| DC 欄位 |
值 |
語言 |
| DC.contributor | 生命科學系 | zh_TW |
| DC.creator | 陳婷軒 | zh_TW |
| DC.creator | Ting-Xuan Chen | en_US |
| dc.date.accessioned | 2024-8-22T07:39:07Z | |
| dc.date.available | 2024-8-22T07:39:07Z | |
| dc.date.issued | 2024 | |
| dc.identifier.uri | http://ir.lib.ncu.edu.tw:444/thesis/view_etd.asp?URN=110821007 | |
| dc.contributor.department | 生命科學系 | zh_TW |
| DC.description | 國立中央大學 | zh_TW |
| DC.description | National Central University | en_US |
| dc.description.abstract | Neuroblastoma (NB) is the most common extracranial solid tumor in children, with high-risk NB patients facing a survival rate of less than 50%. Therefore, a novel therapeutic avenue for NB is imperative. Notably, EGFRs, ErbB1 and ErbB2, are highly expressed in NB cells, and activating these receptors significantly promotes the proliferation of NB cells. Targeting ErbB1 and ErbB2 may be a potential treatment for NB. The preliminary data showed that the ErbB1 and ErbB2 dual inhibitor, CL -387785, exerts notable inhibitory effects on NB cell proliferation, migration, and invasion. Additionally, transcriptomic analysis via qPCR array showed that TIMP3 was upregulated in CL-387785-treated cells. In this study, I would like to examine the therapeutic efficacy of CL-387785 in vivo and further explore the regulatory mechanism of TIMP3 in NB. By the mouse subcutaneous xenograft and tail-vein metastasis model, I found that CL-387785 effectively inhibits the tumor growth and the liver metastasis of NB cells. After EGF treatments, the mRNA expression of TIMP-3 was inhibited, while DNMT1 and EZH2 were induced. Conversely, treatments of the epigenetic regulation inhibitors, 5-Azacytidine (5-Aza), Tazemetostat (EPZ-6438), and Trichostatin A (TSA), upregulated the TIMP3 mRNA level. These in-vitro findings suggest that the EGFR pathway likely regulates TIMP3 both transcriptionally and epigenetically. However, further investigations are warranted to elucidate the precise mechanism through which EGFR modulates TIMP3 expression and consequently impacts NB progression. | zh_TW |
| dc.description.abstract | Neuroblastoma (NB) is the most common extracranial solid tumor in children, with high-risk NB patients facing a survival rate of less than 50%. Therefore, a novel therapeutic avenue for NB is imperative. Notably, EGFRs, ErbB1 and ErbB2, are highly expressed in NB cells, and activating these receptors significantly promotes the proliferation of NB cells. Targeting ErbB1 and ErbB2 may be a potential treatment for NB. The preliminary data showed that the ErbB1 and ErbB2 dual inhibitor, CL -387785, exerts notable inhibitory effects on NB cell proliferation, migration, and invasion. Additionally, transcriptomic analysis via qPCR array showed that TIMP3 was upregulated in CL-387785-treated cells. In this study, I would like to examine the therapeutic efficacy of CL-387785 in vivo and further explore the regulatory mechanism of TIMP3 in NB. By the mouse subcutaneous xenograft and tail-vein metastasis model, I found that CL-387785 effectively inhibits the tumor growth and the liver metastasis of NB cells. After EGF treatments, the mRNA expression of TIMP-3 was inhibited, while DNMT1 and EZH2 were induced. Conversely, treatments of the epigenetic regulation inhibitors, 5-Azacytidine (5-Aza), Tazemetostat (EPZ-6438), and Trichostatin A (TSA), upregulated the TIMP3 mRNA level. These in-vitro findings suggest that the EGFR pathway likely regulates TIMP3 both transcriptionally and epigenetically. However, further investigations are warranted to elucidate the precise mechanism through which EGFR modulates TIMP3 expression and consequently impacts NB progression. | en_US |
| DC.subject | 神經母細胞瘤 | zh_TW |
| DC.subject | 表觀遺傳學 | zh_TW |
| DC.subject | Neuroblastoma | en_US |
| DC.subject | TIMP3 | en_US |
| DC.subject | CL-387,785 | en_US |
| DC.subject | EGFR signaling | en_US |
| DC.subject | Epigenetics | en_US |
| DC.title | 探討TIMP-3在EGFR抑制劑治療神經母細胞瘤中的調節機制 | zh_TW |
| dc.language.iso | zh-TW | zh-TW |
| DC.title | Exploring the regulation mechanism of TIMP-3 in the EGFR inhibitor treatment of neuroblastoma | en_US |
| DC.type | 博碩士論文 | zh_TW |
| DC.type | thesis | en_US |
| DC.publisher | National Central University | en_US |