Intestinal Inflammation and Cancer

Ullman, Thomas; Itzkowitz, Steven H.

doi:10.1053/j.gastro.2011.01.057

Cited by 934 publications

(763 citation statements)

References 74 publications

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“…It has been established that environmental and hereditary factors contribute to the initiation and development of CRC, as indicated by the accumulation of mutations in oncogenes (3). Chronic inflammation is regarded as an important risk factor for the development of CRC, especially in patients with inflammatory bowel diseases (IBD) (4). Interleukin-6 (IL-6), a pro-inflammatory cytokine, has been shown to regulate cancer cell growth and thereby contribute to tumor promotion and progression (5).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer

Han

Meng

et al. 2015

International Journal of Oncology

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Abstract. Chronic inflammation is a well-known etiological factor for colorectal cancer (CRC) and cancer cells are known to preferentially metabolize glucose through aerobic glycolysis. However, the connection between chronic inflammation and aerobic glycolysis in the development of CRC is largely unexplored. The present study investigated whether interleukin-6 (IL-6), a pro-inflammatory cytokine, promotes the development of CRC by regulating the aerobic glycolysis and the underlying molecular mechanisms. In colitis-associated CRC mouse, anti-IL-6 receptor antibody treatment reduced the incidence of CRC and decreased the expression of key genes in aerobic glycolysis, whereas the plasma concentrations of glucose and lactate were not affected. Consistently, IL-6 treatment stimulated aerobic glycolysis, upregulated key genes in aerobic glycolysis and promoted cell proliferation and migration in SW480 and SW1116 CRC cells. 6-phoshofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) was the most downregulated gene by anti-IL-6 receptor antibody in colorectal adenoma tissues. Further analysis in human samples revealed overexpression of PFKFB3 in colorectal adenoma and adenocarcinoma tissues, which was also associated with lymph node metastasis, intravascular cancer embolus and TNM stage. In addition, the effect of IL-6 on CRC cells can be abolished by knocking down PRKFB3 through siRNA transfection. Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of CRC.

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Section: Introductionmentioning

confidence: 99%

Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer

Han

Meng

et al. 2015

International Journal of Oncology

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“…However, the underlying tumorigenesis of colitis-associated colorectal adenocarcinoma is different from that of sporadic colorectal adenocarcinoma. 3 This was demonstrated by the distinct histomorphology of colitis-associated colorectal adenocarcinoma. 4 In addition, our previous study on ileal pouch and peri-pouch adenocarcinomas developed in inflammatory bowel disease patients showed that approximately 60% of these tumors expressed CK7, rarely had nuclear b-catenin accumulation, 5 in contrast to the pattern seen in sporadic colorectal adenocarcinoma.…”

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confidence: 99%

Diagnostic utility of TP53 and cytokeratin 7 immunohistochemistry in idiopathic inflammatory bowel disease-associated neoplasia

et al. 2014

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Long-standing inflammatory bowel disease is associated with increased risk of developing colorectal adenocarcinoma. Significant intra-and inter-observers' variability exists in histologic interpretation of dysplasia in surveillance biopsies. In this study, we evaluated the utility of a panel of immunohistochemical markers in diagnosing inflammatory bowel disease-associated neoplasia. We reviewed 39 colectomy specimens with inflammatory bowel disease-associated neoplasia. In these 39 cases, we identified 172 foci of interest (5 normal, 58 negative for dysplasia, 15 indefinite for dysplasia, 59 low-grade dysplasia, 18 highgrade dysplasia, and 17 invasive adenocarcinoma). They were subjected to immunohistochemistry for TP53 and CK7. Logistic regression was used to evaluate their association with the presence of dysplasia. Receiver operating characteristic curves were used to determine the optimal cutoffs and assess the diagnostic performance of TP53 and CK7. Both TP53 nuclear staining and CK7 immunoreactivity gradually increased in the progression of inflammatory bowel disease-associated neoplasia (Po0.0001). CK7 immunoreactivity increased along with the increase of inflammation severity (P ¼ 0.0002) as well as reactive changes (P ¼ 0.04) in the colonic mucosa. But TP53 nuclear staining was independent of either feature. When both TP5348% and CK7430% as identified from logistic regression and receiver operating characteristic curves were used to diagnose dysplasia, the specificity achieved as high as 95%. When either TP5348% or CK7430% was used to diagnose dysplasia, the sensitivity achieved was 82%. Our results suggested that a combination of CK7 and TP53 immunohistochemistry may be helpful in diagnosing inflammatory bowel disease-associated dysplasia in difficult cases.

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“…It is well known that the chronic inflammation associated with inflammatory bowel disease (IBD) increases the risk of developing colitis-associated cancer (CAC) in patients with UC and CD [46]. The European and US guidelines recommended that regular surveillance endoscopy should be initiated from six to eight years after the first manifestation of the disease [47,48].…”

Section: Ulcerative Colitismentioning

confidence: 99%

The efficacy of autofluorescence imaging in the diagnosis of colorectal diseases

Moriichi

Fujiya

Okumura

2016

Clin J Gastroenterol

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Image-enhanced endoscopy (IEE) has been developed and is applied in the clinical setting throughout the world. Most reports regarding IEE have evaluated the efficacy of narrow-band imaging (NBI) in the diagnosis of gastrointestinal disorders. Although autofluorescence imaging (AFI) is a form of IEE, its usefulness remains unclear. The present review focused on the efficacy of AFI in the diagnosis of colorectal disease, particularly neoplasia and ulcerative colitis (UC). AFI-based diagnoses are made via the subjective judgment of the color on the monitor. The efficacy of AFI in detection and differentiation in patients with colorectal neoplastic lesions remains controversial, which may be dependent on the study design and the diagnostic procedures. Although the number of the reports related to UC is very small, most suggest that AFI is effective in UC patients. AFI is distinct from other modalities in that it can quantitatively assess the lesion based on the fluorescence intensity without any morphological assessments. AFI could be useful for patients with colorectal disease.Keywords Autofluorescence imaging (AFI) Á Colorectal neoplasia Á Ulcerative colitis (UC) Á Colitis-associated cancer Á Narrow-band imaging (NBI) Á Image-enhanced endoscopy (IEE) Á White light endoscopy (WLE)

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Intestinal Inflammation and Cancer

Cited by 934 publications

References 74 publications

Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer

Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer

Diagnostic utility of TP53 and cytokeratin 7 immunohistochemistry in idiopathic inflammatory bowel disease-associated neoplasia

The efficacy of autofluorescence imaging in the diagnosis of colorectal diseases

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