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| 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 | Polycyclic aromatic hydrocarbons (PAHs) concentrations and related carcinogenic potencies in soil at a semi-add region of India 显示文摘 | Masih A Taneja A | 2006 | Chemosphere2006，65，3： | 1 |
| 3 | Energy Consumption, Real Income and Temporal Causality: Results from a Multi-Country Study Based on Cointegrafion and Error-Correction Modeling Techniques显示文摘 | A M M Masih R Masih | 1996 | Energy Economics1996，18，3： | 1 |
| 4 | Energy consumption and real income temporal causality, results for a multi-country study based on cointegration and error-correction tech- niques显示文摘 | MASIH A MASIH R | 1996 | Energy Economies1996，18，3： | 1 |
| 5 | Energy consumption,real income and temporal causality:results from a multi-country study based on cointegration and error-correction modelling techniques显示文摘 | Masih R | 1996 | Energy Economics1996，，18： | 1 |
| 6 | Concentrations, sources, and exposure profiles of polycyclic aromatic hydrocarbons (PAHs) in particu- late matter (PMlo) in the north central part of India显示文摘 | MASIH A SAINI R SINGHVI R | 2010 | Environmental monitoring and assessment2010，163，： | 1 |
| 7 | A Multivariate Cointegrated Modeling Approach in Testing Temporal Causality Between Energy Consumption,Real Income and Prices with an Application to Two Asian LDCs显示文摘 | MASIH R | 1998 | Applied Economics1998，3，10： | 1 |
| 8 | Effects of sweetpotato flour on quality of cookies 显示文摘 | Saeed S Ahmad M M Kausar H Parveen S Masih S Salam A | 2012 | Journal of Agricultural Research2012，50，4： | 1 |
| 9 | Energy Consumption, Real Income and Temporal Causality: Results from a Multi-country Study Based on Cointegration and Error- correction Modeling Techniques 显示文摘 | Masih A M M Masih R | 1996 | Energy Economics1996，，18： | 1 |
| 10 | Soft tissue Langerhans ' cell histiocytosis in an adult:a case presentation with flow cytometric analysis and literature review显示文摘 | aI-Abbadi M Masih A Braylan RC | | 0，，： | 1 |
| 11 | Energy consumption,real income and temporal causality:results from a multi-country study based on co-integration and error-correction modeling techniques显示文摘 | Masih A M Masih R | 1996 | Energy Economics1996，18，3： | 1 |
| 12 | Imaging of pigmented villonodular显示文摘 | Masih S Antebi A | | 0，，： | 1 |
| 13 | Energy consumption,real income and temporal causality:results from a mulli-country study based on cointegration and error-correction modeling techniques显示文摘 | MASIH A MASIH R | 1996 | Energy Economics1996，，： | 1 |
| 14 | Polycyclic aromatic hydrocarbons (PAHs) concentrations and related carcinogenic potencies in soil at a semi-arid region of India显示文摘 | Masih A Taneja A | 2006 | Chemosphere2006，65，3： | 1 |
| 15 | Energy consumption,real income and tempo-ral causality : results from a mulli-country study based on cointeration and error- correction modeling techniques 显示文摘 | Mash A Masih R | 1996 | EnergyEconomics1996，，： | 1 |
| 16 | Energy consumption, real income and tempo- ral cansality:Resuhs from a multi-country study based on cointe- gration and error-correction modeling techniques 显示文摘 | Masih A M Masih R | 1996 | Energy Eco- nomics1996，18，3： | 1 |
| 17 | On the Temporal Relationship between Energy Consumption, Real Income and Prices: Some New Evidence from Asian-Energy Dependent NICs Based on a Multivariate Co- integration Vector Error Correction Approach 显示文摘 | Masih A M M Masih R | 1997 | Journal of Policy Modeling1997，，19： | 1 |
| 18 | On the temporal causal relationship between energy consumption, real income, and prices, some new evidence from Asian-energy dependent NICs Based on a multivariate cointegration vector error-correction approach 显示文摘 | Masih A M M Masih R | 1997 | Journal of Policy Modeling1997，19，： | 1 |
| 19 | Energy consumption,real incomeand temporal causality : results from a multi - country studybased on cointegration and error - correction modelling tech-niques 显示文摘 | MASIH A M M MASIH R | 1996 | Energy Economics1996，18，3： | 1 |
| 20 | Are Asian stock market fluctuations due mainly to intra - regional contagion effects? evidence based on Asian emerging stock markets显示文摘 | MASIH A M M MASIH R | 1999 | Pacific - Basin Finance Journal1999，，7： | 1 |
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