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題 名 | 肝癌病患淋巴球粒線體DNA D-loop突變性與單碳代謝及肝癌風險因子之相關性=Mutations in the D-Loop Region of Mitochondrial DNA in Lymphocytes of Patients with Hepatocellular Carcinoma and Their Associations with One-Carbon Metabolism and Cancer Risk Factors |
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作 者 | 張緯弘; 郭常勝; 林勤益; 陳俊杰; 許瑞芬; | 書刊名 | 臺灣營養學會雜誌 |
卷 期 | 33:2 2008.06[民97.06] |
頁 次 | 頁45-54 |
分類號 | 416.246 |
關鍵詞 | 肝癌; 淋巴球粒線體DNA D-loop突變; 單碳代謝因子; 肝癌風險因子; Hepatocellular carcinoma; Lymphocyte mitochondrial DNA D-loop mutations; One carbon metabolism; Liver cancer risk factor; |
語 文 | 中文(Chinese) |
中文摘要 | 本研究探討肝癌病患淋巴球粒腺體DNA D-loop突然性與肝癌風險因子的相關性。由臺南奇美醫院肝膽科肝癌患者選取25名為病例組,並篩選年齡性別配對之健康對照組18名,由分離出血液單核淋巴球萃取之DNA,以聚合?連鎖反應擴增特定粒腺體DNA D-loop片段。將擴增粒線體DNA片段純化後定序,並與正常人類粒線體DNA D-loop序列進行比對,鑑定其突變性。研究結果發現在所有受試者淋巴球粒線體DNA D-loop中共攜帶61個突變點,包含點突變、斷損突變、插入突變。相較於健康對照組淋巴球粒線體DNa D-loop突變性,有22個突變點是僅發現於肝癌樣本。此22個突變中有5點(427 C to A、432 A to C、527 C to G、548 C to A、548 C to A)分別坐落於light-strand promoter (LSP) 和heavy strand promoter (HSP)區域,為轉錄粒線體DNA和合成RNA引子的位置。在功能位置CSB2的插入突變309 CT insertion則發現,肝癌組比對照組更易有突弈的趨勢(突變頻率:對照組 4/22 vs. 肝癌組 12/48; p=0.08)。肝癌組和對照組其淋巴球粒線體DNA D-loop突變數與隨著老化年齡增加(□60歲)而顯著上升(p=0.008)。淋巴球粒線體DNA D-loop突變總數和抽菸,飲酒,病毒感染與單碳代謝因子如血清葉酸、淋巴球葉酸與同半胱胺酸濃度均無顯著相關性。肝癌病患淋巴球粒線體DNA D-loop 突變性與肝癌風險因子單碳代謝相關性需在後續研究增加樣本數來印證。 |
英文摘要 | The aims of this study were to characterize mutations in the D-loop region of mitochondrial (mt) DNA in lyphocytes of patients with hepatocellular carcinoma (HCC), and their associations with risk factors for HCC. Lymphocytic DNA samples were obtained from 25 HCC patients and 18 healthy controls which were recruited from Chi Mei Medical Center, Tainan, Taiwan. The D-loop region of mtDNA was amplified by a polymerase chain reaction (PCR), and then the PCR products were sequenced to determine the numbers and types of mutations. The results revealed that 61 mutations including point mutations, deletions, and insertions were detected in the D-loop region of lymphocytic mtDNA from all study subjects. Twenty-two of 61 mutations were only found in HCC patients, among which 5 mutations (427 C to A, 432 A to C, 527 C to G, 548 C to A, and 548 C to A) were located in the light- (LSP) and heavy-strand promoter (HSP) of mtDNA. These are functional regions for mtDNA transcription and synthesis of RNA primers for transcription, respectively? A higher frequency of mtDNA mutations with the CSB2 309 CT insertions was found in HCC patients than in the controls (mutation frequency: control 4/22 vs. HCC 12/48; p=0.08). The total numbers of mtDNA D-loop mutations in lymphocytes of study subjects were associated with age (4.43±1.81 for those < 60 years vs. 7.08±3.20 for those □ 60 year, p=0.008). The numbers of mutations in the mtDNA D-loop region were not associated with serum folate, lymphocytic folate, homocysteine levels, or other HCC risk factors. Further studies with larger sample sizes are warranted to confirm the association between mtDNA mutaitons and 1-carbon metabolites |
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