Carbon-ion Radiotherapy for Colorectal Cancer

Yamada, Shigeru; Takiyama, Hirotoshi; Isozaki, Yuka; Shinoto, Makoto; Makishima, Hirokazu; Yamamoto, Naoyoshi; Tsuji, Hiroshi

doi:10.23922/jarc.2020-082

Cited by 12 publications

(8 citation statements)

References 63 publications

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“…To investigate the association between the RBE of carbon ions and cellular 64 Cu-ATSM uptake in cancer cells in vitro, we first assessed the X-ray- or carbon ion-sensitivity of ten human cancer cell lines originated from the cancer types targeted by CIRT in the clinic ( Supplementary Table S1 ) [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. The cell lines showed various sensitivities to the radiation; however, the cell killing effect was greater for carbon ions than for X-rays in all cell lines examined ( Figure 1 A).…”

Section: Resultsmentioning

confidence: 99%

“…Carbon ion radiotherapy (CIRT) is an emerging cancer treatment modality that has a greater therapeutic window than conventional photon radiotherapy [ 1 ]. Clinical evidence suggests that CIRT shows promising antitumor effects against a wide spectrum of cancers, including head and neck cancer [ 2 ], lung cancer [ 3 , 4 ], colorectal cancer [ 5 ], prostate cancer [ 6 , 7 ], and sarcoma [ 8 ]. Preclinical evidence suggests that carbon ions exert strong cell killing effects even against photon-resistant cells and that the relative biological effectiveness (RBE) of carbon ions over photons varies widely among different cell lines [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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64Cu-ATSM Predicts Efficacy of Carbon Ion Radiotherapy Associated with Cellular Antioxidant Capacity

Nachankar

Oike

Hanaoka

et al. 2021

Cancers

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Carbon ion radiotherapy is an emerging cancer treatment modality that has a greater therapeutic window than conventional photon radiotherapy. To maximize the efficacy of this extremely scarce medical resource, it is important to identify predictive biomarkers of higher carbon ion relative biological effectiveness (RBE) over photons. We addressed this issue by focusing on cellular antioxidant capacity and investigated 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM), a potential radioligand that reflects an over-reduced intracellular environment. We found that the carbon ion RBE correlated with 64Cu-ATSM uptake both in vitro and in vivo. High RBE/64Cu-ATSM cells showed greater steady-state levels of antioxidant proteins and increased capacity to scavenge reactive oxygen species in response to X-rays than low RBE/64Cu-ATSM counterparts; this upregulation of antioxidant systems was associated with downregulation of TCA cycle intermediates. Furthermore, inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2) sensitized high RBE/64Cu-ATSM cells to X-rays, thereby reducing RBE values to levels comparable to those in low RBE/64Cu-ATSM cells. These data suggest that the cellular activity of Nrf2-driven antioxidant systems is a possible determinant of carbon ion RBE predictable by 64Cu-ATSM uptake. These new findings highlight the potential clinical utility of 64Cu-ATSM imaging to identify high RBE tumors that will benefit from carbon ion radiotherapy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

64Cu-ATSM Predicts Efficacy of Carbon Ion Radiotherapy Associated with Cellular Antioxidant Capacity

Nachankar

Oike

Hanaoka

et al. 2021

Cancers

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“…Many studies have reported that traditional photon radiotherapy can activate tumor angiogenesis, besides its capability in killing the tumor cells [7,32]. However, patients who received carbon ion radiotherapy were reported to have decreased metastasis and recurrence rates [12,13]. TGF-β1 and its downstream target VEGF play important roles in tumor angiogenesis and metastasis process.…”

Section: Resultsmentioning

confidence: 99%

“…Meanwhile, heavy ion radiation has an excellent killing effect for hypoxia tumors, which is obviously better than conventional photon radiation that relied on oxygen free radicals to kill tumor cells. More importantly, several studies have suggested that proton and heavy-ion radiation suppress tumor angiogenesis and metastasis compared with photon radiation [11][12][13][14]. Akino et al reported that X-ray irradiation of lower doses promoted cell proliferation, migration and invasion; whereas carbon ion irradiation suppressed the migration and invasion of A549 cells without enhancing cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Carbon ion irradiation suppresses angiogenic response in human lung adenocarcinoma cells mediated by LINC00167/miR-663a/TGF-β1 axis

Huang¹,

Xu²,

Guo³

et al. 2022

Preprint

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Background Radiotherapy plays an important role in numerous tumor clinical treatments and over 65% of cancer patients need to accept radiotherapy all over the world. However, tumor angiogenesis and metastasis induced by conventional photon radiotherapy adversely impact the survival of patients, and limit the clinical radiotherapy efficiency. Heavy-ion radiotherapy has attracted wide attention in recent years because of its excellent physical property and outstanding tumor control rate, however, the underlying gene expression regulation mechanism response to heavy-ion irradiation remains elusive. Methods RNA-sequencing (RNA-seq) and public database analysis were employed to identify the differential molecular changes in lung adenocarcinoma cells exposed to both X-ray and carbon ion (C-ion) irradiation. The expression of the identified LINC00167 was verified by real-time quantitative PCR in different lung cancer cell lines and pulmonary bronchial epithelial cell lines. The content of serum vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGF-β1) of 8 lung cancer patients who received X-ray or carbon ion radiotherapy were detected by ELISA experiment. Loss-of-function and gain-of-function experiments were performed to explore the biological roles of LINC00167 and miR-663a in lung cancer cell angiogenesis and metastasis. Comprehensive biochemical and biological techniques were utilized to explore the functions of LINC00167 in tumor angiogenesis and metastasis induced by different radiation types. Results In this study, we confirmed that LINC00167 was highly expressed and induced by X-ray irradiation in lung cancer cells. Moreover, increased LINC00167 expression was positively correlated with tumor angiogenesis and metastasis caused by conventional photon radiotherapy. LINC00167 worked as a sponge of miR-663a to positively regulate the expression of TGF-β1 and the downstream VEGF signaling and then promoted the tumor angiogenesis and metastasis of lung cancer cells. LINC00167 could strengthen the pro-angiogenesis and metastasis ability of lung cancer cells. Photon radiation-induced LINC00167 promoted angiogenesis both in vitro and in vivo. Conclusion Our data suggest that LINC00167/miR-663a/TGF-β1 axis is involved in the differential angiogenic response of lung adenocarcinoma cells exposed to X-ray or C-ion irradiation, providing the molecular mechanisms underlying the suppressed angiogenic response induced by carbon ion radiotherapy.

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“…revealed that CIRT yields more beneficial and favorable long-term outcomes, i.e., fewer side effects or less metastasis and secondary cancers [ 416 , 456 ]. In particular, radioresistant tumor types such as glioblastoma, chondrosarcoma and head and neck cancers, non-small cell lung cancers, hepatocellular carcinoma, colorectal and gastrointestinal cancers, sinonasal malignancies, prostate and gynecological cancers have been successfully treated [ 456 , 477 , 478 , 492 , 493 , 494 , 495 , 496 , 497 , 498 , 499 , 500 ]. For that the radiation quality of C-ions matters a lot.…”

Section: Discussionmentioning

confidence: 99%

Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts

Averbeck

Rodriguez-Lafrasse

2021

IJMS

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Until recently, radiation effects have been considered to be mainly due to nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures to ionizing radiation (IR) highly depend on activation and regulation through other molecular components of organelles that determine cell survival and proliferation capacities. As typical epigenetic-regulated organelles and central power stations of cells, mitochondria play an important pivotal role in those responses. They direct cellular metabolism, energy supply and homeostasis as well as radiation-induced signaling, cell death, and immunological responses. This review is focused on how energy, dose and quality of IR affect mitochondria-dependent epigenetic and functional control at the cellular and tissue level. Low-dose radiation effects on mitochondria appear to be associated with epigenetic and non-targeted effects involved in genomic instability and adaptive responses, whereas high-dose radiation effects (>1 Gy) concern therapeutic effects of radiation and long-term outcomes involving mitochondria-mediated innate and adaptive immune responses. Both effects depend on radiation quality. For example, the increased efficacy of high linear energy transfer particle radiotherapy, e.g., C-ion radiotherapy, relies on the reduction of anastasis, enhanced mitochondria-mediated apoptosis and immunogenic (antitumor) responses.

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Carbon-ion Radiotherapy for Colorectal Cancer

Cited by 12 publications

References 63 publications

64Cu-ATSM Predicts Efficacy of Carbon Ion Radiotherapy Associated with Cellular Antioxidant Capacity

64Cu-ATSM Predicts Efficacy of Carbon Ion Radiotherapy Associated with Cellular Antioxidant Capacity

Carbon ion irradiation suppresses angiogenic response in human lung adenocarcinoma cells mediated by LINC00167/miR-663a/TGF-β1 axis

Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts

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