|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Plecanatide-mediated activation of guanylate cyclase-C suppresses inflammation-induced colorectal carcinogenesis in Apc+/Min-FCCC mice显示文摘AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC) mice with dextran sodium sulfate(DSS)-induced inflammation. METHODS Inflammation driven colorectal carcinogenesis was induced in Apc^(+/Min-FCCC) mice by administering DSS in their drinking water. Mice were fed a diet supplemented with plecanatide(0-20 ppm) and its effect on the multiplicity of histopathologically confirmed polypoid,flat and indeterminate dysplasia was evaluated. Plecanatide-mediated activation of guanylate cyclase-C(GC-C) signaling was assessed in colon tissues by measuring cyclic guanosine monophosphate(cG MP) by ELISA, protein kinase G-II and vasodilator stimulated phosphoprotein by immunoblotting. Ki-67, c-myc and cyclin D1 were used as markers of proliferation. Cellular levels and localization of b-catenin in colon tissues were assessed by immunoblotting and immunohistochemistry, respectively. Uroguanylin(UG) and GC-C transcript levels were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR). A mouse cytokine array panel was used to detect cytokines in the supernatant of colon explant cultures. RESULTS Oral treatment of Apc^(+/Min-FCCC) mice with plecanatide produced a statistically significant reduction in the formation of inflammation-driven polypoid, flat and indeterminate dysplasias. This anti-carcinogenic activity of plecanatide was accompanied by activation of cG MP/GC-C signaling mediated inhibition of Wnt/b-catenin signaling and reduced proliferation. Plecanatide also decreased secretion of pro-inflammatory cytokines(IL-6, IL-1 TNF), chemokines(MIP-1, IP-10) and growth factors(GCSF and GMCSF) from colon explants derived from mice with acute DSS-induced inflammation. The effect of plecanatidemediated inhibition of inflammation/dysplasia on endogenous expression of UG and GC-C transcripts was measured in intestinal tissues. Although GC-C expression was not altered appreciably, a statistically significant increase in the level of UG transcripts was detected in the proximal small intestine and colon, potentially due to a reduction in intestinal inflammation and/or neoplasia. Taken together, these results suggest that reductions in endogenous UG, accompanied by dysregulation in GC-C signaling, may be an early event in inflammation-promoted colorectal neoplasia; an event that can potentially be ameliorated by prophylactic intervention with plecanatide.CONCLUSION This study provides the first evidence that orally administered plecanatide reduces the multiplicity of inflammation-driven colonic dysplasia in mice, demonstrating the utility for developing GC-C agonists as chemopreventive agents. | Wen-Chi L Chang Shet Masih Anusha Thadi Viren Patwa Apoorva Joshi Harry S Cooper Vaseem A Palejwala Margie L Clapper Kunwar Shailubhai | 2017 | World Journal of Gastrointestinal Pharmacology and Therapeutics2017，8，1： | 5 |
| 2 | Effects of high-protein/low-carbohydrate swine diets during the final finishing phase on pork muscle quality显示文摘 | Leheska J M Wulf D M Clapper J A Thaler R C Maddock R J | 2002 | Journal of Animal Science2002，80，1： | 1 |
| 3 | A red blood cell autoanti- body with mimicking anti-E specificity显示文摘 | Dwyre DM Clapper A Heintz M | 2004 | Transfusion2004，44，9： | 1 |
| 4 | Joint development of an environmentally acceptable ester based drilling fluid显示文摘 | Amin R A M Clapper D K Norfleet J E | | SPE0，，： | 1 |
| 5 | Effects of high-protein/low-carbohydrate swine diets during the final finishing phase on pork muscle quality显示文摘 | Leheska J M Wulf D M Clapper J A Thaler R C Maddock R J | 2002 | J Anim Sci2002，80，： | 1 |
| 6 | Aluminum Based HP WBM Successfully Replaces Oil Based Mud to Drill Exploratory 显示文摘 | Ramirez M A Clapper D K | | SPE0，，： | 1 |
| 7 | Plasma ghrelin concentrations of beef cattle consuming a similar amount of dietary energy supplied by different ingredients 显示文摘 | Wertz-Lutz A E Jennings J S Clapper J A | 2010 | J Anita Sci2010，88，7： | 1 |
| 8 | The Effect of Multiple Internal Reflections on the Densities of Halftone Prints on Paper显示文摘 | CLAPPER F R YULE J A C | 1953 | Opt Soc Am1953，43，7： | 1 |
| 9 | Influence of daily njections of porcine somatotropin on growth, puberty, and reproduction in gilts显示文摘 | Andres C J Green M L Clapper J A | 1991 | J Journal of Animal Science1991，69，9： | 1 |
| 10 | Prolonged, moderate nutrient restriction in beef cattle results in persistently elevated circulating ghrelin concentrations显示文摘 | Werta-Lutz A E Daniet J A Clapper J A | 2008 | Journal of Animal Science2008，86，： | 1 |
| 11 | The effect of multiple internal reflections on the densities of halftone prints on paper显示文摘 | Clapper F R Yule J A C | 1953 | Journal of the Optical Society of America1953，43，7： | 1 |
| 12 | The Effect of Multiple Inter-nal Reflections on the Densities of Halftone Prints on Paper 显示文摘 | CLAPPER F R YULE J A C | 1953 | Opt Soc Am1953，43，7： | 1 |
| 13 | Reducdon in age of puber- ty in gilts consuming MLT during decreasing or increasing daylength 显示文摘 | Diekman M A Clapper J A Green M L | 1991 | Jouranl of Animal Science1991，69，： | 1 |
| 14 | The effect of multiple internal reflections on the densities of halftone prints on paper显示文摘 | CLAPPER F R YULE J A C | 1953 | Journal of the Optical Society of America1953，43，7： | 1 |
| 15 | The Effect of Multiple In-ternal Reflections on the Densities of Halftone Prints onPaper显示文摘 | CLAPPER F R YULE J A C | 1953 | J Opt Soc Am1953，43，： | 1 |
| 16 | Prolonged, moderate nutrient restriction in beef cat- tle results in persistently elevated circulating ghre- lin concentrations 显示文摘 | Wertz - Lutz A E Daniel J A Clapper J A | 2007 | Journal of Animal Science2007，86，3： | 1 |
| 17 | Components of the porcine anterior pituitary insu- lin -like growth factor system throughout the estrous cycle显示文摘 | Clapper J Taylor A | 2011 | Domest Anim Endocrinol2011，40，2： | 1 |
| 18 | The Effect of Multiple internal Reflections on the Densities is Half-tone Prints on Paper显示文摘 | CLAPPER F R YULE J A C | 1953 | Opt Soc Am1953，43，： | 1 |
| 19 | Effect of Multiple Internal Reflections on the Densities of Halftone Prints on Paper显示文摘 | CLAPPER F R YULE J A C | 1953 | Opt Soc Am1953，43，： | 1 |
| 20 | The Effect of Multiple Internal Reflections on the Densities of Halftone Prints on Paper显示文摘 | CLAPPER F R YULE J A C | 1953 | J Opt Soc Am1953，43，： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员