Colorectal neoplasia in ulcerative colitis—recent advances

Wong, Newton A C S; Harrison, DJ

doi:10.1046/j.1365-2559.2001.01292.x

Cited by 74 publications

(44 citation statements)

References 86 publications

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“…Down-regulated p27 expression in inflamed and IBD-associated nondysplastic mucosa is indistinguishable from that in transitional mucosa adjacent to sporadic colorectal carcinomas. In contrast, p27 is overexpressed in dysplastic lesions, perhaps as an attempt to counterbalance proliferative stimuli (Wong and Harrison, 2001). Thus, up-regulated p27 expression by bFGF treatment seems to recover a balance between cell cycle inhibition and cell proliferation, preventing loss of control on the cell cycle progression during UC healing.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of Basic Fibroblast Growth Factor Effect on Healing of Ulcerative Colitis in Rats

Paunovic¹,

Deng²,

Khomenko³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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We demonstrated previously that basic fibroblast growth factor (bFGF) accelerated the healing of experimental duodenal ulcers, and we now hypothesize that bFGF might also accelerate the healing of experimental ulcerative colitis (UC). We also explored the potential molecular mechanisms involved in the accelerated healing of UC in rats treated with bFGF. The results demonstrated that colonic lesions were significantly reduced by bFGF treatment, whereas neutralization of bFGF aggravated iodoacetamide-induced UC. Protein expression of bFGF was increased during the healing stage of UC. Tumor necrosis factor-␣ levels and myeloperoxidase activity were significantly decreased in UC rats treated with bFGF, whereas they increased in rats treated with anti-bFGF antibody. Real-time polymerase chain reaction and immunohistochemistry showed decreased levels of p27 in the UC rats compared with the healthy controls, which was reversed by bFGF treatment in a dose-dependent manner. By immunohistochemistry and double labeling of Ki-67 and CD34, prominent positive staining of Ki-67 and CD34 was seen after bFGF treatment, indicating the enhanced proliferation of fibroblasts and epithelial and endothelial cells, i.e., angiogenesis. We conclude that bFGF plays a beneficial role in the healing of UC in rats. The molecular mechanisms of bFGF in UC healing not only involve the expected increased cell proliferation, especially angiogenesis, but also encompass the reduction of inflammatory cytokines and infiltration of inflammatory cells. Thus, bFGF enema may be a new therapeutic option for UC.

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Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of Basic Fibroblast Growth Factor Effect on Healing of Ulcerative Colitis in Rats

Paunovic¹,

Deng²,

Khomenko³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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“…Instability is defined as a microsatellite insertion or deletion mutation in genomic DNA isolated from the target tissue or tumor compared with an autologous control (usually peripheral blood) (18). Many studies demonstrate an association among MSI, DNA damage, and development of neoplasia (19,36,37).…”

Section: Discussionmentioning

confidence: 99%

Microsatellite Instability and Suppressed DNA Repair Enzyme Expression in Rheumatoid Arthritis

Lee

Chang

Goel

et al. 2003

The Journal of Immunology

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Reactive oxygen and nitrogen are produced by rheumatoid arthritis (RA) synovial tissue and can potentially induce mutations in key genes. Normally, this process is prevented by a DNA mismatch repair (MMR) system that maintains sequence fidelity during DNA replication. Key members of the MMR system include MutSα (hMSH2 and hMSH6) and MutSβ (hMSH2 and hMSH3). To provide evidence of DNA damage in inflamed synovium, we analyzed synovial tissues for microsatellite instability (MSI). MSI was examined by PCR on genomic DNA of paired synovial tissue and peripheral blood cells of RA patients using specific primer sequences for five key microsatellites. Surprisingly, abundant MSI was observed in RA synovium compared with osteoarthritis tissue. Western blot analysis for the expression of MMR proteins demonstrated decreased hMSH6 and increased hMSH3 in RA synovium. To evaluate potential mechanisms of MMR regulation in arthritis, fibroblast-like synoviocytes (FLS) were isolated from synovial tissues and incubated with the NO donor S-nitroso-N-acetylpenicillamine. Western blot analysis demonstrated constitutive expression of hMSH2, 3, and 6 in RA and osteoarthritis FLS. When FLS were cultured with S-nitroso-N-acetylpenicillamine, the pattern of MMR expression in RA synovium was reproduced (high hMSH3, low hMSH6). Therefore, oxidative stress can relax the DNA MMR system in RA by suppressing hMSH6. Decreased hMSH6 can subsequently interfere with repair of single base mutations, which is the type observed in RA. We propose that oxidative stress not only creates DNA adducts that are potentially mutagenic, but also suppresses the mechanisms that limit the DNA damage.

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“…Patients with chronic inflammatory bowel disease, either ulcerative colitis or Crohn's disease, are at increased risk of developing CRC (22,36), indicating that chronic intestinal inflammation is a major risk for CRC (47,67). Consistently, anti-inflammatory therapies with nonsteroidal anti-inflammatory drugs such as aspirin reduce the risk of cancer (10,18).…”

mentioning

confidence: 99%

Colitis and Colitis-Associated Cancer Are Exacerbated in Mice Deficient for Tumor Protein 53-Induced Nuclear Protein 1

Gommeaux

Cano

García

et al. 2007

Molecular and Cellular Biology

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Tumor protein 53-induced nuclear protein 1 (TP53INP1) is an antiproliferative and proapoptotic protein involved in cell stress response. To address its physiological roles in colorectal cancer and colitis, we generated and tested the susceptibility of Trp53inp1-deficient mice to the development of colorectal tumors induced by injection of the carcinogen azoxymethane followed by dextran sulfate sodium (DSS)-induced chronic colitis. Trp53inp1-deficient mice showed an increased incidence and multiplicity of tumors compared to those of wild-type (WT) mice. Furthermore, acute colitis induced by DSS treatment was more severe in Trp53inp1-deficient mice than in WT mice. Treatment with the antioxidant N-acetylcysteine prevented colitis and colitisassociated tumorigenesis more efficiently in WT mice than in Trp53inp1-deficient mice, suggesting a higher oxidative load in the latter. Consistently, we demonstrated by electron spin resonance and spin trapping that colons derived from deficient mice produced more free radicals than those of the WT during colitis and that the basal blood level of the antioxidant ascorbate was decreased in Trp53inp1-deficient mice. Collectively, these results indicate that the oxidative load is higher in Trp53inp1-deficient mice than in WT mice, generating a more-severe DSS-induced colitis, which favors development of colorectal tumors in Trp53inp1-deficient mice.

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Colorectal neoplasia in ulcerative colitis—recent advances

Cited by 74 publications

References 86 publications

Molecular Mechanisms of Basic Fibroblast Growth Factor Effect on Healing of Ulcerative Colitis in Rats

Molecular Mechanisms of Basic Fibroblast Growth Factor Effect on Healing of Ulcerative Colitis in Rats

Microsatellite Instability and Suppressed DNA Repair Enzyme Expression in Rheumatoid Arthritis

Colitis and Colitis-Associated Cancer Are Exacerbated in Mice Deficient for Tumor Protein 53-Induced Nuclear Protein 1

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