ヒトiPS細胞由来間葉系幹細胞を用いたラット気管軟骨再生

京都大学新制・課程博士博士(医学)甲第25861号医博第5146号京都大学大学院医学研究科医学専攻(主査)教授 後藤 慎平, 教授 川口 義弥, 教授 廣田 誠学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

7. Neutron Capture Therapy

In case that corrections are made, overwrite the modified version in the following web page: https://www.rri.kyoto-u.ac.jp/PUB/report/PR/ProgRep2024/ProgRep2024.htmlCO7-1 Antitumor effect of boron neurton capture therapy in cervical cancer mouse model/ A Toji et al. (R6001) [193]CO7-2 The effect of boron neutron capture therapy (BNCT) to gastrointestinal stromal tumor cell line GIST-T1/ S. Hagihara et al. (R6002) [194]CO7-3 The effect of boron neutron capture therapy (BNCT) to liver metastasis of colorectal cancer/ Y. Ueda et al. (R6003) [195]CO7-4 Development of a Therapeutic Agent for Bone Metastases with Nuclear Imaging and Boron Neutron Capture Therapy/ K. Ogawa et al. (R6006) [196]CO7-5 Examination of improvement of BNCT treatment efficiency by L-phenylalanine deficiency in mice tumor models/ Y. Tamari et al. (R6010) [197]CO7-6 Basic research on new BNCT strategies for melanoma/ H. Michiue et al. (R6012) [198]CO7-7 Cytosolic Delivery Technology Using Cationic Lipids in BNCT/ S. Hirase et al. (R6017) [199]CO7-8 Neutron irradiation experiments using a novel BPA formulation based on ionic liquids/ M. Shirakawa et al. (R6018) [200]CO7-9 Investigation of boron drug using albumin-binding polymer modified with boron clusters/ K. Banshoya et al. (R6019) [201]CO7-10 Development of boron rich nanostructure with amphiphilic block polymers as boron agents for BNCT/ R. Kawasaki et al. (R6022) [202]CO7-11 Development of a Water-Soluble Small Molecule Boron Carrier Targeting Biotin Receptors for Neutron Capture Therapy/ H. Nakamura et al. (R6024) [203]CO7-12 BNCT Effect of PBC-IP on Head and Neck Squamous Cell Carcinoma Mouse Model/ K. Miura et al. (R6025) [204]CO7-13 Construction of novel Boron-containing silica nanoparticles and BNCT experiments/ F. Tamanoi et al. (R6030) [205]CO7-14 Synthesis of PEPT1-targeted boron containing dipeptids for pancreatic cancer therapy/ F. Tamanoi et al. (R6032) [206]CO7-15 Sensitization of BPA-BNCT by Regulating the Polarity of Tumor-Associated Macrophage Using Shikonin/ N. Takabayashi et al. (R6037) [207]CO7-16 Boosting Antitumour Efficacy and Immunity by BNCT with Size-Controlled Nanoparticles/ W. Huang et al. (R6038) [208]CO7-17 Development of boron carriers based on the characteristics of energy metabolism of cancer/ R. Yamamoto et al. (R6040) [209]CO7-18 Tumour Growth Suppression by Neutron Capture Therapy using Intratumoral Administration of ¹⁰Boro-plex encapsulated Water-in-Oil-in-Water Emulsion/ H. Yanagie et al. (R6053) [210]CO7-19 Optimization of polymer-BPA conjugates for non-clinical studies/ T. Nomoto et al. (R6065) [211]CO7-20 Development of novel boron delivery systems improving accumulation contrast/ T. Nomoto et al. (R6066) [212]CO7-21 Development of Novel Small-molecule Boron Neutron Capture Therapy Drugs Targeting Tumor-specific Enzymatic Activity/ S. Kanai et al. (R6071) [213]CO7-22 Synthesis and evaluation of a novel boron neutron capture therapy agent/ H. Kimura et al. (R6072) [214]CO7-23 Measurements of two kinds of thimble-type ionization chambers for an intense epi-thermal neutron beam/ T. Matsumoto et al. (R6077) [215]CO7-24 Development of Nanogels Loaded with Gd(III)-Thiacalixarene Complex for Gd-NCT/ N. Iki et al. (R6092) [216]CO7-25 Research and Development of New Technology for Boron Neutron Capture Therapy/ M. Xu et al. (R6094) [217]CO7-26 Mechanism of Glioma Resistance After BNCT via Small Extracellular Vesicles/ N. Kondo et al. (R6096) [218]CO7-27 Characterization of Solar Cell-Based Radiation Detectors for BNCT Applications/ Y. Okuno et al. (R6098) [219]CO7-28 Establishment of innovative BNCT treatment method for intractable bladder cancer/ P. Huang et al. (R6109) [220]CO7-29 Evaluation of a novel cyclodextrin-based polyrotaxane boron compound for BNCT/ Y. Matsumoto et al. (R6111) [221]CO7-30 Attempts to sensitize tumor cells by exploiting the tumor microenvironment/ Y. Sanada et al. (R6115) [222]CO7-31 Tumor responses after BNCT at early stages/ Y. Tong et al. (R6119) [223]CO7-32 BNCT with a novel boron drug, BBCIP, for a rat brain tumor model/ K. Eza et al. (R6123) [224]CO7-33 Pathological Assessment of Boron Neutron Capture Therapy with CED-Based Delivery of FRα-Targeting PBC-IP in Non-Tumor-Bearing Rats/ K. Tsujino et al. (R6124) [225]CO7-34 Exploring Boron Neutron Capture Therapy for Chordoma: Experimental Study/ Y. Fujikawa et al. (R6125) [226]CO7-35 Deviation of Important Elements for Activation in Three Types of Ordinary Concrete for Radiation Shielding/ K. Kimura et al. (R6127) [227]CO7-36 Detection of -Borono-L-phenylalanine (BPA) Absorbed in Rice Seeds Using a Boron Neutron Capture Reaction/ T. Kinouchi et al (R6142) [228]CO7-37 Investigation of Potential Adverse Effects of Boron Neutron Capture Therapy on Host Immunity/ T. Watanabe et al. (R6144) [229]CO7-38 Investigation of Potential Adverse Effects of Boron Neutron Capture Therapy on Host Immunity/ T. Watanabe et al. (R6146) [230]CO7-39 Combining GdNCT and anti-PD-1 immunotherapy to boost abscopal effect/ L. Zhao et al. (R6150) [231]CO7-40 Investigation of nano-boron drugs for BNCT/ Z. Zhang et al. (R6151) [232]CO7-41 Analysis of the Structural Change of Boron Compounds after Boron Neutron Capture Reaction/ H. Ueda et al. (R6156) [233]CO7-42 Evaluation of a Retinoid X Receptor-Binding BSH Derivative for Inhibition of Cell Proliferation Under Neutron Irradiation/ A. Mashimo et al. (R6163) [234]CO7-43 Investigation of Boron Neutron Capture Reaction by Iodine-containing BSH Derivatives/ A. Mashimo et al. (R6164) [235]CO7-44 Safety of Boronated matrix metalloproteinase ligand 1 / N. Kondo et al. (R6165) [236]CO7-45 Investigation of cellular senescence by BNCT/ M. Suzuki et al. (R6167) [237]CO7-46 Clarification of the normal cell fractionation as a trigger for radiation-induced liver injury/ M. Suzuki et al. (R6168) [238

Gravid green turtles employ a mixed capital-income breeding strategy where food is abundant

Sea turtles are marine ectotherms commonly considered capital breeders that use accumulated energy stores for reproduction. In some green turtle Chelonia mydas populations, gravid females feed during the inter-nesting period, indicating that they are not exclusively capital breeders but may supplement energy stores with energy gained through feeding during inter-nesting periods. However, the significance of this feeding remains unknown, as does the time allocation between energy intake and energy-saving behaviors during inter-nesting periods. In this study, we deployed video, head-mounted acceleration, and GPS loggers on 9 green turtles nesting on Ishigaki Island, Japan, to monitor their feeding behavior during the inter-nesting period. We found that the turtles spent nearly half of the inter-nesting period resting (42.1% on average), but also dedicated 3.4% of their time to foraging, exhibiting a bimodal daily pattern with peaks in activity during the early morning and evening. Most feeding occurred around the algae/seagrass meadows in close vicinity to resting sites, so little energy is required to shuttle between feeding and resting sites. In such cases, the energy stores acquired prior to the breeding migration can be 'topped up' with feeding during inter-nesting intervals. Our results indicate that gravid green turtles employ a mixed capital-income breeding strategy in which females mostly rely on capital energy, but may supplement this with small amounts of income energy gained by feeding during inter-nesting periods

Synthesis and electron-transporting properties of phenazine bisimides

The dual incorporation of imide substituents and imine-type nitrogen atoms into π-systems represents an emerging guideline for the design of robust and high-performance n-type semiconductors. Herein, we have adapted this strategy to a simple molecular motif: anthracene, and thus synthesized phenazine bisimides (PzBIs). PzBIs exhibit superior electron affinity compared to anthracene bisimide and phenazine due to the presence of two types of functional electron-withdrawing units. The existence of imine-type nitrogen atoms in PzBI leads to the formation of two-dimensionally extended brickwork arrangements while anthracene bisimide forms one-dimensionally slipped-stacked arrays. Consequently, the electron mobility of the vacuum-deposited film of N, N′-dicyclohexyl PzBI is ten times higher than that of the corresponding anthracene bisimide. Furthermore, the OFET device of N, N′-bisheptafluorobutyl PzBI exhibits good air persistency, and its intrinsic electron mobility has been estimated to be approximately 0.7 cm² V⁻¹ s⁻¹ by the time-resolved microwave conductivity measurement. The current study demonstrates that the dual incorporation strategy endows even a simple and small π-system with good performance as an n-type semiconductor

Quantitative Live Imaging Reveals Phase Dependency of PDAC Patient-Derived Organoids on ERK and AMPK Activity

Patient-derived organoids represent a novel platform to recapitulate the cancer cells in the patient tissue. While cancer heterogeneity has been extensively studied by a number of omics approaches, little is known about the spatiotemporal kinase activity dynamics. Here we applied a live imaging approach to organoids derived from 10 pancreatic ductal adenocarcinoma (PDAC) patients to comprehensively understand their heterogeneous growth potential and drug responses. By automated wide-area image acquisitions and analyses, the PDAC cells were non-selectively observed to evaluate their heterogeneous growth patterns. We monitored single-cell ERK and AMPK activities to relate cellular dynamics to molecular dynamics. Furthermore, we evaluated two anti-cancer drugs, a MEK inhibitor, PD0325901, and an autophagy inhibitor, hydroxychloroquine (HCQ), by our analysis platform. Our analyses revealed a phase-dependent regulation of PDAC organoid growth, where ERK activity is necessary for the early phase and AMPK activity is necessary for the late stage of organoid growth. Consistently, we found PD0325901 and HCQ target distinct organoid populations, revealing their combination is widely effective to the heterogeneous cancer cell population in a range of PDAC patient-derived organoid lines. Together, our live imaging quantitatively characterized the growth and drug sensitivity of human PDAC organoids at multiple levels: in single cells, single organoids, and individual patients. This study will pave the way for understanding the cancer heterogeneity and promote the development of new drugs that eradicate intractable cancer

Phylogenetic origin of dioecious Callicarpa (Lamiaceae) species endemic to the Ogasawara Islands revealed by chloroplast and nuclear whole genome analyses

Oceanic islands offer excellent opportunities to study the ecology, evolutionary biology, and biogeography of plants. To uncover the genetic basis of various evolutionary trends commonly observed on these islands, the origins and phylogenetic relationships of the species being studied should be understood. Callicarpa glabra, Callicarpa parvifolia, and Callicarpa subpubescens are evergreen woody plants endemic to the Ogasawara Islands, which are remote oceanic islands located off of the Japanese Archipelago. These species are ideal for studying evolutionary changes on oceanic islands because of their adaptive radiation and shift toward dioecious sex expression. We used a phylogenomic perspective to determine the evolutionary relationship of the three species within the genus and infer their colonization time. Based on the analysis of both chloroplast genomes and 86 nuclear single-copy genes, we found that these three species were monophyletic and embedded in a backbone clade that included multiple East Asian species. The phylogenetic tree based on over 10, 000 nuclear genes placed the insular species in the East Asian clade, although the topology did not entirely correspond to the chloroplast tree, probably because of incomplete lineage sorting and interspecific hybridization. The three endemic species were estimated to have diverged from continental species approximately three million years ago (Mya). The results of this study suggested that the ancestor of the Ogasawara endemic species originated from long-distance dispersal from East Asia mainland in the late Pliocene, and then progressively speciated within the islands

Coalescence of carbon nanotubes while preserving the chiral angles

カーボンナノチューブを融合して直径2倍のチューブへと効率よく変換 --太いナノチューブの構造制御や後処理による物性改変に道-- . 京都大学プレスリリース. 2025-02-06.Atomically precise coalescence of graphitic nanocarbon molecules is one of the most challenging reactions in sp² carbon chemistry. Here, we demonstrate that two carbon nanotubes with the same chiral indices (n, m) are efficiently coalesced into a single (2n, 2 m) nanotube with preserved chiral angles via heat treatment at less than 1000 °C. The (2n, 2 m) nanotubes constitute up to ≈ 20%–40% of the final sample in the most efficient case. Additional optical absorption peaks of the (2n, 2 m) nanotubes emerge, indicating that the reaction occurs over the entire sample. The reaction efficiency strongly depends on the chiral angle, implying that C–C bond cleavage and recombination occurs sequentially. Furthermore, the reaction occurs efficiently even at 600 °C in an atmosphere containing trace amounts of oxygen. These findings offer routes for the structure-selective synthesis of large-diameter nanotubes and modification of the properties of nanotube assemblies via postprocessing

Clinical evaluation of performance, stability, and longevity of an accelerator system designed for boron neutron capture therapy utilising a beryllium target

Boron neutron capture therapy for recurrent head and neck cancer has been approved as an insurance covered treatment in Japan since June 2020. The Kansai BNCT Medical Center has installed the NeuCure® BNCT system developed by Sumitomo Heavy Industries. This system utilises a beryllium target with a 30 MeV proton beam to generate neutrons. To date, the center has treated over 300 patients and the system is also used for quality control and fundamental research experiments. Information on the stability and longevity of the system is important for facilities and hospitals considering installation of a BNCT system in the future, particularly after an exchange of a major component, such as the target. The beam output (neutron and gamma ray) was measured before and after the exchange of the target. The thermal neutron, fast neutron and gamma ray distribution inside a water phantom was evaluated and the results showed no significant change in the beam quality after the exchange of the target. Furthermore, no significant change in the neutron flux as a function of increasing number of accumulated protons on the target was observed up to a value of just under 400 mAh. The NeuCure® BNCT system has been shown to be highly stable and the frequency of target replacement was much less than lithium target-based accelerators

Suspected Fatal Arrhythmic Events in Japanese Patients With Coronary Artery Disease -- From the CREDO-Kyoto PCI/CABG Registries Cohorts-2 and -3 --

BACKGROUND: Fatal arrhythmic events (FAEs), such as sudden cardiac death (SCD) and fatal ventricular arrhythmias, are a devastating complication in patients with coronary artery disease (CAD). Therefore, in this study we aimed to assess the incidence of FAEs in more recent Japanese patients with CAD and to examine whether risk stratification of FAEs can still be feasible using the left ventricular ejection fraction (LVEF). METHODS and RESULTS: In the CREDO Kyoto PCI/CABG registry cohorts-2 and -3, there were 25, 843 patients with LVEF data who received a first coronary revascularization (LVEF ≤35% group: N=1, 671, 35%45%: N=21, 503). FAEs were defined as a composite of SCD or hospitalization for serious ventricular arrhythmias. The cumulative 5-year incidence of FAEs was 2.4% and it increased with decreasing LVEF (LVEF ≤35%: 8.84%, 35%45%: 1.67%, log-rank P<0.0001). The adjusted risk of FAEs also increased with decreasing LVEF. CONCLUSIONS: LVEF is still a strong independent factor for predicting FAEs in patients with CAD in the PCI era. There was no obvious decrease in the incidence of FAEs between the 2 cohorts. The risk factors for FAEs through the 2 cohorts, other than low LVEF, included age ≥75 years, diabetes, heart failure, hemodialysis, atrial fibrillation, and anemia