跳到主要內容

臺灣博碩士論文加值系統

(3.235.120.150) 您好!臺灣時間:2021/08/06 03:10
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:歐蕙綾
研究生(外文):Hui-Ling Ou
論文名稱:第二型環氧酵素抑制劑NS-398在人類卵巢顆粒層細胞中對於介白素-1b所調控介白素-8與第二型環氧酵素表現量之影響
論文名稱(外文):Novel effects of COX-2-selective inhibitor NS-398 on IL-1b-induced COX-2 and IL-8 expression in human ovarian granulosa cells
指導教授:吳鈺琳
指導教授(外文):Yuh-Lin Wu
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:89
中文關鍵詞:介白素-1bNS-398卵巢顆粒層細胞介白素-8第二型環氧酵素
外文關鍵詞:NS-398ovarian granulosa cellIL-1bIL-8COX-2
相關次數:
  • 被引用被引用:0
  • 點閱點閱:159
  • 評分評分:
  • 下載下載:25
  • 收藏至我的研究室書目清單書目收藏:0
排卵乃是生殖過程中極為重要的一環,因此該過程本應受到相當嚴密的調控。卵巢過度刺激症候群之發生則是由於在排卵過程中一些因子的過量產生所導致而成為常見的促性腺激素治療的併發症。由於排卵的過程與發炎反應之相關性,會引起發炎的因子在此病變中可能佔有其重要性。另一卵巢病變,常發生於接近停經年齡或者已停經的婦女身上的卵巢顆粒層細胞癌,有假說提出人類卵巢顆粒層細胞的癌化可能是由於卵巢受到過度刺激所導致。在調控卵巢功能的細胞介素當中,介白素-1b已被指出是許多癌症的重要指標因子且能調控其他促進發炎反應的因子之表現,例如介白素-8以及第二型環氧酵素這兩個在癌症過程中的重要因子,進而影響卵巢功能。另一方面,非固醇類抗發炎藥物例如NS-398,除了已知抗發炎之功能外,也被指出能做為具有潛力的抗癌症治療方式。因此本篇論文在於探討NS-398這個藥物在人類卵巢顆粒層細胞中對於介白素-1所引起介白素-8與第二型環氧酵素之影響。我們發現NS-398不僅沒有抑制介白素-8與第二型環氧酵素之表現量,反而具有促進之效果。而我們也發現NS-398對於介白素-8與第二型環氧酵素蛋白質穩定度並不具任何效果。為了釐清NS-398是透過何種訊息傳遞路徑來進行介白素-8與第二型環氧酵素表現量之調控,我們利用了MAPK,PKA,PKC以及NF-kB 的抑制劑阻斷這些訊息路徑,結果發現MAPK與NF-kB可能是調控路徑,於是我們進一步研究NS-398對於MAPK磷酸化以及NF-kB轉移至細胞核內的影響,根據結果推測NF-kB才是主要之訊息路徑。此外,我們也發現介白素-8對於人類卵巢顆粒層細胞具有促進其增生的效果;而NS-398與介白素-1b的共同刺激能抑制細胞循環中的調控因子p21waf-1/cip-1與p27kip-1之表現量。綜而言之,在人類卵巢顆粒層細胞中,NS-398能夠促進由介白素-1b所引發之介白素-8與第二型環氧酵素之表現,並且可能主要經由NF-kB訊息路徑進行此調控;增加之介白素-8則能促進人類卵巢顆粒層細胞之增生,另外NS-398與介白素-1�猁漲@同刺激可能透過抑制細胞循環中的調控因子p21waf-1/cip-1與p27kip-1之表現量而影響人類卵巢顆粒層細胞之細胞週期。
The process of ovulation is the key event for reproduction and therefore should be well-regulated. Ovarian hyperstimulation syndrome (OHSS), which results from excess production of some factors during ovulation, has been recognized as a dramatic complication of gonodotrophin therapy. Since ovulation has been proposed to be associated with inflammatory responses, inflammatory factors may be implicated in the occurrence of OHSS. In addition, ovarian granulosa cell tumor (GCT) is most commonly found in women between peri- and post-menopausal ages; therefore a hypothesis arises that ovarian hyperstimulation may lead to carcinogenesis of granulosa cells, which are implicated in sex hormone and growth factor production during ovarian development. Among the multiple cytokines that regulate ovarian functions, interleukin (IL)-1b is about the best-known one that have been characterized as an indicator of several cancers and could mediate the expression of other pro-inflammatory factors, such as IL-8 and cyclooxygenase 2 (COX)-2, which in turn participate in the process of ovulation. On the other hand, non-steroidal anti-inflammatory drugs (NSAIDs), for example NS-398, in addition to its traditional anti-inflammatory feature, it has also been proposed as a potential option to retard cancer development. Here we presented that, instead of attenuating the inflammatory response, NS-398 further enhanced IL-1b-induced COX-2 and IL-8 mRNA and protein expression as well as IL-8 secretion in human granulosa KGN cell line. We also examined on whether NS-398 would enhance the protein stability of COX-2 and IL-8 and we found that NS-398 did not have post-translational effect, indicating that NS-398 may act mostly at the transcriptional level. To evaluate what signaling pathways are involved in the enhancement effect by NS-398, we pretreated KGN cells with inhibitors of MAPK (ERK, JNK, p38) as well as NF-kB before the inclusion of IL-1b in the absence or presence of NS-398. Inhibition of MAPKs and NF-kB significantly reduced NS-398-mediated enhancement on IL-1b-induced COX-2 and IL-8 expression. We also found that NS-398 could promote IL-1b-mediated NF-kB p65 translocation from cytosol into nucleus but have no effect on MAPK phosphorylation. These results suggest that NS-398 may augment IL-1b-induced COX-2 and IL-8 expression through NF-kB signal pathways. In addition, IL-8 appeared to increase proliferation of KGN cells according to the alamarBlue assay. NS-398 combined with IL-1b could reduce p21waf-1/cip-1 and p27kip-1 expression, which are regulators of cell cycle. In conclusion, our data identify a novel role of NS-398 that it could amplify IL-1b-induced COX-2 and IL-8 expression possibly through an NF-kB signal pathway; the increase of IL-8 secretion may contribute to proliferation of granulosa tumor cells and NS-398 combined with IL-1b might mediate cell cycle through down-regulating p21waf-1/cip-1 and p27kip-1 expression.
INDEX 1
Abstract 3
中文摘要 6
CHAPTER 1: INTRODUCTION 8
1. INFLAMMATION AND OVARIAN FUNCTIONS 8
2. GRANULOSA CELL TUMOR OVARIAN AND OVARIAN HYPERSTIMULATION SYNDROME 10
3. INTERLEUKIN-1 13
4. INTERLEUKIN-8 15
5. CYCLOOXYGENASE-2 18
6. NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) 21
7. OBJECTIVE 24
CHAPTER 2: MATERIALS AND METHODS 26
1. CHEMICALS AND REAGENTS 26
2. CELL CULTURE 27
3. WESTERN BLOT 28
4. PROTEIN STABILITY DETECTION 30
5. REVERSE TRANSCRIPTION PCR 30
6. QUANTITATIVE REAL-TIME PCR 34
7. IL-8 ENZYME LINKED IMMUNOSORBENT ASSAY 36
8. PGE2 ENZYME LINKED IMMUNOSORBENT ASSAY 37
9. CELL PROLIFERATION ASSAY 39
10. EXTRACTION OF NUCLEAR AND CYTOSOLIC PROTEINS 39
11. STATISTICAL ANALYSIS 40
CHAPTER 3: RESULTS 41
1. NS-398 enhanced IL-1b-induced COX-2 and IL-8 expression in human ovarian granulosa cells 41
2. NS-398 increased IL-1b-induced IL-8 secretion in ovarian granulosa cells but effectively inhibited PGE2 production 41
3. NS-398 had no effect on COX-2 and IL-8 protein stability 42
4. NS-398 promoted IL-1b-mediated COX-2 and IL-8 mRNA expression 43
5. NS-398-potentiated IL-1b-mediated COX-2 and IL-8 expression might be through NF-kB signaling pathway 43
6. IL-8 promoted proliferation of ovarian granulosa cells 45
7. IL-1b combined with NS-398 attenuated expression of two cell cycle regulators -- p21waf-1/cip-1 and p27kip-1 45
CHAPTER 4: DISCUSSION 47
CHAPTER 5: REFERENCES 52
FIGURES AND FIGURE LEGENDS 63
Figure 1. Augmentation of IL-1b-induced COX-2 and IL-8 expression by NS-398 in KGN ovarian granulosa cells. 65
Figure 2. Enhancement of IL-1b-induced IL-8 secretion by NS-398. 66
Figure 3. Effective inhibition of PGE2 production by NS-398. 67
Figure 4. No effect of NS-398 on COX-2 and IL-8 protein stability at post-translational stage. 69
Figure 5. Increase of IL-1b-induced COX-2 and IL-8 mRNA expression by NS-398. 73
Figure 6. Attenuation of NS-398-enhanced IL-1b-induced COX-2 and IL-8 expression and secretion by MAPK and NF-kB inhibitors. 76
Figure 7. No involvement of PKA or PKC in NS-398-enhanced IL-1b-induced COX-2 expression. 78
Figure 8. No enhancement on the IL-1b-induced MAPK phosphorylation by NS-398. 81
Figure 9. Promotion of IL-1b-induced NF-kB p65 tranlocation by NS-398. 84
Figure 10. Proliferation of KGN cells induced by IL-8. 86
Figure 11. Decrease of cell cycle regulator p21waf-1/cip-1 and p27kip-1 by combined treatment of IL-1b and NS-398. 88
ACKNOWLEDGEMENT 89
Aihara, M., D. Tsuchimoto, H. Takizawa, A. Azuma, H. Wakebe, Y. Ohmoto, K. Imagawa, M. Kikuchi, N. Mukaida, and K. Matsushima. 1997. Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45. Infect Immun. 65:3218-24.
Albini, A., and M.B. Sporn. 2007. The tumour microenvironment as a target for chemoprevention. Nat Rev Cancer. 7:139-47.
Apte, R.N., S. Dotan, M. Elkabets, M.R. White, E. Reich, Y. Carmi, X. Song, T. Dvozkin, Y. Krelin, and E. Voronov. 2006. The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions. Cancer Metastasis Rev. 25:387-408.
Bachelor, M.A., S.J. Cooper, E.T. Sikorski, and G.T. Bowden. 2005. Inhibition of p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase decreases UVB-induced activator protein-1 and cyclooxygenase-2 in a SKH-1 hairless mouse model. Mol Cancer Res. 3:90-9.
Balasch, J., V. Arroyo, F. Fabregues, J. Salo, W. Jimenez, J.C. Pare, and J.A. Vanrell. 1994. Neurohormonal and hemodynamic changes in severe cases of the ovarian hyperstimulation syndrome. Ann Intern Med. 121:27-33.
Baud, V., Z.G. Liu, B. Bennett, N. Suzuki, Y. Xia, and M. Karin. 1999. Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes Dev. 13:1297-308.
Brasier, A.R., M. Jamaluddin, A. Casola, W. Duan, Q. Shen, and R.P. Garofalo. 1998. A promoter recruitment mechanism for tumor necrosis factor-alpha-induced interleukin-8 transcription in type II pulmonary epithelial cells. Dependence on nuclear abundance of Rel A, NF-kappaB1, and c-Rel transcription factors. J Biol Chem. 273:3551-61.
Brat, D.J., A.C. Bellail, and E.G. Van Meir. 2005. The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro Oncol. 7:122-33.
Caivano, M., and P. Cohen. 2000. Role of mitogen-activated protein kinase cascades in mediating lipopolysaccharide-stimulated induction of cyclooxygenase-2 and IL-1 beta in RAW264 macrophages. J Immunol. 164:3018-25.
Cannistra, S.A. 1993. Cancer of the ovary. N Engl J Med. 329:1550-9.
Cha, Y.I., L. Solnica-Krezel, and R.N. DuBois. 2006. Fishing for prostanoids: deciphering the developmental functions of cyclooxygenase-derived prostaglandins. Dev Biol. 289:263-72.
Chan, G., J.O. Boyle, E.K. Yang, F. Zhang, P.G. Sacks, J.P. Shah, D. Edelstein, R.A. Soslow, A.T. Koki, B.M. Woerner, J.L. Masferrer, and A.J. Dannenberg. 1999. Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res. 59:991-4.
Chandrasekharan, N.V., H. Dai, K.L. Roos, N.K. Evanson, J. Tomsik, T.S. Elton, and D.L. Simmons. 2002. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A. 99:13926-31.
Chen, J.J., W.C. Huang, and C.C. Chen. 2005. Transcriptional regulation of cyclooxygenase-2 in response to proteasome inhibitors involves reactive oxygen species-mediated signaling pathway and recruitment of CCAAT/enhancer-binding protein delta and CREB-binding protein. Mol Biol Cell. 16:5579-91.
Choi, H.C., H.S. Kim, K.Y. Lee, K.C. Chang, and Y.J. Kang. 2008. NS-398, a selective COX-2 inhibitor, inhibits proliferation of IL-1beta-stimulated vascular smooth muscle cells by induction of HO-1. Biochem Biophys Res Commun. 376:753-7.
Chun, K.S., and Y.J. Surh. 2004. Signal transduction pathways regulating cyclooxygenase-2 expression: potential molecular targets for chemoprevention. Biochem Pharmacol. 68:1089-100.
Cook, N.R., I.M. Lee, J.M. Gaziano, D. Gordon, P.M. Ridker, J.E. Manson, C.H. Hennekens, and J.E. Buring. 2005. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA. 294:47-55.
Copeland, R.A., J.M. Williams, J. Giannaras, S. Nurnberg, M. Covington, D. Pinto, S. Pick, and J.M. Trzaskos. 1994. Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase. Proc Natl Acad Sci U S A. 91:11202-6.
Coussens, L.M., and Z. Werb. 2002. Inflammation and cancer. Nature. 420:860-7.
Cuzick, J., F. Otto, J.A. Baron, P.H. Brown, J. Burn, P. Greenwald, J. Jankowski, C. La Vecchia, F. Meyskens, H.J. Senn, and M. Thun. 2009. Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol. 10:501-7.
Daheshia, M., and J.Q. Yao. 2008. The interleukin 1beta pathway in the pathogenesis of osteoarthritis. J Rheumatol. 35:2306-12.
Davis, B.J., D.E. Lennard, C.A. Lee, H.F. Tiano, S.G. Morham, W.C. Wetsel, and R. Langenbach. 1999. Anovulation in cyclooxygenase-2-deficient mice is restored by prostaglandin E2 and interleukin-1beta. Endocrinology. 140:2685-95.
de Visser, K.E., A. Eichten, and L.M. Coussens. 2006. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 6:24-37.
DeForge, L.E., A.M. Preston, E. Takeuchi, J. Kenney, L.A. Boxer, and D.G. Remick. 1993. Regulation of interleukin 8 gene expression by oxidant stress. J Biol Chem. 268:25568-76.
Denkert, C., A. Furstenberg, P.T. Daniel, I. Koch, M. Kobel, W. Weichert, A. Siegert, and S. Hauptmann. 2003. Induction of G0/G1 cell cycle arrest in ovarian carcinoma cells by the anti-inflammatory drug NS-398, but not by COX-2-specific RNA interference. Oncogene. 22:8653-61.
Derry, S., and Y.K. Loke. 2000. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ. 321:1183-7.
DeWitt, D.L. 1999. Cox-2-selective inhibitors: the new super aspirins. Mol Pharmacol. 55:625-31.
Dinarello, C.A. 1996. Biologic basis for interleukin-1 in disease. Blood. 87:2095-147.
Dinchuk, J.E., B.D. Car, R.J. Focht, J.J. Johnston, B.D. Jaffee, M.B. Covington, N.R. Contel, V.M. Eng, R.J. Collins, P.M. Czerniak, and et al. 1995. Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature. 378:406-9.
Donovan, J., and J. Slingerland. 2000. Transforming growth factor-beta and breast cancer: Cell cycle arrest by transforming growth factor-beta and its disruption in cancer. Breast Cancer Res. 2:116-24.
Eberhart, C.E., R.J. Coffey, A. Radhika, F.M. Giardiello, S. Ferrenbach, and R.N. DuBois. 1994. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 107:1183-8.
Eliopoulos, A.G., C.D. Dumitru, C.C. Wang, J. Cho, and P.N. Tsichlis. 2002. Induction of COX-2 by LPS in macrophages is regulated by Tpl2-dependent CREB activation signals. EMBO J. 21:4831-40.
Espey, L.L. 1980. Ovulation as an inflammatory reaction--a hypothesis. Biol Reprod. 22:73-106.
Espey, L.L. 1994. Current status of the hypothesis that mammalian ovulation is comparable to an inflammatory reaction. Biol Reprod. 50:233-8.
Ferrer, F.A., L.J. Miller, R.I. Andrawis, S.H. Kurtzman, P.C. Albertsen, V.P. Laudone, and D.L. Kreutzer. 1998. Angiogenesis and prostate cancer: in vivo and in vitro expression of angiogenesis factors by prostate cancer cells. Urology. 51:161-7.
Friedlander, M.A., J.R. Loret de Mola, and J.M. Goldfarb. 1993. Elevated levels of interleukin-6 in ascites and serum from women with ovarian hyperstimulation syndrome. Fertil Steril. 60:826-33.
Fujii, A., T. Harada, N. Yamauchi, T. Iwabe, Y. Nishi, T. Yanase, H. Nawata, and N. Terakawa. 2003. Interleukin-8 gene and protein expression are up-regulated by interleukin-1beta in normal human ovarian cells and a granulosa tumor cell line. Fertil Steril. 79:151-7.
Funk, C.D. 2001. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 294:1871-5.
Futaki, N., K. Yoshikawa, Y. Hamasaka, I. Arai, S. Higuchi, H. Iizuka, and S. Otomo. 1993. NS-398, a novel non-steroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions. Gen Pharmacol. 24:105-10.
Gann, P.H., J.E. Manson, R.J. Glynn, J.E. Buring, and C.H. Hennekens. 1993. Low-dose aspirin and incidence of colorectal tumors in a randomized trial. J Natl Cancer Inst. 85:1220-4.
Gans, K.R., W. Galbraith, R.J. Roman, S.B. Haber, J.S. Kerr, W.K. Schmidt, C. Smith, W.E. Hewes, and N.R. Ackerman. 1990. Anti-inflammatory and safety profile of DuP 697, a novel orally effective prostaglandin synthesis inhibitor. J Pharmacol Exp Ther. 254:180-7.
Garcia Rodriguez, L.A., S. Hernandez-Diaz, and F.J. de Abajo. 2001. Association between aspirin and upper gastrointestinal complications: systematic review of epidemiologic studies. Br J Clin Pharmacol. 52:563-71.
Gerard, N., M. Caillaud, A. Martoriati, G. Goudet, and A.C. Lalmanach. 2004. The interleukin-1 system and female reproduction. J Endocrinol. 180:203-12.
Gery, I., and B.H. Waksman. 1972. Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s). J Exp Med. 136:143-55.
Green, A.R., V.L. Green, M.C. White, and V. Speirs. 1997. Expression of cytokine messenger RNA in normal and neoplastic human breast tissue: identification of interleukin-8 as a potential regulatory factor in breast tumours. Int J Cancer. 72:937-41.
Greenhough, A., H.J. Smartt, A.E. Moore, H.R. Roberts, A.C. Williams, C. Paraskeva, and A. Kaidi. 2009. The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis. 30:377-86.
Hensley, C., S. Spitzler, B.E. McAlpine, M. Lynn, J.C. Ansel, A.R. Solomon, and C.A. Armstrong. 1998. In vivo human melanoma cytokine production: inverse correlation of GM-CSF production with tumor depth. Exp Dermatol. 7:335-41.
Hobbie, S., L.M. Chen, R.J. Davis, and J.E. Galan. 1997. Involvement of mitogen-activated protein kinase pathways in the nuclear responses and cytokine production induced by Salmonella typhimurium in cultured intestinal epithelial cells. J Immunol. 159:5550-9.
Hoffmann, E., O. Dittrich-Breiholz, H. Holtmann, and M. Kracht. 2002. Multiple control of interleukin-8 gene expression. J Leukoc Biol. 72:847-55.
Holmes, W.E., J. Lee, W.J. Kuang, G.C. Rice, and W.I. Wood. 1991. Structure and functional expression of a human interleukin-8 receptor. Science. 253:1278-80.
Holtmann, H., R. Winzen, P. Holland, S. Eickemeier, E. Hoffmann, D. Wallach, N.L. Malinin, J.A. Cooper, K. Resch, and M. Kracht. 1999. Induction of interleukin-8 synthesis integrates effects on transcription and mRNA degradation from at least three different cytokine- or stress-activated signal transduction pathways. Mol Cell Biol. 19:6742-53.
Ivarsson, K., E. Runesson, K. Sundfeldt, M. Haeger, L. Hedin, P.O. Janson, and M. Brannstrom. 1998. The chemotactic cytokine interleukin-8--a cyst fluid marker for malignant epithelial ovarian cancer? Gynecol Oncol. 71:420-3.
Iwabe, T., T. Harada, T. Tsudo, M. Tanikawa, Y. Onohara, and N. Terakawa. 1998. Pathogenetic significance of increased levels of interleukin-8 in the peritoneal fluid of patients with endometriosis. Fertil Steril. 69:924-30.
Jobin, C., L. Holt, C.A. Bradham, K. Streetz, D.A. Brenner, and R.B. Sartor. 1999. TNF receptor-associated factor-2 is involved in both IL-1 beta and TNF-alpha signaling cascades leading to NF-kappa B activation and IL-8 expression in human intestinal epithelial cells. J Immunol. 162:4447-54.
Jobling, T., P. Mamers, D.L. Healy, V. MacLachlan, H.G. Burger, M. Quinn, R. Rome, and A.J. Day. 1994. A prospective study of inhibin in granulosa cell tumors of the ovary. Gynecol Oncol. 55:285-9.
Kasahara, T., N. Mukaida, K. Yamashita, H. Yagisawa, T. Akahoshi, and K. Matsushima. 1991. IL-1 and TNF-alpha induction of IL-8 and monocyte chemotactic and activating factor (MCAF) mRNA expression in a human astrocytoma cell line. Immunology. 74:60-7.
Kaye, S.B., and E. Davies. 1986. Cyclophosphamide, adriamycin, and cis-platinum for the treatment of advanced granulosa cell tumor, using serum estradiol as a tumor marker. Gynecol Oncol. 24:261-4.
Kitadai, Y., Y. Takahashi, K. Haruma, K. Naka, K. Sumii, H. Yokozaki, W. Yasui, N. Mukaida, Y. Ohmoto, G. Kajiyama, I.J. Fidler, and E. Tahara. 1999. Transfection of interleukin-8 increases angiogenesis and tumorigenesis of human gastric carcinoma cells in nude mice. Br J Cancer. 81:647-53.
Knall, C., G.S. Worthen, and G.L. Johnson. 1997. Interleukin 8-stimulated phosphatidylinositol-3-kinase activity regulates the migration of human neutrophils independent of extracellular signal-regulated kinase and p38 mitogen-activated protein kinases. Proc Natl Acad Sci U S A. 94:3052-7.
Knall, C., S. Young, J.A. Nick, A.M. Buhl, G.S. Worthen, and G.L. Johnson. 1996. Interleukin-8 regulation of the Ras/Raf/mitogen-activated protein kinase pathway in human neutrophils. J Biol Chem. 271:2832-8.
Kniss, D.A. 1999. Cyclooxygenases in reproductive medicine and biology. J Soc Gynecol Investig. 6:285-92.
Landino, L.M., B.C. Crews, M.D. Timmons, J.D. Morrow, and L.J. Marnett. 1996. Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis. Proc Natl Acad Sci U S A. 93:15069-74.
Lane, A.H., M.M. Lee, A.F. Fuller, Jr., D.J. Kehas, P.K. Donahoe, and D.T. MacLaughlin. 1999. Diagnostic utility of Mullerian inhibiting substance determination in patients with primary and recurrent granulosa cell tumors. Gynecol Oncol. 73:51-5.
Lappohn, R.E., H.G. Burger, J. Bouma, M. Bangah, M. Krans, and H.W. de Bruijn. 1989. Inhibin as a marker for granulosa-cell tumors. N Engl J Med. 321:790-3.
Lee, L.F., J.S. Haskill, N. Mukaida, K. Matsushima, and J.P. Ting. 1997. Identification of tumor-specific paclitaxel (Taxol)-responsive regulatory elements in the interleukin-8 promoter. Mol Cell Biol. 17:5097-105.
Lee, S.H., E. Soyoola, P. Chanmugam, S. Hart, W. Sun, H. Zhong, S. Liou, D. Simmons, and D. Hwang. 1992. Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. J Biol Chem. 267:25934-8.
Li, S., K. Miner, R. Fannin, J. Carl Barrett, and B.J. Davis. 2004. Cyclooxygenase-1 and 2 in normal and malignant human ovarian epithelium. Gynecol Oncol. 92:622-7.
Liu, Y., G.L. Borchert, and J.M. Phang. 2004. Polyoma enhancer activator 3, an ets transcription factor, mediates the induction of cyclooxygenase-2 by nitric oxide in colorectal cancer cells. J Biol Chem. 279:18694-700.
Machelon, V., and D. Emilie. 1997. Production of ovarian cytokines and their role in ovulation in the mammalian ovary. Eur Cytokine Netw. 8:137-43.
Mastronarde, J.G., M.M. Monick, N. Mukaida, K. Matsushima, and G.W. Hunninghake. 1998. Activator protein-1 is the preferred transcription factor for cooperative interaction with nuclear factor-kappaB in respiratory syncytial virus-induced interleukin-8 gene expression in airway epithelium. J Infect Dis. 177:1275-81.
Medzhitov, R. 2008. Origin and physiological roles of inflammation. Nature. 454:428-35.
Morham, S.G., R. Langenbach, C.D. Loftin, H.F. Tiano, N. Vouloumanos, J.C. Jennette, J.F. Mahler, K.D. Kluckman, A. Ledford, C.A. Lee, and O. Smithies. 1995. Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell. 83:473-82.
Murayama, T., Y. Ohara, M. Obuchi, K.S. Khabar, H. Higashi, N. Mukaida, and K. Matsushima. 1997. Human cytomegalovirus induces interleukin-8 production by a human monocytic cell line, THP-1, through acting concurrently on AP-1- and NF-kappaB-binding sites of the interleukin-8 gene. J Virol. 71:5692-5.
Murphy, P.M., and H.L. Tiffany. 1991. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science. 253:1280-3.
Nakayama, G.R., M.C. Caton, M.P. Nova, and Z. Parandoosh. 1997. Assessment of the Alamar Blue assay for cellular growth and viability in vitro. J Immunol Methods. 204:205-8.
Nishi, Y., T. Yanase, Y. Mu, K. Oba, I. Ichino, M. Saito, M. Nomura, C. Mukasa, T. Okabe, K. Goto, R. Takayanagi, Y. Kashimura, M. Haji, and H. Nawata. 2001. Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor. Endocrinology. 142:437-45.
Nourbakhsh, M., S. Kalble, A. Dorrie, H. Hauser, K. Resch, and M. Kracht. 2001. The NF-kappa b repressing factor is involved in basal repression and interleukin (IL)-1-induced activation of IL-8 transcription by binding to a conserved NF-kappa b-flanking sequence element. J Biol Chem. 276:4501-8.
Nurnberg, W., D. Tobias, F. Otto, B.M. Henz, and D. Schadendorf. 1999. Expression of interleukin-8 detected by in situ hybridization correlates with worse prognosis in primary cutaneous melanoma. J Pathol. 189:546-51.
Oyesanya, R.A., Z.P. Lee, J. Wu, J. Chen, Y. Song, A. Mukherjee, P. Dent, T. Kordula, H. Zhou, and X. Fang. 2008. Transcriptional and post-transcriptional mechanisms for lysophosphatidic acid-induced cyclooxygenase-2 expression in ovarian cancer cells. FASEB J. 22:2639-51.
Park, S.W., M.W. Sung, D.S. Heo, H. Inoue, S.H. Shim, and K.H. Kim. 2005. Nitric oxide upregulates the cyclooxygenase-2 expression through the cAMP-response element in its promoter in several cancer cell lines. Oncogene. 24:6689-98.
Pectasides, D., E. Pectasides, and A. Psyrri. 2008. Granulosa cell tumor of the ovary. Cancer Treat Rev. 34:1-12.
Pellicer, A., C. Albert, A. Mercader, F. Bonilla-Musoles, J. Remohi, and C. Simon. 1999. The pathogenesis of ovarian hyperstimulation syndrome: in vivo studies investigating the role of interleukin-1beta, interleukin-6, and vascular endothelial growth factor. Fertil Steril. 71:482-9.
Perrier, S., F. Caldefie-Chezet, and M.P. Vasson. 2009. IL-1 family in breast cancer: potential interplay with leptin and other adipocytokines. FEBS Lett. 583:259-65.
Pride, S.M., B. Ho Yuen, and Y.S. Moon. 1984. Clinical, endocrinologic, and intraovarian prostaglandin F responses to H-1 receptor blockade in the ovarian hyperstimulation syndrome: studies in the rabbit model. Am J Obstet Gynecol. 148:670-4.
Radke, J., D. Schmidt, M. Bohme, U. Schmidt, W. Weise, and J. Morenz. 1996. -Cytokine level in malignant ascites and peripheral blood of patients with advanced ovarian carcinoma. Geburtshilfe Frauenheilkd. 56:83-7.
Ratnasinghe, D., J. Tangrea, M.J. Roth, S. Dawsey, N. Hu, M. Anver, Q.H. Wang, and P.R. Taylor. 1999. Expression of cyclooxygenase-2 in human squamous cell carcinoma of the esophagus; an immunohistochemical survey. Anticancer Res. 19:171-4.
Revel, A., V. Barak, Y. Lavy, E. Anteby, Y. Abramov, J.J. Schenker, A. Amit, Z. Finci-Yeheskel, M. Mayer, A. Simon, N. Laufer, and A. Hurwitz. 1996. Characterization of intraperitoneal cytokines and nitrites in women with severe ovarian hyperstimulation syndrome. Fertil Steril. 66:66-71.
Rey, R.A., C. Lhomme, I. Marcillac, N. Lahlou, P. Duvillard, N. Josso, and J.M. Bidart. 1996. Antimullerian hormone as a serum marker of granulosa cell tumorsof the ovary: comparative study with serum alpha-inhibin and estradiol. Am J Obstet Gynecol. 174:958-65.
Richards, J.S., D.L. Russell, S. Ochsner, and L.L. Espey. 2002. Ovulation: new dimensions and new regulators of the inflammatory-like response. Annu Rev Physiol. 64:69-92.
Richardson, R.M., H. Ali, B.C. Pridgen, B. Haribabu, and R. Snyderman. 1998. Multiple signaling pathways of human interleukin-8 receptor A. Independent regulation by phosphorylation. J Biol Chem. 273:10690-5.
Rizk, B., M. Aboulghar, J. Smitz, and R. Ron-El. 1997. The role of vascular endothelial growth factor and interleukins in the pathogenesis of severe ovarian hyperstimulation syndrome. Hum Reprod Update. 3:255-66.
Rodgers, K.E., J.F. Marks, D.D. Ellefson, D.L. Yanagihara, S.A. Tonetta, S.A. Vasilev, C.P. Morrow, F.J. Montz, and G.S. diZerega. 1990. Follicle regulatory protein: a novel marker for granulosa cell cancer patients. Gynecol Oncol. 37:381-7.
Schenker, J.G., and D. Weinstein. 1978. Ovarian hyperstimulation syndrome: a current survey. Fertil Steril. 30:255-68.
Schottenfeld, D., and J. Beebe-Dimmer. 2006. Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin. 56:69-83.
Schumer, S.T., and S.A. Cannistra. 2003. Granulosa cell tumor of the ovary. J Clin Oncol. 21:1180-9.
Shapiro, L., and C.A. Dinarello. 1995. Osmotic regulation of cytokine synthesis in vitro. Proc Natl Acad Sci U S A. 92:12230-4.
Singh, R.K., M.L. Varney, C.D. Bucana, and S.L. Johansson. 1999. Expression of interleukin-8 in primary and metastatic malignant melanoma of the skin. Melanoma Res. 9:383-7.
Sirois, J., D.L. Simmons, and J.S. Richards. 1992. Hormonal regulation of messenger ribonucleic acid encoding a novel isoform of prostaglandin endoperoxide H synthase in rat preovulatory follicles. Induction in vivo and in vitro. J Biol Chem. 267:11586-92.
Smartt, H.J., D.J. Elder, D.J. Hicks, N.A. Williams, and C. Paraskeva. 2003. Increased NF-kappaB DNA binding but not transcriptional activity during apoptosis induced by the COX-2-selective inhibitor NS-398 in colorectal carcinoma cells. Br J Cancer. 89:1358-65.
Smith, W.L., D.L. DeWitt, and R.M. Garavito. 2000. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem. 69:145-82.
Sonoda, Y., T. Kasahara, Y. Yamaguchi, K. Kuno, K. Matsushima, and N. Mukaida. 1997. Stimulation of interleukin-8 production by okadaic acid and vanadate in a human promyelocyte cell line, an HL-60 subline. Possible role of mitogen-activated protein kinase on the okadaic acid-induced NF-kappaB activation. J Biol Chem. 272:15366-72.
Tao, M., H. Kodama, S. Kagabu, J. Fukuda, M. Murata, Y. Shimizu, H. Hirano, and T. Tanaka. 1997. Possible contribution of follicular interleukin-1beta to nitric oxide generation in human pre-ovulatory follicles. Hum Reprod. 12:2220-5.
Tipton, D.A., D.C. Gay, and V.A. DeCoster. 2007. Effect of a cyclooxygenase-2 inhibitor on interleukin-1beta-stimulated activation of the transcription factor nuclear factor-kappa B in human gingival fibroblasts. J Periodontol. 78:542-9.
Trifan, O.C., R.M. Smith, B.D. Thompson, and T. Hla. 1999. Overexpression of cyclooxygenase-2 induces cell cycle arrest. Evidence for a prostaglandin-independent mechanism. J Biol Chem. 274:34141-7.
Tsatsanis, C., A. Androulidaki, M. Venihaki, and A.N. Margioris. 2006. Signalling networks regulating cyclooxygenase-2. Int J Biochem Cell Biol. 38:1654-61.
Ueda, T., E. Shimada, and T. Urakawa. 1994. Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis. J Gastroenterol. 29:423-9.
Unkila-Kallio, L., A. Tiitinen, T. Wahlstrom, P. Lehtovirta, and A. Leminen. 2000. Reproductive features in women developing ovarian granulosa cell tumour at a fertile age. Hum Reprod. 15:589-93.
Veltri, R.W., M.C. Miller, G. Zhao, A. Ng, G.M. Marley, G.L. Wright, Jr., R.L. Vessella, and D. Ralph. 1999. Interleukin-8 serum levels in patients with benign prostatic hyperplasia and prostate cancer. Urology. 53:139-47.
Venkatakrishnan, G., R. Salgia, and J.E. Groopman. 2000. Chemokine receptors CXCR-1/2 activate mitogen-activated protein kinase via the epidermal growth factor receptor in ovarian cancer cells. J Biol Chem. 275:6868-75.
Vig, E., M. Green, Y. Liu, D.B. Donner, N. Mukaida, M.G. Goebl, and M.A. Harrington. 1999. Modulation of tumor necrosis factor and interleukin-1-dependent NF-kappaB activity by mPLK/IRAK. J Biol Chem. 274:13077-84.
Wang, Q., Y. Zhou, X. Wang, and B.M. Evers. 2006. Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase. Oncogene. 25:43-50.
Watanabe, H., K. Nagai, M. Yamaguchi, T. Ikenoue, and N. Mori. 1993. Interleukin-1 beta stimulates prostaglandin E2 and F2 alpha synthesis in human ovarian granulosa cells in culture. Prostaglandins Leukot Essent Fatty Acids. 49:963-7.
Waugh, D.J., and C. Wilson. 2008. The interleukin-8 pathway in cancer. Clin Cancer Res. 14:6735-41.
Willemsen, W., R. Kruitwagen, B. Bastiaans, T. Hanselaar, and R. Rolland. 1993. Ovarian stimulation and granulosa-cell tumour. Lancet. 341:986-8.
Winzen, R., M. Kracht, B. Ritter, A. Wilhelm, C.Y. Chen, A.B. Shyu, M. Muller, M. Gaestel, K. Resch, and H. Holtmann. 1999. The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. EMBO J. 18:4969-80.
Wolff, H., K. Saukkonen, S. Anttila, A. Karjalainen, H. Vainio, and A. Ristimaki. 1998. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res. 58:4997-5001.
Wu, D., M. Marko, K. Claycombe, K.E. Paulson, and S.N. Meydani. 2003. Ceramide-induced and age-associated increase in macrophage COX-2 expression is mediated through up-regulation of NF-kappa B activity. J Biol Chem. 278:10983-92.
Wu, M.H., C.A. Wang, C.C. Lin, L.C. Chen, W.C. Chang, and S.J. Tsai. 2005. Distinct regulation of cyclooxygenase-2 by interleukin-1beta in normal and endometriotic stromal cells. J Clin Endocrinol Metab. 90:286-95.
Wulfing, P., R. Diallo, C. Muller, C. Wulfing, C. Poremba, A. Heinecke, A. Rody, R.R. Greb, W. Bocker, and L. Kiesel. 2003. Analysis of cyclooxygenase-2 expression in human breast cancer: high throughput tissue microarray analysis. J Cancer Res Clin Oncol. 129:375-82.
Xie, W.L., J.G. Chipman, D.L. Robertson, R.L. Erikson, and D.L. Simmons. 1991. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci U S A. 88:2692-6.
Yang, C.Y., H.W. Kuo, and H.F. Chiu. 2007. Age at first birth, parity, and risk of death from ovarian cancer in Taiwan: a country of low incidence of ovarian cancer. Int J Gynecol Cancer. 17:32-6.
Yokoe, T., Y. Iino, H. Takei, J. Horiguchi, Y. Koibuchi, M. Maemura, S. Ohwada, and Y. Morishita. 1997. Changes of cytokines and thyroid function in patients with recurrent breast cancer. Anticancer Res. 17:695-9.
Yokoyama, C., T. Takai, and T. Tanabe. 1988. Primary structure of sheep prostaglandin endoperoxide synthase deduced from cDNA sequence. FEBS Lett. 231:347-51.
Zahner, G., G. Wolf, M. Ayoub, R. Reinking, U. Panzer, S.J. Shankland, and R.A. Stahl. 2002. Cyclooxygenase-2 overexpression inhibits platelet-derived growth factor-induced mesangial cell proliferation through induction of the tumor suppressor gene p53 and the cyclin-dependent kinase inhibitors p21waf-1/cip-1 and p27kip-1. J Biol Chem. 277:9763-71.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
1. 在人類肺腫瘤細胞株A549細胞中NS-398和NU6102影響細胞內環氧合酵素相關路徑之研究
2. 第一型小窩蛋白促進第二型環氧酶蛋白降解
3. 探討活化態Notch1受體所誘導COX-2之基因表現於胃癌形成過程中所扮演的角色
4. 氨基葡萄糖對於介白素-1beta(IL-1beta)刺激攝護腺癌細胞表達介白素-8(IL-8)之調節作用探討
5. IL-8與GRO-α在全反式維甲酸治療之急性前骨髓性白血病細胞趨化遷移至肺泡表皮細胞過程中的角色
6. 開發以微載體與微流體系統抓取、培養與觀察循環性癌細胞的簡易方法
7. 飢餓素GHRP-2在人類卵巢顆粒層細胞中抑制蛋白激酶C所誘發第二型環氧酵素與介白素-8的表現
8. 消炎藥物及環氧合酶II影響人類成骨細胞增殖分子機制之探討
9. 組織蛋白去乙醯酶抑制劑TSA在人類肺腺癌細胞中抑制介白素-1β所誘發的第二型環氧酵素與介白素-8的表現
10. 溶血脂酸在老鼠巨噬細胞中對於脂多醣所誘發第二型環氧化酶及誘發型一氧化氮合成酶表現之抑制作用探討
11. 薑黃素對於溶血磷脂酸刺激卵巢癌細胞表達介白素-8之調節作用探討
12. 卵巢癌生存者生活品質之探討—急性存活期、延續存活期及持續存活期個案對照研究
13. HDAC4參與sumoylation修飾之LAP1所抑制的COX-2基因轉錄
14. 第二型環氧酵素在溶血磷脂酸所引發卵巢癌細胞增生中的角色
15. 某醫學中心婦產科門診45-60歲婦女更年期症狀與生活品質之關係