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DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 江俊斌 | |
dc.contributor.author | Pin-Yi Lin | en |
dc.contributor.author | 林秉毅 | zh_TW |
dc.date.accessioned | 2021-06-13T16:32:46Z | - |
dc.date.available | 2005-07-20 | |
dc.date.copyright | 2005-07-20 | |
dc.date.issued | 2005 | |
dc.date.submitted | 2005-07-11 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/38410 | - |
dc.description.abstract | 背景:缺氧誘導因子-1α(Hypoxia inducible factor-1α, HIF-1α)蛋白於人類許多癌腫瘤中有過度表現。目前已經發現HIF-1α蛋白之過度表現與許多腫瘤的侵犯、淋巴結轉移、臨床分期、病人存活率及預後都有顯著相關性。
方法:本研究利用免疫組織化學染色法,探討HIF-1α於57例口腔鱗狀細胞癌(OSCC),41例口腔上皮變異(OED, 12 輕度, 17中度, 14重度),和14例正常口腔黏膜(NOM)之表現。計算各組中核標記指數,染色強度,及核標記指數和染色強度相乘所得到的核標記分數,並比較各組差異。進一步利用統計分析,探討HIF-1α的表現和OSCC患者臨床病理參數及存活率之相關性,以研究是否HIF-1α之表現和OSCC的腫瘤進展及預後有關。 結論:HIF-1α之平均核標記指數,從NOM 的6±9%,到輕度OED 的25±18%,中度OED 的41±27%,重度OED 的42±22%,至OSCC 之55±23%,在統計學上有隨著惡性程度的增加而顯著增高之情形 (P = 0.000)。HIF-1α之核平均標記分數,從NOM 的16±15%,到輕度OED 的62±63%,中度 OED 的106±91%,重度OED 的97±74%,至OSCC 之129±82%,在統計學上有隨著惡性程度的增加而顯著增高之情形 (P = 0.000)。統計分析結果顯示,HIF-1α在OSCC中之較高表現與患者男性、較大的OSCC腫瘤、有淋巴結轉移和較高之臨床期數,有統計學上有意義之相關。HIF-1α核標記指數大於60%或核標記分數大於120%的OSCC患者,在統計上有顯著較差的存活率(log-rank test, P <0.05)。 結論:我們的結果顯示,HIF-1α之表現是在台灣口腔癌形成的早期現象。HIF-1α在OSCC之核標記指數及核標記分數可預測台灣OSCC的腫瘤進展及OSCC患者之預後。 | zh_TW |
dc.description.abstract | Background: Overexpression of hypoxia-inducible factor-1α (HIF-1α) has been demonstrated in a variety of human cancers and found to be significantly associated with the tumor invasion, lymph node metastasis, clinical stage, survival rate, and prognosis of these cancers.
Methods: In this study, we examined the expression of HIF-1α in 57 specimens of oral squamous cell carcinoma (OSCC), 41 specimens of oral epithelial dysplasia (OED, 12 mild, 17 moderate, and 12 severe OED cases), and 14 specimens of normal oral mucosa (NOM) by immunohistochemistry. The nuclear HIF-1α labeling indices (LIs, defined as the percentage of positive cells in total cells), staining intensity (SI), and labeling scores (LSs, defined as LI × SI) in OSCC, OED, and NOM samples were calculated and compared between groups. The correlation between the nuclear HIF-1α LIs or LSs in OSCCs and clinicopathological parameters or survival of OSCC patients was analyzed statistically to evaluate the possible influence of HIF-1α on the progression and prognosis of OSCCs in Taiwan. Results: The mean nuclear HIF-1α LIs increased significantly from NOM (6±9%) through mild OED (25±18%), moderate OED (41±27%), and severe OED (42±22%) to OSCC samples (55±23%, P=0.000). The mean nuclear HIF-1α LSs also increased significantly from NOM (16±15%) through mild OED (62±63%), moderate OED (106±91%), and severe OED (97±74%) to OSCC samples (129±82%, P=0.000). Male OSCC patients and OSCC patients with larger tumor size, regional lymph node metastasis, or more advanced clinical stages were prone to have a significantly higher mean nuclear HIF-1α LI or LS in OSCC samples. Moreover, OSCC patients with nuclear HIF-1α LI≧60% or nuclear HIF-1α LS≧120% had a significantly poorer survival rate than OSCC patients with nuclear HIF-1α LI<60% or nuclear HIF-1α LS<120%, respectively (log-rank test, P <0.05). Conclusion: Our results suggest that the expression of HIF-1α is an early event in oral carcinogenesis in Taiwan. The nuclear HIF-1α LI or LS in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients in Taiwan. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T16:32:46Z (GMT). No. of bitstreams: 1 ntu-94-R91422022-1.pdf: 903331 bytes, checksum: 490632c1dde86662d4c9b3cfb288a235 (MD5) Previous issue date: 2005 | en |
dc.description.tableofcontents | 中文摘要…………………………………………………………………9
Abstract.………………………………………………………….10 Introduction………………………………………………………..12 Background…………………………………………………………..16 Purposes of this study…………………………………………18 Literature Review 1.Angiogenesis………………………………………………………19 2.Structure of HIF-1………………………………………………20 3.Mechanisms of HIF-1 Activation………………………………21 4.Role of Protein Kinase Pathways…………………………….24 5.HIF-1α and the PI3K/Akt pathway……………………………..27 6.HIF-1α and the MAP kinase pathway…………………………..30 7.HIF-1α in carcinogenesis……………………………………….31 8.Implications for anti-tumor therapy……………………….35 Materials and methods Part 1: Patients and specimens…………………………….. …38 Part 2: Immunohistochemical staining for HIF-1α …………. 39 Part 3: Statistical analysis…………………………………40 Results Part 1: The nuclear HIF-1α positive staining rates, mean nuclear HIF-1α LIs, medians of nuclear HIF-1α SI, and mean nuclear HIF-1α LSs for NOM, OED, and OSCC samples………………………………………………………………..42 Part 2: Correlation between nuclear HIH-α LIs or LSs in OSCCs and clinicopathological parameters of OSCC patients…………………………………43 Part 3: Correlation between nuclear HIF-1α LIs or LSs in OSCCs and oral habits of OSCC patients……………………..44 Part 4: Correlation between nuclear HIF-1α LIs or LSs in OSCCs and survival of OSCC patients………………………..44 Discussion………………………………………………………… 46 Conclusion…………………………………….…………………… 55 Tables Table 1. Genes regulated by HIF-1 …………………………… 56 Table 2. The nuclear HIF-1α positive staining rates (PSRs), mean nuclear HIF-1α labeling indices (LIs), medians of nuclear HIF-1α staining intensity (SI), and mean nuclear HIF-1α labeling scores (LSs) in normal oral mucosa (NOM), oral epithelial dysplasia (OED), and oral squamous cell carcinoma (OSCC) samples……………57 Table 3. Correlation between the nuclear HIF-1α labeling indices (LIs) or labeling scores (LSs) in OSCC samples and clinicopathological parameters of OSCC patients……………58 Table 4. Correlation between nuclear HIF-1α labeling indices (LIs) or labeling scores (LSs) in OSCC samples and oral habits of OSCC patients…………………………59 Table 5. Univariate & Multivariate survival analysis of HIF-1α and clinicopathologic parameters in patients of OSCC (Cox regression)...................................60 Figures Figure 1. Schematic representation of HIF-1α and HIF-1β..61 Figure 2. Oxygen-dependent regulation of HIF depends on site-specific hydroxylation of the HIF-1α subunit…………62 Figure 3. Schematic overview of the receptor-mediated and hypoxic signal pathways and the mechanisms they employ to activate HIF and induce transcription of downstream target genes…………………………………………………………….63 Figure 4. Schematic representation of the molecular interactions controlling receptor-mediated signals leading to HIF-1α dependent transcription of downstream target genes…………………………………………………………………64 Figure 5. Phosphorylation of HIF-1α: the 2 main pathways leading to phosphorylation of HIF-1α…………………………………………65 Figure 6. Immunohistochemical staining for HIF-1α……………….66 Figure 7. Kaplan-Meier survival curves showing relation between nuclear HIF-1α LIs in primary tumors and survival in 57 patients with OSCC………………………….68 Figure 8. Kaplan-Meier survival curves showing relation between nuclear HIF-1α LSs in primary tumors and survival in 57 patients with OSCC……………….………….69 References……………………………………………………………70 | |
dc.language.iso | en | |
dc.title | 缺氧誘導因子-1α於口腔鱗狀細胞癌之表現 | zh_TW |
dc.title | Expression of Hypoxia Inducible Factor-1α (HIF-1α) in oral squamous cell carcinomas | en |
dc.type | Thesis | |
dc.date.schoolyear | 93-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 郭英雄 | |
dc.contributor.oralexamcommittee | 張龍昌 | |
dc.subject.keyword | 缺氧誘導因子-1α,口腔癌,口腔癌前病變, | zh_TW |
dc.subject.keyword | hypoxia-inducible factor-1α,oral cancer,oral precancer, | en |
dc.relation.page | 92 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2005-07-11 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
顯示於系所單位: | 臨床牙醫學研究所 |
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