应用免疫双标记法研究MIB1TopoⅡα在弥漫大B细胞淋巴瘤的表达及预后意义
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的研究MIB1TopoⅡα在弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma DLBCL)的表达情况,探讨其临床分期及生存时间的关系。
     方法收集山西省肿瘤医院病理科在1996年-2001年确诊的DLBCL病例66例,应用免疫双标记ABC-DAB/SABAP-vector red显示CD20阳性细胞表达MIB1,ABC-DAB/免疫胶体金显示CD20阳性细胞表达TopoⅡα,不进行苏木精复染。收集临床资料并完善随访。
     结果MIB1TopoⅡα标记指数临床分期有关,在低级别临床分期(Ⅰ、Ⅱ)的表达指数低于高级别的(Ⅲ、Ⅳ),有统计学差异(P<0. 05)。MIB1TopoⅡα的表达生存时间呈线性相关(依次r=-0.487, 0.251, P<0.05),但年龄、性别、B症状、LDH水平、体能状态无相关性。
     结论MIB1TopoⅡα可以作为DLBCL独立的预后指标。
Objective To investigate the expression of MIB1 and TopoⅡα, and their relation to the clinical grades and biological behavior in diffused large-B cell lymphomas (DLBCLs).
     Method 66 cases of DLBCL were selected from the Pathological Deparment of Shanxi Tumor Hospital from 1996 to 2001. An ABC method was used to detecte the expression of CD3、CD20、CD79α、Pax5, and a double immunogolden technique was used to detect the expression of MIB1 and TopoⅡα. Patients related clinical data including follow-up materials were selected.
     Results Expression of MIB1 and TopoⅡαwere increased along with the clinical stage of the DLBCL. There was a significant difference between more ealy stage (Ⅰ、Ⅱ)and later stage (Ⅲ、Ⅳ) in DLBCL(P<0. 05). The expression of MIB1 and TopoⅡαwere also significantly related to the survival (r=-0·487, 0·251 respectively, all P<0.05), but had no association with ages, genders, B symptoms, LDH level and performance status? (P>0.05).
     Conclusions Expression of MIB1 and TopoⅡαmay serve as two independent prognostic predictors in DLBCL.
引文
[1] Gatter K, Warnke RA. Diffuse large B-cell lymphoma. In: Jaffe ES,Stein H, Vardiman JW, editors. World Health Organization classification of tumors: pathology and genetics of tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. p. 171–4.
    [2]陆锦标、朱雄增.弥漫大B细胞淋巴瘤基因表达谱的研究进展中华病理学杂志2006 11 684-686..
    [3] Engelhard M, Brittinger G, Huhn D, Gerhartz HH,Meusers P, Siegert W, Thiel E, Wilmanns W.Aydemir U, Bierwolf S, and other 3 authors: Subclassifi- cation of diffuse large B-cell lymphomas according to the Kiel classification: distinction of centroblastic and immunoblastic lymphomas is a significant prognostic risk factor.Blood, 89,2291-2297 (1997.
    [4] Malpas JS. Pediatric lymphomas. In: Hancock B, Selby P, MacLennan K, Armitage J, editors. Malignant Lymphoma. London: Arnold Publishing Ltd., 2000, 373–84.
    [5] Grovas A, Fremgen A, Raugh A, Ruymann FB, Hutchinson CL, Winchester DP, Menck HR. The National Cancer Data Base report on patterns of child- hood cancers in the United States. Cancer,1997;80:2321-32.
    [6] Sanger W, Lones M, Perkins S, Heerema N, Shiramizu B, Sposto R, Daven- port V,Goldman S, Cairo MS. Chromosome abnormalities in B-cell non- Hodgkin’s lymphoma (NHL) of children and adolescents:A report from Children’s Cancer Group (CCG) study CCG- 5961.Ann Oncol 2002;13:138.
    [7] Heerema NA, Sanger WG, Perkins S, Sposto R, Davenport V, Goldman SC, Cairo MS. High Frequency of CMYC rearrangements, 1q21–1q23 duplica- tions and complex karyotypes in B-cell non-Hodgkin’s lymphoma (NHL) of children and adolescents: a report from Child- ren’s Cancer Group (CCG) study CCG-5961. Blood 2002;100:566.
    [8] Lones MA, Sanger W, Sposto R, Perkins S, Buckley J, Kadin M,Kjeldsberg C, LeBeau M, Meadows A, Siegel S, Bergeron S,Cairo MS.Chromosome abnormalities in Burkitt’s/Burkitt- like lymphomas of children and adolescents may correlate with prognosis: a report from Children’s Cancer Group (CCG) study CCG-E-08. Proc AmAssoc Cancer Res 2002;43:1072.
    [9] Gordon B, Sanger W, Weisenburger D, Bast M, Pickering D, Hess M, Bierman P, Vose J,Harper J, Abromowitch M, Armitage J,Coccia P. Cytogenetic abnormalities in non- Hodg- kin’s lymphoma (NHL) and Hodgkin’s disease (HD) in children: the Nebraska Lymphoma Study Group Experience. J Pediatr Hematol Oncol 1999;21:331.
    [10]造血与淋巴组织肿瘤病理学和遗传学周小鸽陈辉树主译人民卫生出版社2006 187-192.
    [11] Cairo MS, Sposto R, Hoover-Regan M, Meadows AT, Anderson JR, Siegel SE, Kadin ME, Kjeldsberg CR, Wilson JF, Perkins SL,LonesMA,Morris E, Finlay JL. Childhood and adole- scent large cell lymphoma (LCL): a review of the Children’s Cancer Group experience. Am J Hematol 2003;72:53-63.
    [12] Harris NL, Ferry JA. Biologic basis for classification of lymphoid neoplasms. In: Handin RI, Lux SE, Stossel TP, editors.Blood: principles and practice of hematology.Philadelphia Lippincott Williams & Wilkens; 2003. 733-78.
    [13] Coiffier B. Diffuse large cell lymphoma. Curr Opin Oncol 2001;13: 325–34.
    [14] Reiter A, Schrappe M, Tiemann M, Ludwig WD, Yakisan E, Zimmermann M, Mann G,Chott A, Ebell W, Klingebiel T, Graf N, Kremens B, Muller- Weihrich S, Pluss HJ, Zintl F, Henze G, Riehm H. Improved treatment results in childhood B-cell neoplasms with tailored inten- sification of therapy: a report of the Berlin-Frankfurt-Mu¨nster Group Trial NHL-BFM 90. Blood 1999;94:3294.
    [15] Patte C, Auperin A, Michon J, Behrendt H, Leverger G, Frappaz D, Lutz P, Coze C, Perel Y, Raphael M, Terrier-Lacombe MJ. The Society Franc?aise d’Oncologie Pe′diatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood 2001; 97:3370
    [16]. Yaniv I, Fischer S, Mor C, Stark B, Goshen Y, Stein J, Cohen IJ,Zaizov R. Improved outcome in childhood B-cell lymphoma with the intensified French LMB protocol. Med Pediatr Oncol 2000;35:8-12.
    [17] Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non- Hodgkin’s lymphoma.
    [18] Armitage JO,Weisenburger DD(1998).New approach to classifying non- Hodg- kin’s lymphoma:clinical features of the major histologic subtypes. Non- Hodgkin’s Lymphoma Classification Project.J Clin Oncol 16:2780-2795.
    [19] Alison H. Banham, Joseph M. Connors,Philip J. Brown, et al.Expression of the FOXP1 Transcription Factor Is Strongly Associated with Inferior Survival in Patients with Diffuse Large B-Cell Lymphoma. Clinical Cancer Research 2005 Feb; 11:1065–1072)gl J Med 1993;328:1002-6.
    [20] Miller TP,Grogan TM,Dahlderg S,Spier CM,Braziel RM,Banks PM,Foucar K,Kjeldsberg CR,Levy N,Nathwani BN(1994).Prognostic significance of the MIB1-associated proliferative antigen in aggressive non-Hodgkin’s lympho- mas:a prospective Southwest Oncology Group trial.Blood 83:1460-1466.
    [21] KawasakiH,ToyodaM,ShinoharaH,etal. Expression of survivin correlates with apoptosis , proliferation , and angiogenesis during hu2 mancolorectal tumorigenesis[J]. Cancer, 2001,91 (11 ):2026-2032.
    [22] Sarela AI,Verbeke CS,Ramsdale J,et al. Expression of survivin,a novel inhibitor of apoptosis and cell cycle regulatory protein , in pancreatic adenocarcinoma[J].BrJ Cancer ,2002,86 (6) :886-892.
    [23] Slymen DJ,Miller TP, Lippman SM, et al. J Clin Oncol, 1990; 8: 986.
    [24] Kamel OW, Lebrun DP, Eric DR, et al. Am J Pathol, 1991;138: 1471.
    [25] Duchrow M,Gerdes J, Schluter C. The proliferation associated MIB1 protein: definition in molecular terms[J].CellProlif 1994, 27:235.
    [26] Nakano T,Oka K.Differential values of MIB1 index and mitotic index of proliferating cell population. An assessment of cell cycle and prognosis in radiation therapy for cervical cancer[J].Cancer, 1993, 72: 2401.
    [27]吕方芳,陆洪芬,印季良等.survivin、bcl-2及MIB1在弥漫大B细胞淋巴瘤中的表达及临床意义临床研究.
    [28] Mckeever PE, Ross DA, Strawderman MS, et al. A comparison of the predic- tive power for survival in gliomas provided by MIB-1,bromo deo xyuridine and proli- ferating cell nuclear antigen with histopathologic and clinical parame- ters [J]. J Neuropathol Exp Neu-ro,l 1997, 56: 798.
    [29] Onda K, davis RR, Shibuya M, et a.l Correlation between the bromo deo- xyruidine labeling index and the MIB-1 proliferating cell in dices in cerebral gliomas[J]. Cancer, 1994, 74: 1921.
    [30] Mochen C, Giardini R, Costa A, et al. MIB1 and S-phase cell fraction predict survival innon-Hodgkin's lymphomas. Cell Prolif, 1997,30: 37-47.
    [31] Fournel Fleury C, Magnol JD, Chabanne L, et al. Growth fraction in canine non-Hodgkin’s lymphoma deter mind in situ by the expression of the MIB1 antigen. J Comp Pathol, 1997, 17: 61-72.
    [32]徐卫,盛瑞兰国外医学输血及血液学分册1999, 22 (5 ): 337-339.
    [33] Slymen DJ,Miller TP, Lippman SM, et al. J Clin Oncol, 1990; 8: 986.
    [34] Schmitt F, Tani E, Tribukait B, et al. Assessment of cell proliferation by MIB1 staining and flowcytometry in fine needle aspirate (FNAs) of reactive lymphadenitis and non-Hodgkin’s lymphoma. Pathology, 1999, 10: 87-96.
    [35] Grogan TM, Lippman SM, Spier CM, et al. Blood, 1998; 71:1157.
    [36] Garcia-Marco JA, Price CM, Ellis J, et al. Leukemia, 1996; 10: 1705.
    [37] Mochen C, Giardini R, Costa A, et al. MIB1 and S-phase cell fraction predict survival in non-Hodgkin's lymphomas. Cell Prolif, 1997,30: 37-47.
    [38]王斌,梁维邦,王汉东,倪红斌,蒋健临床神经外科杂志2007年第4卷第2期52-53.
    [39] BrittingerG,Bartels H,CommonH,Duhmke E,Fulle HH,Gunzer U,Gyenes T,Heinz R,Konig E,Meusers P(1984).Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymohomas results of a prospective multi- center study by the Kiel Lymphoma Study Group.Hematol Oncol 2:269-306.
    [40] EngelhardM,Brittinger G,Huhn D,Gerhartz HH,Meusers P,Siegert W,Thiel E,Wilmanns W,Aydemir U,Bierwolf S,Griesser H,Tiemann M,Lennert K(1997)。Subclassification of diffuse large B-cell lymphoma according to the Kiel classification :distinction of centroblastic and immunoblastic lymphomas is a significant prognostic risk factor.Blood 89:2291-2297.
    [41] Melnyk A,Rodriguez A,Pugh WC,Cabannillaas F(1997).Evaluation of the Revised European-American Lymphoma classification confirms the clinical relevance of immunophenotype in 560 cases of aggressive non-Hodgkin’s lymphoma.Blood 89;4514-4520.
    [42] Salar A,Fernandez Ds,Romagosa V,Domingo-ClarosA,Gonzalez-BarcanE,Pera J,Climent J,Granena A(1998).Diffuse large-B ceii lymphoma :is morphologic subdivision useful in clinical management?Eur J Haematol 60:202-208.
    [43] Alizadeh AA,Eisen MB,Davis RE,Ma c,Lossos IS,Rosenwald A,Boldrick JC,Sabet H,TranT,Yu X,Powell JI,Yang L,Marti GE,Moore T,Hudson J,Jr,Lu L,Lewis DB,Tibshirani R,Sherlock G,Chan WC,Greiner TC,Weisenburger DD,Armitage JO,Warnke R,Staudt(2000).Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling,Nature 403:503-511.
    [44] A predictive model for aggressive non-Hodgkin’s lymphoma.The International Non-Hodgkin’s Lymphoma Prognostic Factors Project.N Engl J Med,1993 Sep30,329(14):987-94.
    [45] Janssen-Heijnen ML,van Spronsen DJ,Lemmens VE,Houterman S,verheij KD,Coebergh JW.A population-based study of severity of comorbidity among patients with non-Hodgkin’s lymphoma:prognostic impact independent of International Prognostic Index.Br Haematol 2005 Jun,129(5):597-606.
    [46] Barrans SL,Carter I,Owen RG,et a1.Germinal center phenotype and Bcl-2 ex- pression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma. Blood .2002, Feb 15; 99(4):1136-43.
    [47] Guinee DG, Holden JA,Benfiedd JR,et al.ComPaRison of DNA Topoisomerase II aIpha expression in small cell and non-small cell carcinoma of the lung:In search of a mechanism of chemotherapeutic response[J].Caneer,1996,78(4):729-735.
    [48] Holden JA,Perkins SL,Snow GW , et al.Immunohistochemical saining for DNA Topoisomerase II in non-Hodgkins lymphomas [J]. Am J Chin Pathol,1995,104(l):54-59.
    [49]肖立,陆孝禹.CK34βE12PSA顺序免疫组化双染色在前列腺病变中的表达[J].老年医学保健,2003,9(1):14-15.
    [50]王平、董德平、张剑平等. MIB1、NET-1CD34免疫组化三重染色技术临床实验病理学杂志2006 618-620.
    [51]刘艳.恶性淋巴瘤病理诊断中的误区临床实践病理学杂志2006 22.
    [52]刘霆.恶性淋巴瘤WHO分型―以病理学为基础的治疗策略[J].临床内科杂志2005;22(9)583-588.
    [53] Coiffier B. Diffuse large cell lymphoma. Curr Opin Oncol 2001;13: 325–34.)。
    [54] Reiter A, Schrappe M, Tiemann M, Ludwig WD, Yakisan E, Zimmermann M, Mann G,Chott A, Ebell W, Klingebiel T, Graf N, Kremens B, Muller-Weihrich S, Pluss HJ, Zintl F, Henze G, Riehm H. Improved treatment results in childhood B-cell neoplasms with tailored inten- sification of therapy: a report of the Berlin-Frankfurt-Mu¨nster Group TrialNHL-BFM 90. Blood 1999;94:3294.
    [55] Patte C, Auperin A, Michon J, Behrendt H, Leverger G, Frappaz D, Lutz P, Coze C, Perel Y, Raphael M, Terrier-Lacombe MJ. The Society Franc?aise d’Oncologie Pe′diatrique LMB89 protocol: highly effective multi-agent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood 2001; 97:3370
    [56] Yaniv I, Fischer S, Mor C, Stark B, Goshen Y, Stein J, Cohen IJ,Zaizov R. Improved outcome in childhood B-cell lymphoma with the intensified French LMB protocol. Med Pediatr Oncol 2000;35:8-12.
    [57] Wang JC.DNA Topoisomerases[J].Annu Rev Biochem,1996,65∶635-692.
    [58] Berger JM.Structure of DNA Topoisomerase[J].BioehimBioPhysAeta.1998,l:3-18.
    [59] Villman K,stah1 E,Lilje G, et al. TopoisomeraseⅡalpha expression in different cell cycle Phases in fresh human breast carcinomas[J].Mod Pathol,2002,15(5):486-491.
    [60] Wang JC. Recent studies of DNA Topoisomerases[J].Biochem Biophy Acta,1987,909(1):1-9.
    [61] Turley h, ComleyM,Houlbrook S, et a.l The distribution and expression of the two isoforms of DNA TopoisomeraseⅡin normal and neoplastic human tissues[J]. Br JCancer, 1997, 75: 1340.
    [62]周爱儒.第六版生物化学人民卫生出版社2007(4),226.
    [63] Turley h, Comley M,Houlbrook S, et al. The distribution and expression of the two isoforms of DNA TopoisomeraseⅡin normal and neoplastic human tissues[J]. Br JCancer, 1997, 75: 1340.
    [64]郑少江,吴焕明,王伟. LRP, Topo2α在非小细胞肺癌中的协同表达及其临床意义[J ].中国组织化学细胞化学杂志,2004,13 (2): 180-184.
    [65] Scheper RI,Broxterman HJ,Scheffer GL,et a1.Overexpression of a M(r)110.000 vesicular protein in non-P-glycoprotein-mediated muitidrug resistance.Cancer Res,1993,53:1475-1479 .
    [66]黄兆琦,吴波.DNA拓扑异构酶细胞凋亡[J].医学研究生学报,2002,15(6):539-541.
    [67] Wang JC.Recent studies of DNA Topoisomerases[J].Biochem BiophyActa,1987,909(1):1-9.
    [68] Champoux JJ. DNA Topoisomerases:structure , function , and mechanism[J].Annu RevBiochem,2001,70:369-413.
    [69] Bakshi RP,Galande S,Muniyappa K.Functional and regulatory characteristics of eukaryotic typeⅡDNA Topoisomerase [J].Crit.Rev. Biochem.Mol.Biol,2001,36(1):l-5.
    [70] Drake FH,Zimmerman JP,Mccabe FL,et al.Purification of TopoisomeraseⅡfrom amsacrine-resistant P388 leukemia cells:Evidence for two forms of the enzyme[J].J.Biol.Chem,1987,262:16739-16747.
    [71] Kellner U,Sehested M,Jensen PB.et al,CulPrit and victim-DNA TopoisomeraseⅡ[J]Lancet oncol,2002,3(4):235-243.
    [72] Marie JP,Littoun R,sik J.Multidrug resistance gene expression in adult acute leukemias[J].Blood,1991;78:586.
    [73] Cheffer GL,Wijngaard PL,Flens MJ,et a1.The drug resistance related proteinLRP is the human major vault protein[J].Nat Med,1995,6:578-582.
    [74]蒙凌华,张永炜,丁健.Chinese Journal of New Drugs 2002(11) 9:675-683.
    [75] Kimura K,Saijo M,Ui M,et al.Growth state and cell cycle-dependent fluctuation in the expression of two forms of DNA TopoisomeraseⅡand possible specific modification of the higher molecular weight form in the M phase[J].J Biol Chem,1994,269.
    [76] Kas E,Laemmli UK.In vivo TopoisomeraseⅠcleavage of the Drosophila histo and SatellitⅡrepeats:DNA sequence and structural characetristics[J].EMBO J, 1992 ,11(2):705-716.
    [77] M istry P, Stewart AJ , Dangerfield W , et al. Invitro and invivo characterization of XR 11576, anovel, orally active, dual inhibitor of Topoisomeraseα[J]. AnticancerDrugs,2002,13 (1):152.
    [78] Scheper RI,Broxterman HJ,Scheffer GL,et a1.Overexpression of a M(r)110.000 vesicular protein in non-P-glycoprotein-mediated muitidrug resistance.Cancer Res,1993,53:1475-1479.
    [79] Cheffer GL,Wijngaard PL,Flens MJ,et a1.The drug resistance related protein LRP is the human major vault protein[J].Nat Med,1995,6:578-582.
    [80] Hsiung Y,Elsea SH,Osheroff N,et al.A mutation in yeast TOPO2 homologous to a quinolone-resistant mutation in bacteria.Mutation of the amino acid homologous to Ser83 of Escherichia coli gyrA alters sensitivity to eukaryotic Topoisomerase inhibitors [J].JBiol Chem,1995,270(35)∶20359-20364.
    [81] Cheffer GL,Wijngaard PL,Flens MJ,et a1.The drug resistance related proteinLRP isthe human major vault protein.Nat Med,1995,6:578-582.
    [82] Cheffer GL,Wijngaard PL,Flens MJ,et a1.The drug resistance related proteinLRP is the human major vault protein.Nat Med,1995,6:578-582.
    [83] Haralampos S.Zorzo S,Andreas C et al.Multidrug resistance proteins and Topoisomerase IIαexpression in colon cancer:association with metastaticpotential [J].Pathology.August 2003,35(4),315–318.
    [84]卞寿庚.白血病[M].第一版.中国医药科技出版社.2003,150.
    [85] Miao ZH ,Ding J. Transcription factor c2Jun activation represses mdr21 gene expression [J ]. Cancer Res, 2003, 63 (15): 4527-4532.
    [86] Volm M,Matten J,Effeah T,et a1.Expression of several resistant mechanisma inuntreated human kidney and lung carcinonlasLJ].Anticancer Research,1992,12:1063-1068.
    [87] Webb CD,Latham MD,Lock RB,et a1.Attenuated Topoisomerase I contentdirectly correlates with low level of drug resistance in a Chinese hamster ovary cellline[J].Cancer Res,1991,51:6543-6549.
    [88]高鹏,周庚寅,殷钢等.负向调节多药耐药基因1转录逆转肿瘤多药耐药[J].中华病理学杂志.2003,12,32(6),563-566.
    [89]赵永同,朱峰.凋亡的分子机理[J].生命科学,1996, 419:23.
    [90]曾益新主编.肿瘤学,2001,人民卫生出版社300-301.
    [91] Robbert H.Cool,Marloes K.Veenstra,Wim van Klompenburg,et al.S-Decyl-glutathione nonspecifically stimulates the ATPase activity of thenucleotide-binding domains of the human multidrug resistance associated protein,MRP1(ABCC1) [J].Eur.J.Biochem.2002,269, 3470–3478.
    [92] Nathalie Perek,Delphine Denoyer.The Multidrug Resistance Mechanisms and their Interactions with the Radiopharmaceutical Probes Used for an In VivoDetection[J].Current Drug Metabolism.2002,3,97-113.
    [93]梁巍,杨纯正,郑德先.蛋白激酶C多药耐药相关性的研究进展[J].中国药理学通报.1998,8,14(4),303-305.
    [94] Parminder K.Gill,Andreas Gescher,Timothy W.Gant.Regulation of MDR1 promoter activity in human breast carcinoma cells by protein kinase cisozymesαandμ[J].Eur.J.Biochem.2001,268,4151-4157.
    [95]王涛.肿瘤多药耐药性型号转导.国外医学呼吸系统分册[J].2003,23(3),154-156.
    [96] Matsumoto Y , Kunishio K , Nagao S , et al.Increased phosphorylation of DNA TopoisomeraseⅡin eToposide resistant mutants of human glioma cell line[J].J Neurooncol,1999 45(l):37-46.
    [97] Scheper RI,Broxterman HJ,Scheffer GL,et a1.Overexpression of a M(r)110.000 vesicular protein in non-P-glycoprotein-mediated muitidrug resistance.Cancer Res,1993,53:1475-1479.
    [98] Matsumoto Y,Takano H,Fojo T ,cell adaptation to drug exposure:evolution of the drug,resistant phenotype[J].Cancer Res,1997,57(15):5086-5092.
    [99] Coles B,Ketterer B.The role of glutathione and glutathione transferases in chemical carcinogenesis[J].Cris Rev Biochem Mol Biol.1990,25:47-70.
    [100] Nicolletta Z , Alberto M , Patrizia S , et al.The 180-kDa isoform of TopoisomeraseⅡi slocalized in the nucleolus and belongs to the structural elements of the nucleolar remnant[J].Experimental CellReseareh,1992,200:460-467.
    [101] Nitiss JL.Using yeast to study resistance to Topoisomerase II targeting drugs[J].Cancer Chemother Pharmacol,1994,(Suppl)∶S 6-S13.
    [102] Mistry P, Stewart AJ , Dangerfield W , et al. Invitro and invivo characterization of XR 11576, anovel, orally active, dual inhibitor of Topoisomerase and [J]. Anticancer Drugs,2002,13 (1):152.
    [103] Kim WJ,Kakehi Y,Yoshida O.Multi-factorial involvement of multidrug resistance associated [correction of resistance] protein.DNA TopoisomeranseⅡandglutathione/glutathione- s-transferase in non P-glycoprotein-mediated multidrugresistance inhuman baldder cancer cells[J].Int J Urol,1997,4:583-590.
    [104] Saleem A,Ibrahim N,Patel M,et al.Mechanisms of resistance in a human cell line exposed to sequential Topoisomerase poisoning.Cancer Res,1997,57(22):5100-5106.
    [105] M iao ZH ,Ding J. Transcription factor c2Jun activation represses mdr21 gene expression [J ]. Cancer Res, 2003, 63 (15): 4527-4532.
    [106]张新宇,肿瘤细胞多药耐药机理的研究进展.实用癌症杂志,1999;14(3):233-236.
    [107] Binaschi M,Farinosi R,Austin CA,et al.Human DNA Topoisomerase IIalpha-dependent DNA cleavage and yeast cell killing by anthracycline analogues[J].Cancer Res,1998,58(9)∶1886-1892.
    [108] Bakshi RP,Galande S,MuniyaPPa K.Functional and regulatory characteristics ofEukaryotic typeⅡDNA Topoi- somerase[J].Crit.Rev.Biochem.Mol.Biol,2001,36(1):l-5.
    [109] Burden DA,Kingma PS,Froelich-Ammon SJ,et al.TopoisomeraseⅡ. Toposide interactions direct the formation of drug-induced enzyme-DNA cleavage complexes[J].J Biol Chem,1996,271(46)∶29238-29244.
    [110] Jarvinen TA,Kononen J,Pelto-Huikko M,et al.Expression of TopoisomeraseⅡalpha is associaetd with rapid cell proliferation,aneuploidy, and,c-erbB2 over experssion in breast cancer[J].AmJPathol,1996,148(6):2073-2082.
    [111] Coleman LW,Pekrins SL,Bronstein IB,et al.Expression of DNA ToposiomeraseⅠand DNA TopoisomeraseⅡalpha in testicular seminomas[J].HumPathol, 2000 ,31(6):728-733
    [112] Nakopoulou L , Lazaris AC , Kavantzas N , et al.DNA Topoisomerase Alpha immunoreactivity as a marker of tumor aggressiveness in invasive breast cancer[J].Pathobiology,2000,68(3):137-143.
    [113] Tanoguchi K,Sasano H,Yabuki N,et al.Immunohistochemical and two-parameter flow cytometric, studies of DNA TopoisomeraseⅡalpha in human epithelial ovarian carcinoma and germ cell tumor[J].Mod Pathol,1998,11(2):186-193.
    [114] Brustmann H,Naude S.Experssion of TopoisomeraseⅡalpha,MIB1,proliferating cell nuclear antigen,P53, and argyrophilic nucleolar organizer regions in vulvar squamous lesions[J].Gyne col Oncol,2002,86(2):192-199.
    [115] Willman JH,Holden JA.Immunohistochemical staining for DNA TopoisomeraseⅡalpha in benign,premalignant, and malignant lesions of the prostate[J].Prostate,2000,42(4):280-286.
    [116] SM, Gatterbauer B,Birner P, et al. Experssion of DNA TopoisomeraseⅡalpha in oligodendroglioma[J].Anticancer Res,2002,22(2B):1301-1304.
    [117] Bredel M,Slavcl,Briner P,et al.DNA TopoisomeraseⅡalpha expression in optic pathway gliomas of chilhdood[J].Eur J Cancer2002,38(3):393-400.
    [118] Staley BE,Samowitz WS,Bronstein IB,et al.Expression of DNA TopoisomeraseⅠAnd DNA TopoisomeraseⅡalpha in carcinoma of the colon[J]. ModPatho 1999,12(4):356-361.
    [119] Hirabayashs.Immunohistochemical detection of DNA Topoisomerase typeⅡalpha andMIB1 in adenoid cystic carcinoma and peomorphic adenoma of the salivary gland[J].J OralPathol Med,1999,28(3):131-136.
    [120] Rees M,Stah lM,Klum PB,et al.The Prognostic significance of proliferative activity apoptosis and expression of DNA TopoisomeraseⅡalpha in multimodally- treated oesophageal squamous cell carcinoma[J].Anticancer Res,2001,21(5):3637-3642.
    [121]吴波,黄兆琦,孟奎等.DNA拓扑异构酶Ⅱ在扁桃体程序性坏死细胞中的表达分布[J].医学研究生学报,2002,15(4):295-297.
    [122] Holden JA,Pekrins SL,Snow GW,et al.Immunohistochemical staining for DNA TopoisomeraseⅡin non-Hodgkin’s lymphomas[J].Am J Clin Pathol,1995,104(l):54-59.
    [123] Dingemans AM,Witlox MA,Stallaert RA,et al.Experssion of DNA Topoisomerase Il alpha and TopoisomeraseⅡbeta genes predicts survival and response to chemotherapy in patients with small cell lung cancer[J].Clin Cancer Res,1999,5(8):2048-2058.
    [124] Brown MS,Holden JA,Rahn MP,et al.Immunohistochemical staining for DNA TopoisomeraseⅡαin Hodgkin’s disease[J].Am J Clin Pathol,1998,109(l):39-44.
    [125] Oudard S , Levalois C , Andrieu JM , et al.Expression of genes involved in chemoresistance,proliefartion and apoptosis in clinical samples of renal cell carcinoma and correlation with clinical outcome[J].Anticancer Res,2002,22(IA):121-128.
    [126] Monnin KA,Bronstein IB,Gaffney DK,et al.Elevations of DNA TopoisomeraseⅠintransitional cell carcinoma of the urinary bladder:correlation with DNA TopoisomeraseⅡalpha and P53 expression[J].HumPathol,1999,30(4):384-391.
    [127] Wilson CS,Medeiros LJ,Lai R,et al.DNA TopoisomeraseⅡalpha in multiple myeloma:a markerof cell Proliferation and not drug resistance[J].Mod pathol,2001,14(9):886-891.
    [128] Korkolopoulou P , Patsouris E , Konstantinidou AE , et al.Mitosin and DNA TopoisomeraseⅡalpha:two novel proliferation markers in the prognostication of diffuse astrocytoma patient survival[J].APPI Immunohistochemistry Mol Morphol,2001,9(3):207-214.。
    [129] Malonne H,Atassi G.DNA Topoisomerase targeting drugs:mechanisms of action and perspectives[J].Anti Cancer Drugs,1997,8(9)∶811-822.
    [130] Krishnan P,Bastow KF.Novel mechanism of cellular DNA TopoisomeraseⅡinhibition by the pyranonaphthoquinone derivatives alpha-lapachone and beta-lapachone [ J].Cancer Chemother Pharmacol,2001,47(3)∶187-198.
    [131] Malonne H,Atassi G. DNA Topoisomerase targeting drugs:mechanisms of action and perspectives[J].Anti Cancer Drugs,1997,8(9)∶811-822.
    [132] Krishnan P,Bastow KF.Novel mechanism of cellular DNA TopoisomeraseⅡinhibition by the pyranonaphthoquinone derivatives alpha-lapachone and beta-lapachone [J].Cancer Chemother Phar- macol ,2001,47(3)∶187-198.
    [133] Hirabauashi S, Machi S, Maebashi K, et al. Immunohistochemical detection of DNA Topoi- somerase type II (alpha) and MIB1 in adenoid cystic carcinoma and pleomorphic adenoma of the salivary gland. J Oral Pathol Med. 1999;28:131-6.
    [134] Villman K, Stahl E, Liljegren G, et al. Tipoisomerase II expressionin different cell cycle phases in fresh human breast carcinomas.Mod Pathol. 2002; 15: 486-91.
    [135] Wilson CS, Medeiros J, Lai R, et al. DNA tipoisomerase II in multiple mye- loma: a marker of cell proliferation and not drug resistance. Mod Pathol. 2001; 14:886-91.
    [136] Kancherta RR, Nair JS, Ahmed A, et al. Evaluation of Topotecan and Toposide for non- Hodg kin’s lymphoma. Cancer. 2001;91:463-471.
    [137] DePowski PL,Rosenthal SI,Brien TP,et al. TopoisomeraseⅡalpha expression in breast cancer:correlation with outcome variables[J]Mod Pathol,2000,13(5):542-547.
    [138] Ohashi Y,Sasano H,Yamaki H ,et al. TopoisomeraseⅡa1pha expression in esophageal squamous cell carcinoma[J].Anticancer Res,1999,19(3A):1873-1880.
    [139] Korshunov A,Shishikina L,Golanov A.DNA TopoisomeraseⅡalpha and cyclin a immunoexpression in meningiomas and its prognostic significance: an analysis of 263 cases [J].Arch Pathol Lab Med,2002,126(9):1709-1786.
    [140] Staley BE,Samowitz WS,Bronstein IB,et al.Expression of DNA TopoisomeraseⅠand DNA TopoisomeraseⅡalpha in carcinoma of the colon[J]. ModPatho 1999,12(4):356-361.
    [141] Jarvinen TA,Holli K,Kuukasjarvi T,et al.predictive value of TopoisomeraseⅡalpha and other prongostic factors for epirubicin chemotherapy in advanced breast cancer[J].BrJCancer 1998,77(12):2267-2273.
    [142] Giacc G, Gazdar AF,Beck H.The multidrug sensitivity phenotype of human lung cancer cells associated with TopoisomeraseⅡexpression[J].Cancer Res,1992,52(2):1666-1674.
    [143]叶传忠,黄勤.DNA拓扑异构酶Ⅱ多药耐药研究进展[J].福建医科大学学报,1998.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700