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The present report describes a case of Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) with an ulcerative lesion on the right tongue. A 69-year-old Japanese woman with awareness of pain in the right lingual margin visited our hospital. The patient had rheumatoid arthritis and had been treated with methotrexate (MTX) for 9 years. Vitiligo was found throughout the oral cavity, and ulceration was found on the right tongue. Under a diagnosis of oral candidiasis and suspected right tongue tumor, treatment for candidiasis and biopsy of the right tongue ulcer were performed. Histopathological results were positive for CD20 and CD30 and negative for CD3 and CD5. EBV-encoded small RNA in situ hybridization confirmed positive results in large, atypical cells, suggesting involvement of EBV. EBVMCU was diagnosed based on the history of MTX use associated with rheumatoid arthritis, blood biochemical findings, and histopathological findings. The ulcer on the right tongue margin resolved spontaneously after treatment for oral candidiasis prior to discontinuation of MTX. No recurrence was seen for 18 months.

Burkitt lymphoma (BL) is an aggressive form of non-Hodgkin B-cell lymphoma, with three subtypes: endemic, sporadic, and human immunodeficiency associated subtypes. Endemic BL typically involves the mandible, maxilla, and abdomen, whereas sporadic BL usually presents as an abdominal mass involving the mesenteric lymph nodes or ileocecal region, and jaw involvement is uncommon. In pediatric patients, oral BL commonly presents as facial swelling with an intraoral exophytic mass and is usually accompanied by mobile, displaced, and/or painful teeth. We report sporadic BL initially presented as orofacial manifestations in an 8-year-old boy, and conduct a mini-review. He had left facial and gingival swelling. CT revealed the lesions were located at the left anterior maxilla and the masticator muscle, and PET showed multiple lesions. An incisional biopsy of left anterior maxillary gingiva was performed, and the pathological diagnosis was BL. Oral management has been performed since initial chemotherapy, and tumor remission was achieved by chemotherapy with the B-NHL03 study regimen at our pediatric department. There was no recurrence of the tumor 5 years after chemotherapy. Dentists and oral surgeons should be aware that dental problems including floating teeth and/or alveolar bone resorption might be the first clinical manifestation of BL. Because the success of intensive treatment relies on good supportive care, oral management plays an important role to maintain oral hygiene.

Introduction: EP4 is one of the prostaglandin E2 (PGE2) receptors. We previously reported that EP4 promoted cell migration via Ca2+ signaling, however the underlying mechanism has remained unclear. In Ca2+ signaling, Store-operated Ca2+entry (SOCE) is a major mechanism of Ca2+ import from the extracellular to the intracellular space. Orai1, one of the selective Ca2+ channels, plays an important role in SOCE. We focused on the correlation with EP4 and Orai1. Additionally, we found that EP4 promoted the phosphorylation of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and AMP-activated protein kinase (AMPK) located downstream of CaMKK2, i.e., cell energy regulators. AMPK activation can control positively or negatively the cellular adenosine triphosphate (ATP) supply. Therefore, we investigated how EP4 regulated the mitochondrial function via Ca2+ and promoted the cell migration in oral cancer cells. Materials and Methods: HSC-3, human tongue squamous cell carcinoma cell line was used. ONO-AE1-437 was used as EP4 agonist. HSC-3 cells were transduced with Orai1 shRNA, and control shRNA using lentivirus. The migration ability was evaluated by scratch assay. Measurement of intracellular Ca2+ concentration was measured using Fura-2. Immunoprecipitation was performed to evaluate the interaction between EP4 and Orai1. XF Cell Mito Stress Test and XF Real-Time ATP Rate Assay were performed to evaluate the mitochondrial aspiration and the ATP production using Extracellular Flux Analyzer. Results: Scratch assay showed EP4 promoted cell migration in oral cancer cells (n=4, p Conclusion: We concluded that EP4 regulated the mitochondrial function via Ca2+ through Orai1 and promoted the cell migration in oral cancer cells. Citation Format: Rina Nakakaji, Masanari Umemura, Kohei Osawa, Soichiro Ishikawa, Kenji Mitsudo, Yoshihiro Ishikawa. EP4 increases the mitochondrial respiration and promotes cell migration in oral cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4835.

Introduction: Lymph node metastasis caused by migration of oral cancer cells is an important prognostic factor. We previously reported that EP4, a prostaglandin E2 (PGE2) receptor, regulates the cell migration in oral cancer cells via Ca2+ signaling. However, how Ca2+ signaling regulates cell migration remains unclear. The intracellular Ca2+ regulates a variety of signaling pathways, either directly or by forming complexes with proteins such as calmodulin (CaM), and then phosphorylates calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2). Furthermore, Ca2+ signaling is directly or indirectly involved in cancer cell proliferation and migration. Therefore, we hypothesized that EP4 regulates the cell migration via CaMKK2 and its downstream signaling in oral cancer. Materials and Methods: Human gingival fibroblasts, HGnF and Human tongue squamous cell carcinoma cell lines, HSC-3 were used. EP4 agonist (ONO-AE1-437) and CaMKK2 inhibitor (STO-609) were used. HSC-3 cells were transduced with CaMKK2 shRNA, and scramble control shRNA using lentivirus. The protein expressions were evaluated by western blotting. The intracellular calcium concentrations were measured using Fura-2, the Fluorescent Ca2+ Indicator. The cell migration ability was evaluated by scratch assay. Immunocytochemistry was performed to evaluate the lamellipodium. The mRNA transcriptions of the mitochondrial associated genes were evaluated by real-time qPCR. The intracellular adenosine triphosphate (ATP) production and the reactive oxygen species (ROS) production were also evaluated by luciferase activity assay and DCFH-DA staining. Results: EP4 protein expression of HSC-3 cells was higher than that of HGnF cells (n=4, p Conclusion: EP4/CaMKK2/AMPK pathway is a novel signal transduction in oral cancer and may be a new target for oral cancer therapy. Citation Format: Soichiro Ishikawa, Masanari Umemura, Rina Nakakaji, Akane Nagasako, Kagemichi Nagao, Yuto Mizuno, Fumina Suzuki, Kohei Osawa, Mitomu Kioi, Kenji Mitsudo, Yoshihiro Ishikawa. EP4 promoted cell migration via mitochondrial biogenesis in oral cancer cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3619.

A highly fluorescent 2,2′-bianthryl derivative bearing urea groups (2) was prepared as an anion receptor. The UV-vis and fluorescence titrations of 2 in various organic solvents revealed that the a...

We examined blood and protein dynamics potentially influenced by implant threads and hydrophilic/hydrophobic states of implant surfaces.A computational fluid dynamics model was created for a screw-shaped implant with a water contact angle of 70° (hydrophobic surface) and 0° (superhydrophilic surface). Movements and density of blood and fibrinogen as a representative wound healing protein were visualized and quantified during constant blood inflow.Blood plasma did not occupy 40-50% of the implant interface or the inside of threads around hydrophobic implants, whereas such blood voids were nearly completely eliminated around superhydrophilic implants. Whole blood field vectors were disorganized and random within hydrophobic threads but formed vortex nodes surrounded by stable blood streams along the superhydrophilic implant surface. The averaged vector within threads was away from the implant surface for the hydrophobic implant and towards the implant surface for the superhydrophilic implant. Rapid and massive whole blood influx into the thread zone was only seen for the superhydrophilic implant, whereas a line of conflicting vectors formed at the entrance of the thread area of the hydrophobic implant to prevent blood influx. The fibrinogen density was up to 20-times greater at the superhydrophilic implant interface than the hydrophobic one. Fibrinogen density was higher at the interface than outside the threads only for the superhydrophilic implant.Implant threads and surface hydrophilicity have profound effects on vector and distribution of blood and proteins. Critically, implant threads formed significant biological voids at the interface that were negated by superhydrophilicity-induced contact hemodynamics.

The EP4 prostanoid receptors are one of four receptor subtypes for prostaglandin E2 (PGE2). Therefore, EP4 may play an important role in cancer progression. However, little information is available regarding their function per se, including migration and the cellular signaling pathway of EP4 in oral cancer. First, we found that mRNA and protein expression of EP4 was abundantly expressed in human‐derived tongue squamous cell carcinoma cell lines HSC‐3 and OSC‐19. The EP4 agonist (ONO‐AE1‐437) significantly promoted cell migration in HSC‐3 cells. In contrast, knockdown of EP4 reduced cell migration. Furthermore, we confirmed that knockdown of EP4 suppressed metastasis of oral cancer cells in the lungs of mice in vivo. Therefore, we focused on the mechanism of migration/metastasis in EP4 signaling. Interestingly, EP4 agonist significantly induced intracellular Ca2+ elevation not in only oral cancer cells but also in other cells, including normal cells. Furthermore, we found that EP4 activated PI3K and induced Ca2+ influx through Orai1 without activation of store depletion and stromal interaction molecule 1 (STIM1). Immunoprecipitation showed that EP4 formed complexes with Orai1 and TRPC1, but not with STIM. Moreover, the EP4 agonist ONO‐AE1‐437 phosphorylated ERK and activated MMP‐2 and MMP‐9. Knockdown of Orai1 negated EP4 agonist‐induced ERK phosphorylation. Taken together, our data suggested that EP4 activated PI3K and then induced Ca2+ influx from the extracellular space through Orai1, resulting in ERK phosphorylation and promoting cell migration. Migration is regulated by EP4/PI3K/Orai1 signaling in oral cancer., EP4 activated PI3K and then induced Ca2+ influx from the extracellular space through Orai1, resulting in ERK phosphorylation and promoting cell migration.

Objective Intra-oral minor salivary gland tumors are relatively rare. This study aimed to clarify the frequency and distribution of intra-oral minor salivary gland tumors in Japanese patients. Methods We retrospectively analyzed the histopathological records of 131 patients with minor salivary gland tumors that were surgically treated between 1967 and 2017 at a single institution. Results Of the 131 minor salivary gland tumors, 61 (47%) were benign and 70 (53%) were malignant. The male:female ratio was 1:1.8 for benign cases and 1:1 for malignant cases. Most of the tumors occurred in the palate, followed by the floor of the mouth. The most frequent minor salivary gland tumor was pleomorphic adenoma among benign tumors and adenoid cystic carcinoma among malignant tumors. The rarest minor salivary gland tumors were Warthin tumors and basal cell adenocarcinoma, accounting for only 0.8% of all cases. Conclusions The present study determined the incidence rates of these rare tumors.

Chiral recognition abilities of tetraamide-based receptors 1 and 2 bearing l-serine and l-threonine as recognition sites, respectively, and terminal pyrenyl groups as signaling units for enantiomers of biologically important N-acetyl amino acid tetrabutylammonium salts were studied in acetonitrile. The receptors showed ratiometric fluorescence changes upon the addition of chiral guest anions. The binding constants for amino acid derivatives were in the 104–105 mol−1 dm3 range. The chiral discrimination abilities (K11,D/K11,L) of 1 and 2 were significantly large, for instance K11,D/K11,L for Ac-Leu-O− were found to be 3.9 and 4.6, respectively. The complex structures were evaluated by 1H NMR titrations and DFT calculations implying that the effective hydrogen bond formations by six N-H and O-H groups and a CH-π interaction of the acetyl group of d-enantiomer with a terminal pyrenyl group of the receptor.

Osteomas are benign, slow-growing osteogenic tumors that consist of compact or cancellous bone. They sometimes arise from the craniomaxillofacial region. Among the peripheral, central, and extraskeletal types, peripheral osteomas arise from the periosteum, usually as unilateral, pedunculated, mushroom-like masses. Here, we report an unusual peripheral osteoma arising from the lateral surface of the mandibular ramus. A 57-year-old woman with a mass at the left mandibular ramus was referred to us. The hard and immobile mass had been growing for 15 years, and she had facial asymmetry. She had no trismus, temporomandibular joint dysfunction, previous facial trauma, or infection. Computed tomography showed a mushroom-like lesion (21.1 × 13.4 × 13.1 mm) arising from the lateral surface of the left mandibular ramus. Clinical diagnosis was peripheral osteoma. The lesion was removed using rotary instruments and a chisel through an intraoral approach under general anesthesia. The lesion had intruded into the masseter muscle. Pathological diagnosis was compact osteoma. The postoperative course was uneventful and there has been no recurrence 1.5 years after surgery.

Silanediols possess unique and complementary catalytic activity in reactions that are likely to proceed through anion binding. This article directly compares silanediols, thioureas, and squaramides in three separate anion-binding processes. The catalytic abilities of select members of each family are directly correlated to association constants.

Highly regio-/stereoregular (trans-head-to-tail) polymers with amide side chains on every eighth backbone carbon were successfully synthesized by ring-opening metathesis polymerization (ROMP) of 3-substituted cis-cyclooctene (3RCOE) using Grubbs second-generation catalyst (G2). Regioregular linear ethylene–acrylamide copolymers were also prepared via hydrogenation of the obtained poly(3RCOE)s. The thermal properties and solubility of the obtained polymers were strongly influenced by the presence of amide hydrogen in the side chains, the presence of unsaturated bonds in the carbon backbone, and the side chain density. The presence of amide hydrogen in the side chains resulted in the formation of crystalline polymers and the lack of solubility of these polymers in common organic solvents. In contrast, the absence of amide hydrogen in the side chains led to the formation of amorphous polymers exhibiting good solubility in common organic solvents, and decreasing values of Tg were observed for amorphous polyme...

BACKGROUND The aim of this study was to evaluate the prognostic factors and treatment outcomes of advanced maxillary gingival squamous cell carcinoma (SCC) treated with intra-arterial infusion chemotherapy concurrent with radiotherapy. METHODS A total of 46 patients were reviewed retrospectively in this study. The treatment schedule comprised intra-arterial chemotherapy (total, 60 mg/m2 docetaxel and 150 mg/m2 cisplatin) and three-dimensional computed tomography based, daily conventional radiotherapy (total, 60 Gy/30 fr) for 6 weeks. RESULTS The median follow-up period was 40 months (range, 3-110 months). The 3-year overall survival and locoregional control rates for all patients were 64.3% and 84.3%, respectively. The OS rate of the patients with N0-1 was significantly higher than that of the patients with N ≥ 2 (P

Cyber-Physical Systems (CPS) are tight integrations of computational and physical worlds for various kinds of applications. For example, a humanoid robot, which is a typical application of CPS, has required timing constraints, low-latency execution, and parallel processing to achieve fine-grained real-time execution. Therefore low-latency parallel real-time computing is an important factor for CPS. In order to achieve such CPS applications, commercial off-the-shelf systems including processors and operating systems are difficult due to many requirements including such system performance and space constraints, and hence proprietary systems are favored. We had developed Dependable Responsive Multithreaded Processor I (D-RMTP I), which has one Responsive Multithreaded Processing Unit (RMT PU) with an 8-way prioritized Simultaneous Multithreading architecture, for parallel real-time computing. In addition, we have developed a high-end processor of D-RMTP I, called Dependable Responsive Multithreaded Processor II (D-RMTP II). D-RMTP II has two RMT PUs for high throughput and eight Flower cores for I/O processing. Our previous work presented Responsive Task, which is a low-latency real-time task with the interrupt wake-up structure to occupy a hardware thread in D-RMTP I for fine-grained real-time execution. Responsive Task can be executed in dozens of microsecond periods with low-jitter though executing real-time tasks simultaneously. Unfortunately, Responsive Task does not support parallel computing. This paper presents Parallel Responsive Task, which is an extension to Responsive Task for parallel computing on D-RMTP II. Evaluations show that Parallel Responsive Task improves the throughput and achieves fine-grained real-time execution with reasonable overhead.