Neulasta Regimen for the Hematopoietic Acute Radiation Syndrome: Effects Beyond Neutrophil Recovery

Legesse, Betre; Kaur, Amandeep; Kenchegowda, Doreswamy; Hritzo, Bernadette; Culp, William E.; Moroni, Maria

doi:10.1016/j.ijrobp.2018.11.043

Cited by 16 publications

(10 citation statements)

References 59 publications

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“…Furthermore, other pathological stimuli such as ROS and inflammatory cytokines can cause selective inhibition of the IRS/PI3K/Akt pathway and even enhance the MAPK signal pathway [47]. Selective IGF-1 resistance has recently been considered to be a new radiation injury mechanism related to inflammation and endothelial dysfunction [52]. The inhibition of the IRS/PI3K/Akt/eNOS signal transduc-tion pathway and the activation of the Grb/Shc/MAPK/ET pathway lead to an imbalance between NO and ET-1, resulting in endothelial dysfunction and CVD [47].…”

Section: Igf-1 and Oxidative Stressmentioning

confidence: 99%

Oxidative Stress in Radiation-Induced Cardiotoxicity

Zhang

Yang

Liu

et al. 2020

Oxidative Medicine and Cellular Longevity

121

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There is a distinct increase in the risk of heart disease in people exposed to ionizing radiation (IR). Radiation-induced heart disease (RIHD) is one of the adverse side effects when people are exposed to ionizing radiation. IR may come from various forms, such as diagnostic imaging, radiotherapy for cancer treatment, nuclear disasters, and accidents. However, RIHD was mainly observed after radiotherapy for chest malignant tumors, especially left breast cancer. Radiation therapy (RT) has become one of the main ways to treat all kinds of cancer, which is used to reduce the recurrence of cancer and improve the survival rate of patients. The potential cause of radiation-induced cardiotoxicity is unclear, but it may be relevant to oxidative stress. Oxidative stress, an accumulation of reactive oxygen species (ROS), disrupts intracellular homeostasis through chemical modification and damages proteins, lipids, and DNA; therefore, it results in a series of related pathophysiological changes. The purpose of this review was to summarise the studies of oxidative stress in radiotherapy-induced cardiotoxicity and provide prevention and treatment methods to reduce cardiac damage.

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Section: Igf-1 and Oxidative Stressmentioning

confidence: 99%

Oxidative Stress in Radiation-Induced Cardiotoxicity

Zhang

Yang

Liu

et al. 2020

Oxidative Medicine and Cellular Longevity

121

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“…(Gottlober et al 2001;Engin et al 2015). Indeed, the critical involvement of bone marrow injury in the development of the acute radiation syndrome has been well documented (Grande and Bueren 2004;Gluzman-Poltorak et al 2015;MacVittie et al 2015) and has been the subject of significant recent research for countermeasure development purposes (Farese and MacVittie 2015;Legesse et al 2018). However, the long-term consequences of radiation injury in the bone marrow niche, particularly with respect to the most immature HSC populations (Otsuka et al 2010;Udroiu et al 2017;Sivananthan et al 2018) and in the context of nonuniform exposures (Smirnova 2015), are only just beginning to emerge.…”

Section: Introductionmentioning

confidence: 99%

Acute and late effects of combined internal and external radiation exposures on the hematopoietic system

Calvi

Frisch

Kingsley

et al. 2019

International Journal of Radiation Biology

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Purpose: Incidents, such as nuclear facility accidents and the release of a 'dirty bomb', might result in not only external irradiation of personnel, but additional internal exposures through concomitant inhalation and/or ingestion of radioactive particulates. The purpose of this study was to define the impact of such a combination of radiation injuries on the hematopoietic niche. Material and methods: To assess changes in the murine hematopoietic system, we used a combined exposure of total body irradiation (TBI, 6 Gy) followed immediately by an internal (intraperitoneal) administration of 100 mCi of soluble 137 Cs. We then evaluated acute survival in combined versus single modality exposure groups, as well as assessing hematopoietic function at 12 and 26 week time points. Results: Acutely, the combination of external and internal exposures led to an unexpected delay in excretion of 137 Cs, increasing the absorbed dose in the combined exposure group and leading to mortality from an acute hematopoietic syndrome. At 12 weeks, all exposure paradigms resulted in decreased numbers of phenotypic hematopoietic stem cells (HSCs), particularly the short-term HSCs (ST-HSC); long-term HSCs (LT-HSC) were depleted only in the internal and combined exposure groups. At 26 weeks, there was significant anemia in both the TBI alone and combined exposure groups. There were decreased numbers in both the LT-and ST-HSCs and decreased functionality, as measured by competitive repopulation, was seen in all radiation groups, with the greatest effects seen in the internal and combined exposure groups. Conclusions: Our data indicate that a combined injury of sublethal external irradiation with internal contamination induces significant and persistent changes in the hematopoietic system, as may have been predicted from the literature and our own group's findings. However, a novel observation was that the combined exposure led to an alteration in the excretion kinetics of the internal contamination, increasing the acute effects beyond those anticipated. As a result, we believe that a combined exposure poses a unique challenge to the medical community during both the acute and, possibly, delayed recovery stages.

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“…Over the last ten years, there has been significant progress with the characterization of minipigs as an animal model to study radiation injuries and to evaluate the efficacy of various medical countermeasures. Several radiation countermeasures for hematopoietic and cutaneous sub-syndromes, such as Neupogen [18], Neulasta [19,20], and adipose-derived stem cells [17,21], have been tested for efficacy using irradiated minipigs (Table 3). Additional agents have also been investigated for beneficial effects against radiation injury such as curcumin and basic fibroblast growth factor.…”

Section: Characterization Of Minipig As Animal Model For Acute Radiatmentioning

confidence: 99%

“…It is important to note that evaluating a given agent does not necessarily constitute 'proof-of-characterization' and that the minipig's basic anatomical, physiological, central nervous system, genetic, etc., features are all appropriate for a given endpoint [22]. In general, however, medical countermeasures demonstrating efficacy in NHPs have also shown efficacy in minipigs [18][19][20].…”

Section: Characterization Of Minipig As Animal Model For Acute Radiatmentioning

confidence: 99%

What are the practical, ethical, and pathobiological considerations in the use of minipigs as an animal model in drug discovery for acute radiation syndrome and delayed effects of acute radiation exposure?

Kenchegowda

Seed²,

Singh

2020

Expert Opinion on Drug Discovery

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Neulasta Regimen for the Hematopoietic Acute Radiation Syndrome: Effects Beyond Neutrophil Recovery

Cited by 16 publications

References 59 publications

Oxidative Stress in Radiation-Induced Cardiotoxicity

Oxidative Stress in Radiation-Induced Cardiotoxicity

Acute and late effects of combined internal and external radiation exposures on the hematopoietic system

What are the practical, ethical, and pathobiological considerations in the use of minipigs as an animal model in drug discovery for acute radiation syndrome and delayed effects of acute radiation exposure?

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