Endometrial adenocarcinoma, originating from the glandular epithelial cells of the uterine endometrial lining, is one of the most prevalent cancers amongst women in the Western world. The prostaglandin F2α (PGF2α) receptor (FP) is upregulated in endometrial adenocarcinoma. A previous microarray analysis of endometrial adenocarcinoma cells (Ishikawa) identified numerous targets of PGF2α-FP signalling including angiogenic factors, VEGF-A, FGF-2, CXCL1 and CXCL8 and antiangiogenic factors ADAMTS1. The regulation of VEGF-A, FGF-2, CXCL1 and CXCL8 was confirmed by previous studies using an in vitro model system, of Ishikawa cells stably expressing the FP receptor to levels observed in cancer (FPS cells). In this thesis, ADAMTS1 expression was found to be upregulated in endometrial adenocarcinoma samples compared to normal endometrium. Using FPS cells, ADAMTS1 expression was regulated in an extracellular signal regulated kinase 1/2 (ERK1/2) independent manner involving activation of nuclear factor of activated T cells (NFAT). Angiogenic and antiangiogenic proteins secreted by epithelial cells, in response to PGF2α-FP receptor signalling, could therefore regulate vascular function in a paracrine manner. Hence this thesis examines the role of angiogenic factors FGF2, CXCL1 and CXCL8, secreted into PGF2α-treated FPS cell conditioned medium (P CM), in the regulation of endothelial cell function in vitro. Firstly, using an in vitro model system, treatment of human umbilical vein endothelial cells (HUVECs) with P CM increased endothelial network formation and proliferation, compared to control CM. Immunoneutralisation of FGF2, CXCL1 and CXCL8 from the P CM reduced endothelial cell network formation and proliferation (P<0.05). In addition, inhibition of their receptors (FGFR1 and CXCR2) with chemical antagonists decreased endothelial cell network formation and proliferation (P<0.05) in response to treatment with P CM. This indicates that FGF2, CXCL1 and CXCL8 are paracrine effectors of FP-mediated endothelial cell network formation and proliferation. Next, the mechanisms by which FGF2 regulates P CM-induced endothelial cell network formation and proliferation were investigated. Using specific inhibitors of cell signalling, FGF2-FGFR1 was found to regulate endothelial cell proliferation via the mTOR pathway. In contrast, FGF2-FGFR1 signalling mediated endothelial cell network formation via the regulation of COX-2 expression and PGF2α synthesis in endothelial cells. Endometrial adenocarcinoma, originating from the glandular epithelial cells of the uterine endometrial lining, is one of the most prevalent cancers amongst women in the Western world. The prostaglandin F2α (PGF2α) receptor (FP) is upregulated in endometrial adenocarcinoma. A previous microarray analysis of endometrial adenocarcinoma cells (Ishikawa) identified numerous targets of PGF2α-FP signalling including angiogenic factors, VEGF-A, FGF-2, CXCL1 and CXCL8 and antiangiogenic factors ADAMTS1. The regulation of VEGF-A, FGF-2, CXCL1 and CXCL8 was confirmed by previous studies using an in vitro model system, of Ishikawa cells stably expressing the FP receptor to levels observed in cancer (FPS cells). In this thesis, ADAMTS1 expression was found to be upregulated in endometrial adenocarcinoma samples compared to normal endometrium. Using FPS cells, ADAMTS1 expression was regulated in an extracellular signal regulated kinase 1/2 (ERK1/2) independent manner involving activation of nuclear factor of activated T cells (NFAT). Angiogenic and antiangiogenic proteins secreted by epithelial cells, in response to PGF2α-FP receptor signalling, could therefore regulate vascular function in a paracrine manner. Hence this thesis examines the role of angiogenic factors FGF2, CXCL1 and CXCL8, secreted into PGF2α-treated FPS cell conditioned medium (P CM), in the regulation of endothelial cell function in vitro. Firstly, using an in vitro model system, treatment of human umbilical vein endothelial cells (HUVECs) with P CM increased endothelial network formation and proliferation, compared to control CM. Immunoneutralisation of FGF2, CXCL1 and CXCL8 from the P CM reduced endothelial cell network formation and proliferation (P<0.05). In addition, inhibition of their receptors (FGFR1 and CXCR2) with chemical antagonists decreased endothelial cell network formation and proliferation (P<0.05) in response to treatment with P CM. This indicates that FGF2, CXCL1 and CXCL8 are paracrine effectors of FP-mediated endothelial cell network formation and proliferation. Next, the mechanisms by which FGF2 regulates P CM-induced endothelial cell network formation and proliferation were investigated. Using specific inhibitors of cell signalling, FGF2-FGFR1 was found to regulate endothelial cell proliferation via the mTOR pathway. In contrast, FGF2-FGFR1 signalling mediated endothelial cell network formation via the regulation of COX-2 expression and PGF2α synthesis in endothelial cells. Angiogenesis is maintained by a balance of pro-and antiangiogenic factors. Hence, concomitantly with the upregulation of proangiogenic factors, antiangiogenic proteins ADAMTS1 and regulator of calcineurin 1 (RCAN1) were upregulated by P CM treatment of HUVECs. They were subsequently shown to limit endothelial cell network formation and proliferation in response to P CM. Finally, the role of PGF2α in angiogenesis was investigated using two in vivo models. PGF2α treatment did not increase angiogenesis in a sponge matrigel mouse model. In a xenograft mouse model, PGF2α-FP signalling increased expression of angiogenic factors in human epithelial cells and mouse stroma but this did not enhance microvessel density. Taken together, this thesis had highlighted that PGF2α-FP receptor signalling stimulates expression of pro-and antiangiogenic factors that in turn regulate endothelial cell function. However, in vivo studies demonstrate that PGF2α-FP receptor interaction does not impact on the level of angiogenesis but may control other aspects of vascular function.

Uterine inflammation is one of the causes of a poor uterine environment. This can result in early embryonic loss in the mare due to an inhibition of or an increased secretion of prostaglandin F2α (PGF2α ). Oxytocin binds to endometrial cell receptors to activate prostaglandin synthesis. Increased secretion or accumulation of PGF2α within the uterus due to uterine inflammation can cause luteolysis and result in early embryonic loss. Supplementation with polyunsaturated fatty acids (PUFAs) has been shown to influence prostaglandin production in many species, although the effects on the mare remain unknown. Equine endometrial biopsies were collected and used to establish endometrial epithelial cell and explant cultures to determine the release of PGF2α and PGFM in response to oxytocin stimulation. Endometrial explant cultures were used to determine the inhibitory effects of Atosiban, an oxytocin receptor antagonist, and Indomethacin, a cyclooxygenase –2 inhibitor, on PGF2α secretion. Endometrial explant cultures were challenged with oxytocin (250 nM) and PGF2α concentrations were measured over time. The effects of PUFAs on equine endometrial prostaglandin production were determined using endometrial biopsies harvested on day two of behavioral estrus. Equine endometrial cells were established and shown to replicate in culture and on a basement membrane matrix. Equine endometrial explants stimulated with oxytocin had increased secretion of PGF2α and PGE2 and the secretion of PGF2α was inhibited through an oxytocin receptor antagonist and Cox inhibition. Endometrial explants stimulated with lipopolysaccharide had increased secretion of PGF2α and PGE2, however oxytocin stimulated to a greater extent than LPS. Supplementation with PUFAs, specifically DHA, decreased the secretion of PGF2α and PGE2, however AA and EPA failed to influence this response. Expression of mRNA was not influenced by fatty acid supplementation, however was altered by stimulus. Therefore DHA influences the inflammatory response in vitro through mechanisms other than enzyme expression. Decreased PGF2α production associated with PUFA supplementation in vivo, creates a likely approach for decreasing early embryonic loss associated with post breeding inflammation commonly seen in the equine industry.

No description available.

Final publication is available at http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=26018088 / Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(医科学) / 甲第19635号 / 医科博第73号 / 32671 / 京都大学大学院医学研究科医科学専攻 / (主査)教授 妹尾 浩, 教授 渡邊 直樹, 教授 椛島 健治 / 学位規則第4条第1項該当

Kan Ka-wing. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. [161]-[184]). / 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.

Cheuk Lai-Yee. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 153-184). / 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.

by William, Wai-lun Lam. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 85-95). / Chapter I. --- Introduction --- p.1 / Chapter II. --- Our Approach --- p.9 / Chapter III. --- Results and Discussion - Synthetic Strategy --- p.29 / Chapter IV. --- Results and Discussion - Pharmacological Activity --- p.44 / Chapter V. --- Conclusion --- p.49 / Chapter VI. --- Further Development --- p.53 / Chapter VII. --- Experimental Section --- p.55 / Chapter VIII. --- References --- p.85 / Chapter IX. --- Supplementary Materials --- p.96

Rowlands Dewi Kenneth. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 113-121). / Abstract --- p.i / Acknowledgements --- p.iii / Publications --- p.iv / Abbreviations --- p.v / Contents --- p.vii / Chapter Chapter 1 --- Prostaglandins --- p.1 / Chapter 1.1 --- Introduction --- p.1 / Chapter 1.2 --- Prostanoid biosynthesis and metabolism --- p.1 / Chapter 1.3 --- Prostaglandin receptors --- p.3 / Chapter 1.3.1 --- DP-receptors --- p.3 / Chapter 1.3.2 --- EP1-receptors --- p.4 / Chapter 1.3.3 --- EP2-receptors --- p.4 / Chapter 1.3.4 --- EP3-receptors --- p.5 / Chapter 1.3.5 --- EP4-receptors --- p.6 / Chapter 1.3.6 --- FP-receptors --- p.7 / Chapter 1.3.7 --- IP-receptors --- p.8 / Chapter 1.3.8 --- TP-receptors --- p.11 / Chapter 1.4 --- Agonists and antagonists --- p.11 / Chapter Chapter 2 --- Role of prostacyclin in pain modulation --- p.14 / Chapter 2.1 --- Pain --- p.14 / Chapter 2.2 --- Prostaglandins and pain --- p.15 / Chapter 2.3 --- Prostacyclin and pain --- p.16 / Chapter 2.3.1 --- [3H]-Iloprost binding sites --- p.16 / Chapter 2.3.2 --- IP-receptor mRNA --- p.17 / Chapter 2.3.3 --- IP-receptor knockout mice --- p.17 / Chapter 2.3.4 --- Direct nociceptive action of prostacyclin --- p.18 / Chapter 2.4 --- Treatment of prostanoid-induced pain --- p.19 / Chapter Chapter 3 --- Dorsal root ganglion cells --- p.21 / Chapter 3.1 --- In vitro model of pain --- p.21 / Chapter 3.2 --- Characteristics of cultured DRG cells --- p.22 / Chapter 3.2.1 --- Size and distribution --- p.22 / Chapter 3.2.2 --- Biochemical and physiological characteristics --- p.22 / Chapter 3.2.2.1 --- Gapsaicin-sensitive neurones --- p.23 / Chapter 3.2.2.2 --- Neuropeptide content --- p.23 / Chapter 3.2.2.3 --- Elevation of [Ca2+］i --- p.24 / Chapter 3.3 --- Effect of nerve growth factor --- p.24 / Chapter Chapter 4 --- Materials and solutions --- p.26 / Chapter 4.1 --- Materials --- p.26 / Chapter 4.2 --- Solutions --- p.30 / Chapter 4.2.1 --- Culture medium --- p.30 / Chapter 4.2.2 --- Buffers --- p.31 / Chapter 4.2.3 --- Solutions --- p.32 / Chapter Chapter 5 --- Development of dorsal root ganglion cell preparation --- p.33 / Chapter 5.1 --- Introduction --- p.33 / Chapter 5.2 --- Methods --- p.34 / Chapter 5.2.1 --- Dissection of dorsal root ganglia --- p.34 / Chapter 5.2.2 --- Preparation of a single-cell suspension --- p.34 / Chapter 5.2.2.1 --- Effect of trimming dorsal root ganglia --- p.34 / Chapter 5.2.2.2 --- Enzymatic dissociation --- p.35 / Chapter 5.2.2.3 --- Mechanical dissociation --- p.36 / Chapter 5.2.3 --- Neuronal cell enrichment --- p.36 / Chapter 5.2.3.1 --- Differential adhesion --- p.36 / Chapter 5.2.3.2 --- BSA gradient --- p.37 / Chapter 5.2.3.3 --- Combination of BSA gradient and differential adhesion --- p.37 / Chapter 5.2.4 --- Cell counting --- p.37 / Chapter 5.2.5 --- Culture conditions --- p.38 / Chapter 5.2.6 --- Size distribution of DRG cells --- p.39 / Chapter 5.2.7 --- Immunocytochemistry --- p.39 / Chapter 5.3 --- Results and discussion --- p.40 / Chapter 5.3.1 --- Preparation of single-cell suspension --- p.40 / Chapter 5.3.2 --- Neuronal cell enrichment --- p.42 / Chapter 5.3.3 --- Size distribution of DRG cells --- p.32 / Chapter 5.3.4 --- Effects of mitotic inhibitors and NGF --- p.45 / Chapter 5.3.5 --- Immunocytochemistry --- p.48 / Chapter 5.4 --- Conclusions --- p.48 / Chapter Chapter 6 --- Methods --- p.53 / Chapter 6.1 --- Dorsal root ganglion cell preparation --- p.53 / Chapter 6.1.1 --- Preparation of tissue culture plates and coverslips --- p.54 / Chapter 6.1.2 --- Preparation of Pasteur pipettes --- p.54 / Chapter 6.2 --- Measurement of adenylate cyclase activity --- p.55 / Chapter 6.2.1 --- Introduction --- p.55 / Chapter 6.2.2 --- Preparation of columns --- p.55 / Chapter 6.2.3 --- Measurement of [3H]-cyclic AMP production --- p.56 / Chapter 6.2.4 --- Data analysis --- p.57 / Chapter 6.3 --- Measurement of phospholipase C activity --- p.58 / Chapter 6.3.1 --- Introduction --- p.58 / Chapter 6.3.2 --- Preparation of columns --- p.58 / Chapter 6.3.3 --- Measurement of [3H]-inositol phosphate production --- p.59 / Chapter 6.3.4 --- Data analysis --- p.60 / Chapter 6.4 --- Measurement of [Ca2+]i --- p.60 / Chapter 6.4.1 --- Introduction --- p.60 / Chapter 6.4.2 --- Preparations of cells --- p.61 / Chapter 6.4.3 --- Measurement of Fura-2 fluorescence --- p.62 / Chapter 6.5 --- Measurement of neuropeptides --- p.62 / Chapter 6.5.1 --- Introduction --- p.62 / Chapter 6.5.2 --- Preparation of cells --- p.63 / Chapter 6.5.3 --- CGRP assay --- p.64 / Chapter 6.5.4 --- Substance P assay --- p.64 / Chapter 6.5.5 --- Purification of samples using Sep-Pak cartridges --- p.65 / Chapter Chapter 7 --- Characterisation of prostacyclin receptors on adult rat dorsal root ganglion cells --- p.66 / Chapter 7.1 --- Stimulation of adenylate cyclase --- p.66 / Chapter 7.1.1 --- Introduction --- p.66 / Chapter 7.1.2 --- Agonist concentration-response curves --- p.67 / Chapter 7.1.3 --- Cross-desensitisation experiments --- p.72 / Chapter 7.1.4 --- Evidence for EP3-receptors --- p.77 / Chapter 7.1.5 --- G-protein coupling of the IP-receptor --- p.77 / Chapter 7.1.6 --- Discussion --- p.78 / Chapter 7.1.7 --- Conclusions --- p.82 / Chapter 7.2 --- Stimulation of phospholipase C --- p.82 / Chapter 7.2.1 --- Introduction --- p.82 / Chapter 7.2.2 --- Agonist concentration-response curves --- p.83 / Chapter 7.2.3 --- G-protein coupling --- p.83 / Chapter 7.2.4 --- Discussion and Conclusions --- p.84 / Chapter 7.3 --- Stimulation of changes in [Ca2+]i --- p.87 / Chapter 7.3.1 --- Introduction --- p.87 / Chapter 7.3.2 --- Preliminary results --- p.87 / Chapter 7.3.3 --- Discussion and conclusions --- p.89 / Chapter Chapter 8 --- Neuropeptide release by adult rat dorsal root ganglion cells --- p.90 / Chapter 8.1 --- Introduction --- p.90 / Chapter 8.2 --- Methods and Results --- p.91 / Chapter 8.3 --- Discussion --- p.91 / Chapter 8.4 --- Conclusions --- p.92 / Chapter Chapter 9 --- Regulation of prostacyclin receptors on adult rat DRG cells --- p.93 / Chapter 9.1 --- Introduction --- p.93 / Chapter 9.2 --- Contribution of non-neuronal cells --- p.93 / Chapter 9.3 --- Effect of DRG cell density --- p.94 / Chapter 9.4 --- Effect of indomethacin --- p.99 / Chapter 9.5 --- Contribution of endogenously-produced non-prostanoid ligands --- p.100 / Chapter 9.6 --- Effect of PKC activation --- p.102 / Chapter 9.7 --- Discussion --- p.104 / Chapter 9.8 --- Conclusions --- p.106 / Chapter Chapter 10 --- General Discussion and Conclusions --- p.107 / Chapter 10.1 --- Development of DRG cell preparation --- p.107 / Chapter 10.2 --- Effect of prostanoid mimetics on intracellular messengers --- p.108 / Chapter 10.3 --- Regulation of prostacyclin receptors --- p.109 / Chapter 10.4 --- Role of prostacyclin in pain modulation --- p.111 / References --- p.113

Chu Kit Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 142-168). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iii / Acknowledgement --- p.iv / Abbreviations --- p.v / Publications Based on Work in this thesis --- p.viii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- G protein-coupled receptors --- p.1 / Chapter 1.1.1 --- Introduction --- p.1 / Chapter 1.1.2 --- Heterotrimeric G proteins --- p.3 / Chapter 1.1.3 --- Second messenger systems --- p.4 / Chapter 1.1.4 --- Mechanism of GPCR activation --- p.6 / Chapter 1.2 --- Prostacyclin and its receptors --- p.9 / Chapter 1.2.1 --- General properties of prostacyclin --- p.9 / Chapter 1.2.1.1 --- Synthesis of prostacyclin --- p.9 / Chapter 1.2.1.2 --- Prostacyclin analogues --- p.10 / Chapter 1.2.2 --- Characterization of IP-receptors --- p.12 / Chapter 1.2.2.1 --- Distribution of IP-receptors --- p.12 / Chapter 1.2.2.2 --- Cloning of IP-receptors --- p.14 / Chapter 1.2.2.3 --- Structure of IP-receptors --- p.15 / Chapter 1.2.3 --- Coupling of IP-receptors to G proteins --- p.16 / Chapter 1.2.3.1 --- Interaction with Gs --- p.16 / Chapter 1.2.3.2 --- Interaction with Gq --- p.17 / Chapter 1.2.3.3 --- Interaction with Gi --- p.18 / Chapter 1.2.3.4 --- Interaction with PPARs --- p.20 / Chapter 1.2.4 --- Role of prostacyclin in mitogenesis/anti-mitogenesis --- p.20 / Chapter 1.3 --- Signal transduction network of MAPK family --- p.27 / Chapter 1.3.1 --- MAPK modules in mammalian cells --- p.29 / Chapter 1.3.1.1 --- Extracellular regulated kinase (ERK) cascade --- p.30 / Chapter 1.3.1.2 --- Stress-activated protein kinase (JNK and p38) cascades --- p.33 / Chapter 1.3.2 --- Activation ofERKl/2 through GPCRs --- p.35 / Chapter Chapter 2 --- Materials and solutions --- p.53 / Chapter 2.1 --- Materials --- p.53 / Chapter 2.2 --- "Culture media, buffer and solutions" --- p.58 / Chapter 2.2.1 --- Culture media --- p.58 / Chapter 2.2.2 --- Buffers --- p.59 / Chapter 2.2.3 --- Solutions --- p.62 / Chapter Chapter 3 --- Methods --- p.65 / Chapter 3.1 --- Maintenance of cell lines --- p.65 / Chapter 3.1.1 --- Chinese Hamster ovary (CHO) cells --- p.65 / Chapter 3.1.2 --- Human neuroblastoma (SK-N-SH) cells --- p.66 / Chapter 3.1.3 --- Rat/mouse neuroblastoma/glioma hybrid (NG108-15) cells --- p.66 / Chapter 3.2 --- Transient transfection of mammalian cells --- p.67 / Chapter 3.3 --- Measurement of ERK activity --- p.68 / Chapter 3.3.1 --- PathDetect® Elkl trans-Reporting System --- p.68 / Chapter 3.3.1.1 --- Introduction --- p.68 / Chapter 3.3.1.2 --- β-galactosidase assay --- p.72 / Chapter 3.3.1.3 --- Transient transfection of cells --- p.72 / Chapter 3.3.1.4 --- Cell assay --- p.73 / Chapter 3.3.1.5 --- Luciferase assay --- p.74 / Chapter 3.3.1.6 --- Micro β-gal assay --- p.74 / Chapter 3.3.1.7 --- Data analysis --- p.75 / Chapter 3.3.2 --- Western Blotting --- p.79 / Chapter 3.3.2.1 --- Introduction --- p.79 / Chapter 3.3.2.2 --- Transient transfection of cells --- p.79 / Chapter 3.3.2.3 --- Cell assay --- p.79 / Chapter 3.3.2.4 --- Protein electrophoresis and transfer --- p.80 / Chapter 3.3.2.5 --- Immunodetection --- p.80 / Chapter 3.4.1 --- Measurement of adenylyl cyclase activity --- p.83 / Chapter 3.4.1 --- wyo-[3H]-inositol labelling method --- p.83 / Chapter 3.4.1.1 --- Preparation of columns --- p.83 / Chapter 3.4.1.2 --- Incubation of cells --- p.84 / Chapter 3.4.1.3 --- Measurement of [3H]-cyclic AMP production --- p.84 / Chapter 3.4.1.4 --- Data analysis --- p.85 / Chapter 3.5 --- Measurement of phospholipase C activity --- p.85 / Chapter 3.5.1 --- wyo-[3H]-inositol labelling method --- p.85 / Chapter 3.5.1.1 --- Preparation of columns --- p.86 / Chapter 3.5.1.2 --- Incubation of cells --- p.86 / Chapter 3.5.1.3 --- Measurement of [3H]-inositol phosphate production --- p.87 / Chapter 3.5.1.4 --- Data analysis --- p.88 / Chapter Chapter 4 --- Results --- p.89 / Chapter 4.1 --- Validation of PathDetect® Elkl Trans-Reporting System --- p.89 / Chapter 4.1.1 --- Introduction --- p.89 / Chapter 4.1.2 --- Internal control --- p.89 / Chapter 4.1.3 --- Response to cicaprost and ATP --- p.91 / Chapter 4.1.4 --- Normalisation of ERK1/2 activity with transfection efficiency --- p.92 / Chapter 4.1.5 --- Cicaprost response in CHO cells in the absence of mIP- receptor --- p.93 / Chapter 4.1.6 --- Normalised luciferase activity reflecting ERK1/2 activation --- p.93 / Chapter 4.1.7 --- Conclusion --- p.95 / Chapter 4.2 --- Characterization of IP-receptors --- p.101 / Chapter 4.2.1 --- IP-receptor activation of adenylyl cyclase and phospholipase C --- p.101 / Chapter 4.2.2 --- IP-receptor activation ofERKl/2 in mIP-CHO cells --- p.102 / Chapter 4.2.2.1 --- PathDetect System --- p.102 / Chapter 4.2.2.2 --- Western Blotting --- p.103 / Chapter 4.2.2.3 --- Conclusion --- p.104 / Chapter 4.2.3 --- Role of the Gs-mediated pathway in cicaprost-stimulated ERK1/2 activation --- p.104 / Chapter 4.2.3.1 --- Role of cyclic AMP --- p.105 / Chapter 4.2.3.2 --- Role of protein kinase A --- p.106 / Chapter 4.2.4 --- Role of the Gq-mediated pathway in cicaprost-stimulated ERK1/2 activation --- p.106 / Chapter 4.2.4.1 --- Role of IP3 --- p.107 / Chapter 4.2.4.2 --- Role of protein kinase C --- p.108 / Chapter 4.2.4.3 --- Conclusion --- p.108 / Chapter 4.2.5 --- IP-receptor activation of ERKl/2 in hIP-CHO cells --- p.109 / Chapter 4.2.5.1 --- Activation ofERKl/2 in hIP-CHO cells --- p.109 / Chapter 4.2.5.2 --- Role of the Gq-mediated pathway in cicaprost- stimulated ERK 1/2 activation --- p.110 / Chapter 4.2.5.3 --- Role of the Gs-mediated pathway in cicaprost- stimulated ERK 1/2 activation --- p.111 / Chapter 4.2.5.4 --- Conclusions --- p.113 / Chapter 4.2.6 --- IP-receptor activation of ERX1/2 in neuroblastoma cells --- p.114 / Chapter 4.2.6.1 --- Rat/mouse neuroblastoma/glioma (NG108-15) cells --- p.114 / Chapter 4.2.6.2 --- Human neuroblastoma (SK-N-SH) cells --- p.115 / Chapter Chapter 5 --- General Discussion and Conclusions --- p.137 / References --- p.142

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.