跳到主要內容

臺灣博碩士論文加值系統

(44.201.97.0) 您好!臺灣時間:2024/04/14 03:08
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:吳銘芳
研究生(外文):Ming-Fang Wu
論文名稱:人類乳突瘤病毒感染在台灣女性肺癌形成之角色研究
論文名稱(外文):The Role of Human Papillomavirus Infection in Tumorigenesis of Female Lung Cancer in Taiwan
指導教授:周明智周明智引用關係李輝李輝引用關係
學位類別:博士
校院名稱:中山醫學大學
系所名稱:醫學研究所
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:2005
畢業學年度:93
語文別:中文
論文頁數:126
中文關鍵詞:人類乳突瘤病毒血液循環p16INK4a促進子甲基化肺癌
外文關鍵詞:Human papillomavirusBlood circulationp16INK4a promoter hypermethylationLung cancer
相關次數:
  • 被引用被引用:1
  • 點閱點閱:246
  • 評分評分:
  • 下載下載:37
  • 收藏至我的研究室書目清單書目收藏:3
自民國七十五年開始,肺癌一直是台灣女性和男性癌症的第一和第二大癌症死亡原因。已知抽菸是導致肺癌的最重要原因,歐美國家的肺癌有90 % 以上可用抽菸來解釋。但是台灣地區則有一半的肺癌無法以抽菸來解釋,尤其台灣女性肺癌患者有90 % 以上是不抽菸者。由本研究室先前研究發現,HPV 16/18 感染和不抽菸台灣女性肺癌形成有關 (Cheng et al., 2001)。最近又發現,在肺癌病患肺腫瘤組織切片上的血球抹片上可測得HPV DNA。本研究擬探討台灣女性肺癌患者HPV的感染路徑,以及評估血液循環中之血球中HPV DNA存在,是否可做為罹患肺癌之危險指標。因此本研究選取149位肺癌患者及175位非癌症的成人,以巢疊式聚合酶連鎖反應(nested-PCR)分析血球中HPV的感染率,並比較同時具有組織檢體與血液檢體之70例肺癌病患,其HPV表現在肺腫瘤組織中與患者血液檢體中之相關性。我們發現肺癌患者血球中HPV 16/18感染率均高於非癌症者 (HPV 16, 47.7% vs 12.6%, P < 0.0001; HPV 18, 30.9% vs 5.2%, P < 0.0001)。HPV 16的感染頻率於女性肺癌患者高於男性肺癌患者(57.6% vs 41.1% , P=0.048),第三期與第四期肺癌患者高於第一期與第二期患者(54.6% vs 29.3%, P=0.006)。由多變項統計分析的結果顯示,參與肺癌之危險因子中,在HPV 16或HPV 18單獨感染方面,感染者比未感染者分別有6.5倍 (P < 0.0001)及9.2倍(P < 0.0001)罹患肺癌之危險性,而同時感染HPV 16/18者比未感染者罹患肺癌之危險性高達75.7倍(P < 0.0001)。由此顯示血球中有HPV 16/18 DNA的感染可做為罹患肺癌的危險指標。
由先前的研究可推論HPV可能與女性肺癌的形成有關,但致癌的機轉仍不清楚,其他研究指出,p16INK4a 基因的去活化在肺癌中發生的頻率很高。p16INK4a基因的高度甲基化與抽菸有關。而台灣女性肺癌患者大多為不抽菸者,因此假設不抽菸之女性肺癌之p16 基因的去活化機制上,可能與男性肺癌患者不同。為了查驗環境暴露對p16INK4a 高度甲基化的影響,包括抽菸、環境致癌物的暴露和HPV感染,我們以methylation-specific PCR分析了162個肺癌患者腫瘤組織,包括67位抽菸男性肺癌,41位不抽菸男性肺癌和58位不抽菸女性肺癌。結果顯示在67位抽菸男性肺癌,59.7 ﹪(40/67位)可偵測到p16INK4a 高度甲基化,不抽菸男性肺癌36.6 ﹪(15/41位),不抽菸女性肺癌60.3 ﹪(35/58位)。這個結果似乎透露性別和抽菸對p16INK4a 高度甲基化有相同的影響。因此,我們推測HPV感染可能促進不抽菸女性的肺癌p16INK4a 高度甲基化。由我們的結果知道,不抽菸女性肺癌腫瘤有HPV感染,其p16INK4a高度甲基化的頻率高達70 ﹪(30/43位),相較於無HPV感染的僅33 ﹪(5/15位)。有HPV感染和p16INK4a 高度甲基化僅於不抽菸女性肺腫瘤有相關性(P=0.017),於抽菸男性或不抽菸男性肺癌腫瘤則無相關性。更進一步分析,p16INK4a 免疫染色和p16INK4a 促進子高度甲基化的負相關性僅見於不抽菸女性肺癌。這些結果高度建議著HPV感染的台灣女性肺癌,HPV感染可能有部分經由促進子甲基化涉及p16INK4a基因的不活化。我們的結果可以提供環境-超越基因(environment-epigenetic)的相互作用在人類腫瘤發展因地域的變化扮演一個角色的證據。
Lung cancer is the leading cause of cancer death in Taiwan, and the paucity of dependable risk markers has impeded the early management of lung cancer. An association of human papillomavirus 16/18 infection with lung cancer among non-smoking Taiwanese women was revealed in our previous study. Nested PCR was employed to detect HPV 16/18 DNA in blood circulation of 149 lung cancer patients and 174 non-cancer controls. Additionally, correlation of prevalence of HPV DNA between the blood circulation and lung tumor tissue was compared from 70 sets of paired tumor tissues and peripheral blood samples available. The results showed that the prevalence rate of HPV 16/18 in the blood circulation of lung cancer cases was significantly higher than that of non-cancer controls (47.7% vs. 12.6% for HPV 16, P<0.0001; 30.9% vs. 5.2% for HPV 18, P<0.0001). A significantly higher HPV 16 prevalence was detected in female lung cancer patients than that of male (57.6% vs. 41.1%, P=0.048), as well as in cases with tumor stages III/IV than those with tumor stages I /II (54.6% vs. 29.3%, P=0.006). After adjusting the effects of age, gender, and smoking status, a 6.5-fold greater risk of lung cancer was demonstrated for those subjects with HPV type 16 positive (95% CI 3.7-11.3, P<0.0001), a 9.2-fold for HPV type 18 positive (95% CI 4.2-20.2, P<0.0001), and a 75.7-fold greatest risk for those with both HPV type 16 and 18 positive (95% CI 9.8-582.1, P<0.0001). These results suggested that the presence of HPV DNA in the blood circulation may serve as a feasible risk marker of lung cancer.
Inactivation of p16 INK4a gene through promoter hypermethylation has been frequently observed in non small cell lung cancer; however, various studies have shown a controversial correlation between p16 INK4a hypermethylation and cigarette smoking. Our recent report showed that human papillomarvirus (HPV) 16/18 infections were associated with the development of nonsmoking female lung cancer in Taiwan and we further speculated that HPV infection may be linked with p16INK4a hypermethylation. To verify the influence of environmental exposure, including cigarette smoking, environmental carcinogen exposure and HPV infections on p16 INK4a hypermethylation, tumors from 162 lung patients, including 67 smoking males, 41 nonsmoking males and 58 nonsmoking females, were subjected to p16INK4a hypermethylation analysis by methylation-specific PCR. As the results showed, p16 INK4a hypermethylation was detected in 40 (59.7%) of 67 smoking male, 15 (36.6%) of 41 nonsmoking male and 35 (60.3%) of 58 nonsmoking female lung tumors. This result seemed to reveal that gender and cigarette smoking both possess an equal influence on p16INK4a hypermethylation. This result also led to a speculation that HPV infection may promote p16 INK4a hypermethylation in nonsmoking female lung cancer patients. From our data, p16 INK4a hypermethylation frequency in nonsmoking female lung tumors with HPV infection was as high as 70% (30 of 43) compared to those without HPV infection (33%; 5 of 15). In fact, the correlation between HPV infection and p16 INK4a hypermethylation was only observed in nonsmoking female lung tumors (p = 0.017), but not in smoking male or nonsmoking male lung tumors. Moreover, the reverse correlation between p16INK4a immunostaining and p16INK4a promoter hypermethylation was also only observed in nonsmoking female lung tumors. These results strongly suggested that the involvement of HPV infection in lung tumorigenesis of nonsmoking female cancer patients in Taiwan may be mediated at least in part through the increase of hypermethylation to cause p16 INK4a inactivation.
目 錄
壹、 中文摘要 1
貳、文獻綜論 4
一、肺癌之流行病學 4
二、與肺癌形成有關之環境因子 5
三、抑癌基因與肺癌 7
3.1. p53基因 7
3.2. p16 INK4a基因 10
四、人類乳突瘤病毒在人類腫瘤之研究 17
4.1. 人類乳突瘤病毒與人類腫瘤形成之相關性 17
4.2. 人類乳突瘤病毒與肺癌形成之相關性 18
4.3. 人類乳突瘤病毒 (Human papillomavirus, HPV) 20
4.3.1早期基因 (early gene) 21
4.3.2晚期基因 (late gene) 26
4.3.3 Long control region (LCR) 27
4.4 人類乳突瘤病毒感染路徑 27
4.5 病毒與p16蛋白高度甲基化的關係 28
參、研究動機 30
肆、材料與方法 32
一、 材料與藥品 32
1. DNA的製備 32
2.免疫組織化學染色(Immunohistochemistry) 32
3. Methylation-Specific PCR (MS-PCR) 33
二、 檢體收集 35
三、 實驗方法 35
1. 肺癌患者組織與血球之DNA萃取 35
2. 血球及肺腫瘤組織HPV DNA之測定 37
3. 肺腫瘤組織切片之來源 38
4. 免疫組織化學染色法(Immunohistochemistry) 39
5. Promoter Hypermethylation的分析 40
6. 定序分析 42
7. 統計分析 43
伍、結果 44
一、 肺癌患者與非癌症控制組血球高危險型HPV16/18感染之比較 44
二、 血球中高危險型HPV感染與臨床因子的相關性 45
三、 HPV感染做為肺癌的危險生物指標之多變項統計分析 46
四、 HPV感染在肺癌組織與血液檢體之相關性 47
五、 肺癌患者p16INK4a 促進子高度甲基化與臨床因子之相關性 48
六、 肺癌患者p16INK4a 促進子高度甲基化與蛋白表現之相關性 49
七、 HPV16/18 與p16INK4a基因促進子高度甲基化相關性之分析 50
八、 HPV16/18 與p16INK4a 蛋白表現相關性之分析 51
陸、討論
一、 週邊血液HPV 16/18 DNA的存在可做為台灣肺癌患者之危險
生物標記 52
二、 台灣女性肺癌HPV感染與p16促進子高度甲基化之相關性 60
三、 結論 66
柒、參考文獻 68
捌、表與圖 92玖、英文摘要 124
拾、附錄 收錄發表期刊文獻參篇 126
Adlkofer F. (2001) Lung cancer due to passive smoking- a review. Int Arch Occup Environ Health, 74:231-241.
Bagchi S, Raychaudhuri P, Nevins JR. (1990) Adenovirus E1A proteins can dissociate heteromeric complexes involving the E2F transcription factor: a novel mechanism for E1A trans-activation. Cell, 62:659-669.
Bandara LR, Adamczewski JP, Hunt T, La Thangue NB. (1991) Cyclin A and the retinoblastoma gene product complex with common transcription factor. Nature, 352:249-251.
Barnard P, McMillan NA. (1999) The human papillomavirus E7 oncoprotein abrogates signaling mediated by interferon-alpha. Virology, 259:305-313.
Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL, Vousden KH. (1998) p14ARF links the tumour suppressors RB and p53. Nature, 395:124-125.
Bauer HM, Ting Y, Greer CE. (1991) Genital human papillomavirus infection in female university students as determined by a PCR- based method. J Nat Cancer Int, 265:472-477.
Bauer HM, Hildesheim A, Schiffman MH, Glass AG, Rush BB, Scott DR, Cadell DM, Kurman RJ, Manos MM. ( 1993) Determinants of genital human papillomavirus infection in low-risk women in Portland, Oregon. Sex Transm Dis, 20:274-278.
Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP. (1998)
Alterations in DNA methylation: A fundamental aspect of neoplasia. Adv Cancer Res, 72:141-196.
Belinsky SA, Nikula KJ, Palmisano WA, Michels R, Saccomanno G, Gabrielson E, Baylin SB, Herman JG. (1998) Aberrant methylation of p16INK4a is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci USA , 95: 11891-6.
Belinsky SA, Snow SS, Nikula KJ, Finch GL, Tellez CS, Palmisano WA. (2002) Aberrant CpG island methylation of the p16 (INK4a) and estrogen receptor genes in rat lung tumors induced by particulate carcinogens. Carcinogenesis, 23:335-339.
Bernard HU, Chan SY, Manos MM, Ong CK, Villa LL, Delius H, Peyton CL, Bauer HM, Wheeler CM. (1994) Identification and assessment of known and novel human papillomaviruses by polymerase chain reaction amplification, restriction fragment length polymorphisms, nucleotide sequence, and phylogenetic algorithms. J Infect Dis, 170: 1077-1085.
Bird A. (1992) The essential of DNA methylation. Cell, 70:5-8.
Bonne-Andreac C, Santucci S, Clertant P, Tillier F. (1995) Bovine papillomavirus E1 protein binds specifically DNA polymerase alpha but not replication protein A . J Virol, 69:2341-2350.
Bohlmeyer T, Le TN, Shroyer AL, Markham N, Shroyer KR. (1998) Detection of human papillomavirus in squamous cell carcinomas of the lung by polymerase chain reaction. Am J Respir Cell Mol Biol, 18:265-269.
Bouvard V, Storey A, Pim D, Banks L. (1994) Characterization of the human papillomavirus E2 protein: evidence of trans-activation and trans-repression in cervical keratinocyte. EMBO, 13:5451-5459.
Brabender J, Usadel H, Metzger R, Schneider PM, Park J, Salonga D, Tsao-Wei DD, Groshen S, Lord RV, Takebe N, Schneider S, Holscher AH, et al. (2003) Quantitative O (6)-methylguanine DNA methyltransferase methylation analysis in curatively resected non-small cell lung cancer: associations with clinical outcome. Clin Cancer Res, 9:223-7.
Brotherton DH, et al. (1998) Crystal structure of the complex of the cyclinD-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d. Nature, 395:244-250.
Cavenee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL, Murphree AL, Strong LC, White RL. (1983) Expression of recessive alleles by chromosomal mechanism in retinoblastoma. Nature, 305:779-784.
Chan EC, Lam SY, Tsang KW, Lam B, Ho JCM, Fu KH, Lam WK, Kwong YL. (2002) Aberrant promoter methylation in Chinese patients with non-small cell lung cancer: patterns in primary tumors and potential diagnostic application in bronchoalevolar larvage. Clin Cancer Res, 8: 3741-6.
Chan SY, Delius H, Halpern AL, and Bernard HU. (1995) Analysis of genomic sequence of 95 papillomavirus types: uniting typing, phylogeny, and taxonomy. J Virol, 69:3074-3083.
Chen CJ, Wu HY, Chuang YC, Chang AS, Luh KT, Chao HH, Chen KW, Chen SG, Lai GM, Huang HH, and Lee HH. (1990) Epidemiologic characteristics and multiple risk factors of lung cancer in Taiwan. Anticancer Res, 10:971-976.
Chen SL, Han CP, Tsao YP, Lee JW, Yin CS. (1993) Identification and typing of human papillomavirus in cervical cancers in Taiwan. Cancer, 72:1939-1945.
Chen S, Xue K, Xu L, Ma G, and Wu J. (2001) Polymorphisms of the CYP1A1 and GSTM1 genes in relation to individual susceptibility to lung carcinoma in Chinese population. Mutation Res, 458(1-2):
41-47.
Cheng YW, Chiou HL, Sheu GT, Hsieh LL, Chen JT, Chen CY, Su JM, Lee H. (2001) The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women. Cancer Res, 61:2799-2803.
Cheng YW, Hsien LL, Lin PP, Chen CP, Chen CY, Lin TS, Su JM, Lee H. (2001) Gender difference in DNA adduct levels among nonsmoking lung cancer patients. Environ and Mol Mutagenesis, 37:304-310.
Chiou HL, Wu MF, Liaw YC, Cheng YW, Wong RH, Lee H. (2003) The presence of human papillomavirus type 16/18 DNA in blood circulation may act as a risk marker of lung cancer in Taiwan. Cancer, 97: 1558-63
Ciechanover A, Schwartz AL. (1994) The ubiquitin-mediated proteolytic pathway: mechanisms of recognition of the proteolytic substrate and involvement in the degradation of native cellular proteins. FASEB J, 8:182-191.
Clavel CE, Nawrocki B, Bosseaux B, Poitevin G, Putaud IC, Mangeonjean CC, Monteau M, Birembaut PL. (2000) Detection of human papillomavirus DNA in bronchopulmonary carcinomas by hybrid capture II: a study of 185 tumors. Cancer, 88:1347-1352.
Cohen Y, Singer G, Lavie O, Dong SM, Beller U, Sidransky D. (2003) The RASSFiA tumor suppressor gene is commonly inactivated in adenocarcinoma of the uterine cervix. Clin Cancer Res, 9:2981-4.
Cooper DN, Krawczak M. (1989) Cytosine methylation and the fate of CpG dinucleotides in vertebrate genomes. Hum Genet, 83:181- 188.
Cordon-Cardo C. (1995) Mutations of cell cycle regulators: Biological and clinical implications for human neoplasia. Am J Pathol, 147: 545-60.
Cripe TP, Haugen TH, Turk JP, Tabatabai F, Schmid PG 3rd, Durst M, Gissmann L, Roman A, Turek LP. (1987) Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte- dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis. EMBO, 6:3745-3753.
Cullen AP, Reid R, Campion M, LÖrincz AT. (1991) Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. J Virol, 65:606-612.
Da J, Chen L, Hu Y. (1996) Human papillomavirus infection and p53 gene mutation in primary lung cancer. Zhonghua Zhong Liu Za Zhi, 18:27-29.
Diehl JA, Zindy F, Sherr CJ. (1997) Inhibition of cyclin D1 phosphorylation on threonine-286 prevents its rapid degradation via the ubiquitin proteasome pathway. Genes Dev, 11:957-972.
Doorbar J, Ely S, Sterling J, McLean C, Crawford L. (1991) Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature, 352:824-827.
Dong SM, Pai SI, Rha SH, Hildesheim A, Kurman RJ, Schwartz PE, Mortel R, McGowan L, Greenberg MD, Barnes WA, Sidransky D. (2002) Detection and quantitation of human papillomavirus DNA in the plasma of patients with cervical carcinoma. Cancer Epidemiol Biomarkers Prev, 11:3-6
Dubrow R, and Wegman DH. (1984) Cancer and occupation in Massachusetts: a death certificate study. Am J Indus Med, 6:207-230.
Dyson N, Howley PM, Munger K, Harlow E. (1989) The human papillomavirus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science, 243:934-937.
Dyson N, Guida P, Munger K, Harlow E. (1992) Homologous sequence in adenovirus E1A and human papillomavirus E7 proteins mediate internation with same set of cellularproteins. J Virol, 66:6893-6902.
Ekalaksananan T, Pientong C, Kotimanusvanij D, Kongyingyoes B, Sriamporn S, Jintakanon D. (2001) The relationship of human papillomavirus (HPV) detection to pap smear classification of cervical-scraped cells in asymptomatic women in northeast Thailand. J Obstet Gynaecol Res, 27:117-124.
Ernster VL. (1994) The epidemiology of lung cancer in women. Annals of Epidemiology, 4:102-110.
Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG. (1999) Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res, 59: 67-70.
Esteller M, Corn PG, Baylin SB, Herman JG. (2001) A gene
hypermethylation profile of human cancer. Cancer Res, 61:3225
-3229.
Esteller M, Herman JG. (2002) Cancer as an epigenetic disease: DNA
methylation and chromatin alterations in human tumors. J Pathol, 196:1-7.
Ewen ME. (1994) The cell cycle and the retinoblastoma protein family. Metastasis Rev, 13:45-66.
Feinberg AP. (2001) Methylation meets genomics. Nat Genet, 27: 9-10.
Ferenczy A, Bergeron C, Richart RM. (1989) Human papillomavirus DNA in fomites on objects used for the management of patients with gential human papillomavirus infection. Obstet Gynecl, 74: 950-954.
Finzer P, Kuntzen C, Soto U, zur Hausen H, Rosl F. (2001) Inhibitors of histone deacetylase arrest cell cycle and induce apoptosis in cervical carcinoma cells circumventing human papillomavirus oncogene expression. Oncogene, 20: 4768-76.
Flores ER, Allen-Hoffmann BL, Lee D, Lambert PF. (2000) The human papillimavirus type 16 E7 oncogene is required for the productive stage of the viral life cycle. J Virol, 74:6622-6631.
Franceschi S, Doll R, Gallwey J, La Vecchia C, Peto R, Spriggs AI. (1983) Genital warts and cervical neoplasia: an epidemiological study. Br J Cancer, 48:621-628.
Franco EL, Villa LL, Ruiz A. (1995) Transmission of cervical papillomavirus infection by sexual activity: Differences between high and low oncogenic types. J Infect Dis., 172:756-763.
Free A, Wakefield RI, Smith BO, Dryden DT, Barlow PN, Bird AP. (2001) DNA recognition by the methyl-CpG binding domain of MeCP2. J Biol Chem, 276: 3353-3360.
Funk JO, Waga S, Harry JB, Wspling E, Stillman B, Galloway DA (1997) Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV 16 E7 oncoprotein. Genes Dev, 11:2090-2100.
Galloway DA. (1992) Serological assays for the detection of HPV antibodies. IARC Sci Publ, 119:147-161.
Gao YT, Blot WJ, Zheng W, Ershow AG, Hsu CW, Levin LI, Zhang R. Fraumeni JF Jr. (1987) Lung cancer among Chinese women. Int J Cancer, 40:604-9.
Gazzeri S, Gouyer V, Vour’ch C, Brambilla C, Brambilla E. (1998)
Mechanism of p16INK4a inactivation in non-small cell lung cancers. Oncogene, 16: 497-504.
Gorgoulis VG, Zacharatos P, Kotsinas A, Liloglou T, Kyroudi A,
Veslemes M, Rassidakis A, Halazonetis TD, Field JK,
Kittas C (1998) Alternation of the p16-pRb pathway and the
chromosome locus 9p21-22 in non-small cell lung carcinomas.
Am J Pathol, 153:1749-1765.
Greenblatt MS, Bennett WP, Hollstein M, Harris CC. (1994) Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res, 54:4855-4878.
Harris CC. (1996) p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology, and cancer risk assessment. Environ Health Perspect, 104:435-9.
Hengstermann A, Linares L, Ciechanover A, Whitaker N, Scheffner M. (2001) Complete switch from Mdm2 to human papillomavirus E6-mediated degradation of p53 in cervical cancer cells. Proc Natl Acad Sci U S A, 98:1218-1223.
Herman JG, Latif F, Weng Y, Lerman MI., Zbar B, Liu S, Samid D, Duan DR, Gnarra JR, Linehan WM, Baylin SB. (1994) Silencing of the VHL tumor suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA, 91: 9700-9704.
Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. (1996)
Methylation specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA, 93: 9821-6.
Hirai H, Sherr CJ. (1996) Interaction of D-type cyclins with a novel myb-like transcription factor, DMP1. Mol Cell Biol, 16:6457-6467.
Hirayasu T, Iwamasa T, Kamada Y, Koyanagi Y, Usuda H, Genka K. (1996) Human papillomavirus DNA in squamous cell carcinoma of the lung. J Clin Pathol, 49:810-817.
Ho WL, Chang JW, Tseng RC, Chen JT, Chen CY, Jou YS, Wang YC. (2002) Loss of heterozygosity at loci of candidate tumor suppressor genes in microdissected primary non-small cell lung cancer. Cancer Detect Prev, 26:343-349.
Hochstrasser M. (1996) Protein degradation or regulation: Ubiquitin the judge. Cell, 84:813-5.
Honda R, Tanaka H, Yasuda H. (1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett, 420:25-27.
Hsu YH, Wei TC, Horng IJ, Jan WC, Su IJ. (1997) Prevalence of human papilloma virus 16 or 18 in cervical cancer in Hualien, eastern Taiwan. Kaohsiung J Med Sci, 13:315-319.
Huang S, Afonina I, Miller BA, Beckmann AM. (1997) Human papillomavirs types 52 and 58 are prevalent in cervical cancers from Chinese women. Int J Cancer, 70:408-411.
Hui R, Macmillan RD, Kenny FS, Musgrove EA, Blamey RW, Nicholson RI, Robertson JF, Sutherland RL. (2000) INK4a gene expression and methylation in primary breast cancer: over-expression p16INK4a messenger RNA is a marker of poor prognosis. Clin Cancer Res, 6: 2777-2787.
Huschtscha LI, Reddel RR. (1999) p16INK4a and the control of cellular proliferative life span. Carcinogenesis, 20: 921-926.
Hussain SP, Harris CC. (1998) Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes. Cancer Res, 58: 4023-4037.
Hussain SP, Amstad P, Raja K, Sawyer M, Hofseth L, Shields PG, Hewer A, Phillips DH, Ryberg D, Haugen A, and Harris CC. (2001) Mutability of p53 hotspot codons to benzo(a)pyrene diol epoxide (BPDE) and the frequency of p53 mutations in nontumorous human lung. Cancer Res, 61:6350-5
Hwang SG, Lee D, Kim J, Seo T, Choe J. (2002) Human papillomavirus type 16 E7 binds to E2F1 and activates E2F1-driven transcription in a retinoblastoma protein-independent manner. J Biol Chem, 277: 2923-2930.
Issa JPJ, Baylin SB, Belinsky SA. (1996) Methylation of the estrogen receptor CpG island in lung tumors is related to the specific type of carcinogen exposure. Cancer Res, 56: 3655-8.
Iwamasa T, Miyagi J, Tsuhako K, Kinjo T, Kamada Y, Hirayasu T, Genka K. (2000) Prognostic implication of human papillomavirus infection in squamous cell carcinoma of the lung. Pathol Res Pract, 196: 209-218.
Jarmalaite S, Kannio A, Anttila S, Lazutka JR, Husgafvel-Pursiainen K. (2003) Aberrant p16 promoter methylation in smokers and former smokers with nonsmall cell lung cancer. Int J Cancer, 106: 913-8.
Janicek MF, Averette HE. (2001) Cervical cancer: prevention, diagnosis, and therapeutics. CA Cancer J Clin, 51:92-114. Review.
Jentsch S, Schlenker S. (1995) Selective protein degradation: a journey''s end within the proteasome. Cell, 82:881-884.
Jewers RJ, Hildebrandt P, Ludllow JW, Kell B, McCane DJ. (1992) Regions of human papillomavirus type 16 E7 oncoprotein required for immortalization of human keratinocyte. J Virol, 66:1329-1335.
Jones DL, Alani RM, Munger K. (1997) The human papillomavirus E7 oncoprotein can uncouple cellular diffferentitation and proliferation in human keratinocytes by abrogating p21Cip-mediated inhibition of cdk2. Genes Dev, 11:2101-2111.
Jones PA, Laird PW. (1999) Cancer epigenetics comes of age. Nat Genet, 21:163-166.
Jones PA, Takai D. (2001) The role of DNA methylation in mammalian 57 epigenetics. Science, 10: 1068-1070.
Juttermann R, Li E, Jaenisch R. (1994) Toxicity of 5-aza-2’- deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci. USA, 91:1797-11801.
Kashiwabara K, Oyama T, Sano T, Fukuda T, Nakajima T. (1998)
Correlation between methylation status of the p16/CDKN2 gene and the expression of p16 and Rb proteins in primary non-small cell lung cancers. Int J Cancer, 79:215-20.
Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res, 51(23 Pt 1): 6304-11.
Kenny JW. (1996) Differences in risk factors associated with genital human papillomavirus infections. J Adv Nurs, 23:1221.
Khleif SN, Degregori J, Yee CL, Otterson GA, Kaye FJ, Nevins JR, Howley PM. (1996) Inhibition of Cyclin D-CDK4/ CDK6activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc Natl Acad Sci. USA, 93: 4350-4354.
Kim DH, Nelson HH, Wiencke JK, Zheng S, Christiani DC, Wain JC, Mark EJ, Kelsey KT. (2001) p16(INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer. Cancer Res, 61:3419-24.
Kim SK. (1997) Polarized signaling: basolateral receptor localization in epithelial cells by PDZ-containing proteins. Curr Opin Cell Biol, 9: 853-859. Review.
Kinoshita I, Dosaka-Akita H, Shindoh M, Fujino M, Akie K, Kato M, Fujinaga K, Kawakami Y. (1995) Human papillomavirus type 18 DNA and E6-E7 mRNA are detected in squamous cell carcinoma and adenocarcinoma of the lung. Br J Cancer, 71:344-349.
Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, Petry U,
Dallenbach-Hellweg G, Schmidt D, Magnus von Knebel Doeberitz. (2001) Over-expression of p16INK4a as a specific maker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J
Cancer, 92:276-284.
Klingelhutz AJ, Foster SA, McDougall JK. (1996) Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature, 380:79-82.
Koo LC, Ho JH, Lee N. (1985) An analysis of some risk factors for lung cancer in Hong Kong. Int J Cancer, 35:149-55.
Koo LC, Ho JH. (1990) Worldwide epidemiological patterns of lung cancer in nonsmokers. Int J Epidemiol, 19 Suppl 1:S14-23.
Koo LC, Ho JHC. (1996) Diet as confounder of the association between air pollution and female lung cancer: Hong Kong studies on exposures to environmental tobacco smoke, incense, and cooking fumes as examples. Lung Cancer, 14 Suppl 1: S47-S61.
Kuzmin I, Liu L, Dammann R, Ceil L, Stanbridge EJ, Wilezynski SP, Lerman MI, Pfeifer GP. (2003) Inactivation of RAS association family 1A gene in cervical carcinomas and the role of human papillomarvirus infection. Cancer Res, 63:1888-93.
Lee MF, Chang MC, Wu CH. (1998) Detection of human papillomavirus types in cervical adenocarcinoma by the polymerase chain reaction. Int J Gynaecol Obstet, 63:265-270.
Lenner P, Dillner J, Wiklund F. (1995) Serum antibody responses against human papillomavirus in relation to tumor characteristic, response to treatment , and survival in carcinoma of the uterine cervix. Cancer Immunol Immunother, 40:201-205.
Li E, Beard C, Jaenisch R. (1993) Role for DNA methylation in genomic imprinting. Nature, 366:362-365.
Liaw KL, Hsing AW, Chen CJ, Schiffman MH, Zhang TY, Hsieh CY, Greer CE, You SL, Huang TW, Wu TC. (1995) Human papillomavirus and cervical neoplasia: a case-control study in Taiwan. Int J Cancer, 62:565-571.
Liggett WH Jr., Sidransky D. (1998) Role of the p16 tumor suppressor genein cancer. J Clin Oncol, 16:1197-1206.
Lin TS, Lee H, Chen RA, Ho ML, Lin CY, Chen YH, Tsai YY, Chou MC, Cheng YW. (2005) An association of DNMT3b protein expression with p16INK4a promoter hypermethylation in non-smoking female lung cancer with human papillomavirus infection. Cancer Letter, accepted.
Liu HR, Xing LQ, Si JY. (1994) A study of human papillary virus infection by in situ hybridization and histopathology in squamous cell carcinomas of the lung. Zhonghua Bing Li Xue Za Zhi, 23: 299-301.
Liu VW, Tsang P, Yip A, Ng TY, Wong LC, Ngan HY. (2001) Low incidence of HPV DNA in sera of pretreatment cervical cancer patients. Gynecol Oncol, 82:269-272.
Lo YM, Chan LY, Lo KW, et al. (1999) Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res, 59:1188-1191.
Lu X, Lane DP. (1993) Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell, 75:765-78.
Matsukura S, Soejima H, Nakagawachi T, Yakushiji H, Ogawa A, Fukuhara M, Miyazaki K, Nakabeppu Y, Sekiguchi M, Mukai T. (2003) CpG methylation of MGMT and hMLH1 promoter in hepatocellular carcinoma associated with hepatitis viral infection. Br J Cancer, 88: 521-9.
McNicol PJ, Paraskevas M, Guijon FB. (1999) The effect of vaginal microbes on in vivo and in vitro expression of human papillomavirus 16 E6-E7 genes. Cancer Detect Prev, 23:13-21.
Mead LJ, Gillespie MT, Hung JY, Rane US, Rayeroux KC, Irving LB, Campbell LJ. (1997) Frequent loss of heterozygosity in early non-small cell lung cancers at chromosome 9p21 proximal to the CDKN2A gene. Int J Cancer, 71:213-217.
Mendelsohn John et al. (1995) The molecular basis of cancer. Philadephia: W.B. Saunders, 574.
Merlo A, Gabrielson E, Askin F, Sidransky D. (1994) Frequent loss of chromosome 9 in human primary non-small cell lung cancer.
Cancer Res, 54: 640-642.
Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB, Sidransky D.(1995) 5 -CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/
MTS1 in human cancers. Nat Med, 1: 686-92.
Miasko A, Niklinska W, Niklinski J, Chyczewska E, Naumnik W, Chyczewski L. (2001) Detection of human papillomavirus in non-small cell lung carcinoma by polymerase chain reaction. Folia Histochem Cytobiol, 39:127-128.
Milde-Langosch K, Riethdorf S, Kraus-Poppinghaus A, Loning L.
p16MTS1, p21WAF1, and p27KIP1 in HPV-positive and HPV negative cervical adenocarcinomas. Virchows Arch, 439:55-61.
Miyagi J, Tsuhako K, Kinjo T, Iwamasa T, Hirayasu T. (2000) Recent striking change in histological differentiation and rate of human papillomavirus infection in squamous cell carcinoma of the lung in Okinawa, a subtropical island in southern Japan. J Clin Pathol, 53: 676-684.
Miyagi J, Kinjo T, Tsuhako K, Higa M, Iwamasa T, Kamada Y, Hirayasu T. (2001) Extremely high Langerhans cell infiltration contributes to the favourable prognosis of HPV-infected squamous cell carcinoma and adenocarcinoma of the lung. Histopathology, 38:355-367.
Momparler RL, Bovenzi V. (2000) DNA methylation and cancer. J Cell Physiol, 183: 145-154.
Munger K, Basile JR, Duensing S, Eichten A, Gonzalez SL, Grace M, Zacny VL. (2001) Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene, 20:7888-7898. Review
Nakachi K, Imai K, Hayashi S, Watanabe J, Kawajiri K. (1991) Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. Cancer Res, 51:5177-80.
Nakamura M, Sakaki T, Hashimoto H, Nakase H, Ishida E, Shimada K, Konishi N. (2001) Frequent alteration of the p14ARF and p16INK4a genes in primary central nervous system lymphomas. Cancer Res, 61:6335-6339.
Nakazato I, Hirayasu T, Kamada Y, Tsuhako K, Iwamasa T. (1997) Carcinoma of the lung in Okinawa, Japan: with special reference to squamous cell carcinoma and squamous metaplasia. Pathol Int, 47: 659-672.
Nuorva K, Soini Y, Kamel D, Pollanen R, Bloigu R, Vahakangas K, Paakko P. (1995) p53 protein accumulation and the presence of human papillomavirus DNA in bronchiolo-alveolar carcinoma correlate with poor prognosis. Int J Cancer, 64:424-429.
Omura-Minamisawa M, Diccianni MB, Chang RC, Batova A, Bridgeman LJ, Schiff J, Cohn SL, London WB, Yu AL. (2001) p16/p14ARF cell cycle regulatory pathways in primary neuroblastoma: p16 xpression is associated with advanced stage disease. Clin Cancer Res, 7:3481- 3490.
Palevfsky JM, Winkler B, Rabannus JP, Clark C, Chan S, Nizet V, Schoolnik GK. (1991) Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues.
J Clin Invest, 87:2132-2141.
Panning B, Jaenisch R. (1998) RNA and the epigenetic regulation of X
chromosome inactivation. Cell, 93:305-308.
Pao CC, Hor JJ, Yang FP, Lin CY, Tseng CJ. (1997) Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis. J Clin Oncol, 15: 1008- 1012.
Papadopoulou K, Labropoulou V, Davaris P, Mavromara P, Tsimara- Papastamatiou H. (1998) Detection of human papillomaviruses in squamous cell carcinomas of the lung. Virchows Arch, 433:49-54.
Phelps WC, Howley PM. (1987) Transcriptional trans-activation by the human papillomavirus type 16 E2 gene product. J Virol, 61:1630- 1638.
Piccini A, Storey A, Massimi P, Banks L. (1995) Mutations in the human papillomavirus type 16 E2 protein identify multiple regions of the protein involved in binding to E1. J Gen Virol, 76:2909-2913.
Reed AL, Califano J, Cairns P, Westra WH, Jones RM, Koch Wayne, Ahrendt S, Eby Y, Sewell D, Nawroz H, Bartek J, Sidransky D. (1996) High frequency of p16(CDKN2/MTS- 1/INK4A)inactivation in head and neck squamous cell carcinomas. Cancer Res, 56:3630- 3633.
Robertson KD, Jones PA. (2000) DNA methylation: past, present and future directions. Carcinogenesis, 21:461-467.
Robertson KD. (2001) DNA methylation, methyltransferase, and cancer. Oncogene, 20:3139-3155.
Rocco JW, Sidransky D. (2001) p16(MTS-1)/CDK2/INK4a in cancer
progression. Exp Cell Res, 264:42-55.
Roussel MF. (1999) The INK4a family of cell cycle inhibitors in cancer.
Oncogene, 18:5311-5317.
Ruas M, Peters G. (1998) The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochimica et Biophsica Acta, 1378: F115-F177.
Russo AA, et al. (1998) Structure basis for inhibition of the cyclin-
dependent kinase Cdk6 by the tumor suppressor p16INK4a. Nature, 395:237-243.
Sakai T, et al. (1991) Allele- specific hypermethylation of the retinoblastoma tumor suppressor gene. Am J Hum Genet, 48: 880- 888.
Sanchez-Cespedes M, Ahrendt SA, Piantadosi S, Rosell R, Monzo M, Wu L, Westra WH, Yang SC, Jen J, Sidransky D. (2001a) Chromosomal alternations in lung adenocarcinoma from smokers and nonsmoker. Cancer Res, 61:1309-1313.
Sanchez-Cespedes M, Decker PA, Doffek KM, Esteller M, Westra WH, Alawi EA, Herman JG, Demeure MJ, Sidransky D, Ahrendt SA. (2001b) Increased loss of chromosome 9p21 but not p16 inactivation in primary non-small cell lung cancer from smokers. Cancer Res, 61: 2092-2096.
Sano T, Oyama T, Kashiwabara K, Fukuda T, Nakajima T. (1998)
Expression status of p16 protein is associated with human
papillomavirus oncogenic potential in cervical and gential lesions.
Am J Pathol, 153:1741-1748.
Schiffman MH, Brinton LA. (1995) The epidemiology of cervical carcinogenesis. Cancer, Suppl 76:1888-1901.
Schutte M, Hruban RH, Geradts J, Maynard R, Hilgers W, Rabindran SK, Moskaluk CA, Hahn SA, Schwarte-Waldhoff I, Schmiegel W, Baylin SB, Kern SE, Herman JG. (1997) Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res, 57:3121-3125.
Schwarz E, Freese UK, Gissmann L, Mayer W, Roggenbuck B, Stremlau A, zur Hausen H. (1985) Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature, 314: 111-4.
Seavey SE, Holubar M, Saucedo LJ, Perry ME. (1999) The E7 oncoprotein of human papillomavirus type 16 stabilizes p53 through a mechanism independent of p19(ARF). J Virol, 73:7590-7598.
Serraino D, Piselli P, Scognamiglio P. (2001) Viral infections and cancer: epidemiological aspects. J Biol Regul Homeost Agents, 15:224-228.
Serrano M, Hannon GJ, Beach D. (1993) A new regulatory motif in cell cycle control causing specific inhibition of cyclinD/CDK4. Nature, 366:704-707.
Shah KV, Howley PM. (1990) Papillomavirus. Fields Virology, 1651.
Shamanin V, Delius H, EM de Villiers. (1994) Development of a broad spectrum PCR assay for papillomaviruses and its application in screening lung cancer biopsies. J Gen Virol, 75:1149-1156.
Shapiro GI, Park JE, Edwards CD, Mao L, Merlo A, Sidransky D, Ewen ME, Rollins BJ. (1995a) Multiple mechanism of p16INK4a inactivation in non-small lung cancer cell lines. Cancer Res, 55:6200-6209.
Shapiro GI, Edwards CD, Kobzik L, Godleski J, Richards W, Sugarbaker DJ, Rollins BJ. (1995b) Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines. Cancer Res, 55: 505-509.
Shen L, Ahuja N, Shen Y, Habib NA, Toyota M, Rashid A, Issa JP. (2002) DNA methylation and environmental exposures in human hepatocellular carcinoma. J Natl Cancer Inst, 94:755-61.
Sherr CJ. (1994) G1 phase progression: cycling on cue. Cell, 79:551-5.
Sherr CJ. (1996) Cancer cell cycles. Science, 274: 1672-1677.
Sherr CJ, Roberts JM. (1999) CDK inhibitors: positive and negative
regulators of G1-phase progression. Genes Dev, 13: 1501-1512.
Shotelersuk K, Khorprasert C, Sakdikul S,Pornthanakasem W, Voravud N, Mutirangura A. (2000) Epstein-Barr virus DNA in serum/plasma as a tumor marker for nasopharyngeal cancer. Clin Cancer Res, 6:
1046-1051.
Shyu JS, Chen CJ, Chiu CC, Huang SC, Harn HJ. (2001) Correlation of human papillomavirus 16 and 18 with cervical neoplasia in histological typing and clinical stage in Taiwan: an in-situ polymerase chain reaction approach. J Surg Oncol, 78:101-9.
Sidransky D. (1996) High frequency of p16(CDKN2/MTS- 1/INK4A) inactivation in head and neck squamous cell carcinomas. Cancer Res, 56: 3630-3633.
Smith SE. Koegl M. Jentsch S. (1996) Role of the ubiquitin/proteasome system in regulated protein degradation in Saccharomyces cerevisiae. Biological Chemistry, 377:437-446.
Soini Y, Nuorva K, Kamel D, Pollanen R, Vahakangas K, Lehto VP, Paakko P. (1996) Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma. Thorax, 51: 887-893.
Song SH, Jong HS, Choi H, Kang SH, Ryu MH, Kim NK, Kim WH, Bang YJ. (2000) Methylation of specific CpGsites in the promoter region could significantly down-regulate p16INK4a expression in gastric adenocarcinoma. Int J Cancer, 87:236-240.
Sun CA, Liu JF, Wu DM, Nieh S, Yu CP, Chu TY. (2002) Viral load of high-risk human papillomavirus in cervical squamous intraepithelial lesions. Int J Gynaecol Obstet, 76:41-47.
Syrjanen K, Syrjanen S, Kellorski J, Karja J, Mantyrjarvi R. (1989) Human papillomavirus (HPV) type 6 and 16 DNA sequences in bronchial squamous cell carcinomas demonstrated by in situ hybridization. Lung, 167:33-42.
Szabo I, Sepp R, Nakamoto K, Maeda M, Sakamoto H, Uda H. (1994) Human papillomavirus not found in squamous and large cell lung carcinomas by polymerase chain reaction. Cancer, 73:2740-2744.
Taga S, Osaki T, Ohgami A, Imoto H, Yoshimatsu T, Yoshino I., Yano K, Nakanishi R, Ichiyoshi Y, Yasumoto K. (1997) Prognostic value of immunohistochemical detection of p16INK4a expression in non-small cell lung carcinomas. Cancer, 80: 389-395.
Tang X, Khuri FR, Lee JJ, Kemp BL, Liu D, Hong WK, Mao L. (2000)
Hypermethylation of the death-associated protein (DAP) kinase promoter and aggressiveness in stage I non-small-cell lung cancer. J Natl Cancer Inst, 92: 1511-6.
Tsao YP, Yang KY, Han CP, Yin CS, Yang YF, Chen SL. (1994) Genital human papillomavirus infections in Taiwan. Int J Gynaecol Obstet, 44:39-45.
Testa JR, Liu Z, Feder M, Bell DW, Balsara B, Cheng JQ, Taguchi, T. (1997) Advances in the analysis of chromosome alterations inhuman lung carcinomas. Cancer Genet Cytogenet, 95:20-32.
Thomas M, Banks L. (1998) Inhibition of Bak-induced apoptosis by HPV-18 E6. Oncogene, 10:2943-2954.
Thomas M, Banks L. (1999) Human papillomavirus (HPV) E6 internations with Bak are conserved amongst E6 protein from high and low risk HPV types. J Gen Virol, 80:1513-1517.
Thomas P, De Lamballerie X, Garbe L, Douagui H, Kleisbauer JP. (1995) Detection of human papillomavirus DNA in primary lung carcinoma by nested polymerase chain reaction. Cell Mol Biol, 41:1093-1097.
Thorland EC, Myers SL, Persing DH, Sarkar G, McGovem RM, Gostout BS, Smith DI. (2000) Human papillomavirus type 16 integrations in cervical tumors frequently occur in common fragile sites. Cancer Res, 60:5916-5921.
Tierney RJ, Ellis JR, Winter H, Kaur S, Wilson S, Woodman CB, Young LS. (1993) PCR for the detection of cervical HPV 16 infection: the need for standardization. Int J Cancer, 54:700-701.
Torroella-Kouri M, Morsberger S, Carrillo A, Mohar A, Meneses A, Ibarra M, Daniel RW, Ghaffari AM, Solorza G, Shah KV. (1998) HPV prevalence among Mexican women with neoplastic and normal cervixes. Gynecol Oncol, 70:115-120.
Toyooka S, Pass HI, Shivapurkar N, Fukuyama Y, Maruyama R, Toyooka KO, Gilcrease M, Farinas A, Minna JD, Gazdar AF. (2001) Aberrant methylation and simian virus 40 tag sequences in malignant mesothelioma. Cancer Res, 61: 5727-30.
Toyooka S, Carbone M, Toyooka KO, Bocchetta M, Shivapurkar N, Minna JD, Gazdar AF. (2002) Progressive aberrant methylation of the RASSF1A gene in simian virus 40 infected human mesothelial cells. Oncogene, 21:4340-4.
Toyooka S, Maruyama R, Toyooka KO, McLerran D, Feng Z, Fukuyama Y, Virmani AK, Zochbauer-Muller S, Tsukuda K, Sugio K, Shimizu N, Shimizu K, et al. (2003) Smoke exposure, histologic type and geography-related differences in the methylation profiles of non- small cell lung cancer. Int J Cancer, 103: 153-60.
Tseng HH, Wang JS, Kan YY. (1996) Human papillomavirus detection in adenocarcinoma and adenosquamous carcinoma of the uterine cervix in Taiwan. Zhonghua Yi Xue Za Zhi, 57:47-53.
Tsuhako K, Nakazato I, Hirayasu T, Sunakawa H, Iwamasa T. (1998) Human papillomavirus DNA in adenosquamous carcinoma of the lung. J Clin Pathol, 51:741-749.
Tycko B. (2000) Epigenetic gene silencing in cancer. J Clin Invest, 105: 401-407.
Van Ranst MA, Tachezy R, Delius H, Burk RD. (1993) Taxonomy of the human papillomavirus. Papillomavirus Rep, 4:61-65.
Velculescu VE. El-Deiry WS. (1996) Biological and clinical importance of the p53 tumor suppressor gene. Clin Chem, 42(6 Pt 1):858-68.
Wade PA. (2001) Methyl CpG-binding proteins and transcriptional repression. Bio Essays, 23:1131-1137.
Wang YC, Chen CY, Chen SK, Cherng SH, Ho LW, Lee H. (1998) High frequency of deletion mutations in p53 gene from squamous cell lung cancer patients in Taiwan. Cancer Res, 58:328-33.
Weinberg RA. (1995) The retinoblastoma protein and cell cycle control. Cell, 81:323-30.
Werness BA, Levine AJ, Howley PM. (1990) Association of human papillomavirus type 16 and 18 E6 proteins with p53. Science, 248:76-79.
Wheeler CM, Parmenter CA, Hunt MS. (1993) Determinants of genital human papillomavirus infection among cytologically normal women attending the University of New Mexico Student Health Center. Sex Transm Dis, 20:286-289.
Wu MF, Cheng YW, Lai JC, Hsu MC, Chen JT, Liu WS, Chiou MC, Chen CY, Lee H. (2004) Frequent p16INK4a promoter hypermethylation in human papillomavirus-infected female lung cancer in Taiwan. Int J Cancer, 113:440-445.
Xing LQ, Liu HR, Si JY. (1993) Detection of human papillomavirus DNA in squamous cell carcinomas of the lung by multiple polymerase chain reaction. Zhonghua Jie He He Hu Xi Za Zhi, 16:275-277.
Yanagawa N, Tamura G, Oizumi H, Takahashi N, Shimazaki Y, Motoyama T. (2002) Frequent epigenetic silencing of the p16 gene in non-small cell lung cancers of tobacco smokers. Jpn J Cancer Res, 93: 1107-13.
Yang B, Guo M, Herman JG, Clark DP. (2003) Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma. Am J Pathol, 163: 1101-7.
Yang SC, Jeng SN, Kang ZC and Lee H. (2000) Identification of benzo[a]pyrene-7,8-diol-9,10-epoxide-N2-deoxyguanosine in human adenocarcinoma cells exposed to cooking oil fumes from frying fish under domestic condition. Chem Res Toxicol, 13:1046-1050.
Yu KY.(2000) Gender difference in p53 gene mutations, p53, mdm2 protein expressions and mdm2 splicing transcripts in Taiwanese nonsmall cell lung cancer patients. Master Thesis. Institute of
Toxicology, Chung Shan Medical University.
Zerfass-Thome K, Zwerschke W, Mannhardt B, Tindle R, Botz JW, Jansen-Durr P. (1996) Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein. Oncogene, 13:2323-2330.
Zhang HS, Postigo AA, Dean DC. (1999) Active transcriptional
repression by the Rb-E2F complex mediates G1 arrest triggered byp16INK4a, TGF beta, and contact inhibition. Cell, 97: 53-61.
Zhong S, Yeo W, Tang MW, Wong N, Lai PB, Johnson PJ. (2003)
Intensive hypermethylation of the CpG island of Ras association domain family 1A in hepatitis B virus-associated hepatocellular carcinomas. Clin Cancer Res, 9: 3376-82.
Zhou JA, Sun XY, Stenzel DJ, Frazer IH. (1991) Expression of vaccinia recombinant HPV 16 L1 and L2 ORF proteins in epithelial cells is sufficient for assembly of HPV virion-like particles. Virology, 181:203-10.
Zhu WG, Dai Z, Ding H, Srinivasan K, Hall J, Duan W, Villalona-Calero MA, Plass C, Otterson GA. (2001) Increased expression of unmethylated CDKN2D by 5-aza-2’-deoxycytidine in human lung cancer cells. Oncogene, 20: 7787-7796.
Zielinski GD, Snijders PJ, Rozendaal L, Voorhorst FJ, van der Linden HC, Runsink AP, de Schipper FA, Meijer CJ. (2001) HPV presence precedes abnormal cytology in women developing cervical cancer and signals false negative smears. Br J Cancer, 85:398-404.
ZÖchbauer-MÜller S, Fong KM, Virmani AK, Geradts J, Gazdar AF, Minna JD. (2001) Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer, 61: 249-55.
Zochbauer-Muller S, Gazdar AF, Minna JD. (2002) Molecular pathogenesis of lung cancer. Annu Rev Physiol, 64:681-708. Review.
Zur Hausen H. (1991) Human papillomavirus in the pathogenesis of anogenital cancer. Virology, 184:9-13.
Zur Hausen H. (1994) Human pathogenic papillomaviruses. Berlin: Springer-Verlag, 83-100.
Zur Hausen H. (2000) Papillomavirus causing cancer: evasion from host-cell control in early events in carcinogenesis. J Nat Cancer Int, 92: 690-698.
廖國盟、陳建仁 (1997) 肺癌之流行病學特徵、危險因子及防治策略 中華衞誌 16:375-3
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊