金属蛋白酶组织抑制剂(多西环素)对大肠癌裸鼠移植瘤的影响研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的观察多西环素对大肠癌裸鼠皮下移植瘤的影响,为大肠癌的治疗寻求一个新的可能治疗途径。
     方法将10只BALB/C(nu/nu)裸鼠按随机数字表法均分为对照组和实验组,人大肠癌细胞系LoVo细胞种植入裸鼠皮下,建立裸鼠皮下人大肠癌移植瘤模型。对照组应用生理盐水瘤内多点直接注射,实验组应用多西环素瘤内多点直接注射治疗。然后记录肿瘤大小,观察肿瘤生长曲线,计算肿瘤生长抑制率。
     结果实验表明实验组肿瘤较对照组肿瘤生长明显抑制,第18天起实验组和对照组肿瘤体积出现差别,对照组肿瘤和实验组肿瘤体积分别为(1.0691±0.2148)cm~3、(0.6337±0.1088)cm~3,第26天对照组肿瘤和实验组肿瘤体积分别为(1.7558±0.2038)cm~3、(0.8898±0.0808)cm~3。实验组肿瘤体积较对照组体积明显减小,生长抑瘤率为49.7%(F=78.041 p<0.01)。
     结论多西环素可以抑制大肠癌裸鼠皮下移植瘤的的生长。有可能应用于人大肠癌的治疗。
Objective To investigate the inhibitory effects of Doxycycline on the growth of human colorectal cancer implanted in nude mice.So that we can look for a new therapy for human colorectal cancer.
     Methods Ten BALB/C nude mice were randomly divided into control group and study group equally.Human colorectal cancer cell line LoVo was inoculated subcutaneously into nude mice to form transplantation tumors.Saline was injected to mice in control group and Doxycycline was injected to mice in study group.The changes of tumors in both groups were recorded and the curve of tumor growth was also observed and the inhibitory rate of tumor was calculated.
     Results Doxycycline significantly inhibited the growth of colorectal cancer xenograf- ts in nude mice. The first 18 days from the experimental group and control group differences in tumor size(1.0691±0.2148)cm3、(0.6337±0.1088)cm3, the first 26 days of tumor control group and experimental group were tumor size (1.7558±0.2038) cm3, (0.8898±0.0808) cm3.The volume of transplantation tumor reduced with the inhibitory rate of 49.7%,which showed that the former was significantly lower than that of the control group (F=78.041 p<0.01).
     Conclusion Doxycycline may inhibit the growth of colorectal cancer bearing nude mice.Which maybe uses for the therapy of human colorectal cancer.
引文
[1] Weir HK, ThunMJ, HankeyBF, et al. Annual report to the nation on the status of cancer 1975-2000, featuring the uses of surveillance data for cancer p revention and control [ J ]. J N atl CancerInst, 2003, 95 (17) : 1276-1299.
    [2] Liotta LA,Steeg PS,Stetler WG.Cancer metastasis and angiogenesis:an imbalance of positive and negative regulation[J].Cell,1991,64:327-336
    [3] Visse R,Nagase H.Matrix metalloproteinases and tissue inhibitors of Metalloroteinases: structure,function,and biochemistry[J].Circ Res,2003,92:827-839
    [4] Zucker S,Vacirca J.Role of matrix metalloproteinases(MMPs) in colorectal cancer[J].Cancer Meta Res,2004,23:101-117
    [5] Nelson AR,Fingleton B,Rothenberg MI,et a1.J Clin Oncol,2000,18:l135-1149
    [6] Stetler-Stevenson WG. The role of matrix metalloproteinases in tumor invasion, metastasis, and angiogenesis[J],Surg Oncol Clin N ,Am,2001,10:383-392.
    [7] Stamenkovic I.Matrix metalloproteinases in tumor invasion and metastases [J]Semin Cancer Biol,2000,10:415-433.
    [8] Hideki M,Hisaguki A.Host expreesion of matrix metalloproteinase-2 and tissue inhibitot of metaHopmteinase-2 in normal coIon tissue afects metastatic potential of colorectalcancer[J]. Dis colon Recturn,1998,42:383-402.
    [9] Liabakk NB,Talbot I,Smith RA.et al.Matrix metalloproteinase-2(MMP-2)and matrix meta1loproteirmse-9(MMP-9)type Ⅳ collagenase in colorectal cancer[J]. Cancer Res,1996. 56:199-206.
    [10] Marray GI.Duncan ME.ONeil P.MMP-1 is associated with poor prognose in colorectal cancer[J].Nat Med.1996,2: 461-462
    [11] Curran S,Murray GL.Matrix metalloproteinases in tumor invasion and metastasis[J].J Pathol,1999,189:300-308
    [12] Yamamoto H,Itoh F,Adachi Y,et al.Messager RNA expression of matrixmetalloproteinasas and tissue inhibitors of metalloproteinases in human hepatocellular carcinoma[J].Jpn J Clin Oncol,1999,29(2):58~62
    [13] 杜月光,陈慰浙.基质金属蛋白酶在胃肠癌中的表达及其抑制剂的研究进展[J].中国 癌症杂志,2002,12(1):81-83。
    [14] 万进,吴泽宇,林华欢,等.中下段直肠癌基质金属蛋白酶-2表达与直肠系膜转移的关系[J].中华胃肠外科杂志,2006,9(2):136-138.
    [15] 谢宗佑,刘岩雪,孙保存,等.基质金属蛋白酶9及其抑制剂与大肠癌分期和预后的相关性研究[J].中国肿瘤临床,2004,31(10):560-562.
    [16] Johansson N,Ahonen M, Kahari VM. Matrix metalloproteinases in tumor invasion [J]Cell Mol Life Sci,2000,57:5-15
    [17] Miyazaki K,Higashi S.Matrix mettalloproteinases:their structures and functions,with special reference to their role in tumor invasion and metastasis [J].Seikagaku,1996,68: 1791-1807
    [18] Kahari VM,Saarialho-Kere U.Matrix metalloproteinases and their inhibitors in tumor growth and invasion[J].Ann Med,1999,31:34-45
    [19] Nagase H,Woessner F.Matrix metalloproteinases[J].J Biol Chem,1999,274:21491~21494
    [20] Vander Stappen J,WJ,Hendriks T,WobbesT.Correlation between collagenalytica ctivity and grade of histological differentiation in colorectal tumor[J].Int J cancer,1990,45(11): 1071-1078
    [21] Albm A.Melchiori A.Santi.et a1.Tumor cancer invasion inhibited by TIMP-2 [J].Natl Cancer Inst,1991.83(10):775-782.
    [22] Khokher Zimmmer MJ.Graham CH.Suppression 0f invasion bv inducible expression of tissue inhibitor 0f metalloproteinases1(TIMP-1)in B16-Fl0 melanoma cells [J]. Natl Cancer Inst,1992,84(11)1017-1022
    [23] 王晓光,罗荣城.抗肿瘤新生血管靶向治疗进展[J].临床肿瘤学杂志,2006,11(2)155-158
    [24] 毛立民,于世凤,孙开华,等.金属蛋白酶抑制剂BB-94抑制腺样囊性癌侵袭转移的实验[J].中华口腔医学杂志,2001,35(4):304-306
    [25] 高晓康,王禾,杨波,等.强力霉素抑制PC-3细胞基质金属蛋白酶-2表达及侵袭的体外研究[J].中华泌尿外科杂志,2003,24(1):37-40
    [26] 马曾辰,裸小鼠人癌异种移植及影响移植成功的因素.国外医学肿瘤学分册[J],1982,1(2):73
    [27] 吴秉铨,唐尧,王洁良,等.人大肠粘液腺癌的裸鼠移植瘤及其生物学特性的研究[J]北京医学院学报,1982,14(3):205
    [28] Rygard J,Puvlsen CO. Heterotransplantation of a human malignant tumour to “nude”mice [J].Acta Parh Microbiol Scand,1969,7(7):758-760
    [29] Giovanella B C.Yim S O.Stenhlin JS.et al.Brief communication:Development of invasive Tumors in the “nude”mouse after injection of cultured[J]. Natl Cancer Inst, 1972,4 (8): 1531-1933
    [30] 邹移海,张永斌,连至诚,等.实验性大肠癌动物模型研究述评[J].广州中医药大学学报1997,14(4):277-279.
    [31] Yamada K,Kemler R.Cell-to-cell contact and extracellular matrix[J].Curr Opin Cell Biol, 2002,14:527-530
    [32] Lewis M.Cell-to-cell contact and extracellular matrix[J]. Curr Opin Cell Biol,2002,14:525- 527
    [33] Pupa SM,Menard S,Forti S,et al.New insights into the role of extracellular mtrix during tumor onset and progression[J].J Cell Physiol,2002,192:259-267
    [34] Robers CR, Walker DC, Schellenberg RR.Extracellular matrix[J]. Clin Allergy Immunol, 2002,16;143-178
    [35] Hanahan D, Weinberg RA.The hallmarks of cancer[J]. Cell,2000,100:57-70
    [36] Stetler-Stevenson WG.The role of matrix metalloproteines in tumor invasion,metastasis, and angiogenesis[J]. SrgOncol Clin N Am,2001,10:383-392
    [37] Stamenkovic I.Matrix metalloproteinases in tumor invasion and metastasis[J].Semin Cancer Biol,2000,10:415-433
    [38] Peschon JJ.An essential role for ectodomain shedding in mammalian development[J].Scien -ce,1998,282:1281-1284
    [39] Agrez M,Chen A,Cone R I,et al.The αvβ6 integrin promotes proliferation of colon Carcino- ma cells through a unique region of the β6 cytoplasmic domain.J Cell Biol,1994,127:547- 556
    [40] Durko M,Navab R,Shibata HR,et al.Suppression of basement membrane type IV collagen degradation and cell invasion in human melanoma cells expressing an antisense RNA for MMP-1.Biochim.Biophys[J].Acta,1997,1356:271-280
    [41] Lichtinghagen R,Musholt P,Lein M,et al.Different mRNA and protein expression of matrixmetalloproteinases 2 and 9 and tissue inhibitor of metllopr-oteinases1 in benign and mali-gnant prostate tissue[J].Eur Urol,2002,42:398-402
    [42] Hasegawa S,Koshikawa N,Momiyama N,et al.Matrilysin specific antisense oligonucleotide inhibits liver metastasis of human colon cancer cells in a nude mouse model[J].Int J Canc- er,1998,76:812-816
    [43] Johansson N,Ahonen M,Kahsri VM.Matrix metalloproteinases in tumor invasion[J].Cell Mol Life Sci,2000,57:5-15
    [44] Miyazaki K,Higashi S.Matirx metalloproteinases:their structures and functions,with special reference to their roles in tumor invasion and metastsis[J]. Seikagaku,1996,68:1791-1807
    [45] Coussens L M,Werb Z.Inflammatory cells and cancer:think different[J].J Exp Med,2001, 193:F23-F26
    [46] Hanahan D,Folkman J.Patterns and emerging mechanisms of the angiogenic switch during Tumorigenesis[J].Cell,1996,86:353-364
    [47] Bergers G.Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogen- Nesis[J].Nature Cell Biol, 2000,2:737-744
    [48] Vu T H.MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes[J].Cell,1998,93:411-422
    [49] Zhou Z.Impaired endochondral ossification and angiogenesis in mice deficient in membr- ane-type matrix metalloproteinase I[J].Proc Natl Acad Sci,2000,97:4052-4057
    [50] Dong Z,Kumar R,Yang X.Macrophage-derivedmetalloelastase is responsible for the gener- ation of angiostatin in Lewis lung carcinoma[J].Cell,1997,88:801-810
    [51] Cornelius L A.Matrix metalloproteinases generate-angostatin:effects on neovasculariza- Tion[J].J Immunol,1998,161:6845-685
    [52] Gorrin-Rivas MJ.Mouse macrophage metalloelastase gene transfer into a murine melanoma suppresses primary tumor growth by halting angiogenesis[J].Clin Cancer Res,2000,6:1647- 1654
    [53] Ferreras M,Felbor U,Lenhard T.Generation and degradation of human endostatin proteins by various proteinases[J].Febs Lett,2000,486:247-251
    [54] Koolwijk P.Proteolysis of the urokinase-type plasminogen activator receptor by metallop- roteinase-12:implication for angiogenesis in fibrin matrices[J].Blood,2001,97:3123-3131
    [55] Hayakawa T,Yamashita K,Ohuchi E,Cell growth-promoting activity of tissue inhibitor of metalloproteinases-2(TIMP-2)[J].J Cell Sci,1994,107:2373-2379
    [56] Wang Z,Juttermann R,Soloway P D.TIMP-2 is requiredfor efficient activation of proMMP- 2 in vivo[J].J Biol Chem,2000,275:26411-26415
    [57] Gomez DE,Alonso DF,Yoshiji H.Tissue inhibitors of metalloproteinases:structure,regulat- ion and biologicalfunctions[J].Eur J Cell Biol,1997,74:111-122
    [58] Folkman J.Tumour angiogenesis:therapeutic implications[J].N Engl J Med,1971,285:1182- 1186
    [59] Folkman J,Hanahan D.Switch to the angiogenic phonotype during tumorigenesis[J].Prince- ss Takamatsu Symp,1991,22:339-342
    [60] Katasuhiko,Matsuyama MD.Tumor angiogenesis as a prognostic marker in operable non- samll cell lung cancer[J].AnnThorac SURG,1998,65:1405-1409
    [61] XiaoSD,Li DH,et al. A multi-center randomized study on MECCUN,5-Fu and AD Mvers- us ACNU,5-Fu and ADM in treatment of advanced gastric cancer[J].China Natl J New Gastroenterd, 1997,3:238-239.
    [62] Feng GG, Zhou XG,Yu BM,et al.Prevention of metastasis to liver by using 5-Fu IntrapeIt- oned chemotherapy in nude mice inoculated with human colonic cancer cell[J].China Natl JNEW Gastroenteral,1996,2:134-135.
    [63] Hartwell H,Kastan MB.Cell cycle control and cancer[J].scince.1994,266:1821-1828.
    [64] Darzynkiewicz Z.Apoptosis in anticancer stratagies:modulation of celll cycle Differenti- Ation[J].J Cell Biochem,1995,58:151-159.
    [65] Sher CJ.Cancer cell cycles[J].Science,1996,274:1672-1677.
    [66] Bemhard KI,Grnh er SB,Muschel RJ.et a1.Direct evidence linking expression of matrix metaloproteinase-9(92-kDa gelatinase/colanenase)to metastatic phenotype in transformed rat embryocels[J].Prac Nail Acad Sci USA.2002,95.4293
    [67] Khokha R,W aterhouse P,Yagel S,et a1.Antisense RNA-induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells[J].Science.2003.243:947
    [68] Khokha R.Suppression of the tumorigenic and metastatic abilities of murine Bl6-F-l0 melanoma cells in vivo by the overexpression of the tissue inhibitor of the Metalpr Otein- ase-1[J].J Nail CancerInst,2004,86:299
    [69] Taroboletti G,Garofalo A,Belotti D,et a1.Inhibition of antigiogenesis and merine hema- gioma growth by batimastat, a syntheticinh inhibitor of matrix metalloproteinase[J].J Nail Cancer Inst,1995,87:293
    [70] Lozonshi L,Sanamura M,Kobari M,et a1.Controlling tulnor angiogenesis and metastasis of C2b murine colon adeno-carcinomaby a new matrix metallop Roteinase inhibitor,kB-R7785,in two tumor models[J].Cancer Res,2003,59(6):1252
    [71] Tierney GM,Griffin NR,Stuart RC,et al.A pilotstudy of the safety and effects of the matrix metalloproteinase inhibitor marimastat in gastric cancer[J].Eur J Cancer,1999.35:563-568
    [72] 耿素芳,曹采方,陈智滨,等.盐酸米诺四环素软膏对龈沟液中胶原酶的影响[J],中华口腔 医学杂志,2000,35(25)336-338.
    [73] Onoda T,Ono T,Dhar DK,et al..Doxycycline inhibits cell proliferation and invasive poten- tial:combination therapy with cyclooxygenase-2 inhibitor in humor colorectal cancer cells [J].J Lab Clin Med,2004,143(4):207-216
    [74] 徐海涛,杜杰,董欣舒.Doxycycline抑制大肠癌LS174T细胞侵袭的体外实验研究[J].中国肿瘤临床,2007,34(11):625-626
    [75] Cheung PY, Sawick G,Wozniak M,et al.Matrix metalloproteinase-2 contribute to ischemia reperfusion injury in the heart[J].Circulation,2000,101(15):1833-1839.
    [76] Cakir Y,Hahn KA.Direct action by Doxycycline against canine osteosarcoma cell proliferation and collagenase activity in vitro[J].In vivo,1999,13(4):327-331.
    [1] Weir HK,ThunMJ, HankeyBF,et al. Annual report to the nation on the status of cancer 1975-2000,featuring the uses of surveillance data for cancer p revention and control[J]. J N atl CancerInst,2003, 95 (17):1276-1299.
    [2] Meluyk 0,Shuman MA,Kim KJ.Vascular endothelial growth factor promotes tumor dissemunation by a mechuanism distinct from its effect onprimary tumor growth[J]. Cancer Res,1996.56:921-925
    [3] Van der Wurrf A,Venmeuten SJ.Van der Linden EP.et.al Pattems of a-and B-catenin and E-cadheria expression in colorectal adenomas and carcinomas[J].J Pathot.2005.182:325- 330
    [4] Junji G,Hiuoshu S,Toshimasa T.et.al. Expression of E-cadherin and a-catenin in patients with colorectal cancer,Correlation with cancer invision and metastasis[J]. Am Jain pathol,2003,111:29-42
    [5] Alexiou D, KarayiannakisAJ,Syrigos Kn, et al. Serum levels of E-selectin, CAM-1 and VCAM-1 in colorectal cancer patients correlationswith clinicopathological features, patient survival and tumour surgery[J]. Eur J Cancer, 2001,37 (18):2392-2397.
    [6] Choi SH,Takahashi K,Eto H,et al. CD44 s exp ression in human colon carcinomas influences growth of liver metastases[J].Int J Cancer,2003,85 (4) :523-526.
    [7] Stallmach A, Wittig BM, Kremp K, et al. Downregulation of CD44v6 in colorectal carcinomas is associated with hypermethylation of the CD44 promoter region [J]. Exp Mol Pathol, 2003, 74(3) : 262-266.
    [8] 孟冬娅,薛文成,胡晓等.血管内皮生长因子的大肠癌诊治中的应用研究[J].实用癌症杂志,2001;16(1):46-48
    [9] Kraft A,Weindel K,Ochs A td,et al.Yascular endothelial growth factor in the sera and effusions of patients with malignant and nonmali gnant disease [J].Cancer.1999;85(1):178
    [10] Kunr H,Heer k,Lee PW,et a1.Preoperative serum vascular endothelial growth factor can predict stage in colorectal cancer [J] .Clin Cancer Res.1998;4 (5):1279
    [11] O,Connor DS,Schechner JS,Adida C,et a1.Control of apoptosis during angiogenesis by survivin expression in endothelial cells[J].Am J Pathol,2004.156(2):393-398.
    [12] Mesri M,Morales Ruiz M,Ackernlann EJ,et a1.Suppression of vascular endothelial growth factor-mediated endothelial cell protection by survivin targeting[J].Am J Pathol,2001,158(5):1757-1765.
    [13] Papapetropoulos A,Fulton D.Mahboubi K,et a1.Angiopoietin-1 inhibits endothelial cellapoptosis via the Akt/survivin pathway[J].J Biol Chem,2003,275(13):9102-9105.
    [14] Williams NS,Gaynor RB,Scoggin S,et a1.htentifieation and validation of genes involved in the pathogenesis of colorectal cancer using cDNA mieroarays and RNA interference[J]. Clin Caner Res,2003,9(3):931-946.
    [15] Rodel C,Haas J, Groth A,et a1.Spontaneous and radiation-induced apoptosis in cotorectal careinoma cells with different intrinsic radio-sensitivities:survivin as a radioresistance fator[J].Int J Radiat Oncol Biol Phys,2003,55(5):1341-1347.
    [16] Mesri M,Wall NR,Li J.et a1.Cancer gerle therapy using a survivinmutant adenovirus.J Clin Invcst,2001,108(7):981-990
    [17] Zhang H,Arbman G,Sun XF.Codon 20 1 polymorphism of DCC gene is a prognostic faetor in patients with colorectal cancer[J].Cancer Detect Prey,2003,27(3):216-221.
    [18] Tachibana M,Kawamata H,Fujimori T,et a1.Dysfunction of p53 pathway in human colorectal cancer:analysis of p53 gene mutation and the expression of the p53-associated factors pl4ARF,p331NG1,p21WAF1 and MDM2[J]. 1nt J Oncol,2004,25(4):913-920.
    [19] Kern A,Tauhert H,Scheele J,et a1.Association of p53 mutations.Mi-crovessel density and neoangiogenesis in pairs of colorectal cancers and corresponding liver metastases[J].Int J Oncol,2002,21(2):243-249.
    [20] Wang JY,Hsieh JS,Chang MY,et a1.Molecular detection of APC.K-ras,and p53 mutations in the serum of colorectal cancer patients as circulating biomarkers[J].World J Surg,2004, 28(7):721-726.
    [21] Li GQ.Zhang HF.Mad2 and p27 expression profiles in coloreetal cancer and its clinical significance[J].World J Gastroentero1.2004,10(21):3218-3220.
    [22] Fan JW,Fan PX.Wang Y.et a1.Relationship between expression of p27 and DNA ploidy in eolorectal carcinoma[J].Ai Zheng.2002.21(1):54-57.
    [23] Song SY,Lee SK,Kim DH .et a1.Expression of maspin in colon cancers:its relationship with p53 expression and microvessel density[J].Dig Dis Sci,2002,47(8):1831-1835.
    [24] Juliano RL.Signal transduction by cell adhesion receptors and the cytoskeleton:functions of integrins.cadherins,seleetins,and immunoglohulin-superfamily members[J].Annu Rev Pharmaeol Toxicol,2002,42:283-323.
    [25] Odintsova E,Sugiura T,Berditchevski F.Attenuation of EGF receptor signaling by a metastasis supperion,the tetraspanin CD82/KAI-1[J].Cur Biol,2003,10(16):1009-1012.
    [26] Wei JB,Chen LS,Gao F.Mutation,Loss of Heterozygosity,and Expression of Tumor Suppress or Gene ING(1)in Sporadic Coloreetal Carcinoma[J].Ai Zheng,2005,24(2):141-144
    [27] Mortensen K,Christensen J J,Nielsen HJ,et al.High expression of endothelial cell nitric oxide synthase in peritumoral microvessels predicts increased disease-free survival in colorectal cancer[J].Cancer Lett,2004,216 (1) :109-114.
    [28] Kondo S,Toyokuni S,Tsuruyama T,et al. Peroxynitrite-mediated stress is associated with proliferation of human metastatic colorectal carcinoma in the liver[J]. Cancer Lett,2002,179 (1):87-93
    [29] Yamamoto H,Itoh F,Hinoda Y. et a1.Suppression of metrilysin inhibits colon cancer cell invasion in vitro[J].Int J Cancer,2003.61(1):1
    [30] Itoh F,Yamamto H,Hinoda Y,et a1.Enhanced secretion and activation of matrilysin during malignant conversion of human colorectal epithelium and its relationship with invasive potential of colon cells[J].Cancer,2005,77-1717
    [31] Adachi Y,Yamamoto H,Itoh F.et a1.Contribution of matrilysin(MMP-7)to the metastatic pathway of human colorectal cancers[J].Gut,1999,45(2):252
    [32] Borehers AH,Powell MB,Fusening NE,et a1.Paracfine factor an cell-cell contact-mediated induction of protease and c-ets gene expression in malignant keratinocyte/dermal fibroblast eoeulture[J].Exp CeⅡ Res,2001,213:143
    [33] Ambim SJ iyazaki M,Ito H,et al A Prospective study of prognosis value of type IV collagenase activity in colorectal cancer tissue[J].Dig Dis Sci,1997;42(8):1660
    [34] Masuda H,Aoki H.Expression of matrix metalloproteinase-2 and tissue inhibitor of metaloproteinase-2 in normal colon tisue affect smetastatic potential of colorectal cancer[J].Dis Colon Rectum,2004,42(3):393
    [35] Tokurraku M,Sato H,Murakami S,et a1.Activation of the precursor of gelatinase A/72kDa type IV colagenasc/MMP-2 in lung carcinomas correlates with the expresion of membrane -type matrix metlloproteinase(MT-MMP)and lymph node metastasis[J].Jnr J Cancer,2003. 64:355
    [36] Ohuchi E,Imai K,Fujii K,et a1.Digests interstial collagens and other extrac ellular matrix macromelecules[J].J Biol Chem,1997,272-2446
    [37] Sardinha TS,Nagueras JJ,Ciong H.et a1.Membrane-type l matrix metalloproteinase mRNA expresion in colorectal cancer[J].Dis Colon Rectum,2000,43(3):389
    [38] Tsujii M,Kawano S,DuBois RN.et a1.Cyclooxygenase-2 expression in human colon cancer ceels increases metastatic potentia1[J].Proc Nail Sci USA,1997,94:3336
    [39] Bemhard KI,Grnher SB,Muschel RJ.et a1.Direct evidence linking expression of matrix metaloproteinase-9(92-kDagelatinase/colanenase)to metastatic phenotype in transformed rat embryocels[J].Prac Nail Acad Sci USA.2002,95.4293
    [40] Khokha R,W aterhouse P,Yagel S,et a1.Antisense RNA-induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells[J].Science.2003.243:947
    [41] Khokha R.Suppression of the tumorigenic and metastatic abilities of murine Bl6-F-l0 melanoma cells in vivo by the overexpression of the tissue inhibitor of the metalprote- inase-1[J].J Nail CancerInst,2004,86:299
    [42] Taroboletti G,Garofalo A,Belotti D,et a1.Inhibition of antigiogenesis and merine Hemagi- oma growth by batimastat, a syntheticinh inhibitor of matrix metalloproteinase[J].J Nail Cancer Inst.1995.87:293
    [43] Lozonshi L,Sanamura M,Kobari M,et a1.Controlling tulnor angiogenesis and metastasis of C2b murine colon adeno- carcinomaby a new matrix metalloproteinase inhibitor,kB-R7785,in two tumor models[J].Cancer Res,2003,59(6):1252
    [44] Troy AM, Sheahan K, Mulcahy HE, et al. Expression of Cathepsin B and L antigen and activity is associated with early colorectal cancer progression [J]. Eur J Cancer, 2004,40 ( 10 ):1610-1616.
    [45] Inuzuka K, Ogata Y, Nagase H, et al. Significance of coexpression of urokinase-type plasminogen activator, and matrixmetallo-proteinase 3 ( stromelysin) and 9 ( gelatinase B ) in colorectal carcinoma[J]. J Surg Res, 2003, 93 (2) : 211-218
    [46] 李祖国,丁彦青,邓永键.大肠癌细胞缝隙连接细胞间通迅功能与大肠癌转移相关性研究[J].解放军医学杂志.1998:23(4):248-249
    [47] Vlodavsky l,friendmann Y, Elkin M.et al.Mammalian Heparanase:gene cloning, expression and function in tumor progression and metastasis[J].Nat Med,2003; 5(7): 739-802
    [48] Hulett Md,Freeman C,Hamdorf BJ, et al.Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis [J]. Nat Med,1999,5(7):803
    [49] Eceles SA,Heparanase: breaking down barriers in tumors[J].Nat Med,1999,5(7):735-736
    [50] 赵坡,吕亚莉,结肠直肠癌端粒酶肝素酶表达升高预后关系[J].癌症志.2001:20(6): 624-627.

© 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