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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 | 显示文摘 | Meleti Z Shapiro IM Adams CS | 2000 | Bone2000，27，： | 1 |
| 3 | 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 |
| 4 | Matrix regulation of skeletal cell apoptosis III: mechanism of ion pair-induced apoptosis 显示文摘 | Saunders R Szymczyk KH Shapiro IM | 2007 | J Cell Biochem2007，100，3： | 1 |
| 5 | RGDS peptides immobilized on titanium alloy stimulatebone cell attachment, differentiation and conferresistance to apoptosis显示文摘 | SECCHI A G GRIGORIOU V SHAPIRO IM | 2007 | J Biomed Mater Res A2007，83，3： | 1 |
| 6 | Low - level methylmercury exposure causes human T - cells to undergo apoptosis: evidence of mitochondrial dysfunction显示文摘 | Shenker BJ Guo TL Shapiro IM | 1998 | Environ Res1998，77，2： | 1 |
| 7 | Stem cell regeneration of the nucleus pulposus显示文摘 | Risbud MV Shapiro IM Vaccaro AR | 2004 | Spine J2004，4，6： | 1 |
| 8 | 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 |
| 9 | Boning up on autophagy:the role of autophagy in skeletal biology显示文摘 | Shapiro IM Layfield R Lotz M | 2014 | Autophagy2014，10，1： | 1 |
| 10 | HIF-I regu- lation of chondrocyte apoptosis induction of the autophagic pathway 显示文摘 | Bohensky J Shapiro IM Leshinsky S | 2007 | Autophagy2007，3，3： | 1 |
| 11 | Fate of the hypertrophic chondrocyte: microenvironmental perspectives on apoptosis and survival in the epiphyseal growth plate显示文摘 | Shapiro IM Adams CS Freeman T Srinivas V | 2005 | Birth Defects Res C Embryo Today2005，75，4： | 1 |
| 12 | Primary Carcinoid Tumor of the Parotid gland:a Case Report and Review of the Literature显示文摘 | Modlin IM Shapiro MD Kidd M | 2006 | Ear Nose Throat J2006，85，8： | 1 |
| 13 | HIF-1 regulation of chondrocyte apoptosis, induction of the autophagic pathway 显示文摘 | Bohensky J Shapiro IM Leshinsky S | 2007 | Autophagy2007，3，3： | 1 |
| 14 | HIF-1 regulation of chondrocyte apoptosis: induction of the autophagic path- way 显示文摘 | Bohensky J Shapiro IM Leshinsky S | 2007 | Autophagy2007，3，3： | 1 |
| 15 | RGDS peptides immobilized on titanium alloy stimulate bone cell attachment,differentiation and confer resistance to apoptosis显示文摘 | Secchi AG Grigoriou V Shapiro IM | 2007 | J Biomed Mater Res A2007，83，3： | 1 |
| 16 | Role of Cytokines in Intervertebral Disc De- generation :Pain and Disc-content 显示文摘 | Risbud MV Shapiro IM | 2014 | Nat Rev Rheumatol2014，10，1： | 1 |
| 17 | Akt-1 mediates survival of chondrocytesfrom endoplasmic reticulum-induced stress 显示文摘 | Price J Zaidi A K Bohensky J Srinivas V Shapiro IM Ali H | 2010 | J CellPhysiol2010，222，： | 1 |
| 18 | Autophagy: a new phase in the maturation of growth plate chondrocytes is regulated by HIF, mTOR and AMP kinase 显示文摘 | Srinivas V Bohensky J Shapiro IM | 2009 | Cells Tissues Organs2009，189，14： | 1 |
| 19 | Extracellular phosphate ions cause apoptosis of terminally differentiated epiphyseal chondrocytes 显示文摘 | MANSFIELD K RAJPUROHIT R SHAPIRO IM | 1999 | J Cell Physiol1999，179，3： | 1 |
| 20 | Role of cytokines in intervertebral disc degeneration: pain and disc content 显示文摘 | Risbud MV Shapiro IM | 2014 | Nat Rev Rheumatol2014，10，1： | 1 |
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