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Effects of LY294002 on the invasiveness of human gastric cancer in vivo in nude mice

World Journal of Gastroenterology 2009年第40期15卷 5044-5052页

作者： Chun-Gen Xing Bao-Song Zhu Xiao-Qing Fan Hui-Hui Liu Xun Hou Kui Zhao Zheng-Hong Qin Department of General Surgery The Second Affiliated Hospital Soochow University Suzhou 215006 Jiangsu Province China Department of General Surgery The Second Hospital of Jiaxing City Jiaxing 314000 Jiangsu Province China Department of Neurology The Second Affiliated Hospital Soochow University Suzhou 215006 Jiangsu Province China Laboratory of Aging and Nervous Diseases Soochow University School of Medicine Suzhou 215123 Jiangsu Province China

AIM: To investigate the effects of class phosphatidy-linositol 3-kinase (PI3K) inhibitor LY294002 on the invasiveness and related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice. METHODS: Nude mice were randomly divided into model control groups and LY294002 treatment groups. On days 5, 10 and 15 after treatment, the inhibitory rate of tumor growth, pathological changes in tumor specimens, expression levels of matrix metalloproteinase (MMP)-2, MMP-9, CD34 [representing microvessel density (MVD)] and vascular endothelial growth factor (VEGF), as well as apoptosis indexes in tumor samples were ***: In this study, we showed that treatingthe tumors with LY294002 could significantly inhibit carcinoma growth by 11.3%, 29.4% and 36.7%, after 5, 10 and 15 d, respectively, compared to the control group. Hematoxylin & eosin staining indicated that the rate of inhibition increased progressively (23.51% ± 3.11%, 43.20% ± 3.27% and 63.28% ± 2.10% at 5, 10 and 15 d, respectively) along with apoptosis. The expression of MMP-2 was also downregulated (from 71.4% ± 1.6% to 47.9% ± 0.7%, 31.9% ± 0.9% and 7.9% ± 0.7%). The same effects were observed in MMP-9 protein expression (from 49.4% ± 1.5% to 36.9% ± 0.4%, 23.5% ± 0.9% and 7.7% ± 0.6%), the mean MVD (from 51.2% ± 3.1% to 41.9% ± 1.5%, 30.9% ± 1.7% and 14.9% ± 0.8%), and the expression of VEGF (from 47.2% ± 3.1% to 25.9% ± 0.5%, 18.6% ± 1.2% and 5.1% ± 0.9%) by immunohistochemical ***: The classPI3K inhibitor LY294002could inhibit the invasiveness of gastric cancer cells by downregulating the expression of MMP-2, MMP-9, and VEGF, and reducing MVD.

关键词： Phosphatidylinositol 3-kinase LY294002 Gastric cancer neoplasm invasiveness

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UROKINASE-TYPE PLASMINOGEN ACTIVATOR,ITS RECEPTOR AND INHIBITOR EXPRESSION IN HEPATOCELLULAR CARCINOMA RELATION TO CANCER invasiveness AND PROGNOSIS

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Chinese Journal of Cancer Research 1998年第4期10卷 36-39页

作者：郑起汤钊猷吴志全施达仁唐辉滨朱运松宋后燕 Department of General Surgery Shanghai 6th People Hospital Shanghai 200233 China Liver Cancer Institute Zhongshan Hospital Shanghai Medical UniversityShanghai China 200032 Department of General Surgery Shanghai 6th People Hospital600 Yishan Road Shanghai 200233 China

Objective: To study the relevance of uPA, uPAR and PAI 1 to hepatocellular carcinoma (HCC) Methods: The expression at protein level of uPA, uPAR and PAI 1 was determined in 48 cases of HCC and 12 cases of benign tumors of liver (as control) by immunohistochemistry Results: When compared to cancer adjacent liver tissue and the control, positive rate of immune staining for uPA, uPAR and PAI 1 on cell membrane were significantly higher in HCC cells ( P <0 05) Positive staining of uPA and uPAR was seen in 16 of 22 and 19 of 22 cases of HCC with invasion, respectively ( P <0 01 and P <0 001) In 8 of 8 cases with cancer embolus, and in 6 of 6 cases with lymph node metastasis was the expression of positive uPAR Compared with 2 of 17 cases without recurrence, uPAR was positive in 15 of 17 recurrent cases ( P <0 01) In 36 cases who survived, 17 was positive uPAR and 15 positive PAI 1, while in 12 cases who died 2 years after surgery, 12 were positive for uPAR and 9 positive PAI 1, respectively ( P <0 01 and P <0 05) In 15 positive cases for all three parameters, 11 had cancer invasion and 7 died within 2 years, while in negative cases, 2 had invasion and none died within 2 years ( P <0 05) Conclusion: Expression of uPA, uPAR and PAI 1 is increased in HCC, uPA and uPAR may contribute significantly to HCC invasion and metastasis uPAR and PAI 1 are associated with poor prognosis of HCC

关键词： Carcinoma Hepatocellular Plasminogen Activators neoplasm invasiveness neoplasm metastasis Immunohistochemistry

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Effects of Taxotere on invasive potential and multidrug resistance phenotype in pancreatic carcinoma cell line SUIT-2

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World Journal of Gastroenterology 2001年第1期7卷 143-148页

作者： Edgar Staren Takeshi Iwamura Hubert Appert John Howard Department of Surgery Medical College of Ohio Toledo Ohio USA Department of Surgery Miyazaki Medical College Miyazaki Japan

INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].

关键词： Carcinoma Pancreatic neoplasms Taxoids Antineoplastic Agents, Phytogenic Biocompatible Materials Collagen Drug Combinations Drug Resistance, Multiple Drug Resistance, neoplasm Fluorescent Dyes Humans In Vitro Laminin neoplasm invasiveness P-Glycoprotein Paclitaxel derivatives Phenotype Proteoglycans RNA, neoplasm Research Support, Non-U.S. Gov't Rhodamine 123 Tumor Cells, Cultured

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Relationship between phenotypes of cell-function differentiation and pathobiological behavior of gastric carcinomas

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World Journal of Gastroenterology 2001年第1期7卷 53-59页

作者： Yan Xin Xiao Ling Li Yan Ping Wang Su Min Zhang Hua Chuan Zheng Dong Ying Wu Yin Chang Zhang The Fourth Laboratory of Cancer Institute, China Medical University, Shenyang 110001, Liaoning Province, China The Fourth Laboratory of Cancer Institute China Medical University Shenyang 110001 Liaoning Province China.

AIM: To reveal the correlation between the functional differentiation phenotypes of gastric carcinoma cells and the invasion and metastasis by a new way of cell-function ***:Surgically resected specimens of 361 gastric carcinomas(GC) were investigated with enzyme-, mucin-, and tumor-related marker immunohistochemistry. According to the direction of cell-function differentiation, stomach carcinomas were divided into five functionally differentiated types. RESULTS: (1) Absorptive function differentiation type (AFDT): there were 82 (22.7%) patients including 76 (92.7%) aged 45 years. Sixty-nine (84.1%) cases belonged to the intestinal type. Thirty-eight (46.3%) expressed CD44v6 and 9 (13.6%) of 66 male patients developed liver *** 5-year survival rate of patients in this group (58.5%) was higher than those with the other types (P<0.01). (2) Mucin secreting function differentiation type (MSFDT): 54 (15%) cases. Fifty-three (98.1%) tumors had penetrated the serosa, 12 (22.2%) expressed ER and 22 (40.7%) expressed CD44v6. The postoperative 5-year survival rate was 28.6%. (3) Absorptive and mucin-producing function differentiation type (AMPFDT): there were 180 (49.9%) cases, including 31 (17.2%) aged younger than 45 years. The tumor was more common in women (62, 34.4%,) and expressed more frequently estrogen receptors (ER) (129, 81.7%) than other types (P<0.01). Ovary metastasis was found in 12 (19.4%) out of 62 female subjects. The patients with this type GC had the lowest 5-year survival rate (24.7%) among all types. (4) Specific function differentiation type (SFDT): 13 (3.6%) cases. Nine (69.2%) tumors of this type derived from APUD system, the other 4 (30.7%) were of different histological differentiation. Sixty per cent of the patients survived at least five years. (5) Non-function differentiation type (NFDT): 32 (8.9%) cases. Nineteen (59.4%) cases had lymph node metastases but no one with liver or ovary metastasis. The 5-year surv

关键词： Antigens, CD44 Cell Differentiation Female Glycoproteins Humans Immunohistochemistry Liver neoplasms Lymphatic Metastasis Male Middle Aged neoplasm invasiveness Ovarian neoplasms Phenotype Prognosis Receptors, Estrogen Research Support, Non-U.S. Gov't Stomach neoplasms Survival Rate Tumor Markers, Biological

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Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97

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World Journal of Gastroenterology 2001年第5期7卷 630-636页

作者： Yan Li Zhao-You Tang Sheng-Long Ye Yin-Kun Liu Jie Chen Qiong Xue Jun Chen Dong-Mei Gao Wei-Hua Bao Liver Cancer Institute and Zhongshan Hospital of Fudan University (Former Liver Cancer Institute of Shanghai Medical University),Shanghai 200032,China Liver Cancer Institute & Zhongshan Hospital of Fudan University 136 Yixueyuan Road Shanghai 200032China.

AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.

关键词： Albumins Animals Carcinoma, Hepatocellular Cell Division Chromosomes Clone Cells Flow Cytometry Hepatitis B Hepatitis B Surface Antigens Hepatitis B virus purification Humans Keratin Liver Liver neoplasms, Experimental Male Mice Mice, Inbred BALB C Mice, Nude neoplasm invasiveness Research Support, Non-U.S. Gov't Tumor Cells, Cultured Virus Integration alpha-Fetoproteins

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CT and MR imaging for detecting neoplastic invasion of esophageal inlet

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World Journal of Gastroenterology 2005年第3期11卷 377-381页

作者： BinChen Shan-KaiYin Qi-XinZhuang Ying-ShengCheng DepartmentofOtolaryngology AffiliatedSixthPeople'sHospitalShanghaiJiaotongUniversityShanghai200233China DepartmentofRadiology AffiliatedSixthPeople'sHospitalShanghaiJiaotongUniversityShanghai200233China DepartmentofOtolaryngology AffiliatedSixthPeople'sHospitalShanghaiJiaotongUniversityShanghai200233China

AIM: Direct neoplastic invasion of esophageal inlet is an uncommon but significant sequela of advanced head and neck carcinomas. The aim of this study was to seek an optimal CT or MRI criterion for determining the neoplastic esophageal inlet involvement in order to help tumor staging and surgical planning. METHODS: CT and MRI of 78 head and neck tumor cases were investigated retrospectively. At the level of the esophageal inlet on axial CT and MRI scans, the distance between the posterior aspect of cricoid cartilage and the anterior aspect of vertebra (d-CV) was measured by two senior radiologists who were unaware of clinical findings. Then, according to pathologie evidence and follow-up findings, these patients were divided into patients group, including 32 cases with neoplastic invasion of esophageal inlet and control group, including 46 cases without neoplastic esophageal inlet involvement. The statistical difference based on d-CV between the two groups was determined. The optimal criterion of d-CV on CT or MRI was assessed and lts accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were evaluated respectively. RESULTS: In control group, d-CV at the esophageal inlet level was 0.94±0.15 cm on axial CT and 0.91±0.18 cm on axial MRI, whereas in patient group, d-CV was 1.24±0.32 cm on CT and 1.31±0.36 cm on MRI. There was a statistical significance in d-CV between the two groups on CT and MRI modalities (P<0.01). d-CV greater than 1.0 cm was the typicall feature of neoplastic invasion of the esophageal inlet with 73% sensitivity, 83% specificity, 79% accuracy, 76% PPV, 80% NPV on CT and 84% sensitivity, 77% specificity, 80% accuracy, 70% PPV, 88% NPV on MRI respectively. CONCLUSION: Except for other CT and MR imaging features of neoplastic invasion of esophageal inlet, d-CV greater than 1.0 cm is an optimal adjunct criterion for esophageal inlet invasion by advanced head and neck carcinomas.

关键词： Esophageal neoplasms Esophageal inlet CT MRI neoplasm invasiveness

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Hematemesis as the initial complication of pancreatic adenocarcinoma directly invading the duodenum: A case report

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World Journal of Gastroenterology 2005年第5期11卷 767-769页

作者： Yueh-Hung Lin Chih-Yen Chen Chih-Ping Chen Tien-Yin Kuo Full-Young Chang Shou-Dong Lee Division of Gastroenterology Department of Medicine Taipei Veterans General Hospital and School of MedicineNational Yang-Ming UniversityTaipeiTaiwanChina Department of HealthTao-Yuan General Hospital Tao-Yuan TaiwanChina Division of Gastroenterology

Pancreatic carcinoma is a debilitating disease and carries a poor prognosis. It is a rare cause of upper gastrointestinal bleeding, even though pancreas, stomach, duodenum and jejunum are adjacent organs. The incidence of pancreatic adenocarcinoma directly invading the gastrointestinal tract leading to gastrointestinal hemorrhage is very low, and most of them present with melena and hematochezia. Here, we describe one unique case manifesting characteristically severe and unremitting hematemesis as an initial presentation of pancreatic adenocarcinoma. This tumor directly invaded the duodenal mucosa as a bleeding protruding tumor mass. Our MEDLINE search has confirmed that this is the first reported case with an initial manifestation of hematemesis from pancreatic adenocarcinoma in *** adenocarcinoma directly invading duodenum complicated by hemorrhage can be a rare cause of hematemesis, and clinicians should be reminded of it while they are making differential diagnosis.

关键词： Pancreatic adenocarcinoma Duodenum tumor Hematemesis neoplasm invasiveness

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Effect of a nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on invasion of human colorectal cancer cell line SL-174T

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World Journal of Gastroenterology 2005年第40期11卷 6385-6388页

作者： Li-Bo YU Xin-Shu Dong Wen-Zhou sun Dong-Lu Zhao Yue Yang Department of GeneralSurgery the Affiliated Tumor Hospital of Harbin MedicalUniversity Harbin 150040 Heilongiiang Province China Cancer Research Institute of HarbinMedical University Harbin 150040 Heilongjiang Province China

AIML To investigate the effect and mechanism of action of the nitric oxide synthase （NOS） inhibitor NG-nitro-L-arginine methyl ester （L-NAME） on invasion and metastasis of human colorectal cancer cell line SL-174T. METHODS： Human colorectal cancer cel4 line SL-174T was cultured and treated separately with four different dosages of L-NAME for 72 h, Nitric oxide （NO） production was measured with Griess reagent, The effect of L-NAME on invasion and migration of SL-174T cells were evaluated by using Transwell chambers attached with polycarbonate filters and reconstituted basement membrane （Matrigel）, RT-PCR was performed to determine the mRNA levels of matrix metalloproteinase-2 （MMP-2） and tissue inhibitor metalloproteinase-2 （TIMP-2）,RESULTS： L-NAME could significantly inhibit NO production of SL-174T in a dose-dependent manner. After being treated for 72 h with 0.2, 0.4, 0.8, and 1.0 mmol/L L- NAME, respectively, the ability of the L-NAME treated SL- 174T cells to invade the reconstituted basement membrane decreased significantly （t = 8.056, P〈0.05; t= 14.467, P〈0.01; t= 27.785, P〈0.01; and t= 29.405, P〈0.01, respectively） and the inhibition rates were 10.29%, 19.62%, 34.08%, and 42.23%, respectively. Moreover, L-NAME could inhibit migration of SL-174T cells, and the inhibition rates were 20.76%, 24.95%, 39.43%, and 46. 85% for L-NAME at 0.2, 0.4, 0.8, and 1.0 mmol/L, respectively （t = 15.116, P〈0.01）. In addition, after treatment with L-NAME, expression of MMP-2 mRNA was significantly decreased （t = 71.238, P〈0.01） and that of TIMP-2 mRNA was markedly increased （t = -13.020, P〈0.01）. CONCLUSION： L-NAME exerts anti-invasive and anti- metastatic effects on SL-174T cell line via downregulating MNP-2 mRNA expression and upregulating TIMP-2 mRNA expression.

关键词： Colorectal neoplasms neoplasm invasiveness Cell Line, Tumor Cell Movement Dose-Response Relationship, Drug Female Gelatinase A Humans Male NG-Nitroarginine Methyl Ester Nitric Oxide Nitric Oxide Synthase inhibitors Tissue Inhibitor of Metalloproteinase-2

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Detection of Syndecan-1 and Heparanase-1 Genes in Esophageal Carcinoma by Quantitative RT-PCR

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Clinical oncology and cancer researeh 2010年第4期7卷 253-258页

作者： Jun-li SI Yu-qin QI Jing-yuan CUI Song-mei WANG He WANG Mei LU Department of Gastroenterology Affiliated Qingdao Municipal Hospital of Qingdao University Medical College Qingdao 266011 Shan- dong Province China. Department of General Surgery Affiliated Qingdao Municipal Hospital of Qingdao University Medical College Qingdao 266011 Shandong Province China. Department of Hepatology Qingdao Infectious Diseases Hospital Qingdao 266033 Shandong Province China.

OBJECTIVE To quantitatively explore the expression of Syndecan-1 and heparanase-1 in esophageal cancer tissue as well as their relationship with the clinicopathological factors, in order to evaluate their roles in tumor invasion and *** Real-time fluorescence quantitative PCR （Q-PCR） was used to analyze the expression levels of Syndecan-1 and heparanase-1 genes￡？participants included 67 cases with esophageal cancers and 32 healthy *** The expression of Heparanase-1 gene in esophageal cancers was higher than that in normal esophageal tissue （P 〈 0.001）, and the expression of Syndecan-1 gene in the normal esophageal tissue was higher compared with esophageal cancers （P 〈 0.001）. The positive rates of Syndecan-1 and Heparanase-1 gene in esophageal cancer were 13.4% （9/67） and 85.1% （57/67）.The expression of Syndecan-1 and Heparanase-1 genes was signifi cantly related to di. erentiation, depth of infi ltration, lymph node metastasis, vessel metastasis, and TNM stages of disease （P 〈 0.05）. In an attempt to measure the association between the 2 agents, this study found that the expression of Syndecan-1 mRNA had a significantly negative correlation with the expression of Heparanase-1 mRNA by using Spearman rank correlation test （OR = -0.572, P 〈 0.001）.CONCLUSION Syndecan-1 and Heparanase-1 play important roles in the invasion and metastasis of esophageal cancer. The reduction of Syndecan-1 and/or the increase of Heparanase-1 may influence the invasion and metastasis of malignant *** the combination assay of Syndecan-1 and Heparanase-1 may contribute to the diagnosis and treatment of malignant tumors.

关键词： Syndecan-1 esophageal neoplasms neoplasm invasiveness neoplasm metastasis PCR

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Activated vascular endothelia regulate invasion of glioma cells through expression of fibronectin

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Chinese Medical Journal 2010年第13期123卷 1754-1761页

作者： LIN Zhi-xiong YANG Li-juan HUANG Qiang FU Jin Department of Neurosurgery the First Affiliated Hospital Fujian Medical University Fuzhou Fujian 350005 China Department of Pharmacology Fujian Medical University Fuzhou Fujian 350004 China Department of Neurosurgery the Second Hospital Suzhou University Suzhou Jiangsu 215004 China Department of Pharmacology the School of Medicine Xiamen University Xiamen 361005 China Department of Pharmacology University of California Irvine USA

Background Previous researches have indicated that glioma invasion may occur within a tumor-host microecology, and that fibronectin may be involved in glioma invasion as an important component of the extracellular matrix. However, how the interaction between tumor cells and vascular endothelial cells affects glioma invasion is poorly understood. The aim of this study was to investigate the effects of the interaction between tumor cells and vascular endothelial cells on glioma invasion, and the relationship of this interaction to fibronectin. Methods The localization of fibronectin in different brain astrocytoma tissues was determined by immunohistochemistry Then, vascular endothelial cells and glioma cells were co-cultured in a Transwell co-culturing system. Fibronectin expression was detected by reverse transcriptase-polymerase chain reaction, immunocytochemistry, and enzyme-linked immunosorbent assay. Additionally, the influence of the interaction between tumor cells and vascular endothelial cells on glioma cell invasion was determined by an in vitro rapid invasion test. Results In brain astrocytoma tissues, fibronectin was present on the endothelial cells, in the extracellular matrix. Fibronectin expression was greater in higher grade tumors than in lower grade tumors. The interaction of glioma cells and vascular endothelial cells in vitro induced fibronectin release from vascular endothelial cells, which in turn stimulated glioma cell migration. This effect was inhibited by fibronectin blocking antibody. Conclusion Glioma cells may induce vascular epithelial cells to express fibronectin, and in turn fibronectin could promote glioma cell invasion.

关键词： glioma fibronectin neoplasm invasiveness tumor-host microecology cell-to-cell communication

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