肺癌、乳腺癌患者外周血淋巴细胞体外MTT法药敏试验的研究
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:该课题采用MTT法筛选出敏感的化疗药物用于肺癌、乳腺癌患者的临床治疗,并与传统经验化疗进行比较,以期提高癌症患者的疗效和生存率,避免不必要的毒副作用,为临床个体化化疗提供理论依据。
     方法:共收集40例恶性肿瘤患者,采用MTT法测定其外周血淋巴细胞(PBL)对8种临床常用化疗药的敏感性,筛选敏感药物进行“个体化”化疗,并取48例不作药敏试验行常规化疗的肺癌和乳腺癌患者作为对照组,然后分别对两组进行临床评效,比较两组之间的差异是否存在统计学意义。
     结果:
     1.肺癌患者PBL对8种化疗药物的敏感顺序依次为:顺铂、紫杉醇、吉西他滨、卡铂、长春瑞滨、环磷酰胺、氟尿嘧啶、阿霉素;乳腺癌患者PBL对8种化疗药物的敏感顺序依次为:环磷酰胺、阿霉素、氟尿嘧啶、紫杉醇、顺铂、卡铂、吉西他滨、长春瑞滨。
     2.试验组的临床有效率为87.1%,与对照组(55%)相比具有统计学意义(P=0.004)。
     3.肺癌组中,不同治疗阶段的患者,试验组的有效率与对照组相比有统计学差异(P<0.05);对于不同病理类型来说,试验组的有效率也是明显高于对照组(P<0.05)。乳腺癌组中,对于不同治疗阶段的患者,试验组与对照组相比并无统计学意义(P>0.05)。
     4.肺癌组中,试验组根据药敏结果选择的药物联合方案,临床有效率明显高于对照组(P<0.05);乳腺癌组中,虽然两组总的有效率无统计学差异(P>0.05),但是对照组主要选择常规组合方式,选择其他方案仅14%,有效率只有33.3%,而实验组选择其他方案达25%,有效率为80.0%,差异具有统计学意义(P<0.05)。
     5.试验组和对照组的6个月、1年生存率并无明显差别(P>0.05)。
     6.将对照组中评效为临床无效的患者全部列出,抽取其外周血标本进行MTT法药敏试验,结果发现:这些患者选择的化疗药物中几乎都包含了药敏试验显示的不敏感药物。
     结论:
     1.本文关于肺癌对临床8种常用化疗药物的敏感顺序与既往研究基本一致,但乳腺癌对8种化疗药物的敏感顺序与既往的研究有所差异,考虑为本试验采集的标本例数较少所致,仍需进一步扩大样本量,进行深入研究。
     2.根据药敏试验结果选用敏感的化疗药物,可以有效地提高临床有效率,与传统经验化疗之间具有显著性差异。与国内外其他学者的研究结论相符,再次验证了PBL可替代肿瘤细胞进行药敏试验的理论。
     3.体外药敏试验不仅可以指导临床医师选择敏感药物来提高化疗效果,而且可以帮助医师排除不敏感的药物,避免/减轻无效化疗或耐药性的发生。
     4.药敏试验组的化疗方案更灵活,治疗更有针对性,说明在体外药敏试验指导下实现了肿瘤化疗的个体化。
Purpose: the subject using MTT method to select the sensitive drug to lung cancer and breast cancer patients, and compare to the conventional chemotherapy. We wish to explore the relevance of the two and its clinical significance, with a view to improve cancer efficacy and survival rate of patients to avoid unnecessary side effects, and provide a theoretical basis for clinical chemotherapy individual. Methods: select 40 cases with malignant tumors, using MTT method to measured PBL’s sensitivity to eight kinds chemotherapy drugs, then choose the sensitive drug to "individuation" of chemotherapy. In another, select 48 cases of lung cancer and breast cancer patients as a control group, which does not take drug sensitivity test, but use the conventional chemotherapy. Finally, evalute the effect of the two group, whether there is statistically significance compared between the two groups.
     Results:
     1. The chemosensitivity order for lung cancer, which is DDP, taxinol, Gemcitabine, carboplatin, vinorelbine, Cytoxan, fluorouracil, ADM; The chemosensitivity order for mammary cancer, which is Cytoxan, ADM, fluorouracil, taxinol, DDP, carboplatin, Gemcitabine, vinorelbine.
     2. The therapeutic effects of the test group is 87.1%,there is statistical significance compared with the control group(55%)( P=0.004).
     3. In the lung cancer group, there is significant difference between the two groups with different stages of treatment (P <0.05); for the different pathological types, the test group is also significantly higher efficiency than the control group (P <0.05). In the breast cancer group, we don’t find the statistical significance between the two groups (P>0.05).
     4. In the lung cancer group, select the joint programs according to drug sensitivity results, the clinical efficiency has increased significantly (P<0.05); in the breast cancer group, there is no significant difference between the two group (P>0.05), but in the test group, there is 25% choose other ways of drug selection compare to the control group, and the clinical efficiency has the statistical significance between the two groups.
     5.There is no obvious difference (P<0.05) between the two group about half an year and 1-year survival rate. We think it result for taking as a fewer example and shorter follow-up, so we should expand the sample size and increase a longer period of comparative study of survival.
     6. Choose all the patients whose clinical efficiency was 0(except the death of patients), for 21 cases, taken their peripheral blood samples, and use the MTT method to measure drug sensitivity, results were as follows: almost the patients choose the drug which sensitivity test showed that non-sensitive drugs.
     Conclusion:
     1. In this paper, the research about sensitive sequence of lung cancer to 8 kinds of commonly used clinical chemotherapy drugs basically consistent with previous research. But sensitive sequence of breast cancer was different from previous studies. We think that fewer sample and shorter study due to it. We should to expand the sample size and take a further, in-depth study.
     2. Select the chemotherapeutic drugs according to sensitivity tests result, can significantly improve clinical efficiency. Compare to the traditional chemotherapy, there is significantly different. The conclusions of the study in accordance with other scholars at home and abroad, once again verify the theory that PBL can be an alternative for tumor cells to take sensitivity test.
     3. Drug sensitivity test in vitro not only can guide clinicians to select drugs to enhance chemotherapy effect, but also can help doctors rule out non-sensitive drugs, to avoid/reduce the ineffective chemotherapy or the occurrence of drug resistance.
     4. We found the joint programs of drug selection in test group were more flexible, and had more targeted treatment. It illustrate that we achieve the individual chemotherapy under the guidance of the drug sensitivity test in vitro.
引文
1 De Vita VT Jr,Hellman S,Rosenb SA.Cancer:principles and practice of oncology(Sixth edition)[M].Philadelphia:JB Lippin- cott,2001:21-22
    2 Levi F.From circadian to cancer chronotherapeutics[J].Chrvno- biology International,2002,19(1):1-19
    3钱晓蕾,彭芝兰,刘珊玲,等. ATP和MTT法在卵巢恶性肿瘤化疗药物敏感性试验中的对照研究[J].中华肿瘤杂志,2003,24(2):204-205
    4唐亚辉,马葵,韩居然,等.MTT药物敏感试验在指导胃癌及原发性肝癌化疗中的作用[J].肿瘤防治研究,2001,28(1):37-38
    5 Yamaue H, Tanimura H, Noguchi K, et al. Chemosensitivity testing of fresh human gastic cancer with purified tumor cells using the MTT assary[J]. Br J Cancer, 1992,66:794
    6 Sargent JM.The use of the MTT assay to study drug resistance in fresh tumour samples[J].Recent Results Cancer Res,2003,161:13-25
    7刘毅.卵巢癌细胞凋亡的体外药敏研究[J].中华现代妇产科学杂志,2005,2:193-197
    8周载平,胡泽民,李明芳,等.三磷酸腺苷生物荧光法检测肿瘤药敏的价值[J].肿瘤防治杂志,2003,10(7):689-691
    9管睿,崔英. ATP-CSA化疗药物敏感试验及在卵巢癌中的应用[J].国外医学临床生物化学与检验学分册,2003,24(5):291-292
    10 Kurbacher CM,Greeu OM,Stier U,et a1.ATP chemosensitivity testing in ovarian and breast cancer:early clinical trials[J].Recent Results Can cer Res,2003,161:221-230
    11 Ugurel S , Tilgen W , Reinhdd U . Chcmosensitivity testing in malignant melanoma[J].Recent Results Cancer Res,2003,161:81-92
    12 Tsuhei Kon Do, Tetsuro Kubota, Hiroshi Tanim Ura, et al. Cummlative Results of chemosensitivity test for antitumor agents in Japan[J]. Cancer Research, 2000,20:2389-2392
    13 Mehta RS,Bornstein R,Yu IR,et a1.Breast cancer survival and in vitro tumor response in the extreme drug resistance assay.Breast Cancer Research and Treatment,2001,66:225-237
    14 Do TK,Kubota T,Ura HT,et al.Cumulative results of chemosensitivity tests for antitumor agents in Japan.Anticancer Res,2000,20(4):2389-2392
    15郑裕明,汤敏中,李军,等.肝癌患者外周血淋巴细胞与肿瘤细胞体外化疗药敏实验研究[J].广西医学杂志,2006,28(8):1192-1193
    16王静,王秋波.胃癌病人外周血单个核细胞替代癌细胞的体外化疗药敏试验[J].青岛大学医报,2001,37(4):303-305
    17王艳萍,袁淑兰,陈晓禾,等.肿瘤患者外周血淋巴细胞与肿瘤细胞体外化疗药敏研究[J].肿瘤防治杂志,2004,11(5):515-517
    18梁永钜,周昕熙,潘启超,等.肝癌体外药物敏感性试验[J].肿瘤,2001,21(1):17-19
    19李孟达,李艳芳,李俊东,等.卵巢恶性肿瘤体外药物敏感试验及其临床意义[J].癌症,2000,19(12):1155-1157
    20 Kabeshima Y, Kubota T, Watanabe M, et al. Clinical usefulness of chemosensitivity test for advanced colorectal cancer[J]. Anticancer Res,2002,22:3033-3037
    21 Taylor CG, Sargent JM, Elgie AW, et al. Chemosensitivity testig predicts survival in ovarian cancer[J]. Eur J Gynaecol Oncol,2001,22:278-282
    22 Sargent JM, Taylor CG. Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia[J]. Br J Cancer,1989,60:206-210
    23 Saikawa Y, Kubota T, Furukawa T, et al. Single-cell suspension assay with an MTT end point is useful for evaluating the optimal adjuvant chemotherapy for advanced gastric cancer[J]. Jpn J Cancer Res,1994,85:762-765
    24辛华雯,吴笑春,李罄,等.胃癌体外化疗药物敏感性及临床疗效研究[J].中国临床药理学与治疗学杂志,2002,7:147-149
    25 Hongo T, Yajima S, Sakurai M, et al. In vitro drug sensitivity testing canpredict induction failure and early relapse of childhood acute lymphoblastic leukemia[J]. Blood, 1997,89:2959-2960
    26 Sargent JM, Elgie AW, Taylor CG, et al. The identification of drug resistance in ovarian cancer and brest cancer: application of the MTT assary[J]. Contrib Gynecol Obstet,1994,19:64-67
    27 Iwahashi M,Nakamori M,Nakamm M,et a1.Individualized adjuvant chemotherapy guided by chemmensltivity test sequential to extended surgery for advanced gastric cancer[J].Anticancer Res,2005,25(5):3453-3459
    28孙燕.临床肿瘤内科手册[M].第2版.北京:人民卫生出版社,1994;43
    29韩锐.肿瘤化学预防及药物治疗[M].第1版.北京:北京医科大学、中国协和医科大学出版社,1991;557-582
    30汤钊猷.现代肿瘤学[M].上海:上海医科大学出版社,1993.521
    31 Behrens BC, Hamilton TC, Masuda H. Characterization of a cis-diamminedichloroplatinum(Ⅱ)- resistant human ovarian cancer cell line and its use in evaluation of platinum analogues. Cancer Res,1987,47(2):414-418
    32 Rhedin AS, Tidefelt U, Jensson K, et al. Comparison of a bioluminescence assay with differential staining cytotoxicity for cytostatic drug testing in vitro in human leukemic cells. Leuk Res,1993,17:271-276
    33 Konecny G, Crohns C, Pegram M, et al. Correlation of drug response with the ATP tumorchemosensitivity assay in primary FIGO stageⅢovarian cancer. Gynecol Oncol,2000,77:258-263
    34 Sevin BU, Perras JP. Chemosensitivity testing in ovarian cancer. Cancer,1993,71(Suppl)4:1613-9
    35 Kurbacher CM, Cree IA, Bruckner HW. Use of an ex vitro ATP luminescence assay to direct chemotherapy for recurrent ovarian cancer. Anticancer Drugs,1998,9(1):51-7
    36 O’Meara AT, Sevin BU. Predicitive value of the ATP chemosensitivity assay in epithelial ovarian cancer. Gynecol Oncol,2001,83(2):334-42
    37 Cree IA, Kurbacher CM. ATP-based tumor chemosensitivity testing: assisting new agent development. Anticancer Drugs,1999,10(5):431-5
    38 Letw in R. Chemosensitivity testing[J]. C lin J OncolNurs, 200,5(5):195-200
    39 Untch M, D itsch N, Langer E, et al. Chemosensitivity testing in gy-necologic oncology-dream or reality[J]. Recent Results CancerRes, 2003,161: 146-158
    40 Sevin BU, Peng ZL, Perras JP, et al. Application of an ATP-bioluminescence assay in human tumor chemosensitivity testing. Gynecol Oncol, 1988,31(1):191-204
    41霍红旗,刘爱民,李鹏,等.检测癌症患者外周血淋巴细胞评估化疗药物敏感性的研究[J].现代检验医学杂志,2008,(2)
    42李胜水,于翠珍,崔克勤,等.预制检测板MTT法检测癌症患者外周血淋巴细胞化疗药物敏感性的研究[J].实用医技杂志,2007,(9)
    43艾军,单保恩,梁索源,等.贲门癌患者肿瘤细胞与外周血淋巴细胞化疗药敏试验的相关性研究[J].中华肿瘤防治杂志,2006,(5)
    44 H Fridborg, B Jonsson, P Nygren, et al. Activity of cyclesporins as reseeistance modifiers in primary culture of human haematological and solid tumors. British Journal of Cancer, 1994,70:11-17
    45 Omeara AT, Sevin BU. In vitro sensitivity of fresh ovarian carcinoma specimens to CPT-11(irinotecan). Gynecologic Oncology, 1999,72(2):143
    46丁国善,徐冠南,付志仁,等.原发性肝癌对化疗药物敏感性的研究[J].肝胆仪胰外科杂志,1999,(4)
    47张援平.恶性肿瘤体外化疗药敏试验的进展[J].国外医学.临床生物化学与检验分册,1995,(4)
    48 Singh B, Li R, Xu L, et al. Prediction of survival in patients with hend and neck cancer using the histoculture drug response assay. Head & Neck, 2002,24(5):437-422
    49宋海平.胰腺癌体外药物敏感性实验及化疗增敏作用研究[D].华中科技大学,2006
    50 Bellamy WT. Prediction of response to drug therapy of cancer: a review of in vitro assays. Drugs, 1992,44:690
    51赵小华,张为强,蒋阳平,等.MTT法药敏试验应用于晚期乳腺癌[J].中国肿瘤,2003,(8)
    52郭军,王宝成,尹格平,等.三苯氧胺对淋巴细胞MDR1表达阳性的非小细胞肺癌病人多药耐药性的逆转作用[J].临床肿瘤学杂志,1998,3(4):19
    53白玉贤,吴瑾,崔滨滨.人初发及复发转移大肠癌组织与外周血MDR1基因表达相关性的研究[J].肿瘤防治研究,2002,29(4):264-266
    54 Maung ZT, Reid MM, Mateson, E, et al. Corticosteroid resistance is increased in lymphoblasts from adults compared with children: preliminary results of invitro drug sensitivity study in adults with acute lymphoblastic leukemia. Br J Haemol, 1995,91(1):93
    55 Lambert E, Rees JKH, Twentyman PR. Resistance circumvention strategies tested in clinical leukemia specimens using the MTT colorimetric assay. Lejkemia, 1992,6(10):1063
    56 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Meth, 1983,65(1-2):55-63
    57 Hiroki Y, Masaji T, Hironobu O, et al. Locoregional chemotherapy for patients with panereatic cancer intra-arterial adjurant chemotherapy after pancreatectomy with portalvein resection. Pancreas, 2002,25(4): 366-372
    1 Levi F. From circadian rhythms to cancer chronotherapeutics. Chronobiol Int . 2002,19(1):1~19
    2唐亚辉,马葵,韩居然,等. MTT药物敏感试验在指导胃癌及原发性肝癌化疗中的作用.肿瘤防治研究,2001,28(1):37~38
    3 Iwahashi M, Nakamori M,Nakamura M, et a1. Individualized adjuvant chemotherapy guided by chemosensitivity test sequential to extendedsurgery for advanced gastric cancer. Anticancer Res ,2005,25 (5):3453~3459
    4 Mehta RS ,Bornstein R ,Yu IR ,et a1. Breast cancer survival and in vitro tumor response in the extreme drug resistance assay. Breast Cancer Research and Treatment ,2001,66:225~237
    5刘毅.卵巢癌细胞凋亡的体外药敏研究.中华现代妇产科学杂志,2005,2(3):193~197
    6 Do TK, Kubota T ,Ura HT ,et a1. Cumulative results of chemosensitivity tests for antitumor agents in Japan. Anticancer Res ,2000,20(4):2389~2392
    7 Kaspers GJ ,Pieters R ,Van Zantwijk CH ,et al . In vitro drug sensitivity of normal peripheral blood lymphocytes and childhood leukemic cells from bone marrow and peripheral blood.Br J Cancer.,1991,64(3):469~474
    8郑裕明,汤敏中,李军,等.肝癌患者外周血淋巴细胞与肿瘤细胞体外化疗药敏实验研究.广西医学杂志,2006,28(8):1192~1193
    9王静,王秋波.胃癌病人外周血单个核细胞替代癌细胞的体外化疗药敏试验.青岛大学医报,2001,37(4):303~305
    10马玉彦,李殿俊,刘巍,等.肿瘤患者外周血淋巴细胞代替癌细胞体外检测抗癌药敏的相关性研究.实用肿瘤学杂志,1999,13(1):19~21
    11王艳萍,袁淑兰,陈晓禾,等.肿瘤患者外周血淋巴细胞与肿瘤细胞体外化疗药敏研究.肿瘤防治杂志,2004,11(5):515~517
    12 Maung ZT, Reid MM, Mateson E, et al. Corticosteroid resistance is increased in lymphoblasts from adults compared with children: preliminary results of invitro drug sensitivity study in adults with acute lymphoblastic leukemia. Br J Haemol, 1995,91(1):93
    13 Lambert E, Rees JKH, Twentyman PR. Resistance circumvention strategies tested in clinical leukemia specimens using the MTT colorimetric assay. Lejkemia, 1992, 6(10):1063
    14 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Meth, 1983,5(1-2):55~63
    1 Kaye SB.Multidrug resistance:clinical relevance in solid tumours and strategies for circumvention[J].Curt Opin Oneol,1998,10:15~19
    2 De Vita VT Jr,Hellman S,Rosenb SA.Cancer:principles and practice of oncology(Sixth edition)[M].Philadelphia:JB Lippin- cott,2001:21~22
    3 Levi F.From circadian to cancer chronotherapeutics[J].Chrvno- biology International,2002,19(1):1~19
    4钱晓蕾,彭芝兰,刘珊玲,等. ATP和MTT法在卵巢恶性肿瘤化疗药物敏感性试验中的对照研究[J].中华肿瘤杂志,2003,24(2):204~205
    5唐亚辉,马葵,韩居然,等.MIT药物敏感试验在指导胃癌及原发性肝癌化疗中的作用[J].肿瘤防治研究,2001,28(1):37~38
    6 Iwahashi M,Nakamori M,Nakamm M,et a1.Individualized adjuvant chemotherapy guided by chemmensltivity test sequential to extended surgery for advanced gastric cancer[J].Anticancer Res,2005,25(5):3453~3459
    7 Sargent JM.The use of the MTT assay to study drug resistance in fresh tumour samples[J].Recent Results Cancer Res,2003,161:13~25
    8刘毅.卵巢癌细胞凋亡的体外药敏研究[J].中华现代妇产科学杂志,2005,2(3):193~197
    9周载平,胡泽民,李明芳,等.三磷酸腺苷生物荧光法检测肿瘤药敏的价值[J].肿瘤防治杂志,2003,10(7):689~691
    10管睿,崔英. ATP-CSA化疗药物敏感试验及在卵巢癌中的应用[J].国外医学临床生物化学与检验学分册,2003,24(5):291~292
    11 Sevin BU, Perras JP, Averette HE, et al. Chemosensitivity testing in ovarian cancer[J]. Cancer, 1993,71:1613
    12 Kurbacher CM,Greeu OM,Stier U,et a1.ATP chemosensitivity testing in ovarian and breast cancer:early clinical trials[J].Recent Results Can cer Res,2003,161:221~230
    13 Kurbachcr CM,Crec IA,Bruckner HW,et a1.Use of an ex vivo ATP luminescence assay to direct chemotherapy for recurrent ovarian cancer[J].Anticancer Drugs,1998,9:51~57
    14 Ugurel S,Tilgen W,Reinhdd U.Chcmosensitivity testing in malignant melanoma [J].Recent Results Cancer Res,2003,161:81~92
    15李自新.卵巢恶性肿瘤亿疗及药物敏感试验[J].实用肿瘤杂志,1993,8(4):199
    16 Tsuhei Kon Do, Tetsuro Kubota, Hiroshi Tanim Ura, et al. Cummlative Results of chemosensitivity test for antitumor agents in Japan[J]. Cancer Research, 2000,20:2389~2392
    17梁永钜,周昕熙,潘启超,等.肝癌体外药物敏感性试验[J].肿瘤,2001,21(1):17~19
    18李孟达,李艳芳,李俊东,等.卵巢恶性肿瘤体外药物敏感试验及其临床意义[J].癌症,2000,19(12):1155~1157
    19宋海平.胰腺癌体外药物敏感性实验及化疗增敏作用研究[D].华中科技大学,2006
    20赵小华,张为强,蒋阳平,等.MTT法药敏试验应用于晚期乳腺癌[J].中国肿瘤,2003,(8)
    21 Bellamy WT. Prediction of response to drug therapy of cancer: a review of in vitro assays. Drugs, 1992,44:690

© 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