NTx在小细胞肺癌骨转移裸鼠模型中疗效预测作用的研究
|
摘要
目的:探讨溶骨性骨代谢生化指标血Ⅰ型胶原交联氨基末端肽(NTx)的定量测定对肺癌骨转移治疗的意义。本文用人肺小细胞肺癌细胞株H446种植于免疫缺陷小鼠制成小细胞肺癌骨转移裸鼠动物模型,通过观察NTx在氯膦酸二钠对小细胞肺癌骨转移荷瘤鼠的实验疗效中的变化,进一步探讨NTx定量测定预测氯膦酸二钠治疗小细胞肺癌骨转移的疗效的意义。方法:(1)将18只BALB/c-nu/nu雄性裸鼠随机分成正常组、实验组(予灌胃给药氯膦酸二钠)和对照组(予灌胃给药0.9%氯化钠注射液)。(2)将人肺小细胞肺癌细胞株H446种植于治疗组和对照组裸鼠右后肢胫骨,制成小细胞肺癌骨转移裸鼠动物模型。(3)细胞接种2周后利用放射学检查手段初步判定骨转移动物模型建立,始服药6周,第一次服药前及处死前半小时留血样各1次,每1周测体重,观察存活情况。(4)给药6周后处死裸鼠,所有裸鼠行放射学检查并取各裸鼠的右后肢行病理分析;用ELISA方法测定血NTx水平。结果:放射学及病理检查显示裸鼠接种H446细胞后引起明显的肿瘤性骨损伤;经氯膦酸二钠治疗后,实验组与对照组相比肿瘤进程有差异。实验组、对照组裸鼠血清NTx高于正常组裸鼠血清NTx ( P < 0. 01),实验组裸鼠经氯膦酸二钠血治疗前后血清NTx水平差别有统计学意义( P < 0. 01)。结论:实验证实定量测定NTx水平变化可用于预测氯膦酸二钠治疗小细胞肺癌骨转移的疗效。血清NTx对小细胞肺癌骨转移的诊断有重要参考意义,可协助及时诊断恶性肿瘤骨转移。且氯膦酸二钠可明显减轻小细胞肺癌骨转移程度。
Objective: To establish a skeletal metastasis model of lung caner, and evaluate the prognosis effects of serum cross-linked N-telopeptide of typeⅠcollagen(NTx) in disodium clodronate against skeletal metastasis model of lung cancer.Methods:A skeletal metastasis model of lung caner was established by injection of small cell lung carcinoma line(SCLC) H446 cells into the right leg of nude mice, and disodium clodronate was given to the animals after radiologically small but de-fined osteolytic metastasis were observed. Both X-ray and histological assay were applied to diagnose establishment of bone metastasis. The levels of serum NTx were measured using ELISA. Results: Both X-ray detection and histological studies showed markedly injury after injection cells into the right leg of nude mice.The level of serum NTx in the nude mice with bone metastasis was significantly higher than in the nude mice without bone metastasis ( P < 0. 01), and it was also significantly different in the nude mice with disodium clodronate.Conclusion: The measurement of serum NTx is significant utility as biochemical markers of bone metastasis with malignant carcinoma and can be used to achieve a timely diagnosis for bone metastasis of the malignant tumor.And disodium clodronate may be a choice for the treatment of metastasis cancer in bone.
Objective: To establish a skeletal metastasis model of lung caner, and evaluate the prognosis effects of serum cross-linked N-telopeptide of typeⅠcollagen(NTx) in disodium clodronate against skeletal metastasis model of lung cancer.Methods:A skeletal metastasis model of lung caner was established by injection of small cell lung carcinoma line(SCLC) H446 cells into the right leg of nude mice, and disodium clodronate was given to the animals after radiologically small but de-fined osteolytic metastasis were observed. Both X-ray and histological assay were applied to diagnose establishment of bone metastasis. The levels of serum NTx were measured using ELISA. Results: Both X-ray detection and histological studies showed markedly injury after injection cells into the right leg of nude mice.The level of serum NTx in the nude mice with bone metastasis was significantly higher than in the nude mice without bone metastasis ( P < 0. 01), and it was also significantly different in the nude mice with disodium clodronate.Conclusion: The measurement of serum NTx is significant utility as biochemical markers of bone metastasis with malignant carcinoma and can be used to achieve a timely diagnosis for bone metastasis of the malignant tumor.And disodium clodronate may be a choice for the treatment of metastasis cancer in bone.
引文
[1] Jemal Al.Jemal A, Siegtel R, Ward E, et al. Cancer Statistics,2007.CA Cancer J Clin.2007,57(1)∶43-66
[2] Carney DN.Lung cancer-time to move on from chemotherapy.N Engl J Med. 2003,346(2):126-128
[3]李林法.现代骨转移瘤诊治学.2006,3:2
[4] Coleman RE.Skeletal complications of malignancy [J]. Cancer.1997, 80 (suppl)∶1588-1594.
[5]谢启超.现代肿瘤学.2007, 15(8):1100
[6]张远鹰,段德生.骨转移癌的分布和发生机制[J].吉林医学.1987,8(5):12.
[7]李林法.现代骨转移瘤诊治学.2006,3:124
[8]李林法.现代骨转移瘤诊治学.2006,3:60
[9]孙燕,周清华.《肺癌骨转移临床诊疗专家共识2006版》.
[10] Hneak H.Schoder H, Puear D,et al.Advances inimaging in the postopetative patient with a rising prostate-specific antigen level.Semin Oncol.2003, 30 (5):616-634
[11] National Comprehensive Cancer Network.NCCN Clinical Practice Guidelines in OncologyV.2.2008Non-smallcellLungCancer[EB/OL]http://www.nccn.org/professionals/physician_gls/PDF/nscl.pdf.
[12] Hamaoka T, Madewell JE, Podoloff DA, et al. Bone imaging in metastatic breast cancer[J].J Clin Oncol.2004,22(14): 2942-2953
[13] Hetzel M,Hetzel J,Arslandemir C,et al.Reliability of symptoms to determine use of bone scans to identify bone metastases in lung cancer: prospective study [J].BMJ.2004,328(7447):1051-1052.
[14]余靖,邸立军,宛凤玲,等.骨代谢生化指标诊断恶性肿瘤骨转移的临床意义[J].中国肿瘤临床.2005,32(20):1193-1196
[15] Demers LM,Costa L, Lipton A, et al. Biochemical markers and skeletal metastases[J].Clin Orthop Relat Res.2003,415(Suppl):138-147
[16] Coleman RE.The clinical use of bone resorption markers in patients with malignant bone disease[J]. Cancer.2002,94 (10):2521-2533
[17] Kiuchi K, Ishikawa T, Hamaguchi Y, et al. Cross- linked collagenC- and N- telopeptides for an early diagnosis of bone metastasis from breast cancer [J]. Oncol Rep. 2002, 9(3): 595~ 598
[18] Brown JE,Cook RJ,Major P,et al. Bone turnover markers as predictors of skeletalcomplications in prostate cancer, lung cancer, and other solid tumors [J].J Natl Cancer Inst.2005,7(1):59-69
[19] Clines GA, Guise TA. Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone [J].Endocr Relat Cancer,.2005,12 (3) : 5492
[20] R. Bell. Bisphosphonates for metastatic bone disease: a thera-peutic ratio nale [J]. EJC Supplements.2004,2(5):1-4.
[21] RE Coleman.Bisphosphonates in breast cancer [J]. Annals of Oncology.2005, 16(5):687-695.
[22] Bauss F, Body JJ. Ibandronate in metastatic bone disease: areview of preclinical data [J]. Anticancer Drugs.2005,16(2):107-118.
[23]杭晓声,陈晓萍.伊班膦酸钠治疗肺癌骨转移的疗效分析[J].现代医学.2005,33(4):261-262.
[24] Corey E, Brown LG, Quinn JE, et al. Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer[J]. Clin Cancer Res.2003, 9(1):295-306.
[25]张贺龙.癌症骨转移诊断和治疗现状[J].中国医刊.2006,41(3):5
[26] Quint LE, Tummala S, Bressin LJ,et al.Distribution ofdistant metastases from newly diagnosed non-small-cell lung cancer [J].Ann Thorac Surg.1996,62(1): 246-250.
[27]荆鑫,吴海山,周维江.转移性骨肿瘤发生机制的研究进展[J].中华骨科杂志.2002,22(6):377
[28] Payne R. Mechanisms and management of bone pain.Cancer.1997,80:160-61
[29] Manabe J, Kawaguch N, Matsumoto S, et al Surgical treatment of bone metastasis indications and outcomes[J].Int J Clin Oncol,2005,10(2)∶103-111.
[30]范明,赵国旗,许奕等.骨转移癌的放射治疗疗效分析[J].中华现代临床医学杂志.2006,4(5):122-4
[31]宋小莲,白冲.肺癌骨转移诊治的研究进展[J].中国癌症杂志.2005,15(6): 584-585.
[32] Coleman RE.Future directions in the treatment and Prevention of bonemetastases. Am J Clin Oncol.2002,25(Suppl1): 32-38.
[33] Arguello F,Cohen HJ. Structral and microenvironment bonemar-row factors invoived in the pathogenesis of bonemetastasis. 11O rrFW, SinghG, eds. Bone metastasis-mecbanisms and palhophysi-ology.New York:Chapman & Hall 1996: 31-45.
[34] Janjan NA.Radiation for bonemetastases conventional techniqlles and the role ofsystemic radiopharmaceuticals.Cancer.1997,80: 1628-1645.
[35]李琦,张贺龙,姬统理,宋扬.恶性肿瘤骨转移综合治疗的疗效分析[J].第四军医大学学报.2005,25(2):76-8
[36] Hortobagyi GN, Theriault RL, Porter L, et al Efficacy of pam-idranate in reducing skeletal complications in patients with breast cancer and lytic bone metastases[ J].N Engl J Med.1996,335∶1785-179
[37] Body JJ, Bart lR, Burckhardt P, et al Current use of bisphosphonates in oncology[J].J Clin Oncol.1998,16∶3890-3899
[38] Coleman RE. Future directions in the treatment and Prevention of Bone metastases Am J Clin Oncol.2002,25(Suppl1): 32-38.
[39] Santini D,VesPasiani G,Vincenzi B, et al The antineo Plastic role Of bisphosphonates: from basic research to clinical evidence.Am J Clin Oncol. 2003,14: 1468-1476.
[40] Boissier S,Magnetto S, FrappartL, et al Biophosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res.1997,57:3890-3894.
[41]董梅,冯奉仪.双膦酸盐治疗恶性肿瘤骨转移肺癌骨转移的基础研究与临床实践[J].癌症进展.2006,12:7
[42] Purcell PM, Boyd IW.Bisphosphonates and osteonecrosis of the jaw.Med J Aust.2005,182(8):417
[43] Ruggiero SL, Mehrotra B, Rosenberg TJ,et al.Osteone-crisis of 63 case.J Oral Maxillfac Uug.2004,62(5):527
[44] Durie BG, Katz M,CrowleyJ.osteonecrosisof the jaw and Bisphosphonates. N Engl J Med.2005,353(1):99
[45]张贺龙.癌症骨转移诊断和治疗现状[J].中国医刊.2006,41(3):5-6
[46]钱军.氯膦酸二钠在减少骨相关事件中的应用[J].癌症进展.2006,12:4
[47]于世英.双膦酸盐在癌症骨转移中的地位[J].癌症进展.2006,12:1
[48] Body JJ, et al.Metastic Bone Disease:Clinical and Therapeutic Aspects Bone, 1992,3,S57 -S62 Paterson AHG. Bone metastases in breast cancer,prostate cancer and myeloma[J].Bone.1987,8(suppl1):17-22
[49]李永宾,李连财,孙贵林,等.骨转移瘤的诊断及治疗〔J〕.实用肿瘤学杂志. 1999,13(1): 31.
[50]王惠生.放射性核素骨显像ECT在诊断骨肿瘤的应用及注意事项〔J〕.中华骨科杂志.1994,5: 274.
[51]施庆新,吴照,赵惠扬,等.放射性核素全身骨骼显像在转移性骨肿瘤的应用〔J〕.中华肿瘤杂志.1989,3:196.
[52] Coleman RE, Mashiter G, Whitaker KB systemic therapy for bone metastases [J].Med J Nucl.1988,29(8):1354-9
[53]杨可扬,林志雄.骨转移癌的早期影像学诊断[J].现代临床生物工程学杂志.2000,6(2):16- 17.
[54] Grosfield E,Alavi A, Kneeland B.Comparison of radionuclide bone scans and magnetic resonace imaging in detcting spinal metastases [J]. Nucl Med . 1993,34:2191
[55]王继琛,刘树学,王霄英等.前列腺癌的骨转移:MRI与核素骨扫描的中国医学影像技术.2000,16(3):191 -2.
[56]邸立军,刘淑俊,宛凤玲,等.尿吡啶酚和脱氧吡啶酚在恶性肿瘤骨转移中的临床意义[J].中国肿瘤临床.2000,27(7):521-522
[57]王德元主编.胸部肿瘤学.天津:天津科学技术出版社.1994:27,86
[58]文苑等.骨碱性磷酸酶的检测方法和临床应用[J].国外医学生物化学与检学分册.1999,209(2):641
[59] Demers LM,Costa L,Lipton A,et al.Biochemical markers and skeletal metastases[J].Clin Orthop Relat Res.2003,415(Suppl):S138-S147
[60] Coleman RE.The clinical use of bone resorption markers in patients with malignant bone disease[J].Cancer.2002,94(10):2521-2533
[61] Kiuchi K,Ishikawa T,Hamaguchi Y,et al.Cross-linked collagen C-and N-telopeptides for an early diagnosis of bone metastasis from breast cancer[J].Oncol Rep,2002,9(3):595-598
[62]吕晓芳.骨代谢生化指标在恶性肿瘤骨转移诊断中的价值[J].中国肿瘤临床.2007,34(3):156
[63] Demers LM, Costa L, Chinchilli VM, et al.Biochemical markers of bone turnover in patients with metastatic bone disease [J].Clin Chem,1995, 41(10):1489-1494
[64] Hanson DA, Weis MAE, Bollen AM, et al.A specific immunoassay for monitoring human bone resorption:Quantitition of type 1 collagen cross-linked N-telopeptides [J].Bone miner Res,1992,7:1251-1258.
[65] Izumi M,Nakanishi Y,Takayama K,et al.Diagnostic value of bone- turnoverme -tabolites in the diagnosis of bone metastases in patients with lung carcinoma [J]. Cancer,2001,91(8):1487-1493.
[66] Demers LM, Costa L, Lipton A. Biochemical markers and skeletal metastases [J].Cancer.2000,88(12 Suppl):2919-26.
[67] Demers LM , Costa L , Lipton A. Biochemical markers and skeletal metastases [J].Clin Orthop.2003,(415 Suppl):2138-2147.
[68] Miura H, YamanotoI, Takada M,et al.Diagnostic valiclity of bone metabolic markers for bone metastasis [J].Endoer J.1997,44:751-757
[69] Souberbielle JC, Cormier C, kindemans C.Bone markers in clinical practice[J].Curren Opin Rheumatol.1999,11:312-319
[70] Watts NB. Clinical utility of biochemica [J].1999,45:1359-1368
[71] Woitge HW.Pecherstorfer M,Li Y,et al.Novel serum markers of resorptioon:clinnical assessment and comparison with established urinary indices[J].Bone Miner Res.1999,14(5):792-801
[72] Vinholes JJ, Purohit OP, Abbey ME, et al.Relationship between and symptomatic response in a doubleblind ranomized trial of pamidronate for metastatic bone disease[J].Ann Oncol.1997,8:1243-1250
[73] Ali SM,Demers LM,Leitzed K,et al.Baseline serum NTx levels are prognostic in metastatic breast cancer patients with bone-only metastasis [J].Ann Oncol.2004,15:455-459
[74]彭鹏,杜秀平.肺癌动物模型的制作概况[J].徐州医学院报.2005,25(3):263-267
[75]成泽东,陈以国.肺癌动物模型研究进展[J].辽宁中医杂志.2006,33(4):507-508
[76] Critofanilli M, Hortobagyi GN. Bisphosphonates in the Management of Breast Cancer.Cancer Control.1999,6:241-246
[77]方喜业主编.医学实验动物学.北京:人民出版社,1995,188
[78]魏泓主编.医学实验动物学.四川:1998,422.
[1] Salmon JM , Kilpatrick SE.Pathology of skeletai metastases.OrthopClin North Am.2000,31:537-544
[2] Buckwalter JA,Brandser EA.Metastatic disease of the skeleton.Am Fam Physician.1997,55:1761-1768
[3] Quint LE, Tummala S, Bressin LJ, et a.l Distribution of distant metastases from newly diagnosed non-small-cell lung cancer [J].Ann Thorac Surg. 1996,62(1): 246-250.
[4] Mundy GR. Mechanisms of bone metastases.Cancer.1997, 80:1546-1556.
[5] Payne R.Mechanisms and management of bone pain.Cancer.1997,80: 160-161.
[6] Hayward MI,Howell DA,Donnell JF, et al. Hypercalcemiacom-plicating small cell carcinoma Cancer.1981,48:1643-1646.
[7]孙燕,周清华.《肺癌骨转移临床诊疗专家共识2006版》.
[8] SilvestriGA, Littenberg B, Colice GL, et a.l The clinical evalua-tion for detecting metastatic lung cancer: ameta-analysis[J].Am J Respir Crit Care Med.1995,152(1):225-230.
[9]龙为红,李德仁,吴文.肺癌骨转移99Tc-MDP骨显像的临床价值及与CT、X-rays检查对比观察[J].中国肿瘤临床与康复.2002,9(2):9-11.
[10]于立明,毕燕妮,龙再颖.骨显像、X线、CT及MRI对骨转移瘤的诊断价值[J].医学影像学杂志.2003,13(5):331-333.
[11]成向阳,吴哲凡,杨德康,等.ⅠCTP诊断肺癌骨转移的初步研究[J].癌症. 2000,19(2):166-167.
[12] Demers LM,Costa L,Lipton A. Bioche Cancer. 2000,88 (12 Suppl) :2919-26.
[13] DemersLM, Costa L, Lipton A. Bioch Clin Orthop.2003, (415 Suppl): 2138-2147.
[14] Bury T, Barreto A, Daenen F, et a.l Fluorine-18 deoxyglucose positron emission tomography for the detection of bonemetastases in patients with non-small-cell lung cancer [J].Eur J Nucl Med.1998,25(9):1244-1247.
[15] PantelK, WoelfleU.Micrometastasis in breast cancer and other solid tumors [J].J Biol RegulHomeost Agents,.2004,18(2):120-125.
[16] MullerV, PantelK. Bonemarrowmicrometastases and circulating tumor cells: current aspects and future perspectives [J].Breast Cancer Res. 2004,6(6):258-261.
[17] Gangnus R, Langer S, BreitE, eta.l Genomic profiling of viable and proliferative micrometastatic cells from early-stage breast cancerpatients [J].Clin CancerRes. 2004,10(10):3457-3464.
[18]鲁继斌,戴兵,鞠培新.186铼标记单克隆抗体在荷人肺腺癌裸鼠体内的放射免疫显像研究[J].中国医科大学学报.2002,31(3):192-194.
[19]樊卫,刘宇英.芬太尼透皮贴剂治疗多发性骨转移性癌痛的近期疗效观察[J].中国肿瘤临床.2001,28(2):112.
[20]郭剑锋,吴永忠,陈晓品.肺癌骨转移性癌痛放射治疗方法研究[J].重庆医学. 2002,31(3):211-213.
[21]赵月霞,韩东亮,王璞.低分割与常规放疗治疗骨转移癌疗效观察[J].中华放射医学与防护杂志.2004,24(1):68.
[22]刘原,徐海峰,周润锁,等.89SrCL-2和153Sm-EDTMP对肺癌骨转移性疼痛疗效比较[ J].西安医科大学学报(中文版).2000,21(6):543-545.
[23]邓候富,谭天秩,张锡英,等.153Sm-EDTMP治疗肺癌骨转移[J].中国肺癌杂志. 2000,3(3):186-188.
[24] Liepe K, FrankeWG, Kropp J, et a.l Comparison of rhenium-188, rhenium- 186-HEDP and strontium-89 in palliation of pain-ful bone metastasis[J]. Nuklear -medizin.2000,39(6):146-151.
[25] MagnettoS, Boissier S, Delmas PD, eta.l Additive antitumor ac-tivities of taxoids in combination with the bisphosphonate ibandr-onate against invasion and adhesion of human breast carcinoma cells to bone[J].IntJCancer. 1999,83 (2):263-269.
[26] Hiraga T, W illiams PJ, Mundy GR, et a.l The bisphosphonate ibandronate promotes apoptosis in MDA-MB-231 human breast cancer cells in bone metastases[J].CancerRes.2001,61(11):4418-4424.
[27] Ruggiero SL, Mehrotra B, Rosenberg TJ,et al.Osteone-crisis of 63 case.J Oral Maxillfac Uug.2004,62(5):527
[28] Durie BG, Katz M,Crowley J.osteonecrosis of the jaw and Bisphosphonates. N Engl J Med. 2005,353(1):99
[2] Carney DN.Lung cancer-time to move on from chemotherapy.N Engl J Med. 2003,346(2):126-128
[3]李林法.现代骨转移瘤诊治学.2006,3:2
[4] Coleman RE.Skeletal complications of malignancy [J]. Cancer.1997, 80 (suppl)∶1588-1594.
[5]谢启超.现代肿瘤学.2007, 15(8):1100
[6]张远鹰,段德生.骨转移癌的分布和发生机制[J].吉林医学.1987,8(5):12.
[7]李林法.现代骨转移瘤诊治学.2006,3:124
[8]李林法.现代骨转移瘤诊治学.2006,3:60
[9]孙燕,周清华.《肺癌骨转移临床诊疗专家共识2006版》.
[10] Hneak H.Schoder H, Puear D,et al.Advances inimaging in the postopetative patient with a rising prostate-specific antigen level.Semin Oncol.2003, 30 (5):616-634
[11] National Comprehensive Cancer Network.NCCN Clinical Practice Guidelines in OncologyV.2.2008Non-smallcellLungCancer[EB/OL]http://www.nccn.org/professionals/physician_gls/PDF/nscl.pdf.
[12] Hamaoka T, Madewell JE, Podoloff DA, et al. Bone imaging in metastatic breast cancer[J].J Clin Oncol.2004,22(14): 2942-2953
[13] Hetzel M,Hetzel J,Arslandemir C,et al.Reliability of symptoms to determine use of bone scans to identify bone metastases in lung cancer: prospective study [J].BMJ.2004,328(7447):1051-1052.
[14]余靖,邸立军,宛凤玲,等.骨代谢生化指标诊断恶性肿瘤骨转移的临床意义[J].中国肿瘤临床.2005,32(20):1193-1196
[15] Demers LM,Costa L, Lipton A, et al. Biochemical markers and skeletal metastases[J].Clin Orthop Relat Res.2003,415(Suppl):138-147
[16] Coleman RE.The clinical use of bone resorption markers in patients with malignant bone disease[J]. Cancer.2002,94 (10):2521-2533
[17] Kiuchi K, Ishikawa T, Hamaguchi Y, et al. Cross- linked collagenC- and N- telopeptides for an early diagnosis of bone metastasis from breast cancer [J]. Oncol Rep. 2002, 9(3): 595~ 598
[18] Brown JE,Cook RJ,Major P,et al. Bone turnover markers as predictors of skeletalcomplications in prostate cancer, lung cancer, and other solid tumors [J].J Natl Cancer Inst.2005,7(1):59-69
[19] Clines GA, Guise TA. Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone [J].Endocr Relat Cancer,.2005,12 (3) : 5492
[20] R. Bell. Bisphosphonates for metastatic bone disease: a thera-peutic ratio nale [J]. EJC Supplements.2004,2(5):1-4.
[21] RE Coleman.Bisphosphonates in breast cancer [J]. Annals of Oncology.2005, 16(5):687-695.
[22] Bauss F, Body JJ. Ibandronate in metastatic bone disease: areview of preclinical data [J]. Anticancer Drugs.2005,16(2):107-118.
[23]杭晓声,陈晓萍.伊班膦酸钠治疗肺癌骨转移的疗效分析[J].现代医学.2005,33(4):261-262.
[24] Corey E, Brown LG, Quinn JE, et al. Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer[J]. Clin Cancer Res.2003, 9(1):295-306.
[25]张贺龙.癌症骨转移诊断和治疗现状[J].中国医刊.2006,41(3):5
[26] Quint LE, Tummala S, Bressin LJ,et al.Distribution ofdistant metastases from newly diagnosed non-small-cell lung cancer [J].Ann Thorac Surg.1996,62(1): 246-250.
[27]荆鑫,吴海山,周维江.转移性骨肿瘤发生机制的研究进展[J].中华骨科杂志.2002,22(6):377
[28] Payne R. Mechanisms and management of bone pain.Cancer.1997,80:160-61
[29] Manabe J, Kawaguch N, Matsumoto S, et al Surgical treatment of bone metastasis indications and outcomes[J].Int J Clin Oncol,2005,10(2)∶103-111.
[30]范明,赵国旗,许奕等.骨转移癌的放射治疗疗效分析[J].中华现代临床医学杂志.2006,4(5):122-4
[31]宋小莲,白冲.肺癌骨转移诊治的研究进展[J].中国癌症杂志.2005,15(6): 584-585.
[32] Coleman RE.Future directions in the treatment and Prevention of bonemetastases. Am J Clin Oncol.2002,25(Suppl1): 32-38.
[33] Arguello F,Cohen HJ. Structral and microenvironment bonemar-row factors invoived in the pathogenesis of bonemetastasis. 11O rrFW, SinghG, eds. Bone metastasis-mecbanisms and palhophysi-ology.New York:Chapman & Hall 1996: 31-45.
[34] Janjan NA.Radiation for bonemetastases conventional techniqlles and the role ofsystemic radiopharmaceuticals.Cancer.1997,80: 1628-1645.
[35]李琦,张贺龙,姬统理,宋扬.恶性肿瘤骨转移综合治疗的疗效分析[J].第四军医大学学报.2005,25(2):76-8
[36] Hortobagyi GN, Theriault RL, Porter L, et al Efficacy of pam-idranate in reducing skeletal complications in patients with breast cancer and lytic bone metastases[ J].N Engl J Med.1996,335∶1785-179
[37] Body JJ, Bart lR, Burckhardt P, et al Current use of bisphosphonates in oncology[J].J Clin Oncol.1998,16∶3890-3899
[38] Coleman RE. Future directions in the treatment and Prevention of Bone metastases Am J Clin Oncol.2002,25(Suppl1): 32-38.
[39] Santini D,VesPasiani G,Vincenzi B, et al The antineo Plastic role Of bisphosphonates: from basic research to clinical evidence.Am J Clin Oncol. 2003,14: 1468-1476.
[40] Boissier S,Magnetto S, FrappartL, et al Biophosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res.1997,57:3890-3894.
[41]董梅,冯奉仪.双膦酸盐治疗恶性肿瘤骨转移肺癌骨转移的基础研究与临床实践[J].癌症进展.2006,12:7
[42] Purcell PM, Boyd IW.Bisphosphonates and osteonecrosis of the jaw.Med J Aust.2005,182(8):417
[43] Ruggiero SL, Mehrotra B, Rosenberg TJ,et al.Osteone-crisis of 63 case.J Oral Maxillfac Uug.2004,62(5):527
[44] Durie BG, Katz M,CrowleyJ.osteonecrosisof the jaw and Bisphosphonates. N Engl J Med.2005,353(1):99
[45]张贺龙.癌症骨转移诊断和治疗现状[J].中国医刊.2006,41(3):5-6
[46]钱军.氯膦酸二钠在减少骨相关事件中的应用[J].癌症进展.2006,12:4
[47]于世英.双膦酸盐在癌症骨转移中的地位[J].癌症进展.2006,12:1
[48] Body JJ, et al.Metastic Bone Disease:Clinical and Therapeutic Aspects Bone, 1992,3,S57 -S62 Paterson AHG. Bone metastases in breast cancer,prostate cancer and myeloma[J].Bone.1987,8(suppl1):17-22
[49]李永宾,李连财,孙贵林,等.骨转移瘤的诊断及治疗〔J〕.实用肿瘤学杂志. 1999,13(1): 31.
[50]王惠生.放射性核素骨显像ECT在诊断骨肿瘤的应用及注意事项〔J〕.中华骨科杂志.1994,5: 274.
[51]施庆新,吴照,赵惠扬,等.放射性核素全身骨骼显像在转移性骨肿瘤的应用〔J〕.中华肿瘤杂志.1989,3:196.
[52] Coleman RE, Mashiter G, Whitaker KB systemic therapy for bone metastases [J].Med J Nucl.1988,29(8):1354-9
[53]杨可扬,林志雄.骨转移癌的早期影像学诊断[J].现代临床生物工程学杂志.2000,6(2):16- 17.
[54] Grosfield E,Alavi A, Kneeland B.Comparison of radionuclide bone scans and magnetic resonace imaging in detcting spinal metastases [J]. Nucl Med . 1993,34:2191
[55]王继琛,刘树学,王霄英等.前列腺癌的骨转移:MRI与核素骨扫描的中国医学影像技术.2000,16(3):191 -2.
[56]邸立军,刘淑俊,宛凤玲,等.尿吡啶酚和脱氧吡啶酚在恶性肿瘤骨转移中的临床意义[J].中国肿瘤临床.2000,27(7):521-522
[57]王德元主编.胸部肿瘤学.天津:天津科学技术出版社.1994:27,86
[58]文苑等.骨碱性磷酸酶的检测方法和临床应用[J].国外医学生物化学与检学分册.1999,209(2):641
[59] Demers LM,Costa L,Lipton A,et al.Biochemical markers and skeletal metastases[J].Clin Orthop Relat Res.2003,415(Suppl):S138-S147
[60] Coleman RE.The clinical use of bone resorption markers in patients with malignant bone disease[J].Cancer.2002,94(10):2521-2533
[61] Kiuchi K,Ishikawa T,Hamaguchi Y,et al.Cross-linked collagen C-and N-telopeptides for an early diagnosis of bone metastasis from breast cancer[J].Oncol Rep,2002,9(3):595-598
[62]吕晓芳.骨代谢生化指标在恶性肿瘤骨转移诊断中的价值[J].中国肿瘤临床.2007,34(3):156
[63] Demers LM, Costa L, Chinchilli VM, et al.Biochemical markers of bone turnover in patients with metastatic bone disease [J].Clin Chem,1995, 41(10):1489-1494
[64] Hanson DA, Weis MAE, Bollen AM, et al.A specific immunoassay for monitoring human bone resorption:Quantitition of type 1 collagen cross-linked N-telopeptides [J].Bone miner Res,1992,7:1251-1258.
[65] Izumi M,Nakanishi Y,Takayama K,et al.Diagnostic value of bone- turnoverme -tabolites in the diagnosis of bone metastases in patients with lung carcinoma [J]. Cancer,2001,91(8):1487-1493.
[66] Demers LM, Costa L, Lipton A. Biochemical markers and skeletal metastases [J].Cancer.2000,88(12 Suppl):2919-26.
[67] Demers LM , Costa L , Lipton A. Biochemical markers and skeletal metastases [J].Clin Orthop.2003,(415 Suppl):2138-2147.
[68] Miura H, YamanotoI, Takada M,et al.Diagnostic valiclity of bone metabolic markers for bone metastasis [J].Endoer J.1997,44:751-757
[69] Souberbielle JC, Cormier C, kindemans C.Bone markers in clinical practice[J].Curren Opin Rheumatol.1999,11:312-319
[70] Watts NB. Clinical utility of biochemica [J].1999,45:1359-1368
[71] Woitge HW.Pecherstorfer M,Li Y,et al.Novel serum markers of resorptioon:clinnical assessment and comparison with established urinary indices[J].Bone Miner Res.1999,14(5):792-801
[72] Vinholes JJ, Purohit OP, Abbey ME, et al.Relationship between and symptomatic response in a doubleblind ranomized trial of pamidronate for metastatic bone disease[J].Ann Oncol.1997,8:1243-1250
[73] Ali SM,Demers LM,Leitzed K,et al.Baseline serum NTx levels are prognostic in metastatic breast cancer patients with bone-only metastasis [J].Ann Oncol.2004,15:455-459
[74]彭鹏,杜秀平.肺癌动物模型的制作概况[J].徐州医学院报.2005,25(3):263-267
[75]成泽东,陈以国.肺癌动物模型研究进展[J].辽宁中医杂志.2006,33(4):507-508
[76] Critofanilli M, Hortobagyi GN. Bisphosphonates in the Management of Breast Cancer.Cancer Control.1999,6:241-246
[77]方喜业主编.医学实验动物学.北京:人民出版社,1995,188
[78]魏泓主编.医学实验动物学.四川:1998,422.
[1] Salmon JM , Kilpatrick SE.Pathology of skeletai metastases.OrthopClin North Am.2000,31:537-544
[2] Buckwalter JA,Brandser EA.Metastatic disease of the skeleton.Am Fam Physician.1997,55:1761-1768
[3] Quint LE, Tummala S, Bressin LJ, et a.l Distribution of distant metastases from newly diagnosed non-small-cell lung cancer [J].Ann Thorac Surg. 1996,62(1): 246-250.
[4] Mundy GR. Mechanisms of bone metastases.Cancer.1997, 80:1546-1556.
[5] Payne R.Mechanisms and management of bone pain.Cancer.1997,80: 160-161.
[6] Hayward MI,Howell DA,Donnell JF, et al. Hypercalcemiacom-plicating small cell carcinoma Cancer.1981,48:1643-1646.
[7]孙燕,周清华.《肺癌骨转移临床诊疗专家共识2006版》.
[8] SilvestriGA, Littenberg B, Colice GL, et a.l The clinical evalua-tion for detecting metastatic lung cancer: ameta-analysis[J].Am J Respir Crit Care Med.1995,152(1):225-230.
[9]龙为红,李德仁,吴文.肺癌骨转移99Tc-MDP骨显像的临床价值及与CT、X-rays检查对比观察[J].中国肿瘤临床与康复.2002,9(2):9-11.
[10]于立明,毕燕妮,龙再颖.骨显像、X线、CT及MRI对骨转移瘤的诊断价值[J].医学影像学杂志.2003,13(5):331-333.
[11]成向阳,吴哲凡,杨德康,等.ⅠCTP诊断肺癌骨转移的初步研究[J].癌症. 2000,19(2):166-167.
[12] Demers LM,Costa L,Lipton A. Bioche Cancer. 2000,88 (12 Suppl) :2919-26.
[13] DemersLM, Costa L, Lipton A. Bioch Clin Orthop.2003, (415 Suppl): 2138-2147.
[14] Bury T, Barreto A, Daenen F, et a.l Fluorine-18 deoxyglucose positron emission tomography for the detection of bonemetastases in patients with non-small-cell lung cancer [J].Eur J Nucl Med.1998,25(9):1244-1247.
[15] PantelK, WoelfleU.Micrometastasis in breast cancer and other solid tumors [J].J Biol RegulHomeost Agents,.2004,18(2):120-125.
[16] MullerV, PantelK. Bonemarrowmicrometastases and circulating tumor cells: current aspects and future perspectives [J].Breast Cancer Res. 2004,6(6):258-261.
[17] Gangnus R, Langer S, BreitE, eta.l Genomic profiling of viable and proliferative micrometastatic cells from early-stage breast cancerpatients [J].Clin CancerRes. 2004,10(10):3457-3464.
[18]鲁继斌,戴兵,鞠培新.186铼标记单克隆抗体在荷人肺腺癌裸鼠体内的放射免疫显像研究[J].中国医科大学学报.2002,31(3):192-194.
[19]樊卫,刘宇英.芬太尼透皮贴剂治疗多发性骨转移性癌痛的近期疗效观察[J].中国肿瘤临床.2001,28(2):112.
[20]郭剑锋,吴永忠,陈晓品.肺癌骨转移性癌痛放射治疗方法研究[J].重庆医学. 2002,31(3):211-213.
[21]赵月霞,韩东亮,王璞.低分割与常规放疗治疗骨转移癌疗效观察[J].中华放射医学与防护杂志.2004,24(1):68.
[22]刘原,徐海峰,周润锁,等.89SrCL-2和153Sm-EDTMP对肺癌骨转移性疼痛疗效比较[ J].西安医科大学学报(中文版).2000,21(6):543-545.
[23]邓候富,谭天秩,张锡英,等.153Sm-EDTMP治疗肺癌骨转移[J].中国肺癌杂志. 2000,3(3):186-188.
[24] Liepe K, FrankeWG, Kropp J, et a.l Comparison of rhenium-188, rhenium- 186-HEDP and strontium-89 in palliation of pain-ful bone metastasis[J]. Nuklear -medizin.2000,39(6):146-151.
[25] MagnettoS, Boissier S, Delmas PD, eta.l Additive antitumor ac-tivities of taxoids in combination with the bisphosphonate ibandr-onate against invasion and adhesion of human breast carcinoma cells to bone[J].IntJCancer. 1999,83 (2):263-269.
[26] Hiraga T, W illiams PJ, Mundy GR, et a.l The bisphosphonate ibandronate promotes apoptosis in MDA-MB-231 human breast cancer cells in bone metastases[J].CancerRes.2001,61(11):4418-4424.
[27] Ruggiero SL, Mehrotra B, Rosenberg TJ,et al.Osteone-crisis of 63 case.J Oral Maxillfac Uug.2004,62(5):527
[28] Durie BG, Katz M,Crowley J.osteonecrosis of the jaw and Bisphosphonates. N Engl J Med. 2005,353(1):99