Mechanism and modification of gastrointestinal soft tissue response to radiation: Role of growth factors

Okunieff, Paul; Cornelison, Terri L.; Mester, Marcelo; Liu, Weimin; Ding, Ivan; Chen, Yuchyau; Zhang, Hong; Williams, Jacqueline P.; Finkelstein, Jacob N.

doi:10.1016/j.ijrobp.2005.01.034

Cited by 40 publications

(40 citation statements)

References 41 publications

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“…Radiation has been shown to result in the activation of a number of early response cytokines that act through diverse signaling pathways (18). This continuous cascade of cytokines has been proposed to induce a chronic inflammatory phase, which is in turn followed by late stromal alterations, such as fibrosis (19). Radiation injury has also been likened to a ''complex wound'' in which persistent damage to the vascular endothelium results in eventual dysregulation of the coagulation system, which in turn causes a chronic inflammatory response leading to fibrotic changes (20).…”

Section: Discussionmentioning

confidence: 99%

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

Schuller¹,

Binns

Riley

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received wholebody epithermal neutron irradiation at a dose rate of 0.57 ؎ 0.04 Gy⅐min ؊1 . An additional dose was selectively targeted to endothelial cells from the short-ranged (5-9 m) particles released from neutron capture reactions in 10 B confined to the blood by incorporation into liposomes 70 -90 nm in diameter. Different liposome formulations produced 45 ؎ 7 or 118 ؎ 12 g͞g 10 B in the blood at the time of neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 ؎ 0.09 or 1.90 ؎ 0.16 Gy⅐min ؊1 , respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2-to 3-fold increased doses to the microvasculature, relative to the nonspecific wholebody neutron beam doses, caused no additional crypt stem cell loss beyond that produced by the neutron beam alone. The threshold dose for death from the GI syndrome after neutron-beam-only irradiation was 9.0 ؎ 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received neutron beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome.gastrointestinal syndrome ͉ boron ͉ liposomes ͉ neutron capture R adiation-induced changes seen in normal tissues are traditionally separated into early and late effects. Stem-cellbased, rapidly renewing normal tissues, such as the bone marrow and the intestinal epithelium, are early responding tissues in which the time courses of the radiation syndromes are directly related to the turnover time of the differentiated functional cell compartments. The intestinal stem cells reside in the crypts of Lieberkühn at the base of the finger-like villi that comprise the intestinal epithelium. Epithelial cells differentiate as they migrate up the crypt and the villus and are eventually sloughed off at the tip into the intestinal lumen: the transit time takes Ϸ3-4

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Section: Discussionmentioning

confidence: 99%

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

Schuller¹,

Binns

Riley

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…These experimental data demonstrate long-term cytokine expression changes in the bowel wall after irradiation that parallel the responses noticed in other tissues prone to radiation-induced fibrosis, such as cutaneous and pulmonary tissues, thereby having implications for the prediction, treatment and/or prevention of chronic radiation colitis. For instance, chronic IL-6 elevations, even prior to the start of irradiation, may predict patients at risk of radiation fibrotic bowel damage in the same way that IL-6 baseline elevations have been shown to identify patients with an increased risk of radiation pneumonitis and pulmonary fibrosis following thoracic irradiation [33] . Since studies in animal models of IBD have shown that various antibodies to pro-inflammatory cytokines and their receptors, such as IL-6 receptor (IL-6R) or TNF, appear to suppress chronic intestinal inflammation by inducing T-cell apoptosis [34] , it is reasonable to assume that such antibodies (anti-IL-6R) might also be used to manage radiation colitis.…”

Section: Chronic Radiation Colitis (Table 2)mentioning

confidence: 98%

“…Therefore, surgical inter vention appears to be appropriate when the diagnosis of chronic radiation colitis is confirmed [32] . Nevertheless, chronic changes in cytokine levels after abdominal irradiation in rodents have recently been documented [33] . Structural injury of the bowel wall and mesentery were scored and correlated with the levels of TNF-α, IL-6, transforming growth factor (TGF)-β1, -β2, -β3 and interferon (IFN)-γ mRNA in large and small bowel of mice 18-25 wk after whole abdominal irradiation with 12.5 and 13.5 Gy.…”

Section: Chronic Radiation Colitis (Table 2)mentioning

confidence: 99%

“…Recent advances in the approaches to its prevention or amelioration are therefore particularly encouraging. Research to uncover the mechanisms of fibrosis and the molecular events underlying radiation bowel disease could lead to the development of new therapeutic and/or preventive approaches and provide the basis for predicting the risk of bowel damage and oncogenesis using levels and expressions of the mentioned cytokine IL-6, oncogene p53 or cadherincatenin complexes, and for amelioration of bowel damage through inhibition, for example, of the COX-2 and Rho/Rho kinase pathways [33,87] . In this regard, the COX-2 inhibitor Rofecoxib® has been shown to suppress cytokine expression and to reduce acute bowel damage in rodents following abdominal irradiation [36] .…”

Section: Prevention Of Radiation Colitismentioning

confidence: 99%

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Recent advances in the management of radiation colitis

Kountouras¹,

Zavos²

2008

WJG

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“…The pathogenesis of radiation proctitis has not been clarified totally yet. However, it is known that firstly mucosal damage is observed due to the radiation, subsequently connective tissue is enlarged and remodeled, lastly fibrosis and ischemia are observed 5 . These kinds of pathological damage are varied in ARP and CRP.…”

Section: ■ Introductionmentioning

confidence: 99%

Evaluation of prophylactic and therapeutic effects of sildenafil on acute radiation proctitis in rats

Yavuz¹,

Ercan²,

Karagülle³

et al. 2018

Acta Cir. Bras.

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Purpose: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). Methods: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. Results: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group. While the prophylaxis group and the treatment group had significantly lower scores. High-dose group showed similar results as prophylaxis group. Histopathological findings of the prophylaxis group was more significant than the treatment group. Immunoreactivities of IL-1β, FGF-2, TNF-α and HIF-1α increased in the control group especially in the epithelial and cryptic regions. On the contrary, sildenafil application caused significant decreases of inflammatory markers in all treatment groups, specifically better results in the prophylaxis group. Conclusion: The sildenafil has anti-inflammatory effects on ARP, as well as protective effects against ARP and the protective effect of sildenafil surpasses its therapeutic effect histopathologically.

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Mechanism and modification of gastrointestinal soft tissue response to radiation: Role of growth factors

Cited by 40 publications

References 41 publications

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

Recent advances in the management of radiation colitis

Evaluation of prophylactic and therapeutic effects of sildenafil on acute radiation proctitis in rats

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