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| 1 | Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia显示文摘AIM:To determine the expression of neurokinin-1receptor(NK-1R),phosphorylated epidermal growth factor receptor(p EGFR),cyclooxygenase-2(Cox-2),and vitamin D receptor(VDR)in normal,inflammatory bowel disease(IBD),and colorectal neoplasia tissues from Puerto Ricans.METHODS:Tissues from patients with IBD,colitisassociated colorectal cancer(CAC),sporadic dysplasia,and sporadic colorectal cancer(CRC),as well as normal controls,were identified at several centers in Puerto Rico.Archival formalin-fixed,paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R,p EGFR,Cox-2,and VDR.Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a4-point scale that assessed intensity of staining.Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia,in addition to the areas of cancer,within each tissue.Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test.The mean scores for normal tissues and tissues with IBD,dysplasia,CRC,and CAC were calculatedand statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test.Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient.Data are presented as mean±SE.RESULTS:On average,patients with IBD were younger(34.60±5.81)than normal(63.20±6.13,P<0.01),sporadic dysplasia(68.80±4.42,P<0.01),sporadic cancer(74.80±4.91,P<0.001),and CAC(57.50±5.11,P<0.05)patients.NK-1R in cancer tissue(sporadic CRC,1.73±0.34;CAC,1.57±0.53)and sporadic dysplasia(2.00±0.45)were higher than in normal tissues(0.73±0.19).p EGFR was significantly increased in sporadic CRC(1.53±0.43)and CAC(2.25±0.47)when compared to normal tissue(0.07±0.25,P<0.05,P<0.001,respectively).Cox-2 was significantly increased in sporadic colorectal cancer(2.20±0.23 vs 0.80±0.37 for normal tissues,P<0.05).In comparison to normal(2.80±0.13)and CAC(2.50±0.33)tissues,VDR was significantly decreased in sporadic dysplasia(0.00±0.00,P<0.001 vs normal,P<0.001 vs CAC)and sporadic CRC(0.47±0.23,P<0.001 vs normal,P<0.001 vs CAC).VDR levels negatively correlated with NK-1R(r=-0.48)and p EGFR(r=-0.56)in normal,IBD,sporadic dysplasia and sporadic CRC tissue,but not in CAC.CONCLUSION:Immunohistochemical NK-1R and p EGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia.VDR immunoreactivity can distinguish CAC from sporadic cancer. | Raymond A Isidro Myrella L Cruz Angel A Isidro Axel Baez Axel Arroyo William A González-Marqués Carmen González-Keelan Esther A Torres Caroline B Appleyard | 2015 | World Journal of Gastroenterology2015，21，6： | 7 |
| 2 | Serum vitamin D and colonic vitamin D receptor in inflammatory bowel disease显示文摘AIM: To determine serum vitamin D levels and colonic vitamin D receptor(VDR) expression in inflammatory bowel disease(IBD) and non-IBD patients and correlate these with histopathology.METHODS: Puerto Rican IBD(n = 10) and non-IBD(n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire and provided a serum sample and a colonic biopsy of normal-appearing mucosa. For IBD patients, an additional biopsy was collected from visually diseased mucosa. Serum vitamin D levels were measured by ultra-performance liquid chromatography and mass spectrometry. Hematoxylin and eosin stained tissue sections from colonic biopsies were classified histologically as normal or colitis(active/inactive), and scored for the degree of inflammation present(0-3, inactive/absent to severe). Tissue sections from colonic biopsies were also stained by immunohistochemistry for VDR, for which representative diagnostic areas were photographed and scored for staining intensity using a 4-point scale.RESULTS: The IBD cohort was significantly younger(40.40 ± 5.27, P < 0.05) than the non-IBD cohort(56.70 ± 1.64) with a higher prevalence of vitamin D deficiency(40% vs 20%, respectively) and insufficiency(70% vs 50%, respectively). Histologic inflammation was significantly higher in visually diseased mucosa from IBD patients(1.95 ± 0.25) than in normalappearing mucosa from control patients(0.25 ± 0.08, P < 0.01) and from IBD patients(0.65 ± 0.36, P < 0.05) and correlated inversely with VDR expression in visually diseased colonic tissue from IBD patients(r =-0.44, P < 0.05) and from IBD patients with Crohn's disease(r =-0.69, P < 0.05), but not in normal-appearing colonic tissue from control patients or IBD patients. Control and IBD patient serum vitamin D levels correlated positively with VDR expression in normal colon from control and IBD patients(r = 0.38, P < 0.05) and with patient age(r = 0.54, P < 0.01). CONCLUSION: Levels of serum vitamin D correlate positively with colonic VDR expression in visually normal mucosa whereas inflammation correlates negatively with colonic VDR expression in visually diseased mucosa in Puerto Rican patients. | Yamilka Abreu-Delgado Raymond A Isidro Esther A Torres Alexandra González Myrella L Cruz Angel A Isidro Carmen I González-Keelan Priscilla Medero Caroline B Appleyard | 2016 | World Journal of Gastroenterology2016，22，13： | 5 |
| 3 | Erlotinib inhibits progression to dysplasia in a colitis-associated colon cancer model显示文摘AIM:To investigate the role of epidermal growth factor receptor(EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib.METHODS:Sprague-Dawley rats received trinitrobenzene sulfonic acid(TNBS;30 mg in 50% ethanol,ic),followed 6 wk later by reactivation with TNBS(5 mg/kg,iv) for 3 d.To induce colitis-associated dysplasia,rats then received TNBS(iv) twice a week for 10 wk.One group received erlotinib(10 mg/kg,ip) for 1 wk before the start of the reactivation of the colitis and 2 wk after(21 d);the rest received the vehicle.After rats were euthanized,the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1/2 and c-Myc.RESULTS:Ninety percent of the vehicle-treated animals had dysplasia in any region of the colon.Erlotinib-treated animals had a significant decrease in the incidence of dysplasia compared to vehicle-treated animals in all regions of the colon(50.00% ± 11.47% vs 90.00% ± 10.00% in proximal,P < 0.05;15.00% ± 8.19% vs 50.00% ± 16.67% in mid,P < 0.05;and 20.00% ± 9.17% vs 70.00% ± 15.28% in distal,P < 0.01).Erlotinib-treated animals also had reduced cell proliferation,reduced active Erk1/2,and reduced c-Myc in colon epithelium compared with the vehicle-treated animals.In vitro,erlotinib treatment was shown to markedly decrease c-Myc and pErk1/2 levels in rat epithelial cells.Proliferation of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib(P < 0.05).CONCLUSION:Erlotinib can decrease the development of colitis-associated dysplasia,suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis. | Beatriz Pagán Angel A Isidro Myrella L Cruz Domenico Coppola Caroline B Appleyard | 2011 | World Journal of Gastroenterology2011，17，44： | 1 |
| 4 | 显示文摘 | Appleyard S P Rand B | 2002 | Carbon2002，40，： | 1 |
| 5 | Prefarrowing behaviour distinguishes piglet-savaging gilts from non-savaging gilts显示文摘 | Appleyard S J Hall A D Lawrence A B | 2000 | Proceedings of the 34th ISAE2000，，： | 1 |
| 6 | The stabilisa- tion of carbon fibres studied by micro-thermal analysis 显示文摘 | C Blanco S Lu S P Appleyard B Rand | 2003 | Carbon2003，41，： | 1 |
| 7 | The Urban Form and Climate Change Gamble显示文摘 | Frank L S Kavage B Appleyard | 2007 | Planning2007，8，： | 1 |
| 8 | Population structure of yellowfin tuna (Thunnus albacares) in the western Pacific Ocean,inferred from microsatellite loci显示文摘 | APPLEYARD S A GREWE P M INNES B H | | 0，，02： | 1 |
| 9 | Shoulder pain in elite swimmers:primarily due to swim volume induced supraspinatus tendinopathy显示文摘 | Sein ML Walton J Linklater J Appleyard R Kirkbride B Kuah D | | 0，，： | 1 |
| 10 | When more is not better: the role of cumulative risk in child behavior outcomes 显示文摘 | Appleyard K Egeland B van Dulmen MHM | 2004 | J Child Psychol Psychiatry2004，46，3： | 1 |
| 11 | Toward an Urban Design Manifesto显示文摘 | APPLEYARD D ALLAN B J | 1987 | Journal of the American Planning Association1987，，1： | 1 |
| 12 | The stabilization of carbon fibers studied by micro-thermal analysis显示文摘 | Blanco C Lu S Appleyard SP Rand B | 2003 | Carbon2003，，41： | 1 |
| 13 | The urban form and climate change gamble 显示文摘 | FRANK L D KAVAGE S APPLEYARD B | 2007 | Planning2007，73，8： | 1 |
| 14 | Experi- mental iratestinal endometriosis is characterized by increased lev- els of soluble TNFRSF1B and downregulation of Tnfrsfl a and Tn- frsfl b gene expression 显示文摘 | Rojas-Cartagena C Appleyard C B Santiago O I | 2005 | Biology of Reproduction2005，73，6： | 1 |
| 15 | Study of carbon fibers and carbon carbon composites by scanning thermal microscopy显示文摘 | Blanco C Appleyard S P Rand B | 2002 | Journal of Microscopy2002，205，1： | 1 |
| 16 | Prevalence and causes of visual impairment and blindness among 9980 Scandinavian adults显示文摘 | Helena Buch Troels Vinding Morten la Cour Merete Appleyard Gorm B Jensen Niels Vesti Nielsen | 2004 | Ophthalmology2004，，1： | 1 |
| 17 | Toward An Urban Design Manifesto显示文摘 | Appleyard Donald and Allan B Jacobs | 1987 | Journal of the American Planning Association1987，53，1： | 1 |
| 18 | When moreis not better: The role of cumulative risk in child behavioroutcomes显示文摘 | Appleyard K Egeland B Dulmen MHM | 2005 | Journal of Child Psychology and Psychia-try2005，46，3： | 1 |
| 19 | Population structure of yellowfin tuna (Thunnus albacores) in the western Pacific Ocean, inferred from microsatellite loci 显示文摘 | APPLEYARD S A GREWE P M INNES B H | 2001 | Marine Biology2001，139，2： | 1 |
| 20 | Genetic structures of Haliotis rubra and Haliotis conicorpora populations using microsatellite markers and mtDNA-RFLP analysis显示文摘 | LI Z B APPLEYARD S A ELLIOT T N G | 2005 | Marine Freshwater Research2005，，9： | 1 |
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