Real-time imaging reveals radiation-induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damage
Radiotherapy exerts significant effects on the tumor microenvironment. Radiation is known to induce direct tumor cell death through intrinsic factors (e.g., DNA repair activity and p53-mediated radiation sensitivity). It also induces indirect cell death by altering the tumor microenvironment. Howeve...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329925000669 |
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| author | Go Kagiya Ryohei Ogawa Toshihide Matsumoto Fuminori Hyodo Nanako Abe Ami Yuzawa Haru Takeuchi Miki Aoyagi Ayaka Sato Kei Yamashita Masanori Hatashita |
| author_facet | Go Kagiya Ryohei Ogawa Toshihide Matsumoto Fuminori Hyodo Nanako Abe Ami Yuzawa Haru Takeuchi Miki Aoyagi Ayaka Sato Kei Yamashita Masanori Hatashita |
| author_sort | Go Kagiya |
| collection | DOAJ |
| description | Radiotherapy exerts significant effects on the tumor microenvironment. Radiation is known to induce direct tumor cell death through intrinsic factors (e.g., DNA repair activity and p53-mediated radiation sensitivity). It also induces indirect cell death by altering the tumor microenvironment. However, current knowledge is based on indirect evidence. We focused on apoptosis, a form of cell death, to elucidate the mechanisms underlying radiation-induced apoptosis in tumors. Using apoptosis-imaging cells and real-time imaging technology, we investigated the pathways involved in radiation-induced apoptosis in the tumor environment and found that the mechanism triggering early apoptosis following X-ray exposure involves minimal participation of the immune system. Furthermore, we demonstrated that apoptosis in tumors is an indirect form of cell death as well, primarily driven by radiation-induced damage to the tumor vasculature, which leads to reduced blood flow, resulting in nutrient and oxygen deprivation within cancerous tissue, which induces apoptosis. The presence of nutrient deprivation and hypoxia, mediated by tumor vascular damage, suggests the possibility of inducing not only apoptosis but also other forms of cell death (e.g., autophagic cell death and necrosis-like cell death) based on these mechanisms. These pathways provide valuable insights for the development of more effective radiotherapy strategies. |
| format | Article |
| id | doaj-art-bcd31939b8614d94bc1ea8d2a68afad4 |
| institution | OA Journals |
| issn | 2950-3299 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-bcd31939b8614d94bc1ea8d2a68afad42025-08-20T02:17:06ZengElsevierMolecular Therapy: Oncology2950-32992025-06-0133220099710.1016/j.omton.2025.200997Real-time imaging reveals radiation-induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damageGo Kagiya0Ryohei Ogawa1Toshihide Matsumoto2Fuminori Hyodo3Nanako Abe4Ami Yuzawa5Haru Takeuchi6Miki Aoyagi7Ayaka Sato8Kei Yamashita9Masanori Hatashita10School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan; Regenerative Medicine and Cell Design Research Facility, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan; Corresponding author: Go Kagiya, PhD, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.Department of Radiology, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanSchool of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan; Regenerative Medicine and Cell Design Research Facility, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, JapanDepartment of Pharmacology, Graduate School of Medicine Gifu University, 1-1 Yanagido, Gifu 501-1194, JapanThe Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, JapanGraduate School of Human Health Sciences, Tokyo Metropolitan University, 7-2-10 Higashi-Ogu, Arakawa-ku, Tokyo 116-8551, Japan; Department of Radiation, The Jikei University Hospital, 3-19-18 Nishishinbashi, Minato-ku, Tokyo 105-8471, JapanDepartment of Radiation, The Jikei University Hospital, 3-19-18 Nishishinbashi, Minato-ku, Tokyo 105-8471, JapanRadiological Center, NTT Medical Center Tokyo, 5-9-22 Higashigotanda, Shinagawa-ku, Tokyo 141-8625, JapanDepartment of Radiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, JapanDepartment of Radiation Oncology, Chiba Cancer Center, 666-2 Nitona-chou, Chuo-ku, Chiba 260-8717, JapanBiotechnology Division, The Wakasa Wan Energy Research Center, 64-52-1 Nagatani, Tsuruga, Fukui 914-0192, JapanRadiotherapy exerts significant effects on the tumor microenvironment. Radiation is known to induce direct tumor cell death through intrinsic factors (e.g., DNA repair activity and p53-mediated radiation sensitivity). It also induces indirect cell death by altering the tumor microenvironment. However, current knowledge is based on indirect evidence. We focused on apoptosis, a form of cell death, to elucidate the mechanisms underlying radiation-induced apoptosis in tumors. Using apoptosis-imaging cells and real-time imaging technology, we investigated the pathways involved in radiation-induced apoptosis in the tumor environment and found that the mechanism triggering early apoptosis following X-ray exposure involves minimal participation of the immune system. Furthermore, we demonstrated that apoptosis in tumors is an indirect form of cell death as well, primarily driven by radiation-induced damage to the tumor vasculature, which leads to reduced blood flow, resulting in nutrient and oxygen deprivation within cancerous tissue, which induces apoptosis. The presence of nutrient deprivation and hypoxia, mediated by tumor vascular damage, suggests the possibility of inducing not only apoptosis but also other forms of cell death (e.g., autophagic cell death and necrosis-like cell death) based on these mechanisms. These pathways provide valuable insights for the development of more effective radiotherapy strategies.http://www.sciencedirect.com/science/article/pii/S2950329925000669MT: Regular Issuecell deathapoptosisprotein trans-splicingapoptosis imaging reportersplit-luciferase reconstitution |
| spellingShingle | Go Kagiya Ryohei Ogawa Toshihide Matsumoto Fuminori Hyodo Nanako Abe Ami Yuzawa Haru Takeuchi Miki Aoyagi Ayaka Sato Kei Yamashita Masanori Hatashita Real-time imaging reveals radiation-induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damage Molecular Therapy: Oncology MT: Regular Issue cell death apoptosis protein trans-splicing apoptosis imaging reporter split-luciferase reconstitution |
| title | Real-time imaging reveals radiation-induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damage |
| title_full | Real-time imaging reveals radiation-induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damage |
| title_fullStr | Real-time imaging reveals radiation-induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damage |
| title_full_unstemmed | Real-time imaging reveals radiation-induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damage |
| title_short | Real-time imaging reveals radiation-induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damage |
| title_sort | real time imaging reveals radiation induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damage |
| topic | MT: Regular Issue cell death apoptosis protein trans-splicing apoptosis imaging reporter split-luciferase reconstitution |
| url | http://www.sciencedirect.com/science/article/pii/S2950329925000669 |
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