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

Flattened 1D fragments of fullerene C₆₀ that exhibit robustness toward multi-electron reduction

フラーレンに迫る電子受容能をもつ平坦な一次元π共役炭化水素の開発. 京都大学プレスリリース. 2023-05-15.Flat fullerene fragments attractive to electrons. 京都大学プレスリリース. 2023-06-01.Fullerenes are compelling molecular materials owing to their exceptional robustness toward multi-electron reduction. Although scientists have attempted to address this feature by synthesizing various fragment molecules, the origin of this electron affinity remains unclear. Several structural factors have been suggested, including high symmetry, pyramidalized carbon atoms, and five-membered ring substructures. To elucidate the role of the five-membered ring substructures without the influence of high symmetry and pyramidalized carbon atoms, we herein report the synthesis and electron-accepting properties of oligo(biindenylidene)s, a flattened one-dimensional fragment of fullerene C₆₀. Electrochemical studies corroborated that oligo(biindenylidene)s can accept electrons up to equal to the number of five-membered rings in their main chains. Moreover, ultraviolet/visible/near-infrared absorption spectroscopy revealed that oligo(biindenylidene)s exhibit enhanced absorption covering the entire visible region relative to C₆₀. These results highlight the significance of the pentagonal substructure for attaining stability toward multi-electron reduction and provide a strategy for the molecular design of electron-accepting π-conjugated hydrocarbons even without electron-withdrawing groups

口腔内所見を用いた新たな年齢推定法

In forensic science, age estimation is an important step in identifying unidentified cadavers. As teeth are resistant to environmental degradation for long periods of time, they are often used to estimate age. Although there have been many reports of age estimation based on dental morphology, these methods tend to be subjective and cannot be used i n the case of edentulous jaws. In the present study, we developed a new method of age estimation from dental parameters (number of upper teeth [UT], lower teeth [LT], and prostheses [NP]; tooth attrition [TA]; and occlusal area [OA]) and the mandibular angle (MA) measured at proposed an equation for calculating the age. The results show that the mean error of this method is similar to that of previous methods, and even demonstrated improved accuracy in subjects aged >60 years. We also proposed an equation for age estimation from only the MA, and showed that we can perform age estimation even in edentulous cases using this equation. Because our method is superior in its simplicity, objectivity, and applicability when compared with previous methods, we believe our method wll prove useful for age estimation in a wide variety of cases.博士（医学）・甲611号・平成26年3月17

[18F]fluoro-2-deoxyglucose-positron emission tomography を用いた進行口腔扁平上皮癌における術前化学放射線療法による治療効果判定の検討

BACKGROUND: [18F]fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) is widely used to evaluate tumor metabolic activity. The aim of this study was to evaluate the usefulness of FDG-PET in assessing the histopathological response to preoperative concurrent chemoradiotherapy (CRT) in patients with oral squamous cell carcinoma (OSCC). METHODS: Forty-five patients with resectable advanced OSCC who had received preoperative CRT followed by tumor ablative surgery between January 2004 and December 2011 were included in the study. All patients underwent FDG-PET before and after preoperative CRT. The maximum standardized uptake value (SUVmax) before (pre-SUV) and after preoperative CRT (post-SUV) and the SUVmax reduction rate (ΔSUV %) were used to evaluate the response to preoperative CRT. Correlations among SUVmax, histopathological response, and expression of cancer antigen Ki-67 and hypoxia-inducible factor-1α (HIF-1α) were analyzed. RESULTS: Preoperative CRT significantly reduced intratumoral FDG uptake (P < 0.001). The pre-SUV and post-SUV were significantly lower in patients with a pathological complete response (pCR) than in those with a non-pCR (pre-SUV P = 0.037; post-SUV P = 0.001). ΔSUV % was higher in patients with pCR than in those with non-pCR (P = 0.029). The pre-SUV was significantly correlated with Ki-67 and HIF-1α expression in pretreatment biopsy specimens (Ki-67 P = 0.046, R = 0.292; HIF-1α P = 0.007, R = 0.385). The expression of both Ki-67 and HIF-1α was significantly lower in patients with pCR than in those with non-pCR (Ki-67 P < 0.001; HIF-1α P < 0.001). CONCLUSIONS: Low pre-SUV and post-SUV and high ΔSUV % may predict a good histopathological response to preoperative CRT. Ki-67 and HIF-1α expression in pretreatment biopsy specimens were predictors of histopathological response to preoperative CRT.博士（医学）・乙第1357号・平成27年3月16日© Springer International Publishing AG, Part of Springer Science+Business Media© Japan Society of Clinical Oncology 201

ATR阻害は非相同末端結合および相同組換え修復と非依存的に5-FUを増感する

The anticancer agent 5-fluorouracil (5-FU) is cytotoxic and often used to treat various cancers. 5-FU is thought to inhibit the enzyme thymidylate synthase, which plays a role in nucleotide synthesis and has been found to induce single- and double-strand DNA breaks. ATR Ser/Thr kinase (ATR) is a principal kinase in the DNA damage response and is activated in response to UV- and chemotherapeutic drug-induced DNA replication stress, but its role in cellular responses to 5-FU is unclear. In this study, we examined the effect of ATR inhibition on 5-FU sensitivity of mammalian cells. Using immunoblotting, we found that 5-FU treatment dose-dependently induced the phosphorylation of ATR at the autophosphorylation site Thr-1989 and thereby activated its kinase. Administration of 5-FU with a specific ATR inhibitor remarkably decreased cell survival, compared with 5-FU treatment combined with other major DNA repair kinase inhibitors. Of note, the ATR inhibition enhanced induction of DNA double-strand breaks and apoptosis in 5-FU-treated cells. Using gene expression analysis, we found that 5-FU induced the activation of the intra-S cell-cycle checkpoint. Cells lacking BRCA2 were sensitive to 5-FU in the presence of ATR inhibitor. Moreover, ATR inhibition enhanced the efficacy of the 5-FU treatment, independently of the nonhomologous end-joining and homologous recombination repair pathways. These findings suggest that ATR could be a potential therapeutic target in 5-FU-based chemotherapy.博士（医学）・甲第791号・令和3年3月15日© 2020 Ito et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.This is an Open Access article under the CC BY license(https://creativecommons.org/licenses/by/4.0/)

One-dimensional fragments of fullerene C60 that exhibit robustness toward multi-electron reduction and pronounced light absorption

Fullerenes are compelling molecular materials owing to their exceptional robustness toward multi-electron reduction. Although scientists have attempted to address this feature by synthesizing various fragment molecules, the origin of this electron affinity remains unclear. Several structural factors have been suggested, including high symmetry, curved structures, and five-membered ring substructures. To elucidate the role of the five-membered ring substructures without the influence of high symmetry and curved structure, we herein report the synthesis and electron-accepting properties of oligo(biindenylidene)s, a one-dimensional fragment of fullerene C60. Electrochemical studies corroborated that oligo(biindenylidene)s accept electrons equal to the number of five-membered rings in their main chains. Moreover, ultraviolet/visible/near-infrared absorption spectroscopy revealed that oligo(biindenylidene)s exhibit significantly enhanced absorption covering the entire visible region in relation to C60. These results highlight the significance of the pentagonal substructure for attaining stability toward multi-electron reduction and provide a new strategy for the molecular design of electron-accepting -conjugated hydrocarbons

Relationship Between EGFR Expression in Oral Cancer Cell Lines and Cetuximab Antibody-dependent Cell-mediated Cytotoxicity.

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）identifier:Anticancer research Vol.39 No.3 p.1275-1282 (2019 Mar)identifier:02507005identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3666identifier:Anticancer research, 39(3): 1275-128

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/)

A New Quantitative Multi-parameter Method Improves the Accuracy of Age Estimation from Oral Findings.

In forensic science, age estimation is an important step in identifying unidentified cadavers. As teeth are resistant to environmental degradation for long periods of time, they are often used to estimate age. Although there have been many reports of age estimation based on dental morphology, these methods tend to be subjective and cannot be used i n the case of edentulous jaws. In the present study, we developed a new method of age estimation from dental parameters (number of upper teeth [UT], lower teeth [LT], and prostheses [NP]; tooth attrition [TA]; and occlusal area [OA]) and the mandibular angle (MA) measured at proposed an equation for calculating the age. The results show that the mean error of this method is similar to that of previous methods, and even demonstrated improved accuracy in subjects aged >60 years. We also proposed an equation for age estimation from only the MA, and showed that we can perform age estimation even in edentulous cases using this equation. Because our method is superior in its simplicity, objectivity, and applicability when compared with previous methods, we believe our method wll prove useful for age estimation in a wide variety of cases.博士（医学）・甲611号・平成26年3月17日identifier:法医学の実際と研究 56号 p.211-218identifier:02890755identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2690identifier:法医学の実際と研究(56): 211-21