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Cancer cells show altered antioxidant defense systems, dysregulated redox signaling, and increased generation of reactive oxygen species (ROS). Targeting cancer cells through ROS-mediated mechanisms has emerged as a significant therapeutic strategy due to its implications in cancer progression, survival, and resistance. Extensive research has focused on selective generation of H2O2 in cancer cells for selective cancer cell killing by employing various strategies such as metal-based prodrugs, photodynamic therapy, enzyme-based systems, nano-particle mediated approaches, chemical modulators, and combination therapies. Many of these H2O2-amplifying approaches have demonstrated promising anticancer effects and selectivity in preclinical investigations. They selectively induce cytotoxicity in cancer cells while sparing normal cells, sensitize resistant cells, and modulate the tumor microenvironment. However, challenges remain in achieving selectivity, addressing tumor heterogeneity, ensuring efficient delivery, and managing safety and toxicity. To address those issues, H2O2-generating agents have been combined with other treatments leading to optimized combination therapies. This review focuses on various chemical agents/approaches that kill cancer cells via H2O2-mediated mechanisms. Different categories of compounds that selectively generate H2O2 in cancer cells are summarized, their underlying mechanisms and function are elucidated, preclinical and clinical studies as well as recent advancements are discussed, and their prospects as targeted therapeutic agents and their therapeutic utility in combination with other treatments are explored. By understanding the potential of these compounds, researchers can pave the way for the development of effective and personalized cancer treatments.
RESUMO
OBJECTIVE: Childhood maltreatment is indisputably linked to adverse mental health outcomes, including an increased risk to develop posttraumatic stress disorder (PTSD) in adulthood. The role of childhood maltreatment in the context of recovery from a trauma later in adulthood is not well understood. A variable related to both childhood maltreatment and PTSD symptoms, and a potential link between the two, is sleep. The current study aimed to understand how sleep disturbances may play a mechanistic role in the effect of subtypes of childhood maltreatment on PTSD symptom severity in an adult trauma sample. METHOD: 160 adults (90 women; Mage = 33.73, SD = 10.86) were recruited from the emergency department at a Level-1 trauma center in southeastern Wisconsin after experiencing a traumatic injury. Experiences of childhood maltreatment and sleep were self-reported at 2-week and 3-month posttrauma, respectively. PTSD symptoms were clinically assessed 6 months later. RESULTS: Sleep disturbances 3-month posttrauma mediated the effect of emotional abuse, physical neglect, and emotional neglect on PTSD symptom 6 months after the traumatic injury. The effect of sexual and physical abuse on PTSD symptoms was not significantly mediated by sleep disturbances. CONCLUSIONS: These findings highlight the differential impact of subtypes of childhood maltreatment on PTSD symptoms, the mechanistic role of sleep, and the need to consider early life adversity when assessing adult posttrauma experiences. These results also suggest that interventions aimed at improving sleep quality might improve PTSD symptoms in those who have experienced childhood maltreatment and a subsequent traumatic injury in adulthood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
