口腔癌細胞株におけるcetuximabを介した抗体依存性細胞障害(ADCC)活性と細胞表面EGFR発現との関連

BACKGROUND/AIM: Cetuximab treatment targets the epidermal growth factor receptor (EGFR) overexpressed in oral cancer. This study aimed to investigate the anti-tumour activity of cetuximab against oral cancer cell lines with respect to antibody-dependent cell-mediated cytotoxicity (ADCC), and determine the correlation between ADCC and EGFR expression. MATERIALS AND METHODS: EGFR expression in oral cancer cells was measured by quantitative flow cytometric analysis and immunohistochemistry. ADCC activity was measured by 4-h calcein release assays. RESULTS: Cetuximab-mediated ADCC against oral cancer cells was detectable at a concentration of 0.1 μg/ml. A high correlation was observed between the number of EGFR molecules on the surface of oral cancer cells and ADCC (correlation coefficient: 0.847; p=0.032). CONCLUSION: ADCC is an important mechanism underlying the therapeutic effect of cetuximab, and EGFR expression in tumour cells might serve as a predictive marker to evaluate the effect of cetuximab treatment.博士（医学）・甲第721号・令和元年9月27日Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.発行元の規定により、本文の登録不可。本文は以下のURLを参照 "http://dx.doi.org/10.21873/anticanres.13238"（※全文閲覧は学内限定

骨形成シートによる顎顔面の再生 : ラットにおける実験研究

OBJECTIVE: Regeneration of maxillofacial bone defects, characterized by relatively small but complicated shapes, poses a significant clinical challenge. Osteogenic matrix cell sheets (OMCSs) have osteogenic ability and good shaping properties and may be ideal graft materials. Here, we assessed whether implantation of OMCSs could be used to repair maxillofacial bone defects. DESIGN: We adopted a rat mandibular symphysis model. The rat mandible is formed by a paired bone and the central portion consisting of fibrous tissue. There is no bone tissue at the site; accordingly, this site was interpreted as a physiological bone gap and was used for evaluation. Rat bone marrow cells were cultured in medium containing dexamethasone and ascorbic acid phosphate to create OMCSs. The OMCSs were implanted into the rat mandibular symphysis without a scaffold. Microcomputed tomography and histological analyses were conducted after 2, 4, and 8 weeks. RESULTS: Two weeks after implantation, microcomputed tomography images and histological sections showed some sparse granular calcification tissue within the bone gap at the mandibular symphysis. At 4 weeks, the calcification tissue spread, and the gap of the mandibles were continued. At 8 weeks, this continuous new bone tissue was matured. The experimental group showed abundant new bone tissue in the group with OMCS implantation, but not in the group with sham implantation. CONCLUSIONS: Our present results indicated that use of OMCSs may be an optimal approach towards achieving maxillofacial regeneration.博士（医学）・甲第668号・平成29年3月15日Copyright © 2016 Elsevier Ltd. All rights reserved

Impact of beta-tricalcium phosphate on preventing tooth extraction-triggered bisphosphonate-related osteonecrosis of the jaw in rats

Abstract Antiresorptive or antiangiogenic drugs can cause medication-related osteonecrosis of the jaw that is refractory. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) may be caused by procedures such as tooth extraction damage the alveolar bone, release bisphosphonates (BPs) and impede healing. This study investigated strategies for BRONJ prevention and molecular mechanisms of its onset. We assessed the effectiveness of filling extraction sockets with beta-tricalcium phosphate (β-TCP). Rats were administered zoledronic acid (ZA) 1.2 mg/kg once per week for 2 weeks, and a molar was extracted. They were randomly assigned to the β-TCP group (bone defects filled with 0.01 g of β-TCP) or control group. Tissue content measurements indicated 2.2 ng of ZA per socket in the β-TCP group and 4.9 ng in the control group, confirming BP distribution and BP adsorption by β-TCP in vivo. At 4 weeks after extraction, the β-TCP group had normal mucosal coverage without inflammation. Moreover, at 8 weeks after extraction, enhanced bone healing, socket coverage, and new bone formation were observed in the β-TCP group. Connective tissue in the extraction sockets suggested that local increases in BP concentrations may suppress the local autophagy mechanisms involved in BRONJ. Filling extraction sockets with β-TCP may prevent BRONJ

A Foreign Body Granuloma of the Buccal Mucosa Induced by Honeybee Sting

A foreign body granuloma of the buccal mucosa induced by honeybee sting was reported. The patient was an 82-year-old female who presented with a submucous mass at the right buccal mucosa. The mass was 20 mm in diameter, elastically firm, partly mobile without pain or tenderness, and covered with almost normal mucosa. MR image did not delineate the lesion clearly. Under clinical diagnosis of a benign tumor, the lesion was excised under local anesthesia. The excised lesion was 14×11×9 mm in size and solid and yellowish in cut surface. Histologically, the lesion consisted of granulomatous tissue with a few narrow, curved, eosinophilic structures compatible with decomposed fragments of a honeybee sting and was diagnosed as a foreign body granuloma, although the patient did not recall being stung

Prevention of tooth extraction-triggered bisphosphonate-related osteonecrosis of the jaws with basic fibroblast growth factor: An experimental study in rats

Osteonecrosis of the jaw induced by administration of bisphosphonates (BPs), BP-related osteonecrosis (BRONJ), typically develops after tooth extraction and is medically challenging. As BPs inhibit oral mucosal cell growth, we hypothesized that suppression of the wound healing-inhibiting effects could prevent BRONJ onset after tooth extraction. Since basic fibroblast growth factor (bFGF) promotes wound healing, but has a short half-life, we examined whether the initiation of BRONJ could be prevented by applying a bFGF-containing gelatin hydrogel over the extraction sockets of BRONJ model rats. Forty-three rats, received two intravenous injections of zoledronic acid 60 μg/kg, once per week for a period of 2 weeks, underwent extraction of a unilateral lower first molar. The rats here were randomly assigned to the bFGF group (n = 15 rats, gelatin hydrogel sheets with incorporated bFGF applied over the sockets); the phosphate-buffered saline (PBS) group (n = 14 rats, gelatin hydrogel sheets without bFGF applied over the sockets); or the control group (n = 14 rats, nothing applied over the sockets). One rat in the bFGF group was sacrificed immediately after tooth extraction. Twenty-one rats were sacrificed at 3 weeks, and the remaining 21 rats were sacrificed at 8 weeks after tooth extractions. The harvested mandibles were analyzed using micro-computed tomography and sections were evaluated qualitatively for mucosal disruption and osteonecrosis. The incidence of osteonecrosis at 8 weeks after tooth extraction was 0% in the bFGF group, 100% in the PBS group, and 85.7% in the control group. The frequency of complete coverage of the extraction socket by mucosal tissue was significantly greater in the bFGF group than in the other groups. These results suggest that application of bFGF in the extraction socket promoted socket healing, which prevented BRONJ development. The growth-stimulating effects of bFGF may have offset the inhibition of wound healing by BP

Cepharanthine and Oral Lichen Planus Efficacy (COLE) study: protocol for a multicentre randomised controlled study assessing the efficacy and safety of cepharanthine with topical corticosteroids in oral lichen planus

Introduction Oral lichen planus (OLP) is a chronic, inflammatory oral condition leading to a range of symptoms from mild discomfort to severe pain, affecting patients’ quality of life. Standard therapy involves the use of topical corticosteroids, although some patients respond insufficiently or develop resistance to therapy. We aim to explore if adding cepharanthine, an herbal extract from Stephania cepharantha Hayata, can enhance the efficacy of corticosteroid therapy in symptomatic OLP.Methods and analysis This open-label, parallel-group, multi-centre, randomised controlled study will be conducted at three Japanese hospitals. It will compare safety and efficacy of integrated oral cepharanthine and corticosteroid therapy versus standard corticosteroid therapy. 50 symptomatic OLP patients will be randomised 1:1 to receive cepharanthine (30 mg/day) plus topical dexamethasone, or topical dexamethasone alone for 8 weeks. The primary outcome will be changed in pain intensity while drinking room-temperature water, measured on a visual analogue scale. The primary outcome is the change in pain intensity from baseline when drinking room-temperature water, evaluated using a visual analogue scale. Secondary outcomes are changes in the longest diameter of the target lesion from baseline to weeks 4 and 8, improvement and deterioration rates according to appearance and severity criteria at weeks 4 and 8, change in pain intensity when drinking room-temperature water from baseline to week 4, changes in pain intensity at rest from baseline to weeks 4 and 8, and the rates of adverse events.Ethics and dissemination This protocol was approved by the Certified Review Board of Nara Medical University (CRB5200002). Participants will provide informed consent. Results will be disseminated in peer-reviewed journals and conferences.Trial registration number Japan Registry of Clinical Trials (jRCTs051220130)

下顎再建後の三次元画像計測による顔面対称性の評価：主観的評価との比較

Introduction: The assessment of facial symmetry, after mandibular reconstruction, currently relies on subjective esthetic assessment by an evaluator. The present study aimed to compare conventional subjective assessment with quantitative evaluation by three-dimensional (3D) stereophotogrammetry of facial cosmetic symmetry. Methods: This retrospective study enrolled 20 patients who underwent mandibular reconstruction with free fibula flap after segmental resection between 2014 and 2018. Subjective assessments were performed by seven clinicians at 6-12 months after surgery. Simultaneously, lower face symmetry was measured by 3D stereophotogrammetry with the VECTRA H1 system and recorded as the root mean square deviation (RMSD). Data from the subjective and quantitative evaluations were compared using Spearman's rank correlation coefficient. Results: The results showed that subjective assessments were strongly and negatively correlated with RMSD (P=0.00000128). This confirmed that RMSD, obtained by 3D stereophotogrammetry, reflected the subjective assessment of symmetry in our cohort. Conclusions: Three-dimensional stereophotogrammetry of facial cosmetic symmetry will be an available quantitative method for patients with head and neck cancer after mandibular reconstruction.博士（医学）・乙第1475号・令和2年9月30日© 2020 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Data from: Risks of postextraction bleeding after receiving direct oral anticoagulants or warfarin: a retrospective cohort study

Objective: The effect of direct oral anticoagulants (DOACs) on the risk of bleeding after tooth extraction remains unclear. This study aimed to evaluate the incidence of post-extraction bleeding among patients who received DOAC and vitamin K antagonists (VKAs), such as warfarin. Design: This study was a retrospective cohort analysis. Incidence rates and propensity score matched regression models were used to compare the risks of bleeding after tooth extractions involving DOACs and VKAs. Setting: The study took place in a single university hospital in Japan. Participants: Between April 2013 and April 2015, 543 patients underwent a total of 1,196 simple tooth extractions. Primary outcome measure: The primary outcome measure was the occurrence of post-extraction bleeding, which was defined as bleeding that could not be stopped by biting down on gauze and required medical treatment between 30 minutes and 7 days after the extraction. Results: A total of 1,196 tooth extractions (634 procedures) in 541 patients fulfilled the study criteria, with 72 extractions (41 procedures) involving DOACs, 100 extractions (50 procedures) involving VKAs, and 1,024 extractions (543 procedures) involving no anticoagulants. The incidences of post-extraction bleeding per tooth for the DOAC, VKA, and no anticoagulant extractions were 10.4%, 12.0%, and 0.9%, respectively. The incidences of post-extraction bleeding per procedure for DOACs, VKAs, and no anticoagulants were 9.7%, 10.0%, and 1.1%, respectively. In comparison to the VKA extractions, the DOAC extractions did not significantly increase the risk of post-extraction bleeding (odds ratio: 0.69; 95% confidence intervals: 0.24–1.97; p=0.49). Conclusions: The risk of post-extraction bleeding was similar for DOAC and VKA extractions

bmjopen-2017-015952R2data

bmjopen-2017-015952R2dat