Thesis (doctoral)--Københavns universitet.

Thesis (doctoral)--Lund University, 1991. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1991. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1991. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1991. / Added t.p. with thesis statement inserted.

Chemerin是一種新近發現的脂肪因數，其與肥胖，代謝綜合症和炎症密切相關。Chemerin通過G蛋白偶聯受體ChemR23 發揮生物學效應。脂肪組織為分泌型Chemerin的最主要來源。最近的研究顯示Chemerin 可能與腫瘤的發生相關。本研究的目的在於確定胃癌細胞上是否存在ChemR23,以及Chemerin/ChemR23 在腫瘤侵襲過程中的作用。 / 我們首先用western blot和免疫組織化學技術在人腫瘤組織及兩株腫瘤細胞AGS和MKN28上尋找ChemR23。我們首次證實ChemR23 在胃癌細胞上表達。 / 既往研究表明，炎症因數IL-6 可上調人類內皮細胞上表達的ChemR23。為了證明IL-6 對胃癌細胞表達ChemR23的調節作用，我們將兩株胃癌細胞培養於含有不同濃度的Chemerin 的溶液中。研究證明IL-6 對於ChemR23 的表達具有濃度和時間依賴性的上調作用。 / 接下來，我們關注於Chemrin/ChemR23 在VEGF，MMP-7和IL-6 表達中的作用。我們將胃癌細胞用含有或者不含有Chemerin的溶液培養，進而測量VEGF ，MMP-7和IL-6 的表達量。進而我們將研究Chemerin 對mammalian family of mitogen-activated protein kinases (MAPKs)即：Erk，P38，Jnk的調節作用，MAPKs對於VEGF，MMP-7和IL-6 的產生起著重要的作用。我們發現Chemerin對VEGF，MMP-7和IL-6 的上調作用具有濃度和時間依賴性。Chemrin對MAPKs的啟動亦具有時間依賴性。MAPKs抑制劑可減弱Chemein相關的VEGF, MMP-7和IL-6的生成。 / 因為VEGF，MMP-7和IL-6與腫瘤的侵襲相關，我們進一步對Chemerin 在腫瘤轉移中的作用進行探索。我們使用transwell實驗工具盒來檢測腫瘤的侵襲能力。我們將AGS或MKN28細胞懸液裡加入不同濃度的Chemerin,結果是Chemerin增強腫瘤的侵襲能力（P<0.001）。為了驗證chemeri 引發的腫瘤侵襲是否通過MAPKs信號通路，我們將AGS和MKN28細胞用MAPK抑制劑處理2小時候，再加入Chemerin 0.1ng/ml。結果是Chemerin引發的腫瘤細胞侵襲可被MAPK抑制劑所抑制。 / 隨後，我們將探索人血清Chemerin濃度是否與胃癌TNM分型及組織學分型相關。研究包括36例胃癌患者的血清。TNM分型與組織病理檢查及臨床評估為依據。對於組織分型的分析，患者分為兩組，腸型和非腸型。人血清Chemerin濃度用Elisa方法測定。用one way ANOVA 進行統計學分析， II，III+IV型胃癌患者血清 Chemrin濃度明顯高於I型患者. 用獨立樣本 T test 分析，結果是非腸型胃癌患者血清Chemerin 濃度 明顯高於腸型患者 (P<0.05) / 總之，我們首次證明了胃癌細胞表達ChemR23。Chemerin /ChemR23 對腫瘤細胞分泌VEGF，MMP-7 和IL-6具有重要上調作用，該作用通過MAPKs信號通路實現。人類血清Chemerin濃度與胃癌患者TNM分析及組織性分型相關。Chemerin 可被看作是促進腫瘤侵襲的因素之一。 / Chemerin is a newly discovered adipokine which is closely associated with obesity, metabolic syndrome, and inflammatory conditions. It acts via its distinct G protein-coupled receptor ChemR23. While Chemerin is predominantly released by adipocytes, recent studies have also shown its possible correlation with carcinogenesis. This thesis aims to determine whether ChemR23 is expressed in gastric cancer, and to clarify the roles of Chemerin/ChemR23 in the invasive capacity of gastric carcinoma. / We first started by investigating the native expression of ChemR23 in human gastric cancer tissue samples and two gastric cancer cell lines, namely AGS and MKN28, using immunohistochemistry and Western blot techniques. In this set of initial experiments, ChemR23 was found to be present in gastric cancer cells with different magnitudes of expression. / Previous studies have also shown that ChemR23 synthesis in human endothelial cells was upregulatable by proinflammatory cytokines, such as IL-6. We thus investigated the biological effect of IL-6 on ChemeR23 expression in gastric cancer. By incubating the two cell lines with different concentration of recombinant IL-6, a dose- and time- dependent upregulation of ChemR23 expression was seen in both MKN28 and AGS. / We next sought to investigate the effect of Chemerin/ChemR23 on VEGF，MMP-7 and IL-6 expression. Gastric cancer cells were cultured with or without recombinant Chemerin. Corresponding VEGF, MMP-7 and IL-6 expressions were measured at sequential time points. In addition, the effect of Chemrerin on activation of mammalian family of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), P38MAPK, and c-Jun NH(2)-terminal kinase (JNK), which play a key role in VEGF, MMP-7 and IL-6 expression, was determined. Our Results revealed that Chemerin induced VEGF, MMP-7 and IL-6 expressions in gastric cancer cells in a dose- and time- dependent manner, and such an effect was reversible by MAPK inhibitors. / As VEGF, MMP-7, IL-6 are known to be associated with invasion of cancer, we therefore proceeded to determine whether Chemerin had any effect on invasiveness of gastric cancer in vitro. Commercial transwell invasion chambers were used. We found that Chemerin up-regulated the ability of invasion of gastric cancer (P<0.001). To test whether Chemerin induced gastric cancer cells invasion was mediated through MAPKs pathway, we pretreated AGS and MKN28 with or without MAPKs inhibitors 2 hours before adding Chemerin. This experiment proved that Chemerin enhanced cancer invasions were reversible by MAPK inhibitor. / In the last part of this project, the correlation between human serum Chemerin level and TNM stage/ histology of clinically collected gastric cancer samples was analyzed. This study included 36 gastric cancer patients. The cancer staging was based on a routine histopathological assessment according to the 6th UICC TNM (tumor-nodulus-metastases) system. One way ANOVA analysis showed that the mean Chemerin levels of stage II and III+IV groups were significantly higher than that of stage I cases. When serum Chemerin level was analyzed according to Lauren’s histological subtypes of the tumours, it was found to be significantly higher in the non-intestinal group when compared to the intestinal group. (P<0.05) / In conclusion, I have demonstrated for the first time that ChemR23 is expressed by gastric cancer cells. Chemerin/ChemR23 has upregulating effect on VEGF, MMP-7and IL-6 expression through the MAPK pathways. The invasive capacity of gastric cancer was significantly potentiated by Chemerin in vitro. The serum Chemerin level also has correlation with TNM stage and histology of gastric cancer. So Chemerin may be a functional onco-protein modulating the invasiveness of human gastric cancer. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Wang, Chunhu. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 129-138). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / ABSTRACT --- p.II / ACKNOWLEDGEMENTS --- p.VII / LIST OF ABBREVIATIONS --- p.VIII / LIST OF FIGURES --- p.IX / LIST OF TABLES --- p.XI / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- General introduction of Gastric Cancer --- p.1 / Chapter 1.1.1 --- Epidemiology --- p.1 / Chapter 1.1.2 --- Risk Factors --- p.2 / Chapter 1.1.3 --- Therapy --- p.6 / Chapter 1.2 --- Gastric cancer invasion --- p.8 / Chapter 1.2.1 --- The role of mitogen activated protein kinases (MAPKs) and other signaling pathways in gastric cancer invasion --- p.9 / Chapter 1.2.2 --- VEGF, MMP-7 and IL-6 and their roles in gastric cancer invasion --- p.14 / Chapter 1.3 --- Novel mediators: Chemerin/ChemR23 --- p.16 / Chapter 1.3.1 --- What is Chemerin and ChemR23 --- p.17 / Chapter 1.3.2 --- The role of Chemerin/ChemR23 in pathological conditions --- p.20 / Chapter 2.1 --- Experiment 1 :ChemR23 expression in gastric cancer --- p.24 / Chapter 2.1.1 --- Materials and methods --- p.24 / Chapter 2.1.2 --- Results --- p.26 / Chapter 2.2 --- Experiment 2: In vitro ChemR23 expression in Gastric Cancer cell culture and its interaction with IL-6 --- p.32 / Chapter 2.2.1 --- Materials and methods --- p.32 / Chapter 2.2.2 --- Results: --- p.35 / Chapter 2.3 --- Discussion --- p.45 / Chapter Chapter 3 --- Chemerin activates FAK, MAPK and Akt signal pathway on gastric cancer --- p.50 / Chapter 3.1 --- Materials and methods --- p.50 / Chapter 3.1.1 --- Reagents and antibodies： --- p.51 / Chapter 3.1.2 --- Cell cultures and treatment --- p.51 / Chapter 3.1.3 --- MTT assay for the effect of Chemerin on gastric cancer proliferation --- p.52 / Chapter 3.1.4 --- ChemR23 siRNA transfection --- p.52 / Chapter 3.1.5 --- Western blot analysis. --- p.53 / Chapter 3.1.5 --- Statistical analysis. --- p.54 / Chapter 3.2 --- Results --- p.54 / Chapter 3.2.1 --- MTT assay result --- p.54 / Chapter 3.2.2 --- Chemerin activates FAK signal pathways --- p.56 / Chapter 3.2.3 --- Chemerin activate MAPK signal pathways --- p.58 / Chapter 3.2.4 --- Chemerin induced Akt activation --- p.63 / Chapter 3.2.5 --- Chemerin activates MAPK pathways through ChemR23 --- p.65 / Chapter 3.3 --- Discussion --- p.69 / Chapter Chapter 4 --- Chemerin up-regulates VEGF, MMP-7 and IL-6 expression throug MAPK pathway on gastric cancer --- p.73 / Chapter 4.1 --- Materials and methods --- p.73 / Chapter 4.1.1 --- Reagents and antibodies： --- p.73 / Chapter 4.1.2 --- Cell cultures and treatment --- p.74 / Chapter 4.1.3 --- ChemR23 siRNA transfection --- p.74 / Chapter 4.1.4 --- Treatment MAPK inhibitors --- p.75 / Chapter 4.1.5 --- uantitative reverse transcript (RT)-PCR assay --- p.75 / Chapter 4.1.6 --- Western blot analysis --- p.76 / Chapter 4.1.7 --- Statistical analysis. --- p.77 / Chapter 4.2 --- Results --- p.78 / Chapter 4.2.1 --- Chemerin up-regulated VEGF, MMP-7, IL-6 expression --- p.78 / Chapter 4.2.2 --- Chemerin induced VEGF and MMP-7expression through ChemR23 --- p.87 / Chapter 4.2.3 --- Chemerin induced VEGF, MMP-7 and IL-6 expression through MAPK pathways --- p.91 / Chapter 4.3 --- Discussion: --- p.96 / Chapter Chapter 5 --- Chemerin enhances gastric cancer invasiveness through the MAPK pathways --- p.100 / Chapter 5.1 --- Materials and methods --- p.100 / Chapter 5.1.1 --- Reagents and antibodies： --- p.100 / Chapter 5.1.2 --- Cell culture and treatments --- p.101 / Chapter 5.1.3 --- Tumor invasion potential evaluated with Transwell invasion chambers --- p.101 / Chapter 5.1.4 --- Statistical analysis. --- p.102 / Chapter 5.2 --- Results: --- p.103 / Chapter 5.2.1 --- Chemerin increased gastric cancer cells invasion abilities --- p.103 / Chapter 5.2.2 --- Chemerin increased gastric cancer cells invasion abilities through MAPK pathways --- p.104 / Chapter 5.3 --- Discussion: --- p.109 / Chapter Chapter 6 --- Chemerin relates with TNM stage and histology of gastric cancer --- p.113 / Chapter 6.1 --- Materials and methods --- p.113 / Chapter 6.1.1 --- Study population --- p.113 / Chapter 6.1.2 --- Serum Chemerin level measurements --- p.114 / Chapter 6.1.3 --- Statistical analysis --- p.115 / Chapter 6.2 --- Results: --- p.115 / Chapter 6.2.1 --- Serum Chemerin level in healthy subject plus gastric cancer patients followed normal distribution but did not follow homogeneity of variances --- p.115 / Chapter 6.2.2 --- Serum Chemerin level in gastric cancer patients was higher than healthy subjects --- p.116 / Chapter 6.2.3 --- Serum Chemerin level in gastric cancer followed normal distribution and homogeneity of variances --- p.120 / Chapter 6.2.4 --- Human serum Chemerin level was related to gastric cancer TNM stage --- p.121 / Chapter 6.2.5 --- Association between human serum Chemerin level and histology --- p.123 / Chapter 6.3 --- Discussion --- p.125 / Chapter Chapter 7: --- Conclusion and future plan --- p.127 / Reference --- p.129

by Chan Chi Wai, Michael. / "July 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 238-272). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Lee Tin Lap. / "January 2001." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 161-185). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Li Chung Yi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 110-123). / Abstracts in English and Chinese. / ABSTRACT --- p.i / ACKNOWLEDGEMENTS --- p.iv / TABLE OF CONTENTS --- p.v / LIST OF FIGURES --- p.ix / LIST OF TABLES --- p.xi / Chapter I. --- INTRODUCTION --- p.1 / Chapter I.1 --- Gastric Carcinoma --- p.1 / Chapter I.2 --- Etiology of Gastric Carcinoma --- p.2 / Chapter I.2.1 --- Environmental Factors: --- p.2 / Chapter I.2.2 --- Helicobacter Pylori Infection: --- p.2 / Chapter I.2.3 --- Genetic Factors: --- p.3 / Chapter I.2.4 --- Other Factors: --- p.4 / Chapter I.3 --- The Lauren Classification of Gastric carcinoma --- p.5 / Chapter I.3.1 --- Histolopathology of Intestinal Type of Gastric Carcinoma --- p.5 / Chapter I.3.2 --- Histopathology of Diffuse Type of Gastric Carcinoma --- p.8 / Chapter I.4 --- Cytogenetics Studies in Gastric Carcinoma --- p.10 / Chapter I.4.1 --- Cytogenetic Studies of Gastric carcinoma --- p.10 / Chapter I.5 --- Molecular Studies of Gastric Carcinoma --- p.14 / Chapter I.5.1 --- Genetic Instability --- p.14 / Chapter I.5.2 --- Amplification/ Mutation of Oncogenes --- p.15 / Chapter I.5.3 --- Alterations of Tumor Suppressor Genes --- p.20 / Chapter I.5.4 --- Cell Adhesion Molecules --- p.23 / Chapter I.5.5 --- Molecular Studies on Intestinal Metaplasia --- p.27 / Chapter II. --- LONG ARM OF CHROMOSOME 6 --- p.28 / Chapter III. --- BRIEF REVIEWS OF THE TECHNIQUES USED IN THIS STUDY --- p.34 / Chapter III.1 --- Comparative Genomic Hybridization (CGH) --- p.34 / Chapter III.2 --- Loss of Heterozygosity (LOH) --- p.37 / Chapter III.3 --- Methylation-Specific PCR (MSP) --- p.38 / Chapter IV. --- OBJECTIVES OF STUDY --- p.40 / Chapter V. --- MATERIALS AND METHODS --- p.41 / Chapter V.l --- Sample Collections --- p.41 / Chapter V.1.1 --- Patients Information for CGH Studies --- p.42 / Chapter V. 1.2 --- Patients Information for LOH Studies --- p.42 / Chapter V.2 --- Extraction of Genomic DNA for Tumor and Normal Tissues --- p.47 / Chapter V.2.1 --- Extraction of Genomic DNA from Frozen Tissues or Paraffin Embedded Sections --- p.47 / Chapter V.2.2 --- Extraction of Genomic DNA from Blood --- p.48 / Chapter V.3 --- Comparative Genomic Hybridization (CGH) of Gastric Carcinoma --- p.49 / Chapter V.3.1 --- Preparation of Normal Metaphase Slides --- p.49 / Chapter V.3.2 --- Metaphase Slide Denaturation --- p.49 / Chapter V.3.3 --- Nick Translation for DNA Labeling --- p.50 / Chapter V.3.4 --- Dot Blot Assay for Biotin and Digoxigenin-Labeled DNA --- p.51 / Chapter V.3.5 --- "Probe Preparation, Denaturation and Hybridization" --- p.51 / Chapter V.3.6 --- Post hybridization Washing and Detection --- p.52 / Chapter V.3.7 --- Image Acquisition and Analysis of CGH Images --- p.53 / Chapter V.4 --- Loss of Heterozygosity (LOH) Analysis on Chromosome 6q --- p.55 / Chapter V.4.1 --- Microsatellite Markers --- p.55 / Chapter V.4.2 --- Polymerase Chain Reaction (PCR) --- p.57 / Chapter V.4.3 --- Denaturing Polyacrylamide Gel Electrophoresis --- p.58 / Chapter V.4.4 --- SYBR Gold Nucleic Acid Gel Staining and Image Viewing --- p.58 / Chapter V.4.5 --- Assessment of Loss of Heterozygosity (LOH) --- p.59 / Chapter V.4.6 --- Statistical Analysis --- p.61 / Chapter V.5 --- Methylation Specific Polymerase Chain Reaction (MSP) --- p.62 / Chapter V.5.1 --- Bisulfite Modification of DNA --- p.62 / Chapter V.5.2 --- Mehtylation Specific PCR --- p.63 / Chapter VI. --- RESULTS --- p.66 / Chapter VI.1 --- Results of CGH --- p.66 / Chapter VI. 1.1 --- Chromosomal Copy Number Aberrations in Gastric Carcinoma --- p.66 / Chapter VI. 1.2 --- Comparison of CGH Results with Intestinal and Diffuse Type of Gastric Carcinoma --- p.67 / Chapter VI.2 --- LOH Analysis of Chromosome 6q --- p.73 / Chapter VII. --- DISCUSSIONS --- p.83 / Chapter VII.l --- Discussions on CGH --- p.83 / Chapter VII.2 --- Discussions on LOH Study --- p.89 / Chapter VII.2.1 --- Two Distinct Deletion Regions --- p.89 / Chapter VII.2.2 --- Possible Candidate Suppressor Genes in Two Deletion Regions --- p.93 / Chapter VII.2.3 --- Infrequent Loss of IGF2R Gene --- p.95 / Chapter VII.3 --- Relationship Between Intestinal Metaplasia and Gastric Carcinoma --- p.99 / Chapter VII.4 --- Microsatellite Instability --- p.100 / Chapter VII.5 --- Correlations --- p.103 / Chapter VII.6 --- Comparison Between CGH and LOH Results on Chromosome 6 --- p.104 / Chapter VII.7 --- Conclusions --- p.106 / Chapter VII.8 --- Limitations of the Study --- p.107 / Chapter VII.8.1 --- Limitation of CGH --- p.107 / Chapter VII.8.2 --- Limited Information Supply by LOH Analysis --- p.107 / Chapter VII.8.3 --- Small Sample Size --- p.107 / Chapter VII.9 --- Future Studies --- p.108 / Chapter VIII. --- REFERENCES --- p.110

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.