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AKASAKA HiroakiGraduate School of Medicine / Faculty of Medical SciencesAssistant Professor
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■ Paper- Springer Science and Business Media LLC, Jul. 2025, Scientific Reports, 15(1) (1), English[Refereed]Scientific journal
- Elsevier BV, Apr. 2025, Physica Medica, 132, 104915 - 104915, English[Refereed]Scientific journal
- Purpose: This study aims to investigate the radiation enhancement effects of ultrasound-stimulated microbubbles (USMB) with X-rays and nanoparticles on pancreatic cancer cells in vitro. Methods: Sonazoid™ microbubbles were used for USMB treatment with a commercially available ultrasound unit. The characterization of the microbubbles before and after ultrasound exposure with different mechanical parameters was evaluated microscopically. Two pancreatic cancer cell lines, MIAPaCa-2 and PANC-1, were treated with different concentrations of microbubbles in combination with 150 kVp X-rays and hydrogen peroxide-modified titanium dioxide nanoparticles. Cell viability was evaluated using a water-soluble tetrazolium dye and a colony formation assay. In addition, intracellular reactive oxygen species (ROS) induced by the combined treatment were assessed. Results: The number of burst microbubbles increased with ultrasound’s higher mechanical index and the exposure time. A significant radiation enhancement effect with a significant increase in ROS levels was observed in MIAPaCa-2 cells treated with USMB and 6 Gy X-rays, whereas it was not significant in PANC-1 cells treated with the same. When a higher concentration of USMB was applied with X-rays, no radiation enhancement effects were observed in either cell line. Moreover, there was no radiation enhancement effect by USMB between cells treated with and without nanoparticles. Conclusions: The results indicate that USMB treatment can additively enhance the therapeutic efficacy of radiation therapy on pancreatic cancer cells, while the synergistic enhancement effects are likely to be cell type and microbubble concentration dependent. In addition, USMB did not improve the efficacy of nanoparticle-induced radiosensitization in the current setting.Medknow, Jul. 2024, Journal of Medical Physics, 49(3) (3), 326 - 334, English[Refereed]Scientific journal
- Titanium dioxide nanoparticles (TiO2 NPs) have been investigated as one of the potential dose enhancement agents for radiation therapy. The role of TiO2 NPs as a photodynamic sensitiser has been well documented, but its sensitisation with X-rays is not highlighted. Unlike other metal NPs, such as gold NPs, the main challenge for TiO2 NPs as radiosensitisers is their low atomic number, resulting in a small cross-section for X-rays. This review summarises the results of current research in this area to explore the dose enhancement inflicted by TiO2 NPs, which could potentially be of great value in improving radiation therapy efficiency.MDPI AG, May 2024, Journal of Nanotheranostics, 5(2) (2), 60 - 74, English[Refereed]Scientific journal
- Springer Science and Business Media LLC, Jan. 2024, Physical and Engineering Sciences in Medicine, 47(2) (2), 465 - 475, English[Refereed]Scientific journal
- Abstract Purpose The CyberKnife system is a specialized device for non‐coplanar irradiation; however, it possesses the geometric restriction that the beam cannot be irradiated from under the treatment couch. Prone positioning is expected to reduce the dose to normal lung tissue in spinal stereotactic body radiotherapy (SBRT) owing to the efficiency of beam arrangement; however, respiratory motion occurs. Therefore, the Xsight spine prone tracking (XSPT) system is used to reduce the effects of respiratory motion. The purpose of this study was to evaluate the motion‐tracking error of the spine in the prone position. Materials and Methods Data from all 25 patients who underwent spinal SBRT at our institution between April 2020 and February 2022 using CyberKnife (VSI, version 11.1.0) with the XSPT tracking system were retrospectively analyzed using log files. The tumor motion, correlation, and prediction errors for each patient were examined. Furthermore, to assess the potential relationships between the parameters, the relationships between the tumor‐motion amplitudes and correlation or prediction errors were investigated using linear regression. Results The tumor‐motion amplitudes in each direction were as follows: superior–inferior (SI), 0.51 ± 0.39 mm; left–right (LR), 0.37 ± 0.29 mm; and anterior–posterior (AP), 3.43 ± 1.63 mm. The overall mean correlation and prediction errors were 0.66 ± 0.48 mm and 0.06 ± 0.07 mm, respectively. The prediction errors were strongly correlated with the tumor‐motion amplitudes, whereas the correlation errors were not. Conclusions This study demonstrated that the correlation error of spinal SBRT in the prone position is sufficiently small to be independent of the tumor‐motion amplitude. Furthermore, the prediction error is small, contributing only slightly to the tracking error. These findings will improve the understanding of how to compensate for respiratory‐motion uncertainty in the prone position.Wiley, Jan. 2023, Journal of Applied Clinical Medical Physics, 24(5) (5), English[Refereed]Scientific journal
- PURPOSE: Real-time tracking systems of moving respiratory targets such as CyberKnife, Radixact, or Vero4DRT are an advanced robotic radiotherapy device used to deliver stereotactic body radiotherapy (SBRT). The internal target volume (ITV) of lung tumors is assessed through a fiducial marker fusion using four-dimensional computed tomography (CT). It is important to minimize the ITV to protect normal lung tissue from exposure to radiation and the associated side effects post SBRT. However, the ITV may alter if there is a change in the position of the fiducial marker with respect to the tumor. This study investigated the relationship between fiducial marker position and the ITV in order to prevent radiation exposure of normal lung tissue, and correct target coverage. MATERIALS AND METHODS: This study retrospectively reviewed 230 lung cancer patients who received a fiducial marker for SBRT between April 2015 and September 2021. The distance of the fiducial marker to the gross tumor volume (GTV) in the expiratory (dex ) and inspiratory (din ) CT, and the ratio of the ITV/V(GTVex ), were investigated. RESULTS: Upon comparing each lobe, although there was no significant difference in the ddiff and the ITV/V(GTVex ) between all lobes for dex < 10 mm, there was significant difference in the ddiff and the ITV/V(GTVex ) between the lower and upper lobes for dex ≥ 10 mm (p < 0.05). Moreover, there was significant difference in the ddiff and the ITV/V(GTVex ) between dex ≥10 mm and dex < 10 mm in all lung regions (p < 0.05). CONCLUSION: The ITV that had no margin from GTVs increased when dex was ≥10 mm for all lung regions (p < 0.05). Furthermore, the increase in ITV tended to be greater in the lower lung lobe. These findings can help decrease the possibility of adverse events post SBRT, and correct target coverage.Lead, Jun. 2022, Journal of applied clinical medical physics, 23(6) (6), e13596, English, International magazine[Refereed]Scientific journal
- Apr. 2022, JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 41(1) (1), English[Refereed]Scientific journal
- Gold-nanoparticle-incorporated molecularly imprinted nanogels acquire stealth capabilities in vivo through protein corona regulation using intrinsic dysopsonic proteins. The composite can be used in radiation therapy to treat mouse pancreatic cancer.Royal Society of Chemistry (RSC), 2022, Journal of Materials Chemistry B, English[Refereed]Scientific journal
- Oct. 2021, PHYSICS & IMAGING IN RADIATION ONCOLOGY, 20, 94 - 97, English[Refereed]Scientific journal
- Lead, Cambridge University Press, Sep. 2021, Journal of Radiotherapy in Practice, 20(3) (3), 294 - 299, English[Refereed]Scientific journal
- Apr. 2021, ONCOLOGY REPORTS, 45(4) (4), English[Refereed]Scientific journal
- Elsevier BV, Feb. 2021, Colloids and Surfaces B: Biointerfaces, 198, 111451 - 111451, English[Refereed]Scientific journal
- Lead, Cambridge University Press, 2021, Journal of Radiotherapy in Practice, English[Refereed]Scientific journal
- BACKGROUND/AIM: We aimed to investigate the dosimetric effects of a spacer placed between the pancreas and surrounding gastrointestinal structures in intensity-modulated radiation therapy (IMRT) planning to provide more effective radiation therapy for locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Treatment planning was performed for six patients with LAPC based on computed tomography images without spacers and with 5-mm or 10-mm spacers virtually inserted under the supervision of a hepatobiliary pancreatic surgeon. The prescription dose was 63 Gy in 28 fractions. RESULTS: With the exception of one case of pancreatic head cancer, planning target volume receiving ≥95% of the prescribed dose (PTV V95) was achieved by 90% or more by inserting a spacer, and by 95% or more in all 3 cases of pancreatic body and tail cancer by inserting a 10-mm spacer. CONCLUSION: IMRT with appropriate spacer placement may help provide high-dose treatment for LAPC and improve associated patient outcomes.Jan. 2021, Anticancer research, 41(1) (1), 503 - 508, English, International magazine[Refereed]Scientific journal
- Wiley, Oct. 2020, Medical Physics, 47(10) (10), 5235 - 5249, English[Refereed]Scientific journal
- Gastrointestinal toxicity is frequently observed secondary to accidental or therapeutic radiation exposure. However, the variation in the intestinal metabolites after abdominal radiation exposure remains ambiguous. In the present study, C57BL/6 mice were exposed to 0, 2, and 20 Gy irradiation dose. The Head and chest of each mouse were covered with a lead shield before x-ray irradiation. 24 h post-irradiation treatment, intestinal tissue of each mouse was excised and prepared for metabolites measurement using gas chromatography-mass spectrometry (GC-MS). Our comprehensive analysis of metabolites in the intestinal tissues detected 44 metabolites after irradiation, including amino acids, carbohydrates, organic acids, and sugars. Amino acid levels in the intestinal tissue gradually rose, dependent on the radiation dose, perhaps as an indication of oxidative stress. Our findings raise the possibility that amino acid metabolism may be a potential target for the development of treatments to alleviate or mitigate the harmful effects of oxidative stress-related gastrointestinal toxicity due to radiation exposure.Sep. 2020, Biochemistry and biophysics reports, 23, 100789 - 100789, English, International magazine[Refereed]Scientific journal
- PURPOSE: Develop a novel biocompatible solid fiducial marker that prevents radiopaque imaging artifacts and also maintains high imaging contrast for kilovoltage X-ray image-guided radiation therapy. METHODS: The fiducial marker was made of pure zinc. An in-house water-equivalent phantom was designed to evaluate artifacts and visibility under various simulated treatment scenarios. Image artifacts were quantitatively assessed in terms of the metal artifact index (MAI) on kilovoltage computed tomography (CT) and cone-beam CT (CBCT) scans. Marker visibility was evaluated on two types of kilovoltage planar X-ray images in terms of the contrast-to-background ratio (CBR). Comparisons with a conventional gold fiducial marker were conducted. RESULTS: Use of a zinc rather than a gold marker mitigates imaging artifacts. The MAI near the zinc marker decreased by 76, 79, and 77 % in CT, and by 77 (81), 74 (80), and 79 (85) % in CBCT full-fan (half-fan) scans, when using one-, two- and three-marker phantom settings, respectively. The high-contrast part of the zinc marker exhibited CBRs above 2.00 for 28/32 exposures under four (lung, tissue, low-density bone, and high-density bone) different simulation scenarios, making its visibility comparable to that of the gold marker (30/32 exposures with CBRs > 2.00). CONCLUSIONS: We developed a biocompatible, artifact-robust, and highly visible solid zinc fiducial marker. Although further evaluation is needed in clinical settings, our findings suggest its feasibility and benefits for kilovoltage X-ray image-guided radiation therapy.Jul. 2020, Medical physics, English, International magazine[Refereed]Scientific journal
- The development of potentially safe radiosensitizing agents is essential to enhance the treatment outcomes of radioresistant cancers. The titanium peroxide nanoparticle (TiOxNP) was originally produced using the titanium dioxide nanoparticle, and it showed excellent reactive oxygen species (ROS) generation in response to ionizing radiation. Surface coating the TiOxNPs with polyacrylic acid (PAA) showed low toxicity to the living body and excellent radiosensitizing effect on cancer cells. Herein, we evaluated the mechanism of radiosensitization by PAA-TiOxNPs in comparison with gold nanoparticles (AuNPs) which represent high-atomic-number nanoparticles that show a radiosensitizing effect through the emission of secondary electrons. The anticancer effects of both nanoparticles were compared by induction of apoptosis, colony-forming assay, and the inhibition of tumor growth. PAA-TiOxNPs showed a significantly more radiosensitizing effect than that of AuNPs. A comparison of the types and amounts of ROS generated showed that hydrogen peroxide generation by PAA-TiOxNPs was the major factor that contributed to the nanoparticle radiosensitization. Importantly, PAA-TiOxNPs were generally nontoxic to healthy mice and caused no histological abnormalities in the liver, kidney, lung, and heart tissues.Jun. 2020, Nanomaterials (Basel, Switzerland), 10(6) (6), English, International magazine[Refereed]Scientific journal
- Jun. 2020, RADIATION MEASUREMENTS, 134, English[Refereed]Scientific journal
- (一社)日本小児血液・がん学会, Sep. 2019, 日本小児血液・がん学会雑誌, 56(2) (2), 148 - 152, Japanese放射線治療 QOLを考慮した局所治療 小児がんに対する吸収性スペーサー留置を併用した粒子線治療[Refereed]
- Jul. 2019, Radiation Physics and Chemistry, 165(108390) (108390), EnglishGe-doped silica fibre for proton beam dosimetry[Refereed]Scientific journal
- Elsevier {BV}, May 2019, Advances in Radiation Oncology[Refereed]
- Apr. 2019, Advances in radiation oncology, 4(2) (2), 237 - 245[Refereed]
- Mar. 2019, International Journal of Nanoelectronics and Materials, 11, EnglishGe-doped Silica Fibre Proton Beam Measurements: Thermoluminescence Dose-Response and Glow Curve Characteristics[Refereed]Scientific journal
- American Chemical Society, Feb. 2019, Applied Bio Materials, 2(3) (3), 1177 - 1183, English[Refereed]Scientific journal
- 2019, Journal of Physics, 1248(012069) (012069), EnglishCharacterisation of delaminated GAFCHROMIC™ EBT3 films in clinical photon, proton and 192Ir brachytherapy source[Refereed]Scientific journal
- Lead, 2019, Applied Nanoscience (Switzerland), 1 - 6, English[Refereed]Scientific journal
- Nov. 2018, OPEN NANO, 4(100027) (100027), 1 - 8, EnglishRADIOSENSITIZATION EFFECTS AND ROS GENERATION BY HIGH Z METALLIC NANOPARTICLES ON HUMAN COLON CARCINOMA CELL (HCT116) IRRADIATED UNDER 150 MEV PROTON BEAM[Refereed]Scientific journal
- This study aimed to compare dosimetric parameters between non-optimized and optimized treatment planning (NOP and OP, respectively) of magnetic resonance imaging (MRI) -based intracavitary (IC) image-guided adaptive brachytherapy (IGABT) using the central shielding (CS) technique for cervical cancer. Fifty-three patients treated with external beam radiotherapy using CS and MRI-based IGABT with the IC approach alone were evaluated. The total high-risk clinical target volume (HR-CTV) D90 was aimed at >70 Gy equivalent dose in 2 Gy fractions (EQD2). In the small HR-CTV group (≤30 cm3), the mean D90s for NOP/OP were 98.6/80.7 Gy. In the large (30.1-40 cm3) and extensive (>40 cm3) HR-CTV groups, the mean D90s were 81.9/77.5 and 71.1/73.6 Gy, respectively. The mean D2cc values for organs at risks (OARs) in OP were acceptable in all groups, despite the high bladder D2cc in the NOP. The correlation between HR-CTV at first brachytherapy (BT) and NOP D90 was stronger than that between HR-CTV at first BT and OP D90. The targeted HR-CTV D90 and dose constraints of D2cc for OARs were both achieved in 16 NOP/47 OP patients for the bladder, 39/50 for the rectum, and 47/50 for the sigmoid colon (P < 0.001, P = 0.007, and P = 0.34, respectively). For small tumors, the role of optimization was to reduce the D2cc for OARs while maintaining the targeted D90. However, optimization was of limited value for extensive tumors. Methods of optimization in IGABT with CS for cervical cancer should be standardized while considering its effectiveness and limitations.May 2018, Journal of radiation research, 59(3) (3), 316 - 326, English, International magazine[Refereed]Scientific journal
- Elsevier Inc., Mar. 2018, Practical Radiation Oncology, 8(2) (2), e63 - e70, English[Refereed]Scientific journal
- Aug. 2017, PHYSICS IN MEDICINE AND BIOLOGY, 62(15) (15), 6226 - 6245, English[Refereed]Scientific journal
- Institute of Physics Publishing, May 2017, Journal of Physics: Conference Series, 851(1) (1), English[Refereed]International conference proceedings
- 2017, Kobe Journal of Medical Sciences (Web), 63(3) (3), E84‐E91 (WEB ONLY), EnglishEvaluation of a Small Animal Irradiation System for Animal Experiments Using EBT3 Model GAFCHROMIC Film[Refereed]
- Jan. 2017, JOURNAL OF RADIATION RESEARCH, 58(1) (1), 17 - 23, English[Refereed]Scientific journal
- Jan. 2017, Kobe Journal of Medical Sciences, 63(3) (3), E84 - E91, EnglishEvaluation of a small animal irradiation system for animal experiments using EBT3 model GAFCHROMIC ™ film[Refereed]Scientific journal
- Lead, Nov. 2016, RADIATION ONCOLOGY, 11(1) (1), 153, English[Refereed]Scientific journal
- Sep. 2016, INTERNAL MEDICINE REVIEW, 2(9) (9), 1 - 15, EnglishThe current status of space modulated radiotherapy[Refereed]Scientific journal
- BACKGROUND: Biological applications of nanoparticles are rapidly increasing, which introduces new possibilities to improve the efficacy of radiotherapy. Here, we synthesized titanium peroxide nanoparticles (TiOxNPs) and investigated their efficacy as novel agents that can potently enhance the effects of radiation in the treatment of pancreatic cancer. METHODS: TiOxNPs and polyacrylic acid-modified TiOxNPs (PAA-TiOxNPs) were synthesized from anatase-type titanium dioxide nanoparticles (TiO2NPs). The size and morphology of the PAA-TiOxNPs was evaluated using transmission electron microscopy and dynamic light scattering. The crystalline structures of the TiO2NPs and PAA-TiOxNPs with and without X-ray irradiation were analyzed using X-ray absorption. The ability of TiOxNPs and PAA-TiOxNPs to produce reactive oxygen species in response to X-ray irradiation was evaluated in a cell-free system and confirmed by flow cytometric analysis in vitro. DNA damage after X-ray exposure with or without PAA-TiOxNPs was assessed by immunohistochemical analysis of γ-H2AX foci formation in vitro and in vivo. Cytotoxicity was evaluated by a colony forming assay in vitro. Xenografts were prepared using human pancreatic cancer MIAPaCa-2 cells and used to evaluate the inhibition of tumor growth caused by X-ray exposure, PAA-TiOxNPs, and the combination of the two. RESULTS: The core structures of the PAA-TiOxNPs were found to be of the anatase type. The TiOxNPs and PAA-TiOxNPs showed a distinct ability to produce hydroxyl radicals in response to X-ray irradiation in a dose- and concentration-dependent manner, whereas the TiO2NPs did not. At the highest concentration of TiOxNPs, the amount of hydroxyl radicals increased by >8.5-fold following treatment with 30 Gy of radiation. The absorption of PAA-TiOxNPs enhanced DNA damage and resulted in higher cytotoxicity in response to X-ray irradiation in vitro. The combination of the PAA-TiOxNPs and X-ray irradiation induced significantly stronger tumor growth inhibition compared to treatment with either PAA-TiOxNPs or X-ray alone (p < 0.05). No apparent toxicity or weight loss was observed for 43 days after irradiation. CONCLUSIONS: TiOxNPs are potential agents for enhancing the effects of radiation on pancreatic cancer and act via hydroxyl radical production; owing to this ability, they can be used for pancreatic cancer therapy in the future.Jul. 2016, Radiation oncology (London, England), 11(1) (1), 91 - 91, English, International magazine[Refereed]Scientific journal
- Jun. 2016, 日本婦人科腫瘍学会雑誌, 34(3号) (3号), 494, Japanese子宮頸癌に対するMRIガイド下画像誘導小線源治療の初期経験[Refereed]Research society
- Feb. 2016, Japanese Journal of Radiology, 34(Suppl.) (Suppl.), 54, Japanese限局性前立腺癌に対する永久刺入小線源単独治療の経験[Refereed]Research society
- Lead, Dec. 2014, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 90(5) (5), 1177 - 1185, English[Refereed]Scientific journal
- Lead, Mar. 2013, BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1830(3) (3), 2517 - 2525, English[Refereed]Scientific journal
- Jun. 2012, Radiat Oncol, 7, 104, English[Refereed]Scientific journal
- Apr. 2011, プロフェッショナルがんナーシング, 1(2号) (2号), 225 - 235, Japanese【治療に伴う看護特集 一問一答でいちからわかる、きちんとわかる!がん放射線療法と看護】 患者説明のための見通しを知ろう 放射線治療の有害事象[Refereed][Invited]Scientific journal
- (一社)日本小児血液・がん学会, Sep. 2019, 日本小児血液・がん学会雑誌, 56(2) (2), 148 - 152, Japanese放射線治療 QOLを考慮した局所治療 小児がんに対する吸収性スペーサー留置を併用した粒子線治療
- 日本DDS学会, Jun. 2019, 日本DDS学会学術集会プログラム予稿集, 35回, 152 - 152, Japanese金ナノ粒子内包分子インプリントポリマーナノゲルによる放射線治療
- 2019, 日本小児血液・がん学会雑誌(Web), 56(2) (2)小児がんに対する吸収性スペーサー留置を併用した粒子線治療
- 日本バイオマテリアル学会, Nov. 2018, 日本バイオマテリアル学会大会予稿集, 40回, 146 - 146, Japanese放射線治療のための金ナノ粒子内包分子インプリントポリマーナノゲルの開発
- 日本DDS学会, May 2018, 日本DDS学会学術集会プログラム予稿集, 34回, 173 - 173, JapaneseIn situステルス性獲得にもとづく長期血中滞留性金ナノ粒子内包分子インプリントナノゲルの創製
- (公社)日本医学放射線学会, Feb. 2018, Japanese Journal of Radiology, 36(Suppl.) (Suppl.), 31 - 31, Japanese子宮頸癌化学放射線療法中のADC値の変化に関する検討 治療前と腔内照射直前の比較
- (公社)日本医学放射線学会, Feb. 2017, Japanese Journal of Radiology, 35(Suppl.) (Suppl.), 41 - 41, JapaneseMLCの違いによる照射野外線量の検討
- (公社)日本医学放射線学会, Feb. 2016, Japanese Journal of Radiology, 34(Suppl.) (Suppl.), 44 - 44, Japanese眼瞼周囲皮膚癌に対する新規眼球シールド使用時の線量分布の検討
- (公社)日本医学放射線学会, Feb. 2015, Japanese Journal of Radiology, 33(Suppl.) (Suppl.), 70 - 70, Japanese鼻腔・副鼻腔腫瘍の治療計画における不均質補正の影響
- Sep. 2014, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 90, S804 - S804, EnglishDose Estimation of Normal Brain Tissue Tolerance for Microbeam Radiation TherapySummary international conference
- (公社)日本医学放射線学会, Feb. 2014, Japanese Journal of Radiology, 32(Suppl.) (Suppl.), 37 - 37, Japanese過酸化チタンナノ粒子による放射線増感の検討
- (一社)日本癌治療学会, Sep. 2011, 日本癌治療学会誌, 46(2) (2), 786 - 786, Japanese上顎洞扁平上皮癌に対する放射線治療成績
- Editor, 一般財団法人 日本医学物理士会, May 2025米国医学物理学会タスクグループ302:体表面画像誘導放射線治療
- Editor, 一般財団法人 日本医学物理士会, Mar. 2024強度変調放射線治療における独立計算に基づいた線量/MU検証に関する 米国医学物理学会タスクグループ219レポート
- Joint editor, Mar. 2023測定ベースのIMRT QAにおける許容限界及び方法論 米国医学物理学会治療物理委員会タスクグループ218勧告
- Editor, 一般財団法人 日本医学物理士会, Mar. 2022放射線治療中の画像誘導におけるイメージング線量: 定量化,管理および低減 米国医学物理学会治療物理委員会タスクグループ180レポート
- Editor, 編集, 一般財団法人 日本医学物理士会, Mar. 2021放射線治療における陽子線に対する放射線生物学的効果 AAPM TG-256 Report
- Others, INTECH, 2017, EnglishRadiotherapy / A Comparison of Physical vs. Nonphysical Wedge Modalities in RadiotherapyScholarly book
- Others, INTECH, Mar. 2016, EnglishMedical Application of Nonwoven Fabrics - Intra-abdominal Spacers for Particle TherapyScholarly book
- Others, 日本看護協会出版社, Jun. 2015, Japanese多職種チームで実践する頭頸部がんの化学放射線療法 / 多職種チームで実践する頭頸部がんの化学放射線療法General book
- 日本化学会 第99春季年会 (2019), Mar. 2019, English, 日本化学会, 神戸市, Domestic conference放射線治療のための金ナノ粒子内包アルブミンインプリントナノゲルの創製Oral presentation
- 日本化学会 第99春季年会 (2019), Mar. 2019, English, 日本化学会, 神戸市, Domestic conferenceRadiation therapy for pancreatic cancer using moluculaly imprintednanogels imcopolating gold nanoparticlesPoster presentation
- 第66回応用物理学会春季学術講演会, Mar. 2019, English, 応用物理学会, 東京都目黒区, Domestic conferenceGold nanoparticle incorporated polymer nanogels for radiation therapyPoster presentation
- 第40回日本バイオマテリアル学会大会, Nov. 2018, Japanese, 日本バイオマテリアル学会, 神戸市, Domestic conference放射線治療のための金ナノ粒子内包分子インプリントポリマーナノゲルの開発Oral presentation
- 第40回日本バイオマテリアル学会, Nov. 2018, Japanese, 日本バイオマテリアル学会, 京都, Domestic conference放射線治療のための金ナノ粒子内包分子インプリントポリマーナノゲルの開発Oral presentation
- 第40回日本バイオマテリアル学会, Nov. 2018, Japanese, 日本バイオマテリアル学会, 京都, Domestic conferenceIn situステルス性獲得にもとづく長期血中滞留性金ナノ粒子内包分子インプリントナノゲルの創製Oral presentation
- 日本放射線腫瘍学会第31回学術大会, Oct. 2018, Japanese, 日本放射線腫瘍学会, 京都, Domestic conference肺不均質ファントムにおける線量計算アルゴリズム精度の検討Oral presentation
- 日本放射線腫瘍学会第31回学術大会, Oct. 2018, Japanese, 日本放射線腫瘍学会, 京都, Domestic conference当院における悪性脳神経膠腫に対するIMRTの治療成績Oral presentation
- 日本放射線腫瘍学会第31回学術大会, Oct. 2018, Japanese, 日本放射線腫瘍学会, 京都, Domestic conference還元型コエンザイムQ10の摂取形状による放射線防護効果の変化Poster presentation
- 第12回バイオ関連化学シンポジウム, Sep. 2018, Japanese, 日本化学会, 吹田市, Domestic conference放射線治療のための金ナノ粒子内包ステルス性分子インプリントナノゲルPoster presentation
- 第67回高分子討論会, Sep. 2018, Japanese, 高分子学会, 札幌市, Domestic conference放射線治療に用いる金ナノ粒子内包アルブミンインプリントナノゲルの創製Oral presentation
- 第43回神戸放射線腫瘍懇話会, Sep. 2018, Japanese, 神戸放射線腫瘍懇話会, 神戸, Domestic conference呼吸同期IMRTにおけるInterplay Effectの検討Oral presentation
- 第67回高分子討論会, Sep. 2018, Japanese, 高分子学会, 札幌市, Domestic conference金ナノ粒子内包血清アルブミンインプリントナノゲルの放射線増感効果Poster presentation
- 第116回日本医学物理学会学術大会, Sep. 2018, Japanese, 日本医学物理学会, 岩手, Domestic conferenceガントリー取付式2次元検出器を用いたVMAT検証の可能性・3次元検出器と比較してOral presentation
- The 10th International Conference on Molecular Imprinting, Jun. 2018, English, The Society for Molecular Imprinting, Jerusalem,Israel, International conferenceMOLECULARLY IMPRINTED NANOGELS ACQUIRING STEALTH PROPERTY VIA REGULATING PROTEIN CORONA USING INTRINSIC SERUM ALBUMIN IN SITUOral presentation
- 第34回日本DDS学会学術集会, Jun. 2018, Japanese, 長崎市, Domestic conferenceIn situステルス性獲得にもとづく長期血中滞留性金ナノ粒子内包分子インプリントナノゲル の創製Poster presentation
- World Congress on Medical Physics and Biomedical Engineering 2018, Jun. 2018, English, Prague, International conferenceApplication of dual-energy CT to suppression of metal artifacts caused by spinal implant in radiotherapyOral presentation
- 第67回高分子学会年次大会, May 2018, Japanese, 高分子学会, 名古屋市, Domestic conferenceDDSのための金ナノ粒子含有血清アルブミンインプリントナノゲルの創製Oral presentation
- 第115回日本医学物理学会学術大会, Apr. 2018, Japanese, 日本医学物理学会, 横浜, Domestic conferenceDosimetric accuracy of dose calculation algorithms for lung heterogeneity phantomOral presentation
- 日本放射線腫瘍学会第30回学術大会, Nov. 2017, Japanese, 日本放射線腫瘍学会, 大阪, Domestic conference頭頸部領域における固定具を用いたCT画像とMR画像のRegistration精度評価Poster presentation
- 日本放射線腫瘍学会第30回学術大会, Nov. 2017, Japanese, 日本放射線腫瘍学会, 大阪, Domestic conference当院における低・中リスク前立腺癌に対するヨード永久刺入療法の治療成績Poster presentation
- 日本放射線腫瘍学会小線源部会第19回学術大会, Nov. 2017, Japanese, 日本放射線腫瘍学会, 奈良, Domestic conference当院における低・中リスク前立腺癌に対するヨード永久刺入療法の治療成績Oral presentation
- 日本放射線腫瘍学会第30回学術大会, Nov. 2017, Japanese, 日本放射線腫瘍学会, 大阪, Domestic conference金ナノ粒子との比較による過酸化チタンナノ粒子の放射線増感効果の有用性の検討Oral presentation
- 8th Japan-Korea Joint Meeting on Medical Physics, Nov. 2017, English, 日本医学物理学会, 大阪, International conferenceThe process of the determination of Dosimetric leaf gap and Transmission for VMAT using TrueBeamTM STxOral presentation
- 日本放射線腫瘍学会第30回学術大会, Nov. 2017, English, 日本放射線腫瘍学会, 大阪, Domestic conferenceNovel application of Dual Energy CT for the suppression of metal artifact in RadiotherapyPoster presentation
- AAPM 59th Annual Meeting & Exhibition, Nov. 2017, English, American Association of Physicists in Medicine, Denver, CO, International conferenceInfluence of the applied voltage on the ion recombination correction factor using the two-voltage technique in FFF beamsPoster presentation
- 日本放射線腫瘍学会第30回学術大会, Nov. 2017, Japanese, 日本放射線腫瘍学会, 大阪, Domestic conferenceDIRソフトウェアを用いたAdaptive radiation therapyの検討Oral presentation
- AAPM 59th Annual Meeting & Exhibition, Nov. 2017, English, American Association of Physicists in Medicine, Denver, CO, International conferenceAssessment of adaptive radiation therapy with deformable image registration softwarePoster presentation
- 第113回日本医学物理学会学術大会, Nov. 2017, Japanese, 日本医学物理学会, 横浜, Domestic conferenceAssessment of adaptive radiation therapy with deformable image registration softwareOral presentation
- 日本放射線腫瘍学会第30回学術大会, Nov. 2017, Japanese, 日本放射線腫瘍学会, 大阪, Domestic conference2点電圧法を用いたFFFビームのイオン再結合補正係数の印加電圧の影響Poster presentation
- 日本放射線腫瘍学会第30回学術大会, Oct. 2017, Japanese, 日本放射線腫瘍学会, 大阪, Domestic conferenceメタボロミクスにおける放射線消化管機能不全指標の解明Oral presentation
- 日本放射線腫瘍学会第30回学術大会, Sep. 2017, Japanese, 日本放射線腫瘍学会, 大阪, Domestic conference還元型コエンザイムQ10による腸管の有害事象軽減の検討Poster presentation
- 日本放射線腫瘍学会第30回学術大会, Sep. 2017, Japanese, 日本放射線腫瘍学会, 大阪, Domestic conferenceCT、MRIでの検討に基づく過酸化チタンナノ粒子を用いたTheranostic drugの基礎的検討Poster presentation
- The 29th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2016, Japanese, Japanese Society for Radiation Oncology, 京都, Domestic conferenceThe process of thedetermination of Dosimetric leaf gap and Transmission for VMAT using TrueBeam STxOral presentation
- The 29th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2016, Japanese, Japanese Society for Radiation Oncology, 京都, Domestic conferencePhysical analysis of the animal irradiation system in the Kobe UniversityPoster presentation
- The 29th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2016, Japanese, Japanese Society for Radiation Oncology, 京都, Domestic conferenceNext-stage Bioabsorbable Spacer in Particle TherapyPoster presentation
- The 29th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2016, Japanese, Japanese Society for Radiation Oncology, 京都, Domestic conferenceExperience of IGABT using interstitial needles for locally advanced gynecologic malignanciesPoster presentation
- The 29th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2016, Japanese, Japanese Society for Radiation Oncology, 京都, Domestic conferenceElucidation of the radiation gastrointestinal dysfunction index using metabolomicsOral presentation
- The 29th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2016, Japanese, Japanese Society for Radiation Oncology, 京都, Domestic conferenceEffectiveness of micro-slit beam radiation therapy for multiplelung-metastatic tumorOral presentation
- The 29th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2016, Japanese, Japanese Society for Radiation Oncology, 京都, Domestic conferenceDevelopment of quality management system for LaserLocalizer in LinacPoster presentation
- The 29th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2016, Japanese, Japanese Society for Radiation Oncology, 京都, Domestic conferenceComparison of dosimetric parameters in the MRI based IGABT with and without optimizationPoster presentation
- The 29th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2016, Japanese, Japanese Society for Radiation Oncology, 京都, Domestic conferenceAssessment of dose calculation accuracy with lung heterogeneity phantomPoster presentation
- The 29th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2016, Japanese, Japanese Society for Radiation Oncology, 京都, Domestic conferenceA case of uterine cervical cancer presenting with dermatomyositis as a paraneoplastic syndromePoster presentation
- The 112th Annual Meeting of the Japanese Society of Medical Physics, Sep. 2016, Japanese, Japanese Society of Medical Physics, 沖縄, Domestic conference肺不均質ファントムにおける線量計算アルゴリズム精度の検討Poster presentation
- The 75th Annual Meeting of the Japan Radiological Society, Apr. 2016, Japanese, Japan Radiological Society, 横浜, Domestic conferenceOne-year Experience of MRI Based Image Guided Adaptive Brachytherapy for Cervical CancerPoster presentation
- The 4th International Symposium of Training Plan for Oncology Professionals, Feb. 2016, English, 大阪, International conferenceDiscovery of novel Index of radiation gastrointestinal disorders via metabolomicsOral presentation
- The 4th International Symposium of Training Plan for Oncology Professionals, Feb. 2016, English, 大阪, International conferenceAssessment of Apparent Diffusion Coefficient during Image Guided Adaptive Brachytherapy for the Prediction of Local Controllability in Cervical Cancer Treatment: A preliminary histogram analysisPoster presentation
- The 28th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2015, Japanese, JASTRO, 群馬, Domestic conferenceResponse of multiple lung-metastatic tumor to microplanar beam irradiationOral presentation
- The 28th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2015, Japanese, JASTRO, 群馬, Domestic conferenceImprovement of Abdominal Radiation-induced Anorexia by RikkunshitoPoster presentation
- The 28th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2015, Japanese, JASTRO, 群馬, Domestic conferenceHow changes of Auto beam modeling in TPS according to difference Geometric Resolutions ?Oral presentation
- The 28th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2015, Japanese, JASTRO, 群馬, Domestic conferenceEffects of the synchrotron X-ray microbeam spacing on mouse normal brain tissueOral presentation
- The 28th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2015, English, JASTRO, 群馬, Domestic conferenceEarly Experience of Image Guided Adaptive Brachytherapy using Magnetic Resonance ImagingOral presentation
- The 28th Annual Meeting of the Japanese Society for Radiation Oncology, Nov. 2015, Japanese, JASTRO, 群馬, Domestic conferenceA Future Radiosensitizor from the Spinach, MGDG, Induced Apoptosis in the Pancreatic Cancer Cells Combined with Radiation In vitro and In vivoOral presentation
- 第3回神緑会YIA発表会, Oct. 2015, Japanese, 神緑会, 神戸, Domestic conference新規体内吸収性スペーサーを用いた腹部放射線治療法の基礎開発検討Poster presentation
- ASTRO 57th Annual Meeting, Oct. 2015, English, ASTRO, San Antonio, USA, International conferenceA Novel Radiosensitizor from the Component of Spinach, MGDG, Induced Apoptosis in the Pancreatic Cancer Cells Combined with RadiationPoster presentation
- 神戸放射線腫瘍懇話会, Sep. 2015, Japanese, 神戸, Domestic conference当院におけるMRIを用いた婦人科癌画像誘導小線源治療の運用と初期経験Oral presentation
- 第56回JROG 関西若手放射線治療勉強会, Jun. 2015, Japanese, JROG, 奈良, Domestic conferenceVolumetric modulated arc therapy (VMAT) for head and neck cancer: A planning study on our institutionOral presentation
- 4th Congress of Asian Society of Head and Neck Oncology, 39th Annual Meeting of Japan Society for Head and Neck Cancer, Jun. 2015, English, Japan Society for Head and Neck Cancer, 神戸, International conferenceA Novel method of Radioprotection for the Gastointestinal System: Efficacy of the reduced form of Coenzyme Q10.Poster presentation
- The 3rd Japan-Taiwan Radiation Oncology Symposium, Jun. 2015, English, The 3rd Japan-Taiwan Radiation Oncology Symposium, 山梨, International conferenceA Future Method: Space Modulated Particle Therapy (SMPT) Using a Novel Bioabsorbable SpacerOral presentation
- 15th International Congress of Radiation Research, May 2015, English, ICRR, 京都, International conferenceTolerance for Micro-slit beam X-ray radiation to Central Nervous SystemPoster presentation
- 15th International Congress of Radiation Research, May 2015, English, ICRR, 京都, International conferenceRadiosensitizor extracted from Spinach, MGDG, Enhanced the Cytotoxic Effect for Pancreatic Cancer Cells when combined with Radiation TreatmentPoster presentation
- 15th International Congress of Radiation Research, May 2015, English, 京都, International conferenceNext-stage Bioabsorbable Spacer in Particle TherapyPoster presentation
- The American Association of Physicists in MedicineJul. 2016 - Present
- Japanese Society for Radiation OncologyApr. 2010 - Present
- Japan Society of Medical PhysicsApr. 2008 - Present
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2024 - 31 Mar. 2027Bio-active過酸化チタンナノ粒子を併用した革新的放射線免疫療法の開発
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2024 - 31 Mar. 2027腫瘍を可視化する金属ナノ粒子を用いたセラノスティクス放射線治療法の開発
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for JSPS Fellows, Kobe University, Apr. 2024 - Mar. 2027Development of an innovative antigen expression therapy for triple negative breast cancer using mRNA nanoparticles.
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Fund for the Promotion of Joint International Research (Fostering Joint International Research), Kobe University, 2024 - 2026International collaboration on innovative antigen expression therapy using MPN-mRNA nanoparticles.
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2022 - 31 Mar. 2025Space-making radiotherapy using bioabsorbable spacer我々は、ポリグルコール酸(PGA)縫合糸を3次元的に加工した「不織布型吸収性スペーサー」の独自開発を行い、これを用いた粒子線治療期間のみ腫瘍と正常組織を分離する「体内空間可変治療」を提唱した。この方法は、我々の First-in-Human での臨床治験を経て薬事承認(2018年)と保険収載(2019年)に至っている。本研究では、1) 本邦における粒子線治療の実績調査による本治療の現状把握と問題点の抽出を行いつつ、これをX線定位放射線治療へと展開させ、2) 切除不能膵臓がんに対する体内空間可変・定位放射線治療のPhase I/II臨床試験を実施する。3) 吸収性スペーサーの新規 Biomaterial としての生物学的特性の解明と、4) 腹腔鏡対応可能な圧縮型の次世代吸収性スペーサーの開発を通じ、本治療の秀逸な特徴を更に生かし、標準治療として広く普及させて行くための礎とする計画を立てた。実績として本治療法はこれまでの知見に加えてX線で広く普及している回転IMRTを想定した物理的検証を実施し、PMDAとの開発前相談を経て追加申請を行い承認を得て、更には、X線放射線治療においても保険収載され、現在、本邦で広く普及し粒子線治療とX線治療症例を合わせて、400例以上の治療実績を有している。自施設ではその安全性と有効性を評価する目的で、体内空間可変・定位放射線治療のPhase I/II臨床試験の申請が承認され、現在4例に対して実施しその経過観察中である。小児悪性腫瘍でのPhase I 試験の症例登録が完了し、安全に使用可能というデータが得られつつある。また成人例では100例以上の多施設での使用実績が得られ、臨床試験を目的としたスペーサー治療研究会(JSMART)にて長期成績、有害反応を含む付随研究調査である。また圧縮性スペーサーを新規に開発し、その吸収率を動物実験で評価中である。
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2022 - 31 Mar. 2025Development of radiosensitized nanoparticles for all cancers using simple and innovative surface-modified DDS
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2022 - 31 Mar. 2025Space-making radiotherapy using bioabsorbable spacer
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2021 - 31 Mar. 2024A Novel immunoradiotherapy using TiOxNPs and tumor-derived exosomeこれまでの研究で申請者らの研究グループは独自に合成した過酸化チタンナノ粒子がX線照射により活性酸素種(ROS)を生成し、細胞・動物実験で放射線増感効果が得られることを報告した。放射線増感効果をもつナノ粒子として、金、銀、ハフニウム等いくつかの無機ナノ粒子が広く研究されているが、これらのナノ粒子間で増感効果の優劣や性質の違いは評価されておらず、ナノ粒子の材質や粒子サイズ、生成されるROSの種類といった物理的性質の違いが実際の生物学的効果にどのように影響を及ぼすのか明らかになっていない。そこで本研究では、過酸化チタンナノ粒子と最も広く報告されている金ナノ粒子を比較し、それぞれのラジカル産生能、その分子機序、抗腫瘍効果を検討し、その成果がNanomaterial誌に掲載された。またIn vivoでの過酸化チタンナノ粒子の動態とその生物学的評価を実施してその成果がColloids Surf B Biointerfaces誌に掲載された。さらに安定した過酸化チタンナノ粒子の生成方法を確立し、ナノ粒子の表面修飾の方法を改良中である。しかしながら、最も重要なことを投与経路とその腫瘍への集積性を向上させることであり、そのためにはナノ粒子の生体内の動態を解明しなければならない。金属ナノ粒子が医学応用されるためには,その効果や利用価値(メリット)が、リスクや随伴する有害反応(デメリット)を大きく上回る場合に限定されるため、がんや肉腫等の生命に直結する悪性疾患や病態では、その治療効果や診断能が極めて重要でありが、特に放射線療法との併用ではメリットが大きい場面が多いため、臨床を目指した粒子の最適化をさらに進めていく予定である。
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)), Kobe University, 27 Oct. 2020 - 31 Mar. 2024Novel radiosensitizer with inorganic nanoparticles and antibodies assembly我々のグループは放射線と併用することで大量の活性酸素(Reactive Oxygen Species: ROS)を産生し、放射線増感効果を著明に増加させる過酸化チタンナノ粒子の開発に成功し、世界的にも先駆的な立場で過酸化チタンナノ粒子を利用した放射線増感剤の開発に取り組んでいる。この素材を臨床応用するには、過酸化チタンナノ粒子が①腫瘍に特異的に集積し、②生体安全性を有する必要がある。これらを達成するためには、過酸化チタンナノ粒子の表面修飾技術が必要不可欠である。メルボルン大学のFrank Caruso教授のグループはPMAP(Polyphenol-Mediated Assembly of Proteins)と呼ばれる独自のナノ粒子コーティング技術を開発しており、PMAPを応用することで、過酸化チタンナノ粒子にDrug Delivery System(DDS)と体内毒性低減をもたらすことが可能であると期待できる。世界最大級のROS産生能を有する過酸化チタンナノ粒子とPMAPの融合は、これまでに類を見ない革新的ながん治療の開発に繋がることが大いに期待できる。我々は日本・オーストラリアを基軸としたナノ粒子放射線増感研究ネットワークを形成し、画期的な放射線増感剤の開発から臨床応用まで取り組む。本年度には、検討項目の一つとして、がん幹細胞に高発現しているCD44を認識するモノクロナール抗体と過酸化チタンナノ粒子を結合させるPMAPシステムをに応用することを手掛け、in vitroの実験系で確認した。その結果、CD44を高頻度に発現するがん細胞へのPMAP を介して高効率な過酸化チタンナノ粒子の輸送に成功した。
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Exploratory), Kobe University, 30 Jul. 2020 - 31 Mar. 2023A novel immuno-radiotherapy using autologus T cell and pH-responsive capsule for delivery of inorganic nanoparticles本研究では、細胞傷害性T(CD8陽性)細胞由来のエクソソームを単離し、優れた放射線増感作用を有する過酸化チタンナノ粒子の運搬役として利用し、治療抵抗性固形悪性腫瘍に対する新たな免疫放射線療法を提案することである。今回の提案は異なる機能のT細胞同士の情報伝達が、IL-2等のサイトカインによる液性免疫だけでなく、それぞれが放出するエクソソームによる細胞間情報伝達でも制御されている事を見いだした事に端を発する。CD8細胞はその増幅が困難であり、その理由に制御性T細胞(Treg)の強力な抑制機構があると考えられる。今回の申請では、ナノ粒子と放射線照射による抗原刺激を介して、CD8細胞を著明に増加させる方法を立案した。 放射線治療は、その治療経過に伴い腫瘍細胞がPD-L1等の腫瘍抗原を発現が増強し、CD8細胞の膜表面上のPD-1と腫瘍細胞のPD-L1が免疫チェックポイントを形成し治療抵抗性の原因となる。大きな治療効果のためには、放射線増感剤を特異的に取り込ませ、治療効果比の高い免疫放射線療法を構築する事が有効である。腫瘍細胞の標的化に腫瘍細胞からの抗原提示を受けたCD8細胞由来のエクソソームを用い、放射線増感剤には独自開発した過酸化チタンナノ粒子を用いてそれらをEx vivoで融合させ、再投与後に放射線療法を実施し高い治療効果を得ることを検討している。 本年度の研究成果は、過酸化チタンナノ粒子が免疫放射線療法を著明に増感させ、これまでにない治療効果を得た。その分子機序は過酸化チタンナノ粒子がの活性酸素増幅効果に起因し、抗原提示を受けた樹状細胞によるCD8細胞の増幅など、二次リンパ組織における免疫系細胞の関与を明らかにしてきた。
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2020 - 31 Mar. 2023超高線量率スリットビームと金属ナノ粒子を併用した異次元・放射線治療法の開発今年度は新型コロナウィルス感染症の影響もあり、SPring-8での放射光照射実験が実施できなかった。しかしながら、動物実験における腫瘍モデルの作成や、肺転移モデルマウスの作成は問題なく実施できており、未治療での生存期間の検討などを実施した。放射光の照射実験が実施できれば非常に有用な実験データが得られると考えられる。 腫瘍モデルの生着期間や生存期間は癌種によって異なるが、ヒト膵癌由来のMIAPaca2では生着までやく3週間、生存期間は生着後約1か月であり、生着後なるべく早い段階での放射光照射が治療に有用だと考えられる。肺転移モデルマウスの作成では生着まで約1か月、生存期間は約3か月でありこちらも腫瘍モデルと同様に生着後期間を空けずに照射実験を行う予定である。 SPring-8での放射光照射実験までに、神戸大学医学部にある放射線照射装置においても照射実験を行い、放射光と通常のX線照射装置における線量率の違いによる抗腫瘍効果の検討を追加し、FLASH Radio Therapyの抗腫瘍効果や正常組織反応の解明の一助になるよう検討を加える。 金属ナノ粒子の腫瘍への局所注射や尾静脈からの注入に関しても検討し安全性を評価している。 SPring-8のビームラインに設置していたマイクロスリットビーム照射を行うためのコリメータが破損し、急遽その開発を優先することとした。放射線治療分野で品質管理機器などの開発経験が豊富なクオリタ社と開発を行った。コリメータシステムはビームラインへの設置を簡略化し、実験毎に持ち運びが可能なものとした。システムは完成しビームラインへの設置時期を調整中である。持ち運びが可能なコリメータシステムにより多くの放射光施設での使用が可能になると考えられる。
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2020 - 31 Mar. 2023金属ナノ粒子を応用した新規・免疫放射線増感療法の開発近年、放射線療法と免疫療法はその併用効果が高いことが報告され、頭頸部がんや肺がん等の多種類の悪性腫瘍で注目されている。現状では腫瘍抗原の一つであるPD-L1発現の有無を免疫染色で確認し治療効果を推測しているが、ヒトがん免疫応答を正確に再現する動物実験モデルはない。また抗PD-L1抗体に不応性の場合もしばしば経験され、特にそのような症例でどのような分子により腫瘍免疫が形成されているかの探索が重要である。我々はこれまで、前臨床試験モデルとして、患者由来のがん組織をマウスで増殖させるPatient-Derived Xenograftモデル(PDXモデル)を作製に成功してきた。このPDX腫瘍モデルは、患者由来の新鮮な腫瘍組織を用いているため、従来のがん細胞株をヌードマウスに移植した動物モデルでとは全く異なる特徴を持ち、より実臨床に近い重要な情報を検討することができる。本研究では、がん症例からの腫瘍組織を採取し、放射線感受性と、ヒトがん免疫応答を再現できる新規動物実験モデルを開発し、免疫応答に関連する新たな腫瘍抗原の探索など新規の放線免疫療法の開発に取り組む。このモデルは、患者個別の放射線感受性、ヒトがん免疫応答の研究、放射線療法との併用療法のトランスレーショナルリサーチに有用である。がんの前臨床試験やトランスレーショナルリサーチに使用する動物実験モデルとして、患者のがん組織を超免疫不全マウス(NOD/SID/IL2rgKOマウス:NSGマウス)に直接移植して継代培養する「患者由来がん異種移植マウスモデル(Patient-Derived Xenograft(PDX) mouse model)」が、広く活用されている。我々の 研究室ではPDXモデルの着手として、乳がんや大腸がん等の様々ながん種によるPDXモデルを精力的に作製してきた.
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2020 - 31 Mar. 20233次元積層造形技術を用いた革新的な新規頭頸部放射線治療用固定具の研究開発現行の固定具は、枕やマスクを患者ごとに臨床現場で成型加工しており、その作成には緻密な用手的工程(熱可塑性素材を用手的に患者頭頸部にむらなく密着させ冷却して固める工程)が必要であり、その固定精度は作成担当者(主に診療放射線技師)の技術・熟練度に依存する部分が多く、熟練者であっても1時間程度の時間を要するという非効率を生み出していることが臨床上の問題となっている。元より体調が低下しているがん患者に不動の姿勢を長時間保持させて作成しているのが現状である。しかも、固定具の素材は経時的に改善されて来てはいるが、基本的な作業工程は、この20年以上、ほとんど変化していない。今後のさらなる放射線治療の発展に向け、補助固定具を自動で且つ可及的正確に作成出来る全く新しい発想に基づいた精密な新技術の開発が必要である。 本年度は、前年度から引き続き①頭頸部データの取得および解析、②頭頸部データに基づいた固定具の設計、③頭頸部固定具の試作を予定していた。 ②頭頸部データに基づいた固定具の設計③頭頸部固定具の試作に関しては、何度かの設計・作成を繰り返し、現時点で最適と思われる固定具の設計と作成手法を確立することが出来た。 また新規固定具の材料に対して、X線の透過性・減衰について新たに検証を行った。現在臨床使用されている吸引式固定具よりも低い値であることを確認し、臨床で使用することには大きな問題が無い材料であることを確認した。 患者のCTデータを用いた患者用新規固定具作成に関して、倫理委員会に申請済みであり、承認がおり次第、患者用の新規固定具作成を行う予定としている。
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2020 - 31 Mar. 2023獣医療における過酸化チタンナノ粒子を用いた新規・高精度放射線増感療法の開発放射線治療は人医療だけでなく、獣医療でも有効ながん・肉腫の治療手段である。獣医療分野では放射線照射の分割回数を増やせば、全身麻酔回数が増え、疾患動物への負担や侵襲も大きくなるという問題がある。放射線治療は、細胞に対して外因的にエネルギー付与により水の電離を介して活性酸素種(Reactive Oxygen Species, ROS)の発生が細胞傷害性を導くが、がん細胞自体も内因性のROSを持続的に発生し、その消去にためにグルタチオンやカタラーゼなどの還元系酵素の活性が上昇しており、通常のX線照射で発生するROSだけは相殺されてしまうため事が腫瘍の放射線抵抗性の原因と考えられる。申請者らは独自過酸化チタンナノ粒子をがん細胞内に取り込ませX線照射によりROSの著明な発生によって培養細胞やマウス腫瘍モデルにおいて優れた併用効果を確認しているが、今回の申請では種々の肉腫や猫の口腔内扁平上皮癌などの難治性腫瘍に罹患している犬や猫の実際の臨床例における過酸化チタンナノ粒子とIMRT技術を融合させた高精度放射線増感療法の開発とその検証を目的とする。昨年度の研究成果としては、がん細胞に高効率で過酸化チタンナノ粒子を輸送するシステムを確立したことである。そこで、過酸化チタンナノ粒子と最も広く報告されている金ナノ粒子を比較し、それぞれのラジカル産生能、その分子機序、抗腫瘍効果を検討し、その成果がNanomaterial誌に掲載された。またIn vivoでの過酸化チタンナノ粒子の動態とその生物学的評価を実施してその成果がColloids Surf B Biointerfaces誌に掲載された。さらに安定した過酸化チタンナノ粒子の生成方法を確立し、ナノ粒子の表面修飾の方法を改良中である。また最も重要なことを投与経路とその腫瘍への集積性を向上させることである。
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2019 - 31 Mar. 2022Development of Theranostic particle beam therapy using titanium peroxide nanoparticlesWe developed a novel titanium peroxide nanoparticles and reported that it generates a large amount of reactive oxygen species by X-ray irradiation and amplify the antitumor effect of radiation. Radiation causes cell death by generating reactive oxygen species (ROS) inside and outside the cell, but most radiation-resistant tumors overexpress antioxidants which have a ROS-scavenging effect. And, erasing ROS generated by radiation is one of the causes of intractability, and it is an issue for improving treatment results. A goal during this grant period was adding a drug delivery function to titanium peroxide nanoparticles to induce the target tumor with high efficiency and accuracy. Throughout the subsidy period, research on the addition of drug delivery capability to titanium peroxide nanoparticles has progressed significantly, and we have succeeded in developing a drug delivery system that efficiently transports titanium peroxide nanoparticles to cells expressing specific antibodies.
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2019 - 31 Mar. 2022Space making particle therapy for sarcoma and pediatric tumorThis study is to apply space-making therapy using absorptive spacer, which has been proved useful and safe in particle beam therapy. A Phase 1 clinical trial is planned to verify the consistent safety and efficacy of a series of treatment strategies from absorbable spacer placement in pediatric patients. The absorbable spacer was developed by our group and approved by the Pharmaceutical Affairs (Dec. 11, 2018), preparation of guidelines for proper use (May 2011-June), launch of the absorbable spacer (May 2011.06), and insurance adaptation for the absorbable spacer and its indwelling surgery (December 2019) Class IV medical devices have been clinically applied. The absorbable spacer has published the results of a first-in-human trial in particle beam therapy. Since then, its usefulness has attracted attention worldwide. Feasibility study in pediatic malignancies has been conducted.
- 科学研究費補助金/挑戦的研究(開拓), Jun. 2018 - Mar. 2022Competitive research funding
- 学術研究助成基金助成金/基盤研究(C), Apr. 2018 - Mar. 2021Competitive research funding
- 学術研究助成基金助成金/基盤研究(C), Apr. 2017 - Mar. 2020Competitive research funding
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2016 - 31 Mar. 2019Assessment of polyacrylic acid-modified titanium peroxide nanoparticles as radiosensitisersOur previous studies indicated that titanium peroxide nanoparticles (TiOxNPs) induced reactive oxygen species (ROS) when expose to X-rays and enhanced radiation cytotoxic effect. In this study, the type and amount of ROS generated from TiOxNPs were investigated and compared to those generated by gold nanoparticles (GNPs). The results showed that the amount of ROS generated from TiOxNPs under X-ray irradiation was less than that of GNPs, however TiOxNPs had the ability to release H2O2 regardless of X-ray irradiation. The released H2O2 is assumed to be acted as a strong radiosensitising agent of TiOxNPs in vitro and in vivo set up. On the other hand, only 12% of the TiOxNPs dose had accumulated in the tumour 1 hour after an intravenous injection in vivo experiment. The liver had the largest accumulation of the injected nanoparticles. Future studies will be required to develop the strategies to enhance the tumour targeting ability of TiOxNPs.
- 学術研究助成基金助成金/若手研究(B), Apr. 2017 - Mar. 2019, Principal investigatorCompetitive research funding
- 科学研究費一部基金/基盤研究(B), Apr. 2016 - Mar. 2019Competitive research funding
- 学術研究助成基金助成金/挑戦的萌芽研究, Apr. 2016 - Mar. 2019Competitive research funding
- 学術研究助成基金助成金/基盤研究(C), Apr. 2015 - Mar. 2018Competitive research funding
- 学術研究助成基金助成金/若手研究(B), Apr. 2014 - Mar. 2016, Principal investigatorCompetitive research funding
- 科学研究費一部基金/基盤研究(B)特設, Apr. 2013 - Mar. 2016Competitive research funding
- 学術研究助成基金助成金/挑戦的萌芽研究, Apr. 2013 - Mar. 2016Competitive research funding