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p53和Survivin在交界痣中的表达及其意义
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摘要
目的研究p53和Survivin在交界痣中表达的特点以及在交界痣与恶性黑素瘤中表达的差异性,探讨交界痣恶变的信息。方法收集安徽医科大学第一附属医院病理科及安徽医科大学附属省立医院病理科2002~2007年手术切除标本存档蜡块交界痣47例、皮内痣13例、恶性黑素瘤16例,对47例交界痣和13例皮内痣标本进行HE染色观察,并采用免疫组化S-P法检测所有交界痣、皮内痣及恶性黑素瘤标本中p53、Survivin的表达状况。结果1.交界痣组织病理切片HE染色主要为透明痣细胞,也可有上皮样或梭形痣细胞,大多聚集成巢状;2.p53和Survivin在交界痣及恶性黑素瘤细胞中普遍表达而在皮内痣细胞中不表达或表达较弱,免疫组化染色阳性反应产物呈淡黄至棕黄色细颗粒状,定位于细胞核或细胞浆内,p53阳性物质主要见于阳性细胞的细胞核,少数见于阳性细胞的细胞浆,Survivin阳性物质主要见于阳性细胞的细胞浆,少数见于阳性细胞的细胞核;3.p53在交界痣、皮内痣、恶性黑素瘤中的表达阳性率分别为78.72%(37/47)、30.77%(4/13)、81.25%(13/16),经统计学处理,p53在交界痣中的表达明显高于在皮内痣中的表达,两者之间阳性表达差异有统计学意义(χ~2=8.72,P<0.01=,p53在交界痣与恶性黑素瘤之间阳性表达差异无统计学意义(χ~2=0.02,P>0.05);4.Survivin在交界痣、皮内痣、恶性黑素瘤中的表达阳性率分别为80.85%(38/47)、23.08%(3/13)、87.50%(14/16),经统计学处理,Survivin在交界痣中的表达明显高于在皮内痣中的表达,两者之间阳性表达差异有统计学意义(χ~2=13.15,P<0.01),Survivin在交界痣与恶性黑素瘤之间阳性表达差异无统计学意义(χ~2=0.05,P>0.05);5.p53表达阳性的37例交界痣中,33例Survivin表达阳性,p53表达阴性的10例交界痣中,5例Survivin表达阴性,经统计学处理,p53和Survivin在交界痣中的表达具有相关性(χ~2=7.81,P<0.05),其呈正相关的密切程度为r=0.3775。结论1.p53和Survivin在交界痣中高表达,提示突变型p53和Survivin抑制肿瘤细胞凋亡,从而可能在交界痣的发生发展中起着重要的作用;2.p53和Survivin在交界痣中的表达具有正相关性,提示p53和Survivin在交界痣的发生发展中可能具有协同作用;3.p53和Survivin在交界痣与恶性黑素瘤中的表达具有一致性,提示突变型p53和Survivin抑制肿瘤细胞凋亡,在交界痣恶变的过程中可能起着重要的作用;4.从分子水平检测p53和Survivin在交界痣中的表达,有可能为交界痣恶变提供相关信息。
Objective To study the characteristics of p53 and Survivin expression in junctional nevus and its variability in junctional nevus and malignant melanoma.To investigate the information of junctional nevus turning to malignant melanoma.Methods 47 cases of junctional nevus,13 cases of intrademal nevus and 16 cases of malignant melanoma were studyed from the First Affiliated Hospital and Provincial Hospital Department of Pathology of Anhui Medical University from 2002 to 2007.47 cases of junctional nevus and 13 cases of intrademal nevus were observed by HE staining and all junctional nevus,intrademal nevus and malignant melanoma were investigated using p53 and Survivin protein by S-P immunohistochemical technique.Results It is nested with transparence nevus cells mainly in junctional nevus histologically by HE staining.P53 and survivin protein are general expression in junctioanl nevus and malignant melanoma and did not express or express weak in intrademal nevus by S-P immunohistochemical technique.The positive reaction products are pale yellow to brown granular small localizing in the nucleus or cytoplasm.P53 protein are seen in nucleus mainly and cytoplasm little of positive cells by S-P immunohistochemical technique.Survivin protein are seen in cytoplasm mainly and nucleus little of positive cells by S-P immunohistochemical technique.The positivity rates of p53 in junctional nevus,intrademal nevus and malignant melanoma were 78.72%,30.77%,81.25%.The different expression of p53 between junctional nevus and intrademal nevus was statistically significant(χ~2=8.72,P<0.01=,and the different expression of p53 between junctional nevus and malignant melanoma was not statistically significant(χ~2 = 0.02,P>0.05 ).The positivity rates of Survivin in junctional nevus,intrademal nevus and malignant melanoma were 80.85%,23.08%,87.50%.The different expression of Survivin between junctional nevus and intrademal nevus was statistically significant(χ~2 = 13.15,P<0.01 =,and the different expression of Survivin between junctional nevus and malignant melanoma was not statistically significant(χ~2=0.05,P>0.05).P53 expression was positively correlated with Survivin expression in junctional nevus statistically(χ~2=7.81,P<0.05,r=0.3775).Conclusion By inhibitting apoptosis in junctional nevus,mutant p53 and Survivin may be play important role and synergetic in the progress of junctional nevus and turning to malignant melanoma.It is possible to provide relevant information for malignant transformation of junctional nevus by detecting the expression of p53 and Survivin protein from the molecular level.
引文
1张玉琬.恶性黑素瘤诊疗概况[J].中华中西医杂志,2004,5(5):72.
    2Greenlee RT,Hill-Harmon MB,Murray T,et al.Cancer statistics,2001[J].CA CancerJClin,2001,51(1):15-36.
    3Ohtsuka H,Nagamatsu S.Changing trends in numbers of deaths from malignant melanoma in Japan,1955-2000[J].Dermatology,2003,207(2):162-165.
    4Odom RB,James WD,Berger TG.Andrews' Diseases of the Skin Clinical Dermatology[M].9~(th) edit.Harcourt,2000:872-875.
    5Liloglou T,Ross H,Prime W,et al.p53 gene aberrations in non-small-cell lung carcinomas from a smoking population[J].Br J Cancer,1997,75(8):1119-1124.
    6Reed JC.The Survivin saga goes in vivo[J]._J Clin Invest,2001,108(7):965-969.
    7Clark WH Jr,Elder DE,Guerry D 4th,et al.A study of tumor progression:the precursor lesions of superficial spreading and nodular melanoma[J].Hum Pathol,1984,15(12):1147-1165.
    8Hussein MR,Wood GS.Molecular aspects of melanocytic dysplastic nevi[J].J Mol Diagn,2002,4(2):71-80.
    9Strasser A,O'Connor L,Dixit VM.Apoptosis signaling[J].Annu Rev Biochem,2000,69:217-245.
    10 Kukhta VK, Marozkina NV, Sokolchik IG, et al.Molecular mechanisms of apoptosis [J].Ukr Biokhim Zh, 2003, 75 (6): 5-9.
    11 Rass K, Gutwein P, Welter C, et al.DNA mismatch repair enzyme hMSH2 in malignant melanoma: increased immunoreactivity as compared to acquired melanocytic nevi and strong mRNA expression in melanoma cell lines[J].Histochem J, 2001,33(8): 459-467.
    12 Hussein MR, Wood GS.Microsatellite instability and its relevance to cutaneous tumorigenesis[J].J Cutan Pathol, 2002, 29 (5): 257-267.
    13 Hussein MR, Sun M, Roggero E, et al.Loss of heterozygosity, microsatellite instability, and mismatch repair protein alterations in the radial growth phase of cutaneous malignant melanomas[J].Mol Garcinog, 2002, 34 (1): 35-44.
    14 Shpitz B, Klein E, Malinger P, et al.Altered expression of the DNA mismatch repair proteins hMLH1 and hMSH2 in cutaneous dysplastic nevi and malignant melanoma[J].Int J Biol Markers, 2005, 20 (1): 65-68.
    15 Chiodino C, Cesinaro AM, Ottani D, et al.Communication: expression of the novel inhibitor of apoptosis survivin in normal and neoplastic skin[J].J Invest Dermatol, 1999, 113 (3): 415-418.
    16 Grossman D, McNiff JM, Li F, et al.Expression and Targeting of the apoptosis inhibitor, survivin, in human melanoma[J] J Invest Dermatol, 1999,113(6): 1076-1081.
    17 Vetter CS, Muller-Blech K, Schrama D, et al.Cytoplasmic and nuclear expression of survivin in melanocytic skin lesions [J]. Arch Dermatol Res, 2005, 297(1): 26-30.
    18 Ding Y, Prieto VG, Zhang PS, et al.Nuclear expression of the antiapoptotic protein survivin in malignant melanoma[J]. Cancer, 2006, 106 (5): 1123-1129.
    19 FraserAG, James C, Evan GI, et al.Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR-1 plays a conserved role in cytokinesis[J].Curr Biol, 1999, 9 (6): 292-301.
    20 Li F, Altieri DC.The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression[J].Cancer Res, 1999, 59 (13): 3143-3151.
    21 Finlay CA, Hinds PW, Tan TH, et al.Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life[J].Mol Cell Biol, 1988, 8 (2): 531-539.
    22 Zhao R, Gish K, Murphy M, et al.Analysis of p53-regulated gene expression patterns using oligonucleotide arrays [J]. Genes Dev, 2000, 14 (8): 981-993.
    23 Ben-Porath I, Weinberg RA.The signals and pathways activating cellular senescence[J].Int J Biochem Cell Biol, 2005, 37 (5): 961-976.
    24 Campisi J.Aging, tumor suppression and cancer: high wire-actl[J].Mech Ageing Dev, 2005, 126 (1): 51-58.
    25 Baraz L, Haupt Y, Elkin M, et al.Tumor suppressor p53 regulates heparanase gene expression[J].Oncogene, 2006, 25 (28): 3939-3947.
    26 Beroud C, Soussi T.The UMD-p53 database: new mutations and analysis tools[J].Hum Mutat, 2003, 21 (3): 176-181.
    27 Olivier M, Eeles R, Hollstein M, et al.The IARC TP53 database: new online mutation analysis and recommendations to users [J]. Hum Mutat, 2002, 19(6): 607-614.
    28 Slee EA, O'Connor DJ, Lu X.To die or not to die: how does p53 decide?[J].Oncogene, 2004, 23 (16): 2809-2818.
    29 Bergman R, Shemer A, Levy R, et al.Immunohistochemical study of p53 protein expression in Spitz nevus as compared with other melanocytic lesions[J].Am J Dermatopathol, 1995, 17 (6): 547-550.
    30 Miracco C, Santopietro R, Biagioli M, et al.Different patterns of cell proliferation and death and oncogene expression in cutaneous malignant melanoma[J].J Cutan Pathol, 1998, 25 (5): 244-251.
    31 Ambrosini G, Adida C, Altieri DC.A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma[J].Nat Med, 1997, 3 (8): 917-921.
    32 Ambrosini G, Adida C, Sirugo G, et al.Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting[J] J Biol Chem, 1998, 273 (18): 11177-11182.
    33 Suzuki A, Hayashida M, Ito T, et al.Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16 (INK4a) and Cdk2/cyclin E complex activation[J].Oncogene, 2000, 19 (29): 3225-3234.
    34 LaCasse EC, Baird S, Korneluk RG, et al. The inhibitors of apoptosis (IAPs) and their emerging role in cancer [J]. Oncogene, 1998, 17 (25): 3247-3259.
    35 Shin S, Sung BJ, Cho YS, et al.An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7[J].Biochemistry, 2001, 40 (4): 1117-1123.
    36 Song Z, Yao X, Wu M.Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis [ J]J Biol Chem, 2003, 278 (25): 23130-23140.
    37 Altieri DC.Survivin, versatile modulation of cell division and apoptosis in cancer[J].Oncogene, 2003, 22 (53): 8581-8589.
    38 Suzuki A, Shiraki K.Tumor cell "dead or alive": caspase and survivin regulate cell death, cell cycle and cell survival[J].Histol Histopathol, 2001, 16 (2): 583-593.
    39 Gradilone A, Gazzaniga P, Ribuffo D.et al.Survivin, bcl-2, bax, and bcl-X gene expression in sentinel lymph nodes from melanoma patients[J].J Clin Oncol, 2003, 21 (2): 306-312.
    40 Pennati M, Binda M, Colella G, et al.Radiosensitization of human melanoma cells by ribozyme-mediated inhibition of survivin expression[J]J Invest Dermatol, 2003, 120 (4): 648-654.
    41 Hoffman WH, Biade S, Zilfou JT, et al.Transcriptional repression of the anti-apoptotic survivin gene by wild type p53[J].J Biol Chem, 2002, 277 (5): 3247-3257.
    42 Grossman D, Kim PJ, Blanc-Brude OP, et al.Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53[J].J Clin Invest, 2001, 108 (7): 991-999.
    43 Jiang W, Ananthaswamy HN, Muller HK, et al.p53 protects against skin cancer induction by UV-B radiation[J].Oncogene, 1999, 18 (29): 4247-4253.
    44 Vegran F, Boidot R, Oudin C, et al. Association of p53 gene alterations with the expression of antiapoptotic survivin splice variants in breast cancer [J].Oncogene, 2007, 26 (2): 290-297.
    45 Swana HS, Grossman D, Anthony JN, et al.Tumor content of the antiapoptosis molecule survivin and recurrence of bladder cancer [J] .N Engl J Med, 1999, 341 (6): 452-453.
    46 Lu CD, Altieri DC, Tanigawa N.Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas[J].Cancer Res, 1998, 58 (9): 1808-12.
    47 Martin LJ, Kaiser A, Yu JW, et al.Injury-induced apoptosis of neurons in adult brain is mediated by p53-dependent and p53-independent pathways and requires Bax[J].J Comp Neurol, 2001, 433 (3): 299-311.
    1Sofia JC,Lee HY,Lee JI,et al.Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation[J].Clin Cancer Res,2002,8(5):1178-84.
    2Harris SL,Levine AJ.The p53 pathway:positive and negative feedback loops[J].Oncogene,2005,24(17):2899-2908.
    3Finlay CA,Hinds PW,Tan TH,et al.Activating mutations for transformation by p53produce a gene product that forms an hsc70-p53 complex with an altered half-life[J].Mol CellBiol,1988,8(2):531-539.
    4Popat S,Chen Z,Zhao D,et al.A prospective,blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer[J].AnnOncol,2006,17(12):1810-1817.
    5.Lebedeva IV,Su.ZZ,Sarkar D,et al.Restoring apoptosis as a strategy for Cancer gene therapy:focus on p53 and mda-7[J].Semin Cancer Biol,2003,13(2):169-178.
    6CaspariT.Howtoactivatep53[J].CurrBiol,2000,10(8):R315-317.
    7Yakovleva T,Pramanik A,Terenius L,et al.p53 latency--out of the blind alley[J].TrendsBiochemSci,2002,27(12):612-618.
    8Tachibana M,Shinagawa Y,Kawamata H,et al.RT-PCR amplification of RNA extracted from formalin-fixed,paraffin-embedded oral cancer sections:analysis of p53pathway[J].AnticancerRes,2003,23(3C):2891-2896.
    9Zhao R,Gish K,Murphy M,et al.Analysis of p53-regulated gene expression patterns using oligonucleotide arrays[J].Genes Dev,2000,14(8):981-993.
    10 Scarbrough K.Use of antisense oligodeoxynucleotides to study biological rhythms[J].Methods, 2000, 22 (3): 255-260.
    11 Dominguez G, Silva J, Silva JM, et al.Different expression of P14ARF defines two groups of breast carcinomas in terms of TP73 expression and TP53 mutational status[J].Genes Chromosomes Cancer, 2001, 31 (2): 99-106.
    12 Xue Q, Sano T, Kashiwabara K, et al.Aberrant expression of pRb, p16, p14ARF, MDM2, p21 and p53 in squamous cell carcinomas of lung[J].Jpn J Cancer Res, 2001, 92 (3): 285-292.
    13 Tommasino M, Accardi R, Caldeira S, et al.The role of TP53 in Cervical carcinogenesis[J].Hum Mutat, 2003, 21 (3): 307-312.
    14 Oh MJ, Choi JH, Lee YH, et al. Mutant p53 protein in the serum of patients with cervical carcinoma: correlation with the level of serum epidermal growth factor receptor and prognostic significance [J]. Cancer Lett, 2004, 203 (1): 107-112
    15 Fridman JS, Lowe SW.Control of apoptosis by p53 [J].Oncogene, 2003, 22 (56): 9030-9040.
    16 Kelley ML, Keiger KE, Lee CJ, et al.The global transcriptional effects of the human papillomavirus E6 protein in cervical carcinoma cell lines are mediated by the E6AP ubiquitin ligase[J].J Virol, 2005, 79 (6): 3737-3747
    
    17 Hoffman WH, Biade S, Zilfou JT, et al.Transcriptional repression of the anti-apoptotic survivin gene by wild type p53[J]J Biol Chem, 2002, 277 (5): 3247-3257.
    18 Castillo JP, Kowalik TF.Human cytomegalovirus immediate early proteins and cell growth control[J].Gene, 2002, 290 (1-2): 19-34.
    19 Maeda M, Ampo K, Kiryu-Seo S, et al.The p53-independent nuclear translocation of cyclin G1 in degenerating neurons by ischemic and traumatic insults[J].Exp Neurol, 2005, 193 (2): 350-360.
    20 Lu X.p53: a heavily dictated dictator of life and death[J].Curr Opin Genet Dev, 2005, 15 (1).- 27-33.
    21 Hupp TR, Sparks A, Lane DP.Small peptides activate the latent sequence-specific DNA binding function of p53[J].Cell, 1995, 83 (2): 237-245.
    22 Bennett M, Macdonald K, Chan SW, et al.Cell surface trafficking of Fas: a rapid mechanism of p53-mediatedapoptosis[J].Science, 1998, 282 (5387): 290-293.
    23 Weng XY, Ma RD, Yu LJ. Apoptosis of human nasopharyngeal carcinoma CNE-2Z cells induced by tubeimoside I[J].Ai Zheng, 2003, 22 (8): 806-811.
    24 Slee EA, O'Connor DJ, Lu X.To die or not to die: how does p53 decide?[J].Oncogene, 2004, 23 (16): 2809-2818.
    25 Samuels-Lev Y, O'Connor DJ, Bergamaschi D, et al.ASPP proteins specifically stimulate the apoptotic function of p53[J].Mol Cell, 2001, 8 (4): 781-794.
    26 Yang JP, Hori M, Sanda T, et al.Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor[J].J Biol Chem, 1999,274(22): 15662-15670.
    27 Slee EA, Gillotin S, Bergamaschi D, et al.The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic Iocalization[J].Oncogene, 2004, 23 (56): 9007-9016.
    28 Bergamaschi D, Samuels Y, Jin B, et al.ASPP1 and ASPP2: common activators ofp53 family members [J].Mol Cell Biol, 2004, 24 (3): 1341-1350.
    29 Bergamaschi D, Samuels Y, O'Neil NJ, et al.iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human[J].Nat Genet, 2003, 33 (2): 162-167.
    30 Grossman D, Kim PJ, Blanc-Brude OP, et al.Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of p53[J]J Clin Invest, 2001, 108 (7): 991-999.
    31 Vegran F, Boidot R, Oudin C, et al. Association of p53 gene alterations with the expression of antiapoptotic survivin splice variants in breast cancer[J].Oncogene, 2007, 26 (2): 290-297.
    32 Martin LJ, Kaiser A, Yu JW, et al.Injury-induced apoptosis of neurons in adult brain is mediated by p53-dependent and p53-independent pathways and requires Bax[J].J Comp Neurol, 2001, 433 (3): 299-311.
    33 Oka K, Suzuki Y, Nakano T.Expression of p27 and p53 in cervical squamous cell carcinoma patients treated with radiotherapy alone: radiotherapeutic effect and prognosis[J].Cancer, 2000, 88 (12): 2766-2773.
    34 Volpert OV, Dameron KM, Bouck N.Sequential development of an angiogenic phenotype by human fibroblasts progressing to tumorigenicity[J].Oncogene, 1997, 14 (12): 1495-1502.
    
    35 Gautam A, Densmore CL, Melton S, et al.Aerosol delivery of PEI-p53 complexes inhibits B16-F10 lung metastases through regulation of angiogenesis [J].Cancer Gene Ther, 2002, 9(1): 28-36.
    36 Tyner SD, Venkatachalam S, Choi J, et al.p53 mutant mice that display early ageing-associated phenotypes[J].Nature, 2002, 415 (6867): 45-53.
    37 Rosso A, Balsamo A, Gambino R, et al.p53 Mediates the accelerated onset of senescence of endothelial progenitor cells in diabetes [J]. J Biol Chem, 2006, 281 (7): 4339-4347.
    38 Suzuki M, Suzuki K, Kodama S, et al.Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest[J].Biochem Biophys Res Commun, 2006, 340 (1): 145-150.
    39 Mendrysa SM, Perry ME.Tumor suppression by p53 without accelerated aging: just enough of a good thing?[J]. Cell Cycle, 2006, 5 (7): 714-717.
    40 Reddy VB, Gattuso P, Aranha G, et al.Cell proliferation markers in predicting metastases in malignant melanoma[J].J Cutan Pathol, 1995, 22 (3): 248-251.
    41 Bergman R, Shemer A, Levy R, et al.Immunohistochemical study of p53 protein expression in Spitz nevus as compared with other melanocytic lesions [J]. Am J Dermatopathol, 1995, 17 (6): 547-550.
    42 Miracco C, Santopietro R, Biagioli M, et al.Different patterns of cell proliferation and death and oncogene expression in cutaneous malignant melanoma[J].J Cutan Pathol,1998,25(5):244-251.
    43Alkhalaf M,E1-Mowafy AM.Overexpression of wild-type p53 gene renders MCF-7 breast cancer cells more sensitive to the antiproliferative effect of progesterone[J].J Endocrinol,2003,179(1):55-62.
    44Bolshakov S,Walker CM,Strom SS,et al.p53 mutations in human aggressive and nonaggressive basal and squamous cell carcinomas[J].Clin Cancer Res,2003,9(1):228-234.
    45Demirkan NC,Colakogtu N,Düzcan E.Value of p53 protein in biological behavior of basal cell carcinoma and in normal epithelia adjacent to carcinomas[J].Pathol Oncot Res,2000,6(4):272-274.
    46Chang CH,Tsai RK,Chen GS,et al.Expression of bcl-2,p53 and Ki-67 in arsenical skin cancers[J].J Cutan Pathol,1998,25(9):457-462.
    47王家璧,毛旭明,晋红中,等.皮肤鳞状细胞癌和基底细胞癌中p53和C-myc 突变基因及蛋白的检测[J].中国皮肤性病字杂志,2000,14(2):73-76.
    48Kiuru A,Servomaa K,Grénman R,et al.p53 mutations in human head and neck cancer cell lines[J].Acta Otolaryngol Suppl,1997,529:237-240.
    49Viltuendas R.,Priis-MA,Orradre.JL,et al.P53 protein expression in lymphornas and reactive lymphoid tissue[J].J Pathol,1992,166(3):235-241.
    50Brennan PA,Conroy B,Spedding AV.Expression of inducible nitric oxide synthase and p53 in oral epithelial dysplasia[J].Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2000,90(5):624-629.
    51Béroud C,Soussi T.The UMD-p53 database.,new mutations and analysis tools[J].Hum Mutat,2003,21(3):176-181.
    52Olivier M,Eeles R,Hollstein M,et al.The IARC TP53 database:new online mutation analysis and recommendations to users[J].Hum Mutat,2002,19(6):607-614.
    53张珊文,肖卫群,吕有勇.抑癌基因p53对人胃癌细胞系放射敏感性的作用[J]. 中华放射肿瘤学杂志,1999,8(2):116-120.
    54Meng RD,McDonald ER 3rd,Sheikh MS,et al.The TRAIL decoy receptor TRUNDD(DcR2,TRAIL-R4) is induced by adenovirus-p53 overexpression and can delay TRAIL-,p53-,and KILLER/DR5-dependent colon cancer apoptosis[J].Mol Ther,2000,1(2):130-144.
    55Brand K,Klocke R,Possling A,et al.Induction of apoptosis and G2/M arrest by infection with replication-deficient adenovirus at high multiplicity of infection[J].Gene Ther,1999,6(6):1054-1063.
    56Li JH,Lax SA,Kim J,et al.The effects of combining ionizing radiation and adenoviral p53 therapy in nasopharyngeal carcinoma[J].Int J Radiat Oncol Biol Phys,1999,43(3):607-616.
    57Clayman GL,el-NaggarAK,Lippman SM,et al.Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma[J].J ClinOncol,1998,16(6):2221-2232.
    58Clayman GL,Frank DK,Bruso PA,et al.Adenovirus-mediated wild-type p53 gene transfer as a surgical adjuvant in advanced head and neck cancers[J].Clin Cancer Res,1999,5(7):1715-1722.

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