应用眼眶淋巴瘤组织芯片检测P-gp、GST-π及LRP的表达及其临床意义
|
摘要
研究目的
制作眼眶淋巴瘤组织芯片；利用免疫组织化学检测三种耐药蛋白在眼眶淋巴瘤中的表达情况,初步探索该病的复发及预后不良机制
研究方法
1收集2003年至2008年期间诊断为眼眶淋巴瘤及反应性淋巴增生患者的临床病理资料,并对病人进行随访。
2制作眼眶淋巴瘤组织芯片。
3应用免疫组织化学检测P-gp、GST-π、LRP在眼眶淋巴瘤中的表达。
4应用SPSS13.0统计学软件对数据进行分析,以α=0.05为检验水准,P<0.05认为有统计学意义。
研究结果
1 50例眼眶淋巴瘤和17例眼眶反应性淋巴增生组织芯片经HE染色后,病理诊断结果与原取材的大组织诊断完全一致；有4例眼眶淋巴瘤在免疫组织化学的染色过程中一脱片,因此末对这4例标本的染色结果进行统计。
2三种耐药蛋白,P-gp和GST-π在眼眶淋巴瘤和反应性淋巴增生组织芯片中有不同程度表达,LRP在两种组织中均为阴性表达。P-gp蛋白主要表达于细胞膜,在两种病变的阳性表达率为87.0%和35.3%,其差异有统计学意义；GST-π表达于细胞浆,在两种病变的阳性表达率为76.1%和41.2%,其差异有统计学意义。
3 46例淋巴瘤：P-gp和GST-π这两种蛋白的阳性表达率在≥60岁和<60岁年龄组间、男女性别组间、≥2.5cm和<2.5cm肿瘤组间及≥1年和<1年发病时间组间均无统计学意义。
4将有随访结果的35例眼眶淋巴瘤分为两组,即预后不良组和预后良好组；P-gp在两组间的表达率分别为85.7%和42.9%,其差异有统计学意义；GST-π在两组间的表达率分别为78.7%和38.1%,其差异有统计学意义。
5 P-gp和GST-π在眼眶淋巴瘤中的表达呈正相关(P<0.05)。
结论
1眼眶淋巴瘤组织芯片省时快速,结果可靠,高效经济地研究了该肿瘤的多药耐药基因表达状况。
2 P-gp在眼眶淋巴瘤和反应性淋巴增生组间阳性比率表达差异有统计学意义,说明P-gp对判断眼眶淋巴细胞性疾病的病变性质有一定价值；同时P-gp在眼眶淋巴瘤预后不良组和预后良好组间阳性率表达差异有统计学意义,说明P-gp可以预测眼眶淋巴瘤的预后。
3 GST-π在眼眶淋巴瘤和反应性淋巴增生组间阳性率表达差异有统计学意义,说明P-gp对判断眼眶淋巴细胞性疾病的病理性质有一定意义；同时GST-π在眼眶淋巴瘤预后不良组和预后良好组间阳性率表达差异有统计学意义,说明GST-π可以预测眼眶淋巴瘤的预后
4 LRP在眼眶淋巴瘤和反应性淋巴增生组均呈阴性表达,提示LRP与眼眶淋巴细胞性疾病的发生发展无明确相关性。
5 P-gp和GST-π蛋白在眼眶淋巴瘤中的表达呈正相关,联合检测这两种指标可能对预测眼眶淋巴瘤预后有更大价值。
Objetive
We produce orbital lymphoma tissue microarray and detect the three resistance protein in the orbital lymphoma tissues by Immunohistochemistry to explore the relapse and poor prognosis mechanism of the disease mechanism
Methods
1. Collect the clinical and pathological information of patients as orbital lymphoma and reactive lymphoid hyperplasia from 2003 to 2008 and make a follow up of all patients..
2. Produce produce orbital lymphoma tissue microarray.
3. Immunohistochemical staining was used to detect the expression of P-gp, GST-πand LRP in orbital lymphoma and reactive lymphoid hyperplasia.
4. The data was analyzed by SPSS 17.0 statistical software. P<0.05 was regarded as the standard of statistical significance.
Results
1. The pathological diagnosis of the tissue microarray of fifty orbital lymphoma and seventeen reactive lymphoid hyperplasia is consistant with the original tissue. There are four orbital lymphoma off-chips in the process of Immunohistochemical staining and so we don't cout their results.
2. P-gp and GST-πexpressed in tissue microarray of orbital lymphoma and reactive lymphoid hyperplasia in different levels. LRP doesn't expressed in the both tumors tissue microarray. P-gp maily expressed in the cell membrance. The P-gp expression rates are 87.0% and 64.7% in the two tumors tissue microarray and there is significant difference between them(P<0.05). GST-πmaily expressed in the cytoplasm. The GST-πexpression rates are 76.1% and 47.1% in the two tumors tissue microarray and there is significant difference between them(P<0.05).
3. The expression of P-gp and GST-πhas nothing to do with ages, sexs, tumor size and course of disease in the orbital lymphoma.
4. We divided the orbital lymphoma wih follow-up results into two groups:poor prognosis group and good prognosis group. The P-gp expression rates are 85.7% and 42.9% in the two groups and there is significant difference between them(P<0.05). The GST-πexpression rates are 78.7% and 38.1% in the two groups and there is significant difference between them(P<0.05).
5. The positive correlation was showed between protein expression levels of P-gp and GST-πin the orbital lymphoma.
Conc|usion
1.By orbital lymphoma tissue microarray we detect the MDR gene expression rapidly, reliably, efficiently and economically.
2.The difference of P-gp expression between the orbital lymphoma and reactive lymphoid hyperplasia was statistically significant, which maybe demonstrate that P-gp can reflect the malignancy degree of the orbital lymphoid disease. Meanwhile, in the orbital lymphoma the difference of P-gp expression between the poor prognosis group and good prognosis group was statistically significant, which maybe demonstrate that P-gp can predict the prognosis of the orbital lymphoma.
3.The difference of GST-πexpression between the orbital lymphoma and reactive lymphoid hyperplasia was statistically significant, which maybe demonstrate that GST-πcan reflect the malignancy degree of the orbital lymphoid disease. Meanwhile, in the orbital lymphoma the difference of GST-πexpression between the poor prognosis group and good prognosis group was statistically significant, which maybe demonstrate that GST-πcan predict the prognosis of the orbital lymphoma.
4..The positive correlation was showed between protein expression levels of P-gp and GST-πin the orbital lymphoma, which demonstrate that combined detection of P-gp and GST-πmaybe contribute to predict the prognosis of the orbital lymphoma.
制作眼眶淋巴瘤组织芯片；利用免疫组织化学检测三种耐药蛋白在眼眶淋巴瘤中的表达情况,初步探索该病的复发及预后不良机制
研究方法
1收集2003年至2008年期间诊断为眼眶淋巴瘤及反应性淋巴增生患者的临床病理资料,并对病人进行随访。
2制作眼眶淋巴瘤组织芯片。
3应用免疫组织化学检测P-gp、GST-π、LRP在眼眶淋巴瘤中的表达。
4应用SPSS13.0统计学软件对数据进行分析,以α=0.05为检验水准,P<0.05认为有统计学意义。
研究结果
1 50例眼眶淋巴瘤和17例眼眶反应性淋巴增生组织芯片经HE染色后,病理诊断结果与原取材的大组织诊断完全一致；有4例眼眶淋巴瘤在免疫组织化学的染色过程中一脱片,因此末对这4例标本的染色结果进行统计。
2三种耐药蛋白,P-gp和GST-π在眼眶淋巴瘤和反应性淋巴增生组织芯片中有不同程度表达,LRP在两种组织中均为阴性表达。P-gp蛋白主要表达于细胞膜,在两种病变的阳性表达率为87.0%和35.3%,其差异有统计学意义；GST-π表达于细胞浆,在两种病变的阳性表达率为76.1%和41.2%,其差异有统计学意义。
3 46例淋巴瘤：P-gp和GST-π这两种蛋白的阳性表达率在≥60岁和<60岁年龄组间、男女性别组间、≥2.5cm和<2.5cm肿瘤组间及≥1年和<1年发病时间组间均无统计学意义。
4将有随访结果的35例眼眶淋巴瘤分为两组,即预后不良组和预后良好组；P-gp在两组间的表达率分别为85.7%和42.9%,其差异有统计学意义；GST-π在两组间的表达率分别为78.7%和38.1%,其差异有统计学意义。
5 P-gp和GST-π在眼眶淋巴瘤中的表达呈正相关(P<0.05)。
结论
1眼眶淋巴瘤组织芯片省时快速,结果可靠,高效经济地研究了该肿瘤的多药耐药基因表达状况。
2 P-gp在眼眶淋巴瘤和反应性淋巴增生组间阳性比率表达差异有统计学意义,说明P-gp对判断眼眶淋巴细胞性疾病的病变性质有一定价值；同时P-gp在眼眶淋巴瘤预后不良组和预后良好组间阳性率表达差异有统计学意义,说明P-gp可以预测眼眶淋巴瘤的预后。
3 GST-π在眼眶淋巴瘤和反应性淋巴增生组间阳性率表达差异有统计学意义,说明P-gp对判断眼眶淋巴细胞性疾病的病理性质有一定意义；同时GST-π在眼眶淋巴瘤预后不良组和预后良好组间阳性率表达差异有统计学意义,说明GST-π可以预测眼眶淋巴瘤的预后
4 LRP在眼眶淋巴瘤和反应性淋巴增生组均呈阴性表达,提示LRP与眼眶淋巴细胞性疾病的发生发展无明确相关性。
5 P-gp和GST-π蛋白在眼眶淋巴瘤中的表达呈正相关,联合检测这两种指标可能对预测眼眶淋巴瘤预后有更大价值。
Objetive
We produce orbital lymphoma tissue microarray and detect the three resistance protein in the orbital lymphoma tissues by Immunohistochemistry to explore the relapse and poor prognosis mechanism of the disease mechanism
Methods
1. Collect the clinical and pathological information of patients as orbital lymphoma and reactive lymphoid hyperplasia from 2003 to 2008 and make a follow up of all patients..
2. Produce produce orbital lymphoma tissue microarray.
3. Immunohistochemical staining was used to detect the expression of P-gp, GST-πand LRP in orbital lymphoma and reactive lymphoid hyperplasia.
4. The data was analyzed by SPSS 17.0 statistical software. P<0.05 was regarded as the standard of statistical significance.
Results
1. The pathological diagnosis of the tissue microarray of fifty orbital lymphoma and seventeen reactive lymphoid hyperplasia is consistant with the original tissue. There are four orbital lymphoma off-chips in the process of Immunohistochemical staining and so we don't cout their results.
2. P-gp and GST-πexpressed in tissue microarray of orbital lymphoma and reactive lymphoid hyperplasia in different levels. LRP doesn't expressed in the both tumors tissue microarray. P-gp maily expressed in the cell membrance. The P-gp expression rates are 87.0% and 64.7% in the two tumors tissue microarray and there is significant difference between them(P<0.05). GST-πmaily expressed in the cytoplasm. The GST-πexpression rates are 76.1% and 47.1% in the two tumors tissue microarray and there is significant difference between them(P<0.05).
3. The expression of P-gp and GST-πhas nothing to do with ages, sexs, tumor size and course of disease in the orbital lymphoma.
4. We divided the orbital lymphoma wih follow-up results into two groups:poor prognosis group and good prognosis group. The P-gp expression rates are 85.7% and 42.9% in the two groups and there is significant difference between them(P<0.05). The GST-πexpression rates are 78.7% and 38.1% in the two groups and there is significant difference between them(P<0.05).
5. The positive correlation was showed between protein expression levels of P-gp and GST-πin the orbital lymphoma.
Conc|usion
1.By orbital lymphoma tissue microarray we detect the MDR gene expression rapidly, reliably, efficiently and economically.
2.The difference of P-gp expression between the orbital lymphoma and reactive lymphoid hyperplasia was statistically significant, which maybe demonstrate that P-gp can reflect the malignancy degree of the orbital lymphoid disease. Meanwhile, in the orbital lymphoma the difference of P-gp expression between the poor prognosis group and good prognosis group was statistically significant, which maybe demonstrate that P-gp can predict the prognosis of the orbital lymphoma.
3.The difference of GST-πexpression between the orbital lymphoma and reactive lymphoid hyperplasia was statistically significant, which maybe demonstrate that GST-πcan reflect the malignancy degree of the orbital lymphoid disease. Meanwhile, in the orbital lymphoma the difference of GST-πexpression between the poor prognosis group and good prognosis group was statistically significant, which maybe demonstrate that GST-πcan predict the prognosis of the orbital lymphoma.
4..The positive correlation was showed between protein expression levels of P-gp and GST-πin the orbital lymphoma, which demonstrate that combined detection of P-gp and GST-πmaybe contribute to predict the prognosis of the orbital lymphoma.
引文
[1]魏小勇,罗灼玲等,组织芯片与基因芯片在肿瘤研究中的联合应用[J].解剖学研究,2004,26(4)：305-308.
[2]Kononen J, Bubendorf L, Kallioniemi A, etal. Tissue microarrays for high-throughput molecular profiling of tumor specimens[J].Nat med,1998,4(7):844-7.
[3]Shields JA, Shields CL, Scartozzi R. Survey of 1264 patients with orbital tumors and simulating lesions[J]. Ophthalmlogy,2004,111(5):997-1008.
[4]何彦津,宋国祥,丁莹.3476例眼眶古位性病变的组织病理学分类[J].中华眼科杂志,2002,38：396-398.
[5]Margo CE, Mulla ZD. Malignant tumors of the orbit.Analysis of the Florida Cancer Registry[J]. Ophthalmology,1998,105(1):185-90.
[4].袁伟,王胜资,程庆芳等.眼眶原发淋巴瘤远期疗效分析[J].中华放射肿瘤学杂志,2004,13(4)：257-260
[5].宋国祥,吴中耀,孙丰源,等.眼眶病学[M].北京：人民卫生出版社,1999.300-306
[8]Tang F, Ouyang H, Yang JZ, et al.Bidirectional transport of rhodamine 123 and Hoechst 33342, fluorescence probes of the binding sites on P-glycoprotein, across MD-CK-MDR1 cell monolayers[J].J Pham Sci,2004,93(5):1185-94.
[9]Troutman MD, Thakker DR. Rhodamine 123 requires carrier-mediated influx for its activity as a P-glycoprotein substrate in Caco-2 cells[J].Pham Res,2003,20 (8):1192-9.
[10]李春海,郭亚军主编.肿瘤分子生物学研究进展[M].北京：军事医学科学出版社,1996.103-104.
[11]Chung HC, Rha SY, Kim JH,et al.P-glycoprotein:the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer[J].Breast Cancer Res Treat,1997,42(1):65-72.
[12]戴广海,石廷章,李春海.肺癌MDR1和GST-π mRNA水平测定及临床意义[J].中国肿瘤临床,1999,22(3)：6
[13]付保进,张云汉,王尧河,等.食竹癌发生发展过程GST-π基因表达研究[J]. 中华肿瘤杂志,1999,21(1)：29.
[14]Izquierdo MA, Scheffer GL. Flens MJ, etal.Major Vault Protein LRP-related multidrug resistance[J]. Eur J Cancer,1996,32A(6):979-84.
[15]Filipits M, Jaeger U, Simonitsch I, et al. Clinical relevance of the lung resistance protein in diffuse large B-cell lymphomas[J]. Clin Cancer Res, 2000,6(9):3417-23.
[16]Moch H, Kononen T, Kallioniemi OP,et al. Tissue microarrays:what will they bring to molecular and anatomic pathology?[J]. Adv Anat Pathol,2001,8(1):14-20.
[17]游启生,李彬,周小鹏等.112例眼附属器淋巴增生性病变临床组织病理学初步分析[J].中华眼科杂志,2005,41(10)：871-876.
[18]Coupland SE, Krause L, Deleluse HJ, et al. Lymphoproliferative lesions of the ocular adnexa.Analysis of 112cases[J].Ophthalmology,1998,105(8):1430-41.
[19]Nakata M, MatsunoY, Katsumata N, et al. Histology according to the Revised EuroPean-American LymPhoma Classification significantly predicts the prognosis of ocular adnexal lymphoma[J]. Leuk Lymphoma,1999, 32(5-6):533-43.
[20]Jenkins C, Rose GE, Bunce C, et al. Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival[J]. Br J Ophthalmol,2000,84(8):907-13.
[21]Robert J.Multidrug resistance reversal agents [J].Drugs Fut1997,22(2):149150.
[22]Krishna R, Mayer LD. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the phannacokinetics of anticancer drugs[J]. Eur J Phar m Sci,2000, 11 (4):265-83.
[23]周晓冬,宋国祥,何彦津等,多药耐药基因在眼眶腺样囊性癌中的表达[J].眼科研究,2007,25(3)：164-167.
[24]肿瘤多药耐药基因 p-糖蛋白及其耐药逆转的研究进展[J].临床医药实践,2010,19(4A)：245-46.
[25]Ohsawa M, Ikura Y, Ukushima H, et al. Inununohistochemical expression of multidrug resistance proteins as a predietor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B-cell lymphoma[J].Oncology, 2005,68(4-6):422-31.
[26]Yuen AR, Sikic BI. Multidrug resistance in lymphomas[J]. J Clin Oncol,1994,12 (11):2453-9.
[27]Miller TP, Grogan TM, Dalton WS, et al. P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil[J]. J Clin Oncol,1991,9(1):17-24.
[28]李志革,匡志鹏,于起涛等,多药耐药基因 P-糖蛋白在恶性淋巴瘤组织中的表达[J].右江民族医学院报,2002,24(6)：809-810。
[29]傅小玉,于丁,毛永荣等,非霍奇金淋巴瘤患者P-gp、P26-bc1-2表达的临床研究[J].中华血液学杂志,2001,22(6)：310-311。
[30]刘淑芳,张青山,金仲品等,鼻腔 鼻咽部恶性淋巴瘤多药耐药基因表达的临床研究[J].中国药房,2009,20(11)：843-845.
[31]Meyer DJ, Coles B, Pemble SE, et al.Theta, a new class of glutathione transferases purified from rat and man[J]. Biochem J,1991,274(Pt2):409-14.
[32]Mannervik B, Awasthi YC, Board PG, et al.Nomenclature for human glutathione transferases[J].Biochem J,1992,282(Pt 1):305-6.
[33]冯丹,刘云鹏,GST-π与恶性肿瘤多药耐药的研究进展[J].肿瘤防治杂志,2004,11(6)：663-665.
[34]Hirano T, Kato H, Maeda M, et al.Identification of postoperative adjuvant chemotherapy responders in non-small cell lung cancer by novel biomarker[J]. Int J Cancer.2005,117(3):460-8.
[35]Kaynar H, Meral M, Turhan H, et al.Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu-Zn superoxide dismutase aetivities, total glutathione, nitric oxide, and malondialdehyde levels in erythrocytes of patients with small cell and non-small cell lung cancer[J]. Cancer Lett,2005, 227(2):133-9.
[36]Scheper RJ, Broxterman HJ, Scheffer GL, et al. Overexpression of a M(r) 110,000 vesicular protein in non-p-glycoprotein-mediated multidrug resistance[J]. Cancer Res,1993,53(7):1475-9.
[37]Plaat B E, Molenaar W M, Sagrudny J, et al. The 16p11 breakpoint in myxoid liposarcomas might affect the expression of the LRP gene on 16p11.2 encoding the multidrug resistance associated major vault protein [J]. Eur J Clin Invest, 2000,30 (5):447-53.
[38]Scheffer GL, Wijngaard PL, Izquierdo MA,et al.The drug resistance-related protein LRP is the human major vault protein [J]. Nat Med,1995,1(6):578-82.
[39]Izquierdo MA, Scheffer GL, Flens MJ, et al.Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors[J]. Am J Pathol,1996,148 (3):877-87.
[40]Rybarova S, Hodorova I, Hajdukova M, et al. Expression of MDR proteins in breast cancer and its correlation with some clinical and pathological parameters[J]. Neoplasma,2006,53 (2):128-35.
[41]Paredes Lario A, Blanco Garcia C, Echenique Elizodo M,et al. Expression of proteins associated with multidrug resistance and resistance to chemotherapy in lung cancer [J].Arch Bronconeumol,2007,43 (9):479-84.
[42]陈琦,杨敏,非霍奇金淋巴瘤中肺耐药相关蛋白的表达及意义[J].山东医药,2006,46(16)：5-6.
[43]Huo J, Che C, Huang Q. Coexpression and clinical significance of multidrug-drug resistance factors in lung cancer[J], Chin J Lung Cancer June, 2004:7(3):218-21.
[44]王文静,王明玉,吴宁等,P-gp与GST-π在乳腺癌组织中的表达及其相关性研究[J].中国老年学杂志,2008,28(9)：893-894.
[45]凌斌勋,陈环球,徐新宇等,GST-π和P-gp在胃癌中的表达及其临床意义,临床肿瘤学杂志[J].2010,15(6)：523-525.
[46]P-gp、GST-π、TOPOⅡ在外周T细胞淋巴瘤中的表达及意义[J].现代肿瘤医学,2009,17(8)：1543-1546.
[47]孙丽梅,王鲁建,宋敏等,乳腺癌中耐药蛋白P-gp、GST-π、TopoⅡ的表达[J].中国组织化学与细胞化学杂志,2006；15(2)：169-72.
[1]魏小勇,罗灼玲等,组织芯片与基因芯片在肿瘤研究中的联合应用[J].解剖学研究,2004,26(4)：305-308.
[2]Kononen J, Bubendorf L, Kallioniemi A, etal. Tissue microarrays for high-throughput molecular profiling of tumor specimens[J].Nat med,1998,4(7):844-7.
[3]周小鸽,张劲松,张小平等,组织芯片[J],中华病理学杂志,2002,31(1)：70-72.
[4]Hsu FD, Nielsen TO, Alkushi A, et al.Tissue microarrays are an effective quality assurance tool for diagnostic immunohistochemistry[J].Mod Pathol,2002,15 (12):1374-1380.
[5]Wang Y, Wu MC, Sham JS, et al. Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray[J].Cancer,2002,95 (11):2346-2352.
[6]Moch H, Schraml P, Mirlacher M, et al. High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microrray screening in renal cell carcinoma[J]. Am J Pathol,1999,154(4):981-986.
[7]Gillett CE, Springall RJ, Barnes DM,et al. Mutiple tissue core arrays in histopaholgy research:a validation study[J]. J Pathol,2002,192 (4):549-53.
[8]Barlund M, Monni O, Kononen J, et al. Multiple genes at 17q23 undergo amplification and overexpression in breast cancer[J]. Cancer Res,2000,60 (19):5340-5344.
[9]Yanqiu Zhao, Han You, Fei Liu, et al.Differentially expressed gene profiles between multidrug resistant gastric adenocarcinoma cells and their parental cells [J].Cancer Letters,2002,185(2):211-218.
[10]Krishna R, Mayer LD. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the phannacokinetics of anticancer drugs[J]. Eur J Phar m Sci,2000, 11 (4):265-83.
[11]Tang F, Ouyang H, Yang JZ, et al.Bidirectional transport of rhodamine 123 and Hoechst 33342, fluorescence probes of the binding sites on P-glycoprotein, across MD-CK-MDR1 cell monolayers[J].J Pham Sci,2004,93(5):1185-94.
[12]Troutman MD, Thakker DR. Rhodamine 123 requires carrier-mediated influx for its activity as a P-glycoprotein substrate in Caco-2 cells[J].Pham Res,2003,20 (8):1192-9.
[13]肿瘤多药耐药基因 p-糖蛋白及其耐药逆转的研究进展[J].临床医药实践,2010,19(4A)：245-46.
[14]Chretien A, Chataigner I, L Helias N, et al. Complete and remarkable reversal of chemoselectivity ink[4+2] cycloadditions involving electron-poor indoles as dienophiles. Diels-Alder versus hetero-Diels-Alder processes[J].J Org Chem, 2003,68(21):7990-8002.
[15]Marzolini C, Paus E, Buclin T, et al. Polymorphisms in human MDR1 (P-glycoprotein):recent advances and clinical relevance[J].Clin Phaimacol Ther, 2004,75(1):13-33.
[16]Ohsawa M, Ikura Y, Ukushima H, et al. Inununohistochemical expression of multidrug resistance proteins as a predietor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B-cell lymphoma[J].Oncology, 2005,68(4-6):422-31.
[17]Zenkov AN, Scvortsova NV, Chernolovskaya EL, et al. Expression of the MDR1 and MRP genes in patients with lymphoma with primary bone marrow involvement[J].Nuelcosides Nueleotides Nueleic Acids,2004,23(6-7):843-847.
[18]Yuen AR, Sikic BI. Multidrug resistance in lymphomas[J]. J Clin Oncol,1994,12 (11):2453-9.
[19]Miller TP, Grogan TM, Dalton WS, et al. P-glycoprotein expression in malignant lymphoma and reversal of clinical drag resistance with chemotherapy plus high-dose verapamil[J]. J Clin Oncol,1991,9(1):17-24.
[20]Meyer DJ, Coles B, Pemble SE, et al.Theta, a new class of glutathione transferases purified from rat and man[J]. Biochem J,1991,274(Pt2):409-14.
[21]Mannervik B, Awasthi YC, Board PG, et al.Nomenclature for human glutathione transferases [J].Biochem J,1992,282(Pt 1):305-6.
[22]冯丹,刘云鹏,GST-π与恶性肿瘤多药耐药的研究进展,肿瘤防治杂志, 2004,11(6)：663-665.
[23]Volm M, Mattern J, Samsel B. Overexpression of P-glycoprotein and gultathion S-transrerase-π in resistant non-small cell lung carcionomas of smokers[J]. Br J Cancer,1991,64(4):700-4.
[24]Hirano T, Kato H, Maeda M, et al.Identification of postoperative adjuvant chemotherapy responders in non-small cell lung cancer by novel biomarker[J]. Int J Cancer.2005,117(3):460-8.
[25]Kaynar H, Meral M, Turhan H, et al.Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu-Zn superoxide dismutase aetivities, total glutathione, nitric oxide, and malondialdehyde levels in erythrocytes of patients with small cell and non-small cell lung cancer[J]. Cancer Lett,2005, 227(2):133-9.
[26]周晓冬,宋国祥,何彦津等,多药耐药基因在眼眶腺样囊性癌中的表达[J].眼科研究,2007,25(3)：164-167.
[27]Arai T, Yasuda Y, Takaya T, et al.Immunohistochemical expression of glutathione transferase-pi in untreated primary non-small cell lung cancer[J].Cancer Detect Prev,2000,24(3):252-257.
[28]李春海,郭亚军主编.肿瘤分子生物学研究进展[M].北京：军事医学科学出版社,1996.103-104.
[29]Chung HC, Rha SY, Kim JH,et al.P-glycoprotein:the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer[J].Breast Cancer Res Treat,1997,42(1):65-72.
[30]戴广海,石廷章,李春海.肺癌MDR1和GST-π mRNA水平测定及临床意义[J].中国肿瘤临床,1999,22(3)：6
[31]付保进,张云汉,王尧河,等.食管癌发生发展过程GST-π基因表达研究[J].中华肿瘤杂志,1999,21(1)：29.
[32]Scheper RJ, Broxterman HJ, Scheffer GL, et al. Overexpression of a M(r) 110,000 vesicular protein in non-p-glycoprotein-mediated multidrug resistance[J]. Cancer Res,1993,53 (7):1475-9.
[33]Plaat B E, Molenaar W M, Sagrudny J, et al. The 16p11 breakpoint in myxoid liposarcomas might affect the expression of the LRP gene on 16p11.2 encoding the multidrug resistance associated major vault protein[J]. Eur J Clin Invest, 2000,30 (5):447-53.
[34]Scheffer GL, Wijngaard PL, Izquierdo MA,et al.The drug resistance-related protein LRP is the human major vault protein [J]. Nat Med,1995,1(6):578-82.
[35]Kong LB, Siva AC, Kickhoefer VA,et al.RNA location and modeling of a WD40 repeat domain within the vault[J].RNA,2000,6(6):890-900.
[36]Izquierdo MA, Scheffer GL. Flens MJ, etal.Major Vault Protein LRP-related multidrug resistance[J]. Eur J Cancer,1996,32A(6):979-84.
[37]Izquierdo MA, Scheffer GL, Flens MJ, et al.Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors[J]. Am J Pathol,1996,148 (3):877-87.
[38]Rybarova S, Hodorova I, Hajdukova M, et al. Expression of MDR proteins in breast cancer and its correlation with some clinical and pathological parameters[J]. Neoplasma,2006,53 (2):128-35.
[39]Paredes Lario A, Blanco Garcia C, Echenique Elizodo M,et al. Expression of proteins associated with multidrug resistance and resistance to chemotherapy in lung cancer [J].Arch Bronconeumol,2007,43 (9):479-84.
[40]IzquierdoMA, Van der Zee AG, Vermorker JB, et al. Drug resistance-assoaiated marker LRP for predietion of response to chemotherapy and prognoses in advanced ovarian carcinoma[J].J Natl Cancer Inst,1995,87(16):1230-7.
[41]Huo J, Che C, Huang Q. Coexpression and clinical significance of multidrug-drug resistance factors in lung cancer[J], Chin J Lung Cancer June, 2004:7(3):218-21.(?)
[42]Cheng AL, Su IJ, Chen YC, et al. Expression of P-glycoprotein and glutathione-S-transferase in recurrent lymphomas:the possible role of Epstein-Barr virus, immunophenotypes, and other predisposing factors[J]. J Clin Oncol,1993,11(1):109-15.
[43]王文静,王明玉,吴宁等,P-gp与GST-π在乳腺癌组织中的表达及其相关性研究[J].中国老年学杂志,2008,28(9)：893-894.
[44]凌斌勋,陈环球,徐新宇等,GST-π和P-gp在胃癌中的表达及其临床意义[J].临床肿瘤学杂志,2010,15(6)：523-525.
[45]P-gp、GST-π、TOPOⅡ在外周T细胞淋巴瘤中的表达及意义[J].现代肿瘤医学,2009,17(8)：1543-1546.
[46]FiliPits M, Drach J, Pohl G, et al. Expression of the lung resistance protein poor outcome in patients with multiple myeloma[J]. Clin Caneer Res, 1999:5(9):2426-30.
[47]袁凯,付荣湛,孙勇等,P-糖蛋白和肺耐药蛋白在浸润性乳腺癌中的表达及其临床意义[J].中华乳腺病杂志(电子版),2010,4(4)：410-416.
[48]樊娟,张丽,刘思管等,急性白血病细胞P-gp, LRP的表达及其临床意义[J].中国肿瘤临床,2007,34(7)：374-376.
[49]曲延刚,纪祥瑞,唐爱萍,多药耐药相关蛋白在乳腺浸润性导管癌中的表达[J].青岛大学医学院报,2007,43(1)：70-71.
[50]曲延刚,孙正船,綦瑶等,乳腺癌中LRP、GST-π的表达及临床意义[J].陕西医学杂志,2005,34(2)：156-158.
[51]姜余梅,刘卫平,唐琼兰等,鼻NK-T淋巴瘤耐药基因相关蛋白的检测[J].中国肿瘤临床,2004,31(2)：74-77.
[52]于树娜,蒋吉英,赵世福等,LRP、GST-π在干细胞癌中的表达及意义[J].现代肿瘤医学,2010,18(01)：102-105.
[53]郭杨,杨会钗,王永军等,肺耐药相关蛋白在肺癌组织中的表达及意义[J].山东医药,2005,45(6)：9-11.
[54]Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance[J]. Nat Rev Cancer,2005,5 (4):275-284.
[55]Efferth T, Fabry U, Osieka R. Interleukin-6 affects melphalan-induced DNA damage and repair in human multiple myeloma cells [J]. Anticancer Res,2002, 22(1A):231-234.
[56]Zhang Q, Zhang ZF, Rao JY, et al. Treatment with siRNA and antisense oligonucleotides targeted to HIF-1 alpha induced apoptosis in human tongue squamous cell carcinomas[J]. Int J Cancer,2004,111(6):849-857.
[57]Dumontet C, Jaffrezou JP, Tsuchiya E, et al. Resistance to microtubule-targeted cytotoxins in a K562 leukemia cell variant associated with altered tubulin expression and polymerization[J]. Bull Cancer,2004,91 (5):E81-112.
[58]Tsuruo T, Naito M, Tomida A, et al. Molecular targeting therapy of cancer:drug resistance, apoptosis and survival signal[J]. Cancer Sci,2003,94(1):15-21.
[59]立彦.P-gp介导的肿瘤多药耐药逆转研究进展[J].放射免疫学杂志,2005,18(2)：133.
[60]Naito M, Tsuruo T. New multidrug-resistance-reversing drugs, MS-209 and SDZ PSC 833 [J]. Cancer Chemother Pharmacol,1997,40 Suppl):S20-4.
[61]徐峰,蔡卓夫.肿瘤耐药逆转剂研究进展[J].中南药学,2004,2(5)：301
[62]Zhang Y, Zhou G, Wang H, et al. Transcriptional upregulation of breast cancer resistance protein by 17beta-estradiol in ERalpha-positiveMCF-7 breast cancer cells[J]. Oncology,2006,71 (5-6):446-455.
[63]李旭芬,张苏展,郑树.苦参碱对K562及其多药耐药细胞的细胞生物学影响[J].中国病理生理杂志,2002,18(10)：1233.
[64]李起,刘作金,张俊等,中药复方肝癌-1 号逆转肝癌多药耐药的实验研究[J]消化外科,2006,5(1)：70-73.
[65]杨铭, 高瀛岱, 熊冬生,等.抗P-gp/抗CD3微型双功能抗体裸鼠体内分布研究[J].中国肿瘤临床,2004,31(20)：1182.
[66]Takahashi M, Misawa Y, Watanabe N, et al. Role of P-glycoprotein in human natural killer-like cell line mediated cytotoxicity[J]. Exp Cell Res,1999, 253(2):396-402
[67]Azuma E, Masuda S, Qi J, et al. Cytotoxic T-lymphocytes recognizining P-glycoprotein in murine multidrug-resistant leukemias[J]. Eur J Haematol, 1997,59(1):14-9.
[68]Nieth C, Priebsch A, Stege A. et al. Modulation of the classical multidrug resistance(MDR) phenotype by RNA interference (RNAi)[J]. FEBS Lett,2003, 545(2-3):144-150.
[69]Wu H, Hait WN, Yang JM. Small interfering RNA induced suppression of MDR1 (P-g lycoprotein) restores sensitivity to multidrug resistant cancer cells[J]. Cancer Res,2003,63(7):1515-1519.
[70]Khan O, Middleton MR. The therapeutic potential of O6-alky lguanine DNA alky-ltransferase inhibitors[J]. Expert O pin Investig Drugs,2007,16(10):1573-1584.
[71]李学汤,姜洁,马道新,等.p53基因转染对卵巢癌MDR细胞药物敏感性及 恶性农型的影响[J].现代妇产科进展,2000,9(6)：428
[72]李杰,郭伟剑,许良中.肿瘤坏死因子α和干扰素α逆转K562/A02耐药性的研究[J].中国肿瘤生物治疗杂志,2001,8(3)：186。
[73]Carpinteiro A, Peinert S, Ostertag W, et al. Genetic protection of repopulating hematopoietic cells with an improved MDR1-retrovirus allows administration of intensified chemotherapy following stem cell transplantation in mice [J]. Int J Cancer,2002,98(5):785.
[2]Kononen J, Bubendorf L, Kallioniemi A, etal. Tissue microarrays for high-throughput molecular profiling of tumor specimens[J].Nat med,1998,4(7):844-7.
[3]Shields JA, Shields CL, Scartozzi R. Survey of 1264 patients with orbital tumors and simulating lesions[J]. Ophthalmlogy,2004,111(5):997-1008.
[4]何彦津,宋国祥,丁莹.3476例眼眶古位性病变的组织病理学分类[J].中华眼科杂志,2002,38：396-398.
[5]Margo CE, Mulla ZD. Malignant tumors of the orbit.Analysis of the Florida Cancer Registry[J]. Ophthalmology,1998,105(1):185-90.
[4].袁伟,王胜资,程庆芳等.眼眶原发淋巴瘤远期疗效分析[J].中华放射肿瘤学杂志,2004,13(4)：257-260
[5].宋国祥,吴中耀,孙丰源,等.眼眶病学[M].北京：人民卫生出版社,1999.300-306
[8]Tang F, Ouyang H, Yang JZ, et al.Bidirectional transport of rhodamine 123 and Hoechst 33342, fluorescence probes of the binding sites on P-glycoprotein, across MD-CK-MDR1 cell monolayers[J].J Pham Sci,2004,93(5):1185-94.
[9]Troutman MD, Thakker DR. Rhodamine 123 requires carrier-mediated influx for its activity as a P-glycoprotein substrate in Caco-2 cells[J].Pham Res,2003,20 (8):1192-9.
[10]李春海,郭亚军主编.肿瘤分子生物学研究进展[M].北京：军事医学科学出版社,1996.103-104.
[11]Chung HC, Rha SY, Kim JH,et al.P-glycoprotein:the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer[J].Breast Cancer Res Treat,1997,42(1):65-72.
[12]戴广海,石廷章,李春海.肺癌MDR1和GST-π mRNA水平测定及临床意义[J].中国肿瘤临床,1999,22(3)：6
[13]付保进,张云汉,王尧河,等.食竹癌发生发展过程GST-π基因表达研究[J]. 中华肿瘤杂志,1999,21(1)：29.
[14]Izquierdo MA, Scheffer GL. Flens MJ, etal.Major Vault Protein LRP-related multidrug resistance[J]. Eur J Cancer,1996,32A(6):979-84.
[15]Filipits M, Jaeger U, Simonitsch I, et al. Clinical relevance of the lung resistance protein in diffuse large B-cell lymphomas[J]. Clin Cancer Res, 2000,6(9):3417-23.
[16]Moch H, Kononen T, Kallioniemi OP,et al. Tissue microarrays:what will they bring to molecular and anatomic pathology?[J]. Adv Anat Pathol,2001,8(1):14-20.
[17]游启生,李彬,周小鹏等.112例眼附属器淋巴增生性病变临床组织病理学初步分析[J].中华眼科杂志,2005,41(10)：871-876.
[18]Coupland SE, Krause L, Deleluse HJ, et al. Lymphoproliferative lesions of the ocular adnexa.Analysis of 112cases[J].Ophthalmology,1998,105(8):1430-41.
[19]Nakata M, MatsunoY, Katsumata N, et al. Histology according to the Revised EuroPean-American LymPhoma Classification significantly predicts the prognosis of ocular adnexal lymphoma[J]. Leuk Lymphoma,1999, 32(5-6):533-43.
[20]Jenkins C, Rose GE, Bunce C, et al. Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival[J]. Br J Ophthalmol,2000,84(8):907-13.
[21]Robert J.Multidrug resistance reversal agents [J].Drugs Fut1997,22(2):149150.
[22]Krishna R, Mayer LD. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the phannacokinetics of anticancer drugs[J]. Eur J Phar m Sci,2000, 11 (4):265-83.
[23]周晓冬,宋国祥,何彦津等,多药耐药基因在眼眶腺样囊性癌中的表达[J].眼科研究,2007,25(3)：164-167.
[24]肿瘤多药耐药基因 p-糖蛋白及其耐药逆转的研究进展[J].临床医药实践,2010,19(4A)：245-46.
[25]Ohsawa M, Ikura Y, Ukushima H, et al. Inununohistochemical expression of multidrug resistance proteins as a predietor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B-cell lymphoma[J].Oncology, 2005,68(4-6):422-31.
[26]Yuen AR, Sikic BI. Multidrug resistance in lymphomas[J]. J Clin Oncol,1994,12 (11):2453-9.
[27]Miller TP, Grogan TM, Dalton WS, et al. P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil[J]. J Clin Oncol,1991,9(1):17-24.
[28]李志革,匡志鹏,于起涛等,多药耐药基因 P-糖蛋白在恶性淋巴瘤组织中的表达[J].右江民族医学院报,2002,24(6)：809-810。
[29]傅小玉,于丁,毛永荣等,非霍奇金淋巴瘤患者P-gp、P26-bc1-2表达的临床研究[J].中华血液学杂志,2001,22(6)：310-311。
[30]刘淑芳,张青山,金仲品等,鼻腔 鼻咽部恶性淋巴瘤多药耐药基因表达的临床研究[J].中国药房,2009,20(11)：843-845.
[31]Meyer DJ, Coles B, Pemble SE, et al.Theta, a new class of glutathione transferases purified from rat and man[J]. Biochem J,1991,274(Pt2):409-14.
[32]Mannervik B, Awasthi YC, Board PG, et al.Nomenclature for human glutathione transferases[J].Biochem J,1992,282(Pt 1):305-6.
[33]冯丹,刘云鹏,GST-π与恶性肿瘤多药耐药的研究进展[J].肿瘤防治杂志,2004,11(6)：663-665.
[34]Hirano T, Kato H, Maeda M, et al.Identification of postoperative adjuvant chemotherapy responders in non-small cell lung cancer by novel biomarker[J]. Int J Cancer.2005,117(3):460-8.
[35]Kaynar H, Meral M, Turhan H, et al.Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu-Zn superoxide dismutase aetivities, total glutathione, nitric oxide, and malondialdehyde levels in erythrocytes of patients with small cell and non-small cell lung cancer[J]. Cancer Lett,2005, 227(2):133-9.
[36]Scheper RJ, Broxterman HJ, Scheffer GL, et al. Overexpression of a M(r) 110,000 vesicular protein in non-p-glycoprotein-mediated multidrug resistance[J]. Cancer Res,1993,53(7):1475-9.
[37]Plaat B E, Molenaar W M, Sagrudny J, et al. The 16p11 breakpoint in myxoid liposarcomas might affect the expression of the LRP gene on 16p11.2 encoding the multidrug resistance associated major vault protein [J]. Eur J Clin Invest, 2000,30 (5):447-53.
[38]Scheffer GL, Wijngaard PL, Izquierdo MA,et al.The drug resistance-related protein LRP is the human major vault protein [J]. Nat Med,1995,1(6):578-82.
[39]Izquierdo MA, Scheffer GL, Flens MJ, et al.Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors[J]. Am J Pathol,1996,148 (3):877-87.
[40]Rybarova S, Hodorova I, Hajdukova M, et al. Expression of MDR proteins in breast cancer and its correlation with some clinical and pathological parameters[J]. Neoplasma,2006,53 (2):128-35.
[41]Paredes Lario A, Blanco Garcia C, Echenique Elizodo M,et al. Expression of proteins associated with multidrug resistance and resistance to chemotherapy in lung cancer [J].Arch Bronconeumol,2007,43 (9):479-84.
[42]陈琦,杨敏,非霍奇金淋巴瘤中肺耐药相关蛋白的表达及意义[J].山东医药,2006,46(16)：5-6.
[43]Huo J, Che C, Huang Q. Coexpression and clinical significance of multidrug-drug resistance factors in lung cancer[J], Chin J Lung Cancer June, 2004:7(3):218-21.
[44]王文静,王明玉,吴宁等,P-gp与GST-π在乳腺癌组织中的表达及其相关性研究[J].中国老年学杂志,2008,28(9)：893-894.
[45]凌斌勋,陈环球,徐新宇等,GST-π和P-gp在胃癌中的表达及其临床意义,临床肿瘤学杂志[J].2010,15(6)：523-525.
[46]P-gp、GST-π、TOPOⅡ在外周T细胞淋巴瘤中的表达及意义[J].现代肿瘤医学,2009,17(8)：1543-1546.
[47]孙丽梅,王鲁建,宋敏等,乳腺癌中耐药蛋白P-gp、GST-π、TopoⅡ的表达[J].中国组织化学与细胞化学杂志,2006；15(2)：169-72.
[1]魏小勇,罗灼玲等,组织芯片与基因芯片在肿瘤研究中的联合应用[J].解剖学研究,2004,26(4)：305-308.
[2]Kononen J, Bubendorf L, Kallioniemi A, etal. Tissue microarrays for high-throughput molecular profiling of tumor specimens[J].Nat med,1998,4(7):844-7.
[3]周小鸽,张劲松,张小平等,组织芯片[J],中华病理学杂志,2002,31(1)：70-72.
[4]Hsu FD, Nielsen TO, Alkushi A, et al.Tissue microarrays are an effective quality assurance tool for diagnostic immunohistochemistry[J].Mod Pathol,2002,15 (12):1374-1380.
[5]Wang Y, Wu MC, Sham JS, et al. Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray[J].Cancer,2002,95 (11):2346-2352.
[6]Moch H, Schraml P, Mirlacher M, et al. High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microrray screening in renal cell carcinoma[J]. Am J Pathol,1999,154(4):981-986.
[7]Gillett CE, Springall RJ, Barnes DM,et al. Mutiple tissue core arrays in histopaholgy research:a validation study[J]. J Pathol,2002,192 (4):549-53.
[8]Barlund M, Monni O, Kononen J, et al. Multiple genes at 17q23 undergo amplification and overexpression in breast cancer[J]. Cancer Res,2000,60 (19):5340-5344.
[9]Yanqiu Zhao, Han You, Fei Liu, et al.Differentially expressed gene profiles between multidrug resistant gastric adenocarcinoma cells and their parental cells [J].Cancer Letters,2002,185(2):211-218.
[10]Krishna R, Mayer LD. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the phannacokinetics of anticancer drugs[J]. Eur J Phar m Sci,2000, 11 (4):265-83.
[11]Tang F, Ouyang H, Yang JZ, et al.Bidirectional transport of rhodamine 123 and Hoechst 33342, fluorescence probes of the binding sites on P-glycoprotein, across MD-CK-MDR1 cell monolayers[J].J Pham Sci,2004,93(5):1185-94.
[12]Troutman MD, Thakker DR. Rhodamine 123 requires carrier-mediated influx for its activity as a P-glycoprotein substrate in Caco-2 cells[J].Pham Res,2003,20 (8):1192-9.
[13]肿瘤多药耐药基因 p-糖蛋白及其耐药逆转的研究进展[J].临床医药实践,2010,19(4A)：245-46.
[14]Chretien A, Chataigner I, L Helias N, et al. Complete and remarkable reversal of chemoselectivity ink[4+2] cycloadditions involving electron-poor indoles as dienophiles. Diels-Alder versus hetero-Diels-Alder processes[J].J Org Chem, 2003,68(21):7990-8002.
[15]Marzolini C, Paus E, Buclin T, et al. Polymorphisms in human MDR1 (P-glycoprotein):recent advances and clinical relevance[J].Clin Phaimacol Ther, 2004,75(1):13-33.
[16]Ohsawa M, Ikura Y, Ukushima H, et al. Inununohistochemical expression of multidrug resistance proteins as a predietor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B-cell lymphoma[J].Oncology, 2005,68(4-6):422-31.
[17]Zenkov AN, Scvortsova NV, Chernolovskaya EL, et al. Expression of the MDR1 and MRP genes in patients with lymphoma with primary bone marrow involvement[J].Nuelcosides Nueleotides Nueleic Acids,2004,23(6-7):843-847.
[18]Yuen AR, Sikic BI. Multidrug resistance in lymphomas[J]. J Clin Oncol,1994,12 (11):2453-9.
[19]Miller TP, Grogan TM, Dalton WS, et al. P-glycoprotein expression in malignant lymphoma and reversal of clinical drag resistance with chemotherapy plus high-dose verapamil[J]. J Clin Oncol,1991,9(1):17-24.
[20]Meyer DJ, Coles B, Pemble SE, et al.Theta, a new class of glutathione transferases purified from rat and man[J]. Biochem J,1991,274(Pt2):409-14.
[21]Mannervik B, Awasthi YC, Board PG, et al.Nomenclature for human glutathione transferases [J].Biochem J,1992,282(Pt 1):305-6.
[22]冯丹,刘云鹏,GST-π与恶性肿瘤多药耐药的研究进展,肿瘤防治杂志, 2004,11(6)：663-665.
[23]Volm M, Mattern J, Samsel B. Overexpression of P-glycoprotein and gultathion S-transrerase-π in resistant non-small cell lung carcionomas of smokers[J]. Br J Cancer,1991,64(4):700-4.
[24]Hirano T, Kato H, Maeda M, et al.Identification of postoperative adjuvant chemotherapy responders in non-small cell lung cancer by novel biomarker[J]. Int J Cancer.2005,117(3):460-8.
[25]Kaynar H, Meral M, Turhan H, et al.Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu-Zn superoxide dismutase aetivities, total glutathione, nitric oxide, and malondialdehyde levels in erythrocytes of patients with small cell and non-small cell lung cancer[J]. Cancer Lett,2005, 227(2):133-9.
[26]周晓冬,宋国祥,何彦津等,多药耐药基因在眼眶腺样囊性癌中的表达[J].眼科研究,2007,25(3)：164-167.
[27]Arai T, Yasuda Y, Takaya T, et al.Immunohistochemical expression of glutathione transferase-pi in untreated primary non-small cell lung cancer[J].Cancer Detect Prev,2000,24(3):252-257.
[28]李春海,郭亚军主编.肿瘤分子生物学研究进展[M].北京：军事医学科学出版社,1996.103-104.
[29]Chung HC, Rha SY, Kim JH,et al.P-glycoprotein:the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer[J].Breast Cancer Res Treat,1997,42(1):65-72.
[30]戴广海,石廷章,李春海.肺癌MDR1和GST-π mRNA水平测定及临床意义[J].中国肿瘤临床,1999,22(3)：6
[31]付保进,张云汉,王尧河,等.食管癌发生发展过程GST-π基因表达研究[J].中华肿瘤杂志,1999,21(1)：29.
[32]Scheper RJ, Broxterman HJ, Scheffer GL, et al. Overexpression of a M(r) 110,000 vesicular protein in non-p-glycoprotein-mediated multidrug resistance[J]. Cancer Res,1993,53 (7):1475-9.
[33]Plaat B E, Molenaar W M, Sagrudny J, et al. The 16p11 breakpoint in myxoid liposarcomas might affect the expression of the LRP gene on 16p11.2 encoding the multidrug resistance associated major vault protein[J]. Eur J Clin Invest, 2000,30 (5):447-53.
[34]Scheffer GL, Wijngaard PL, Izquierdo MA,et al.The drug resistance-related protein LRP is the human major vault protein [J]. Nat Med,1995,1(6):578-82.
[35]Kong LB, Siva AC, Kickhoefer VA,et al.RNA location and modeling of a WD40 repeat domain within the vault[J].RNA,2000,6(6):890-900.
[36]Izquierdo MA, Scheffer GL. Flens MJ, etal.Major Vault Protein LRP-related multidrug resistance[J]. Eur J Cancer,1996,32A(6):979-84.
[37]Izquierdo MA, Scheffer GL, Flens MJ, et al.Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors[J]. Am J Pathol,1996,148 (3):877-87.
[38]Rybarova S, Hodorova I, Hajdukova M, et al. Expression of MDR proteins in breast cancer and its correlation with some clinical and pathological parameters[J]. Neoplasma,2006,53 (2):128-35.
[39]Paredes Lario A, Blanco Garcia C, Echenique Elizodo M,et al. Expression of proteins associated with multidrug resistance and resistance to chemotherapy in lung cancer [J].Arch Bronconeumol,2007,43 (9):479-84.
[40]IzquierdoMA, Van der Zee AG, Vermorker JB, et al. Drug resistance-assoaiated marker LRP for predietion of response to chemotherapy and prognoses in advanced ovarian carcinoma[J].J Natl Cancer Inst,1995,87(16):1230-7.
[41]Huo J, Che C, Huang Q. Coexpression and clinical significance of multidrug-drug resistance factors in lung cancer[J], Chin J Lung Cancer June, 2004:7(3):218-21.(?)
[42]Cheng AL, Su IJ, Chen YC, et al. Expression of P-glycoprotein and glutathione-S-transferase in recurrent lymphomas:the possible role of Epstein-Barr virus, immunophenotypes, and other predisposing factors[J]. J Clin Oncol,1993,11(1):109-15.
[43]王文静,王明玉,吴宁等,P-gp与GST-π在乳腺癌组织中的表达及其相关性研究[J].中国老年学杂志,2008,28(9)：893-894.
[44]凌斌勋,陈环球,徐新宇等,GST-π和P-gp在胃癌中的表达及其临床意义[J].临床肿瘤学杂志,2010,15(6)：523-525.
[45]P-gp、GST-π、TOPOⅡ在外周T细胞淋巴瘤中的表达及意义[J].现代肿瘤医学,2009,17(8)：1543-1546.
[46]FiliPits M, Drach J, Pohl G, et al. Expression of the lung resistance protein poor outcome in patients with multiple myeloma[J]. Clin Caneer Res, 1999:5(9):2426-30.
[47]袁凯,付荣湛,孙勇等,P-糖蛋白和肺耐药蛋白在浸润性乳腺癌中的表达及其临床意义[J].中华乳腺病杂志(电子版),2010,4(4)：410-416.
[48]樊娟,张丽,刘思管等,急性白血病细胞P-gp, LRP的表达及其临床意义[J].中国肿瘤临床,2007,34(7)：374-376.
[49]曲延刚,纪祥瑞,唐爱萍,多药耐药相关蛋白在乳腺浸润性导管癌中的表达[J].青岛大学医学院报,2007,43(1)：70-71.
[50]曲延刚,孙正船,綦瑶等,乳腺癌中LRP、GST-π的表达及临床意义[J].陕西医学杂志,2005,34(2)：156-158.
[51]姜余梅,刘卫平,唐琼兰等,鼻NK-T淋巴瘤耐药基因相关蛋白的检测[J].中国肿瘤临床,2004,31(2)：74-77.
[52]于树娜,蒋吉英,赵世福等,LRP、GST-π在干细胞癌中的表达及意义[J].现代肿瘤医学,2010,18(01)：102-105.
[53]郭杨,杨会钗,王永军等,肺耐药相关蛋白在肺癌组织中的表达及意义[J].山东医药,2005,45(6)：9-11.
[54]Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance[J]. Nat Rev Cancer,2005,5 (4):275-284.
[55]Efferth T, Fabry U, Osieka R. Interleukin-6 affects melphalan-induced DNA damage and repair in human multiple myeloma cells [J]. Anticancer Res,2002, 22(1A):231-234.
[56]Zhang Q, Zhang ZF, Rao JY, et al. Treatment with siRNA and antisense oligonucleotides targeted to HIF-1 alpha induced apoptosis in human tongue squamous cell carcinomas[J]. Int J Cancer,2004,111(6):849-857.
[57]Dumontet C, Jaffrezou JP, Tsuchiya E, et al. Resistance to microtubule-targeted cytotoxins in a K562 leukemia cell variant associated with altered tubulin expression and polymerization[J]. Bull Cancer,2004,91 (5):E81-112.
[58]Tsuruo T, Naito M, Tomida A, et al. Molecular targeting therapy of cancer:drug resistance, apoptosis and survival signal[J]. Cancer Sci,2003,94(1):15-21.
[59]立彦.P-gp介导的肿瘤多药耐药逆转研究进展[J].放射免疫学杂志,2005,18(2)：133.
[60]Naito M, Tsuruo T. New multidrug-resistance-reversing drugs, MS-209 and SDZ PSC 833 [J]. Cancer Chemother Pharmacol,1997,40 Suppl):S20-4.
[61]徐峰,蔡卓夫.肿瘤耐药逆转剂研究进展[J].中南药学,2004,2(5)：301
[62]Zhang Y, Zhou G, Wang H, et al. Transcriptional upregulation of breast cancer resistance protein by 17beta-estradiol in ERalpha-positiveMCF-7 breast cancer cells[J]. Oncology,2006,71 (5-6):446-455.
[63]李旭芬,张苏展,郑树.苦参碱对K562及其多药耐药细胞的细胞生物学影响[J].中国病理生理杂志,2002,18(10)：1233.
[64]李起,刘作金,张俊等,中药复方肝癌-1 号逆转肝癌多药耐药的实验研究[J]消化外科,2006,5(1)：70-73.
[65]杨铭, 高瀛岱, 熊冬生,等.抗P-gp/抗CD3微型双功能抗体裸鼠体内分布研究[J].中国肿瘤临床,2004,31(20)：1182.
[66]Takahashi M, Misawa Y, Watanabe N, et al. Role of P-glycoprotein in human natural killer-like cell line mediated cytotoxicity[J]. Exp Cell Res,1999, 253(2):396-402
[67]Azuma E, Masuda S, Qi J, et al. Cytotoxic T-lymphocytes recognizining P-glycoprotein in murine multidrug-resistant leukemias[J]. Eur J Haematol, 1997,59(1):14-9.
[68]Nieth C, Priebsch A, Stege A. et al. Modulation of the classical multidrug resistance(MDR) phenotype by RNA interference (RNAi)[J]. FEBS Lett,2003, 545(2-3):144-150.
[69]Wu H, Hait WN, Yang JM. Small interfering RNA induced suppression of MDR1 (P-g lycoprotein) restores sensitivity to multidrug resistant cancer cells[J]. Cancer Res,2003,63(7):1515-1519.
[70]Khan O, Middleton MR. The therapeutic potential of O6-alky lguanine DNA alky-ltransferase inhibitors[J]. Expert O pin Investig Drugs,2007,16(10):1573-1584.
[71]李学汤,姜洁,马道新,等.p53基因转染对卵巢癌MDR细胞药物敏感性及 恶性农型的影响[J].现代妇产科进展,2000,9(6)：428
[72]李杰,郭伟剑,许良中.肿瘤坏死因子α和干扰素α逆转K562/A02耐药性的研究[J].中国肿瘤生物治疗杂志,2001,8(3)：186。
[73]Carpinteiro A, Peinert S, Ostertag W, et al. Genetic protection of repopulating hematopoietic cells with an improved MDR1-retrovirus allows administration of intensified chemotherapy following stem cell transplantation in mice [J]. Int J Cancer,2002,98(5):785.