記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cisplatin (CDDP) plays a central role in chemotherapy for head and neck squamous cell carcinoma (HNSCC), but drug resistance in HNSCC chemotherapy remains a problem, and the mechanism of CDDP resistance is unclear. We investigated CDDP-resistance mechanisms mediated by extracellular vesicles (EVs) and ATPase copper transporting beta (ATP7B) in HNSCC. METHODS: We established CDDP-resistant sublines of HNSCC cells and verified their ATP7B expression. We used an EV secretion inhibitor (GW4869) and ATP7B short hairpin (sh)RNA transfection to examine the correlation between EV secretion and ATP7B expression. RESULTS: The CDDP-resistant HNSCC sublines showed decreased CDDP sensitivity and increased ATP7B expression. GW4869 suppressed ATP7B expression, and ATP7B shRNA transfection suppressed EV secretion. The suppressions of EV secretion and ATP7B expression both enhanced CDDP's cell-killing effect. CONCLUSIONS: EVs were involved in the ATP7B-mediated mechanism underlying CDDP resistance. Further clarification of the EV-induced CDDP-resistance mechanism may lead to novel therapeutic strategies for HNSCC.

DOI： 10.1002/hed.27620

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms. MATERIALS AND METHODS: Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically. RESULTS: Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models. CONCLUSION: This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate.

DOI： 10.21873/cgp.20464

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: The current supraomohyoid neck dissection (SOHND) is performed above the omohyoid muscle to dissect levels I, II, and III in the levels of cervical lymph nodes. However, the anatomical boundary between levels III and IV is the inferior border of the cricoid cartilage. We investigated the anatomical relationship between the omohyoid muscle and cricoid cartilage using contrast-enhanced CT (CE-CT) images to assess the validity of the current SOHND. Methods: CE-CT images of the head and neck regions in patients were reviewed. The patients were divided into two groups: “malignant tumors” and “others”. The vertebral levels corresponding to the positions of anatomical structures such as the intersection of the omohyoid muscle and internal jugular vein (OM-IJ), and the inferior border of the cricoid cartilage (CC), were recorded. Results: The OM-IJ was located around the seventh cervical to the first thoracic vertebra. There was a significant difference between the malignant tumor and others groups in females (p = 0.036). The CC was located around the sixth to seventh cervical vertebrae. There was a significant sex difference in each group (malignant tumor: p < 0.0001; others: p = 0.008). Both sexes tended to have lower OM-IJ than CC, and females had significantly lower OM-IJ than males. Conclusion: This study provides clear anatomical evidence showing the difference between the SOHND dissection area and levels I, II, and III. It could be considered that in most cases SOHND invades level IV, not just levels I, II, and III, especially in female patients.

DOI： 10.1007/s00276-024-03453-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Amyloidosis is a disease in which amyloid protein is deposited in organs and tissues, resulting in functional impairment. Amyloidosis occurs in 12%-30% of patients with multiple myeloma, but in rare cases, amyloidosis may precede the diagnosis of multiple myeloma. Our patient was a 76-year-old Japanese male on dialysis. Multiple nodules accompanied by ulcers were observed on his tongue. He had no subjective symptoms or clinical findings associated with multiple myeloma. The histopathological findings suggested amyloidosis. We suspected both systemic and localized amyloidosis and performed a comprehensive systemic examination. Since the patient had been on dialysis for only a short period of time (~3 months), dialysis-related amyloidosis was ruled out. After blood and urine tests, a diagnosis of multiple myeloma was made. Chemotherapy treatment was started, but the patient's multiple myeloma could not be suppressed and the tongue amyloidosis worsened, leading to his death 2 years and 2 months after the initial diagnosis.

DOI： 10.1155/2024/8836103

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Rab11(Rab11a and Rab11b) localizes primarily along recycling endosomes in cells and is involved in various intracellular trafficking processes, including membrane receptor recycling and secretion of exosomes or small extracellular vesicles (EVs). Although Rab11 is closely associated with the progression and metastasis of various cancer types, little is known about Rab11' role in head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the roles of Rab11a and Rab11b in HNSCC. METHODS: The clinical significance of Rab11 expression in HNSCC was investigated using a public database and tissue microarray analysis. Stable cell lines with loss and gain of Rab11a or Rab11b were originally established to investigate their roles in the proliferative, migratory, and invasive capabilities of HNSCC cells. RESULTS: Database analysis revealed a significant association between Rab11b mRNA expression and a favorable patient survival rate in HNSCC. Tissue microarray analysis revealed that Rab11b expression was the highest in normal tissues and gradually decreased across the stages of HNSCC progression. Overexpression of Rab11a or Rab11b resulted in a decrease in epidermal growth factor receptor (EGFR), Epithelial cell adhesion molecule (EpCAM) exosome secretion, and the migratory and invasive potential of HNSCC cells. The knockdown of Rab11a or Rab11b increased EpCAM/CD9 exosome secretion in addition to the migratory and invasive potential of HNSCC cells. CONCLUSIONS: Rab11 suppresses HNSCC by regulating EGFR recycling and EpCAM exosome secretion in HNSCC cells. Our results indicate that Rab11b is a superior prognostic indicator of HNSCC and holds promise for developing novel therapeutic strategies.

DOI： 10.1016/j.job.2023.11.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The mylohyoid is one of the suprahyoid muscles along with the geniohyoid, digastric, and stylohyoid muscles that lies between the anterior belly of the digastric muscle inferiorly and the geniohyoid superiorly. In Part II, the radiology and clinical/surgical importance of the mylohyoid muscle will be discussed.

DOI： 10.1097/SCS.0000000000009797

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The mylohyoid is one of the suprahyoid muscles, along with the geniohyoid, digastric, and stylohyoid muscles. It lies between the anterior belly of the digastric muscle inferiorly and the geniohyoid superiorly. In Part I, the anatomy and embryology of the mylohyoid muscle will be reviewed in preparation for the clinical discussion in Part II.

DOI： 10.1097/SCS.0000000000009812

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

DOI： 10.1186/s12903-023-03586-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is the most common malignancy in the head/neck region, and cervical lymph node (CLN) metastasis is a strong poor-prognosis factor. In addition, many patients with OSCC experience recurrence despite multidisciplinary treatment. We sought to identify factors associated with CLN metastasis and recurrence in patients with OSCC. PATIENTS AND METHODS: We evaluated a total of 45 patients and 233 target CLNs. The longest diameter of the target CLN, the shortest diameter of the target CLN (LS), the area of the target CLN, and the relative computed tomography (CT) values of the target CLNs calculated based on the CT values of the internal jugular vein (LCT) were obtained from preoperative CT images, and the maximum standardized uptake values of the primary tumor (pSUV) and target CLN (nSUV) were obtained from preoperative 18F-fluorodeoxyglucose-positron emission tomography/CT images. We performed immunohistochemical staining for cytokeratin 13 (CK13) and 17 (CK17) on neck dissection tissues. RESULTS: A discrimination equation was used that can predict CLN metastasis with a 92.2% discrimination rate using LS, LCT, pSUV, and nSUV. The CLNs were divided into discrimination and non-discrimination groups based on discriminant equations and CK13 and CK17 were used as the objective variables. A significantly higher recurrence rate was observed in the non-discrimination group (CK13: 5-year recurrence rate 28.6% vs. 64.3%, p<0.01; CK17: 5-year recurrence rate 28.0% vs. 76.0%, p<0.01). CONCLUSION: CLN metastases in OSCC can be assessed by combining preoperative imaging. The combined use of CK13 and CK17 expression with imaging findings offers an integrated approach to predict OSCC recurrence.

DOI： 10.21873/anticanres.16698

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The submental island flap is an axial pattern pedicle flap widely used in head and neck surgery because of its ease and success. Indications of the submental island flap range from reconstruction for the malignant tumor resection to loss of temporal bone and facial skin due to trauma. Whereas, intraoperative facial nerve injury is not uncommon. We verified whether it was possible to localize the nerve to the mylohyoid muscle and reanimate the facial nerve during submental island flap procedures by preserving the mylohyoid muscle using human fresh cadaveric specimens. Six cadaveric heads were dissected and the position of the nerve to the mylohyoid muscle identified to the mylohyoid triangle documented. We identified the nerve to the mylohyoid muscle on all sides within the mylohyoid triangle and were able to separate the nerve from the submental island flap completely. Our results suggest that facial nerve reanimation using the nerve to the mylohyoid muscle can be used while reconstructing with a submental island flap in cases of intraoperative facial nerve injury.

DOI： 10.1097/SCS.0000000000009589

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

26歳男性。左側下唇を誤咬した後、滲出液を伴う腫瘤を自覚し、近在病院の歯科を受診した。加療されるも改善なく、腫瘤の増大傾向がみられたため、精査目的で当科へ紹介となった。初診時、左側下唇粘膜には25×12mm大の潰瘍を伴う腫瘤が認められた。造影CT画像では腫瘤は不整な外形を呈するが、明らかな内部性状の異常はみられなかった。アレルギー疾患や梅毒を疑い、血液検査が行われたが否定的で、組織生検によりランゲルハンス細胞組織球症(LCH)と診断された。全身検索の結果、下唇と左側眼瞼皮膚に発生したLCH SM型であり、下唇の病変にはコルチコステロイドを局所注射し、眼瞼の病変にはコルチコステロイド軟膏を塗布した。治療開始8ヵ月後には下唇の病変と左眼瞼皮膚の紅斑は消失し、8年経過現在、再燃や他臓器病変の出現はみられていない。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01073&link_issn=&doc_id=20230630350002&doc_link_id=10.5794%2Fjjoms.69.298&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.69.298&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Cetuximab (Cmab) is a molecularly targeted monoclonal antibody drug for head and neck squamous cell carcinoma (HNSC), although cetuximab resistance is a serious challenge. Epithelial cell adhesion molecule (EpCAM) is an established marker for many epithelial tumors, while the soluble EpCAM extracellular domain (EpEX) functions as a ligand for epidermal growth factor receptor (EGFR). We investigated the expression of EpCAM in HNSC, its involvement in Cmab action, and the mechanism by which soluble EpEX activated EGFR and played key roles in Cmab resistance. MATERIALS AND METHODS: We first examined EPCAM expression in HNSCs and its clinical significance by searching gene expression array databases. We then examined the effects of soluble EpEX and Cmab on intracellular signaling and Cmab efficacy in HNSC cell lines (HSC-3 and SAS). RESULTS: EPCAM expression was found to be enhanced in HNSC tumor tissues compared to normal tissues, and the enhancement was correlated with stage progression and prognosis. Soluble EpEX activated the EGFR-ERK signaling pathway and nuclear translocation of EpCAM intracellular domains (EpICDs) in HNSC cells. EpEX resisted the antitumor effect of Cmab in an EGFR expression-dependent manner. CONCLUSION: Soluble EpEX activates EGFR to increase Cmab resistance in HNSC cells. The EpEX-activated Cmab resistance in HNSC is potentially mediated by the EGFR-ERK signaling pathway and the EpCAM cleavage-induced nuclear translocation of EpICD. High expression and cleavage of EpCAM are potential biomarkers for predicting the clinical efficacy and resistance to Cmab.

DOI： 10.1016/j.oraloncology.2023.106433

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The bony notch on the inferior border of the mandible, anterior to the attachment of the masseter muscle, where the facial vessels commonly pass, has been called different names in the literature, e.g., premasseteric notch, antegonial notch, and notch for the facial vessels. Interestingly, various disciplines have leaned toward different names for this notch. Therefore, to aid in consistent communication among professionals, the present study aimed to analyze usage of these varied terms and make recommendations for the best terminology. Based on the adjacent anatomical structures used to name this notch, three groups were analyzed in this study, a group using masseter in the term, a group using gonion in the term, and a group using facial vessels in the term. A literature search found that the group using gonion in the term was found most in the literature. The orthodontics field used gonion in the term the most (29.0%: 31/107) followed by the oral and maxillofacial surgery field (14.0%: 15/107), the plastic surgery field (4.7%: 5/107), and the anatomy field (3.7%: 4/107). The dental field used gonion in this term the most (43.9%: 47/107) and the medical field used facial vessels in the term the most (33.3%: 6/18). Based on these results, the use of gonial terms for this notch seems to be preferred.

DOI： 10.5115/acb.23.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Current periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p &lt; 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF-α in the periodontal tissues and the serum concentration of TNF-α (both p &lt; 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF-α production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis.

DOI： 10.3390/jof9030314

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Breast cancer (BC) bone metastasis causes bone pain (BP), which detrimentally damages the quality of life and outcome of patients with BC. However, the mechanism of BC‑BP is poorly understood, and effective treatments are limited. The present study demonstrated a novel mechanism of BC‑BP using a mouse model of bone pain, in which mouse (EO771) and human (MDA‑MB‑231) BC cells were injected in the bone marrow cavity of tibiae. Western blot analysis using sensory nerves, in vivo assessment of cancer pain and in vitro calcium flux analysis were performed. These mice developed progressive BC‑BP in tibiae in conjunction with an upregulation of phosphorylated pERK1/2 and cAMP‑response element‑binding protein (pCREB), which are molecular indicators of neuron excitation, in the dorsal root ganglia (DRG) of sensory nerves. Importantly, mice injected with BC cells, in which the expression of the lactic acid transporter monocarboxylate transporter 4 (MCT4) was silenced, exhibited decreased BC‑BP with downregulated expression of pERK1/2 and pCREB in the DRG and reduced circulating levels of lactate compared with mice injected with parental BC cells. Further, silencing of the cell‑surface orphan receptor for lactate, G protein‑coupled receptor 81 (GPR81), in the F11 sensory neuron cells decreased lactate‑promoted upregulation of pERK1/2 and Ca2+ influx, suggesting that the sensory neuron excitation was inhibited. These results suggested that lactate released from BC cells via MCT4 induced BC‑BP through the activation of GPR81 of sensory neurons. In conclusion, the activation of GPR81 of sensory neurons by lactate released via MCT4 from BC was demonstrated to contribute to the induction of BC‑BP, and disruption of the interactions among lactate, MCT4 and GPR81 may be a novel approach to control BC‑BP.

DOI： 10.3892/ijo.2023.5487

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Retrieval of the displaced mandibular third molar in the floor of the mouth is challenging as the lingual nerve is always at risk of injury. However, there are no available data to show the incidence of the injury caused by the retrieval. The goal of this review article is to provide the incidence of the iatrogenic lingual nerve impairment/injury caused by the retrieval based on the review of the existing literature. The retrieval cases were collected with the search words below using PubMed, Google Scholar, and CENTRAL Cochrane Library database on October 6, 2021. A total of 38 cases of lingual nerve impairment/injury in 25 studies were eligible and reviewed. Temporary lingual nerve impairment/injury due to retrieval was found in six cases (15.8%) and all recovered between three to six months after retrieval. General anaesthesia and local anaesthesia were used for retrieval in three cases each. The tooth was retrieved using a lingual mucoperiosteal flap in all six cases. The permanent iatrogenic lingual nerve impairment/injury due to retrieval of the displaced mandibular third molar is considered extremely rare as long as the appropriate surgical approach is chosen based on surgeons' clinical experience and anatomical knowledge.

DOI： 10.1016/j.bjoms.2023.01.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cureus, Inc.  

Background Trigeminal-facial nerve communications have been recognized for over 100 years. More specifically, the mental nerve (MN) and marginal mandibular branch of the facial nerve (MMb) communication have been studied but the termination of these branches remains unclear. Therefore, we aim to classify the anatomical communication between the MN and MMb by its course. Methods Sixty sides from thirty adult cadaveric heads were dissected. The communicating branches were dissected and observed anatomically and histologically. Results Communication between the MN and MMb was found on all sides. Based on the course, the communication was classified into two types, superior and anterior. For the superior type, a small branch of the MN and MMb join and travel superiorly to reach the lower lip area. The communication was observed at the level of the mental foramen or above it. For the anterior type, a small branch of the MN and MMb join and travel anteriorly to reach the chin area. The termination was either in the subcutaneous tissue of the chin or in the mentalis. This communication was observed below the mental foramen. Histological observation revealed that these communications contained two or more perineuria. Conclusions Although the function of such neural communications is still unclear, this study helps better understand the anatomical variants of these unions and provides a novel classification system.

DOI： 10.7759/cureus.33733

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

61歳男性。右側舌下面の擦過痛を主訴に近在の歯科医院を受診し、経過観察をしていたものの、症状の改善がみられないため、精査加療目的で当科へ紹介となった。各種画像所見および生検結果より、右側舌に発生した扁平上皮癌(SCC)および濾胞性リンパ腫(FL)の同時性重複癌と診断された。治療は各専門領域の診療科と連携し、舌SCCに対する治療(術前化学療法、右側根治的頸部郭清術変法+舌可動部半側切除術+大胸筋皮弁を用いた舌再建術)を先行して行われ、初診+204日よりはFLに対しGB療法を開始した。6コース終了後に完全寛解し、現在まで舌SCC、FLともに再発をみられていない。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01073&link_issn=&doc_id=20230201450003&doc_link_id=10.5794%2Fjjoms.69.15&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.69.15&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：岡山歯学会  

8歳4ヵ月男児。7歳5ヵ月時に含歯性嚢胞に対し上顎右側乳側切歯、上顎左側乳中切歯、上顎正中過剰埋伏歯抜去術、上顎正中部歯性嚢胞摘出術を行った。その後、顎骨再生が不完全なため歯列不正を生じ、上顎両側側切歯の萠出遅延を認めた。上顎両側中切歯間の顎骨欠損を伴う骨格性I級、アングルII級、上下顎歯列叢生症例と診断し、オトガイ骨からの自家骨移植術を併用して矯正治療を行った。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Anatomy of the superior labial frenulum (SLF), at first glance, seems to be well established. However, existing studies on the SLF lack description of the incisivus labii superioris (ILS), which cannot be ignored when discussing the SLF. We believe that thorough understanding of the SLF necessitates the anatomical knowledge of the ILS. This study aimed to elucidate the anatomical relationship between the orbicularis oris (OO), ILS, and SLF. A total of twenty formalin fixed human cadaveric specimens were used for gross anatomical and/or histological observation. For histological observation, all specimens were stained with Masson-trichrome. The SLF was a mucosal fold between the gingival mucosa and alveolar mucosa with connective tissue deep to it. The connective tissue attached to the alveolar bone in the junction between the right and left ILS. Skeletal muscle fibers other than orbicularis oris was found in one specimen, which were considered the ILS. During a frenulectomy, removal of the connective tissue bundle is required to prevent recurrence of the high SLF insertion. This article is protected by copyright. All rights reserved.

DOI： 10.1002/ca.23973

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AME Publishing Company  

BACKGROUND: Pleomorphic adenoma (PA) is the most frequent benign salivary gland tumor, but a lip PA is rare. Although this tumor may be definitively diagnosed by imaging or a tissue biopsy if it is reasonably large, PAs on the lip are relatively small, and they present findings that are similar to those of other lip lesions, which can make a preoperative diagnosis difficult. METHODS: We analyzed all PAs in the oral region and lesions on the lips treated in our department over the past 20 years, and we discuss them together with the relevant literature. RESULTS: We found that 11.8% (n=6) of the PAs occurred on a lip (upper lip: 9.8%, lower lip: 2.0%), and ~1% of all mass lesions of the lips were PAs. The average size of the lip PAs was 1.5±0.7 cm (range, 0.7-2.2 cm). For preoperative diagnostic assistance, ultrasonography (US) (n=4), magnetic resonance (MR) (n=3), or no imaging (n=2) was used. An excisional biopsy was performed in all cases, and to date, no recurrence or malignant transformation has been observed. CONCLUSIONS: Lip PA is relatively rare. Because almost all of these lesions are small, a preoperative diagnosis is more difficult compared to palatal lesions. This tumor is also prone to long-term neglect and has the potential for recurrence and malignant transformation. It is thus necessary to perform an excision that includes the capsule and surrounding tissues, and careful postoperative follow-up should be continued.

DOI： 10.21037/gs-22-308

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記述言語：英語  

Fibrous dysplasia (FD) is a fibrous lesion of immature bone, with an incidence of 10-20% in the head and neck region. Most cases are monostotic, but when a lesion occurs on the maxillofacial region and spreads to the surrounding bone, it is classified as polyostotic, despite its localized occurrence. In some cases, surgical intervention is required to improve the cosmetic or functional disturbance of a FD in the maxillofacial region, but it is necessary to confirm symmetry of the maxillofacial region in real time, and a surgical support system is required to compensate. Furthermore, prosthetic intervention is considered when postoperative acquired defects occur or further cosmetic or occlusal function improvement is needed. A comprehensive approach by an oral surgeon and a maxillofacial prosthodontist is necessary for the successful treatment and rehabilitation of such patients. In this article, we describe the case of a craniomaxillofacial FD patient with facial asymmetry and denture incompatibility with improved quality of life measures by integrating surgical treatment using a navigation system and postoperative prosthetic rehabilitation. We also discuss recent diagnostic methods and treatment strategies for craniomaxillofacial FD in the literature.

DOI： 10.3390/diagnostics12092146

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.ijom.2022.08.019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: A dental implant displaced into the maxillary sinus can be removed transorally or transnasally. There is no report investigating any potential positional limitations by the transoral endoscope-assisted approach. The implant's location within the maxillary sinus was reviewed to clarify indications for this approach. Case report: A 36-year-old man was referred to us for removal of a dental implant displaced into the right maxillary sinus. The implant changed position preoperatively, but the transoral endoscope-assisted approach proved successful. Methods: A literature search through October 2020 was performed in PubMed for cases of implant removal from the maxillary sinus via transoral endoscope-assisted and transnasal endoscopic approaches. Results: Sixty-two prior cases were identified, 20 cases by the transoral endoscope-assisted approach and 43 cases by one or two transnasal endoscopic approaches, including one duplicate case. There were no cases in which the implant was not identified by the transoral endoscope-assisted approach, but two cases in which the implant had moved to an unfavorable location and was not identified by only the initial transnasal endoscopic approach. Conclusion: Clinicians can preferentially choose the transoral endoscope-assisted approach, considering the possibility of unfavorable repositioning of the displaced implant within the maxillary sinus.

DOI： 10.1007/s12663-022-01703-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

ABSTRACT: Sufficient knowledge of anatomy is critical for oral and maxillofacial surgeons to provide the best treatment to their patients. The authors have recently established the "Clinical Anatomy Research Association in Oral and Maxillofacial Surgery." There is no doubt as to the benefits of collaboration between oral and maxillofacial surgeons/radiologists and anatomists. In this article, we share what was accomplished at the first annual online conference and discuss our mission for the future.

DOI： 10.1097/SCS.0000000000008053

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Angiogenin is a multifunctional secreted ribonuclease that is upregulated in human cancers and downregulated or mutationally inactivated in neurodegenerative diseases. A role for angiogenin in glioblastoma was inferred from the inverse correlation of angiogenin expression with patient survival but had not been experimentally investigated. METHODS: Angiogenin knockout mice were generated and the effect of angiogenin deficiency on glioblastoma progression was examined. Angiogenin and plexin-B2 genes were knocked down in glioblastoma cells and the changes in cell proliferation, invasion and vascular association were examined. Monoclonal antibodies of angiogenin and small molecules were used to assess the therapeutic activity of the angiogenin-plexin-B2 pathway in both genetic and xenograft animal models. RESULTS: Deletion of Ang1 gene prolonged survival of PDGF-induced glioblastoma in mice in the Ink4a/Arf-/-:Pten-/- background, accompanied by decreased invasion, vascular association and proliferation. Angiogenin upregulated MMP9 and CD24 leading to enhanced invasion and vascular association. Inhibition of angiogenin or plexin-B2, either by shRNA, monoclonal antibody or small molecule inhibitor, decreases sphere formation of patient-derived glioma stem cells, reduces glioblastoma proliferation and invasion and inhibits glioblastoma growth in both genetic and xenograft animal models. CONCLUSIONS: Angiogenin and its receptor, plexin-B2, are a pair of novel regulators that mediate invasion, vascular association and proliferation of glioblastoma cells. Inhibitors of the angiogenin-plexin-B2 axis have therapeutic potential against glioblastoma.

DOI： 10.1038/s41416-022-01814-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Previous studies suggest that the nerve to the mylohyoid muscle could have a cutaneous branch. However, its clinical relevance has rarely been discussed because there is insufficient evidence for it. Our aim in this study was to investigate the anatomy of the cutaneous branch of the nerve to the mylohyoid muscle and extend the discussion to surgical management. METHODS: Twenty sides from ten embalmed cadaveric heads were dissected to identify the cutaneous branch of the nerve to the mylohyoid muscle. The cutaneous branch was traced up to its termination. RESULTS: The cutaneous branch was observed in 90% and classified into types I and II. In type I, the terminal trunk reached the anterior belly of the digastric muscle. In type II there were two types of terminal trunks, superior and inferior branches, which were identified on all sides. The number of the terminal trunk was one in 23.1% (type I; 6/26) and two in 76.9% (type II; 20/26). The terminal points of the cutaneous branch were all located within a 3 cm × 2 cm rectangular segment in the center of the submental area. CONCLUSIONS: We propose a new dermatome including the nerve to the mylohyoid muscle in the center. Understanding the cutaneous branch of the nerve could help surgeons to prevent iatrogenic sensory loss of the submental area.

DOI： 10.1016/j.aanat.2022.151934

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jdd.12922

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記述言語：英語  

Cervicofacial subcutaneous emphysema (SE) is primarily caused by dental treatment introducing gas into the subcutaneous tissue. Air rapidly dissects into the subcutaneous tissue with face and neck swelling, leading to respiratory distress, patient discomfort, and chest pain. Computed tomography (CT) can detect spreading SE patterns. However, the true volume of SE and the degree of air changes in the body over time remain unknown. We evaluated the healing process of SE and the temporal changes in the volume of emphysema in three cases detected using our hospital's electronic health record systems based on inclusion and exclusion criteria over the past 10 years, with CT and three-dimensional (3D) images. The first case was a 46-year-old woman who presented with complaints of swelling from her right eyelid to the neck and clavicles, pain on swallowing, respiratory distress, and hoarseness. The second case was a 35-year-old man who presented with complaints of swelling over the face. The third case was a 36-year-old man who presented with complaints of swelling from the left cheek to the neck. CT revealed SE and pneumomediastinum in all cases. All the patients were administered an antibacterial drug. The CT and 3D images showed an improvement in emphysema 3 days after the onset, with more than half of the volume reduction in emphysema. This made it possible to evaluate the changes in the air content of SE. Observation with CT until the healing process of SE is completed is crucial, and 3D images also help evaluate changes over time.

DOI： 10.3390/healthcare10020290

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aim of this study was to clarify the morphology of the mylohyoid branch of the inferior alveolar artery and the main blood supply to the mylohyoid muscle. METHODS: The maxillary artery (MA) and inferior alveolar artery (IAA) within the infratemporal fossa, the facial and submental arteries within the submandibular triangle, and the nerve to the mylohyoid muscle and related artery were dissected in twelve sides from embalmed cadaveric heads. The main blood supply to the extraoral (inferior) surface of the mylohyoid muscle was recorded. RESULTS: The mylohyoid branch of the inferior alveolar artery was an anastomosis of the descending branch of either the inferior alveolar or maxillary artery and the ascending branch of either the submental or facial artery. The anastomosis was classified into four types according to the origins of the arteries. The main blood supply to the extraoral surface of the mylohyoid muscle was the submental artery. CONCLUSIONS: The results of this study indicate that the mylohyoid branch of the IAA in human adults is an anastomosis of branches of the maxillary and facial arteries.

DOI： 10.1016/j.aanat.2021.151852

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: In this review, cases of herpes zoster (HZ) infection following receipt of COVID-19 vaccines will be analyzed. We also present two cases of oral HZ following the COVID-19 vaccine and discuss this clinical anatomy. MATERIALS AND METHODS: A database search using PubMed was conducted in August 2021 and 20 articles were found to be eligible for review. Patient data and vaccine information were analyzed. In addition, two cases of oral HZ infection following the receipt of COVID-19 vaccines are presented. RESULTS: A total of 399 cases were identified. The affected dermatomes mimicked the regular distribution of HZ. For the dermatomes of the face, the various reports used different ways to describe the areas involved; CNV, CNV1, CNV2, CNV3, lower jaw, forehead, and under the eyebrow (CNV, 2 cases; CNV1, 4 cases; CNV2, 3 cases; and CNV3, 3 cases). Some patients who had a history of varicella zoster virus vaccination had HZ following the COVID-19 vaccination. Two patients with oral HZ following vaccination were found to have involvement of the greater palatine nerve. CONCLUSIONS: Vaccine-related HZ cases have been reported worldwide. Although many studies with a larger number of cases are ongoing, detailed information can be obtained from case reviews as reported herein.

DOI： 10.1002/ca.23790

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Since cone-beam computed tomography was developed, a number of radiological studies on the bifid mandibular canals (BMCs) and trifid mandibular canals (TMCs) have been reported. However, many of the suggested subtypes of the BMC described in the literature seem to be normal branches of the inferior alveolar nerve. This might be due to a lack of revisiting classic anatomical studies in the field of radiology. Therefore, such studies are revisited here. METHODS: A database search using PubMed and Google Scholar was conducted on BMC and TMC. Eighty-nine articles underwent full-text assessment. The reported three classifications of BMC and the six modified classifications were reviewed and compared to the intramandibular inferior alveolar nerve branches. RESULTS: Some subtypes of BMC and TMC simply represent normal inferior alveolar nerve branches, i.e., retromolar branch, molar branch (alveolar branch/dental branch), large mental branch, or communicating branch. Others such as Naitoh's type III BMC and forward canal might be a true BMC. CONCLUSION: We found that the bifid mandibular canal is an additional intramandibular canal running parallel to the mandibular canal with/without confluence with the main canal through comparison of classifications of BMC/TMC between the radiology and anatomy fields.

DOI： 10.1007/s00276-021-02862-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aim: Cancer research has been conducted using cultured cells as part of drug discovery testing, but conventional two-dimensional culture methods are unable to reflect the complex tumor microenvironment. On the other hand, three-dimensional cultures have recently been attracting attention as in vitro models that more closely resemble the in vivo physiological environment. The purpose of this study was to establish a 3D culture method for oral cancer and to verify its practicality. Materials and Methods: Three-dimensional cultures were performed using several oral cancer cell lines. Western blotting was used for protein expression analysis of the collected cell masses (spheroids), and H-E staining was used for structural observation. The cultures were exposed to cisplatin and cetuximab and the morphological changes of spheroids over time and the expression changes of target proteins were compared. Results: Each cell line formed spheroidal cell aggregates and showed enhancement of cell adhesion molecules over time. H-E staining showed tumor tissue-like structures specific to each cell line. Cisplatin showed concentration-dependent antitumor effects due to loss of cell adhesion and spheroid disruption in each cell line, while cetuximab exhibited antitumor effects that correlated with EGFR expression in each cell line. Conclusion: Spheroids made from oral cancer cell lines appeared to have tumor-like characteristics that may reflect their clinical significance. In the future, it may become possible to produce tumor spheroids from tissue samples of oral cancer patients, and then apply them to drug screening and to develop individualized diagnostic and treatment methods.

DOI： 10.7150/ijms.74109

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of the present study was to determine the contribution of the orbicularis oculi (OOc) to the zygomaticus major (Zmj) in connecting the orbital region to the corner of the mouth. The OOc and Zmj of 22 embalmed adult Korean cadavers were dissected in 44 hemifaces. The OOc fibers were traced to determine their contribution to the Zmj. Parts of the superficial bundle in the orbital region of the OOc extended directly or indirectly to the Zmj in 22.7% of the specimens. The anatomical contribution of the OOc to the Zmj was divided into three categories depending on whether the connection between them was direct or indirect: (1) superficial orbital OOc fibers extended directly to the Zmj in 6.8% of the specimens, (2) superficial orbital OOc fibers extended to the zygomaticus minor and their small portion joined to the upper fibers of the Zmj in 15.9% of the specimens, and (3) no connection was identified between the OOc and Zmj in 77.3% of the specimens. The results of this study provide further anatomical insight into the relationship between the OOc and zygomaticus muscle complex. This information could be helpful for elucidating the anatomy of smiling and treatment and surgery designs for balanced or ideal smiles.

DOI： 10.1371/journal.pone.0272060

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The displacement of the tooth/tooth fragment into the floor of mouth sometimes happens during the lower third molar surgery and the patients are usually referred to oral and maxillofacial surgeons. To date, however, there is no consensus how to manage the displaced tooth due to the lack of available data. METHODS: In this study, we have retrospectively analyzed the management of the displaced lower third molar into the floor of mouth. Our institute experienced seven cases during 2010 to 2020. RESULTS: Incidence rate of the lingual nerve injury caused by displacement of the lower third molar was 1/7. Six patients out of seven underwent surgical removal of the displaced fragment. The direct approach was used when the fragment was palpable superficially and the fragment was horizontally located away from the lingual plate (2 cases), while when the fragment was not palpable, or was palpable and adjacent to the lingual plate, the lingual mucoperiosteal flap was selected (4 cases). CONCLUSION: We conclude that the palpation and preoperative diagnosis with computed tomographic images are significantly important to decide a better and most effective surgical approach.

DOI： 10.1007/s10006-021-01012-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The submental artery usually runs anteriorly on the inferior surface of the mylohyoid muscle, giving branches to that muscle and to the anterior belly of the digastric muscle, finally supplying the submental skin. Branches of it often perforate the mylohyoid muscle and enter the sublingual space. During a routine anatomy dissection, we encountered a case in which the main trunk of the submental artery perforated the mylohyoid muscle, where the sublingual artery usually runs. No branches coursed anteriorly to supply the submental skin. To our knowledge, this submental artery variation has not been reported in the English literature. Any surgical procedure in the submandibular area, such as the axial pattern submental local flap, requires knowledge of such arterial variations.

DOI： 10.1007/s00276-021-02830-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Fibers of the facial muscles occasionally extend, cross the midline, and connect to surrounding structures on the contralateral side, perhaps enabling the mouth to make more delicate movements and generate more facial expressions. This case report describes a variant in which the extended fibers of the mentalis crossed the midline and indicates the relationship of these fibers to the surrounding structures. Some of the deepest fibers of the mentalis descended inferomedially and crossed transversely just below the chin prominence to attach to the periosteum of the mandible on the contralateral side. The variation presented in this study shed light on the interactions of the mentalis with the surrounding muscles.

DOI： 10.5115/acb.21.127

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The stromal cells in the tumor microenvironment (TME) can influence the progression of multiple types of cancer; however, data on oral squamous cell carcinoma (OSCC) are limited. In the present study, the effects of verrucous squamous cell carcinoma‑associated stromal cells (VSCC‑SCs), squamous cell carcinoma‑associated stromal cells (SCC‑SCs) and human dermal fibroblasts (HDFs) on the tumor nest formation, proliferation, invasion and migration of HSC‑3 cells were examined in vitro using Giemsa staining, MTS, and Transwell (invasion and migration) assays, respectively. The results revealed that both the VSCC‑SCs and SCC‑SCs inhibited the tumor nest formation, and promoted the proliferation, invasion and migration of OSCC cells in vitro. Furthermore, the effects of VSCC‑SCs, SCC‑SCs and HDFs on the differentiation, proliferation, invasion and migration of OSCC cells in vivo were evaluated by hematoxylin and eosin staining, tartrate‑resistant acid phosphatase staining, immunohistochemistry and double‑fluorescent immunohistochemical staining, respectively. The results demonstrated that the VSCC‑SCs promoted the differentiation, proliferation, invasion and migration of OSCC cells, while the SCC‑SCs inhibited the differentiation, and promoted the proliferation, invasion and migration of OSCC cells in vivo. Finally, microarray data were used to predict genes in VSCC‑SCs and SCC‑SCs that may influence the progression of OSCC, and those with potential to influence the differential effects of VSCC‑SCs and SCC‑SCs on the differentiation of OSCC. It was found that C‑X‑C motif chemokine ligand (CXCL)8, mitogen‑activated protein kinase 3 (MAPK3), phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA), C-X-C motif chemokine ligand 1 (CXCL1) and C‑C motif chemokine ligand 2 (CCL2) may be involved in the crosstalk between VSCC‑SCs, SCC‑SCs and OSCC cells, which regulates the progression of OSCC. Intercellular adhesion molecule 1 (ICAM1), interleukin (IL)1B, Fos proto‑oncogene, AP‑1 transcription factor subunit (FOS), bone morphogenetic protein 4 (BMP4), insulin (INS) and nerve growth factor (NGF) may be responsible for the differential effects of VSCC‑SCs and SCC‑SCs on the differentiation of OSCC. On the whole, the present study demonstrates that both VSCC‑SCs and SCC‑SCs may promote the progression of OSCC, and SCC‑SCs were found to exert a more prominent promoting effect; this may represent a potential regulatory mechanism for the progression of OSCC.

DOI： 10.3892/ijo.2021.5252

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The purpose of this study was to evaluate the risk of injury to the facial (FA) and related arteries during mandibular third molar (MTM) extraction using contrast-enhanced computed tomography (CE-CT). CE-CT images of the MTM region were retrospectively reviewed. The area of the MTM was equally divided into three zones in the coronal images from mesial to distal, that is, zone 1, zone 2, and zone 3. The FA, submental artery (SMA), and sublingual artery (SLA) were identified. The distance from the mandible to FA, SMA, and SLA and the diameter of the FA, SMA, and SLA was measured in three zones, respectively. The thickness of the facial soft tissues and width of the mandible were measured at their maximum. The mean distance from the FA to the buccal cortical bone in zone 1, zone 2 and zone 3 was 2.24 mm, 2.39 mm and 1.67 mm, respectively. The SMA and SLA were found to be distal to the mandible. The mean diameter of the FA was 1.26 mm in males and 1.04 mm in females, respectively (p < 0.0001). The distance between the FA and buccal cortical bone of the mandible, and the patients' weight showed moderate correlation in zones 1 and 2. Based on our findings, the FA can be damaged if the surgical invasion reaches the facial soft tissues during MTM surgery. The patients' weight might be a good predictor for FA injury when CE-CT is not available.

DOI： 10.1002/ca.23779

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記述言語：英語  

Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is an iatrogenic immunodeficiency-associated lymphoproliferative disorder that occurs mainly with MTX use. This disorder has been associated with Epstein-Barr virus (EBV) infection. In 2017, the WHO newly defined the disease concept of EBV-positive mucocutaneous ulcer (EBV-MCU) as a good-prognosis EBV-related disease. Here, we report 10 cases of MTX-LPD or EBV-MCU in the oral mucosa. This retrospective, observational study was conducted with MTX-LPD or EBV-MCU in the oral mucosa patients who visited us during the nine year period from 2012 to 2021. We gathered the basic information, underlying disease, histopathological evaluation, treatment and prognosis for the subjects. All were being treated with MTX for rheumatoid arthritis. EBV infection was positive in all cases by immunohistochemistry. A complete or partial response was obtained in all cases with the withdrawal of MTX. Our results suggests that the most common risk factor for developing EBV-MCU is the use of immunosuppressive drugs. The most common site of onset is the oral mucosa, which may be attributed to the mode of EBV infection and the high incidence of chronic irritation of the oral mucosa. A small number of patients had been diagnosed with MTX-LPD, but we consider that these cases were EBV-MCU based on our study.

DOI： 10.3390/diagnostics11081375

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: In this article we review the literature on the inferior labial gland from a clinical and anatomical perspective. Background: Regardless of its importance in clinical practice, there are no medical literature that comprehensively reviewed the inferior labial gland. Methods: A database search using PubMed and Google Scholar was conducted. The following keywords were used in the search: "lower labial salivary gland", "lower labial gland", "inferior labial salivary gland", AND "inferior labial gland". Conclusions: The human labial glands are types of minor salivary gland that continuously secrete small amounts of mucous and serous substances to maintain oral health. The inferior labial glands are innervated by the inferior labial branch of the mental nerve, and the inferior labial branch of the facial artery is the main arterial supply to the lower lip. Although they only have an auxiliary role in saliva production compared to the major salivary glands, minor salivary glands provide a certain amount of lubrication in the oral cavity by the continuous outflow of saliva. The inferior labial gland not only promotes moisturization in the oral cavity but also secretes substances with antibacterial effects, which is important for the function of the oral cavity. A recent study showed that the rate of salivary secretion from the inferior labial glands does not change with age, and in some cases the inferior labial glands are used for diagnosing intractable diseases such as Sjogren's syndrome and cystic fibrosis. In addition, since the inferior labial glands themselves can be the site of cyst and/or neoplasia development, we should be careful to distinguish them from other diseases. Elucidation of the anatomy, physiology, and pathology of the inferior labial glands, is important for understanding human health and diseases.

DOI： 10.21037/gs-21-143

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The distribution of cells expressing SARS-CoV-2 entry factor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in human oral tissues were tested. The investigation was conducted with normal flesh tissue and paraffin-embedded specimens. The ACE2 and TMPRSS2 expression was detected with all subjects in the normal mucosa of the keratinized stratified squamous epithelia of the tongue and non-keratinized stratified squamous epithelia of the lip and cheek. It was found that ACE2 is expressed in the cytoplasm and on the cell membrane mainly in the stratum granulosum of the epithelia while the TMPRSS2 is strongly expressed on the cell membrane mainly in the stratum granulosum and stratum spinosum, but not in the stratum basale. Antibodies' reactions for ACE2 and TMPRSS2 were not observed in the nuclei or keratin layer. The expression of ACE2 and TMPRSS2 in the oral epithelia appears to be general, and the expression was also observed in the mucous and serous acini of the labial glands. The SARS-CoV-2 may transiently attach to the oral mucosa and the minor salivary glands which are present under all of the oral mucosa. The oral cavity can be considered an important organ for SARS-CoV-2 attachment and may provide a preventive medical avenue to guard against COVID-19 by preventing saliva from scattering.

DOI： 10.1111/joa.13391

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記述言語：英語  

In younger patients of LCH, we should consider that the effectiveness of follow-up without aggressive treatment for SS-type LCH in the oral and maxillofacial bone. However, there are very rare case in which an SS-type LCH recurred after showing a healing tendency. Regular follow-up must be performed even after healing.

DOI： 10.1002/ccr3.4321

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI  

Gingival squamous cell carcinoma (SCC) frequently invades the maxillary or mandibular bone, and bone destruction is known as a key prognostic factor in gingival SCCs. Recently, Neurokinin 3 receptor (NK-3R), the receptor ligand for NK-3, which is a member of the tachykinin family expressed in the central nervous system, was identified through pathway analysis as a molecule expressed in osteoclasts induced by the hedgehog signal. Although the expression of NK-3R has been detected in osteoclast and SCC cells at the bone invasion front, the relationship between NK-3R expression and the prognosis of gingival SCC patients remains unclear. In the present study, we retrospectively reviewed 27 patients with gingival SCC who had undergone surgery with curative intent. Significantly higher NK-3R expression in tumor cells was found in a case of jawbone invasion than in a case of exophytic poor jawbone invasion. On the other hand, no significant association was observed between NK-3R tumor-positive cases and tumor size, TNM stage, or tumor differentiation. The survival rate tended to be lower in NK-3R tumor-positive cases, but not significantly. However, the disease-specific survival rate was significantly lower in patients with a large number of NK-3R-positive osteoclasts than in those with a small number of them at the tumor bone invasion front. Our results suggest that NK-3R signaling in the gingival SCC bone microenvironment plays an important role in tumor bone destruction and should be considered a potential therapeutic target in advanced gingival SCC with bone destruction.

DOI： 10.3390/diagnostics11061044

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The nerve to the mylohyoid muscle has been well studied but there are no specific anatomical landmarks for identifying it. Therefore, we aimed to identify anatomical landmarks for localizing the nerve to the mylohyoid muscle in the submandibular region. Sixteen sides from eight embalmed Caucasian cadaveric heads were used in this study. The mean age at the time of death of the specimens was 80.3 years. The anterior and posterior bellies of the digastric muscle, submental artery, and mylohyoid muscle were dissected to verify their relationships with the nerve to the mylohyoid muscle. The nerve to the mylohyoid muscle was found medial to the submental artery, lateral to the anterior belly of the digastric muscle, and anterior to the posterior border of the mylohyoid muscle on all sides. Herein, we identified what we term the mylohyoid triangle. This anatomical region can help localize the nerve to the mylohyoid muscle.

DOI： 10.5115/acb.21.019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Neurofibromatosis is a disease that causes various abnormalities such as neurofibroma, mainly in the skin and nerves. The common sites in the oral cavity are the palate, gingiva, tongue, buccal mucosa, and lips but, occurrence in the mandible is rare. PRESENTATION OF CASE: A 26-year-old woman was referred to our clinic because of percussion pain. Radiographic findings showed a radiolucent area. The patient was clinically diagnosed with a radicular cyst by a previous doctor. Multiple café-au-lait spots were found disseminated on her body, and she had already been prenatally diagnosed with neurofibromatosis type 1 (NF1). We performed a biopsy and suggested a neurofibroma. Tumor extirpation was performed under general anesthesia. The histopathological diagnosis showed a neurofibroma. CLINICAL DISCUSSION AND CONCLUSION: NF1 is a systemic nevus that causes abnormalities in melanocytes and Schwann cells, and various lesions appear, but intramandibular lesions are extremely rare. Diagnosis of NF1 and radicular cysts in the mandible is difficult due to their image resemblance. However, it should be kept in mind if the underlying disease is NF1. In our case, it was easy to detach and may have originated from small peripheral nerve endings in the mandible.

DOI： 10.1016/j.ijscr.2021.105883

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The general principles of anatomical terminology indicate that the "mandibular canal" should be named the "inferior alveolar canal" as it accommodates the inferior alveolar neurovascular bundles. Therefore, we performed a Delphi study to evaluate the current understanding and use of the terminology in different geographical regions and areas of expertise and to determine the appropriate terminology for this bony canal. A Delphi panel was formed and questions sent and answered via email about: field of expertise (anatomy, oral surgery/oral and maxillofacial (OMF) surgery, oral radiology/OMF radiology, plastic surgery, ENT surgery, or dentistry with the exception of oral/OMF surgery and oral/OMF radiology), years of experience in the field of expertise, country currently working in, "what is the name of the bony canal that contains the inferior alveolar neurovascular bundle," and "what should the structure above be called, in general?" A total of 52 participants responded to the questionnaire. Half or more of the experts in anatomy, oral/OMF surgery, and ENT/plastic surgery considered "mandibular canal" to be the most appropriate name for this bony canal. In contrast, more than half of all experts in oral/OMF radiology and dentistry, that is, most fields of dentistry, considered "either mandibular canal or inferior alveolar canal" to be the appropriate name. The results of the Delphi study and general principles suggest that an alternative term for the "mandibular canal" should be "inferior alveolar canal."

DOI： 10.1002/ca.23740

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記述言語：英語  

DOI： 10.1007/s00276-021-02743-4

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The mandibular canal, as it was formerly named in Terminologia Anatomica (TA), has also been called the inferior alveolar (nerve) canal in many scientific publications. This study was conducted to investigate how these terms have been understood in different regions and different areas of expertise and to discuss the appropriate future application of the term "mandibular canal." METHODS: A literature search was conducted using PubMed, and articles using different terms for this structure were classified into two groups, inferior alveolar canal/inferior alveolar nerve canal (IAC/IANC) and the mandibular canal (MC). The 50 most recent articles in each group were included. Publication year, journal title, country of the first author, and affiliation of all authors were recorded in both groups for all 100 articles. RESULTS: There was a significant difference between the IAC/IANC and MC groups in the numbers of anatomy journals, other journals, and anatomy affiliations. Turkey published most frequently with a total of 15 articles, followed by Iran with 10 articles, and China/India/United States with seven each. When the six countries of the first author that had three or more publications in each group were compared, only Turkey appeared in both groups; otherwise, different countries were in the two groups. CONCLUSIONS: Based on the results of this analysis, and considering that the tentative new term "inferior alveolar foramen" is used in the latest TA, we suggest that the mandibular canal should be renamed the "inferior alveolar canal."

DOI： 10.1002/ca.23648

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Lower third molar removal is the most commonly performed dental surgical procedure. Nevertheless, it is difficult to ensure that all the informed consent forms given to patients are based on the best evidence as many newer publications could change the conclusions of previous research. Therefore, the goal of this review article is to cover existing meta-analyses, randomized control trials, and related articles in order to collect data for improved and more current informed consent.

DOI： 10.1002/ca.23693

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Many anatomical variations of the superficial veins of the head and neck have been reported throughout the literature. Accordingly, anatomists and surgeons must have a comprehensive understanding of these variations to avoid confusion. Duplication of the external jugular vein (EJV) is occasionally observed during routine cadaveric dissections; however, this variation seems to be reported less often than actual experience suggests. Therefore, to gain a better understanding of its anatomical and clinical implications, an analysis of the available data should be available. Thus, in this article, we reviewed the current available literature for studies reporting duplication of the EJV. METHODS: We conducted a search using PubMed and Google Scholar with the following keywords: "duplication of the external jugular vein," "division of the external jugular vein," and "fenestration of the external jugular vein," "double external jugular vein," and "doubled external jugular vein." As a case illustration, we also describe a case of a duplicated EJV found during a right neck dissection of a female cadaver. RESULTS: Twenty sides across sixteen different studies were analyzed including the present case. All studies were published between 2009 and 2020. EJV division patterns were classified as either duplication, fenestration, fenestration followed by duplication, or double fenestrations. CONCLUSIONS: We have reviewed the literature regarding cases documenting duplication/fenestration of the EJV. As it is often difficult to find recent studies that report on classic anatomical variations, therefore, revisiting older articles and textbooks is necessary for achieving a "comprehensive" review, especially across different languages.

DOI： 10.1007/s00276-021-02717-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bone pain is a common complication of breast cancer (BC) bone metastasis and is a major cause of increased morbidity and mortality. Although the mechanism of BC-associated bone pain (BCABP) remains poorly understood, involvement of BC products in the pathophysiology of BCABP has been proposed. Aggressive cancers secrete damage-associated molecular patterns (DAMPs) that bind to specific DAMP receptors and modulate cancer microenvironment. A prototypic DAMP, high mobility group box 1 (HMGB1), which acts as a ligand for the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs), is increased in its expression in BC patients with poor outcomes. Here we show that 4T1 mouse BC cells colonizing bone up-regulate the expression of molecular pain markers, phosphorylated ERK1/2 (pERK) and pCREB, in the dorsal root ganglia (DRGs) innervating bone and induced BCABP as evaluated by hind-paw mechanical hypersensitivity. Importantly, silencing HMGB1 in 4T1 BC cells by shRNA reduced pERK and pCREB and BCABP with decreased HMGB1 levels in bone. Further, administration of a neutralizing antibody to HMGB1 or an antagonist for RAGE, FPS-ZM1, ameliorated pERK, pCREB and BCABP, while a TLR4 antagonist, TAK242, showed no effects. Consistent with these in vivo results, co-cultures of F11 sensory neuron-like cells with 4T1 BC cells in microfluidic culture platforms increased neurite outgrowth of F11 cells, which was blocked by HMGB1 antibody. Our results show that HMGB1 secreted by BC cells induces BCABP via binding to RAGE of sensory neurons and suggest that the HMGB1/RAGE axis may be a potential novel therapeutic target for BCABP.

DOI： 10.1016/j.jbo.2020.100330

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記述言語：英語  

DOI： 10.1016/j.radonc.2020.12.007

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記述言語：英語  

Tracheal intubation for general anesthesia can sometimes be difficult in patients with a large mass in the mouth floor. Preoperative evaluation of the patient's airway is most important when treating large oral disease.

DOI： 10.1002/ccr3.3494

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKCα/βII, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.

DOI： 10.3389/fphar.2021.674366

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background : An accessory parotid gland (APG) is a common anatomical structure that occurs in 10%-56% of individuals. Pleomorphic adenomas are the most common benign tumors of the APG, and their ideal treatment is surgical excision, although there is a risk for aesthetic disorders and facial nerve damage due to the site of origin. Moreover, despite being benign, these tumors are known to recur. Therefore, it is necessary to achieve both reliable excision and avoidance of facial nerve damage. Case presentation : We report a case of a 49-year-old Japanese man with a mass in his left cheek. The lesion was diagnosed as a benign salivary gland tumor derived from the APG by computed tomography imaging, magnetic resonance imaging and fine needle aspiration cytology. We resected the tumor using modified high submandibular incision under the endoscopic-assisted field of view. Discussion and Conclusions : The tumor was less invasive and reliably resected using an endoscope. In surgical treatment, the endoscopic-assisted technique is very useful to achieve complete tumor resection and prevent relapse while avoiding serious complications due to surgical procedures. J. Med. Invest. 68 : 376-380, August, 2021.

DOI： 10.2152/jmi.68.376

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Advanced head and neck cancer (HNC) can invade facial bone and cause bone pain, thus posing a significant challenge to the quality of life of patients presenting with advanced HNC. The present study was designed to investigate HNC bone pain (HNC‑BP) in an intratibial mouse xenograft model that utilized an HNC cell line (SAS cells). These mice develop HNC‑BP that is associated with an expression of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in dorsal root ganglia (DRG) sensory neurons. Our experiments demonstrated that the inhibition of high mobility group box 1 (HMGB1) by short hairpin (shRNA) transduction, HMGB1 neutralizing antibody, and HMGB1 receptor antagonist suppressed the HNC‑BP and the pERK1/2 expression in DRG. It was also observed that HNC‑derived HMGB1 increased the expression of the acid‑sensing nociceptor, transient receptor potential vanilloid 1 (TRPV1), which is a major cause of osteoclastic HNC‑BP in DRG. Collectively, our results demonstrated that HMGB1 originating in HNC evokes HNC‑BP via direct HMGB1 signaling and hypersensitization for the acid environment in sensory neurons.

DOI： 10.3892/or.2020.7788

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記述言語：英語  

Consideration of unexpected metastasis in patients who have undergone neck dissection with advanced tumors must be anticipated with careful follow-up.

DOI： 10.1002/ccr3.3086

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Sarcopenia is characterized by depletion of skeletal muscle mass (SMM) and can cause increased postoperative complication in free flap procedure. One of the most important considerations while deciding the indication of the procedure is patients' survival. This study aimed to verify the relationship between low SMM and survival in patients who undergo oral cancer resection using free flap. METHODS: SMM was evaluated using the skeletal muscle index (SMI cm2 /m2 ), which was defined using cross-sectional areas of skeletal muscles on computed tomography at the level of the third lumbar vertebrae normalized for height. Overall, 111 patients who underwent primary oral cancer resection and free flaps were included. Multivariate Cox regression analyses were used to evaluate the prognostic factors for survival. RESULTS: A total of 25 patients (22.5%) were diagnosed with low SMM. The mean SMI was 42.2 cm2 /m2 . Multivariable analyses showed that increased age (hazard ratio [HR]; 4.98, p = .004), infiltrative growth pattern INF-c (HR; 3.83, p = .037), and low SMM (HR; 2.59, p = .034) were significant negative prognostic factors for overall survival. Increased age (HR; 3.18, p = .005), extra-nodal extension (HR; 3.30, p = .001), and low SMM (HR; 2.42, p = .017) were significant negative prognostic factors for disease-free survival. CONCLUSIONS: Low SMM is a significant negative prognostic factor for overall and disease-free survival in oral cancer patients undergoing free flap. Future prospective studies are warranted to identify effective preoperative exercise and nutrition programs to improve low skeletal muscle and survival rate in patients undergoing free flap procedures.

DOI： 10.1002/micr.30668

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

The purpose of this study is to assess accelerator-based boron neutron capture reaction (BNCR) in human tumor cell lines by colony formation assay and modified high density survival assay (HDS assay). The results of post irradiation survival rate in human oral squamous cell carcinoma and osteosarcoma using both assays were similar. Therefore, HDS assay would be efficient to evaluate BNCR in not only tumor cells but also in normal cells as BNCT screening.

DOI： 10.1016/j.apradiso.2020.109271

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: It is necessary to correlate cancellous bone patterns with cone beam computed tomography (CBCT) images, but this has not been done to date. The goal of this study was to establish how the superior wall of the mandibular canal (MC) on CBCT images correlates with the cancellous bone around the MC on gross anatomical findings. METHODS: Twenty sides from 10 dry mandibles derived from six females and four males were used for this study. In order to observe the MC distally, the specimen was prepared by the method used in our previous study. The cancellous bone around the MC was observed and classified into three types: type I (trabecular pattern), type II (osteoporotic pattern), and type III (dense/irregular pattern). The mandibles were examined with CBCT and the superior wall of the MC on CBCT was scored as visible or non-visible. Finally, the scores (visible or non-visible) were compared to the type by gross observation. RESULTS: For gross observation, a total of 80 areas were available for this study. The data were added to those from our previous study. As a result, 155 areas on 40 sides were analyzed. In dentulous sections, types I, II, and III were found in 55.8%, 20.9%, and 23.3%, respectively. In edentulous sections, the corresponding percentages were 25.0%, 41.1%, and 33.9%, respectively. The dentulous sections was more likely than edentulous to have a type I mandible in both sexes. More females than males had type II (osteoporotic) mandibles. When the superior wall of the MC was non-visible on CBCT, the cancellous bone was type II in 80%. CONCLUSIONS: We believe the results can easily be applied to preoperative diagnosis with not only radiological but also anatomical evidence. This classification now necessitates clinical trials for further evidence.

DOI： 10.1016/j.aanat.2020.151583

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC.

DOI： 10.1016/j.bbrc.2020.07.120

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The anatomical variations of the maxillary sinus septa, greater palatine artery, and posterior superior alveolar arteries might cause unexpected complications when they are damaged. Dentists who know these structures well might hope to learn more practical knowledge to avoid and assess injury preoperatively. Therefore, this review paper aimed to review the reported anatomy and variations of the maxillary sinus septa, greater palatine artery/nerve, and posterior superior alveolar artery, and to discuss what has to be assessed preoperatively to avoid iatrogenic injury. To assess the risk of injury of surgically significant anatomical structures in the maxillary sinus and hard palate, the operator should have preoperative three-dimensional images in their mind based on anatomical knowledge and palpation. Additionally, knowledge of the average measurement results from previous studies is important.

DOI： 10.1007/s00276-020-02468-w

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

小唾液腺由来の腺房細胞癌は非常にまれな唾液腺悪性腫瘍である。今回われわれは69歳女性に発生した小唾液腺腺房細胞癌を経験したので、文献的考察を加えて報告する。患者は右側頬粘膜下に腫瘤を触知したため受診、MRIにて25×20mm大の腫瘤を認め、全身麻酔下で腫瘍切除術を施行した。病理組織学的に腫瘍は小唾液腺に連続し、漿液腺房細胞様の細胞が大部分を占めていた。術後1年8ヵ月経過したが、再発や転移を認めていない。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J02382&link_issn=&doc_id=20200925280003&doc_link_id=10.5843%2Fjsot.32.77&url=https%3A%2F%2Fdoi.org%2F10.5843%2Fjsot.32.77&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.

DOI： 10.1016/j.intimp.2020.106429

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Evidence has been accumulating to indicate that extracellular vesicles (EVs), including exosomes, released by cancer cells can foster tumour progression. The molecular chaperones - CDC37, HSP90α and HSP90β play key roles in cancer progression including epithelial-mesenchymal transition (EMT), although their contribution to EVs-mediated cell-cell communication in tumour microenvironment has not been thoroughly examined. Here we show that triple depletion of the chaperone trio attenuates numerous cancer malignancy events exerted through EV release. Metastatic oral cancer-derived EVs (MEV) were enriched with HSP90α HSP90β and cancer-initiating cell marker CD326/EpCAM. Depletion of these chaperones individually induced compensatory increases in the other chaperones, whereas triple siRNA targeting of these molecules markedly diminished the levels of the chaperone trio and attenuated EMT. MEV were potent agents in initiating EMT in normal epithelial cells, a process that was attenuated by the triple chaperone depletion. The migration, invasion, and in vitro tumour initiation of oral cancer cells were significantly promoted by MEV, while triple depletion of CDC37/HSP90α/β reversed these MEV-driven malignancy events. In metastatic oral cancer patient-derived tumours, HSP90β was significantly accumulated in infiltrating tumour-associated macrophages (TAM) as compared to lower grade oral cancer cases. HSP90-enriched MEV-induced TAM polarization to an M2 phenotype, a transition known to support cancer progression, whereas the triple chaperone depletion attenuated this effect. Mechanistically, the triple chaperone depletion in metastatic oral cancer cells effectively reduced MEV transmission into macrophages. Hence, siRNA-mediated knockdown of the chaperone trio (CDC37/HSP90α/HSP90β) could potentially be a novel therapeutic strategy to attenuate several EV-driven malignancy events in the tumour microenvironment. Abbreviations: CDC37: cell division control 37; EMT: epithelial-mesenchymal transmission; EV: extracellular vesicles; HNSCC: head and neck squamous cell carcinoma; HSP90: heat shock protein 90; TAM: tumour-associated macrophage.

DOI： 10.1080/20013078.2020.1769373

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI  

The process of fracture healing consists of an inflammatory reaction and cartilage and bone tissue reconstruction. The inflammatory cytokine interleukin-1 beta (IL-1 beta) signal is an important major factor in fracture healing, whereas its relevance to retinoid receptor (an RAR inverse agonist, which promotes endochondral bone formation) remains unclear. Herein, we investigated the expressions of IL-1 beta and retinoic acid receptor gamma (RAR gamma) in a rat fracture model and the effects of IL-1 beta in the presence of one of several RAR inverse agonists on chondrocytes. An immunohistochemical analysis revealed that IL-1 beta and RAR gamma were expressed in chondrocytes at the fracture site in the rat ribs on day 7 post-fracture. In chondrogenic ATDC5 cells, IL-1 beta decreases the levels of aggrecan and type II collagen but significantly increased the metalloproteinase-13 (Mmp13) mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. An RAR inverse agonist (AGN194310) inhibited IL-1 beta-stimulated Mmp13 and Ccn2 mRNA in a dose-dependent manner. Phosphorylated extracellular signal regulated-kinases (pERK1/2) and p-p38 mitogen-activated protein kinase (MAPK) were increased time-dependently by IL-1 beta treatment, and the IL-1 beta-induced p-p38 MAPK was inhibited by AGN194310. Experimental p38 inhibition led to a drop in the IL-1 beta-stimulated expressions of Mmp13 and Ccn2 mRNA. MMP13, CCN2, and p-p38 MAPK were expressed in hypertrophic chondrocytes near the invaded vascular endothelial cells. As a whole, these results point to role of the IL-1 beta via p38 MAPK as important signaling in the regulation of the endochondral bone formation in fracture healing, and to the actions of RAR inverse agonists as potentially relevant modulators of this process.

DOI： 10.3390/ijms21072365

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Our goal was to clarify the relationship between the superior wall of the mandibular canal and the presence of teeth. We also sought to study the structural changes of the mandibular canal after tooth loss. Twenty sides from 10 dry mandibles derived from six males and four females were used for this study. The age of the specimens at the time of death ranged from 57 to 91 years. The mandibles were cut in the midline resulting in 20 hemi-mandibles. The presence of teeth (from the second premolar to the third molar) was recorded for each hemi-mandible. The mandibular canal in the body of the mandible was divided into four areas, that is, Areas 1-4. The superior wall of the mandibular canal and a cancellous bone pattern above the mandibular canal were observed. Next, the mandibular canal was horizontally cut at its center and the superior wall of the mandibular canal observed inferiorly. A total of 75 areas (20 dentulous areas and 55 edentulous areas) were produced. The distal view was classified into three groups, Type I (trabecular pattern), Type II (osteoporotic pattern), and Type III (dense/irregular pattern). The Type I pattern was found in 60.0% (12/20) of the dentulous areas and 32.7% of the edentulous areas. While the Type II pattern was found in 15.0% (23/55) of the dentulous areas and 41.8% of the edentulous areas. The inferior view was classified into four groups depending on the surface of the superior wall of the mandibular canal, that is, Class I (trabecular pattern), Class II (osteoporotic pattern), Class III (dense/irregular pattern), and Class IV (smooth).The Class I pattern was seen most frequently (55.0%) in dentulous areas and the Class IV pattern (45.5%) most frequently in edentulous areas. Based on these results, we conclude that the superior wall of the mandibular canal could change following tooth loss. Clin. Anat. 33:223-231, 2020. © 2019 Wiley Periodicals, Inc.

DOI： 10.1002/ca.23456

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse drug reaction represented by destruction and/or death of bone. Fibrous dysplasia (FD) is a rare bony disorder characterised by abnormal fibro-osseous tissue that has lowered resistance to infection. Effective treatments for BRONJ that follows FD are unclear. Here, we report that advanced BRONJ associated with FD was successfully treated by surgical resection. A 69-year-old woman, whose left maxillary bone showed a ground glass appearance on computed tomography (CT) images, was taking alendronate. At 1 year after teeth within the abnormal bone were extracted, exposed bone was observed in the extraction sites and CT images revealed separated sequestrums. Under the clinical diagnosis of Stage 2 BRONJ with FD, we performed not only sequestrectomy but also a partial resection of the FD. Thereafter, the healing was uneventful without recurrence. In conclusion, our case suggests that surgical resection is useful for advanced BRONJ associated with FD.

DOI： 10.1093/jscr/rjaa061

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: An accessory foramen around the mandibular foramen is called an accessory mandibular foramen (AMF). The clinical anatomy of the AMF has not been well described. The aim of this study was to reveal the clinical anatomy of the AMF for a better understanding of its implication during ramus surgeries. METHODS: Twenty-two sides fresh-frozen cadaveric heads with a mean age of 76.2 ± 14.4 years at death underwent dissection. The neurovascular bundles passing through the AMF were observed. Additionally, a hemi-face of a latex injected embalmed cadaver was dissected medially to laterally and the neurovascular bundles of the AMF investigated. RESULTS: A unilateral foramen, bilateral foramina, and absence of foramina were found in 45.4%, 18.2%, and 36.4%, respectively. The origin of the neurovascular bundle entering the AMF was a branch of the maxillary artery in 20% and a tributary of the inferior alveolar vein in 80%. In the latex embalmed cadaver, the AMF was found to contain a branch from the maxillary artery and a tributary of the maxillary vein. CONCLUSION: Given the practical meaning of the specific AMF located in the operative field of the ramus osteotomy, we suggest these be named "foramina for ramus osteotomy."

DOI： 10.1007/s00276-019-02343-3

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記述言語：英語  

A 58-year-old Japanese woman complained of a painful right maxillary premolar gingiva and ulcer. The patient had RA and had been treated with several immunosuppressive drugs such as methotrexate. Head and neck CT indicated no obvious bone destruction with maxillary. However, chest CT indicated the presence of nodular mass of the bilateral lungs. FDG-PET/CT indicated the presence of increased uptake in both lesions. On immunohistochemistry, atypical large-sized lymphocytes were positive for CD20 and EBER-ISH and negative for CD3, CD5, and CD10; the Ki-67 labeling index was high, the histopathological diagnosis was EBV-positive DLBCL, and the clinical diagnosis was MTX-LPD. The patient's treatment with MTX was then discontinued; we removed the alveolar bone which necrosed after 5 weeks. The lesion and the nodular mass at the bilateral lungs had completely disappeared after 7 weeks.

DOI： 10.1155/2020/4814519

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Platinum‑based antitumor agents have been widely used to treat head and neck squamous cell carcinoma (HNSCC) and numerous other malignancies. Cisplatin is the most frequently used platinum‑based antitumor agent, however drug resistance and numerous undesirable side effects limit its clinical efficacy for cancer patients. Cancer cells discharge cisplatin into the extracellular space via copper transporters such as ATPase copper transporting beta (ATP7B) in order to escape from cisplatin‑induced cell death. In the present study, it was demonstrated for the first time that the copper chelator ammonium tetrathiomolybdate (TM) has several promising effects on cisplatin and HNSCC. First, TM suppressed the ATP7B expression in HNSCC cell lines in vitro, thereby enhancing the accumulation and apoptotic effect of cisplatin in the cancer cells. Next, it was revealed that TM enhanced the antitumor effect of cisplatin in HNSCC cell tumor progression in a mouse model of bone invasion, which is important since HNSCC cells frequently invade to facial bone. Finally, it was demonstrated that TM was able to overcome the cisplatin resistance of a human cancer cell line, A431, via ATP7B depression in vitro.

DOI： 10.3892/or.2019.7367

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12663-019-01241-w

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掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Oral cancer and smoking are closely related, because the oral cavity, which is the route of ingestion of tobacco smoke, is in direct contact with the oral mucosa. Nicotine, one of the components of tobacco, can diffuse rapidly to the central nervous system and is responsible for tobacco addiction. Nicotine is present in high concentrations in the bloodstream of smokers; while the addictive effects of this alkaloid have extensively been studied, its effect on tumorigenesis is not clear yet. Therefore, in this study, we examined the effect of nicotine on cell proliferation and the signaling pathways it activates. The human oral squamous cell carcinoma cell line HSC-2 was used as a model system. We demonstrated the correlation between nicotine and epidermal growth factor receptor (EGFR) signaling. Nicotine treatment induced HSC-2 cell proliferation and migration and the phosphorylation of EGFR. Furthermore, nicotine treatment activated the EGFR downstream effectors phosphatidylinositol-3 kinase/AKT and p44/42 mitogen-activated protein kinases (ERK), which, in turn, promoted cell proliferation. Overall, our study suggests that nicotine promotes cell growth and migration through epidermal growth factor (EGF) signaling and plays an important role in oral cancer progression.

DOI： 10.1016/j.bbrc.2018.12.154

PubMed

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掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer International Publishing  

DOI： 10.1007/978-3-319-97961-8_15

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掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

Background/Aim: Retinoid signaling is important for the maturation of growth-plate chondrocytes. The effect of retinoid receptor gamma (RAR gamma) signaling on the expression of genes in hypertrophic chondrocytes is unclear. This study investigated the role of RAR gamma signaling in regulation of hypertrophic chondrocyte-specific genes. Materials and Methods: The gene expression in mouse E17.5 tibial cartilage was examined by in situ hybridization analysis. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting were used for analysis of mRNA and phosphorylated mitogen-activated protein kinase (MAPK). Results: mRNA expression of Rarg and connective tissue growth factor (Ccn2) was detected in maturing chondrocytes throughout the cartilaginous skeletal elements. In chondrogenic ATDC5 cells, an RAR gamma agonist induced the gene expression of type-X collagen (Col10A1), transglutaminase-2 (Tg2), matrix metalloproteinase-13 (Mmp13), and Ccn2 mRNA, whereas a retinoic acid pan-agonist suppressed RAR gamma agonist-stimulated gene expression. Phosphorylated extracellular signal regulated-kinases (pERK1/2), p-p38, and phosphorylated c-Jun N-terminal kinase (pJNK) MAPK were time-dependently increased by RAR gamma agonist treatment. Experimental p38 inhibition led to a severe drop in the RAR gamma agonist-stimulated expressions of Col10A1, Tg2, Mmp13, and Ccn2 mRNA. Conclusion: RARy signaling is required for the differentiation of hypertrophic chondrocytes, with differential cooperation with p38 MAPK.

DOI： 10.21873/invivo.11443

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Epidermal growth factor (EGF) is overexpressed in many cancers and is associated with worse prognosis. EGF binds to its cell surface receptor (EGFR), which induces EGFR phosphorylation. Phosphorylated EGFR (p‑EGFR) is translocated into the nucleus, which increases cancer cell activity. Nicotine, which is one of the main components of tobacco, is absorbed through pulmonary alveoli and mucosal epithelia in the head and neck region by smoking and moves into the blood. Nicotine in blood binds to nicotinic acetylcholine receptor (nAChR) in the central nervous system and serves a crucial role in tobacco addiction. Although nAChR localization is thought to be limited in the nervous system, nAChR is present in a wide variety of non‑neuronal cells, including cancer cells. Recent studies suggest that nicotine contributes to the metastasis and resistance to anti‑cancer drugs of various cancer cells. However, it remains unknown whether head and neck squamous cell carcinoma (HNSCC) cells can utilize nicotine‑nAChR signaling to metastasize and acquire resistance to anti‑cancer drugs, even though the mucosal epithelia of the head and neck region are the primary sites of exposure to tobacco smoke. To the best of our knowledge, the present study is the first to demonstrate the role of nicotine in metastasis and anti‑EGFR‑therapy resistance of HNSCC. The present findings demonstrated that nicotine increased proliferation, migration, invasion, p‑EGFR nuclear translocation and protein kinase B (Akt) phosphorylation in HNSCC cells. It was also demonstrated that nicotine restored cetuximab‑inhibited proliferation, migration and invasion of HNSCC cells. Finally, an in vivo experiment revealed that nicotine increased lymph node metastasis of xenografted tumors, whereas an nAChR inhibitor suppressed lymph node metastasis and p‑EGFR nuclear localization of xenografted tumors. Taken together, these results demonstrated that nicotine induced nuclear accumulation of p‑EGFR, and activation of Akt signaling. These signaling pathways elevated the activities of HNSCC cells, causing lymph node metastasis and serving a role in cetuximab resistance.

DOI： 10.3892/ijo.2018.4631

PubMed

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記述言語：英語  

A 39-year-old Japanese woman presented to the Department of Oral and Maxillofacial Surgery, Okayama University Hospital, with the complaint of a slowly growing buccal mass. The mass was well defined, had rounded margins, and was free from skin and muscles. A color Doppler echographic examination indicated high flow velocity of the blood surrounding the mass. Contrast-enhanced images on CT and contrast-enhanced T1-weighted images on MRI displayed a homogeneous enhanced mass with a well-defined margin. A fine-needle aspiration biopsy and histological examination were performed. On immunohistochemistry, spindle cells were strongly positive for CD34, STAT6, and vimentin and negative for EMA, S100, and α-SMA. The tumor was removed with extracapsular dissection. The tumor was composed of bland spindle cells proliferating in a patternless arrangement with a collagenous background. Most of the tumor mass consisted of hypocellular areas including ectatic blood vessels. A prominent branching vascular pattern was observed. Immunohistochemistry demonstrated that the tumor cells were positive for CD34, STAT6, vimentin, and Bcl-2, and negative for α-SMA, S100, and EMA. Three mitotic cells were observed per 10 high-power fields, and the Ki-67 index was 5.7%. The morphological and immunohistochemical features were consistent with a diagnosis of solitary fibrous tumor.

DOI： 10.1155/2019/9459837

PubMed

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記述言語：日本語   出版者・発行元：岡山歯学会  

症例は40歳代男性で、近医歯科にて左側上顎第二小臼歯歯根破折の診断のもと、抜歯を施行されるも、術中に歯科用切削バーが歯科用タービンヘッドから逸脱し上顎洞内に迷入した。抜歯を中断し、抜歯処置後6日目に当科を紹介され受診した。パノラマX線写真にて、左側上顎洞内に長径約20mmの迷入した歯科切削バーと思われる不透過像を認めた。患者は欠損に対するインプラント治療を希望していたため、口腔内からのアプローチで抜歯と異物除去を同時に行うこととした。洗浄を行い光源下で洞内を観察するため開洞孔より硬性内視鏡を用い上顎洞内を観察し、バーが自然孔付近の上顎洞粘膜内に一部埋伏していることを確認、同孔よりマイクロ鉗子を用いて内視鏡画像上でバーを把持、除去した。さらに、残存していた左側上顎第二小臼歯歯根を抜去し、創を縫合し手術を終了した。術後経過は良好であり、術後3日目に退院とした。

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

UICCのTNM分類は、口腔癌の進行度評価の基準にされているが、2016年に第8版へ改訂され、T分類では浸潤の深さ(Depth of Invasion:DOI)が、N分類では被膜外進展(Extra Nodal Extension:ENE)が導入された。本研究では、当科で手術を行った舌扁平上皮癌症例107例において、第7版と第8版TNM分類により評価を行い、TNM分類改訂と頸部リンパ節後発転移(以下後発転移)および生存率との関連について検討を行った。TNM分類改訂により、17例(15.9%)にcTの変更を、6例(5.6%)にpTの変更を認めた。後発転移数・後発転移率は、cT1とpT1では低下し、cT2とpT2では増加した。また、第7版でcT4a、pT4aの2例が、第8版ではcT3、pT3に変更されたため、第8版は第7版と比較してcT3、pT3の生存率が低下した。第7版でpN2bの3例が、第8版ではpN3bに分類され、3例とも経過不良であった。当科の舌扁平上皮癌症例におけるTNM分類の第7版から第8版への見直しは、主にStage上昇につながった。そして、第8版TNM分類は、舌扁平上皮癌の進行度をより的確に後発転移と生存率へ反映させるため、実用的であると考えられた。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Control of bacterial infection-induced inflammatory responses is one of the effective therapeutic approaches of periodontal diseases. Natural products such as lipid mediators and metabolites from microorganisms have been used for decreasing inflammation. We previously reported that (+)-terrein inhibited activation of STAT3 and ERK1/2 in interleukin-6 (IL-6) signaling cascade, leading to prevent vascular endothelial growth factor (VEGF) secretion in human gingival fibroblasts (HGFs). However, little is still known about the role of (+)-terrein on inflammatory responses. In this study, we provided the possibility of novel action that (+)-terrein inhibits activation of Janus-activated kinase 1 (JAK1), which has a central function in IL-6 signaling cascade, and alters expression of mRNAs and proteins induced by IL-6/soluble IL-6 receptor (sIL-6R) stimulation in HGFs. First, we performed PCR array to examine IL-6/sIL-6R-induced mRNA expression, and then expression of mRNA and protein of colony stimulating factor-1 (CSF1) and VEGF were clearly determined by quantitative RT-PCR and ELISA, respectively. Treatment with (+)-terrein suppressed expression of mRNA and protein of CSF1 and VEGF by IL-6/sIL-6R stimulation. Next, to test the effect of (+)-terrein on IL-6/sIL-6R signaling cascade, we demonstrated whether (+)-terrein affects phosphorylation of JAK1 and its downstream proteins, Akt and SHP-2. Western blotting revealed that (+)-terrein inhibited IL-6/sIL-6R-induced phosphorylation of JAK1, Akt, and SHP-2. Therefore, (+)-terrein suppresses IL-6/sIL-6R-induced expression of CSF1 and VEGF via inhibition of JAK1, Akt, and SHP-2. Based on our results, we suggest that (+)-terrein is a candidate compound for anti-inflammatory effect associated with IL-6 signaling.

DOI： 10.1016/j.heliyon.2018.e00979

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Overexpression and increased signaling from the epidermal growth factor receptor (EGFR) often changes oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed the roles of OSCC-derived extracellular vesicles (EVs), including exosomes in the trafficking of cetuximab and in epithelial-mesenchymal transition (EMT) of epithelial cells. OSCC cells abundantly expressed EGFR, which was secreted from cells with OSCC-EVs upon EGF stimulations. The OSCC-EGFR-EVs were then able to enter into and transform epithelial cells leading to increased mesenchymal traits with increased vimentin and spindle-like shapes. EGF priming of OSCC cells further increased this EMT-initiating effect of the OSCC-EVs. The internalization and pro-EMT effects of the OSCC-EVs were largely blocked by cetuximab. Thus, OSCC-derived EVs transform normal epithelial cells into a mesenchymal phenotype and anti-EGFR therapeutic antibody cetuximab inhibits such a carcinogenic effect of the OSCC-EVs.

DOI： 10.1016/j.oraloncology.2018.09.030

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Oral diverticulum .

DOI： 10.1002/jgf2.205

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Control of bacterial infection-induced inflammatory responses is one of the effective therapeutic approaches of periodontal diseases. Natural products such as lipid mediators and metabolites from microorganisms have been used for decreasing inflammation. We previously reported that (+)-terrein inhibited activation of STAT3 and ERK1/2 in interleukin-6 (IL-6) signaling cascade, leading to prevent vascular endothelial growth factor (VEGF) secretion in human gingival fibroblasts (HGFs). However, little is still known about the role of (+)-terrein on inflammatory responses. In this study, we provided the possibility of novel action that (+)-terrein inhibits activation of Janus-activated kinase 1 (JAK1), which has a central function in IL-6 signaling cascade, and alters expression of mRNAs and proteins induced by IL-6/soluble IL-6 receptor (sIL6R) stimulation in HGFs. First, we performed PCR array to examine IL-6/sIL6R-induced mRNA expression, and then expression of mRNA and protein of colony stimulating factor-1 (CSF1) and VEGF were clearly determined by quantitative RT-PCR and ELISA, respectively. Treatment with (+)-terrein suppressed expression of mRNA and protein of CSF1 and VEGF by IL-6/sIL-6R stimulation. Next, to test the effect of (+)-terrein on IL-6/sIL-6R signaling cascade, we demonstrated whether (+)-terrein affects phosphorylation of JAK1 and its downstream proteins, Akt and SHP-2. Western blotting revealed that (+)-terrein inhibited IL-6/sIL-6R-induced phosphorylation of JAK1, Akt, and SHP-2. Therefore, (+)-terrein suppresses IL-6/sIL-6R-induced expression of CSF1 and VEGF via inhibition of JAK1, Akt, and SHP-2. Based on our results, we suggest that (+)-terrein is a candidate compound for anti-inflammatory effect associated with IL-6 signaling.

DOI： 10.1016/j.heliyon.2018.e00979

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically, as it can invade facial bones and cause bone pain that is undertreated and poorly understood. Here we studied HNSCC bone pain (HNSCC-BP) in an intratibial mouse xenograft model that uses a human HNSCC cell line (SAS cells). These mice develop HNSCC-BP associated with an upregulation of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in the dorsal root ganglia (DRGs) of sensory nerve cell bodies. Our experiments demonstrated that the inhibition of monocarboxylate transporter 4 (MCT4) by short hairpin (shRNA) transduction suppressed the HNSCC-BP, the lactate level in bone marrow, and the pERK1/2 expression in DRG. The sensory nerves also expressed increased levels of the acid-sensing receptor TRPV1. DRG neurons co-cultured with SAS cells showed increased neurite outgrowth, and were inhibited by MCT4 silencing with shRNA. Collectively, our results show that HNSCC induced an acidic bone microenvironment that evokes HNSCC-BP via MCT4 expression.

DOI： 10.3390/ijms19113317

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Genetic amplification, overexpression, and increased signaling from the epidermal growth factor receptor (EGFR) are often found in oral squamous cell carcinoma (OSCC) and thus EGFR is frequently targeted molecularly by the therapeutic antibody cetuximab. We assessed effects of cetuximab in control of EGF-driven malignant traits of OSCC cells. EGF stimulation promoted progression level of mesenchymal traits in OSCC cells, which were attenuated by cetuximab but incompletely. We pursued a potential mechanism underlying such incomplete attenuation of OSCC malignant traits. Cetuximab promoted secretion of EGFR-EVs by OSCC cells and failed to inhibit EGF-driven secretion of EGFR-EVs. Cetuximab was also found to be robustly secreted with the EGFR-EVs by the OSCC cells. Thus, EGF promotes the level of mesenchymal traits of OSCC cells and secretion of EGFR-EVs, which involve cetuximab resistance.

DOI： 10.1016/j.bbrc.2018.07.035

PubMed

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掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group. An immunofluorescence analysis showed that the numbers of primary cilia and cilia/osterix double-positive osteoblasts were increased at the fracture site by LIPUS. LIPUS stimulated not only the number and the length of primary cilia, but also the levels of ciliated protein, Ift88 mRNA, and SHH, Gli1, and Gli2 in MC3T3-E1 cells. Further experiments revealed that LIPUS stimulated osteogenic differentiation in the presence of smoothened agonist (SAG) treatment. These results indicate that LIPUS stimulates osteogenic differentiation and the maturation of osteoblasts by a primary cilium-mediated activation of hedgehog signaling.

DOI： 10.1002/jcb.26418

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3389/fonc.2018.00376.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Clinical and Diagnostic Research  

Basal Cell Adenoma (BCA) is an extremely rare benign salivary gland tumour that usually arises in the parotid gland. The incidence of BCA is 1%-3% of all salivary gland tumours. Here, we report an extremely rare case of BCA arising in the minor salivary gland of the hard palate of a young man.

DOI： 10.7860/JCDR/2018/32765.11364

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

当院で口腔および中咽頭癌に対する放射線治療を受けた60例(口腔癌42例、中咽頭癌18例)を対象とし、放射線性下顎骨壊死(以下ORN)のリスク因子について後方視的に検討を行った。ORNは7例(12%)で認められ、発生までの期間は1〜53ヵ月(中央値15ヵ月)であった。下顎骨全体の検討では放射線治療前1ヵ月以内の抜歯の既往、平均線量(中央値51Gy)とV40およびV50(40Gy、50Gyが照射される下顎骨の体積)に有意差が認められた。片顎ずつの検討では、平均線量およびV40に有意差が認められた。多変量解析で下顎骨全体の検討での放射線治療前1ヵ月以内の抜歯の既往に有意差が認められ、片顎ずつの検討では認められなかったことから、要抜去歯を有する患者はORN発生のリスクが高いと考えられた。ORNを予防するためには、下顎骨に対する最大線量の制約に加え、平均線量の制約を組み込む必要があると考えられた。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically where one of the mechanisms responsible for the invasion into facial bones occurs via the activation of osteoclasts. Copper has been demonstrated to play a key role in skeletal remodeling. However, the role of copper in cancer-associated bone destruction is thus far unknown. Lysyl oxidase (LOX) is a copper-dependent enzyme that promotes osteoclastogenesis. In the present study, we investigated the effects of copper on HNSCC with bone invasion by the copper chelator, ammonium tetrathiomolybdate (TM) in vitro and in vivo. We demonstrate that TM blocks the proliferation of HNSCC cells, inhibits LOX activation and decreases the expression of the receptor activator of nuclear factor-κB ligand (RANKL) in osteoblasts and osteocytes, subsequently suppressing bone destruction. These findings suggest that copper is a potential target for the treatment of HNSCCs associated with bone destruction.

DOI： 10.3892/ijo.2018.4242

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

今回われわれは、舌癌に対して逆行性超選択的動注化学放射線療法を施行中に腫瘍栄養動脈が閉塞したため、腫瘍栄養動脈の吻合枝から急速動注療法を施行した舌癌の1例を経験したので報告する。症例:43歳女性。2012年7月に当科を受診し、左側舌癌・両側頸部リンパ節転移(T4aN2cM0、扁平上皮癌)と診断した。原発巣は逆行性超選択的動注化学放射線療法を行い、頸部リンパ節転移に対しては照射後に頸部郭清術を施行する予定とした。2012年8月に患側は浅側頭動脈から舌動脈と顔面動脈の共通幹に、健側は浅側頭動脈から舌動脈に、それぞれカテーテルを留置した。定期的にインジゴカルミン染色でカテーテル脱落の有無を検査していたが、46Gy照射後から、患側の舌動脈と顔面動脈の共通幹の支配領域が染色されなくなった。Seldinger法で患側の外頸動脈にカテーテルを留置し外頸動脈分枝を造影すると、舌動脈と顔面動脈は造影されず、顎動脈分枝の頬動脈および下歯槽動脈から顔面動脈への吻合枝が描出された。下歯槽動脈をコイルで塞栓し頬動脈からシスプラチンを急速動注した。2012年10月に70Gy照射を終了した。2012年11月に両側頸部郭清術を行った。治療終了から現在までに約5年経過しているが再発および転移なく経過良好である。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J02382&link_issn=&doc_id=20180322250004&doc_link_id=%2Fdy8ortum%2F2018%2F003001%2F004%2F0023-0027%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdy8ortum%2F2018%2F003001%2F004%2F0023-0027%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

Background/Aim: This study evaluated the associations between bone invasion of gingival squamous cell carcinoma (SCC) and clinicopathological manifestations, and aimed to determine whether bone invasion is an independent prognostic factor in gingival SCC. Patients and Methods: The study was a retrospective review of 78 patients with gingival SCC who underwent surgery with curative intent. The level of bone invasion was pathologically categorized as medullary, cortical or no bone invasion. Results: Cortical and medullary bone invasion was present in 29 and 22 patients, respectively. There was a significant association between medullary bone invasion and tumor size (p=0.017), pathological N classification (p<0.001), differentiation (p=0.017) and lymphovascular invasion (p=0.007). Medullary bone invasion and lymphovascular invasion were independent predictors of reduced overall survival (p=0.015, 0.048); medullary bone invasion was also an independent predictor of reduced disease-specific survival (p=0.018). Conclusion: Pathologically-proven medullary bone invasion and lymphovascular invasion were found to be key prognostic factors in gingival SCC. The results suggest that it is necessary to consider adjuvant therapy in patients with medullary bone invasion.

DOI： 10.21873/anticanres.12309

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掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Society for Head and Neck Cancer  

The purpose of this study was to analyze the risk factors for osteoradionecrosis (ORN) of the mandible after radiotherapy for treatment of oral or oropharyngeal cancers. Sixty patients with oral or oropharyngeal cancers who had undergone external radiotherapy from January 2011 to December 2016 were retrospectively reviewed. Seven patients(12%) had ORN, and the median time to the development of ORN was 15 months(range, 1-53 months). In the analysis of the whole mandible, univariate analysis revealed that tooth extractions within one month before radiotherapy (p &lt
0.001), the mean dose of radiotherapy to the mandible (p = 0.04), and the volume of mandible receiving doses of 40Gy (p = 0.02) and 50Gy (p = 0.04) were significant risk factors for ORN. In the analyses of the right and left sides of the mandible, the mean dose of radiotherapy to the mandible and the volume of mandible receiving a dose of 40Gy were significant risk factors(p = 0.04 for each). In the multivariate analysis, tooth extractions in the analysis of the whole mandible was the only significant risk factor for ORN (p &lt
0.01). Incorporation of both mean dose constraints to the mandible in addition to maximal dose constraints might be needed to reduce the occurrence rate of ORN.

DOI： 10.5981/jjhnc.44.57

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Sonic hedgehog (SHH) signaling is related to the pathogenesis of oral squamous cell carcinoma (OSCC), but its role in OSCC is not yet well understood. In this study, we analyzed the role of SHH signaling in OSCC. MATERIALS AND METHODS: We examined the expression pattern of SHH and its signal proteins in clinically resected OSCC samples by immunohistochemistry. We also evaluated the function of SHH signaling using the hedgehog signaling inhibitor cyclopamine in vivo and in vitro by proliferation, migration and angiogenesis analyses. RESULTS: We found that SHH was highly expressed in human tongue OSCC, whereas patched (PTCH1), glioma-associated oncogene 1 (GLI1) and GLI2 proteins were expressed in the microvascular cells in the tumor invasive front. Administration of cyclopamine to mice suppressed the growth and angiogenesis of OSCC xenografts in vivo. Moreover, cyclopamine inhibited endothelial cell proliferation and migration, and reduced aorta vascular length in the rat. CONCLUSION: These findings suggest that OSCC-derived SHH stimulates angiogenesis at the tumor invasive front.

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掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: The neurokinin 3 receptor (NK-3R) is differentially expressed in the central nervous system including cases of human oral squamous cell carcinoma. However, the role of NK-3R signaling in oral squamous cell carcinoma is not well known. MATERIALS AND METHODS: NK-3R expression in surgically resected oral squamous cell carcinoma was examined immunohistochemically and the strength of the expression was quantified. We evaluated the function of NK-3R signaling using NK-3R antagonist in human oral squamous cell carcinoma bone invasion mouse model. RESULTS: NK-3R was significantly expressed in tumor cells that had invaded the bone matrix compared to the oral side tumor cells. SB222200, a selective antagonist of NK-3R, significantly suppressed the radiographic osteolytic lesion and tumorigenesis. CONCLUSION: NK-3R signaling is a potential target for the treatment of oral squamous cell carcinoma in cases of bone destruction.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jgf2.71

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor kappa beta ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Furthermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion.

DOI： 10.3892/ijo.2017.4050

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記述言語：日本語   出版者・発行元：岡山歯学会  

当院高度救命救急センターにおける頭部、顎顔面外傷症例の実態を報告した。調査期間は2012年4月1日から2013年3月31日迄の12ヵ月で、搬送された患者ならびに救急外来受診患者の合計は2970人であった。そのうち外傷患者は425人であり、その中で頭部、顎顔面外傷患者は164人と全外傷患者の38.6%であった。頭部、顎顔面外傷患者164名の受傷原因は交通外傷74人(45%)、転倒41人(25%)、転落31人(19%)、スポーツ13人(8%)であった。受傷項目詳細は裂傷、擦過傷が最も多く71件であった。次いで頭蓋内損傷が57件、顔面打撲が25件であった。頭部、顎顔面外傷のみの受傷患者は100人(61%)であり、他部位の損傷を併発している患者は64人(39%)であった。多発外傷を呈した頭部、顎顔面外傷患者64名における頭部、顎顔面外傷以外の受傷項目について検討した。肋骨骨折は19件、上肢下肢骨折8件、骨盤骨折22件、肺損傷20件、腹部内臓損傷6件であった。

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

顎放線菌症は開口障害や板状硬結、多発性膿瘍といった特徴的な症状を有する特異性炎である。しかし近年典型的な症状を示す症例が減少していることから診断が困難となっている。症例は85歳の女性で、左側頬部の腫脹と開口障害で当院を受診した。X線写真検査で下顎骨の破壊と融解を認めた。悪性腫瘍を疑ったが、病理組織学的診断は放線菌症であった。外科的掻爬を行い、ベンジルペニシリンとアモキシシリンの投与を行った。(著者抄録)

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記述言語：日本語   出版者・発行元：岡山歯学会  

症例は69歳男性で、左側口底癌にて顎下部を含めた口底部分切除術を施行したが、その後、左側上内頸静脈リンパ節の後発転移と節外浸潤を認めた。左側根治的頸部郭清術変法と術後化学放射線療法で頸部腫瘍は一旦縮小したものの再度増大し、さらに右肺下葉に転移を認めたため、多剤併用化学療法の施行目的で入院した。セツキシマブ・シスプラチン・5-FUの多剤併用化学療法を計画した。しかし、セツキシマブ投与開始5分後より意識消失と全身の浮腫が出現し、infusion reaction(IR)と判断して即座にセツキシマブの投与を中止した。IR発症から30分後には循環動態と呼吸状態が安定したため、集中治療室に搬入となった。約8時間後には全身皮膚に皮疹と四肢の浮腫および皮膚そう痒感を認めており、d-クロルフェニラミンマレイン酸塩の静脈内注射を施行した。発症翌日には四肢の浮腫と皮疹は改善し、意識障害等の有害事象もなく一般病棟に帰室した。発症翌日に再度既往歴を問診したところ、マダニ咬傷の既往があることが判明し、IRの原因としてマダニとの関連があることが疑われた。

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掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Society for Contemporary Medical Research  

Introduction: Disadvantages of open reduction of subcondylar fractures include visible facial scars and potential facial nerve damage. Endoscope-assisted procedures have solved these problems, however the anatomical adaptation of osteosynthesis plates to the fractured area is difficult in the limited surgical field. Three-dimensional pre-shaped plates specialized for subcondylar fractures recently became available. They are originally not for endoscope-assisted procedures but it may be useful for endoscopic approach because they are very small and pre-shaped. Case report: This paper presents a case of 43-year-old male patient with subcondylar fracture. The treatment provided was open reduction and internal fixation of a subcondylar fracture with three-dimensional pre-shaped plates via transoral approach under endoscopic visualization. Conclusion: The paper highlights contemporary management of subcondylar fracture to avoid complications associated with open reduction and restore the post-operative functions.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

INTRODUCTION: In recent years, patients with orthognathic surgery in middle-aged and elderly people have come to be a more frequent occurrence. Breast cancer is the most frequently diagnosed cancer in woman worldwide, and its prevalence rate is steadily increasing.PRESENTATION OF CASE: We report a case of a 47-year-old Japanese woman in whom left-side breast cancer (Stage 1) was unexpectedly found just before orthognathic surgery in April 2012. Breast-conserving surgery was performed (estrogen receptor+, progesterone receptor+, HER2-, surgical margin+, sentinel lymph node +) that May. From June to August docetaxel (75 mg/m(2)) and cyclophosphamide (600 mg/m(2)) were administrated four times every 21 days and thereafter radiotherapy (total 60 Gy) was completed. The cancer surgeon declared the prognosis good and the patient had a strong desire to undergo orthognathic surgery, so in November we performed a bimaxillary osteotomy, and administration of tamoxifen began 6 weeks after the osteotomy.DISCUSSION: There are breast cancer cases in which the prognosis is sufficiently good for a planned orthognathic surgery to proceed. Good communication among surgeons and the patient is important.CONCLUSION: We experienced a case in which breast cancer was found just before the orthognathic surgery; we performed a bimaxillary osteotomy, including follow-up tamoxifen administration, during breast cancer treatment. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.

DOI： 10.1016/j.ijscr.2016.12.014

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Tachykinin 3 (TAC3) and its preferred tachykinin receptor 3 (TACR3) that are prominently detected in the central nervous system, play significant roles in physiological development and specifically in the human reproductive system. The roles of TAC3/TACR3 in oral squamous cell carcinoma are unknown. MATERIALS AND METHODS: We examined the expression pattern of TAC3/TACR3 in clinically-resected oral squamous cell carcinoma samples using immunohistochemistry and immunofluorescence analysis. RESULTS: We found that even though the expression level of TACR3 was negative in the normal epithelium, it was highly elevated in tumor cells. A more intense signal was observed in the invasive front of tumor cells that had migrated into the mandible bone matrix. TAC3 was not detected in tumor cells, but was expressed in PGP-9.5-positive sensory nerves in the mandible. CONCLUSION: Our results suggest that peripheral sensory nerve-derived TAC3 may affect gingival oral squamous cell carcinoma cells through TACR3 in the bone matrix.

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

症例は19歳女性で、出生時に、巨舌、腹部膨満、臍ヘルニアを認め、Beckwith-Wiedemann症候群(BWS)と診断された。5歳時に右腎Wilms腫瘍と診断され、右腎摘出を施行後、ステージIIIの診断で放射線治療、化学療法を受け、腫瘍の再発を認めず、経過良好であった。12歳時に前歯の開咬を主訴に矯正歯科を受診した。正貌はほぼ対称で、下顎の前突を認めた。下顎は歯列弓過大による空隙歯列を認めた。オーバージェット-8.0mm、オーバーバイト-16.0mmで、両側第一大臼歯より前方に開咬を認め、臼歯関係は両側ともにAngleクラスIIIであった。また、舌は下顎の臼歯部咬合面を覆い巨舌を呈していた。パノラマX線では上顎切歯の歯間離開、下顎前歯部から小臼歯にかけ空隙歯列を認めた。側面頭部X線規格写真分析ではSNA 87.6°、SNB 87.1°、ANB 0.5°で骨格性の下顎前突を認め、正面頭部X線規格写真分析では顎顔面正中線に対し、上下顎前歯の正中は一致していた。下顎空隙歯列の原因と考えられる巨舌と骨格性下顎前突および開咬を改善するために舌縮小術と外科的矯正治療を行った。その後、14歳よりマルチブラケット装置を装着し、術前矯正治療が開始された。巨舌が残存し、開咬も増悪傾向にあったため17歳時に2回目の舌縮小術を施行した。舌は手術により前後径、幅径の縮小が得られ、安静位で咬合面を覆っていなかったが厚みは残存し、棍棒状の形態を示した。BWSによる巨舌に起因する骨格性開咬症と診断し、上下顎移動術を予定した。全身麻酔下に顎矯正手術を施行した。術直後から術後1年における垂直的移動量はU1、U6、B点でそれぞれ上方に1.5mm、3.5mm、2.5mm、水平移動量はそれぞれ後方に1.0mm、1.0mm、3.0mmであった。保定は上下顎に床装置を用い行い、術後2年の経過観察において良好な被蓋関係が保たれている。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J03047&link_issn=&doc_id=20160914220006&doc_link_id=%2Fdh5jawdf%2F2016%2F002603%2F006%2F0228-0236%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdh5jawdf%2F2016%2F002603%2F006%2F0228-0236%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

Temporomandibular joint (TMJ) dislocation can occur during daily activities and negatively affect a patient's quality of life. Although both nonsurgical and surgical techniques have been used to treat recurrent TMJ dislocation, the former is not always successful and the latter, although having a high success rate, is invasive and requires hospitalization. Recently, autologous blood injection has been used to treat recurrent TMJ dislocation. However, this technique is not yet widely used in clinical practice. We designed this study to obtain further information as to efficacy, safety and stability of autologous blood injection for recurrent TMJ dislocation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Midkine is a heparin-binding growth factor highly expressed in various human malignant tumors. However, its role in the growth of oral squamous cell carcinoma is not well understood. In this study, we analyzed the antitumor effect of a novel midkine inhibitor (iMDK) against oral squamous cell carcinoma. Administration of iMDK induced a robust antitumor response and suppressed cluster of differentiation 31 (CD31) expression in oral squamous cell carcinoma HSC-2 cells and SAS cells xenograft models. iMDK inhibited the proliferation of these cells dose-dependently, as well as the expression of midkine and phospho-extracellular signal-regulated kinase in HSC-2 and SAS cells. Moreover, iMDK significantly inhibited vascular endothelial growth factor and induced tube growth of human umbilical vein endothelial cells in a dose-dependent fashion. These findings suggest that midkine is critically involved in oral squamous cell carcinoma and iMDK can be effectively used for the treatment of oral squamous cell carcinoma.

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記述言語：日本語   出版者・発行元：岡山歯学会  

2000年4月〜2014年3月に一次治療を行った舌扁平上皮癌Stage I・II症例93例(Stage I 40例、Stage II 53例)を対象に、一次治療終了以降に転移が判明した症例(後発転移)の頻度とそれに影響を及ぼす臨床因子、後発転移発現までの期間、生存率について検討した。後発転移は全93例中23例(24.7%)に認められた。ステージ別ではStage I 40例中6例(15.0%)、Stage II 53例中17例(32.1%)、治療法別では手術群81例中17例(21.0%)、放射線療法群12例中6例(50.0%)にそれぞれ後発転移が発現した。後発転移の有無は、分化度、浸潤様式、原発巣の厚みと相関していたが、放射線療法を行った症例ではStage IIで原発巣の厚みが5mm以上であることが強く影響していた。後発転移への期間は、手術群で平均8.1ヵ月、中央値6ヵ月、放射線療法群で平均5ヵ月、中央値6ヵ月で、治療法による有意差は認められなかった。生存率と関連する臨床因子を検討したところ、有意な影響が認められた因子は後発転移のみであった。

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記述言語：日本語   出版者・発行元：岡山歯学会  

2013年5月〜2015年12月の病診連携にてインプラント治療を行った16例(男5例、女11例)の診療録と手術記録を参照し、合併症の有無とその種類、インプラント手術およびその関連手術の内容を検討した。年齢別では50〜60歳代が12例と大部分を占めていた。合併症を有していたのは8例(50%)、骨増生を施行したのは10例(63%)であり、一般歯科診療所では対応が困難な部分を担っていた。患者・紹介医との情報共有には国際インプラント手帳を使用し、紹介医と綿密に連携を行うことにより患者・紹介医との間にトラブルは生じなかった。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Head and neck cancers are the fifth most common cancer type worldwide, affecting more than half a million patients annually. Development of effective therapeutic drugs is, therefore, required for this type of disease. This study assessed the effects of synthetic terrein on head and neck cancer. MATERIALS AND METHODS: Synthetic terrein was prepared by using the modified Altenhach's procedure. The effect of synthetic terrein on cell proliferation of head and neck cancer cells and HUVECs was assessed. Angiogenin secretion and ribosome biogenesis were examined by ELISA and silver staining of the nucleolar organizer region. A mouse xenograft model was prepared by inoculating mice with suspensions of cells of the human head and neck cancer cell line OSC-19 subcutaneously into the dorsal region of each mouse. Ki-67, CD31 and angiogenin expression in xenografted tumors was examined by immunohistochemistry. RESULTS: Synthetic terrein inhibited the growth of various head and neck cancer cells. In addition, an in vivo experiment revealed that synthetic terrein inhibited a xenograft tumor growth in athymic mice. Immunohistochemical analysis revealed that expression of Ki-67, CD31 and ANG was down-regulated in synthetic terrein-treated tumors, compared to controls. Synthetic terrein suppressed the ANG secretion and ribosome biogenesis in cancer cells, and cell proliferation in vascular endothelial cells. CONCLUSION: The mechanism underlying the anti-tumor effects of synthetic terrein against head and neck cancer consists of the inhibition of both tumor cell proliferation and angiogenesis via the suppression of ANG production.

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-kappa B ligand (RANKL) in CD11b(+) mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment.

DOI： 10.1371/journal.pone.0151731

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Ltd  

Purpose Sonic Hedgehog (SHH) is a regulatory protein involved in bone fracture healing. Orthognathic surgery involves surgical osteotomy of the mandible or maxilla to restore the proper anatomic and functional position in patients with dentofacial deformity. The purpose of this study was to analyze SHH local blood serum concentrations after osteotomy to gain further understanding of the molecular regulation of the initial stage of osteotomy healing. Methods Serum samples (local drainage and peripheral venous) of 34 patients (24 females and 10 males, mean age was 23.4 (16–42) years) who underwent orthognathic surgery were isolated from patients at different time points during the perioperative period. The levels of SHH, soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin (OPG) were measured using ELISA. Results SHH was detected in the local drainage immediately after osteotomy (309.5 ± 58.2 pg/ml), and decreased for 2 days after the operation (197.5 ± 43.6 pg/ml). The sRANKL local serum concentrations were at the maximum level immediately after the operation (141.4 ± 22.6 pg/ml) and decreased for 2 days (110.1 ± 23.4 pg/ml). On the other hand, the OPG concentration in the local serum was at a minimum after osteotomy (59.4 ± 4.6 pg/ml) and reached its maximum (181.5 ± 17.8 pg/ml, P &lt
 0.01) at 2 days after osteotomy. SHH and OPG local serum levels on day 2 were associated with the amount of bleeding during the operation. The local drainage serum level of SHH of maxillary/mandibular osteotomy had a tendency to be higher than that of mandible-only osteotomy at 2 days after operation. Conclusions Elevated levels of SHH in local serum after osteotomy, especially during the initial stage of healing, indicates its importance in osteotomy healing.

DOI： 10.1016/j.ijso.2016.09.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sonic Hedgehog (SHH), a neural development inducer, plays a significant role in the bone healing process. Calcitonin gene-related peptide (CGRP), a neuropeptide marker of sensory nerves, has been demonstrated to affect bone formation. The roles of SHH signaling and CGRP-positive sensory nerves in the alveolar bone formation process have been unknown. Here we examined the expression patterns of SHH signaling and CGRP in mouse socket by immunohistochemistry and immunofluorescence analysis. We found that the expression level of SHH peaked at day 3 and was then decreased at 5 days after tooth extraction. CGRP, PTCH1 and GLI2 were each expressed in a similar pattern with their highest expression levels at day 5 and day 7 after tooth extraction. CGRP and GLI2 were co-expressed in some inflammatory cells and bone forming cells. In some areas, CGRP-positive neurons expressed GLI2. In conclusion, SHH may affect alveolar bone healing by interacting with CGRP-positive sensory neurons and thus regulate the socket's healing process after tooth extraction.

DOI： 10.1016/j.bbrc.2015.09.139

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Tumors of the sublingual salivary gland are extremely rare. Most of the sublingual tumors are malignant, adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma being the most common histological types. Here we report the first case of a familial occurrence of ACC in a family in which the father and daughter were treated for ACC of the sublingual salivary gland. A 75-year-old man was referred with a swelling of the floor of the mouth on his right side and diagnosed as ACC of sublingual salivary gland synchronous with adenocarcinoma of the lung. One year later, his daughter presented, at the age of 46 years, with a swelling of the floor of the mouth on her right side, which was also diagnosed as ACC. This is the first case of familial recurring ACC of sublingual salivary gland worldwide. (C) 2014 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.(star)

DOI： 10.1016/j.ajoms.2014.03.008

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記述言語：日本語   出版者・発行元：(一社)日本歯科医学教育学会  

医療系大学においては、全人的医療教育やコミュニケーション教育を目標として患者に付き添う実習が導入されている。しかしながら、その実習内容に振り返りを取り入れた報告は散見するにすぎない。岡山大学歯学部では、早期見学実習の一環として学生が何を学び、感じたかを分かち合う振り返りを取り入れ、外来初診患者を対象としたエスコート実習を実施してきた。本エスコート実習を受講した学生および実習に協力が得られた患者を対象にアンケートを実施し、本実習がどのように評価されているかを検討した。1年次生370名および患者422名の回答を分析した結果、以下の結論を得た。大多数(96.5%)の学生は本実習を有意義だと評価しており、学生は本実習により患者の視点を理解し、医療人にふさわしいコミュニケーションの技能も理解していた。また、本実習が学生にとって医療人を目指す者としての態度の修得や自覚をもつことを促す動機づけになっていた。大多数(96.4%)の患者が学生の態度について肯定的に評価をしており、85.0%がこの実習は有意義なものであると評価していた。その主な理由として、学生が患者の視点や医療人にふさわしいコミュニケーションの技能を理解できることなどが挙げられていた。以上より、本実習は学生が患者の視点を理解し、医療人を目指す者としての態度や自覚を身につけるという学習目標を達成しており、学生および患者から高く評価されていることが示唆された。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

Connective tissue growth factor (CCN2) regulates diverse cellular functions, including tooth development. In order to delineate the precise role of CCN2 in the epithelium during odontogenesis, we investigated how it is expressed and what roles it may have in primary cultures of epithelial cells derived from developing tooth germ of the bovine fetus. Ccn2 mRNA and protein were strongly expressed in the inner dental epithelium, which is consistent with the expression of transforming growth factor-beta 2 mRNA and proliferating cell nuclear antigen. Bone morphogenetic protein 4 (BMP4) and fibroblast growth factor 2 (FGF2) were also expressed in the inner dental epithelium, indicating that CCN2 functionally interacts with these factors in the epithelium. The stimulatory effects of FGF2 on cell proliferation and BMP4 on cell differentiation were additively up-regulated by CCN2 in a newly-established dental epithelium cell culture. Taken together, our data provide clear evidence that CCN2 is synthesized by inner dental epithelial cells, and appears to act as an autocrine factor, which regulates dental epithelial cell proliferation and differentiation in concert with growth factors.

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory condition associated with elevated serum IgG4 levels and tissue infiltration by IgG4-expressing plasma cells. We present a case of adenoid cystic carcinoma (ACC) of the submandibular gland with possible involvement of IgG4-RD.PRESENTATION OF CASE: The patient was a 59-year-old man presenting with a swollen right submandibular gland. Laboratory tests revealed IgG4 levels of 176 mg/dl (reference range: 4.8-105). An initial open biopsy for histological diagnosis showed chronic sialadenitis. The region was monitored on an outpatient basis, and finally the right submandibular was totally resected because malignant tumor could not be excluded. Histological examination of the submandibular gland showed an ACC with lymphocytic infiltration containing many IgG4-positive plasma cells in the tumor stroma.DISCUSSION: We have described a case that indicated a possible involvement of ACC with IgG4-RD. This allows us to speculate that longstanding IgG4-RD may progress to malignancy or infiltration of IgG4-positive plasma cells through the signals of tumor stimuli. Further investigations are required to determine the potential pathogenic mechanism underlying this unique tumor.CONCLUSION: This case underscores that caution is needed in the diagnosis of masses with high serum IgG4 levels, as the differential diagnosis includes malignancy. (C) 2015 The Authors. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd.

DOI： 10.1016/j.ijscr.2015.01.022

Web of Science

PubMed

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記述言語：日本語   出版者・発行元：岡山歯学会  

口腔癌検診研修会基礎コースを修了した歯科医師を対象に、研修会終了後にアンケート調査を行った。2013年に行われた3回の研修会の研修者の合計は46人(3人が2回研修)であった。臨床経験年数は10〜42年(平均23.6年、中央値25年)に比較的長い研修者が多かった。口腔癌症例経験ありは70%に認められ、経験症例数は1〜3例が多かった。口腔癌症例経験者の中で癌の疑いがあると診断して専門機関に紹介した症例が93%と大部分を占めた。しかし、その中で早期癌を診断できた症例は45%に過ぎず、初診時に進行していた症例も46例に認められた。また、紹介が少し遅くなった症例が9%認められたが患者が専門機関をなかなか受診してくれなかった例も1例あった。癌の部位は舌が最も多く41%認められ、下顎歯肉32%、口底13%と続いた。研修会の時間・レベルは概ね適切で、講義・実習・テキストもためになり、今後の臨床に役立つとの回答が得られた。再研修の必要性は91%と多かったが、アドバンスコースの希望者は69%に留まり、ベーシックコースの希望者も22%認められた。また、再研修までの期間は1年の35%を前後にばらつきが認められた。研修者はより実践的に役立つ研修内容を希望していた。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Interleukin (IL)-6 is a proinflammatory cytokine that performs a wide variety of biological functions, including important roles in the progression of chronic inflammatory diseases such as periodontal disease. (+)-Terrein, a secondary bioactive fungal metabolite isolated from Aspergillus terreus, has various biological activities; however, its anti-inflammatory effects are still unknown. The purpose of this study was to examine the effect of synthetic (+)-terrein on IL-6 signaling and related protein production in human gingival fibroblasts. To our knowledge, this study is the first to report that synthetic (+)-terrein is not cytotoxic at concentrations less than 20 μM and suppresses IL-6/soluble IL-6 receptor (sIL-6R)-induced phosphorylation of signal transducer and activator of transcription-3, extracellular signal-regulated kinase 1/2, and c-jun N-terminal kinase 1/2-signaling proteins that are downstream of IL-6 signaling. In addition, synthetic (+)-terrein suppresses IL-6/sIL-6R-induced vascular endothelial growth factor (VEGF) secretion in a concentration-dependent manner (p<0.01). These data suggest that synthetic (+)-terrein has potential anti-IL-6 signaling activity and suppresses VEGF-associated inflammatory disease progression.

DOI： 10.1016/j.bmc.2014.07.047

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Angiogenin undergoes nuclear translocation and stimulates ribosomal RNA transcription in both endothelial and cancer cells. Consequently, angiogenin has a dual effect on cancer progression by inducing both angiogenesis and cancer cell proliferation. The aim of this study was to assess whether neamine, a blocker of nuclear translocation of angiogenin, possesses antitumor activity toward oral cancer. MATERIALS AND METHODS: The antitumor effect of neamine on oral cancer cells was examined both in vitro and in vivo. RESULTS: Neamine inhibited the proliferation of HSC-2, but not that of SAS oral cancer cells in vitro. Treatment with neamine effectively inhibited growth of HSC-2 and SAS cell xenografts in athymic mice. Neamine treatment resulted in a significant decrease in tumor angiogenesis, accompanied by a decrease in angiogenin- and proliferating cell nuclear antigen-positive cancer cells, especially of HSC-2 tumors. CONCLUSION: Neamine effectively inhibits oral cancer progression through inhibition of tumor angiogenesis. Neamine also directly inhibits proliferation of certain types of oral cancer cells. Therefore, neamine has potential as a lead compound for oral cancer therapy.

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

症例は42歳男性で、全身倦怠感を主訴に受診し、慢性骨髄性白血病と診断された。HLAが一致する弟をドナーとした骨髄移植を受け、移植直後に移植片対宿主病(GVHD)を発症し、慢性GVHDによる肝機能低下、GVHDに対するプレドニゾロン長期投与による軽度の腎機能低下を認めた。骨髄移植直後より口内炎を自覚していたが、右側頬粘膜に腫瘤を自覚するようになり、血液腫瘍内科より紹介受診した。体格中等度、栄養状態良好で、顔面、四肢皮膚に慢性GVHDによる色素逸脱を認めた。右側頬粘膜に22×16mmの弾性軟、周囲に硬結を触知する腫瘤を認めた。MR画像で右側頬粘膜に前後径20mm、厚み4mmの境界明瞭なSTIR高信号域を認め、左側下顎小臼歯部舌側歯肉に前後径10mmの境界明瞭なSTIR高信号域を認めた。骨髄移植によるGVHDを伴った二次性多発性口腔癌、白板症の疑いと臨床診断し、全身麻酔下に腫瘍切除術を施行した。左側下顎生検を行い、舌背中央部は軽度上皮異形成、左側下顎大臼歯歯肉頬移行部は高分化扁平上皮癌と病理組織学的に診断され、左側下顎歯肉癌に対し腫瘍切除術を施行した。術後12ヵ月再発を認めず、厳重な経過観察を行っている。

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

症例は2歳男児で、左側下顎部の腫脹を主訴とした。X線で左下D番の近心部から下顎枝までの楕円形の比較的境界明瞭な透過像を認め、内部に斑紋状の不規則な不透過像がみられた。同部の骨削除により組織生検を行い、病理所見は細胞成分に富む線維性組織の増殖からなり、線維骨の骨梁を伴っていた。線維性異形成症と診断し、1ヵ月後に掻爬術を追加し、生検部位から遠心に向かって菲薄化した頬側の骨を除去した。術後6ヵ月頃より患側下顎骨下縁に骨様硬の膨隆を認め、急速に増大して顔面の非対称が著明となったが、再手術は同意が得られず、定期的な経過観察を行った。下顎骨の成長や歯の萠出には問題がなく、18歳時には内部に骨梁構造を認めた。非対称改善のため口外法により左側下顎骨下縁切除術を施行し、病理所見で緻密な皮質骨内に疎な骨組織と線維性組織を認めたが、活動性の病変はなかった。術後6年経過し、下顎骨の形態に著変はない。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J02383&link_issn=&doc_id=20140226330006&doc_link_id=10.15214%2Fjsodom.27.27&url=https%3A%2F%2Fdoi.org%2F10.15214%2Fjsodom.27.27&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：The Japanese Society of Oral Diagnosis/Oral Medicine  

DOI： 10.15214/jsodom.27.27

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

UNLABELLED: The androgen receptor (AR) is a critical effector of prostate cancer development and progression. Androgen-dependent prostate cancer is reliant on the function of AR for growth and progression. Most castration-resistant prostate cancer (CRPC) remains dependent on AR signaling for survival and growth. Ribosomal RNA (rRNA) is essential for both androgen-dependent and castration-resistant growth of prostate cancer cells. During androgen-dependent growth of prostate cells, androgen-AR signaling leads to the accumulation of rRNA. However, the mechanism by which AR regulates rRNA transcription is unknown. Here, investigation revealed that angiogenin (ANG), a member of the secreted ribonuclease superfamily, is upregulated in prostate cancer and mediates androgen-stimulated rRNA transcription in prostate cancer cells. Upon androgen stimulation, ANG undergoes nuclear translocation in androgen-dependent prostate cancer cells, where it binds to the rDNA promoter and stimulates rRNA transcription. ANG antagonists inhibit androgen-induced rRNA transcription and cell proliferation in androgen-dependent prostate cancer cells. Interestingly, ANG also mediates androgen-independent rRNA transcription through a mechanism that involves its constitutive nuclear translocation in androgen-insensitive prostate cancer cells, resulting in a constant rRNA overproduction and thereby stimulating cell proliferation. Critically, ANG overexpression in androgen-dependent prostate cancer cells enables castration-resistant growth of otherwise androgen-dependent cells. Thus, ANG-stimulated rRNA transcription is not only an essential component for androgen-dependent growth of prostate cancer but also contributes to the transition of prostate cancer from androgen-dependent to castration-resistant growth status. IMPLICATIONS: The ability of angiogenin to regulate rRNA transcription and prostate cancer growth makes it a viable target for therapy.

DOI： 10.1158/1541-7786.MCR-13-0072

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本顎顔面インプラント学会  

59歳女。右側頬部の腫脹を主訴に受診し、パノラマX線写真で右側下顎骨にX線透過像を認めた。CT写真では、腫瘍直下に下顎管が存在していた。局研麻酔下で生検を行い、エナメル上皮腫と診断した。全身麻酔下に腫瘍摘出術および抜歯を施行した。病理組織学的所見からエナメル上皮腫と診断した。腫瘍摘出術後3年3ヵ月後にインプラント治療に先立ち、下歯槽神経血管束移動術と右側下顎枝からの骨移植を行った。4ヵ月の治癒期間の後、骨延長を行った。頬側の骨量が不十分であったため、オトガイ部からの骨移植を再度行い、1年2ヵ月後にインプラント体を埋入した。現在、上部構造装着から4年が経過しているが、腫瘍の再発や、インプラント周囲粘膜組織の炎症徴候もなく、正常な咬合・咀嚼機能が維持されている。さらにパノラマX線写真においてもインプラント周囲の異常な骨吸収はなく、歯槽骨頂の骨レベルは維持され、経過は良好である。

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Heat shock protein 90 (HSP90) and mammalian target of rapamycin (mTOR) are involved in the molecular pathogenesis of advanced oral squamous cell carcinoma. HSP90 inhibitors are capable of effectively interfering with multiple signaling pathways, including the mTOR signaling pathway. However, the combined effects of HSP90 and mTOR inhibitors on oral squamous cell carcinoma are still unknown. In this study, we investigated the dual treatment of the novel HSP90 inhibitor NVP-AUY922 and temsirolimus against oral squamous cell carcinoma. MATERIALS AND METHODS: The effect of the combination of NVP-AUY922 and temsirolimus on oral squamous cell carcinoma in vitro and in vivo was determined by MTS assay and mouse xenograft models. The effect of the combination on angiogenesis was determined by tube formation assay and angioreactor. RESULTS: The combination treatment of NVP-AUY922 and temsirolimus significantly inhibited the proliferation of SAS oral squamous cell carcinoma cells in vitro and suppressed the growth of oral squamous cell carcinoma xenografts in vivo. We have clearly shown that the combination treatment of NVP-AUY922 and temsirolimus inhibited vascular formation both in vitro and in vivo. Moreover, the combination treatment of NVP-AUY922 and temsirolimus prolonged the survival rate in mice xenografted with oral squamous cell carcinoma. CONCLUSIONS: Here, we showed the activity of a combination of mTOR and HSP90 inhibitors for the treatment of advanced oral squamous carcinoma.

PubMed

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記述言語：日本語   出版者・発行元：(公財)上原記念生命科学財団  

血管新生因子として発見されたアンギオゲニン(ANG)がリンパ管内皮細胞に与える影響、ANGがリンパ浮腫動物モデルに与える影響について検討した。リンパ管内皮細胞ではANGが核に集積していることが確認された。また、ANGおよびリンパ管新生因子(VEGF-C)はリンパ管内皮細胞の増殖を促進することが明らかとなった。リンパ浮腫モデルマウスでの検討から、ANGやVEGF-Cの投与によりリンパ浮腫の軽減が認められた。Ang遺伝子ノックアウト(KO)マウスを作製し、マトリゲルプラグアッセイにて血管新生の検討を行った結果、KOマウスでは血管新生が抑制されていることが確認された。更に、KOマウスを用いてリンパ管新生の検討を行っている。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Angiogenin (ANG) is a prominent angiogenic factor that has been shown to have a dual effect on tumor progression by inducing both angiogenesis and cancer cell proliferation through stimulating ribosomal RNA transcription in both endothelial cells and cancer cells. In the present study, we investigated the expression profiles of ANG and vascular endothelial growth factor (VEGF) in oral cancer and their correlation with hypoxia and evaluated the possible value of ANG as a therapeutic target for oral cancer. MATERIALS AND METHODS: Immunohistochemistry (IHC), ELISA, real-time RT-PCR and Western blotting were used to examine the expression of ANG, VEGF, and hypoxia-inducible factor 1α (HIF-1α) in oral squamous cell carcinoma (OSCC) specimens and human OSCC cell lines. In order to examine the role of ANG, we knocked down ANG expression in HSC-2 cells by means of plasmid-mediated RNA interference. RESULTS: IHC showed that the expression of ANG was significantly correlated with that of HIF-1α in 50 OSCC specimens (P = 0.031). However, no significant correlation between VEGF and HIF-1α expression was found (P = 0.243). Consistently, ANG secretion increased under hypoxia in all of the 10 OSCC cell lines tested; and a significant increase was observed in 6 of them. In contrast, there was no noticeable increase in VEGF secretion under hypoxia in any of these cell lines. In HSC-2 and SAS OSCC cells, the increase in ANG mRNA expression correlated very well with that of HIF-1α protein expression after hypoxia onset. However, no noticeable increase in VEGF mRNA expression was observed even after 12 h of hypoxia. Down-regulation of ANG expression in HSC-2 cells highly expressing and secreting VEGF inhibited ribosome biogenesis, cell proliferation, tumor angiogenesis, and xenograft growth in athymic mice. CONCLUSION: These results suggest that ANG is up-regulated in the hypoxic environment of oral cancers and that its inhibition can have a therapeutic implication.

DOI： 10.1016/j.oraloncology.2012.05.009

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

1歳7ヵ月女児。左側上顎歯肉の腫瘤を主訴とした。左側上顎歯肉に弾性軟の有茎性腫瘤を認め、腫瘤の先端は分葉状で正常歯肉色であったが、腫瘤基部は血管が豊富で赤色を呈していた。デンタルX線で同部の骨吸収は認めなかった。左側上顎歯肉腫瘍と診断し、腫瘍切除術を行った。腫瘤は有茎性で基部は歯肉と歯槽粘膜の境界部に存在しており、基部から約5mmの安全域を設定し直下の骨膜も切除した。同部の骨面は正常であった。切除部は開放創にして手術を終了した。切除した腫瘍の病理診断は巣状口腔粘液症であった。術後経過は良好で、術後1年の現在、再発は認めていない。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J01073&link_issn=&doc_id=20121003390008&doc_link_id=10.5794%2Fjjoms.58.546&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.58.546&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

我が国では高齢化社会が進んでおり、それとともに高齢口腔癌患者を治療する機会の増加が予想される。本研究では、2000年から2008年に当科を受診した後期高齢者口腔扁平上皮癌症例64例(男性23例、女性41例)について、前期高齢者60例(男性32例、女性28例)および若壮年者63例(男性46例、女性17例)と比較検討した。後期高齢者は前期高齢者や若壮年者と比較してPerformance Status(PS)grade 0・1の症例の割合が有意に低かった。後期高齢者は、根治的治療45例(70.3%)、姑息的治療9例(14.1%)、無治療10例(15.6%)であった。後期高齢者は前期高齢者と比較して根治的治療を選択している割合が低い傾向を示した。また、根治的治療を選択した症例の5年疾患特異的累積生存率は後期高齢者81.3%、前期高齢者88.6%、若壮年者80.9%で後期高齢者は前期高齢者と比較して低い傾向を示した。無治療症例は、その後の経過が追えておらず、今後、対策が必要と考えられた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J02382&link_issn=&doc_id=20120919280005&doc_link_id=%2Fdy8ortum%2F2012%2F002403%2F006%2F0103-0111%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdy8ortum%2F2012%2F002403%2F006%2F0103-0111%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公社)日本矯正歯科学会  

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記述言語：日本語   出版者・発行元：岡山歯学会  

下顎エナメル上皮腫摘出後の骨折・顔貌変形を防止するために、口腔内から下顎骨に比較的大型のチタンプレート(ストライカー社製マンディブラルフラクチャープレート 14穴)を装着し、良好な結果が得られた症例(59歳男性例)を報告した。下顎骨腫瘍に対して摘出術や下顎骨辺縁切除術を施行後、残存骨が少なく顎骨骨折や顔貌変形が懸念される症例に対して本法は治療オプションの一つになりうると考えられた。

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(株)デンタルダイヤモンド社  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語  

Angiogenin (ANG), a 14 kDa angiogenic ribonuclease, is upregulated in human prostate cancers, especially in hormone refractory diseases, and is the highest upregulated gene in Akt-driven prostate intraepithelial neoplasia (PIN) in mice. ANG has been shown to undergo nuclear translocation in both prostate cancer cells and cancer-associated endothelial cells where it binds to the promoter region of ribosomal DNA (rDNA) and stimulates ribosomal RNA (rRNA) transcription. ANG thus plays an essential role in prostate cancer progression by stimulating both cancer cell proliferation and tumor angiogenesis. A variety of ANG antagonists, including its antisense oligonucleotide, siRNA, soluble binding proteins, monoclonal antibody, enzymatic inhibitors, and nuclear translocation blockers, have all been shown to inhibit prostate cancer in various animal models. Accumulating evidence indicates that ANG is a molecular target for prostate cancer drug development.

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記述言語：英語  

BACKGROUND: Breast cancer cells frequently metastasize to the skeleton and produce and secrete proteinases, such as matrix metalloproteinase-13 (MMP-13), which promote destruction of the bone matrix. However, the mechanism of MMP-13 expression induced in areas of bone metastasis is unknown. Here, the interaction between tumors and type I collagen in bone metastasis was investigated. MATERIALS AND METHODS: A mouse model of bone metastasis was prepared by inoculating mice with suspensions of cells of the human metastatic breast cancer cell line MDA-MB-231 via the left cardiac ventricle. MMP-13 expression was examined by immunohistochemical, Western blot, and real-time RT-PCR analyses. RESULTS: MMP-13 expression was highly up-regulated in MDA-MB-231 cells, and attachment of these cells to type I collagen and the induction of MMP-13 were down-regulated by treatment with integrin α1, α2 or β1 neutralizing antibodies. The attachment of MDA-MB-231 cells to type I collagen induced the activation of focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK). Inhibition of FAK and p38 MAPK down-regulated type I collagen-induced MMP-13 expression. CONCLUSION: Our study indicates that metastatic breast cancer cells in the bone microenvironment attached to type I collagen, which stimulated integrins α1β1 and α2β1, via FAK and p38 MAPK pathways, to induce MMP13 expression and further osteolysis.

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記述言語：日本語   出版者・発行元：岡山歯学会  

口腔癌切除後の創部に対してポリグリコール酸フェルトとフィブリン糊を併用した被覆法を用いて治療を行った4例を経験した。症例1は80歳女で、右側舌癌に対して舌部分切除術を行った。術後21日目においてほぼPGAフェルトは吸収し、舌の瘢痕拘縮は軽度であった。症例2は65歳女で、左側頬粘膜悪性黒色腫に対して頬粘膜腫瘍切除術と上顎骨部分切除術を行った。術後28日目においてPGAフェルトは吸収しており、瘢痕拘縮は軽度で開口障害もなかった。症例3は78歳女で、左側下顎歯肉癌に対して下顎骨辺縁切除術と頸部郭清術を行った。術後31日目において、骨露出は認めず肉芽で覆われている。症例4は88歳女で、左側頬粘膜癌に対して原発巣は密封小線源治療、頸部リンパ節転移は頸部郭清術を行うこととした。術後44日目において肉芽の新生は十分でなく、頬粘膜は陥凹している。

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記述言語：英語  

BACKGROUND: Breast cancer (BC) cells often metastasize to bone where they express large amounts of parathyroid hormone-related protein (PTHrP). In this study, we investigated the possibility that PTHrP may have roles in breast cancer bone metastasis independently of, or in addition to, its roles in osteoclastic function. MATERIALS AND METHODS: A mouse model of bone metastasis was prepared by inoculating mice with suspensions of the human BC cell line MDA-MB-231 tumor cells via the left cardiac ventricle. Matrix metalloproteinase-13 (MMP-13) expression in the bone microenvironment was examined by Western blot and Real-time RT-PCR (RT-PCR) analysis, as well as by confocal microscopy. RESULTS: The invading MDA-MB-231 cells contained conspicuous amounts of both PTHrP and MMP-13, an important matrix-degrading enzyme; and treatment of the cells in culture with exogenous PTHrP markedly stimulated MMP13 gene expression. Analysis of signaling mechanisms showed that PTHrP treatment led to rapid increases in the levels of phosphorylated protein kinase C (PKCα) and extracellular signal-regulated kinase (ERK1/2). Pharmacologic inhibition of ERK1/2 and PKC as well as of PKA activities counteracted the PTHrP-dependent stimulation of MMP13 expression. Indeed, pharmacologic activation of PKA or PKC was sufficient for stimulation of MMP13 expression. CONCLUSION: Consistent with these findings, the inhibition of PKC prevented PTHrP-induced activation of ERK1/2, whereas 12-O-tetradecanoylphorbol-13-acetate (TPA), a stimulator of PKC, up-regulated the PTHrP-induced activation of ERK1/2. Taken together, our data indicate that the MDA-MB-231 breast cancer cells may carry out bone destruction and favor their own metastatic behavior by producing MMP-13. Given that the cells expressed PTHrP and that this factor stimulated MMP-13 expression, metastatic bone destruction may result from a PTHrP autocrine loop involving a PKC-ERK1/2 signaling pathway.

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記述言語：英語  

BACKGROUND: Gingival squamous cell carcinoma (SCC) cells frequently invade mandibular bone, and this destruction is associated with a worse prognosis. However, the relationship between bone destruction and associated factors is unclear. In this study, the role and diagnostic utility of transforming growth factor-beta (TGF-beta) type I receptor (TbetaRI) in bone destruction of the mandible was investigated. PATIENTS AND METHODS: The expression of TbetaRI was explored by using an immunohistochemical method on paraffin-embedded tissues from 21 cases of mandibular SCC. An inhibitor of the kinase activity of the TbetaRI (TbetaRI-I) was used to assess the role of TbetaRI in bone destruction by a human oral SCC cell line (HSC-2) that highly expresses TbetaRI. RESULTS: TbetaRI-positive signals were closely associated with destructive invasion of the mandible by oral SCC cells. Consistent with these results, TbetaRI-I greatly reduced HSC-2 cell-induced bone destruction and osteoclast formation in vivo and in vitro. TbetaRI-I treatment reduced the expression of TNF-alpha, RANKL and connective tissue growth factor (CTGF/CCN2), all of which were up-regulated by TGF-beta in HSC-2 cells. CONCLUSION: These data demonstrated an important role for TGF-beta signalling in bone invasion by oral SCC cells, and suggest that the bone destruction is mediated by RANKL, TNF-alpha and CCN2.

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記述言語：英語  

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is a key regulator of osteolytic metastasis of breast cancer (BC) cells, but its targets and mechanisms of action are not fully understood. This study investigated whether/how PTHrP (1-34) signaling regulates expression of vascular endothelial growth factor (VEGF) produced by BC cells. MATERIALS AND METHODS: A mouse model of bone metastasis was prepared by inoculating mice with tumour cell suspensions of the human BC cell line MDA-MB-231 via the left cardiac ventricle. VEGF expression was examined by Western blot and real-time RT-PCR analysis, as well as by confocal microscopy in the bone microenvironment. RESULTS: PTHrP was expressed in cancer cells producing PTH/PTHrP receptor and VEGF that had invaded the bone marrow, and PTHrP was up-regulated VEGF in MDA-MB-231 in vitro. The culture medium conditioned by PTHrP-treated MDA-MB-231 cells stimulated angiogenesis and osteoclastogenesis compared with control medium, giving a response that was inhibited by VEGF-neutralizing antibody treatment. Inhibition of protein kinase C (PKC) prevented PTHrP-induced extracellular signal-regulated kinase (ERK1/2) and p38 activation, and PTHrP-induced VEGF expression. CONCLUSION: PTHrP plays an important role in modulating the angiogenic and bone osteolytic actions of VEGF through PKC-dependent activation of an ERK1/2 and p38 signaling pathway during bone metastasis by breast cancer cells.

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Netherlands  

CCN2/CTGF, previously known as Connective Tissue Growth Factor, is a crucial regulator of extra-cellular matrix (ECM), which promotes ECM synthesis and stabilization. As their family name clearly implies, matrix metalloproteases (MMPs) are also localized in the ECM, where they function as proteases, modulating cell signaling by cleaving proteins such as matrix proteins, growth factors and growth factor receptors. Strong expression of CCN2/CTGF in chondrocytic cells occurs through transcription enhancer dominant in chondrocytes (TRENDIC). Matrix metalloprotease-3 (MMP3) is a novel TRENDIC-binding transcription factor for CCN2/CTGF expression. First, MMP3 cDNA was cloned as a TRENDIC-binding factor by Southwestern screening. The interaction between MMP3 and TRENDIC was confirmed by a gel shift assay and chromatin immunoprecipitation. The CCN2/CTGF promoter was activated by transfected MMP3, whereas a TRENDIC mutant for the promoter lost the response. In addition, the knockdown of MMP3 suppressed CCN2/CTGF expression. Cytochemical and histochemical analyses demonstrated that MMP3 was detected in the nuclei of chondrocytic cells in culture and also in the nuclei of normal and osteoarthritic chondrocytes in vivo. The nuclear translocation of externally added recombinant MMP3 was observed in 30 min after the addition, and six putative nuclear localization signals were found in MMP3. These results indicated a novel trans-activation mechanism of CCN2/CTGF by the nuclear translocation of MMP3 through binding with TRENDIC in chondrocytes. Although MMPs historically had been recognized as a protease for extra-cellular proteins, this study indicated that it also stimulates ECM synthesis through CCN2/CTGF trans-activation. This novel regulatory role of the ECM may contribute to understanding the mechanism of not only the development, but also the pathogenesis of arthritis fibrosis and periodontitis. © Springer Science+Business Media B.V. 2010.

DOI： 10.1007/978-90-481-3779-4_19

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記述言語：日本語   出版者・発行元：岡山歯学会  

2002〜2009年の7年間に著者等の施設でインプラント埋入を施行した162例(男性62例、女性100例、18〜78歳・平均55.3歳)を対象に受診経路、埋入インプラントの種類、埋入本数・部位などについて検討した。その結果、患者の受診経路は院内他科からの紹介141例・他院からの紹介15例・紹介なし7例で、紹介患者が96%を占めた。埋入インプラントの種類はBranemark System;382本・Steri-Oss System;54本・Replace;14本で、埋入本数は2002年(14名34本)から2007年(46名126本)にかけて増加傾向にあった。年齢別患者数とインプラント埋入本数では40〜70歳代の147名に415本と大部分を占めており、埋入部位は上顎235本・下顎215本とほぼ同じであった。前臼歯別では上顎前歯部84本・上顎臼歯部151本、下顎前歯部18本・下顎臼歯部197本であった。経過観察では全例で術後の合併症は認めず、インプラント総残存率は99.5%であった。

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

The role of epithelial-mesenchymal transition (EMT) in metastasis remains controversial. EMT has been postulated as an absolute requirement for tumor invasion and metastasis. Three different models including incomplete EMT, mesenchymal-epithelial transition (MET), and collective migration have been proposed for the role of EMT in cancer invasion and metastasis. However, skepticism remains about whether EMT truly occurs during cancer progression, and if it does, whether it plays an indispensible role in metastasis. Our recent findings suggest that EMT cells are responsible for degrading the surrounding matrix to enable invasion and intravasation of both EMT and non-EMT cells. Only non-EMT cells that have entered the blood stream are able to re-establish colonies in the secondary sites. Here, we discuss an alternative model for the role of EMT in cancer metastasis in which EMT and non-EMT cells cooperate to complete the entire process of spontaneous metastasis. [Cancer Res 2009;69(18):7135-9]

DOI： 10.1158/0008-5472.CAN-09-1618

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記述言語：日本語   出版者・発行元：岡山歯学会  

根治的治療を施行した口腔扁平上皮癌一次症267例において、臨床病理学的諸因子ならびに治療法別の治療成績を評価した。Stage分類、T分類、N分類、原発巣分化度、浸潤様式、再発・転移の因子が、有意に生存率に影響を及ぼした。頬粘膜癌が他の癌に比べ有意に予後不良であった。手術群、術前照射群、術前化学療法群、組織内照射群、放射線動注化学療法群、放射線療法群の5年疾患特異的累積生存率は、それぞれ74.1%、77.1%、100%、97.2%、91.7%.100%であった。根治的治療群における5年累積生存率は全症例77.4%、再発・転移群46.7%であった。N分類および分化度が独立した予後規定因子となった。治療後に評価できる因子である再発・転移(あり/なし)の項目を加え、生存率について多変量解析を行い、再発・転移の因子のみが独立した予後規定因子となった。

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記述言語：英語  

AMP-activated protein kinase (AMPK) serves as a fuel-sensing enzyme that is activated by binding of AMP and subsequent phophorylation by upstream kinases such as the tumor suppressor LKB1, when cells sense an increase in the ratio of AMP to ATP. Acute activation of AMPK stimulates fatty acid oxidation to generate more ATP and simultaneously inhibits ATP-consuming processes including fatty acid and protein syntheses, thereby preserving energy for acute cell-surviving program, whereas chronic activation leads to inhibition of cell growth. The goal of the present study is to explore the mechanisms by which AMPK regulates cell growth. Toward this end, we established stable cell lines by introducing a dominant-negative mutant of AMPK alpha1 subunit or its shRNA into the prostate cancer C4-2 cells and other cells, or wild type LKB1 into the lung adenocarcinoma A549 and breast MB-MDA-231 cancer cells, both of which lack functional LKB1. Our results showed that the inhibition of AMPK accelerated cell proliferation and promoted malignant behavior such as increased cell migration and anchorage-independent growth. This was associated with decreased G1 population, downregulation of p53 and p21, and upregulation of S6K, IGF-1 and IGF1R. Conversely, treatment of the C4-2 cells with 5-aminoimidazole-4-carboxamide 1-D-ribonucleoside (AICAR), a prototypical AMPK activator, caused opposite changes. In addition, our study using microarray and RT-PCR revealed that AMPK regulated gene expression involved in tumor cell growth and survival. Thus, our study provides novel insights into the mechanisms of AMPK action in cancer cells and presents AMPK as an ideal drug target for cancer therapy.

DOI： 10.1038/onc.2009.63

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：英語  

PURPOSE: Angiogenin (ANG) undergoes nuclear translocation and stimulates rRNA transcription in both prostate cancer cells and endothelial cells. The purpose of this study is to assess the antitumor activity of neamine, a nontoxic degradation product of neomycin that blocks nuclear translocation of ANG. EXPERIMENTAL DESIGN: The anti-prostate cancer activity of neamine was first evaluated in a xenograft animal model. It was then examined in the murine prostate-restricted AKT transgenic mice that develop prostate intraepithelial neoplasia (PIN) owing to AKT transgene overexpression. RESULTS: Neamine inhibits xenograft growth of PC-3 human prostate cancer cells in athymic mice. It blocks nuclear translocation of ANG and inhibits rRNA transcription, cell proliferation, and angiogenesis. Neamine also prevents AKT-induced PIN formation as well as reverses fully developed PIN in murine prostate-restricted AKT mice, accompanied by a decrease in rRNA synthesis, cell proliferation, and angiogenesis and an increase in prostate epithelial cell apoptosis. CONCLUSION: We confirmed that ANG is a molecular target for cancer drug development and that blocking nuclear translocation of ANG is an effective means to inhibit its activity. Our results also suggested that neamine is a lead compound for further preclinical evaluation.

DOI： 10.1158/1078-0432.CCR-08-2593

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記述言語：英語  

Angiogenin (ANG), originally identified as an angiogenic ribonuclease, has recently been shown to play a direct role in prostate cancer cell proliferation by mediating rRNA transcription. ANG is up-regulated in human prostate cancer and is the most significantly up-regulated gene in AKT-driven prostate intraepithelial neoplasia (PIN) in mice. Enhanced cell proliferation in the PIN lesions requires increased ribosome biogenesis, a multistep process involving an orchestrated production of ribosomal proteins and rRNA. AKT is known to enhance ribosomal protein production through the mammalian target of rapamycin pathway. However, it was unknown how rRNA is proportionally increased. Here, we report that ANG is essential for AKT-driven PIN formation and survival. We showed that up-regulation of ANG in the AKT-overexpressing mouse prostates is an early and lasting event. It occurs before PIN initiation and lasts beyond PIN is fully developed. Knocking down ANG expression by intraprostate injection of lentivirus-mediated ANG-specific small interfering RNA prevents AKT-induced PIN formation without affecting AKT expression and its signaling through the mammalian target of rapamycin pathway. Neomycin, an aminoglycoside that blocks nuclear translocation of ANG, and N65828, a small-molecule enzymatic inhibitor of the ribonucleolytic activity of ANG, both prevent AKT-induced PIN formation and reverse established PIN. They also decrease nucleolar organizer region, restore cell size, and normalize luminal architectures of the prostate despite continuous activation of AKT. All three types of the ANG inhibitor suppress rRNA transcription of the prostate luminal epithelial cells and inhibit AKT-induced PIN, indicating an essential role of ANG in AKT-mediated cell proliferation and survival.

DOI： 10.1158/1541-7786.MCR-08-0137

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

Epithelial-mesenchymal transition (EMT) has been considered essential for metastasis, a multistep process including local invasion, intravasation, extravasation, and proliferation at distant sites. However, controversy remains as to whether EMT truly happens and how important it is to metastasis. We studied the involvement of EMT in individual steps of metastasis and found that p12(CDK2-AP1), a down-stream effector of transforming growth factor beta, induced EMT of hamster cheek pouch carcinoma-1 cells by promoting the expression of Twist2. EMT cells have an increased invasive but decreased metastatic phenotype. When s.c. inoculated, both EMT and non-EMT cells established primary tumors, but only EMT cells invaded into the adjacent tissues and blood vessels; however, neither cells formed lung metastases. When i.v. inoculated, only non-EMT cells established lung metastases. Moreover, s.c. inoculation of a mixture of the two cell types resulted in intravasation of both cell types and formation of lung metastasis from non-EMT cells. Our results allowed us to propose a novel model for the role of EMT in cancer metastasis. We showed that EMT and non-EMT cells cooperate to complete the spontaneous metastasis process. We thus hypothesize that EMT cells are responsible for degrading the surrounding matrix to lead the way of invasion and intravasation. Non-EMT cells then enter the blood stream and reestablish colonies in the secondary sites. [Cancer Res 2008;68(24):10377-86]

DOI： 10.1158/0008-5472.CAN-08-1444

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記述言語：英語  

Nicotine, one of the major components in tobacco, is at high concentrations in the bloodstream of cigarette smokers. However, the mechanisms of how nicotine affects tumor development and whether nicotine is a potential carcinogen for malignancies induced by secondhand smoking are not fully understood yet. Here, we investigate the signaling pathways by which nicotine potentiates tumorigenesis in human mammary epithelial-like MCF10A or cancerous MCF7 cells. We show that human MCF10A and MCF7 cells both express four subunits of nicotine acetylcholine receptor (nAChR). The treatment of these cells with nicotine enhances the activity of protein kinase C (PKC) alpha without altering the expression level of this kinase. Nicotine also stimulates [(3)H]thymidine incorporation into the genome of these cells as well as forces serum-starved cells to enter S phase of the cell cycle, resulting in growth promotion. Importantly, on nicotine treatment, the mobility of MCF10A and MCF7 cells is enhanced, which can be blocked by the addition of nAChR or PKC inhibitor. Experiments using small interfering RNA knockdown or ectopic expression of cdc42 showed that cdc42 functions as a downstream effector of PKC and is crucial in the regulation of nicotine-mediated migratory activity in the cells. Together, our findings suggest that nicotine, through interacting with its receptor, initiates a signaling cascade that involves PKC and cdc42 and consequently promotes migration in mammary epithelial or tumor cells.

DOI： 10.1158/0008-5472.CAN-08-0131

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記述言語：英語  

Matrix metalloproteinase 3 (MMP3) is well known as a secretory endopeptidase that degrades extracellular matrices. Recent reports indicated the presence of MMPs in the nucleus (A. J. Kwon et al., FASEB J. 18:690-692, 2004); however, its function has not been well investigated. Here, we report a novel function of human nuclear MMP3 as a trans regulator of connective tissue growth factor (CCN2/CTGF). Initially, we cloned MMP3 cDNA as a DNA-binding factor for the CCN2/CTGF gene. An interaction between MMP3 and transcription enhancer dominant in chondrocytes (TRENDIC) in the CCN2/CTGF promoter was confirmed by a gel shift assay and chromatin immunoprecipitation. The CCN2/CTGF promoter was activated by overexpressed MMP3, whereas a TRENDIC mutant promoter lost the response. Also, the knocking down of MMP3 suppressed CCN2/CTGF expression. By cytochemical and histochemical analyses, MMP3 was detected in the nuclei of chondrocytic cells in culture and also in the nuclei of normal and osteoarthritic chondrocytes in vivo. The nuclear translocation of externally added recombinant MMP3 and six putative nuclear localization signals in MMP3 also were shown. Furthermore, we determined that heterochromatin protein gamma coordinately regulates CCN2/CTGF by interacting with MMP3. The involvement of this novel role of MMP3 in the development, tissue remodeling, and pathology of arthritic diseases through CCN2/CTGF regulation thus is suggested.

DOI： 10.1128/MCB.01288-07

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

SOX9 is a transcription factor that plays a critical role in the development of multiple tissues. We previously reported that SOX9 in normal human adult prostate was restricted to basal epithelium. SOX9 was also expressed in a subset of prostate cancer (PCa) cells and was increased in relapsed hormone-refractory PCa. Moreover, SOX9 expression in PCa cell lines enhanced tumor cell proliferation and was beta-catenin regulated. Here we report additional in vivo results showing that SOX9 is highly expressed during fetal prostate development by epithelial cells expanding into the mesenchyme, suggesting it may contribute to invasive growth in PCa. Indeed, SOX9 overexpression in LNCaP PCa xenografts enhanced growth, angingenesis, and invasion. Conversely, short hairpin RNA-mediated SOX9 suppression inhibited the growth of CWR22Rv1 PCa xenografts. These results support important functions of SOX9 in both the development and maintenance of normal prostate, and indicate that these functions contribute to PCa tumor growth and invasion.

DOI： 10.1158/0008-5472.CAN-07-5915

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The mandibular condyle formation during temporomandibular joint (TMJ) development exhibits endochondral bone formation, and the elongation process is dependent on the normal cartilage proliferation and differentiation. Retinoids are important for maturation of growth-plate chondrocytes, but the identity of their downstream effectors remains unclear. In this study, we carried out a series of studies at the cellular, biochemical, and molecular levels to determine whether, and if so how, retinoid signaling is related to the expression and function of Indian hedgehog (Ihh) in chondrocyte proliferation. First we analyzed the RA receptor (RAR) and Ihh expression pattern in E18 mandibular condyle. RAR α and RAR β mRNA were characterized in the per-ichondrium around the condyle, whereas RARy mRNA was expressed in the immature and prehypertrophic chondrocytes and the expression was overlapped with Ihh gene expression. Next we established a high-density culture model of chick cephalic chondrocytes in the prehypertrophic stage. We found that all-trans retinoic acid (RA) induced Ihh mRNA gene expression in this system. The RA pan-antagonist Ro 41-5253 inhibited both endogenous and RA-induced Ihh mRNA in a dose-dependent manner. The Ihh mRNA expression induced by RA required de novo protein synthesis, and was mediated by RARy. Immunoblots showed that the prehypertrophic chondrocytes contained sizable levels of phosphorylated p38 mitogen-activated protein (MAP) kinase that were time- and dose-dependently increased by the RA treatment. Experimental p38 inhibition led to a severe drop in baseline and RA-stimulated Ihh expression. Exogenous recombinant Ihh stimulated the proliferation of proliferating chondrocytes, whereas RA inhibited the proliferation of these chondrocytes through p38 MAPK. Retinoids appear to play a primary role in controlling both the expression and function of Ihh in prehypertrophic chondrocytes and do so via p38 MAP kinase. © 2008, Japanese Stomatological Society. All rights reserved.

DOI： 10.11277/osi.5.1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Osteosarcoma is the most common primary malignant bone tumor, accounting for approximately 20% of all primary sarcomas in bone. Although treatment modalities have been improved over the past decades, it is still a tumor with a high mortality rate in children and young adults. Based on histological considerations, osteosarcoma arises from impaired differentiation of these immature cells into more mature types and that correction of this impairment may reduce malignancy and increase the efficiency of chemotherapy. The purpose of this study was to determine the effect of specific inhibitors of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK) and p38 on the differentiation of human osteosarcoma cell line SaOS-2 cells. We found that PD98059, a specific inhibitor of MEK, inhibited the serum-stimulated proliferation of SaOS-2 cells; whereas SB203580, a specific inhibitor of p38 MAPK, had little effect on it. SB203580 suppressed ALPase activity, gene expression of type I collagen, and expression of ALP and BMP-2 mRNAs; whereas PD98059 upregulated them dose dependently. In addition, immunoblot and immunostaining analysis revealed that phosphorylation of ERK was increased by treatment with SB203580; whereas PD98059 increased the phosphorylation of p38, which implies a seesaw-like balance between ERK and p38 phosphorylation. We suggest that osteosarcoma cell differentiation is regulated by the balance between the activities of the ERK and p38 pathways and that the MEK/ERK pathway negatively regulates osteosarcoma cell differentiation, whereas the p38 pathway does so positively. MEK inhibitor may thus be a good candidate for altering the expression of the osteosarcoma malignant phenotype.

DOI： 10.1007/s12079-007-0010-2

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

今回、口腔癌治療後の肺転移に対してdocetaxel投与を行ったところ、急性呼吸窮迫症候群(ARDS)を来した症例を経験したので報告する。症例は84歳、男性。下顎歯肉癌にて下顎骨部分切除術および頸部郭清術を受けている。経過観察中に両側肺転移と判明。この転移巣に対してdocetaxel投与(40mg/body)を施行したところARDSを発症した。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER CHEMICAL SOC  

Ornithine decarboxylase (ODC) antizyme targets ODC for ubiquitin-independent proteosome degradation, thereby inhibiting polyamine synthesis. It has been shown to regulate DNA methylation and has tumor suppressor activity. Increasing evidence suggested that antizyme may also have ODC-independent functions. Here, we report that antizyme plays a role in DNA double-strand break repairs. A zinc-inducible human antizyme gene expression vector was transfected into UM1 human oral squamous cancer cells that do not express endogenous antizyme. The resultant upregulated genes were screened by cDNA arrays and confirmed by quantitative real-time polymerase chain reaction. DNA-dependent protein kinase including its catalytic subunit DNA-PKcs and regulatory subunit Ku70, two key proteins of the DNA damage repair machinery, was significantly upregulated after ectopic expression of antizyme. Consistently, we found that UM1 cells are sensitive to gamma irradiation and deficient in DNA damage repairs, as shown by radio-sensitivity and Comet assays. Ectopic expression of antizyme increased radio-resistance of UM1 cells and restored their capacity of DNA damage repairs to the level of UM2 cells that have an identical genetic background but express endogenous antizyme. Plasmid end-joining assays confirmed that antizyme enhances the ability of UM1 cells to repair DNA double-strand breaks by the nonhomologous end-joining pathway.

DOI： 10.1021/bi7000328

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記述言語：日本語   出版者・発行元：岡山歯学会  

63歳男。扁平上皮癌であり、舌部分切除及び右側根治的頸部郭清術変法を施行した。局所再発に対しサイバー・ナイフによる放射線治療、肺転移に対して化学療法を施行したが、両部位とも制御不能となった。その後、嚥下障害が著明になり、気管切開及び胃瘻造設術を施行した。以後、自宅療養を続けていたが、全身倦怠感及び呼吸困難が増強し再入院となった。栄養摂取は胃瘻からのみで、総タンパク6.7g/dl、アルブミン3.2g/dlであった。常に左側側臥位をとっていたため、左側大転子部、左側肩部、仙骨部の皮膚に褥瘡を認めた。左側肩部、仙骨部の褥瘡はハイドロコロイド創傷被覆材での治療で良好な結果が得られたが、左側大転子部の褥瘡は重度で表面に壊死組織がみられ、日本褥瘡学会褥瘡分類D3E3s4ilG3N1-P1と評価し、本院褥瘡対策チームに診察を依頼した。生食洗浄、壊死組織除去、2時間毎の体位変換、体圧分散式マットレスへの変更、ポケット内の陰圧持続吸引、栄養サポートチームによる栄養対策などを行ったところ、褥瘡部の肉芽形成は進み、少しずつポケットは改善していった。肉芽組織の形成は良好で、右側顎下部皮膚穿孔部からの出血による循環不全にて死亡する一週間前には、皮膚損傷範囲は入院時の7.0cm×6.0cmから3.0cm×1.6cmへと改善していた。

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

今回われわれは下顎歯肉癌患者の肺転移に対し、外科的治療とadjuvant chemotherapyとしてpaclitaxel(PTX),cisplatin(CDDP),5-fluorouracil(5-FU)の全身投与4コースが有効であった症例を経験したので報告する。症例は47歳、女性。下顎歯肉扁平上皮癌の頸部リンパ節転移症例に対し、外科療法後CDDPと5-FUの化学療法を行った。4ヵ月後肺転移を認め、video-assisted thoracoscopic surgery(VATS)による肺部分切除術を施行した。14ヵ月後肺転移を再び認め、VATSによる肺部分切除術が再施行され、引き続いてadjuvant chemotherapyを施行した(1日目PTX 35mg/m2 3時間点滴静注、2日目CDDP 75mg/m2点滴静注、2〜5日目5-FU 350mg/m2/day持続点滴静注)。終了後、6年以上経過しているが再発は認めていない。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Introduction: Connective tissue growth factor (CTGF/CCN2) is a mediator of local angiogenesis induced by breast cancer, but its role in osteolytic metastasis has not been evaluated. PTH-related peptide (PTHrP) is another critical factor in the development of the osteolytic metastasis. Using both in vivo and in vitro approaches, we studied whether/how neutralization of CCN2 prevented bone metastasis and how PTHrP signaling is related.Materials and Methods: A mouse model of bone metastasis by human breast cancer cell line MDA231 was treated with a CCN2-neutralizing antibody, and osteolytic bone metastases were assessed on radiographs and immunohistochemistry. Ccn2 gene expression and transcription were examined by Northern blot and luciferase analysis. Immunoblot analysis and kinase inhibitors were used to identify the signaling pathways implicated. Anti-angiogenic/osteoclastogenic effects of ccn2 downregulation were also evaluated.Results: Treatment of mice with a CCN2-neutralizing antibody greatly decreased osteolytic bone metastasis, microvasculature, and osteoclasts involved. The antibody also suppressed the growth of subcutaneous tumor in vivo and proliferation and migration of human umbilical vein endothelial cells (HUVECs) in vitro. Downregulation of ccn2 also repressed osteoclastogenesis. CCN2 expression was specifically observed in cancer cells producing PTHrP and type I PTH/PTHrP receptor (PTH1R) invaded the bone marrow, and PTHrP strongly upregulated ccn2 in MDA231 cells in vitro. Activation of protein kinase C (PKC) and protein kinase A (PKA) was necessary and sufficient for the stimulation of ccn2 by PTHrP. Indeed, inhibition of the extracellular signal-regulated kinase (ERK1/2), PKC, or PKA by specific inhibitors counteracted the stimulation of ccn2 expression. Incubation of MDA231 cells with PTHrP induced the activation of ERK1/2. Consistent with these findings, inhibition of PKC prevented PTHrP-induced ERK1/2 activation, whereas 12-O-tetradecanoylphorbol-13-acetate (TPA), a stimulator of PKC, upregulated it.Conclusions: CCN2 was critically involved in osteolytic metastasis and was induced by PKA- and PKC-dependent activation of ERK1/2 signaling by PTHrP. Thus, CCN2 may be a new molecular target for anti-osteolytic therapy to shut off the PTHrP-CCN2 signaling pathway.

DOI： 10.1359/jbmr.060416

Web of Science

PubMed

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：岡山歯学会  

口腔扁平上皮癌における術後再発,頸部後発転移,遠隔転移の頻度ならびに発現時期の検討を行った.根治手術を施行した一次症例175例中,再発,転移をきたした口腔扁平上皮癌56例を対象とした.175例中30例に一次治療終了後に原発巣再発を認めた.全原発巣再発症例の63.3%が6ヵ月以内に再発した.頸部再発は,69例中7例に認めた.頸部再発の時期は,6ヵ月以内が5例で,1年以上が2例であった.原発巣を制御し得た頸部後発転移は19例(17.9%)であった.全頸部後発転移症例の52.6%が6ヵ月以内に転移した.175例中10例(5.7%)に遠隔転移を認めた.全遠隔転移症例の60.0%が6ヵ月以内に転移した.原発巣・頸部ともに制御された遠隔転移2例では,比較的早期に遠隔転移を認めた.原発巣・頸部非制御症例では,全て頸部リンパ節転移が認められた後に遠隔転移が発見された

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：三豊総合病院  

【目的】高齢化が進む三豊及びその周辺地区では,顎関節脱臼を起こす高齢者は多いと推察される。今回,顎関節脱臼を起こして当科に紹介された高齢患者の特徴を明らかにするために臨床的検討を行なったので治療経過を含めて報告する。【方法】2021年4月から2023年3月までの2年間で,顎関節脱臼を起こして当科に紹介された高齢患者17例について臨床的に検討を行なった。【結果および考察】年齢は平均85.9歳で,85歳以上が半数以上を占めた。また性別は女性が男性の2倍以上(男女比1:2.4)を占めた。脱臼様式は両側性と習慣性がそれぞれ15例(88.2%)と多く認められた。既往疾患は脳血管障害が12例(70.6%)と最も多く,次に認知症6例(35.3%),循環器疾患5例(29.4%)と続き,Performance Status 3以上が14例認められた。これらの患者の発症契機は不明であったが,咀嚼筋の拘縮・弛緩がベースにあり,欠伸や咳反射による大開口が原因と推測された。治療は自己整復できた2例を除き15例に徒手整復を試み,12例は一旦整復に成功し,必要に応じて顎バンデージを装着した。そして,家族の同意が得られた4例に顎関節自己血注入療法を施行した結果,その後の再脱臼は認められなかった。しかし,残りの3例は整復できず,全身状態が不良で家族からの治療継続の希望もなく,それ以上の治療を断念せざるを得なかった。【結論】高齢者の顎関節脱臼は,両側性で習慣性に起こる症例が大半を占め,脳血管障害や認知症の患者に多く認められた。徒手整復と顎バンデージによる開口制限に加え,顎関節自己血注入療法は有効な治療法であったが,患者の全身状態と家族の意志が治療の継続に大きく影響した。(著者抄録)

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：日本歯科衛生学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：日本骨形態計測学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：三豊総合病院  

口腔領域における静脈瘤は,高齢者の舌,口唇,頬粘膜に紫色の小さな限局性腫瘤として認められることがある。しかし,これらの病変が10mm以上に大きくなることは非常にまれである。今回我々は,舌癌切除後に発生した血栓形成を伴う大きな舌静脈瘤の1例を経験したので報告する。患者は,90歳の男性で,当科で右側舌癌の切除手術を受けた。その4ヵ月後に,患者は右側舌の義歯による接触痛を訴えた。診察の結果,右側舌に正常粘膜で覆われた弾性硬,可動性の大きな腫瘤を認めた。CT所見では,境界明瞭な24×23×20mm大の腫瘤を認めた。舌癌の再発を疑い,局所麻酔下で切除生検を行った。病理組織学的診断は,血栓性静脈瘤であった。現在,6ヵ月を経過したが,再発・転移は認めていない。(著者抄録)

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記述言語：日本語   出版者・発行元：三豊総合病院  

高齢者の習慣性顎関節脱臼は,患者の日常生活に著しく支障を及ぼすだけでなく,全身状態を悪化させ誤嚥性肺炎を発症するリスクも高める。本院では,習慣性顎関節脱臼を起こす高齢患者に対して,保存的処置から観血的処置まで行っている。そして,2021年4月からは入院下で歯科医師,歯科衛生士,看護師,栄養サポートチームによる多職種連携のもと,全身管理を行いながら自己血注入療法を施行する体制を整えたので,症例を提示し問題点を含めて報告する。症例1は93歳,女性で,アルツハイマー型認知症がある。咳き込む毎に両側顎関節脱臼を起こし全身状態不良となり,当科を受診した。緊急入院後,食事の誤嚥を防止し,自己血注入療法を施行した。症例2は85歳,女性で,脳梗塞発症後は寝たきり状態である。両側顎関節脱臼の陳旧例のため,まず顎間牽引による脱臼整復が必要であった。しかし,全身状態不良のため,治療の同意が家族から得られなかった症例である。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：岡山歯学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：岡山歯学会  

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記述言語：日本語   出版者・発行元：クインテッセンス出版(株)  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：岡山歯学会  

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記述言語：日本語   出版者・発行元：(公社)日本顎顔面インプラント学会  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

UICCのTNM分類は、口腔癌の進行度評価の基準として使用されている。2016年に公表された第8版TNM分類では、T分類に浸潤の深さ(DOI)、N分類に被膜外進展(ENE)が導入された。そして、われわれは、舌扁平上皮癌の手術症例を対象に、第7版と第8版TNM分類による評価を比較し、後者の実用性を本誌において報告した。さらに、2018年にUICCから正誤表が公表され、T2、T3、T4が訂正された。そこで本研究では、当科で手術を施行した舌扁平上皮癌107例について、正誤表に準拠して改めて検討を行った。正誤表に準拠して評価すると、1例がT3からT2に、3例がT3からT4aに変更された。第7版と比較すると、後発転移率がT1では低下し、T2では増加したが、第8版とは同様の結果であった。生存率は、第8版と同様に、Tの上昇とともに低下した。また、pTの変更に伴って、pStageが変更されたため、stageの上昇とともに生存率が低下した。訂正された第8版TNM分類は、進行度に即したTの細分化を舌扁平上皮癌においても実現し、細分化により進行度を的確に後発転移と生存率へ反映させており、実用的であると考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

UICCのTNM分類は、口腔癌の進行度評価の基準として使用されている。2016年に公表された第8版TNM分類では、T分類に浸潤の深さ(DOI)、N分類に被膜外進展(ENE)が導入された。そして、われわれは、舌扁平上皮癌の手術症例を対象に、第7版と第8版TNM分類による評価を比較し、後者の実用性を本誌において報告した。さらに、2018年にUICCから正誤表が公表され、T2、T3、T4が訂正された。そこで本研究では、当科で手術を施行した舌扁平上皮癌107例について、正誤表に準拠して改めて検討を行った。正誤表に準拠して評価すると、1例がT3からT2に、3例がT3からT4aに変更された。第7版と比較すると、後発転移率がT1では低下し、T2では増加したが、第8版とは同様の結果であった。生存率は、第8版と同様に、Tの上昇とともに低下した。また、pTの変更に伴って、pStageが変更されたため、stageの上昇とともに生存率が低下した。訂正された第8版TNM分類は、進行度に即したTの細分化を舌扁平上皮癌においても実現し、細分化により進行度を的確に後発転移と生存率へ反映させており、実用的であると考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

85歳男性。下顎歯右7を抜歯後に右側顎関節部の腫脹と自発痛が出現し、右側関節突起の著明な骨吸収を示す右側下顎骨骨髄炎と診断された。急性冠症候群に対する経皮的肝動脈形成術の既往歴がある。入院し抗菌薬(セファゾリンナトリウム、クリンダマイシン)投与を行ったが、硬結や開口障害は改善せず、第7病日に右側顎関節部を切開排膿した。膿汁にActinomyces israelii菌塊を認めたため顎放線菌症と診断し、抗菌薬をベンジルペニシリン持続投与に変更した。症状は改善したが抗菌薬変更後に頻回の下痢症状、無痛性新鮮血下血が出現した。下部消化管内視鏡で直腸軟膜の潰瘍と同部からの出血を認め、クリッピング術を行った。各検査所見は抗菌薬起因性大腸炎は否定的で、動脈硬化を背景とし感染症を伴う消耗と低栄養状態から臥床状態となったことにより発症した急性出血性直腸潰瘍(AHUR)と診断した。

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：岡山歯学会  

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記述言語：日本語   出版者・発行元：(公社)日本顎顔面インプラント学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本骨代謝学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本骨代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(公社)日本顎顔面インプラント学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本顎変形症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語  

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