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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃佩欣,許世明 | |
| dc.contributor.author | Mu-Fan Tsou | en |
| dc.contributor.author | 鄒牧帆 | zh_TW |
| dc.date.accessioned | 2021-06-13T03:32:39Z | - |
| dc.date.available | 2009-08-04 | |
| dc.date.copyright | 2006-08-04 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-27 | |
| dc.identifier.citation | Antipenko, A., Himanen, J.-P., van Leyen, K., Nardi-Dei, V., Lesniak, J., Barton, W. A., Rajashankar, K. R., Lu, M., Hoemme, C., Puschel, A. W., and Nikolov, D. B. (2003). Structure of the Semaphorin-3A Receptor Binding Module. Neuron 39, 589-598.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32121 | - |
| dc.description.abstract | 惡性卵巢子宮內膜癌在上皮性卵巢癌佔有10-20%的比率，其抵抗化學治療及伴隨著癌症轉移的特性，使卵巢子宮內膜癌成為適合研究卵巢衍生癌症進程的模型。在P0及P4這兩株分別為低及高侵略性的卵巢子宮內膜癌細胞株中，我們發現於第三類semaphorin分子中，Sema3E在高侵略性的P4細胞株中有顯著的表現，而Sema3E的受體Plexin D1和/或neuropilins的表現量則無顯著差異。在35例選自臺大醫院診斷為卵巢子宮內膜癌的病人中，經由免疫組織化學染色法證明，Sema3E的表現量與癌症惡性程度在統計上具有顯著相關性。在wound healing以及Transwell chamber的實驗中，發現轉染到低侵略性P0細胞中的Sema3E，會增加細胞侵略性及其移動的能力，並與Sema3E表現濃度成正相關。活體實驗中，將大量表現Sema3E分子的P0細胞株，異體移植至SCID mice後，發現其兩邊肺臟有多處癌症轉移。不表現Sema3E的P0細胞株則無此情形。再者，p87-Sema3E及furin作用後的p61-Sema3E同樣會對腫瘤細胞的侵略及移動造成影響。在利用siRNA抑制Plexin D1表現後，Sema3E即使大量表現也不再具有刺激細胞侵略生長和轉移的能力。我們的研究提出一個重要的發現：大量表現Sema3E，會以autocrine和/或paracrine的方式促進癌症侵略性與轉移，並且受到Plexin D1訊息傳導的調控。 | zh_TW |
| dc.description.abstract | Malignant ovarian endometrioid carcinomas, usually accompanied with metastasis upon diagnosis, account for 10 to 20% of epithelial ovarian cancers (EOCs) and are refractory to chemotherapy. Consequently, ovarian endometrioid carcinomas can serve as a promising model to study cancer progression originated from ovaries. Using two well-established human endometrioid carcinoma cell lines with different ability in invasion (P0 cells: low invasive, P4 cells: high invasive), we found that among all class 3 semaphorins, Sema3E is significantly over-expressed in the more invasive endometrioid carcinoma cells. However, the receptor for Sema3E, Plexin D1 and/or neuropilin, shows no difference in expression level between these cell lines. Statistical analysis of 35 patients with ovarian endometrioid carcinomas diagnosed from 1999 to 2005 at NTUH demonstrated positive parallel correlation between tumor grade and Sema3E expression level assessed by immunohistochemistry. When exogenous Sema3E was stably introduced into the low-invasive P0 cells, Sema3E augmented cellular invasiveness and migration in a concentration-dependent way as assessed by wound healing and Transwell chamber assay in vitro. In vivo, xenografted P0 cells with stably expressed Sema3E resulted in multi-focal tumor metastasis in bilateral lungs of SCID mice, in strong contrast to non-metastasis of P0 cells without Sema3E expression. We further revealed that both furin-cleaved p61-Sema3E and unprocessed p87-Sema3E enhance cellular invasiveness and migration to the similar effect. When Plexin D1 was functionally knocked-down by siRNA in the presence of over-expressed Sema3E, Sema3E no longer promoted cellular invasive and migratory capability. Our research strongly argues for the pivotal role of Plexin D1 signaling pathway triggered by over-expressed Sema3E in the regulation of invasiveness and migration ability of ovarian endometrioid carcinoma via an autocrine and/or paracrine manner. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T03:32:39Z (GMT). No. of bitstreams: 1 ntu-95-R93444005-1.pdf: 9727083 bytes, checksum: 6b5dcc9634d7882638738d2c9a3be18a (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | FIGURE CONTENT 4
TABLE CONTENT 5 ABBREVIATION 6 ABSTRACT 7 ABSTRACT (CHINESE) 9 INTRODUCTION 10 STUDY PURPOSE 15 MATERIALS AND METHODS 16 RESULTS 22 DISCUSSION 29 FIGURES 34 TABLES 50 APPENDIX 53 REFERENCES 55 Figure Content Figure 1. Semi-quantitative RT-PCR analysis of class 3 semaphorins and their coreceptors. 34 Figure 2. Semi-quantitative RT-PCR analysis of class 3 semaphorins in P0 versus P4 cells 35 Figure 3. Semi-quantitative RT-PCR analysis of coreceptor-Plexins and Neuropilins in P0 versus P4 cells 35 Figure 4. RNA in situ hybridization of P0 and P4 cells. Sema3E-positive cells were observed in more invasive P4 cells. 36 Figure 5. No difference of Sema3E expression in other type ovarian cancer. 36 Figure 6. Expression level of Sema3E in different grade human ovarian endometrioid carcinoma. 37 Figure 7. Indistinguishable PlexinD1 expression level in human ovarian endometrioid carcinoma. 37 Figure 8. RNA in situ hybridization of NRP1 expression in human ovarian endometrioid carcinoma……………………………………………………………………………………...……38 Figure 9. Similar NRP2 expression level was observed in human ovarian endometrioid carcinoma……………………………………………………………………………………….…..38 Figure 10. RNA in situ hybridization of Sema3F and Sema3C expression in human ovarian endometrioid carcinoma. 39 Figure 11. Semi-quantitative RT-PCR analysis of stable Sema3E-transfected P0 cell lines labeled as P0-3Ex……………………………………………………………..……….40 Figure 12. RNA in situ hybridization of P0-Sema3E cells. Stable transfected P0-3E1 and P0-3E10 had positive staining of Sema3E……………………………………………..40 Figure 13. Over-expressed Sema3E did not affect cell proliferation or apoptosis…..…..41 Figure 14. Over-expressed Sema3E in P0 cell stimulates migration…………………………42 Figure 15. Over-expressed Sema3E stimulates cell invasion……………………..……………43 Figure 16. Transwell assay showed that stable transfected P0-E1 cells had rapid migration rate with high invasive capacity. 44 Figure 17. Metastatic lesions in tail vein injected mice 45 Figure 18. p61-Sema3E isoform stimulats cells migration. 46 Figure 19. Diagram of p61-Sema3E isoform stimulats cells migration. 47 Figure 20. Point mutation of p87-Sema3E did not stimulate cells migration 48 Figure 21. Plexin D1 siRNA expression inhibits cells motility. 49 Table content Table 1. Primers for Human Semaphorins, Neuropilins, and Plexins..…50 Table 2. Sema3E expression positive correlated with high grade tumor……………………………………………………..………….…51 Table 3. Statistic analysis of tail vein injected mice………………………..52 | |
| dc.language.iso | en | |
| dc.subject | 卵巢子宮內膜癌 | zh_TW |
| dc.subject | 侵略性生長 | zh_TW |
| dc.subject | invasive growth | en |
| dc.subject | ovarian endometrioid carcinoma | en |
| dc.subject | semaphorin | en |
| dc.title | Semaphorin3E及其受體Plexin D1促進卵巢子宮內膜癌侵略性生長現象之分子機制探討 | zh_TW |
| dc.title | Molecular Mechanism of Semaphorin3E and Its Receptor Plexin D1 in Invasive Growth of Ovarian Endometrioid Carcinomas | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林仁混,鄭安理,林欽塘 | |
| dc.subject.keyword | 卵巢子宮內膜癌,侵略性生長, | zh_TW |
| dc.subject.keyword | semaphorin,ovarian endometrioid carcinoma,invasive growth, | en |
| dc.relation.page | 59 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-28 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 病理學研究所 | zh_TW |
| 顯示於系所單位： | 病理學科所 | |
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