CAFs was significantly correlated with increased depth of tumor invasion. Collectively, our results suggest that OSCC stimulates fibroblasts to produce LIF, which, in turn, participates in cancer-cell invasion. Our finding offers a potential therapeutic strategy targeting the cancer stroma for the treatment of OSCC patients.</p></div

The liver kinase B1 supports mammary epithelial morphogenesis by inhibiting critical factors that mediate epithelial-mesenchymal transition

The liver kinase B1 (LKB1) controls cellular metabolism and cell polarity across species. We previously established a mechanism for negative regulation of transforming growth factor β (TGFβ) signaling by LKB1. The impact of this mechanism in the context of epithelial polarity and morphogenesis remains unknown. After demonstrating that human mammary tissue expresses robust LKB1 protein levels, whereas invasive breast cancer exhibits significantly reduced LKB1 levels, we focused on mammary morphogenesis studies in three dimensional (3D) acinar organoids. CRISPR/Cas9-introduced loss-of-function mutations of STK11 (LKB1) led to profound defects in the formation of 3D organoids, resulting in amorphous outgrowth and loss of rotation of young organoids embedded in matrigel. This defect was associated with an enhanced signaling by TGFβ, including TGFβ auto-induction and induction of transcription factors that mediate epithelial-mesenchymal transition (EMT). Protein marker analysis confirmed a more efficient EMT response to TGFβ signaling in LKB1 knockout cells. Accordingly, chemical inhibition of the TGFβ type I receptor kinase largely restored the morphogenetic defect of LKB1 knockout cells. Similarly, chemical inhibition of the bone morphogenetic protein pathway or the TANK-binding kinase 1, or genetic silencing of the EMT factor SNAI1, partially restored the LKB1 knockout defect. Thus, LKB1 sustains mammary epithelial morphogenesis by limiting pathways that promote EMT. The observed downregulation of LKB1 expression in breast cancer is therefore predicted to associate with enhanced EMT induced by SNAI1 and TGFβ family members

Analysis of overall survival associated with LIF expression in CAFs in human OSCC.

<p><b>A:</b> Kaplan-Meier curve for overall survival in relation to the presence of CAFs in 112 human OSCC cases. <b>B:</b> Kaplan-Meier curve for overall survival in relation to the presence of LIF in CAFs in 112 human OSCC cases.</p

OSCC cell lines stimulate LIF expression in NHDFs.

<p>CM derived from 4 OSCC cell lines were separately added to NHDFs, and increased LIF expression was confirmed through quantitative real-time PCR analysis after 48 h of culture. The experiment was performed in triplicate in 24-well plates. Representative graph from 3 independent experiments is shown. Data represent means ± SEM. Multiple comparisons were performed by using one-way ANOVA with Dunnett’s method. **p < 0.01 compared with control NHDFs.</p

Effect of anti-LIF antibody on migration and invasion of HSC3 cells.

<p>Transwell migration (<b>A</b>) and invasion (<b>B</b>) assays performed using cell-culture inserts. In the upper chamber, 2×10⁴ HSC3 cells were seeded, and 1×10⁵ NHDFs were seeded into the lower well. In each experiment, cells were treated with 0.5 μg/mL of an anti-LIF neutralizing antibody. IgG was used as a control. After 48 h, the migrated or invaded HSC3 cells on the lower surface of the upper chamber were stained and quantified. Representative images and graphs of 3 independent experiments are shown. Multiple comparisons were performed by using one-way ANOVA with Tukey’s method. *p < 0.05, **p < 0.01 compared with control NHDFs. Data represent means ± SEM.</p