DSpace コレクション: 2024年度博士論文

Intra-arterial Therapy Using Micellar Nanoparticles Incorporating SN-38 in a Rat Pancreatic Tumor Model

2026-03-12T16:30:25Z

タイトル: Intra-arterial Therapy Using Micellar Nanoparticles Incorporating SN-38 in a Rat Pancreatic Tumor Model 著者: Maeda, Shinsaku; Sato, Takeshi; Nishiofuku, Hideyuki; Toyoda, Shohei; Taiji, Ryosuke; Matsumoto, Takeshi; Chanoki, Yuto; Tachiiri, Tetsuya; Kunichika, Hideki; Sho, Masayuki; Tanaka, Toshihiro 抄録: Purpose To evaluate advantages of micellar nanoparticles encapsulating SN-38, a biologically active metabolite of irinotecan, in intraarterial therapy for pancreatic cancer. Materials and Methods Rat pancreatic cancer cells (DSL-6A/C1) were implanted in Lewis rats under laparotomy. This study consists of two parts. Firstly, after confirming tumor formation by ultrasonography, celiac arteriography was performed, and tumor blood supply was visually evaluated by dye injection and CT during arteriography. Secondly, 18 rats were divided into two groups; the Micellar Nanoparticles group and the Irinotecan Infusion group. Micellar nanoparticles or irinotecan was injected via the celiac artery, and SN-38 and irinotecan concentrations in the tumor, duodenum and pancreatic parenchyma, were measured at 5 min, 6 h and 24 h. Results The maximum concentration (Cmax) of SN-38 were shown at 6 h in the Micellar Nanoparticles group, while Cmax of irinotecan was shown at 5 min in the Irinotecan Infusion group. Tumor concentration in the Micellar Nanoparticles group maintained elevated for 24 h without significant decrease (P = 0.068). Conversely, a significant decrease was observed in the regular pancreas parenchyma (P = 0.006) and duodenum (P = 0.028). In the Irinotecan Infusion group, tumor irinotecan concentration significantly decreased at 24 h (P = 0.016). Conclusion Micellar nanoparticles may improve arterial infusion chemotherapy for pancreatic cancer. These nanoparticles have the potential to reduce SN-38 accumulation in duodenum, while increasing it in the tumor. Further research is warranted to validate and expand upon these findings. 内容記述: 権利情報：© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00270-024-03939-y.

Prediction of Efficacy for Atezolizumab/Bevacizumab in Unresectable Hepatocellular Carcinoma with Hepatobiliary-Phase Gadolinium Ethoxybenzyl Diethylenetriaminepentaacetic Acid MRI

2026-03-12T16:30:25Z

タイトル: Prediction of Efficacy for Atezolizumab/Bevacizumab in Unresectable Hepatocellular Carcinoma with Hepatobiliary-Phase Gadolinium Ethoxybenzyl Diethylenetriaminepentaacetic Acid MRI 著者: Kunichika, Hideki; Minamiguchi, Kiyoyuki; Tachiiri, Tetsuya; Shimizu, Kozo; Taiji, Ryosuke; Yamada, Aya; Nakano, Ryota; Irizato, Mariko; Yamauchi, Satoshi; Marugami, Aki; Marugami, Nagaaki; Kishida, Hayato; Nakagawa, Hiroyuki; Takewa, Megumi; Kageyama, Ken; Yamamoto, Akira; Ueshima, Eisuke; Sofue, Keitaro; Kita, Ryuichi; Kurakami, Hiroyuki; Tanaka, Toshihiro 抄録: Background: This study aimed to examine whether the coefficient of variation (CV) in the hepatobiliary-phase (HBP) of Gd-EOB-DTPA-MRI could be an independent predictive factor for tumor progression. Methods: Patients who underwent Gd-EOB-DTPA-MRI before Atezolizumab/ bevacizumab therapy at six affiliated institutions between 2018 and 2022 were included. CV for each patient was calculated as the mean value for up to five tumors larger than 10 mm, and CV of the whole tumor was calculated using LIFEx software. The tumor response was evaluated within 6–10 weeks. The primary endpoint was to investigate the predictive factors, including CV, related to tumor progression using logistic regression analysis. The secondary endpoints were tumor response rate and progression-free survival (PFS) based on CV. Results: Of the 46 enrolled patients, 13 (28.3%) underwent early progressive disease. Multivariate analysis revealed that a high CV (≥0.22) was an independent predictive factor for tumor progression (p = 0.043). Patients with a high CV had significantly frequent PD than those with a low CV (43.5 vs. 13.0%, p = 0.047). Patients with a high CV tended to have shorter PFS than those with a low CV (3.5 vs. 6.7 months, p = 0.071). Conclusion: Quantitative analysis using CV in the HBP of Gd-EOB-DTPA-MRI may be useful for predicting tumor progression for atezolizumab/bevacizumab therapy. 内容記述: 権利情報：© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Effects of aging on otolith morphology and functions in mice

2026-03-12T16:30:24Z

タイトル: Effects of aging on otolith morphology and functions in mice 著者: Ueda, Keita; Imai, Takao; Ito, Taeko; Okayasu, Tadao; Harada, Shotaro; Kamakura, Takefumi; Ono, Kazuya; Katsuno, Tatsuya; Tanaka, Tatsuhide; Tatsumi, Kouko; Hibino, Hiroshi; Wanaka, Akio; Kitahara, Tadashi 抄録: Background: Increased fall risk caused by vestibular system impairment is a significant problem associated with aging. A vestibule is composed of linear acceleration-sensing otoliths and rotation-sensing semicircular canals. Otoliths, composed of utricle and saccule, detect linear accelerations. Otolithic organs partially play a role in falls due to aging. Aging possibly changes the morphology and functions of otoliths. However, the specific associations between aging and otolith changes remain unknown. Therefore, this study aimed to clarify these associations in mice. Methods: Young C56BL/6 N (8 week old) and old (108–117 weeks old) mice were used in a micro-computed tomography (μCT) experiment for morphological analysis and a linear acceleration experiment for functional analysis. Young C56BL/6 N (8 week old) and middle-aged (50 week old) mice were used in electron microscopy experiments for morphological analysis. Results: μCT revealed no significant differences in the otolith volume (p = 0.11) but significant differences in the otolith density (p = 0.001) between young and old mice. μCT and electron microscopy revealed significant differences in the structure of striola at the center of the otolith (μCT; p = 0.029, electron microscopy; p = 0.017). Significant differences were also observed in the amplitude of the eye movement during the vestibulo-ocular reflex induced by linear acceleration (maximum amplitude of stimulation = 1.3G [p = 0.014]; maximum amplitude of stimulation = 0.7G [p = 0.015]), indicating that the otolith function was worse in old mice than in young mice. Discussion: This study demonstrated the decline in otolith function with age caused by age-related morphological changes. Specifically, when otolith density decreased, inertial force acting on the hair cells decreased, and when the structure of striola collapsed, the function of cross-striolar inhibition decreased, thereby causing a decline in the overall otolith function. 内容記述: 権利情報：© 2024 Ueda, Imai, Ito, Okayasu, Harada, Kamakura, Ono, Katsuno, Tanaka, Tatsumi, Hibino, Wanaka and Kitahara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Prognosis of asymptomatic endolymphatic hydrops in healthy volunteers: A five-year cohort study

2026-03-12T16:30:22Z

タイトル: Prognosis of asymptomatic endolymphatic hydrops in healthy volunteers: A five-year cohort study 著者: Kimura, Takahiro; Kitahara, Tadashi; Okayasu, Tadao; Sakagami, Masaharu; Shiozaki, Tomoyuki; Inui, Hiroshi; Koizumi, Toshizo; Kakudo, Mariko 抄録: Background: This study aimed to clarify the prognosis of asymptomatic endolymphatic hydrops (EH) in healthy volunteers via five-year follow-ups with inner ear magnetic resonance imaging (MRI). Methods: Inner ear MRI was performed on 115 participants recruited as controls in a previous study on Meniere's disease. The endolymphatic space was visualized using Naganawa's method of contrast-enhanced MRI with intravenous gadolinium injection and evaluated using Nakashima's method of 2D imaging analysis. Results: Cochlear or vestibular EH was present in 7.0% of participants (n = 8), with all cases being unilateral (laterality), moderate (severity), and asymptomatic (onset). Only cochlear-localized EH, only vestibular-localized EH, and both EH were present in 1.7% (n = 2) (C group), 4.3% (n = 5) (V group), and 0.9% (n = 1) (CV group) of participants, respectively. Conducting inner ear MRI after 5 years showed that EH had almost disappeared in two participants in the C and V groups (4/8, 50.0%). EH was still present in three participants in the V group and one in the CV group (4/8, 50.0%). One participant in the V group and another in the CV group presented with residual inner ear EH and developed typical symptomatic Meniere's disease (2/8, 25.0%). Conclusions: Approximately 7% of healthy participants showed asymptomatic EH. Therefore, EH is not the definitive marker for making a diagnosis of Meniere's disease or the suitable predictor for the development of Meniere's disease. Among these participants, 25% maintained EH and subsequently developed typical Meniere's disease within the next 5 years. Schellong-positive participants maintained persistent EH in the inner ear, and participants with higher scores on the self-rating depression scale developed Meniere's symptoms after 5 years. 内容記述: 権利情報：© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.