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MUKUMOTO Naritoshi
University Hospital / Center for Radiology and Radiation Oncology
Assistant Professor

Researcher basic information

■ Research Areas
  • Life sciences / Radiology

Research activity information

■ Paper
  • Mohammed Salah, Masafumi Saito, Hiroki Kawaguchi, Yasuyuki Shimizu, Yoshiko Fujita, Naritoshi Mukumoto, Joji Kotani, Hirotaka Shinomiya, Takeaki Ishihara, Daisuke Miyawaki, Nen-Ichi Nibu, Ryohei Sasaki
    Mar. 2026, Molecular medicine (Cambridge, Mass.), 32(1) (1), English, International magazine

  • Mohammed Salah, Masafumi Saito, Hiroki Kawaguchi, Yasuyuki Shimizu, Yoshiko Fujita, Naritoshi Mukumoto, Joji Kotani, Hirotaka Shinomiya, Takeaki Ishihara, Daisuke Miyawaki, Nen-Ichi Nibu, Ryohei Sasaki
    BACKGROUND: Immunotherapy is a promising treatment for drug-resistant cancers. However, its effectiveness against head and neck squamous cell carcinoma (HNSCC) is limited. This indicates the need to explore additional factors that can predict tumor response to new therapies and improve or supplement their effects. Therefore, we aimed to investigate whether the post-radiation usage of anti-TIGIT and/or anti-CD96 could enhance the antitumor response in HNSCC. METHODS: HNSCC tissues, as well as human and mouse cell lines, were examined to evaluate the effects of radiation on immune checkpoint receptors (TIGIT, CD96, and CD226) and tumor ligands (CD155, CD112, CD113, and CD111). Overall and disease-free survival, along with factors related to these immune checkpoint receptors and ligands, were detected. Moreover, we investigated the effects of radiation dose and exposure time on the expression of these receptors and ligands in vitro and in vivo. Tumor growth and survival rates were then evaluated using TIGIT and/or CD96 inhibitors injected intraperitoneally after exposure to radiation. Finally, various proliferative and immunological parameters of the tumor microenvironment were determined using immunohistochemistry and flow cytometry. Statistical analyses were performed using Student's t-test, one-way analysis of variance, or two-way analysis of variance. RESULTS: Elevated levels of TIGIT, CD96, CD155, CD112, CD113, and CD111 were observed in both HNSCC tissues and the cell lines. Radiation increased the expression of these inhibitory receptors and ligands. Thus, anti-TIGIT and anti-CD96 were used to target the upregulated expression of the receptors TIGIT and CD96, respectively. This treatment combination inhibited tumor growth by boosting apoptosis, reducing tumor cell proliferation, and restoring the cytotoxic functions of CD4+ and CD8+ T cells after radiation therapy. CONCLUSION: Our findings suggest that TIGIT and CD96 could be markers of the clinical stage and treatment response of HNSCC. Therefore, administering anti-TIGIT and anti-CD96 after radiotherapy may provide a novel approach for incorporating immunoradiotherapy into HNSCC treatment.
    Dec. 2025, Molecular medicine (Cambridge, Mass.), 32(1) (1), 5 - 5, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hiroaki Akasaka, Makiko Nakahana, Masao Nakayama, Kenta Morita, Mohammed Salah, Naritoshi Mukumoto, Yasuyuki Shimizu, Ruixain Zhangzhu, Chiaki Ogino, Christina Cortez-Jugo, Joseph J. Richardson, Frank Caruso, Ryohei Sasaki
    American Chemical Society (ACS), Nov. 2025, ACS Applied Bio Materials
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Ai Nakaoka, Mohammed Salah, Zhangzhu Ruixian, Makiko Nakahana, Yasuyuki Shimizu, Qin Qin, Qu Zhang, Naritoshi Mukumoto, Kana Kobayashi, Yukihiro Ikegaki, Hiroaki Akasaka, Sachiko Inubushi, Yu-ichiro Koma, Takeaki Ishihara, Daisuke Miyawaki, Takashi Sasayama, Ryohei Sasaki
    Springer Science and Business Media LLC, Jul. 2025, Scientific Reports, 15(1) (1)
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yuya Tatsuno, Naritoshi Mukumoto, Tomoya Ishida, Yasuyuki Shimizu, Yoshihiko Yamamoto, Satoshi Seno, Takeaki Ishihara, Daisuke Miyawaki, Ryohei Sasaki
    In lung stereotactic body radiation therapy, optimizing plan quality, including dosimetric quality and plan complexity, is paramount for mitigating adverse effects and enhancing dose delivery accuracy. This study evaluated the plan quality of dynamic conformal arc-based volumetric-modulated arc therapy (d-VMAT) as a simplified VMAT compared to conventional VMAT (c-VMAT) across various prescription isodose lines (PIL) and planning target volume (PTV) sizes. Twenty inoperable non-small cell lung cancer patients were retrospectively analyzed (PTV: 7.6-68.7 cm3). The prescribed dose comprised 48 Gy delivered in four fractions, encompassing 95% of the PTV, with the PIL ranging from 60 to 90% in 10% increments, using a 6X-flattening filter-free beam. The d-VMAT and c-VMAT plans were generated for each patient and PIL setting. Dose indices, including the conformity index (CI), gradient index (GI), and plan complexity, were assessed for each plan. The GI of d-VMAT closely mirrored that of c-VMAT at 60% and 70% PIL. Nevertheless, d-VMAT exhibited significantly higher GI values than c-VMAT at 80% and 90% PIL, particularly for smaller PTV sizes. Notably, d-VMAT demonstrated reduced plan complexity across all PIL compared to c-VMAT. Clinically, significant differences in CI and dose coverage between d-VMAT and c-VMAT were not observed across varying PIL settings in the range of 60-80%. The dose to the organs at risk with d-VMAT was comparable to that with c-VMAT, except at 90% PIL. In conclusion, the simplification of VMAT treatment plan using d-VMAT demonstrates superior plan quality across various PTV sizes at 60% and 70% PIL.
    Jun. 2025, Radiological physics and technology, 18(2) (2), 547 - 555, English, Domestic magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Dual Energy MV-CBCTを用いた照合画像の画質改善の検討
    平野 駿太, 椋本 成俊, 中岡 藍, 清水 康之, 江本 裕樹, 小林 加奈, 石原 武明, 宮脇 大輔, 佐々木 良平, 西谷 隆治
    (公社)日本医学放射線学会, Feb. 2023, Japanese Journal of Radiology, 41(Suppl.) (Suppl.), 30 - 30, Japanese

  • 超高線量率マイクロビームX線照射の生体反応と臨床応用への課題(Biological reactions to extremely high dose rate X-ray irradiation to mouse brain and tumor models)
    佐々木 良平, 椋本 成俊, 中山 雅央, 赤坂 浩亮, 清水 康之, 石原 武明, 宮脇 大輔
    (一社)日本放射線影響学会, Sep. 2022, 日本放射線影響学会大会講演要旨集, 65回, 11 - 11, English

  • Mohammed Salah, Hiroaki Akasaka, Yasuyuki Shimizu, Kenta Morita, Yuya Nishimura, Hikaru Kubota, Hiroki Kawaguchi, Tomomi Sogawa, Naritoshi Mukumoto, Chiaki Ogino, Ryohei Sasaki
    Apr. 2022, JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 41(1) (1), English
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • がん細胞から放出されたエクソソームによるバイスタンダー効果
    中岡 藍, 仲波名 真希子, 椋本 成俊, 赤坂 浩亮, 石原 武明, 宮脇 大輔, 吉田 賢史, 佐々木 良平, 西村 勇哉, 荻野 千秋
    (公社)日本医学放射線学会, Feb. 2022, Japanese Journal of Radiology, 40(Suppl.) (Suppl.), 31 - 31, Japanese

  • 当院における中・高リスク前立腺癌に対する外照射併用小線源治療に関する検討
    川口 弘毅, 宮脇 大輔, 石原 武明, 小林 加奈, 椋本 成俊, 赤坂 浩亮, 佐々木 良平, 吉田 賢史, 原 琢人, 古川 順也, 藤澤 正人, 西谷 隆治
    (公社)日本医学放射線学会, Feb. 2022, Japanese Journal of Radiology, 40(Suppl.) (Suppl.), 36 - 36, Japanese

  • Hiroaki Akasaka, Yuya Oki, Kazufusa Mizonobe, Kazuyuki Uehara, Hiroshi Mayahara, Aya Harada, Naoki Hashimoto, Keiji Kitatani, Tomonori Yabuuchi, Takeaki Ishihara, Kazuma Iwashita, Daisuke Miyawaki, Naritoshi Mukumoto, Ai Nakaoka, Ryohei Sasaki
    Cambridge University Press, Sep. 2021, Journal of Radiotherapy in Practice, 20(3) (3), 294 - 299, English
    Scientific journal

  • 奥村 圭祐, 若山 司, 松田 大志, 松本 賢治, 椋本 成俊, 矢田 隆一, 王 天縁, 西谷 隆治, 日下 亜起子, 武村 哲浩
    (公社)日本放射線技術学会, Sep. 2021, 日本放射線技術学会雑誌, 77(9) (9), 959 - 967, Japanese

  • Ai Nakaoka, Makiko Nakahana, Sachiko Inubushi, Hiroaki Akasaka, Mohammed Salah, Yoshiko Fujita, Hikaru Kubota, Mennaallah Hassan, Ryo Nishikawa, Naritoshi Mukumoto, Takeaki Ishihara, Daisuke Miyawaki, Takashi Sasayama, Ryohei Sasaki
    Apr. 2021, ONCOLOGY REPORTS, 45(4) (4), English
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hikaru Kubota, Daisuke Miyawaki, Naritoshi Mukumoto, Takeaki Ishihara, Megumi Matsumura, Takumi Hasegawa, Masaya Akashi, Naomi Kiyota, Hirotaka Shinomiya, Masanori Teshima, Ken-Ichi Nibu, Ryohei Sasaki
    BACKGROUND: To evaluate factors associated with osteoradionecrosis of the jaw (ORNJ) in patients with head and neck squamous cell carcinoma (HNSCC), focusing on jaw-related dose-volume histogram (DVH) parameters. METHODS: We retrospectively reviewed the medical records of 616 patients with HNSCC treated with curative-intent or postoperative radiation therapy (RT) during 2008-2018. Patient-related (age, sex, history of smoking or alcohol use, diabetes mellitus, performance status, pre-RT dental evaluation, pre- or post-RT tooth extraction), tumor-related (primary tumor site, T-stage, nodal status), and treatment-related (pre-RT surgery, pre-RT mandible surgery, induction or concurrent chemotherapy, RT technique) variables and DVH parameters (relative volumes of the jaw exposed to doses of 10 Gy-70 Gy [V10-70]) were investigated and compared between patients with and without ORNJ. The Mann-Whitney U test was used to compare RT dose parameters. Univariate and multivariate Cox regression analyses were used to assess factors associated with ORNJ development. Kaplan-Meier analyses were performed for cumulative ORNJ incidence estimation. RESULTS: Forty-six patients (7.5%) developed ORNJ. The median follow-up duration was 40 (range 3-145) months. The median time to ORNJ development was 27 (range 2-127) months. DVH analysis revealed that V30-V70 values were significantly higher in patients with than in those without ORNJ. In univariate analyses, primary tumor site, pre-RT mandible surgery, post-RT tooth extraction, and V60 > 14% were identified as important factors. In multivariate analyses, V60 > 14% (p = 0.0065) and primary tumor site (p = 0.0059) remained significant. The 3-year cumulative ORNJ incidence rates were 2.5% and 8.6% in patients with V60 ≤ 14% and > 14%, respectively (p < 0.0001), and 9.3% and 1.4% in patients with oropharyngeal or oral cancer and other cancers, respectively (p < 0.0001). CONCLUSIONS: V60 > 14% and oropharyngeal or oral cancer were found to be independent risk factors for ORNJ. These findings might be useful to minimize ORNJ incidence in HNSCC treated with curative RT.
    Jan. 2021, Radiation oncology (London, England), 16(1) (1), 1 - 1, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hiroaki Akasaka, Kazufusa Mizonobe, Yuya Oki, Kazuyuki Uehara, Aya Harada, Shuichiro Miyazaki, Keiji Kitatani, Tomonori Yabuuchi, Takeaki Ishihara, Daisuke Miyawaki, Masao Nakayama, Naritoshi Mukumoto, Ryuichi Yada, Ai Nakaoka, Hikaru Kubota, Hiroki Kawaguchi, Satoshi Seno, Ryohei Sasaki, Hiroshi Mayahara
    Cambridge University Press, 2021, Journal of Radiotherapy in Practice, English
    Scientific journal

  • Keisuke Okumura, Tsukasa Wakayama, Taishi Matsuda, Kenji Matsumoto, Naritoshi Mukumoto, Ryuichi Yada, Tianyuan Wang, Takaharu Nishitani, Akiko Kusaka, Akihiro Takemura
    PURPOSE: For whole-breast irradiation after breast-conserving surgery, computed tomography simulation (CTS) and irradiation are generally performed during free breathing. In treatment planning, there are three techniques: field-in-field (FIF), physical wedge (PW), and enhanced dynamic wedge (EDW). The aim of this study was to investigate the impact of respiratory motion on doses for these three irradiation techniques. METHODS: All doses were measured using an ionization chamber in a cylindrical phantom on a respiratory motion platform. Doses for each technique were measured with and without phantom motion. The dose without phantom motion was defined as the reference. The reference was compared to the dose with the phantom motion. The positions of the isocenter with respect to the ranges of phantom motion were set as exhale and intermediate. The phantom motion amplitude was set to 5 mm or 10 mm. The respiratory phase to initiate irradiation was varied as inhale, intermediate-inhale, exhale and intermediate-exhale. RESULTS: When the motion amplitude was 10 mm, the dose differences for the FIF, PW, and EDW techniques were 4.2%, 0.5%, and 0.8%, respectively, at the maximum. However, the dose difference for the FIF technique was -0.5% when the isocenter position was set to the intermediate phase of phantom motion. CONCLUSION: We found that the dose difference per fraction was reduced when the respiratory phase during CTS image acquisition was set to the intermediate phase. Meanwhile, the dose differences per fraction for the PW and EDW techniques were less affected by the respiratory motion.
    2021, Nihon Hoshasen Gijutsu Gakkai zasshi, 77(9) (9), 959 - 967, Japanese, Domestic magazine
    Scientific journal

  • Hiroki Kawaguchi, Yusuke Demizu, Naritoshi Mukumoto, Takeaki Ishihara, Daisuke Miyawaki, Shohei Komatsu, Hiroaki Akasaka, Makoto Shinoto, Yoshiyuki Shioyama, Katsumasa Nakamura, Takumi Fukumoto, Ryohei Sasaki
    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
    Scientific journal

  • エクソソームを介した腫瘍細胞への放射線増感効果(Exosome-mediated Radiosensitizing Effect on Cancer Cells)
    中岡 藍, 仲波名 真希子, 椋本 成俊, 赤坂 浩亮, 清水 康之, Salah Mohammed, 石原 武明, 宮脇 大輔, 佐々木 良平
    (一社)日本放射線影響学会, Oct. 2020, 日本放射線影響学会大会講演要旨集, 63回, 58 - 58, English

  • エクソソームを介した腫瘍細胞への放射線増感効果(Exosome-mediated Radiosensitizing Effect on Cancer Cells)
    中岡 藍, 仲波名 真希子, 椋本 成俊, 赤坂 浩亮, 清水 康之, Salah Mohammed, 石原 武明, 宮脇 大輔, 佐々木 良平
    (一社)日本放射線影響学会, Oct. 2020, 日本放射線影響学会大会講演要旨集, 63回, 66 - 66, English

  • Ryuichi Yada, Kazusuke Maenaka, Shuji Miyamoto, Go Okada, Aki Sasakura, Motoi Ashida, Masashi Adachi, Tatsuhiko Sato, Tianyuan Wang, Hiroaki Akasaka, Naritoshi Mukumoto, Yasuyuki Shimizu, Ryohei Sasaki
    Wiley, Oct. 2020, Medical Physics, 47(10) (10), 5235 - 5249
    Scientific journal

  • Mohammed Salah, Saki Osuga, Makiko Nakahana, Yasuhiro Irino, Masakazu Shinohara, Yasuyuki Shimizu, Naritoshi Mukumoto, Hiroaki Akasaka, Ai Nakaoka, Daisuke Miyawaki, Takeaki Ishihara, Kenji Yoshida, Yoshiaki Okamoto, Ryohei Sasaki
    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
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Nakayama M, Uehara K, Nishimura H, Tamura S, Munetomo Y, Tsudou S, Mayahara H, Mukumoto N, Geso M, Sasaki R
    Jul. 2019, Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology, 24(4) (4), 383 - 391
    [Refereed]

  • Shimizu Y, Mukumoto N, Idrus N, Akasaka H, Inubushi S, Yoshida K, Miyawaki D, Ishihara T, Okamoto Y, Yasuda T, Nakahana M, Sasaki R
    Elsevier BV, Apr. 2019, Advances in radiation oncology, 4(2) (2), 237 - 245
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hiroaki Akasaka, Naritoshi Mukumoto, Masao Nakayama, Tianyuan Wang, Ryuichi Yada, Yasuyuki Shimizu, Sachiko Inubushi, Katsusuke Kyotani, Keisuke Okumura, Masanori Miyamoto, Ai Nakaoka, Kenta Morita, Yuya Nishimura, Chiaki Ogino, Ryohei Sasaki
    2019, Applied Nanoscience (Switzerland), 1 - 6, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tianyuan Wang, Takeaki Ishihara, Atsushi Kono, Naoki Yoshida, Hiroaki Akasaka, Naritoshi Mukumoto, Ryuichi Yada, Yasuo Ejima, Kenji Yoshida, Daisuke Miyawaki, Kenichiro Kakutani, Kotaro Nishida, Noriyuki Negi, Toshiaki Minami, Yuuichi Aoyama, Satoru Takahashi, Ryohei Sasaki
    Aug. 2017, PHYSICS IN MEDICINE AND BIOLOGY, 62(15) (15), 6226 - 6245, English
    [Refereed]
    Scientific journal

  • Hiroaki Akasaka, Naritoshi Mukumoto, Masao Nakayama, Tianyuan Wang, Ryuichi Yada, Yasuyuki Shimizu, Saki Osuga, Yuki Wakahara, Ryohei Sasaki
    InTech, May 2017, Radiotherapy
    In book

  • Evaluation of a small animal irradiation system for animal experiments using EBT3 model GAFCHROMIC ™ film
    Yasuyuki Shimizu, Hiroaki Akasaka, Daisuke Miyawaki, Naritoshi Mukumoto, Masao Nakayama, Tianyuan Wang, Saki Osuga, Sachiko Inubushi, Ryuichi Yada, Yasuo Ejima, Kenji Yoshida, Takeaki Ishihara, Ryohei Sasaki
    Jan. 2017, Kobe Journal of Medical Sciences, 63(3) (3), E84 - E91, English, Domestic magazine
    [Refereed]
    Scientific journal

  • Evaluation of a Small Animal Irradiation System for Animal Experiments Using EBT3 Model GAFCHROMIC Film
    SHIMIZU Yasuyuki, AKASAKA Hiroaki, MIYAWAKI Daisuke, MIYAWAKI Daisuke, MUKUMOTO Naritoshi, NAKAYAMA Masao, WANG Tianyuan, OSUGA Saki, INUBUSHI Sachiko, YADA Ryuichi, EJIMA Yasuo, YOSHIDA Kenji, YOSHIDA Kenji, ISHIHARA Takeaki, ISHIHARA Takeaki, SASAKI Ryohei, SASAKI Ryohei
    2017, Kobe Journal of Medical Sciences (Web), 63(3) (3), E84‐E91 (WEB ONLY), English

  • Naritoshi Mukumoto, Masao Nakayama, Hiroaki Akasaka, Yasuyuki Shimizu, Saki Osuga, Daisuke Miyawaki, Kenji Yoshida, Yasuo Ejima, Yasushi Miura, Keiji Umetani, Takeshi Kondoh, Ryohei Sasaki
    Jan. 2017, JOURNAL OF RADIATION RESEARCH, 58(1) (1), 17 - 23, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hiroaki Akasaka, Yoshiyuki Mizushina, Kenji Yoshida, Yasuo Ejima, Naritoshi Mukumoto, Tianyuan Wang, Sachiko Inubushi, Masao Nakayama, Yuki Wakahara, Ryohei Sasaki
    BACKGROUND: In our previous study, monogalactosyl diacylglycerol (MGDG) purified from spinach was found to have cytotoxic effects in human cancer cell lines. This study further assessed whether MGDG can enhance the cytotoxic effects of radiation in human pancreatic cancer cells in vitro and in vivo. METHODS: Glycoglycerolipids from spinach including MGDG were extracted from dried spinach. The cytotoxicity of MGDG were evaluated by the MTT assay using four human pancreatic cancer cell lines (MIAPaCa-2, AsPC-1, BxPC-3 and PANC-1) and normal human dermal fibroblasts (NHDFs). The effects of radiation and MGDG alone or in combination in MIAPaCa-2 cells was analyzed with the colony forming and apoptosis assays, western blotting and cell cycle and DNA damage analyses (γ-H2AX foci staining and comet assay). The inhibitory effects on tumor growth were assessed in a mouse xenograft tumor model. RESULTS: MGDG showed dose- and time-dependent cytotoxicity, with half-maximal inhibitory concentrations (IC50) in PANC-1, BxPC-3, MIAPaCa-2 and AsPC-1 cells at 72 h of 25.6 ± 2.5, 26.9 ± 1.3, 18.5 ± 1.7, and 22.7 ± 1.9 μM, respectively. The colony forming assay revealed fewer MIAPaCa-2, BxPC-3 and AsPC-1 cell colonies upon treatment with both MGDG and radiation as compared to irradiation alone (P < 0.05). The combination of MGDG and radiation induced a higher proportion of apoptosis in MIAPaCa-2 cells; this effect was associated with increased mitochondrial release of cytochrome c and activation of cleaved poly (ADP-ribose) polymerase and caspase-3. DNA damage was detected and DNA repair mechanisms were more frequently impaired in cells receiving the combination treatment as compared to either one alone. Tumor growth was inhibited to a greater degree in mice treated by intratumoral injection of MGDG combined with irradiation as compared to either one alone (P < 0.05). CONCLUSIONS: This is the first report demonstrating that MGDG enhances the cytotoxicity of radiation to induce apoptosis of cancer cells in vitro and in vivo. Our findings indicate that this therapeutic combination can be an effective strategy for the treatment of pancreatic cancer.
    Nov. 2016, Radiation oncology (London, England), 11(1) (1), 153 - 153, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Noriaki Minami, Katsu Mizukawa, Hirofumi Iwahashi, Hiroaki Nagashima, Kazuhiro Tanaka, Takashi Sasayama, Kohkichi Hosoda, Naritoshi Mukumoto, Ryohei Sasaki, Eiji Kohmura
    Radiation-induced vasculopathy is a complication of radiation therapy. Most reports regarding post-irradiation ischemic stroke with intracranial tumors are restricted to pediatric cases. Here we report two adult cases of delayed brain infarction due to anterior and middle cerebral artery stenosis or occlusion seemingly caused by focal radiation therapy for malignant glioma. Although radiation-induced ischemic stroke in adults is relatively uncommon, it is possible that the morbidity rate of radiation-induced stroke in malignant glioma patients will increase with prolonged survival due to advances in therapy. Therefore, regular evaluation of intracranial vasculature following radiation therapy is necessary.
    Apr. 2015, No shinkei geka. Neurological surgery, 43(4) (4), 344 - 51, Japanese, Domestic magazine
    [Refereed]

  • Hiroaki Akasaka, Ryohei Sasaki, Daisuke Miyawaki, Naritoshi Mukumoto, Nor Shazrina Binti Sulaiman, Masaaki Nagata, Shigeru Yamada, Masao Murakami, Yusuke Demizu, Takumi Fukumoto
    Dec. 2014, International journal of radiation oncology, biology, physics, 90(5) (5), 1177 - 85, English, International magazine
    [Refereed]
    Scientific journal

  • Kazuyuki Uehara, Takashi Sasayama, Daisuke Miyawaki, Hideki Nishimura, Kenji Yoshida, Yoshiaki Okamoto, Naritoshi Mukumoto, Hiroaki Akasaka, Masamitsu Nishihara, Osamu Fujii, Toshinori Soejima, Kazuro Sugimura, Eiji Kohmura, Ryohei Sasaki
    BACKGROUND: The purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB). METHODS AND MATERIALS: We evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60 Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according to the areas of recurrence as follows: central failure (recurrence in the 95% of 60 Gy); in-field (recurrence in the high-dose volume of 50 Gy; marginal (recurrence outside the high-dose volume) and distant (recurrence outside the RT field). RESULTS: The median follow-up durations were 13 months for all patients and 19 months for those remaining alive. Among AA patients, the 2-year progression-free and overall survival rates were 23.1% and 39.2%, respectively, while in GB patients, the rates were 13.3% and 27.6%, respectively. The median survival time was 20 months for AA patients and 15 months for GB patients. Among AA patients, recurrences were central in 68.7% of patients; in-field, 18.8%; and distant, 12.5%, while among GB patients, 69.0% of recurrences were central, 15.5% were in-field, 12.1% were marginal, and 3.4% were distant. The MIB-1 LI medians were 18.2% in AA and 29.8% in GB. Interestingly, in patients with GB, the MIB-1 LI had a strong effect on the pattern of failure (P = 0.014), while the extent of surgical removal (P = 0.47) and regimens of chemotherapy (P = 0.57) did not. CONCLUSIONS: MIB-1 LI predominantly affected the pattern of failure in GB patients treated with a multimodal approach, and it might be a useful tool for the management of the disease.
    Jun. 2012, Radiation oncology (London, England), 7, 104 - 104, English, International magazine
    [Refereed]
    Scientific journal

■ MISC
  • Mohammed Salah, Hiroki Kawaguchi, Hiroaki Akasaka, Yasuyuki Shimizu, Kenta Morita, Yuya Nishimura, Hikaru Kubota, Tomomi Sogawa, Naritoshi Mukumoto, Chiaki Ogino, Ryohei Sasaki
    01 Apr. 2023, CANCER RESEARCH, 83(7) (7), English
    Summary international conference

  • Ryohei Sasaki, Hiroaki Akasaka, Masao Nakayama, Yoshiko Fujita, Hikaru Kubota, Kenta Morita, Mennaallah Hassan, Mohammed Salah, Yuya Nishimura, Naritoshi Mukumoto, Takeaki Ishihara, Daisuke Miyawaki, Chiaki Ogino
    01 Apr. 2023, CANCER RESEARCH, 83(7) (7), English
    Summary international conference

  • MLCの違いによる照射野外線量の検討
    赤坂 浩亮, 椋本 成俊, 王 天縁, 清水 康之, 大須賀 彩希, 吉田 賢史, 佐々木 良平, 南 利明, 吉田 直碁, 西尾 卓郎, 西谷 隆治, 青山 裕一
    (公社)日本医学放射線学会, Feb. 2017, Japanese Journal of Radiology, 35(Suppl.) (Suppl.), 41 - 41, 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
    椋本 成俊, 宮脇 大輔, 赤坂 浩亮, 王 天縁, 清水 康之, 上薗 玄, 吉田 賢史, 江島 泰生, 佐々木 良平, 吉田 直碁, 表田 真弓, 西谷 隆治, 南 利明, 青山 裕一
    (公社)日本医学放射線学会, Feb. 2016, Japanese Journal of Radiology, 34(Suppl.) (Suppl.), 44 - 44, Japanese

  • 局所放射線治療後に頭蓋内主幹動脈狭窄による脳梗塞を呈した成人神経膠腫の2例
    南 徳明, 水川 克, 岩橋 洋文, 長嶋 宏明, 田中 一寛, 篠山 隆司, 細田 弘吉, 椋本 成俊, 佐々木 良平, 甲村 英二
    症例1は54歳女性で、左片麻痺、構音障害を主訴とした。右前頭葉腫瘍に対し開頭腫瘍摘出術を行い、病理診断結果は神経膠腫グレード4で、その後、放射線療法、ACNUによる化学療法を行った。45ヵ月後、構音障害、左半身の筋力低下が出現し入院した。MRIで摘出腔後方の右中大脳動脈灌流域に新鮮梗塞を認め、抗血小板薬を開始し保存的治療を行った。症例2は41歳男性で、意識障害を主訴とした病理診断結果は線維性星細胞腫グレード2であった。局所放射線療法とテモゾロミドによる化学療法を行い、その後はテモゾロミドによる維持療法を継続した。放射線療法開始14ヵ月後、入浴中に意識を失い救急搬送された。JCSは20、明らかな四肢麻痺はなかった。内科治療後、安静時脳血流SPECTで右中大脳動脈の虚血所見を認め、負荷SPECTではsteal現象を伴う著明なvascular reserveの低下所見を認めた。右浅側動脈-中大脳動脈吻合術を行った。手術は問題なく終了し、術後明らかな過灌流症候群も生じず、術後SPECTで血流改善が得られたが、症状の改善は得られなかった。発症2ヵ月後、転院し、転院1ヵ月後に意識障害が出現し、頭部CTで巨大な右被殻出血を認め、2週間後死亡した。
    (株)医学書院, Apr. 2015, Neurological Surgery, 43(4) (4), 344 - 351, 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
    椋本 成俊, 吉田 賢史, 赤坂 浩亮, 江島 泰生, 宮脇 大輔, 上薗 玄, 佐々木 良平, 大月 直樹, 丹生 健一
    (公社)日本医学放射線学会, Feb. 2015, Japanese Journal of Radiology, 33(Suppl.) (Suppl.), 70 - 70, Japanese

  • Dose Estimation of Normal Brain Tissue Tolerance for Microbeam Radiation Therapy
    M. Nakayama, N. Mukumoto, H. Akasaka, D. Miyawaki, H. Nishimura, K. Umetani, N. Nariyama, T. Kondoh, K. Shinohara, R. Sasaki
    Sep. 2014, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 90, S804 - S804, English
    Summary international conference

  • 過酸化チタンナノ粒子による放射線増感の検討
    中山 雅央, 佐々木 良平, 西村 英輝, 吉田 賢史, 宮脇 大輔, 赤坂 浩亮, 椋本 成俊, 村岡 修, 原田 文, ノル・シャズリナ, 上原 和之, 田中 勉, 荻野 千秋, 近藤 昭彦
    (公社)日本医学放射線学会, Feb. 2014, Japanese Journal of Radiology, 32(Suppl.) (Suppl.), 37 - 37, Japanese

  • 上顎洞扁平上皮癌に対する放射線治療成績
    宮脇 大輔, 西村 英輝, 吉田 賢史, 原田 文, 村岡 修, ノル・シャズリナ, 中山 雅央, 上原 和之, 赤坂 浩亮, 椋本 成俊, 土井 清司, 山下 大介, 長谷川 信吾, 丹生 健一, 佐々木 良平
    (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

  • 【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】一問一答で"きちんと"わかる がん放射線治療の基礎知識
    佐々木 良平, 西村 英輝, 椋本 成俊
    (株)メディカ出版, Apr. 2011, プロフェッショナルがんナーシング, 1(2) (2), 204 - 217, Japanese

■ Lectures, oral presentations, etc.
  • Dual Energy MV-CBCTを用いた照合画像の画質改善の検討
    平野 駿太, 椋本 成俊, 中岡 藍, 清水 康之, 江本 裕樹, 小林 加奈, 石原 武明, 宮脇 大輔, 西谷 隆治, 佐々木 良平
    第328回日本医学放射線学会関西地方会, Jun. 2021
    Oral presentation

  • 同一腫瘍細胞間の放射線応答を制御するエクソソーム内マイクロRNAの網羅的解析
    中岡 藍, 仲波名 真希子, 椋本 成俊, 赤坂 浩亮, 清水 康之, Mohammed Salah, 西川 遼, 平野 駿太, 石原 武明, 宮脇 大輔, 佐々木 良平
    第58回日本放射線腫瘍学会生物部会学術大会
    Oral presentation

  • 神戸大学における医学物理教育
    椋本成俊
    第121回日本医学物理学会学術大会
    [Invited]
    Public symposium

  • Evaluation of dose accuracy in CBCT – based adaptive plan for head and neck radiation therapy.
    Ai Nakaoka, Naritoshi Mukumoto, Syunta Hirano, Yasuyuki Shimizu, Yuki Emoto, Ryuichi Yada, Takeaki Ishihara, Daisuke Miyawaki, Takaharu Nishitani, Ryohei Sasaki
    第121回日本医学物理学会学術大会
    Oral presentation

  • 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
    MUKUMOTO NARITOSHI, YADA RYUICHI, 奥村圭祐, 江口力斗, AKASAKA HIROAKI, SHIMIZU YASUYUKI, 大須賀彩希, 西谷隆治, SASAKI RYOHEI
    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
    Oral presentation

  • 当院における悪性脳神経膠腫に対するIMRTの治療成績
    ISHIHARA TAKEAKI, 妹尾悟史, AKASAKA HIROAKI, MUKUMOTO NARITOSHI, 井上由子, 西川遼, MIYAWAKI DAISUKE, YOSHIDA KENJI, SASAKI RYOHEI, 篠山隆司, TANAKA KAZUHIRO
    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
    Oral presentation

  • 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
    SHIMIZU YASUYUKI, MUKUMOTO NARITOSHI, MIYAWAKI DAISUKE, 犬伏祥子, AKASAKA HIROAKI, YADA RYUICHI, 大須賀彩希, SASAKI RYOHEI
    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
    Poster presentation

  • 頭頸部癌に対する根治放射線治療後の放射線性顎骨壊死に関する臨床的検討
    窪田光, MIYAWAKI DAISUKE, 岸本恵美, 明石昌也, 中岡藍, 戴云涛, MUKUMOTO NARITOSHI, ISHIHARA TAKEAKI, YOSHIDA KENJI, SASAKI RYOHEI
    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
    Oral presentation

  • 呼吸同期IMRTにおけるInterplay Effectの検討
    MUKUMOTO NARITOSHI, 奥村圭祐, YADA RYUICHI, AKASAKA HIROAKI, SHIMIZU YASUYUKI, 大須賀彩希, 中岡藍, 西谷隆治, SASAKI RYOHEI
    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
    Oral presentation

  • 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
    MUKUMOTO NARITOSHI, 奥村圭祐, YADA RYUICHI, AKASAKA HIROAKI, 西谷隆治, SASAKI RYOHEI
    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
    Oral presentation

  • Application of dual-energy CT to suppression of metal artifacts caused by spinal implant in radiotherapy
    Tianyuan Wang, Takeaki Ishihara, Atsushi Kono, Naoki Yoshida, Noriyuki Negi, Kenichiro Kakutani, Hiroaki Akasaka, Ryuichi Yada, Naritoshi Mukumoto, Daisuke Miyawaki, Kenji Yoshida, Ryohei Sasaki
    World Congress on Medical Physics and Biomedical Engineering 2018, Jun. 2018, English, Prague, International conference
    Oral presentation

  • ガントリー取付式2次元検出器を用いたVMAT検証の精度の検討
    奥村 圭祐, MUKUMOTO NARITOSHI, YADA RYUICHI, 表田 真弓, 西谷 隆治, 青山 裕一, 日下 亜起子
    第74回日本放射線技術学会総会学術大会, Apr. 2018, Japanese, 日本放射線技術学会, 横浜, Domestic conference
    Oral presentation

  • Dosimetric accuracy of dose calculation algorithms for lung heterogeneity phantom
    Naritoshi Mukumoto, Ryuichi Yada, Keisuke Okumura, Hiroaki Akasaka, Yasuyuki Shimizu, Tianyuan Wang, Saki Osuga, Takaharu Nishitani, Yuichi Aoyama, Ryohei Sasaki
    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 conference
    Oral presentation

■ Research Themes
  • 呼気凝縮液由来エクソソームを利用した頭頸部がんの革新的な治療効果予測法の開発
    宮脇 大輔, 佐々木 良平, 川口 弘毅, 椋本 成俊, 清水 康之
    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. 2025 - 31 Mar. 2028

  • Novel strategy for cancer using ultra high dose rate X-ray radiation
    佐々木 良平, 椋本 成俊, 城 鮎美, 川口 弘毅, 中山 雅央, 福本 毅
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Fund for the Promotion of Joint International Research (International Collaborative Research), Kobe University, 09 Sep. 2024 - 31 Mar. 2028

  • Bio-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
    岡本 欣晃, 佐々木 良平, 赤坂 浩亮, 宮脇 大輔, 中山 雅央, 椋本 成俊
    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

  • 難治性局所進行乳がんに対する金属ナノ粒子併用・超高線量率放射線治療法の開発
    椋本 成俊, 佐々木 良平, 宮脇 大輔, 清水 康之
    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. 2023 - 31 Mar. 2026

  • Space-making radiotherapy using bioabsorbable spacer
    佐々木 良平, 辰野 佑哉, 赤坂 浩亮, 宮脇 大輔, 出水 祐介, 福本 巧, 椋本 成俊, 岩下 和真, 窪田 光
    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. 2025
    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。

  • Development of radiosensitized nanoparticles for all cancers using simple and innovative surface-modified DDS
    赤坂 浩亮, 荻野 千秋, 佐々木 良平, 宮脇 大輔, 中山 雅央, 椋本 成俊, 清水 康之
    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. 2025

  • Space-making radiotherapy using bioabsorbable spacer
    佐々木 良平, 福本 巧, 宮脇 大輔, 出水 祐介, 窪田 光, 岩下 和真, 赤坂 浩亮, 椋本 成俊
    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. 2025

  • Radioenhancement using ultrasound-stimulated microbubbles and nanoparticles
    中山 雅央, 石原 武明, 椋本 成俊
    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. 2024
    本研究は、放射線抵抗性がんに対するナノ粒子とマイクロバブルによるハイブリッド放射線増感剤の有効性の検証を目的とする。金属ナノ粒子は放射線照射の効果を増強することがすでに多くの研究で示されている。それゆえ有力な放射線増感剤として期待されるものの、その投与方法や細胞へのターゲティングにおいて課題があり、臨床応用には至っていない。一方でマイクロバブルは超音波診断の微小気泡造影剤として臨床使用されているが、いくつかの研究において放射線治療と併用することにより、がんの殺細胞効果を高める効果があると報告されている。さらにマイクロバブルは超音波照射によって一時的に細胞膜に穿孔を生じさせることでき、それにより薬剤の細胞内への導入が容易になるという特徴がある。そこで本研究では、従来のナノ粒子放射線増感治療法にマイクロバブルを加えることにより細胞内へのナノ粒子取り込みを促進させ、かつそれらの放射線増感作用が相乗的に増強するかどうかを検討する。 本年度は主にマイクロバブルとナノ粒子の超音波照射に対する反応に関して基礎的検討を実施した。マイクロバブルに対する照射では、高MI値の超音波照射であるほど多くのマイクロバブルが破裂することを高倍率顕微鏡下で観察した。マイクロバブルに超音波照射をするだけでは活性酸素種の量に有意な変化はなかったが、それにX線照射を加えると、X線照射単独の場合に比べて活性酸素種の増加傾向がみられた。これらの結果はマイクロバブル併用によるX線照射効果の増強を期待させる。一方でナノ粒子は超音波照射とマイクロバブルに対してそのような相加・相乗的な変化は見られなかった。次年度ではがん細胞を用いたin vitro実験を行う予定である。

  • Comprehensive analysis of radiation-response miRNA for cell-to-cell communication
    小林 加奈, 佐々木 良平, 椋本 成俊, 清水 康之, 岩下 和真
    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. 2024
    昨年度の目標は以下の3つであり、そのうち１と2は下記の学会報告、論文発表を行った。 1.ヒト膵がん細胞：MiyaPaca-2細胞を用いたNanosight を用いたエクソソームのサイズ分布、透過型電子顕微鏡（TEM）による形態観察2.ヒト膵がん細胞：MiyaPaca-2細胞を用いてエクソソームを標識し、蛍光顕微鏡で観察による隣接細胞への取込と、ROS産生、DNA障害の変化、放射線感受性評価する。3.ヒト大腸がん細胞株：HCT116は他の大腸がん細胞と比較して極めて肝転移の頻度が高いことが報告されているので、HT29、WiDr、HCT-15, HCC2998などとの比較の中で大腸がんの転移しやすさに関連するエクソソーム内のmiRNAのmiRNA Microarrayにて網羅的解析を実施する。【学会報告】① 同一腫瘍細胞間の放射線応答を制御するエクソソーム内マイクロRNAの網羅的解析、第58回日本放射線腫瘍学会生物部会学術大会2021年6月4日② エクソソーム内マイクロRNAを介した放射線応答制御に関する基礎的検討、第34回放射線腫瘍学会,2021年11月12日～2022年1月15日③放射線照射された腫瘍から放出されたエクソソームによる放射線増感効果, 2021年度 近畿がん診療推進ネットワーク「学術奨励賞選考会」,2022年3月4日 【論文発表】Ai Nakaoka, Kana Kobayashi, Mennaallah Hassan and Ryohei Sasaki, Exosomes in Cancer Diagnosis and Radiation Therapy, IntechOpen Book, 2021年12月21日掲載, Chapter: Extracellular Vesicles, DOI: 10.5772/intechopen.101684 行った。

  • 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
    長田 雅昭, 佐々木 良平, 椋本 成俊, 宮脇 大輔, 赤坂 浩亮
    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2020 - 31 Mar. 2023
    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。

  • 3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
    宮脇 大輔, 赤坂 浩亮, 椋本 成俊
    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2020 - 31 Mar. 2023
    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。

  • 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
    椋本 成俊, 赤坂 浩亮, 佐々木 良平, 宮脇 大輔, 中山 雅央
    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 01 Apr. 2020 - 31 Mar. 2023
    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。

  • Development of Theranostic particle beam therapy using titanium peroxide nanoparticles
    Akasaka Hiroaki
    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. 2022
    We 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.

  • MUKUMOTO Naritoshi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2016 - 31 Mar. 2018, Principal investigator
    Synchrotron X-ray beams permit the delivery of very high radiation doses to tumors in short period of time with a single fraction using arrays of micro-slit beam radiation therapy. In this study, we have challenged to treat multiple metastatic lung tumors by applying MRT to mouse tumor-bearing right lung with comparing to the broad beam treatment from the same radiation source. According to microscopic observations, the areas of tumor on the slides were reduced to one-third compared to the unirradiated region in the slides of 120 Gy MRT while the total lung area was not collapsed and maintained its original size. Such high doses of MRT can diminish the tumor volumes without breaching of lung tissue scaffoldings. There is a good possibility that MRT would control the growth of metastatic lung tumors.
    Competitive research funding

  • MIYAWAKI Daisuke
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2015 - 31 Mar. 2018
    Ultrahigh dose-rate, "FLASH" micro-slit-beam irradiation shifted by a large factor the threshold dose required to initiate lung fibrosis without loss of the antitumor efficiency, suggesting that the method might be used to advantage to reduce the occurrence and severity of early and late complications affecting normal tissue.
    Competitive research funding

  • Okamoto Yoshiaki
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2015 - 31 Mar. 2018
    Effective methods to ameliorate radiation enteropathy have not been developed. To address this issue, reduced CoQ10 was investigated as a potential radioprotective, functional dietary supplement.Reduced CoQ10 was accumulated in all sections of the intestine in supplemented mice. Supplementation with CoQ10 was contributed to suppressing production of reactive oxygen species and inhibiting apoptosis in the crypts, leading to preservation of villi structures after the irradiation. Metabomic analyses were performed. Reduced CoQ10 seemed to be a candidate for amelioration of radiation enteropathy
    Competitive research funding

  • MUKUMOTO Naritoshi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 01 Apr. 2014 - 31 Mar. 2016, Principal investigator
    Synchrotron X-ray beams permit the delivery of very high radiation doses to tumors in a single fraction using arrays of microplanar X-ray beams. Microplanar beam (MPB) radiation is, at present, an experimental approach that has produced, in single exposures, exceptionally high tolerance in the normal tissues while preferentially damaging malignant tumors.
    Competitive research funding

  • EJIMA YASUO, SASAKI Ryohei, YOSHIDA Kenji, MIYAWAKI Daisuke, OSUGA Saki, INUBUSHI Sachiko, MUKUMOTO Naritoshi, AKASAKA Hiroaki, SHIMIZU Yasuyuki, UCHIDA Ray
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2013 - 31 Mar. 2016
    Protection of normal structure of the intestine is important under intense radiation therapy. We focused on the reduced form of Coenzyme Q10 (reduced-CoQ10), which is an antioxidant and naturally available in the human body, and examined its radioprotective effect on the small intestine of mice. Reduced-CoQ10, when administered orally, diminished the radiation-mediated damage of villi and apoptosis in intestinal crypt cells, and also reduced reactive oxygen species (ROS) production upon irradiation. In contrast to that in normal cells, reduced-CoQ10 did not diminish the cytotoxic effects of irradiation in tumor cells in vitro, but decreased their survival by increasing ROS production. Further, to clarify the metabolic changes induced by reduced-CoQ10 and irradiation, metabolomics analysis of mice serum and intestinal tissue samples was performed. Metabolomic profiling identified taurine as a potential biomarker for radiation-mediated damage of the intestine.

  • SASAKI RYOHEI, FUKUMOTO Takumi, EJIMA Yasuo, NISHIMURA Hideki, YOSHIDA Kenji, MIYAWAKI Daisuke, UEZONO Haruka, AKASAKA Hiroaki, MUKUMOTO Naritoshi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2013 - 31 Mar. 2016
    Non-woven fabric bioabsorbable spacer consisted of surgical polyglucolic acid (PGA) sutures has been originaly invented. Characteristics and safety was intensively examined,and animal studies were performed without severe toxicity. The ability of the PGA spacer is to keep its thickness more than 85% for 8 weeks. The spacer reduced gradually, however, it did not cause any toxicity. Clinical study has been started to elucidate efficacy and safety of this spacer for particle therapy
    Competitive research funding

  • MUKUMOTO Naritoshi
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up, Grant-in-Aid for Research Activity Start-up, Kobe University, 31 Aug. 2012 - 31 Mar. 2014, Principal investigator
    Synchrotron X-ray beams permit the delivery of very high radiation doses to tumors in a single fraction using arrays of microplanar X-ray beams. Microplanar beam (MPB) radiation is, at present, an experimental approach that has produced, in single exposures, exceptionally high tolerance in the normal tissues while preferentially damaging malignant tumors. In this study, we have challenged to evaluate normal tissue tolerance and mortality by MPB radiation to mouse brain with comparing to broad beam from the same radiation source. In the experimental setting, 50% and 100% lethal dose by the 200 micrometer spacing MPB beam were 600 Gy and 720Gy, while those by the broad beam were 80 Gy and 96 Gy. Beam paths by MPB irradiation were recognized as bands of cell with hyperchromatic. Micro or partial cerebral hemorrhage was shown in the dead mice brain from both groups.Our results indicated that the MPB enable to deliver extremely high doses without loss of normal tissue function.
    Competitive research funding

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