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Differential changes in intrinsic innervation and interstitial cells of Cajal in small bowel atresia in newborns

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World Journal of Gastroenterology 2010年第45期16卷 5716-5721页

作者： Stefan Gfroerer Roman Metzger Henning Fiegel Priya Ramachandran Udo Rolle Department of Paediatric Surgery Johann Wolfgang Goethe-University Frankfurt/MTheodor-Stern-Kai 760590 Frankfurt/MGermany Department of Paediatric Surgery University of Leipzig04103 LeipzigGermany Department of Pediatric Surgery Kanchi Kamakoti Childs Trust Hospital12-A ChennaiIndia

AIM: To investigate morphological changes of the enteric nervous system (ENS) and the interstitial cells of Cajal (ICCs) in small bowel ***: Resected small bowel specimens from affected patients (n = 7) were divided into three parts (proximal, atretic, distal). Standard histology and enzyme immunohistochemistry anti-S100, anti-protein gene product (PGP) 9.5, anti-neurofilament (NF), antic-kit-receptor (CD117) was carried out on conventional paraffin sections of the proximal and distal part. RESULTS: The neuronal and glial markers (PGP 9.5, NF, S-100) were expressed in hypertrophied ganglia and nerve fibres within the myenteric and submucosal plexuses. Furthermore, the submucous plexus contained typical giant ganglia. The innervation pattern of the proximal bowel resembled intestinal neuronal dysplasia. The density of myenteric ICCs was clearly reduced in the proximal bowel, whereas a moderate number of muscular ICCs were found. The anti-CD117 immunore- action revealed additional numerous mast cells. The distal bowel demonstrated normal morphology and density of the ENS, the ICCs and the mast ***: The proximal and distal bowel in small bowel atresia revealed clear changes in morphology and density of the ENS and ICCs.

关键词： Small bowel atresia Enteric nervous system Gastrointestinal motility interstitial cells of Cajal

Microfluidic three-dimensional biomimetic tumor model for studying breast cancer cell migration and invasion in the presence of interstitial flow

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Chinese Chemical Letters 2019年第5期30卷 1038-1042页

作者： Chao Song Dan Gao Tianying Yuan Yongli Chen Liping Liu Xiaowu Chen Yuyang jiang State Key Laboratory of Chemical Oncogenomics.The Graduate School at Shenzhen Tsinghua UniversityShenzhen 518055China Key Laboratory of Metabolomics at Shenzhen Shenzhen 518055China Department of Hepatobiliary and Pancreatic Surgery Shenzhen People's HospitalSecond Clinical Medical College of Jinan UniversityShenzhen 518000China Shenzhen Kivita Innovative Drug Discovery Institute Shenzhen 518110China

Cell migration and invasion are critical steps in cancer metastasis,which are the major cause of death in cancer ***-associated macrophages(TAMs)and interstitial flow(IF)are two important biochemical and biomechanical cues in tumor microenvironment,play essential roles in tumor ***,their combined effects on tumor cell migration and invasion as well as molecular mechanism remains largely *** this work,we developed a microfluidic-based 3 D breast cancer model by co-culturing tumor aggregates,macrophages,monocytes and endothelial cells within 3 D extracellular matrix in the presence of IF to study tumor cell migration and *** the established platform,we can precisely control the parameters related to tumor microenvironment and observe cellular responses and interactions in *** co-culture of U937 with human umbilical vein endothelial cells(HUVECs)or MDA-MB-231 cells and tri-culture of U937 with HUVECs and MDA-MB-231 cells,we found that mesenchymal-like MDA-MB-231 aggregates activated the monocytes to TAM-like phenotype ***-MB-231 cells and IF simultaneously enhanced the macrophages activation by the stimulation of colony-stimulating factor 1(CSF-1).The activated macrophages and IF further promoted vascular sprouting via vascular endothelial growth factor(VEGFα)signal and tumor cell *** is the first attempt to study the interaction between macrophages and breast cancer cells under IF *** together,our results provide a new insight to reveal the important physiological and pathological processes of macrophages-tumor ***,our established platform with a more mimetic 3 D breast cancer model has the potential for drug screening with more accurate results.

关键词： Microfluidics Breast cancer Tumor microenvironment Cell migration and invasion interstitial flow

Effects of Lizhong Tang on cultured mouse small intestine interstitial cells of Cajal

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World Journal of Gastroenterology 2013年第14期19卷 2249-2255页

作者： Min Woo Hwang Jung Nam Kim Ho Jun Song Bora Lim Young Kyu Kwon Byung Joo Kim Department of Sasang Constitutional Medicine College of Korean MedicineKyung-hee University School of Korean Medicine Pusan National University

AIM:To investigate the effects of Lizhong Tang,an herbal product used in traditional Chinese medicine,on mouse small intestine interstitial cells of Cajal(ICCs).METHODS:Enzymatic digestions were used to dissociate ICCs from mouse small intestine *** ICCs were morphologically distinct from other cell types in culture and were identified using phase contrast microscopy after verification with anti c-kit antibody.A whole-cell patch-clamp configuration was used to record potentials(current clamp) from cultured *** of the experiments were performed at 30-32 ℃.RESULTS:ICCs generated pacemaker potentials,and Lizhong Tang produced membrane depolarization in current-clamp *** application of flufenamic acid(a nonselective cation channel blocker) abolished the generation of pacemaker potentials by Lizhong *** with thapsigargin(a Ca 2+-ATPase inhibi-tor in the endoplasmic reticulum) also abolished the generation of pacemaker potentials by Lizhong ***,pacemaker potentials were completely abolished in the presence of an external Ca 2+-free solution,and under this condition,Lizhong Tang induced membrane ***,When GDPβ-S(1 mmol/L) was in the pipette solution,Lizhong Tang still induced membrane *** addition,membrane depolarizations were not inhibited by chelerythrine or calphostin C,which are protein kinase C inhibitors,but were inhibited by U-73122,an active phospholipase C ***:These results suggest that Lizhong Tang might affect gastrointestinal motility by modulating pacemaker activity in interstitial cells of Cajal.

关键词： interstitial cells of Cajal Lizhong Tang Motility Gastrointestinal tract Whole-cell patch clamp configuration

A new endoscopic ultrasonography image processing method to evaluate the prognosis for pancreatic cancer treated with interstitial brachytherapy

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World Journal of Gastroenterology 2013年第38期19卷 6479-6484页

作者： Wei Xu Yan Liu Zheng Lu Zhen-Dong Jin Yu-Hong Hu Jian-Guo Yu Zhao-Shen Li Department of Gastroenterology Changhai HospitalSecond Military Medical University Department of Gastroenterology 307 Hospital of the Chinese People’s Liberation Army Department of Electronic Engineering Information Science and Engineering SchoolFudan University

AIM:To develop a fuzzy classification method to score the texture features of pancreatic cancer in endoscopic ultrasonography(EUS)images and evaluate its utility in making prognosis judgments for patients with unresectable pancreatic cancer treated by EUS-guided interstitial ***:EUS images from our retrospective database were *** regions of interest were drawn,and texture features were extracted,selected,and scored with a fuzzy classification method using a C++***,patients with unresectable pancreatic cancer were enrolled to receive EUS-guided iodine 125 radioactive seed *** fuzzy classification scores,tumor volumes,and carbohydrate antigen 199(CA199)levels before and after the brachytherapy were *** association between the changes in these parameters and overall survival was analyzed ***:EUS images of 153 patients with pancreatic cancer and 63 non-cancer patients were analyzed.A total of 25 consecutive patients were enrolled,and they tolerated the brachytherapy well without any *** was a correlation between the change in the fuzzy classification score and overall survival(Spearman test,r=0.616,P=0.001),whereas no correlation was found to be significant between the change in tumor volume(P=0.663),CA199 level(P=0.659),and overall *** were 15 patients with a decrease in their fuzzy classification score after brachytherapy,whereas the fuzzy classification score increased in another 10 *** was a significant difference in overall survival between the two groups(67 d vs 151 d,P=0.001),but not in the change of tumor volume and CA199 ***:Using the fuzzy classification method to analyze EUS images of pancreatic cancer is feasible,and the method can be used to make prognosis judgments for patients with unresectable pancreatic cancer treated by interstitial brachytherapy.

关键词： Digital image processing Fuzzy classification Endoscopic ultrasonography Pancreatic cancer interstitial brachytherapy Prognosis

Disruption of interstitial cells of Cajal networks after massive small bowel resection

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World Journal of Gastroenterology 2013年第22期19卷 3415-3422页

作者： Jie Chen Lei Du Yong-Tao Xiao Wei Cai Department of Pediatric Surgery Xin Hua Hospital Shanghai Jiaotong University School of Medicine Department of Pediatric Surgery School of Medicine Affiliated Hospital of Nantong University Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition Shanghai Institute of Pediatric Research Shanghai Jiaotong University

AIM: To investigate the disruptions of interstitial cells of Cajal (ICC) in the remaining bowel in rats after massive small bowel resection (mSBR). METHODS: Thirty male Sprague-Dawley rats fitting entry criteria were divided randomly into three experimental groups (n = 10 each): Group A rats underwent bowel transection and re-anastomosis (sham) and tissue samples were harvested at day 7 post-surgery. Group B and C rats underwent 80% small bowel resection with tissue harvested from Group B rats at day 7 post-surgery, and from Group C rats at day 14 postsurgery. The distribution of ICC at the site of the resid-ual small bowel was evaluated by immunohistochemical analysis of small intestine samples. The ultrastructural changes of ICC in the remnant ileum of model rats 7 and 14 d after mSBR were analyzed by transmission electron microscopy. Intracellular recordings of slow wave oscillations were used to evaluate electrical pacemaking. The protein expression of c-kit, ICC phenotypic markers, and membrane-bound stem cell factor (mSCF) in intestinal smooth muscle of each group were detected by Western blotting. RESULTS: After mSBR, immunohistochemical analysis indicated that the number of c-kit-positive cells was dramatically decreased in Group B rats compared with sham tissues. Significant ultrastructural changes in ICC with associated smooth muscle hypertrophy were also observed. Disordered spontaneous rhythmic contractions with reduced amplitude (8.5 ± 1.4 mV vs 24.8 ± 1.3 mV, P = 0.037) and increased slow wave frequency (39.5 ± 2.1 cycles/min vs 33.0 ± 1.3 cycles/min, P = 0.044) were found in the residual intestinal smooth muscle 7 d post mSBR. The contractile function and electrical activity of intestinal circular smooth muscle returned to normal levels at 14 d post mSBR (amplitude, 14.9 ± 1.6 mV vs 24.8 ± 1.3 mV; frequency, 30.7 ± 1.7 cycles/min vs 33.0 ± 1.3 cycles/min). The expression of Mscf and c-kit protein was decreased at 7 d (P = 0.026), but gradually returne

关键词： interstitial cells of Cajal c-kit Slow wave Massive small bowel resection Intestinal dysfunction

Novel methionyl-tRNA synthetase gene variants/phenotypes in interstitial lung and liver disease: A case report and review of literature

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World Journal of Gastroenterology 2018年第36期24卷 4208-4216页

作者： Kuerbanjiang Abuduxikuer Jia-Yan Feng Yi Lu Xin-Bao Xie Lian Chen Jian-She Wang Department of Hepatology Children’s Hospital of Fudan University Department of Pathology Children’s Hospital of Fudan University Department of Pediatrics Jinshan Hospital of Fudan University

interstitial lung and liver disease(ILLD) is caused by biallelic mutations in the methionyl-tRNA synthetase(MARS) gene. To date, no genetic changes other than missense variants were reported in the literature. Here, we report a five-month old female infant with typical ILLD(failure to thrive, developmental delay, jaundice, diffuse interstitial lung disease, hepatomegaly with severe steatosis, anemia, and thrombocytosis) showing novel phenotypes such as kidney stones, acetabular dysplasia, prolonged fever, and extreme leukocytosis. Whole exome sequencing revealed a novel truncating variant(c.2158 C>T/***720 Stop) together with a novel tri-nucleotide insertion(c.893_894 insTCG that caused the insertion of an arginine at amino acid position 299) in the MARS gene.

关键词： Methionyl-tRNA synthetase Infant Kidney stone Hip dysplasia Leukocytosis interstitial lung and liver disease Methionyl-tRNA synthetase gene

Involvement of interstitial cells of Cajal in experimental severe acute pancreatitis in rats

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World Journal of Gastroenterology 2013年第14期19卷 2179-2186页

作者： Liang-Liang Shi Ming-Dong Liu Min Chen Xiao-Ping Zou Department of Gastroenterology Medical Schoolthe Affiliated Drum Tower Hospital of Nanjing University

AIM:To observe the changes in interstitial cells of Cajal(ICC) in rats with experimental severe acute pancreatitis(SAP).METHODS:A total of twenty-four SD rats were randomly divided into two groups(n = 12),namely the sham(S) group and the SAP group;the SAP rat model was established by retrograde injection of 5% sodium taurocholate(1.0 mL/kg) into the pancreatic ***-four hours later intestinal motility was assessed by testing small intestinal propulsion rate,and then the rats were *** pancreas and jejunum were resected and underwent routine pathologic *** staining was used to detect c-kit-positive cells in the *** of c-kit mRNA was detected by real-time polymerase chain reaction,and the expression of c-kit protein was evaluated by Western *** of ICC was evaluated by transmission electron ***:There was bleeding,necrosis and a largeamount of inflammatory cell infiltration in pancreatic tissue in the SAP group,while in jejunal tissue we observed a markedly denuded mucosal layer,loss of villous tissue and a slightly dilated muscular *** small intestinal propulsion rate was 68.66% ± 2.66% in the S group and 41.55% ± 3.85% in the SAP *** with the S group,the rate of the SAP group decreased *** density of c-kit-positive cells in the SAP group was significantly lower than in the S group;the respective mean densities were 88.47 ± 10.49 in the S group and 56.11 ± 7.09 in the SAP *** levels of c-kit protein and mRNA were 0.36 ± 0.04 and 1.29 ± 0.91 in the SAP group,respectively,which were significantly lower than those in the S group(0.53 ± 0.06,0.64 ± 0.33,respectively).In the SAP group,ICC profiles showed the same change tendency,such as vacuolation of mitochondria,irregular vacuoles and loosened desmosome-like ***:Decreased c-kit-positive cells and ultrastructural changes in ICC resulting from blockade of the c-kit signaling pathway

关键词： Severe acute pancreatitis c-kit interstitial cells of Cajal Real-time polymerase chain reaction Ultrastructure

Inhibition of pacemaker activity in interstitial cells of Cajal by LPS via NF-κB and MAP kinase

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World Journal of Gastroenterology 2013年第8期19卷 1210-1218页

作者： Dong Chuan Zuo Seok Choi Pawan Kumar Shahi Man Yoo Kim Chan Guk Park Young Dae Kim Jun Lee In Yeoup Chang Insuk So Jae Yeoul Jun Department of Physiology College of MedicineChosun UniversityGwangju 501-759South Korea Department of Internal Medicine College of MedicineChosun UniversityGwangju 501-759South Korea Department of Anatomy College of MedicineChosun UniversityGwangju 501-759South Korea Department of Physiology and Biophysics College of MedicineSeoul National UniversitySeoul 56-1South Korea

AIM:To investigate lipopolysaccharide(LPS) related signal transduction in interstitial cells of Cajal(ICCs) from mouse small ***:For this study,primary culture of ICCs was prepared from the small intestine of the *** was treated to the cells prior to measurement of the membrane currents by using whole-cell patch clamp *** was used to examine the expression of the proteins in ***:LPS suppressed the pacemaker currents of ICCs and this could be blocked by AH6809,a prostaglandin E2-EP2 receptor antagonist or NG-Nitro-Larginine Methyl Ester,an inhibitor of nitric oxide(NO) ***-like receptor 4,inducible NO synthase or cyclooxygenase-2 immunoreactivity by specific antibodies was detected on ***(antioxidant agent) had no action on LPS-induced action in *** actions were blocked by nuclear factor kB(NF-kB) inhibitor,actinomycin D(a gene transcription inhibitor),PD 98059(a p42/44 mitogen-activated protein kinases inhibitor) or SB 203580 [a p38 mitogen-activated protein kinases(MAPK) inhibitor].SB 203580 also blocked the prostaglandin E2-induced action on pacemaker currents in ICCs but not ***:LPS inhibit the pacemaker currents in ICCs via prostaglandin E2-and NO-dependent mechanism through toll-like receptor 4 and suggest that MAPK and NF-kB are implicated in these actions.

关键词： interstitial cells of Cajal Lipopolysaccharide Mitogen-activated protein kinases Nuclear factor kB Small intestine

Noninfectious interstitial lung disease during infliximab therapy:Case report and literature review

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World Journal of Gastroenterology 2013年第32期19卷 5377-5380页

作者： Roberta Caccaro Edoardo Savarino Renata D'Incà Giacomo Carlo Sturniolo Department of Surgical Oncological and Gastroenterological SciencesGastroenterology SectionUniversity of Padova

Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel ***,lung toxicity can be induced by conventional medications used to maintain remission,and similar evidence is also emerging for *** present the case of a young woman affected by colonic Crohn’s disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and *** was referred to our clinic with a severe relapse and was treated with infliximab,an antitumor necrosis factor α(TNF-α)antibody,to induce *** an initial benefit,with decreases in bowel movements,rectal bleeding and C-reactive protein levels,she experienced shortness of breath after the *** interstitial lung disease was *** mesalamine and infliximab were discontinued,and steroids were introduced with slow but progressive improvement of symptoms,radiology and functional *** represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung *** the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases,this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy.

关键词： interstitial lung disease Crohn’s disease Infliximab Mesalamine Drug-induced toxicity