Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression

Vozenin, Marie-Catherine; Milliat, Fabien; Sabourin, Jean Christophe; Gouville, A.-C. de; François, Agnès; Lasser, Philipe; Morice, Philippe; Haie-Méder, Christine; Lusinchi, A.; Antoun, Sami; Bourhis, Jean; Mathé, Denis; Girinsky, T; Aigueperse, Jocelyne

doi:10.1016/s0360-3016(02)04601-1

Cited by 90 publications

(70 citation statements)

References 51 publications

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“…Fibroblast proliferation can be augmented by pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha), fibroblast growth factors (FGS II), granulocyte/macrophage colony-stimulating factor (GM-CSF), transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF) (47) but also by endotoxin (lipopolysaccharide) (49). Other growth factors, such as the connective tissue growth factor (CTGF), which is secreted by fibroblasts and endothelial cells, also promote formation of fibrous tissue (47). Collagen is degraded by a family of matrix metalloproteinases that includes the collagenases.…”

Section: Discussionmentioning

confidence: 99%

Severe Cryptogenic Multifocal Ulcerous Stenosing Enteritis. A Report of Three Cases and Review of the Literature

Kohoutová

Bureš

Tyčová

et al. 2010

Acta Med. (Hradec Kralove, Czech Repub.)

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IntroductionCryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare condition characterised by chronic or relapsing moderate ileous episodes resulting from multiple small intestinal strictures, multiple shallow ulcers of the small bowel and beneficial therapeutical effect of glucocorticosteroids (1, 2). Japanese gastroenterologists call this syndrome chronic non-specific multiple ulcers of the small intestine (CNSU) (3). The aetiology of CMUSE has not been clarified yet and pathogenesis is still poorly understood. Some authors even doubt the real existence of this entity.Patients with CMUSE are often referred for surgery because of symptomatic small intestinal strictures and several resections of the small bowel had to be performed.We report three cases of CMUSE diagnosed within the past 10 years at a single tertiary centre, where more than eight thousand GI endoscopies are performed per year. Review of available relevant literature is provided. Case reports Case 1A 35-year-old woman was admitted to our department because of chronic diarrhoea, colicky abdominal pain, weight loss (16 kg during previous five years) and repeated moderate ileous episodes. She was cachectic (body-mass index 12.8 kg/m 2 ). Laboratory tests showed iron-deficiency anaemia (haemoglobin 96 g/L), thrombocytosis (459.10 9 g/L) and proteino-energy malnutrition (serum prealbumin 0.17 g/L). Abdominal ultrasound revealed strenuous small intestinal peristalsis and a large volume of fluid in the intestinal loops. Enteroclysis provided no further information. Gastroscopy and colonoscopy were normal. Push-enteroscopy found multiple shallow ulcers of the distal duodenum and proximal jejunum ( Fig. 1) and increased stagnant fluid content in the proximal part of the small bowel. A non-specific inflammatory process was detected at histology and electron microscopy of small intestinal biopsy specimens. Coeliac disease, lymphoma, Crohn's disease and vasculitis were excluded. No infective agent was found. Total parenteral nutrition and glucocorticosteroids improved her general condition including nutritional status (serum albumin 35.8 g/L, prealbumin 0.29 g/L, body-mass index 13.4 kg/m 2 ). The patient was discharged on enteral nutrition, glucocorticosteroids (prednisone was gradually replaced by budesonide) and 5-aminosalicylates. She was followed-up at regular controls. Nine months later the patient had to be admitted because of a worsened general condition (frequent watery stools, fatigue, oedemas of lower extremities, fluidothorax and ascites). Laboratory tests revealed hypo-25 CASE REPORT Summary: Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare condition characterised by chronic or relapsing moderate ileous episodes resulting from multiple small intestinal strictures, multiple shallow ulcers of the small bowel and favourable therapeutical effect of glucocorticosteroids. The aim of this paper was to evaluate three cases of CMUSE diagnosed within 10 years at a tertiary gastroenterology centre. Three females (35, 50, ...

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Section: Discussionmentioning

confidence: 99%

Severe Cryptogenic Multifocal Ulcerous Stenosing Enteritis. A Report of Three Cases and Review of the Literature

Kohoutová

Bureš

Tyčová

et al. 2010

Acta Med. (Hradec Kralove, Czech Repub.)

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“…Other pleiotropic statin effects that may confer an enteroprotective effect include a reduction of oxidative stress, upregulation of tPA, or downregulation of TF, PAI-1, and connective tissue growth factor (CTGF). CTGF has been implicated in the development of intestinal radiation fibrosis (52)(53)(54)). An effect mediated through CTGF downregulation might explain why the protective effect of statins against delayed toxicity was greater than protection against early toxicity .…”

Section: Discussionmentioning

confidence: 99%

Simvastatin Ameliorates Radiation Enteropathy Development After Localized, Fractionated Irradiation by a Protein C-Independent Mechanism

Wang

Boerma

et al. 2007

International Journal of Radiation Oncology*Biology*Physics

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“…4 As part of an elaborate reaction, also implicating inflammation and angiogenesis, IR-induced fibrosis in noncancerous tissue is a side effect of tumor radiotherapy. For some organs such as the rectum, 123 the small intestine 124 and the lungs, 18 implicated in irradiation of prostate, gynecological and thoracic cancers respectively, fibrosis constitutes a major constraint. TGF-b is a master switch for the initiation and the persistence of IR-induced fibrosis.…”

Section: Characterization and Origin Of A Myofibroblastmentioning

confidence: 99%

Stromal myofibroblasts are drivers of invasive cancer growth

Wever¹,

Demetter²,

Mareel³

et al. 2008

Intl Journal of Cancer

625

609

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Tissue integrity is maintained by the stroma in physiology. In cancer, however, tissue invasion is driven by the stroma. Myofibroblasts and cancer-associated fibroblasts are important components of the tumor stroma. The origin of myofibroblasts remains controversial, although fibroblasts and bone marrow-derived precursors are considered to be the main progenitor cells. Myofibroblast reactions also occur in fibrosis. Therefore, we wonder whether nontumorous myofibroblasts have different characteristics and different origins as compared to tumor-associated myofibroblasts. The mutual interaction between cancer cells and myofibroblasts is dependent on multiple invasive growth-promoting factors, through direct cell-cell contacts and paracrine signals. Since fibrosis is a major side effect of radiotherapy, we address the question how the main methods of cancer management, including chemotherapy, hormonotherapy and surgery affect myofibroblasts and by inference the surrogate endpoints invasion and metastasis.

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Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression

Cited by 90 publications

References 51 publications

Severe Cryptogenic Multifocal Ulcerous Stenosing Enteritis. A Report of Three Cases and Review of the Literature

Severe Cryptogenic Multifocal Ulcerous Stenosing Enteritis. A Report of Three Cases and Review of the Literature

Simvastatin Ameliorates Radiation Enteropathy Development After Localized, Fractionated Irradiation by a Protein C-Independent Mechanism

Stromal myofibroblasts are drivers of invasive cancer growth

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