Macrophage biology plays a central role during ionizing radiation-elicited tumor response

Wu, Qiuji; Allouch, Awatef; Martins, Isabelle; Modjtahedi, Nazanine; Deutsch, Éric; Perfettini, Jean-Luc

doi:10.1016/j.bj.2017.06.003

Cited by 93 publications

(65 citation statements)

References 106 publications

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“…30 Iba1 is a microglia/macrophage-specific calcium-binding protein, which facilitates cell migration and phagocytosis by microglia. 31 Previous studies have shown that RT has a strong impact on tissue microenvironments 25,32 In conclusion, our study provides novel and comprehensive insights into the benefits of dual treatment, including radiosensitizing PCa tumor tissues to RT and radioprotecting normal pelvic organs from RT. The underlying processes are complicated and involve crosstalk between the epithelial, fibroblasts, endothelial, and immune cells as well as soluble paracrine and autocrine factors including cytokines, chemokines, growth factors, and proteases.…”

Section: Discussionmentioning

confidence: 73%

“…Tumor responses to RT and clinical outcomes depend on the intrinsic repair capacity, oxygenation of the tumor tissue, modulation of the tumor microenvironment, and the activation of the immune response, as well as other factors . Several pharmacological strategies have been exploited to develop effective and minimally‐toxic radiosensitizers including small molecules, macromolecules, and nanomaterials .…”

Section: Discussionmentioning

confidence: 99%

“…Iba1 is a microglia/macrophage‐specific calcium‐binding protein, which facilitates cell migration and phagocytosis by microglia . Previous studies have shown that RT has a strong impact on tissue microenvironments and can cause the aggregation of M2 macrophages in avascular hypoxic regions. Macrophages display two different phenotypes, (M1 and M2), each of which possess distinct functions, and can quickly respond and act according to changing circumstances.…”

Section: Discussionmentioning

confidence: 99%

“…22,23 Tumor responses to RT and clinical outcomes depend on the intrinsic repair capacity, oxygenation of the tumor tissue, modulation of the tumor microenvironment, and the activation of the immune response, as well as other factors. 24,25 Several pharmacological strategies have been exploited to develop effective and minimallytoxic radiosensitizers including small molecules, macromolecules, and nanomaterials. 26 Preclinical studies demonstrated that ALA administration sensitized glioma, melanoma, and colon adenocarcinoma cells to RT through the generation of PPIX and enhanced ROS that have physico-chemical interactions with the X-rays being irradiated into malignant cells.…”

Section: Discussionmentioning

confidence: 99%

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Dual benefit of supplementary oral 5‐aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model

et al. 2018

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Background Normal tissue damage caused by radiotherapy remains the largest dose‐limiting factor in radiotherapy for cancer. Therefore, the aim of this study was to investigate the supplementary oral 5‐aminolevulinic acid (ALA) to standard radiation therapy as a novel radioprotective approach that would not compromise the antitumor effect of radiation in normal rectal and bladder mucosa in a syngenic prostate cancer (PCa) model. Methods To evaluate the radiosensitizing effect of ALA in vitro, clonogenic survival assays were performed in DU145, PC3, and MyC‐CaP cell lines. To evaluate the effect of ALA in vivo a single dose (25 Gy) of radiation with or without ALA was given to healthy mice. Next, a syngenic PCa model of MyC‐CaP cells in FVB mice was created, and multiple doses (12 Gy total) of radiation were administered to the mouse pelvic area with or without ALA administration. Resected tumors, recta, and urinary bladders were immunostained with antibodies against Ki‐67, γ‐H2AX, CD204, and uroplakin‐III. Total RNA levels in recta and urinary bladders were analyzed via RT2 Profiler polymerase chain reaction (PCR) arrays related to “Stress & Toxicity PathwayFinder,” “Mitochondria,” and “Inflammasomes.” Results The addition of in vitro single or in vivo repeated administration of exogenous ALA acted as a radiosensitizer for PCa cells. Rectal toxicity was characterized by histological changes including loss of surface epithelium, fibrosis, severe DNA damage, and the aggregation of M2 macrophages. Urinary bladder toxicity was characterized by bladder wall thickening and urothelium denuding. The higher dose (300 mg/kg/day) of ALA exerted a better radioprotective profile than the lower dose (30 mg/kg/day) in normal recta and urinary bladders. Out of the 252 genes tested, 35 (13.4%) were detected as relevant genes which may be involved in the radioprotective role of ALA administration. These included interleukin‐1a (IL‐1a), IL‐1b, IL‐12, chemokine (C‐X‐C motif) ligand 1 (CXCL1), CXCL3, and NLRP3. Conclusions Our study provides novel and comprehensive insights into the dual benefits including radiosensitizing PCa tumor tissues and radioprotection of normal pelvic organs from radiation therapy. Knowledge of the underlying mechanism will facilitate the search for optimal treatment parameters for supplemental oral ALA during radiotherapy for PCa.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Dual benefit of supplementary oral 5‐aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model

et al. 2018

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“…Studies have shown that progression of PD can be mitigated and in some instances reversed via neuroprotective agents (e.g., donepezil; rosiglitazone) that exert hormetic dose‐responses to induce microglia to express and sustain the anti‐inflammatory M2 phenotype (Chen, Hou, Xu, & Wu, ; Pisanu et al, ). Moreover, hormetic bi‐phasic dose‐responses may be involved in the process of macrophage reprogramming and polarization that is produced by chemicals, as well as ionizing radiation (Genard, Lucas & Michiels, ; Walton, ; Wu et al, ). Other studies have shown that preconditioning‐induced protection responses are associated with increased M2 polarization across multiple organs/cell types (e.g., bone, Young et al, ; spinal cord, Hayakawa et al, ; mesenchymal stem cells, Lin et al, , Mountziaris, Tzouanas, & Mikos, ; Kidney, Hato et al, ) reflecting the generality of the adaptive strategy.…”

Section: Discussionmentioning

confidence: 99%

Hormetic approaches to the treatment of Parkinson's disease: Perspectives and possibilities

Calabrese

Santoro

Salinaro

et al. 2018

J of Neuroscience Research

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Age-related changes in the brain reflect a dynamic interaction of genetic, epigenetic, phenotypic, and environmental factors that can be temporally restricted or more longitudinally present throughout the lifespan. Fundamental to these mechanisms is the capacity for physiological adaptation through modulation of diverse molecular and biochemical signaling occurring from the intracellular to the network-systemic level throughout the brain. A number of agents that affect the onset and progression of Parkinson's disease (PD)-like effects in experimental models exhibit temporal features, and mechanisms of hormetic dose responses. These findings have particular significance since the hormetic dose response describes the amplitude and range of potential therapeutic effects, thereby affecting the design and conduct of studies of interventions against PD (and other neurodegenerative diseases), and may also be important to a broader consideration of hormetic processes in resilient adaptive responses that might afford protection against the onset and/or progression of PD and related disorders.

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AOP report: Development of an adverse outcome pathway for deposition of energy leading to learning and memory impairment

Sleiman,

Miller,

Flores

et al. 2024

Environ and Mol Mutagen

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Understanding radiation‐induced non‐cancer effects on the central nervous system (CNS) is essential for the risk assessment of medical (e.g., radiotherapy) and occupational (e.g., nuclear workers and astronauts) exposures. Herein, the adverse outcome pathway (AOP) approach was used to consolidate relevant studies in the area of cognitive decline for identification of research gaps, countermeasure development, and for eventual use in risk assessments. AOPs are an analytical construct describing critical events to an adverse outcome (AO) in a simplified form beginning with a molecular initiating event (MIE). An AOP was constructed utilizing mechanistic information to build empirical support for the key event relationships (KERs) between the MIE of deposition of energy to the AO of learning and memory impairment through multiple key events (KEs). The evidence for the AOP was acquired through a documented scoping review of the literature. In this AOP, the MIE is connected to the AO via six KEs: increased oxidative stress, increased deoxyribonucleic acid (DNA) strand breaks, altered stress response signaling, tissue resident cell activation, increased pro‐inflammatory mediators, and abnormal neural remodeling that encompasses atypical structural and functional alterations of neural cells and surrounding environment. Deposition of energy directly leads to oxidative stress, increased DNA strand breaks, an increase of pro‐inflammatory mediators and tissue resident cell activation. These KEs, which are themselves interconnected, can lead to abnormal neural remodeling impacting learning and memory processes. Identified knowledge gaps include improving quantitative understanding of the AOP across several KERs and additional testing of proposed modulating factors through experimental work. Broadly, it is envisioned that the outcome of these efforts could be extended to other cognitive disorders and complement ongoing work by international radiation governing bodies in their review of the system of radiological protection.

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Macrophage biology plays a central role during ionizing radiation-elicited tumor response

Cited by 93 publications

References 106 publications

Dual benefit of supplementary oral 5‐aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model

Dual benefit of supplementary oral 5‐aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model

Hormetic approaches to the treatment of Parkinson's disease: Perspectives and possibilities

AOP report: Development of an adverse outcome pathway for deposition of energy leading to learning and memory impairment

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