Effects of radiation damage on intestinal morphology

Carr, K. E.

doi:10.1016/s0074-7696(01)08002-0

Cited by 40 publications

(19 citation statements)

References 273 publications

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“…For a comprehensive description of clinical and pathological features of radiation enteropathy, the reader is referred to the chapter on the alimentary tract in Radiation Pathology by Fajardo, Berthrong, and Anderson 21 , to the very comprehensive review by Carr 22 , and to the chapters on the small bowel, colon, rectum, and anus in Human Radiation Injury, edited by Shrieve and Loeffler 23 .…”

Section: Clinical and Pathologic Characteristics Of Radiation Enteropmentioning

confidence: 99%

Radiation enteropathy—pathogenesis, treatment and prevention

Hauer‐Jensen

Denham

Andreyev

2014

Nat Rev Gastroenterol Hepatol

340

319

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There has been only modest change in cancer incidence and mortality during the past several decades, but the number of cancer survivors has almost tripled during the same period. With an increasing cohort of cancer survivors, efforts to prevent, diagnose, and manage side effects of cancer therapy in general and, specifically those of radiation therapy have intensified. Many cancer survivors have undergone radiation therapy of tumors in the pelvis or abdomen, thus rendering the bowel at risk for injury. In fact, the current prevalence of patients with long term radiation-induced intestinal side effects exceeds that of ulcerative colitis and Crohn’s disease combined. Significant progress toward reducing toxicity of radiation therapy has been made by the introduction of so-called dose-sculpting treatment techniques, which allow more precise delivery of the radiation beam. Moreover, new insight into the underlying pathophysiology have resulted in an improved understanding of mechanisms of radiation-induced bowel toxicity and in development of new diagnostic strategies and management opportunities. This article discusses the pathogenesis of early and delayed radiation-induced bowel toxicity, reviews current management options, and outlines priorities for future research. The gastroenterologist by adding insight into molecular and cellular mechanisms of related bowel disorders can substantially strengthen these efforts.

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Section: Clinical and Pathologic Characteristics Of Radiation Enteropmentioning

confidence: 99%

Radiation enteropathy—pathogenesis, treatment and prevention

Hauer‐Jensen

Denham

Andreyev

2014

Nat Rev Gastroenterol Hepatol

340

319

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“…The lesions in the intestine resemble those observed following irradiation and are likely caused by a block in cell proliferation in the crypts. 41,42 In the small intestine, stem cells in the base of the crypts give rise to progenitor cells that differentiate into enterocytes that migrate toward the tip of the villus and are shed. Diminished renewal of enterocytes leads to a reduction in the length of the villi.…”

Section: Discussionmentioning

confidence: 99%

Cul4A is required for hematopoietic cell viability and its deficiency leads to apoptosis

Waning¹,

Li²,

Jia³

et al. 2008

Blood

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In vitro studies indicate that Cul4A ubiquitin ligases target for ubiquitin-mediated proteolysis regulators of cell-cycle progression, apoptosis, development, and DNA repair. In hematopoietic cell lines, studies by our group and others showed that Cul4A ligases regulate proliferation and differentiation in maturing myeloid and erythroid cells. In vivo, Cul4A-deficient embryos die in utero. Cul4A haploinsufficient mice are viable but have fewer erythroid and primitive myeloid progenitors. Yet, little more is known about Cul4A function in vivo. To examine Cul4A function in adults, we generated mice with interferon-inducible deletion of Cul4A. Cul4A deficiency resulted in DNA damage and apoptosis of rapidly dividing cells, and mutant mice died within 3 to 10 days after induction with dramatic atrophy of the intestinal villi, bone marrow, and spleen, and with hematopoietic failure. Cul4A deletion in vivo specifically increased cellular levels of the Cul4A ligase targets Cdt1 and p27Kip1 but not other known targets. Bone marrow transplantation studies with Cul4A deletion in engrafted cells specifically isolated analysis of Cul4A function to hematopoietic cells and resulted in hematopoietic failure. These recipients died within 9 to 11 days, demonstrating that in hematopoietic cells, Cul4A is essential for survival.

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“…Even at radiation doses below the threshold for the full-blown GI syndrome, mucosal barrier breakdown allows bacteria to translocate into the circulation, which can cause sepsis and death in the setting of concomitant immune suppression (64). In the longer term, tissue remodeling subsequent to radiation damage alters the structure, motility and absorption of the gut, and fibrosis renders it more rigid and susceptible to adhesions, stenosis and perforation (65). …”

Section: Gastrointestinal Tractmentioning

confidence: 99%

Animal Models for Medical Countermeasures to Radiation Exposure

et al. 2010

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Since September 11, 2001, there has been the recognition of a plausible threat from acts of terrorism, including radiological or nuclear attacks. A network of Centers for Medical Countermeasures against Radiation (CMCRs) has been established across the U.S.; one of the missions of this network is to identify and develop mitigating agents that can be used to treat the civilian population after a radiological event. The development of such agents requires comparison of data from many sources and accumulation of information consistent with the "Animal Rule" from the Food and Drug Administration (FDA). Given the necessity for a consensus on appropriate animal model use across the network to allow for comparative studies to be performed across institutions, and to identify pivotal studies and facilitate FDA approval, in early 2008, investigators from each of the CMCRs organized and met for an Animal Models Workshop. Working groups deliberated and discussed the wide range of animal models available for assessing agent efficacy in a number of relevant tissues and organs, including the immune and hematopoietic systems, gastrointestinal tract, lung, kidney and skin. Discussions covered the most appropriate species and strains available as well as other factors that may affect differential findings between groups and institutions. This report provides the workshop findings.

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Effects of radiation damage on intestinal morphology

Cited by 40 publications

References 273 publications

Radiation enteropathy—pathogenesis, treatment and prevention

Radiation enteropathy—pathogenesis, treatment and prevention

Cul4A is required for hematopoietic cell viability and its deficiency leads to apoptosis

Animal Models for Medical Countermeasures to Radiation Exposure

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