Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021831 (enteropathy)
 4,403 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than half of cancer patients are treated with radiation therapy. Despite its high therapeutic index, radiation therapy can cause disabling injuries to normal tissues, especially in long-term survivors. Thus, one of the great challenges of modern radiation therapy is to increase tolerance of normal tissue to ionizing radiation in order to improve the quality of life of cancer survivors and/or enhance local control using dose escalation. The physiopathological aspects of normal tissue toxicity have been widely explored; however, none of these descriptive findings has led to the development of effective therapeutic strategies. Several empirical treatments have also been used in clinical trials (superoxide dismutase, pentoxifylline-tocopherol); however, the results are still controversial, and their mechanisms of action have not been clearly defined. The recent development of high-throughput biological approaches will contribute greatly to the characterization of the molecular pathways associated with normal tissue toxicity and the identification of specific and effective molecular targets for therapeutic interventions using already known or new pharmacological compounds. In this paper, we will discuss recent advances made in the characterization of one of the most serious complications of radiation therapy, late intestinal toxicity, using molecular profiling. We will focus on the involvement of the Rho/ROCK pathway in the development and maintenance of late radiation enteropathy. The role of the Rho/ROCK pathway in tissue response to radiation injury will be reviewed, as well as therapeutic perspectives.
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PMID:Rho/ROCK pathway as a molecular target for modulation of intestinal radiation-induced toxicity. 1770 24

The fibrogenic differentiation of resident mesenchymal cells is a key parameter in the pathogenesis of radiation fibrosis and is triggered by the profibrotic growth factors transforming growth factor (TGF)-beta1 and CCN2. TGF-beta1 is considered the primary inducer of fibrogenic differentiation and is thought to control its long-term maintenance, whereas CCN2 is considered secondary effector of TGF-beta1. Yet, in long-term established fibrosis like that associated with delayed radiation enteropathy, in situ TGF-beta1 deposition is low, whereas CCN2 expression is high. To explore this apparent paradox, cell response to increasing doses of TGF-beta1 was investigated in cells modeling initiation and maintenance of fibrosis, i.e., normal and fibrosis-derived smooth muscle cells, respectively. Activation of cell-specific signaling pathways by low TGF-beta1 doses was demonstrated with a main activation of the Rho/ROCK pathway in fibrosis-derived cells, whereas the Smad pathway was mainly activated in normal cells. This leads to subsequent and cell-specific regulation of the CCN2 gene. These results suggested a specific profibrotic role of CCN2 in fibrosis-initiated cells. Furthermore, the modulation of CCN2 expression by itself and the combination of TGF-beta1 and CCN2 was investigated in fibrosis-derived cells. In fibrosis-initiated cells CCN2 triggered its autoinduction; furthermore, low concentration of TGF-beta1-potentiated CCN2 autoinduction. Our findings showed a differential requirement and action of TGF-beta1 in the fibrogenic response of normal vs. fibrosis-derived cells. This study defines a novel Rho/ROCK but Smad3-independent mode of TGF-beta signaling that may operate during the chronic stages of fibrosis and provides evidence of both specific and combinatorial roles of low TGF-beta1 dose and CCN2.
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PMID:Specific signals involved in the long-term maintenance of radiation-induced fibrogenic differentiation: a role for CCN2 and low concentration of TGF-beta1. 1840 Sep 84

The aim of this study was to develop a scale to assess the levels of specific self-efficacy in order to enhance adherence to a gluten-free diet and the life quality of celiac patients. Celiac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed people. The only treatment is a strict lifelong gluten-free diet. Within the framework of Social Cognitive Theory, expectation of self-efficacy is understood as the degree in which a person believes himself to be capable of performing a certain task (e.g., adhering to a gluten-free diet), a construct which has been widely studied in its relation with adopting healthy behaviors, but scarcely in relation to celiac disease. A validation study was carried out in various stages: preparation of the protocol; construction of the questionnaire and a pilot run with 20 patients; validation of the scale with 563 patients and statistical analysis. A 25-item scale was developed. Feasibility was excellent (99.82% of participants completed all the questions). Factorial analysis pointed to the existence of five factors that explained 70.98% of the variance with a Cronbach alpha of 0.81 for the scale overall and between 0.64 and 0.90 for each factor. The scale showed a Spearman's Rho coefficient of 0.279 with the General self-efficacy Scale. This easily administered scale provides good psychometric properties for evaluating specific self-efficacy of celiac patients in adhering to treatment. It seeks to be the first scale that provides not only a measurement of specific self-efficacy in celiac disease, but also to determine its levels for each of the areas as a first step toward designing interventions of self-management and empowerment programs to cope with the disease.
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PMID:Development and Validation of a Specific Self-Efficacy Scale in Adherence to a Gluten-Free Diet. 2961 46

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed medications for alleviating pain and inflammation but may cause gastrointestinal tract damage. Proton pump inhibitors (PPI) prevent NSAID-induced gastric damage but may aggravate intestinal damage via dysbiosis and intestinal permeability alteration. Currently, there is growing interest regarding the influence of potassium competitive acid blockers (PCAB) on NSAID-induced enteropathy. Here, we investigated the relative changes in indomethacin-induced enteropathy by combining indomethacin with pantoprazole (as PPI) or revaprazan (as PCAB). We examined intestinal permeability-related molecular changes in in vitro Caco-2 cell models and in an in vivo indomethacin-induced enteropathy rat model. Indomethacin alone or in combination with pantoprazole significantly increased relative lucifer yellow dye flux and decreased relative trans-epithelial electrical resistance and tight junction protein (TJP) expression compare to normal cells. In contrast, indomethacin combined with revaprazan significantly preserved TJPs compare to indomethacin-treated cells. MLC phosphorylation, Rho activation, and ERK activation responsible for TJP were significantly increased by indomethacin alone or a combination of indomethacin and pantoprazole but not by a combination of indomethacin and revaprazan. Intestinal damage scores significantly increased with indomethacin and pantoprazole combination but not with indomethacin and revaprazan combination. Indomethacin and pantoprazole combination significantly activated Rho-GTPase, p-MLC, and p-ERK but significantly decreased TJP expression. However, indomethacin and revaprazan combination significantly preserved TJPs and inactivated Rho-GTPase, MLC, and ERK. Hence, revaprazan rather than PPIs should be co-administered with NSAIDs to mitigate NSAID-induced intestinal damage.
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PMID:Revaprazan prevented indomethacin-induced intestinal damages by enhancing tight junction related mechanisms. 3307 11