Radiation-induced liver injury and hepatocyte senescence

Zhu, Wenhe; Zhang, Xiaofen; Yu, Mengli; Lin, Bingru; Yu, Chun-Hong

doi:10.1038/s41420-021-00634-6

Cited by 32 publications

(21 citation statements)

References 103 publications

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“…There are various processes which are involved in radiation-induced liver injury and they finally cause liver cell apoptosis or necrosis. 430 In addition to the direct damage of RT, mechanisms of RT‐induced normal tissue injury also involve a large number of immune cells and immunological factors so it is pivotal for immune system in this complex dynamic process.…”

Section: Clinical Practicementioning

confidence: 99%

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Zhang

Liu

Chen

et al. 2022

Sig Transduct Target Ther

231

141

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Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which is called abscopal effect. The view of RT as a simple local treatment has dramatically changed in recent years, and it is now widely accepted that RT can provoke a systemic immune response which gives a strong rationale for the combination of RT and immunotherapy (iRT). Nevertheless, several points remain to be addressed such as the interaction of RT and immune system, the identification of the best schedules for combination with immunotherapy (IO), the expansion of abscopal effect and the mechanism to amplify iRT. To answer these crucial questions, we roundly summarize underlying rationale showing the whole immune landscape in RT and clinical trials to attempt to identify the best schedules of iRT. In consideration of the rarity of abscopal effect, we propose that the occurrence of abscopal effect induced by radiation can be promoted to 100% in view of molecular and genetic level. Furthermore, the “radscopal effect” which refers to using low-dose radiation to reprogram the tumor microenvironment may amplify the occurrence of abscopal effect and overcome the resistance of iRT. Taken together, RT could be regarded as a trigger of systemic antitumor immune response, and with the help of IO can be used as a radical and systemic treatment and be added into current standard regimen of patients with metastatic cancer.

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Section: Clinical Practicementioning

confidence: 99%

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Zhang

Liu

Chen

et al. 2022

Sig Transduct Target Ther

231

141

View full text Add to dashboard Cite

show abstract

“…The main role of the immune system is mediating the expression of pattern recognition receptors (PRRs) and the recognition of dangerous and invasive elements, which are distinguished in pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) [ 55 ]. It is known that DNA damage participates in radiation-induced inflammation, including liver injury and RILI, etc., via initiating innate immunity [ 56 , 57 ]. In this study, many downstream events of immune response were discovered in RP, but the expression of PRRs was kept at a normal level.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptome Analysis of Radiation Pneumonitis Mice

et al. 2022

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Radiation-induced lung injury (RILI), especially radiation pneumonitis (RP), is a common clinical complication associated with thoracic radiotherapy for malignant tumors. However, the specific contributions of each cell subtype to this process are unknown. Here, we provide the single-cell pathology landscape of the RP in a mouse model by unbiased single-cell RNA-seq (scRNA-seq). We found a decline of type 2 alveolar cells in the RP lung tissue, with an expansion of macrophages, especially the Fabp4low and Spp1high subgroup, while Fabp4high macrophages were almost depleted. We observed an elevated expression of multiple mitochondrial genes in the RP group, indicating a type 2 alveolar cell (AT2) response to oxidative stress. We also calculated the enrichment of a cGAS-STING signaling pathway, which may be involved in regulating inflammatory responses and cancer progression in AT2 cells of PR mice. We delineate markers and transcriptional states, identify a type 2 alveolar cell, and uncover fundamental determinants of lung fibrosis and inflammatory response in RP lung tissue of mice.

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“…Radiation, environmental agents, and temperature are other factors that can induce oxidative stress. Studies have been conducted to explore the role of radiation and its link to oxidative stress [ 44 , 45 ]. When the liver of a guinea pig is exposed to mobile phone-like radiofrequency radiation, it has been found that MDA and nitric oxide are increased whereas the level of SOD is decreased [ 46 ].…”

Section: Factors Responsible For Oxidative Stress In the Livermentioning

confidence: 99%

Oxidative Stress, Genomic Integrity, and Liver Diseases

et al. 2022

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Excess reactive oxygen species production and free radical formation can lead to oxidative stress that can damage cells, tissues, and organs. Cellular oxidative stress is defined as the imbalance between ROS production and antioxidants. This imbalance can lead to malfunction or structure modification of major cellular molecules such as lipids, proteins, and DNAs. During oxidative stress conditions, DNA and protein structure modifications can lead to various diseases. Various antioxidant-specific gene expression and signal transduction pathways are activated during oxidative stress to maintain homeostasis and to protect organs from oxidative injury and damage. The liver is more vulnerable to oxidative conditions than other organs. Antioxidants, antioxidant-specific enzymes, and the regulation of the antioxidant responsive element (ARE) genes can act against chronic oxidative stress in the liver. ARE-mediated genes can act as the target site for averting/preventing liver diseases caused by oxidative stress. Identification of these ARE genes as markers will enable the early detection of liver diseases caused by oxidative conditions and help develop new therapeutic interventions. This literature review is focused on antioxidant-specific gene expression upon oxidative stress, the factors responsible for hepatic oxidative stress, liver response to redox signaling, oxidative stress and redox signaling in various liver diseases, and future aspects.

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Radiation-induced liver injury and hepatocyte senescence

Cited by 32 publications

References 103 publications

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Single-Cell Transcriptome Analysis of Radiation Pneumonitis Mice

Oxidative Stress, Genomic Integrity, and Liver Diseases

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