Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), angiostatin, and endostatin are increased in radiotherapy-induced gastrointestinal toxicity

Stansborough, Romany L.; Bateman, Emma; Al‐Dasooqi, Noor; Bowen, Joanne M.; Wignall, Anthony; Keefe, Dorothy; Yeoh, Ann S. J.; Logan, Richard M.; Yeoh, Eric; Stringer, Andrea M.; Gibson, Rachel J.

doi:10.1080/09553002.2018.1483588

Cited by 8 publications

(5 citation statements)

References 42 publications

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“…Dysregulated TGFβ activation has been reported in several infection and inflammatory states including inflammatory bowel disease (IBD) and idiopathic pulmonary fibrosis 120,139 . Similar dysregulation of TGFβ might occur in irradiated tissues, where increased levels of TGFβ have been reported 98,141 . Thus, accumulation of bioactive TGFβ is thought to…”

Section: Box 4 Ecm Remodelling and Immune Regulation By Tgfβsupporting

confidence: 53%

Immunomodulation by radiotherapy in tumour control and normal tissue toxicity

et al. 2021

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Radiotherapy (RT) is a highly effective anti-cancer treatment that is delivered to over half of all cancer patients. In addition to the well documented direct cytotoxic effects, RT can induce immunomodulatory effects to the tumour and surrounding tissues. These effects are thought to underlie the so-called 'abscopal responses', where RT generates systemic antitumour immunity outside of the irradiated tumour. In addition, RT may also result in an inflammatory immune response in the normal tissues surrounding the tumour. The full scope of these immune changes remains unclear but is likely to involve multiple tissue components and immune mediators. These include immune cells, the extracellular matrix, endothelial and epithelial cells and a myriad of chemokines and cytokines, including TGFβ, which is known to play a key role. In normal tissues exposed to RT during cancer therapy, acute immune changes may ultimately lead to chronic inflammation and RT-induced toxicity and organ dysfunction, which limits the quality of life of cancer survivors. Here, we discuss the emerging understanding of RT-induced immune effects with a particular focus on the lung and gut and the potential immune cross-talk that occurs between these tissues.

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Section: Box 4 Ecm Remodelling and Immune Regulation By Tgfβsupporting

confidence: 53%

Immunomodulation by radiotherapy in tumour control and normal tissue toxicity

et al. 2021

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“…In a rat model of RT-induced gut toxicity, 25 Gy irradiation of the gut led to increased expression of MMP2, MMP9, VEGF, TGFb, endostatin and angiostatin. These factors might strongly influence the behavior of endothelial cells (103). In conclusion, most cellular responses associated with lung fibrosis are caused by or linked to infiltration by macrophages with a proinflammatory phenotype.…”

Section: Macrophagesmentioning

confidence: 95%

Radiation-Induced Immunity and Toxicities: The Versatility of the cGAS-STING Pathway

et al. 2021

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In the past decade, radiation therapy (RT) entered the era of personalized medicine, following the striking improvements in radiation delivery and treatment planning optimization, and in the understanding of the cancer response, including the immunological response. The next challenge is to identify the optimal radiation regimen(s) to induce a clinically relevant anti-tumor immunity response. Organs at risks and the tumor microenvironment (e.g. endothelial cells, macrophages and fibroblasts) often limit the radiation regimen effects due to adverse toxicities. Here, we reviewed how RT can modulate the immune response involved in the tumor control and side effects associated with inflammatory processes. Moreover, we discussed the versatile roles of tumor microenvironment components during RT, how the innate immune sensing of RT-induced genotoxicity, through the cGAS-STING pathway, might link the anti-tumor immune response, radiation-induced necrosis and radiation-induced fibrosis, and how a better understanding of the switch between favorable and deleterious events might help to define innovative approaches to increase RT benefits in patients with cancer.

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“…The generated ROS activates the NF-κB pathway, hence increasing expression of TNF-α, IL-1β, IL-6, etc., which plays a vital role in the regulation of inflammation. Radiation can also cause chronic ischemia, intestinal fibrosis and high expression of vascular endothelial growth factor (VEGF) (Kawano et al, 2006;Beenken and Mohammadi, 2009;Stansborough et al, 2018).…”

Section: Irradiation Damages Intestinal Integritymentioning

confidence: 99%

Pathogenesis and therapy of radiation enteritis with gut microbiota

et al. 2023

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Radiotherapy is widely used in clinic due to its good effect for cancer treatment. But radiotherapy of malignant tumors in the abdomen and pelvis is easy to cause radiation enteritis complications. Gastrointestinal tract contains numerous microbes, most of which are mutualistic relationship with the host. Abdominal radiation results in gut microbiota dysbiosis. Microbial therapy can directly target gut microbiota to reverse microbiota dysbiosis, hence relieving intestinal inflammation. In this review, we mainly summarized pathogenesis and novel therapy of the radiation-induced intestinal injury with gut microbiota dysbiosis and envision the opportunities and challenges of radiation enteritis therapy.

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Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), angiostatin, and endostatin are increased in radiotherapy-induced gastrointestinal toxicity

Abstract: Findings of this study support the involvement of VEGF, TGFβ, angiostatin, endostatin, and MMP-2 in the pathobiology of RIGT. However, the relationship between these mediators is complex and needs further investigation to improve understanding of their therapeutic potential in RIGT.

Cited by 8 publications

References 42 publications

Immunomodulation by radiotherapy in tumour control and normal tissue toxicity

Immunomodulation by radiotherapy in tumour control and normal tissue toxicity

Radiation-Induced Immunity and Toxicities: The Versatility of the cGAS-STING Pathway

Pathogenesis and therapy of radiation enteritis with gut microbiota

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