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| 1 | CTGF, intestinal stellate cells and carcinoid fi brogenesis显示文摘AIM: To investigate the role of small intestinal carcinoid tumor-derived fibrotic mediators, TGFβ1 and CTGF, in the mediation of fi brosis via activation of an 'intestinal' stellate cell. METHODS: GI carcinoid tumors were collected for Q RT-PCR analysis of CTGF and TGFβ1. Markers of stellate cell desmoplasia were identified in peritoneal fibrosis by immunohistochemistry and stellate cells cultured from fresh resected fibrotic tissue. CTGF and TGFβ1 were evaluated using quantitative tissue array profi ling (AQUA analysis) in a GI carcinoid tissue microarray (TMA) with immunostaining and correlated with clinical and histologically documented fi brosis. Serum CTGF was analyzed using a sandwich ELISA assay. RESULTS: Message levels of both CTGF and TGFβ1 in SI carcinoid tumors were signifi cantly increased (> 2-fold, P < 0.05) versus normal mucosa and gastric (non-f ibrotic) carcinoids. Activated stellate cells and markers of stellate cell-mediated fi brosis (vimentin, desmin) were identifi ed in histological fibrosis. An intestinal stellate cell was immunocytochemically and biochemically characterized and its TGFβ1 (10-7M) initiated CTGF transcription response (> 3-fold, P < 0.05) demonstrated. In SI carcinoid tumor patients with documented fi brosis, TMA analysis demonstrated higher CTGF immunostaining (AQUA Score: 92 ± 8; P <0.05), as well as elevated TGFβ1 (90.6 ± 4.4, P < 0.05). Plasma CTGF (normal 12.5 ± 2.6 ng/mL) was increased in SI carcinoid tumor patients (31 ± 10 ng/mL, P < 0.05) compared to non-fi brotic GI carcinoids (< 15 ng/mL).CONCLUSION: SI carcinoid tumor fibrosis is a CTGF/ TGFβ1-mediated stellate cell-driven fibrotic response. The delineation of the biology of fibrosis will facilitate diagnosis and enable development of agents to obviate its local and systemic complications. | M Kidd IM Modlin MD Shapiro RL Camp SM Mane W Usinger JR Murren | 2007 | World Journal of Gastroenterology2007，13，39： | 5 |
| 2 | The diagnosis and management of adult intussusception显示文摘 | Begos DC Sandor A Modlin IM | 1997 | Am J Surg1997，173，1： | 1 |
| 3 | A 5-decade analysis of 13715 carcinoid tumors显示文摘 | Modlin IM Lye KD Kidd M | 2003 | Cancer2003，97，4： | 1 |
| 4 | An analysis of 8305 cases of carcinoid tumors显示文摘 | Modlin IM Sandor A | 1997 | Cancer1997，79，4： | 1 |
| 5 | Neuroendocrine tumors of the diffuse neuroendocrine system显示文摘 | Gustafsson BI Kidd M Modlin IM | 2008 | Curr Opin Oncol2008，20，1： | 1 |
| 6 | A 5-decade analysis of 13,715 carcinoid tumors 显示文摘 | Modlin IM Lye KD Kidd M | 2003 | Cancer2003，97，4： | 1 |
| 7 | Carcinoid tumors of the stomach显示文摘 | Modlin IM Lye KD Kidd M | 2003 | Surg Oncol2003，12，2： | 1 |
| 8 | Further delineation of the continuous human neoplastic enterochromaffin cell line,KRJ-I,and the inhibitory effects of lanreotide and rapamycin 显示文摘 | Kidd M Eick GN Modlin IM | 2007 | J Mol Endocrinol2007，38，： | 1 |
| 9 | An analysis of 8305 cases of carcinoid tumors 显示文摘 | Modlin IM Sandor A | 1997 | Cancer1997，79，4： | 1 |
| 10 | A 5-decade ananlysis of 13715 carcinoid tumors显示文摘 | Modlin IM lye KD Kidd M | 2003 | Cancer2003，97，： | 1 |
| 11 | Siegfried Oberndor- fer: origins and perspectives of carcinoid tumors 显示文摘 | Modlin IM Shapiro MD Kidd M | 2004 | Hum Pathol2004，35，12： | 1 |
| 12 | Changes in insulin resistance following bariatric surgery and the adipoinsular axis:role of the adipocytokines,leptin,adiponectin and resistin显示文摘 | Ballantyne GH Gumbs A Modlin IM | 2005 | Obes Stag2005，15，5： | 1 |
| 13 | Surgical triumvirate of Theodor Kocher,Harvey Cush-ing,and William Halsted显示文摘 | Modlin IM | 1998 | World J Surg1998，22，1： | 1 |
| 14 | Gastroesophageal reflux disease:then and now显示文摘 | Modlin IM Moss SF Kidd M | 2004 | J Clin Gastroenterol2004，38，5： | 1 |
| 15 | The adenoma to carcinoma Sequence显示文摘 | Tremey PR Ballantyne GH Modlin IM | 1990 | Gyeneolobetet1990，171，12： | 1 |
| 16 | Current status of gastroin-testinal carcinoids显示文摘 | Modlin IM Kidd M Latich I | 2005 | Gastroenterology2005，128，： | 1 |
| 17 | Gastroenteropan- creatic neuroendocrine tumours显示文摘 | Modlin IM Oberg K Chung DC | 2008 | Lancet 0ncol2008，9，1： | 1 |
| 18 | Diagnosis and management of non-erosive reflux disease-the Vevey NERD Consensus Group显示文摘 | Modlin IM Hunt RH Malfertheiner P | | 0，，2： | 1 |
| 19 | Current status of gastrointes- tinal carcinoids 显示文摘 | Modlin IM Kidd M Latich I t al | 2005 | Gastroenterology2005，125，6： | 1 |
| 20 | An analysis of rare carcinoid tumors:clarifying these clinical conundrums显示文摘 | Modlin IM Shapiro MD Kidd M | 2005 | World J Surg2005，29，1： | 1 |
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