Neuroprotective agents effective against radiation damage of central nervous system

Neural Regeneration Research, Год журнала: 2022, Номер 17(9), С. 1885 - 1885

Опубликована: Янв. 1, 2022

Ionizing radiation caused by medical treatments, nuclear events or even space flights can irreversibly damage structure and function of brain cells. That result in serious damage, with memory behavior disorders, fatal oncologic neurodegenerative illnesses. Currently used treatments drugs are mostly targeting biochemical processes cell apoptosis, toxicity, neuroinflammation, conditions such as cognitive-behavioral disturbances others that from the insult. With most drugs, side effects potential toxicity also to be considered. Therefore, many agents have not been approved for clinical use yet. In this review, we focus on latest effective animal human research, treatments. They could therapeutical cases central nervous system, prevention considering their radioprotecting effect tissue.

Язык: Английский

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Timing of Novel Drug 1A-116 to Circadian Rhythms Improves Therapeutic Effects against Glioblastoma

Pharmaceutics, Год журнала: 2021, Номер 13(7), С. 1091 - 1091

Опубликована: Июль 16, 2021

The Ras homologous family of small guanosine triphosphate-binding enzymes (GTPases) is critical for cell migration and proliferation. novel drug 1A-116 blocks the interaction site Ras-related C3 botulinum toxin substrate 1 (RAC1) GTPase with some its guanine exchange factors (GEFs), such as T-cell lymphoma invasion metastasis (TIAM1), inhibiting motility Knowledge circadian regulation targets can improve chemotherapy in glioblastoma. Thus, efficacy was studied LN229 human glioblastoma cells tumor-bearing nude mice. Wild-type BMAL1-deficient (i.e., lacking a functional clock) LN229E1 were assessed rhythms TIAM1, BMAL1, period protein homolog (PER1), well Tiam1, Bmal1, Rac1 mRNA levels. effects on proliferation, apoptosis, then upon applying at different times. Finally, administered to mice two In cells, oscillations found PER1, TIAM1 (mRNA protein), migration, which abolished cells. Increased survival time observed when treated end light (zeitgeber 12, ZT12) compared either animals beginning (ZT3) or vehicle. These results unveil modulation 1A-116, likely through RAC1 pathway rhythmicity, suggesting that chronopharmacological approach feasible strategy treatment.

Язык: Английский

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Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery

Circulation Research, Год журнала: 2024, Номер 134(6), С. 727 - 747

Опубликована: Март 14, 2024

The blood-brain barrier (BBB) is a critical interface separating the central nervous system from peripheral circulation, ensuring brain homeostasis and function. Recent research has unveiled profound connection between BBB circadian rhythms, endogenous oscillations synchronizing biological processes with 24-hour light-dark cycle. This review explores significance of rhythms in context functions, an emphasis on substrate passage through BBB. Our discussion includes efflux transporters molecular timing mechanisms that regulate their activities. A significant focus this potential implications chronotherapy, leveraging our knowledge for improving drug delivery to brain. Understanding temporal changes can lead optimized administration, enhance therapeutic efficacy neurological disorders while reducing side effects. By elucidating interplay transport across BBB, offers insights into innovative interventions.

Язык: Английский

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The Time for Chronotherapy in Radiation Oncology

Frontiers in Oncology, Год журнала: 2021, Номер 11

Опубликована: Май 11, 2021

Five decades ago, Franz Halberg conceived the idea of ​​a circadian-based therapy for cancer, given differential tolerance to treatment derived from intrinsic host rhythms. Nowadays, different experimental models have demonstrated that both toxicity and efficacy several anticancer drugs vary by more than 50% as a function dosing time. Accordingly, it has been shown chemotherapeutic regimens optimally timed with circadian cycle jointly improved patient outcomes at preclinical clinical levels. Along chemotherapy, radiation is widely used cancer treatment, but its effectiveness relies mainly on ability damage DNA. Notably, DNA response including repair, checkpoints, apoptosis gated clock. Thus, therapeutic potential radiotherapy against dependent upon control molecular clock exerts repair enzymes across cell cycle. Unfortunately, time administration not usually considered in practice varies along daytime working hours. Currently, only few studies evaluated whether timing affects outcome. Several these show possible reduce if applied specific range, although some inconsistencies. In this Perspective, we review main advances field chronoradiotherapy, causes inconsistencies observed so far provide recommendations future trials.

Язык: Английский

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Optimizing Radiotherapy Timing for Nasopharyngeal Carcinoma: The Impact of Radiation Scheduling on Survival

JCO Precision Oncology, Год журнала: 2025, Номер 9

Опубликована: Янв. 1, 2025

PURPOSE Chronoradiobiology has emerged as a potential field of study with therapeutic implications for cancer treatment. We aimed to investigate the association between radiation chronotherapy and efficacy toxicity patients nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS Patients nonmetastatic NPC treated intensity-modulated radiotherapy in Fujian Cancer Hospital January 2017 December 2019 were included. Propensity score matching (PSM) 1:1:1 was used account selection bias. Cox regression analysis performed explore impact timing on patient survival. Sensitivity implemented determine size directional stability. RESULTS One thousand forty met inclusion criteria 332 included PSM cohort. In unmatched cohort analysis, morning exhibited significantly superior overall survival (OS) outcome (hazard ratio [HR], 0.60 [95% CI, 0.40 0.91], adjusted log-rank P = .028) than afternoon one. After it observed that individuals undergoing group (HR, 5.88 2.55 13.58], .004) night 4.81 1.91 12.11], .018) displayed tendency toward shorter OS compared group. No significant differences acute treatment-related adverse effects among three groups. Morning demonstrated consistent robustness multivariable thereby establishing an higher OS. The directionality effect across sensitivity analysis. CONCLUSION These results underscore benefits scheduling management, although prospective studies are needed confirm these findings.

Язык: Английский

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Personalization of Cancer Treatment: Exploring the Role of Chronotherapy in Immune Checkpoint Inhibitor Efficacy

Cancers, Год журнала: 2025, Номер 17(5), С. 732 - 732

Опубликована: Фев. 21, 2025

In the era of precision medicine, mounting evidence suggests that time therapy administration, or chronotherapy, has a great impact on treatment outcomes. Chronotherapy involves planning timing by considering circadian rhythms, which are 24 h oscillations in behavior and physiology driven synchronized molecular clocks throughout body. The value chronotherapy cancer is currently under investigation, notably effects efficacy side effects. Immune checkpoint inhibitor (ICI) promising treatment. However, many patients still experience disease progression need to stop early due There accumulating day at ICI administered can have substantial effect efficacy. Thus, it important investigate intersections this review, we provide brief overview rhythms context immunity cancer. Additionally, outline current applications for We synthesize 29 studies conducted date examine time-of-day administration therapy, its associated effects, sex differences both also discuss potential mechanisms underlying these observed results. Finally, highlight challenges area future directions research, including chronotherapeutic personalized medicine approach tailors individual patients’ rhythms.

Язык: Английский

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A pragmatic, multicenter, randomized trial comparing morning versus evening dosing of adjuvant endocrine therapy (REaCT-CHRONO Study)

npj Breast Cancer, Год журнала: 2025, Номер 11(1)

Опубликована: Май 29, 2025

Язык: Английский

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Clock at the Core of Cancer Development

Biology, Год журнала: 2021, Номер 10(2), С. 150 - 150

Опубликована: Фев. 14, 2021

To synchronize various biological processes with the day and night cycle, most organisms have developed circadian clocks. This evolutionarily conserved system is important in temporal regulation of behavior, physiology metabolism. Multiple pathological changes associated disruption support importance clocks mammals. Emerging links revealed interplay between signaling networks cancer. Understanding cross-talk clock tumorigenesis imperative for its prevention, management development effective treatment options. In this review, we summarize role one metabolic pathway, insulin/IGF1/PI3K/mTOR signaling, how dysregulation pathway could lead to uncontrolled cancer cell proliferation growth. Targeting rhythms either recently discovered pharmaceutical agents or through environmental cues a new direction chronotherapy. Combining approach traditional methods, such as radiation, chemotherapy developed, immunotherapy, may improve tumor response, while simultaneously minimizing adverse effects commonly therapies.

Язык: Английский

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Clinical effects of morning and afternoon radiotherapy on high-grade gliomas

Chronobiology International, Год журнала: 2021, Номер 38(5), С. 732 - 741

Опубликована: Фев. 8, 2021

Initial clinical reports comparing the delivery of radiotherapy (RT) at distinct times day suggest that this strategy might affect toxicity and oncologic outcomes radiation for multiple human tissues, but effects on high-grade gliomas (HGG) are unknown. The present study addresses hypothesis treatment time (RT-TTD) influences outcome and/or toxic events in HGG. Patients treated between 2009–2018 were reviewed (n = 109). Outcomes local control (LC), distant CNS (DCNSC), progression-free survival (PFS), overall (OS). RT-TTD was classified as morning if ≥50% fractions delivered before 12:00 h 70) or afternoon 39) after h. average age 62.6 years (range: 14.5–86.9) 80% glioblastoma. median follow-up 10.9 months 0.4–57.2). 1y/3y LC, DCNSC, PFS were: 61.3%/28.1%, 86.8%/65.2%, 39.7%/10.2%, respectively. Equivalent found groups (HR 1.27; p .3). OS 16.5 months. had worse univariate analysis 1.72; .05), not confirmed multivariate 0.92, .76). with baseline performance status interruptions showed OS. proportion patients developed grade 3 acute toxicity, pseudo progression, definitive 10.1%, 9.2%, 7.3%, respectively, affected by RT-TTD. In conclusion, HGG, there no difference afternoon. Of note, adversely should be avoided, especially low status. Based these findings, glioma cells may best initial model to irradiated order chronotherapy.

Язык: Английский

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Association of genetic variants with fatigue in patients with malignant glioma

Neuro-Oncology Practice, Год журнала: 2017, Номер 5(2), С. 122 - 128

Опубликована: Сен. 19, 2017

Fatigue is a consistently reported, severe symptom among patients with gliomas throughout the disease trajectory. Genomic pathways associated fatigue in glioma have yet to be identified.Clinical factors (performance status, tumor details, age, gender) were collected by chart review on ("I lack of energy" Functional Assessment Cancer Therapy-Brain), as well available genotyping data. Candidate genes clock and inflammatory identified from literature review, which 50 single nucleotide polymorphisms (SNPs) 7 available. Clinical SNPs univariate analyses included multivariate model for moderate-severe fatigue.The study 176 (median age = 47 years, 67% males). Moderate-severe was reported 43%. Results analysis revealed poor performance status 2 severity. more common (OR 3.52, P < .01). For each additional copy minor allele rs934945 (PER2) odds decreased 0.51, .05). rs922270 (ARTNL2) increased 2.38, Both these are important circadian pathway, has been implicated diurnal preference, duration quality sleep. No pathway current study.Identifying at highest risk during treatment allows improved clinical monitoring enrichment patient selection trials.

Язык: Английский

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