Countermeasure development against space radiation-induced gastrointestinal carcinogenesis: Current and future perspectives

Suman, Shubhankar; Fornace, Jr. Albert J

doi:10.1016/j.lssr.2022.09.005

Cited by 4 publications

(2 citation statements)

References 74 publications

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“…Senolytic agents can selectively induce death of senescent cells, whereas senomorphics are known to block the acquisition of SASP and production of inflammatory cytokines from senescent cells. Another alternative strategy is the use of a SASP neutralizing antibody (SNmAb) cocktail [99][100][101][102] that requires identification and neutralization of EGC-released SASP factor. Recently, a pro-inflammatory cytokine and a designated SASP factor, i.e., interleukin-1 (IL1), has been implicated in EGC activation and the onset of enteric gliosis, as well as in IBD [65,103].…”

Section: Plausibility Of Senolytics Intervention For the Management O...mentioning

confidence: 99%

Enteric Nervous System Alterations in Inflammatory Bowel Disease: Perspectives and Implications

Suman

2024

Gastrointestinal Disorders

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The enteric nervous system (ENS), consisting of neurons and glial cells, is situated along the gastrointestinal (GI) tract’s wall and plays a crucial role in coordinating digestive processes. Recent research suggests that the optimal functioning of the GI system relies on intricate connections between the ENS, the intestinal epithelium, the immune system, the intestinal microbiome, and the central nervous system (CNS). Inflammatory bowel disease (IBD) encompasses a group of chronic inflammatory disorders, such as Crohn’s disease (CD) and ulcerative colitis (UC), characterized by recurring inflammation and damage to the GI tract. This review explores emerging research in the dynamic field of IBD and sheds light on the potential role of ENS alterations in both the etiology and management of IBD. Specifically, we delve into IBD-induced enteric glial cell (EGC) activation and its implications for persistent enteric gliosis, elucidating how this activation disrupts GI function through alterations in the gut–brain axis (GBA). Additionally, we examine IBD-associated ENS alterations, focusing on EGC senescence and the acquisition of the senescence-associated secretory phenotype (SASP). We highlight the pivotal role of these changes in persistent GI inflammation and the recurrence of IBD. Finally, we discuss potential therapeutic interventions involving senotherapeutic agents, providing insights into potential avenues for managing IBD by targeting ENS-related mechanisms. This approach might represent a potential alternative to managing IBD and advance treatment of this multifaceted disease.

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Section: Plausibility Of Senolytics Intervention For the Management O...mentioning

confidence: 99%

Enteric Nervous System Alterations in Inflammatory Bowel Disease: Perspectives and Implications

Suman

2024

Gastrointestinal Disorders

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“…Secretion from SASP cells can promote secondary senescence in nearby cells and could result in pro-inflammatory/carcinogenic changes in the GI tissue microenvironment. Recently, a “serotherapeutic approach” to reduce space-radiation-induced GI-cancer risk has been proposed [ 158 ], which includes: (a) inhibition of secondary senescence using senomorphic (or senostatic) drugs; (b) cell death induction in SASP cells using senolytic or immunotherapy strategies; and (c) using SASP neutralizing antibody (SNmAb) to mitigate the pro-inflammatory/carcinogenic effects of SASP factors. Metformin, a commonly used anti-diabetic drug with senomorphic properties, has been recently reported to protect against heavy-ion-induced GI cancer [ 159 ].…”

Section: Space-radiation-induced Gi-cancer Risk Reduction Through Ddr...mentioning

confidence: 99%

High-LET-Radiation-Induced Persistent DNA Damage Response Signaling and Gastrointestinal Cancer Development

Kumar

Datta

et al. 2023

Current Oncology

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Ionizing radiation (IR) dose, dose rate, and linear energy transfer (LET) determine cellular DNA damage quality and quantity. High-LET heavy ions are prevalent in the deep space environment and can deposit a much greater fraction of total energy in a shorter distance within a cell, causing extensive DNA damage relative to the same dose of low-LET photon radiation. Based on the DNA damage tolerance of a cell, cellular responses are initiated for recovery, cell death, senescence, or proliferation, which are determined through a concerted action of signaling networks classified as DNA damage response (DDR) signaling. The IR-induced DDR initiates cell cycle arrest to repair damaged DNA. When DNA damage is beyond the cellular repair capacity, the DDR for cell death is initiated. An alternative DDR-associated anti-proliferative pathway is the onset of cellular senescence with persistent cell cycle arrest, which is primarily a defense mechanism against oncogenesis. Ongoing DNA damage accumulation below the cell death threshold but above the senescence threshold, along with persistent SASP signaling after chronic exposure to space radiation, pose an increased risk of tumorigenesis in the proliferative gastrointestinal (GI) epithelium, where a subset of IR-induced senescent cells can acquire a senescence-associated secretory phenotype (SASP) and potentially drive oncogenic signaling in nearby bystander cells. Moreover, DDR alterations could result in both somatic gene mutations as well as activation of the pro-inflammatory, pro-oncogenic SASP signaling known to accelerate adenoma-to-carcinoma progression during radiation-induced GI cancer development. In this review, we describe the complex interplay between persistent DNA damage, DDR, cellular senescence, and SASP-associated pro-inflammatory oncogenic signaling in the context of GI carcinogenesis.

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Breaking the limit: Biological countermeasures for space radiation exposure to enable long-duration spaceflight

Dynan

Chang²,

Sishc³

et al. 2022

Life Sciences in Space Research

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Countermeasure development against space radiation-induced gastrointestinal carcinogenesis: Current and future perspectives

Cited by 4 publications

References 74 publications

Enteric Nervous System Alterations in Inflammatory Bowel Disease: Perspectives and Implications

Enteric Nervous System Alterations in Inflammatory Bowel Disease: Perspectives and Implications

High-LET-Radiation-Induced Persistent DNA Damage Response Signaling and Gastrointestinal Cancer Development

Breaking the limit: Biological countermeasures for space radiation exposure to enable long-duration spaceflight

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