start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=2 article-no= start-page=35 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development of the Follow-Up Human 3D Oral Cancer Model in Cancer Treatment en-subtitle= kn-subtitle= en-abstract= kn-abstract=As function preservation cancer therapy, targeted radiation therapies have been developed for the quality of life of cancer patients. However, preclinical animal studies evaluating the safety and efficacy of targeted radiation therapy is challenging from the viewpoints of animal welfare and animal protection, as well as the management of animal in radiation-controlled areas under the regulations. We fabricated the human 3D oral cancer model that considers the time axis of the follow up in cancer treatment. Therefore, in this study, the 3D model with human oral cancer cells and normal oral fibroblasts was treated based on clinical protocol. After cancer treatment, the histological findings of the 3D oral cancer model indicated the clinical correlation between tumor response and surrounding normal tissue. This 3D model has potential as a tool for preclinical studies alternative to animal studies. en-copyright= kn-copyright= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IzumiKenji en-aut-sei=Izumi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakuraiYoshinori en-aut-sei=Sakurai en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=2 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= affil-num=3 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= en-keyword=3D cancer model kn-keyword=3D cancer model en-keyword=preclinical study kn-keyword=preclinical study en-keyword=cancer treatment kn-keyword=cancer treatment en-keyword=quality of life kn-keyword=quality of life en-keyword=multidisciplinary treatment kn-keyword=multidisciplinary treatment END start-ver=1.4 cd-journal=joma no-vol=115 cd-vols= no-issue=10 article-no= start-page=3231 end-page=3247 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240809 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Overcoming immunotherapy resistance and inducing abscopal effects with boron neutron immunotherapy (B-NIT) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8(+) T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44(+) effector memory T cells and CD69(+) early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers. en-copyright= kn-copyright= en-aut-name=FujimotoTakuya en-aut-sei=Fujimoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KanehiraNoriyuki en-aut-sei=Kanehira en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsushitaHirokazu en-aut-sei=Matsushita en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakuraiYoshinori en-aut-sei=Sakurai en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KenmotsuNaoya en-aut-sei=Kenmotsu en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MizutaRyo en-aut-sei=Mizuta en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KondoNatsuko en-aut-sei=Kondo en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakataTakushi en-aut-sei=Takata en-aut-mei=Takushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitamatsuMizuki en-aut-sei=Kitamatsu en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtaniYoshihiro en-aut-sei=Otani en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShirakawaMakoto en-aut-sei=Shirakawa en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ShigeyasuKunitoshi en-aut-sei=Shigeyasu en-aut-mei=Kunitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=TeraishiFuminori en-aut-sei=Teraishi en-aut-mei=Fuminori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TogashiYosuke en-aut-sei=Togashi en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=SuzukiMinoru en-aut-sei=Suzuki en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= affil-num=1 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute kn-affil= affil-num=5 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=6 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=9 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=10 en-affil=Faculty of Science and Engineering, Kindai University kn-affil= affil-num=11 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=12 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=13 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=15 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=16 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=18 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=19 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=20 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= en-keyword=abscopal effect kn-keyword=abscopal effect en-keyword=advanced melanoma kn-keyword=advanced melanoma en-keyword=boron neutron capture therapy kn-keyword=boron neutron capture therapy en-keyword=boron-neutron immunotherapy kn-keyword=boron-neutron immunotherapy en-keyword=immune combination therapy kn-keyword=immune combination therapy END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue= article-no= start-page=100297 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202408 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiation evaluation assay using a human three-dimensional oral cancer model for clinical radiation therapy. en-subtitle= kn-subtitle= en-abstract= kn-abstract=With the development of various radiation -based cancer therapies, radiobiological evaluation methods instead of traditional clonogenic assays with monolayer single cell culture are required to bridge gaps in clinical data. Heterogeneity within cancer tissues is the reason for bridging the gap between basic and clinical research in cancer radiotherapy. To solve this problem, we investigated an evaluation assay using a three-dimensional (3D) model of cancer tissue. In this study, a 3D model consisting of tumor and stromal layers was used to compare and verify radiobiological effects with conventional two-dimensional (2D) methods. A significant difference in the response to radiation was observed between the 2D and 3D models. The relative number of cancer cells decreased with X-ray dose escalations in the 2D and 3D models. In contrast, the relative number of normal cells was quite different between the 2D and 3D models. Considering the ability of cells to recover from radiation-induced damage, the histological results of the 3D model were reflected in the clinical data. Histopathological analysis using a 3D model is a potential method for evaluating radiobiological effects on the tumor and tumor margins. en-copyright= kn-copyright= en-aut-name=SercombeLucie en-aut-sei=Sercombe en-aut-mei=Lucie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IzumiKenji en-aut-sei=Izumi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Biomedical Engineering Department, Grenoble Institute of Technology kn-affil= affil-num=2 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=3 en-affil=Division of Biomimetics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University kn-affil= en-keyword=Oral cancer model kn-keyword=Oral cancer model en-keyword=3D-cell culture kn-keyword=3D-cell culture en-keyword=Radiation therapy kn-keyword=Radiation therapy en-keyword=Histopathological assay kn-keyword=Histopathological assay en-keyword=Radiobiological evaluation kn-keyword=Radiobiological evaluation END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=7 article-no= start-page=2300163 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230428 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Particle and Heavy Ion Transport Code System‐Based Microdosimetry for the Development of Boron Agents for Boron Neutron Capture Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Boron neutron capture therapy (BNCT) is a radiation therapy that selectively kills cancer cells at the cellular level using the boron neutron capture reaction (BNCR) (10B(n.α)7Li). The amount of boron 10B delivers in boronophenylalanine (BPA)-BNCT to achieve anti-tumor effects is ≈15–40 ppm. The same is true for all boron drugs; however, whether the same amount of 10B is required for other boron drugs with different accumulation characteristics has not been intensively investigated. Therefore, herein, a virtual cell model with intracellular organelles is prepared, and the BPA equivalent dose concentration to the cell nucleus is analyzed using particle and heavy ion transport code system-based microdosimetry. Additionally, the intranuclear minimal region (IMR) is set as a reference for the concept of the intranuclear domain in the microdosimetric kinetic model, and the BPA equivalent dose concentration to the IMR is estimated. The required boron delivery dose greatly varies depending on the dose assessment based on the accumulation characteristics of boron agents in intracellular organelles. Evaluation of the BNCR effect according to the accumulation characteristics without being influenced by the specified value of 15–40 ppm is recommended. en-copyright= kn-copyright= en-aut-name=ShigehiraTakafumi en-aut-sei=Shigehira en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HanafusaTadashi en-aut-sei=Hanafusa en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KasaiTomonari en-aut-sei=Kasai en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FuruyaShuichi en-aut-sei=Furuya en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MaedaYoshinobu en-aut-sei=Maeda en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=3 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=4 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=5 en-affil=Research Laboratory of Accelerator-Based BNCT system, Graduate School of Engineering Nagoya University kn-affil= affil-num=6 en-affil=Department of Hematology and Oncology Okayama University Hospital Okayama Okayama 700–8558 Japan kn-affil= affil-num=7 en-affil=Department of Hematology and Oncology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=9 en-affil=Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=boron agents kn-keyword=boron agents en-keyword=boron neutron capture therapy kn-keyword=boron neutron capture therapy en-keyword=simulation study kn-keyword=simulation study END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Prevention and early management of carotid blowout syndrome for patients receiving head and neck salvage boron neutron capture therapy (BNCT) en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background/purpose
The incidence rate of oral and pharyngeal cancers in Taiwan has increased gradually over the past few decades. The standard treatment strategy for oral and pharyngeal cancers includes surgery or radiotherapy, with concurrent chemotherapy in certain types of tumors. Unfortunately, in-field recurrence is sometimes inexorable. Furthermore, re-irradiation of the recurrence site may cause severe complications due to the tolerance of normal tissue to radiation therapy. One fatal complication is carotid blowout syndrome (CBS). Boron neutron capture therapy (BNCT) is a new modality of radiation therapy, which is also mentioned as targeted radiotherapy. It is a feasible treatment that has the potential to spare normal tissue from being damaged by irradiation while simultaneously treating the primary tumor. In this presentation, we will share our experience with BNCT in treating recurrent head and neck cancers, as well as the prevention and management of CBS.
Materials and methods
We evaluated 4 patients with head and neck cancers treated by BNCT in Taiwan. All patients had undergone surgery previously and had received postoperative concurrent chemoradiotherapy.
Results
The 4 patients in this study were diagnosed with head and neck malignancies. The median follow-up period after the first course of BNCT was 15.1 months. After BNCT, 2 patients developed impending CBS, and 1 of them died. The remaining 3 patients survived until the last date of follow-up.
Conclusion
Pre-BNCT carotid artery evaluation through computed tomography angiography and early intervention if necessary is crucial when treating patients with recurrent head and neck cancers by BNCT. en-copyright= kn-copyright= en-aut-name=LanTien-Li en-aut-sei=Lan en-aut-mei=Tien-Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChangFeng-Chi en-aut-sei=Chang en-aut-mei=Feng-Chi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WangChun-Wei en-aut-sei=Wang en-aut-mei=Chun-Wei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WuSzu-Hsien en-aut-sei=Wu en-aut-mei=Szu-Hsien kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=LoWen-Liang en-aut-sei=Lo en-aut-mei=Wen-Liang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ChenYi-Wei en-aut-sei=Chen en-aut-mei=Yi-Wei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Division of Radiotherapy, Department of Oncology, Taipei Veterans General Hospital kn-affil= affil-num=2 en-affil=Department of Radiology, Taipei Veterans General Hospital kn-affil= affil-num=3 en-affil=Division of Radiotherapy, Department of Oncology, Taiwan University Hospital kn-affil= affil-num=4 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=5 en-affil=Division of Plastic and Reconstructive Surgery, Taipei Veterans General Hospital kn-affil= affil-num=6 en-affil=Division of Oral and Maxillofacial Surgery, Department of Stomatology, Taipei Veterans General Hospital kn-affil= affil-num=7 en-affil=Division of Radiotherapy, Department of Oncology, Taipei Veterans General Hospital kn-affil= en-keyword=Boron neutron capture therapy kn-keyword=Boron neutron capture therapy en-keyword=Carotid blowout syndrome kn-keyword=Carotid blowout syndrome en-keyword=Head and neck cancerQuality of life kn-keyword=Head and neck cancerQuality of life en-keyword=Recurrence kn-keyword=Recurrence END