Mechanisms of Normal Tissue Injury From Irradiation

Citrin, Deborah E.; Mitchell, James B.

doi:10.1016/j.semradonc.2017.04.001

Cited by 84 publications

(56 citation statements)

References 107 publications

(100 reference statements)

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“…Our findings strongly support the notion that the pretreatment TIES ('hot'-'altered'-'cold') 53 should be considered when delivering radiation, as the appropriate inflamed state of a tumor 54,55 following radiotherapy facilitates tumor kill. Though many clinical trials are testing combinations of immunotherapies with radiation, the optimal dose, fractionation, sequencing and timing of these combinations are unknown.…”

Section: Recent Data Have Suggested An Interesting Connection Betweensupporting

confidence: 81%

Harnessing tumor immune ecosystem dynamics to personalize radiotherapy

Grass

Alfonso²,

Welsh

et al. 2020

Preprint

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Radiotherapy is a pillar of cancer care and augments the response to immunotherapies. However, little is known regarding the relationships between the tumor immune ecosystem (TIES) and intrinsic radiosensitivity, and a pressing question in oncology is how to optimize radiotherapy to improve patient responses to immune therapies. To address this challenge, we profiled over 10,000 primary tumors for their metrics of radiosensitivity and immune cell infiltrate (ICI), and applied a new integrated in silico model that mimics the dynamic relationships between tumor growth, ICI flux and the response to radiation. We then validated this model with a separate cohort of 59 lung cancer patients treated with radiotherapy.These analyses explain radiation response based on its effect on the TIES and quantifies the likelihood that radiation can promote a shift to anti-tumor immunity. Dynamic modeling of the relationship between tumor radiosensitivity and theTIES may provide opportunity to personalize combined radiation and immunotherapy approaches. References 1 Yard, B. D. et al. A genetic basis for the variation in the vulnerability of cancer to DNA damage. Nat Commun 7, 11428, doi:10.1038/ncomms11428 (2016). 2 Tang, L. et al. Role of metabolism in cancer cell radioresistance and radiosensitization methods. Eschrich, S. et al. Systems biology modeling of the radiation sensitivity network: a biomarker discovery platform.

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Section: Recent Data Have Suggested An Interesting Connection Betweensupporting

confidence: 81%

Harnessing tumor immune ecosystem dynamics to personalize radiotherapy

Grass

Alfonso²,

Welsh

et al. 2020

Preprint

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“…; Chen et al. ; Citrin & Mitchell, ). Although oxidative stress appears to be an accident, this is unlikely to be true.…”

Section: Reactive Oxygen Species Needed and Dangerousmentioning

confidence: 99%

“…The nature of oxidative stress includes unspecific oxidation of intracellular molecules, with potentially detrimental effects on cell function and survival (Misra, Sarwat, Bhakuni, Tuteja, & Tuteja, 2009). Oxidative stress often occurs in the course of unpredictable events that mainly target individual cells, such as inflammation, irradiation or poisoning, for example with cigarette smoke (Boukhenouna et al 2018;Chen et al 2018;Citrin & Mitchell, 2017). Although oxidative stress appears to be an accident, this is unlikely to be true.…”

Section: Reactive Oxygen Species Needed and Dangerousmentioning

confidence: 99%

NADPH oxidase‐derived reactive oxygen species: Dosis facit venenum

Schröder

2019

Experimental Physiology

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New Findings What is the topic of this review? Within this review, the role of reactive oxygen species in cellular homeostasis, physiology and pathophysiology is discussed. What advances does it highlight? The review provides new concepts of how reactive oxygen species influence gene expression, energy consumption and other aspects of the life of a cell. Furthermore, a model is provided to illustrate how reactive oxygen species elicit specific oxidation of target molecules. Abstract Reactive oxygen species (ROS) have a long history of bad reputation. They are needed and effective in host defense, but on the contrary may induce situations of oxidative stress. Besides that, within recent years several soft functions (functions that may occur and are not directly connected to an effect, but may influence signaling in an indirect manner) of NADPH oxidases have been discovered, which are slowly eroding the image of the solely dangerous ROS. NADPH oxidase‐derived ROS serve to ease or enable signal transduction and to maintain homeostasis. However, there is still an enormous lag in the knowledge concerning target proteins and how ROS can elicit specific signalling in different cells and tissues. The present review summarizes some important functions of Nox2 and Nox4. Furthermore, although highly speculative, a model is provided of how those NADPH oxidases might be able to oxidize target proteins in a specific way. Many concepts mentioned in this review represent my personal view and are supported only in part by published studies.

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“…Late radiation‐induced toxicities are characterized by vascular ischemia. Edema and cellular destruction cause depletion of normal tissues and the proliferation of fibroblasts, which cause various late symptoms . Thus, late radiation‐induced changes that can appear months after IMRT urinary symptoms may be responsible for the second peak of urinary symptoms in the present study.…”

Section: Discussionmentioning

confidence: 62%