Language：English   Publishing type：Research paper (scientific journal)  

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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Language：Japanese   Publisher：(一社)日本口腔内科学会  

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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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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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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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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/ccr3.4321

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.4321

Language：English   Publishing type：Research paper (scientific journal)  

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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Language：Japanese   Publisher：(NPO)日本顎変形症学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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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Language：Japanese   Publisher：(一社)日本口腔内科学会  

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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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Language：English   Publishing type：Research paper (scientific journal)  

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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Publishing type：Research paper (scientific journal)   Publisher：Spandidos Publications  

DOI： 10.3892/or.2020.7788

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本顎変形症学会  

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Language：Japanese   Publisher：(NPO)日本顎変形症学会  

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Language：English  

The process of fracture healing consists of an inflammatory reaction and cartilage and bone tissue reconstruction. The inflammatory cytokine interleukin-1β (IL-1β) 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-1β and retinoic acid receptor gamma (RARγ) in a rat fracture model and the effects of IL-1β in the presence of one of several RAR inverse agonists on chondrocytes. An immunohistochemical analysis revealed that IL-1β and RARγ were expressed in chondrocytes at the fracture site in the rat ribs on day 7 post-fracture. In chondrogenic ATDC5 cells, IL-1β 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-1β-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-1β treatment, and the IL-1β-induced p-p38 MAPK was inhibited by AGN194310. Experimental p38 inhibition led to a drop in the IL-1β-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-1β 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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Language：English   Publishing type：Research paper (scientific journal)  

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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Language：English  

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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Language：Japanese   Publisher：岡山歯学会  

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Language：Japanese   Publisher：(NPO)日本顎変形症学会  

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Language：English   Publishing type：Research paper (scientific journal)  

CD11b+ myeloid subpopulations, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), play crucial roles in the suppression of T-cell-mediated anti-tumor immunity. Regulation of these cell types is a primary goal for achieving efficient cancer immunotherapy. We found that metformin (Met) induces CD11b+-cell-mediated growth inhibition of a K7M2neo osteosarcoma independent of T cells, as growth inhibition of K7M2neo was still observed in wild-type (WT) mice depleted of T cells by antibodies and in SCID; this contrasted with the effect of Met on Meth A fibrosarcoma, which was entirely T-cell-dependent. Moreover, the inhibitory effect seen in SCID was abrogated by anti-CD11b antibody injection. PMN-MDSCs were significantly reduced in both spleens and tumors following Met treatment. In TAMs, production of IL-12 and TNF-α, but not IL-10, became apparent, and elevation of MHC class II with reduction of CD206 was observed, indicating a shift from an M2- to M1-like phenotype via Met administration. Metabolically, Met treatment decreased basal respiration and the oxygen consumption rate (OCR)/extracellular acidification rate (ECAR) ratio of CD11b+ cells in tumors, but not in the spleen. In addition, decreased reactive oxygen species (ROS) production and proton leakage in MDSCs and TAMs were consistently observed in tumors. Uptake of both 2-deoxy-2-d-glucose (2-NBDG) and BODIPY® decreased in MDSCs, but only BODIPY® incorporation was decreased in TAMs. Overall, our results suggest that Met redirects the metabolism of CD11b+ cells to lower oxidative phosphorylation (OXPHOS) while elevating glycolysis, thereby pushing the microenvironment to a state that inhibits the growth of certain tumors.

DOI： 10.1093/intimm/dxy079

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：English   Publisher：(一社)日本癌学会  

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DOI： 10.3389/fonc.2018.00376.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

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.

DOI： 10.21873/anticanres.12132

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

CD4(+) CD25(+) regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. Wefound thatmetformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103(+) KLRG1(+) population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of naive CD4(+) T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1. Rapamycin and compound C, an inhibitor of AMP-activated protein kinase (AMPK) restored the iTreg generation, further indicating the involvement of mTORC1 and AMPK. The metabolic profile of iTreg, increased Glut1-expression, and reduced mitochondrial membrane-potential and ROS production of Ti-Treg aided in identifying enhanced glycolysis upon Met-treatment. The negative impact of Met on Ti-Treg may help generation of the sustained antitumor immunity. (C) 2017 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license

DOI： 10.1016/j.ebiom.2017.10.009

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

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.

DOI： 10.21873/anticanres.12060

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Language：English   Publisher：(一社)日本癌学会  

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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 (75mg/m2) and cyclophosphamide (600mg/m2) were administrated four times every 21days and thereafter radiotherapy (total 60Gy) 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.

DOI： 10.1016/j.ijscr.2016.12.014

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Publishing type：Research paper (scientific journal)   Publisher：Graphyonline Publications PVT, Ltd.  

DOI： 10.15344/2456-4443/2017/115

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

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.

DOI： 10.21873/anticanres.11230

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：Japanese   Publishing type：Doctoral thesis  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(NPO)日本顎変形症学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(公社)日本栄養・食糧学会  

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Language：Japanese   Publisher：(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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