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Crosstalk between tumor cells and microenvironment via Wnt pathway in colorectal cancer dissemination

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World Journal of Gastroenterology 2008年第12期14卷 1823-1827页

作者： Dan Huang, Xiang Du, department of Pathology, Cancer hospital of{2. department of Oncology, shanghai Medical College,{2., shanghai 200032, china department of Pathology Cancer Hospital Fudan University Shanghai 200032 China.

Invasion and metastasis are the deadly face of malignant tumors. Considering the high rate of incidence and mortality of colorectal cancer, it is critical to determine the mechanisms of its dissemination. In the parallel investigation of the invasive front and tumor center area of colorectal cancer (CRC), observation of heterogeneous β-catenin distribution and epithelial-mesenchymal transition (EMT) at the invasive front suggested that there might be a crosstalk between tumor cells and the tumor microenvironment. Wnt signaling pathway is also involved in the cancer progression due to its key role in CRC tumorigenesis. Moreover, in recent years, there is increasing evidence that the regulators of microenvironment, including extracellular matrix, growth factors and inflammatory factors, are associated with the activation of Wnt pathway and the mobility of tumor cells. In this review, we will try to explain how these molecules trigger metastasis via the Wnt pathway.

关键词： Invasion Microenvironment Colorectalcancer Epithelial-mesenchymal transition Wnt β-catenin

Increased Connexin 43 Expression Improves the Migratory and Proliferative Ability of H9c2.Cells by Wnt-3a Overexpression

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Acta Biochimica et Biophysica Sinica 2007年第6期39卷 391-398页

作者： Xiaoyu LIU~(1#), Wen LIU~(1#), Ling YANG~(1#), Beili XIA~1, Jinyan LI~1, Ji ZUO~(1*), and Xiaotian LI~(2.) 1 department of Celhdar and Genetic medicine, {2. Medical College. fudan university, shanghai 200032, china 2.The Obstetrics and Gynecology hospital of the Medical Center of fudan university, shanghai 200032. china department of Cellular and Genetic medicine Shanghai Medical College Fudan UniversityShanghai 200032 China The Obstetrics and Gynecology hospital of the Medical Center of fudan university{2. 200032 China

The change of connexin 43 （Cx43） expression and the biological behaviors of Cx43 in rat heart cell line H9c2. expressing Wnt-3a （wingless-type MMTV integration site family, member 3A） were evaluated in the present study. Plasmid pcDNA3.1/Wnt-3a was constructed and transferred into H9c2.cells. The cell model Wnt-3a+-H9c2.steadily expressing Wnt-3a was obtained. Compared with H9c2.and pcDNA3.1-H9c2.cells, the expression of Cx43 in Wnt-3a+-H9c2.cells was clearly increased, the proliferation of Wnt-3a+-H9c2.cells was significantly changed, and cell migration abilities were also improved （P2.and pcDNA3.1-H9c2.cells, the G2.hase of the cell cycle increased by 11% in Wnt-3a+-H9c2.cells. Thus, Wnt-3a overexpression is associated with an increase in Cx43 expression and altered migratory and proliferative activity in H9c2.cells. Cx43 might be one of the downstream target genes regulated by Wnt-3a.

关键词： Wnt-3a Cx43 H9c2.cell line cell migration

XbaⅠpolymorphisms of apolipoprotein B gene:Another risk factor of gallstone formation after radical gastrectomy

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World Journal of Gastroenterology 2010年第20期16卷 2549-2553页

作者： Feng-Lin Liu,Wen-Bin Lu,Wei-Xin Niu,department of General Surgery,zhongshan {2.,fudan university,shanghai 200032,china department of General Surgery Zhongshan Hospital Fudan University #180 Fenglin Road Shanghai 200032 China.

AIM:To prospectively investigate the association between the XbaⅠpolymorphisms of apolipoprotein B (APOB)gene and gallstone formation following ***:The study was conducted between January 2.05 and December 2.06.A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaⅠpolymorphisms of APOB gene(X+X-group,n=2. and X-X-group,n =162.and *** XbaⅠpolymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCRRFLP).RESULTS:The incidence of gallstone was significantly higher in the X + X-group than in the X-X-group[54.2. vs 9.3%,RR=5.85(2.2.-15.32.,P2.1.12.vs 3.48±0.88,P=0.004 before surgery and 3.88±1.09 vs 3.40±0.86,P=0.008 after surgery).LDL was 2.2.±0.96 vs 1.89±0.84(P =0.042.before surgery and 2.09±0.95 vs 1.72.0.85 (P=0.02.)after surgery in the two *** relationship was found between XbaⅠpolymorphisms and gallbladder ***:In Chinese patients after radical gastrectomy,X + allele of APOB gene is another risk factor for the development of gallstone besides the gallbladder motility disorder after surgery.

关键词： Gastric cancer Gastrectomy Gallstone Apolipoprotein B gene Polymorphism

The expression of core fucosylated E-cadherin in cancer cells and lung cancer patients: prognostic implications

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Cell Research 2004年第5期14卷 423-433页

作者： Fei GENG1, Bi Zhi SHI , Yun Feng YUAN2. Xing Zhong WU1* 1 1department of Biochemistry and Molecular Biology, fudan university Medical Center,{2., china 2.0} of Thoracic Surgery, zhongshan hospital, fudan university,{2., china department of Biochemistry and Molecular Biology Fudan University Medical Center Shanghai China department of Thoracic Surgery Zhongshan Hospital Fudan University Shanghai China

It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E- cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since α-1,6 Fucosyltransferase (α-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by α-1,6 FucT targeted RNAi and transfecting α-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E- cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after α-1,6 FucT over expression. Our data indicated that α-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asym- metry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.

关键词： Core fucosylated E-cadherin prognosis cancer metastasis RNA interference molecular modeling.

Downregulation of wild-type p53 protein by HER-2.neu mediated PI3K pathway activation in human breast cancer cells: its effect on cell proliferation and implication for therapy

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Cell Research 2004年第6期14卷 497-506页

作者： Li ZHENG, Jia Qiang REN, Hua LI, Zhao Lu KONG, Hong Guang ZHU department of Pathology, shanghai Medical College,{2., shanghai, 200032, china. Institute of Irradiation medicine,{2., shanghai, 200032, china department of Pathology Shanghai Medical College Fudan University Shanghai China Institute of Irradiation medicine Fudan University Shanghai China

Overexpression and activation of HER-2.neu (also known as c-erbB-2., a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy. Wild-type p53 is crucial in regulating cell growth and apoptosis and is found to be mutated or deleted in 60-70% of human cancers. And some cancers with a wild-type p53 do not have normal p53 function, suggesting that it is implicated in a complex process regulated by many factors. In the present study, we showed that the overexpression of HER-2.neu could decrease the amount of wild-type p53 protein via activating PI3K pathway, as well as inducing MDM2.nuclear translocation in MCF7 human breast cancer cells. Blockage of PI3K pathway with its specific inhibitor LY2.4002.caused Gl-S phase arrest, decreased cell growth rate and increased chemo- and radio-therapeutic sensitivity in MCF7 cells expressing wild-type p53. However, it did not increase the sensitivity to adriamycin in MDA-MB-453

关键词： HER-2.neu PI3K breast cancer p53 MDM2

Germline mutation analysis of hPMS2.gene in Chinese families with hereditary nonpolyposis colorectal cancer

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World Journal of Gastroenterology 2010年第30期16卷 3847-3852页

作者： Xia Sheng, Xiao-Yan Zhou, Xiang Du, Tai-Ming Zhang, WeiQi Sheng, Da-Ren Shi, department of Pathology, shanghai Cancer Center,{2., shanghai 200032, china department of Oncology, shanghai Medical College,{2., shanghai 200032, china Heng-Hua Zhou, department of Pathology, shanghai Ninth People’s {12. Affi liated to shanghai Jiao Tong university School of medicine, shanghai 2.0011, china San-Jun Cai, department of Abdominal Surgery, Cancer Center,{2., shanghai 200032, china department of Pathology Shanghai Cancer Center Fudan University Shanghai 200032 China.

AIM: To study the germline mutation of hPMS2.gene in 2. unrelated Chinese hereditary nonpolyposis colorectal cancer (HNPCC) probands and to fulfill the screening strategy for HNPCC in Chinese. METHODS: Genomic DNA was extracted from the peripheral blood. To avoid the interference of pseudogene in detection of the remaining 11 exons (exon 1-5, 9, 11-15), long-range polymerase chain reaction (PCR) was conducted to amplify the complete coding region of hPMS2.gene firstly. Then 1/8 of the PCR productswere used as template to amplify the individual exon respectively and DNA sequencing was done. Direct DNA sequencing of the conventional PCR products of exon 6, 7, 8 and 10 of hPMS2.gene was performed. The same analysis was made in 130 healthy persons without family histories of HNPCC to further investigate the pathological effects of the detected missense mutation. RESULTS: One HNPCC proband fulf illed Bethesda guidelines and was found to carry the germline mutation of hPMS2.gene, which has not been reported in Chinese HNPCC families. It was a missense mutation at c.1532.>T of exon 11. It was detected in three controls as well with an occurrence rate of 2.3% (3/130). Since it could not be found in the PMS2.single nucleotide polymorphism (SNP) database, this missense mutation is a new SNP unreported up to date. Meanwhile, 2.0 reported SNPs of hPMS2.gene were detected in the 2. HNPCC probands. The 2.d and 5th exons were probably the hot SNP regions of hPMS2.gene in Chinese HNPCC families involving 53.1% of all reported SNP. CONCLUSION: The germline mutation of hPMS2.gene may be rare in Chinese HNPCC families. The 2.d and 5th exons are hot SNP regions of hPMS2.gene.

关键词： Hereditary nonpolyposis colorectal cancer hPMS2 Missense mutation Single nucleotide polymorphism Colorectal cancer

Effect of MePEG molecular weight and particle size on in vitro release of tumor necrosis factor-α-loaded nanoparticles

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Acta Pharmacologica Sinica 2005年第2期26卷 242-249页

作者： Chao FANG,Bin SHI,Yuan-ying PEI~2.department of Pharmaceutics,School of Pharmacy,fudan {2.,shanghai 200032,china department of Pharmaceutics School of Pharmacy Fudan University Shanghai China

Aim:To study the in vitro release of recombinant human tumor necrosis factor-alpha(rHuTNF-α)encapsulated in poly(methoxypolyethyleneglycol cyanoacry-late-co-n-hexadecyl cyanoacrylate)(PEG-PHDCA)nanoparticles,and investigatethe influence of methoxypolyethyleneglycol(MePEG)molecular weight and par-ticle ***:Three sizes(approximately 80,170,and 2.0 nm)of PEG-PHDCA nanoparticles loading rHuTNF-α were prepared at different MePEG mo-lecular weights(Mr=2.00,5000,and 10000)using the double emulsion *** in vitro rHuTNF-α release was studied in PBS and rat ***:Ahigher burst-release and cumulative-release rate were observed for nanoparticleswith higher MePEG molecular weight or smaller particle size.A decreased cu-mulative release of rHuTNF-α following the initial burst effect was found in PBS,while the particle sizes remained constant and MePEG *** contrast,inrat plasma,slowly increased cumulative-release profiles were obtained after theburst *** a 5-h incubation in rat plasma,more than 50% of the PEG-PHDCA nanoparticles ***:The MePEG molecular weightand particle size had an obvious influence on rHuTNF-α release,rHuTNF-αreleased from PEG-PHDCA nanoparticles in a diffusion-based pattern in PBS,but in a diffusion and erosion-controlled manner in rat plasma.

关键词： tumor necrosis factor-alpha stealth nanoparticles polyethylene glycols poly(methoxypolyethyleneglycol cyanoacrylate-con-hexadecyl cyanoacrylate)

Celiomesenteric trunk demonstrated by 3-dimensional contrast-enhanced magnetic resonance angiography

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Hepatobiliary & Pancreatic Diseases International 2005年第3期4卷 472-474页

作者： Jiang Lin Author Affiliations:department of Radiology, zhongshan hospital,{2., shanghai 200032, china (Lin J) department of Radiology Zhongshan Hospital Fudan University Shanghai 200032 China. linjiang@***

Celiomesenteric trunk is a rare vascular anomaly, which has significant clinical implications. 3-di-mensional contrast-enhanced magnetic resonance angiography (3D CE MRA) is a new imaging modality, non-invasive , fast and easy to perform. We describe a patient with a common celiomesenteric trunk demonstrated by 3D CE MRA. METHODS: A 45-year-old man was subjected to 3D CE MRA before transarterial chemoembolization (TACE) for hepatocellular carcinoma. The examination was performed on a 1.5T MR imager with a body coil. The contrast medium was gadopentetate dimeglumine. Source images from the hepatic arterial phase acquisition were reconstructed into MRA images. Intra-arterial digital subtraction angiography (DSA) during TACE was carried out 3 days after 3D CE MRA. RESULTS:On 3D CE MRA, a common trunk of the celiac and superior mesenteric artery was clearly depicted. The origin and course of the hepatic, splenic and superior mesenteric arteries were also visualized. These findings were confirmed by intra-arterial DSA. CONCLUSIONS: Celiomesenteric trunk can be well delineated by 3D CE MRA. The image is correlated precisely with that from DSA.

关键词： celiomesenteric trunk magnetic resonance angiography

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Distribution of nimodipine in brain following intranasal administration in rats

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Acta Pharmacologica Sinica 2004年第4期25卷 124-129页

作者： Qi-zhi ZHANG, Xin-guo JIANG2. Chun-hua WU department of Pharmaceutics, School ofPharmacy, fudan university,{2., china department of Pharmaceutics School of Pharmacy Fudan University 上海 200032

AIM: To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain. METHODS: NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (CSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed byHPLC. RESULTS: Oral systemic bioavailability of NM in rats was 1.17 %, nasal dosing improved bioavailibility to 67.4 %. Following intranasal administration, NM concentrations in olfactory bulb (OB) within 30 min post dose were found significant higher than in the other brain tissues. However, similar NM levels in different brain regions were observed after iv injection. AUC in CSF and OB from the nasal route was 1.2. and 1.39 fold compared with the iv route, respectively. The brain-to-plasma AUC ratios were significantly higher after nasal administration than after iv administration (P<0.01). CONCLUSION: Nasally administered NM could markedly improve the bioavailability and a fraction of the NM dose could be transported into brain via the olfactory pathway in rats.

关键词： intranasal administration nimodipine olfactory bulb olfactory pathways