中期因子、VEGF-A在卵巢上皮性肿瘤组织中的表达及其临床意义
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:研究MK、VEGF—A在卵巢上皮性肿瘤组织中的表达,并探讨其临床意义。
     结果:MK在卵巢上皮性癌组织中为高表达,与卵巢上皮性良性肿瘤及卵巢交界性肿瘤之间有显著性差异(P<0.01),且与肿瘤临床分期及淋巴结转移相关(P<0.05),但与病理类型、及年龄均无相关性(P>0.05)。VEGF—A高表达于卵巢上皮性癌组织中,与卵巢上皮性良性肿瘤及交界性肿瘤之间有显著性差异,并与肿瘤临床分期及淋巴结转移相关(P<0.05),与病理类型及年龄无相关性(P>0.05)。MK与VEGF-A在卵巢上皮性癌中表达具有一致性。
     结论:1.MK、VEGF—A的表达上调可能对卵巢上皮性肿瘤的发生发展中起重要作用。
     2.MK、VEGF—A与卵巢上皮性癌侵袭转移密切相关,其异常高表达可能成为卵巢上皮性癌的预后判断指标。
     3.在卵巢上皮性癌中,MK、VEGF—A两者之间的表达具有一致性,提示两者可能通过共同的途径参与卵巢上皮性癌的发生、发展及转移过程。
Objective: To investigate the expression and clinical significances of midkine(MK)、vascular endothelial growth factor—A(VEGF—A) in epithelial ovarian tumors.
     Results: MK in epithelial ovarian cancer is higher in the expression, and benign tumors and ovarian tumor at the junction between a siginificant difference (P <0.01), and the clinical stage and tumor metastasis and related (P <0.05), But with the pathological type and age were not related (P> 0.05). VEGF-A high expression in epithelial ovarian cancer, and benign tumors and ovarian tumor at the junction between a significant difference, and clinical stages of tumor metastasis and related (P <0.05), and no pathological type and age Correlation (P> 0.05). MK and VEGF-A in epithelial ovarian cancer in the expression of consistency.
     Conclusion: (1)、MK, VEGF-A may increase the expression of epithelial ovarian tumors and development play an important role.
     (2)、MK, VEGF-A with epithelial ovarian cancer is closely related to the invasion and metastasis, the expression may become abnormal epithelial ovarian cancer prognostic indicators.
     (3)、Epithelial ovarian cancer, MK, VEGF-A between the expression of consistency, suggesting that the two may be the way through the common epithelial ovarian cancer to participate in the occurrence and development and transfer process.
引文
[1]Disaia PJ,Creasman WT.Clinical Gynecologic Oncology.北京:人民卫生出版社,2003.269.
    [2]连利娟,刘彤华,刘炽明,等.林巧稚妇科肿瘤学.北京:人民卫生出版社,2006.551-552.
    [3]Shimada H,Nabeya Y,Tagawa M.et al.Preoperative serum midkine concentration is a prognostic maker for esophageal squarrous cell carcinoma.Caneer Sci,2003,94(7):628-632.
    [4]Qi M,Ikematsu S,Ichihara-Tanaka K,et al.Midkine rescues Wilms' tumor cells from cisplatin-induced apoptosis:regulation of Bcl-2 expression by Midkine.Biochem(Tokyo),2000,127:269-277.
    [5]Nakanishi T,Kadonatsu K,Okamoto T,et al.Expression of midkine and pleiotropin in ovarian rumors.Obstet Gynecol.1997 Aug:90(2):258-90.
    [6]Adachi Y,Matsubara S,Muramatsu T,et al.Midkine promoter-based adenoviral suicide gene therapy to midkine-positive pediatric tumor.Pediatr Surg,2002,37:588-592.
    [7]Muramatsu T.Midkine and pleiotrophin:two related proteins involved in development,survival,inflammation and tumorigenesis.Biochem (Tokyo),2002,122(2):250-271.
    [8]O'Brien T,Cranston D,Fuggle S,Bicknell R.et al.The angiogenic factor midkine is expressed in bladder cancer,and overexpression correlates with a poor outcome in patients with invasive cancers.Cancer Res.1996 Jun 1:56(11):2515-2518.
    [9]Mishima K,Asai A,Kadomatsu K,et al.Increased expression of midkine during the progression of human astrocytomas.Neurosci Lett.1997,Sep,12;233(1):29-32.
    [10]Konishi N,Nakamura M,Nakaoka S,et al.Immunohistochemical analysis of midkine expression in human prostate carcinoma.Karger Publiser(Oncology),1999,57(3):253-257.
    [11]Ikematsu S,Yano A,Aridome K,et al.Serum midkine levels are increased in patients with various types of carcinomas.Br J Cancer,2000Sep;83(6):701-706.
    [12]Lkematsu S,Yoshida Y,et al.High levels of urinary midkine in various cancer patients.Biochem Biophys Res Commun.2006,306(2):329.
    [13]Muramaki M,Miyake H,Hara I,et al.Introduction of midkine gene into human bladder cancer cells enhances their malignant phenotype but increases their sensitivity to antiangiogenic therapy.Clin Cancer Res,2003,9(14):5152-5160.
    [14]Neufole G;Cohen T,Gengrinovitch S,et al.Vascular endothelial growth factor(VEGF)and its receptors.FASEB J,1999,13:9-22.
    [15]Carmeliet P,Jain PK.Angiogenesis in cancer and other diseases.Nature J 2000,407,(6801):249-257.
    [16]Shariat S F,Anwuri V A,Lamb D J,et al.Association of preoperative plasma levels of vascular endothelial growth factor and soluble vascular cell adhesion molecule-1 with lymph mode status and biochemical progression after radical prostatectomy.Clin Oncol 2004,22(9):1655-1663.
    [17]Mashour GA,Rather N,Khan GA,et al.The angiogenic factor midkine is aberrantly expressed in NF1 deficient Schwann cells and is a mitogen for neurofibroma derived cells.[J].Oncongene,2001,20(1):97-105.
    [18]殷正丰,罗祥基,康晓燕,等.肝细胞癌高表达中期因子与肝癌细胞血行播散的关系.[J].中国肿瘤临床,2004,31(7):361-364.
    [1]Muramatsu T.Midkine and pleiotrophin:two related proteins involved in development,survival,inflammation and tumorigenesis.[J]J Biochem,2002,132(3):359-371.
    [2]C.Pedraza.S.Matsubara.T.Muranatsu.A retinoic acid-responsive element in human midkine gene.[J]Biochem.1995.117:845.
    [3]罗详基,殷正丰,康晓燕,等.中期因子转录物及其蛋白在肝细胞癌中的定位与表达研究.中华普通外科杂志,2002,17(4):220-222。
    [4]Dai L,Xu D,Yao X,et al.Conformational determinants of the intracellular localization of midkine.Elsevier Publiser(Biochem.Res.Comman.),2005,330(1):310-317.
    [5]Kadomatsu K,Muramatsu T.Midkine and pleiotrophin in neural development and cancer.Cancer Lett,2004,204(2):127-143.
    [6]Garver RI Jr,Radford DM,Donis-Keller H,et al.Midkine and pleiotrophin expression in normal and malignant breast tissue.[J].Cancer.1994.Sep.1:74(5):1584-1590.
    [7]Aridome K,Tsutsui J,Takao S,et al.Increased midkine gene expression in human gastrointestinal cancers.Jpn Cancer Res.1995 Jul:86(7):655-661.
    [8]Nakagawara A,Milbrandt J,Muramatsu T,et al.Differential expression of pleiotrophin and midkine in advanced neuroblastomas.[J].Cancer Res.1995Apr 15:55(8):1792-1797.
    [9]O'Brien T,Cranston D,Fuggle S,Bicknell R.et al.The angiogenic factor midkine is expressed in bladder cancer,and overexpression correlates with a poor outcome in patients with invasive cancers.[J]Cancer Res.1996 Jun 1:56(11):2515-2518.
    [10]Mishima K,Asai A,Kadomatsu K,et al.Increased expression of midkine during the progression of human astrocytomas.[J].Neurosci Lett.1997,Sep,12;233(1):29-32.
    [11]殷正丰,罗详基,康晓燕,等.肝细胞癌高表达中期因子蛋白与肝内转移的关系.[J].中华肿瘤杂志,2002,24(1):361-364.
    [12]Konishi N,Nakamura M,Nakaoka S,et al.Immunohistochemical analysis of midkine expression in human prostate carcinoma.[J].Karger Publiser (Oncology),1999,57(3):253-257.
    [13]Ikematsu S,Yano A,Aridome K,et al.Serum midkine levels are increased in patients with various types of carcinomas.[J].Br J Cancer,2000Sep;83(6):701-706.
    [14]Obata Y,Kikuchi S,Lin Y,et al.Serum midkine concentrations and gastric cancer.[J].Blackwell Synerrgy(Cancer Sci)2005,96(1):54-56.
    [15]Ikematsu S,Okamoto K,Yoshida Y,et al.High levels of urinary midkine in various cancer patients.[J].Elsevier Publiser(Biochem.Biophys.Res.Commun.).2003,306(2):329-332.
    [16]Lkematsu S,Yoshida Y,et al.High levels of urinary midkine in various cancer patients.Biochem Biophys Res Commun.2006,306(2):329.
    [17]Dennett NS,Barcia RN,Mcleod JD.Age associated decline in CD25 and CD28 expression correlate with an increased susceptibility to CD95 mediated apoptosis in T cell.[J].Exp Geronted,2002,37:271.
    [18]Shibata Y,Muramatsu T,Hirai M,et al.Nuclear targetin by the growth factor midkine,.[J]the American Society for Cell Biology(Mol.Cell.Biol.),2002,22(19):6788-6796.
    [19].Sandra F,Harada H,Nakamura N,et al.Midkine induced growth of ameloblastoma through MAPK and Akt pathways.[J].Elsevier Publiser(Oral Oncol).2004,40(3):274-280.
    [20]Kojima S,Inui T,Kinura T,et al.Synthetic peptides derived from midkine enhance plasminogen activator activity in bovine aortic endothelial cells.Biochem Biophys Res Commun.1995 Jan 17:206(2):468-73.
    [21]M.Horiba,K.Kadomatsu,Y.Yuzawa,et al.Neointima formation in a restenosis model is suppressed in midkine deficient mice.[J].Clin Incest.2000,10:489.
    [22]Qi M,Ikematsu S,Maeda N,et al.Haptotactic migration induced by Midkine.Involvement of protein-tyrosine phosphatase.Mitogen-activated protein kinase,and phosphatidylionsitol 3-kinase.ASBMB(J.Biol.Chem.)2001.276(19):15868-15875.
    [23]Muramaki M,Miyake H,Hara I,et al.Introduction of midkine gene into human bladder cancer cells enhances their malignant phenotype but increases their sensitivity to antiangiogenic therapy.[J].Clin Cancer Res,2003,9(14):5152-5160.
    [24]陆永康,姚行,戴利成,等.中期因子在胰腺癌组织中的表达及其临床意 义.[J].中华普通外科杂志,2003, 18 (1): 1.
    
    [25] Friedrich C, Holtkamp H, Cinatl J, et al. Overexpression of Midkine in malignant peripheral nerve sheath tumor cells inhibits apoptosis and increase angiogenic potency. Int J Oncol,2005,27(5):1433-1440.
    [26] Ren YJ, Zhang QY. Expression of midkine and its clinical significance in esophageal squamous cell carcinoma. World J Gastrorenter. 2006,12(13):2006-2010.
    [27] Ruan M, Ji T, Wu Z, et al. Evaluation of expression of midkine in oral squamous cell carcinoma and its correlation with tumour angiogeriesis. Int J Oral Maxillofac Surg,2007,4(2):135-140.
    [28] Qi M, Ikematsu S, Ichihara-Tanaka K. Midkine rescues wilms tumor cells from cisplatin induced apoptosis: regulation of Bcl-2 expression by midkine.[J].Biochem(Tokyo),2000,127(2):269-277.
    [29] Takashi T. Midkine and pleiotrophin:Two related proteins involved in development, survival, inflammation and tumorigenesis.[J].Biochem.2002,132(6):359-371.
    [30] Ohuchida T, Okamoto K, Akahame K, et al. Midkine protects hepatocellular carcinoma cells against TRAIL-mediated apoptosis through down regulation of caspase-3 activity. [J]. Cancer ,2004,100(11):2430-2436.
    [31] Kawai H, Sato W, Yuzawa Y, et al. Lack of the growth factor midkine enhances survival against cisplatin-induced renal damage. [J]. Am J Pathol,2004,165(6):1603-1612.
    [32] Aridome K, Takao S, Kaname T, et al. Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas. [J].Br J Cacer,1998;78(4):472-477.
    [33] Paul S, Mitsumoto T, Asano Y, et al. Detection of truncated midkine in Wilm's tumor by a monoclonal antibody against human recombinant truncated midkine.[J]. Elsevier Publiser(Cancer Letters.), 2001,163(2):245-251.
    [34] Nobata S, Mogi H, Shinozawa T, et al. Exon skipping of midkine pre-mRNA is enhanced by intronic polymorphism in a colon cancer cell line.[J]. Elsevier Publiser (Cancer Letters.),2004,207(1):89-93.
    [35] Konishi N, Nakamura M, Nakaoka S, et al. Immunohistochemical analysis of midkine expression in human prostate carcinoma. Oncology, 1999,57(3):253-257
    [36] Ye C, Qi M, Fan QW, et al. Expression of midkine in the early stage of carcinogenesis in human colorectal cancer. Br J Cancer,1999,799(1):179-184
    [37] Shimada H, Nabeya Y, Tagawa M, et al. Preoperative serum midkine concentration is a prognostic marker for esophagesl squamous cell carcinoma.Cancer Ser,2003,94(7):628-632
    [38] Takei Y, Kadomatsu K, Matsuo S, et al. Antisense oligodenxynueleotide targeted to Midkine, a heparin-binding growth factor suppresses tumorigenicity of mouse rectal carcilloma cells. [J]. Cancer Res,2001,61(23):8486
    [39] Dai LC, Wang X, Yao X, et al. Antisense oligonucleotides targeting midkine inhibit tumor growth in an insitu human hepatocellular carcinoma model. [J].Acta Phamacol Sin,2007,28(3):453-458
    [40] Yu L. Lgai S, O-Wang J, et al. Cell growth and P53 dependent transcriptional activity of the midkine promoter confers suicide gene expression in tumor cells. [J]. Oncol Rep,2003,10(5):1301-1305
    [41] Adachi Y, Reynolds PN, Yamamoto M, et al. A midkine promoter based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging. [J]. Cancer Res,2001,61(21):7882-7888
    [42] Yu L, Yamamoto N, Kadomatsu K, et al. Midkine promoter can mediate transcriptional activation of a fused suicide gene in a broader range of human breast cancer compared with c-erbB-2 promoter. [J].Oncology,2004,66(2):143-149
    [43] Takei Y, Kadomatsu K, Goto T, et al. Combinational antitum or effect of a sRNA against midkine and paclitaxel on growth of human prostate cancer xenografts. [J]. Cancer,2006,107(4):864-873
    [44] Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor,microvascular hyermeability, and angiogenesis. Am J Pathol,1995,146:1029-1039.
    [45] Neufold G, Cohen T, Gengrinovitch S, et al. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J, 1999,13:9-22.
    [46] Yoko Hasumi, Hiroaki Mizukami, Masashi Yrabe, et al, Soluble FLT-1 expression suppresses carcinomatous ascites in nude mice bearing ovarian cancer. [J]. Cancer Research, 2002,62:2019.
    [47] Neufeld G, Cohen T, Gengrinovitch S, et al. Vascular endothelial growth factor(VEGF) and its receptor. [J]. FASEB J, 1999,13:9.
    [48] Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor,microvascular hyermeability, and angiogenesis. Am J Pathol, 1995,146:1029-1039.
    [49] Debabrate Mukhopadhyay, Kausthbh Datta. Multiple regulatory pathways of vascular permeability factor/vascular endothelial growth factor(VPF/VEGF) expression in rumors.[J].Seminars in Cancer Biology,2004,14(2): 123.
    [50] Fujimoto J, Saksguchi H, H irose R, et al. Progetins Suppress estrogen induced expression of 12 Goldberg MA, Schneider TJ, Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin.[J]. Biol Chem, 1994,269:4355-4359.
    [51] Suzuma I, Mandai M, Takagi H, et al. 17Beta-estradiol increases VEGF receptor and promotes DNA sythesis in retinal microvascular endothelial cells.Invest ophthalmol vis Sci, 1999,40:211-219.
    [52] Vasir B, Aiello LP, Yoon KH, et al. Hypoxia induces vascular endothelial growth factor gene and protein expression in cultured rat islet cells. Diabetes,1998,47:1894-1903.
    [53] Francesea Spinella, Laura Rosano, Valeriana Di Castro, et al. Endothelin-1 induces Vascular Endothelial Growth Factor by increasing Hypoxia-inducible factor-1 in Ovarian Carcinoma cells. [J].The Journal of Biological Chemistry,2002,277(31):27850.
    [54] Abu-Jawdeh-GM, et al. Strong expression of Vascular permeability factor (vascular endothelial growth factor ) and its receptors in ovarian borderline and malignant neoplasma. Lab-incvest, 1996,74(6):1105-1115.
    [55] Yamamoto S, et al. Expression of VEGF in the epithelial ovarian neoplasmas:correlation with clinic pathology and patient survival and analysis of serum VEGF levels. Cancer, 1997,(9):1221-1227.
    [56] Fujimoto-J, et al. Biologic implications of the expression of vascular endothelial growth factor subtypers in ovarian carcinoma. Cancer, 1998,83(12):2528-2533.
    [57] Kraft, et al. Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease. Cancer, 1999,85(1):178-187.
    
    [58] A. Harlazinska, P. sedlacaek, J. Kulpa, et al. Vascular endothelial growth factor (VEGF) concentration in sera and tumor effusions from patients with ovarian carcinoma. [J]. Anticancer research, 2004,24:1149.
    [59] M. Richarson, J Gunawan, M W C Harron, et al. Malignant Ascites Fluid (MAF), including Ovarian-Cancer-Associated MAF, Contains Angiostatin and other Factors Which Inhibit Angiogenesis. [J]. Gynecologic Oncology,2002,86:279.
    [60]. Yoko Hasumi, Hiroaki Miaukami, Masashi Urabe, et al. Soluble Flt-1 expression suppresses carcinomatous ascites in nude mice bearing Ovarian Cancer. [J]. Cancer Research, 2002,62:2019.
    [61] Noriyuki Akuragwa, Akira Nishikawa, Mashiro Iwasaki, et al. Expression of Vascular Endothelial Growth Factor and E- Cadherin in human Ovarian Cancer : association with ascites Fluid Accumulation and Peritoneal Dissemination in Mouse Ascites Model. [J] .Jpn J Cancer Res, 2002,93:644.
    [62] Kin KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo.[J]. Nature,1993,362:841.
    [63] Luo J C, Toyoda M, Shibuya M. Differential Inhibition of fluid accumulation and tumor growth in two mouse ascites tumors by an antivascular endothelial growth factor/permeability factor neutralizing antibody.[J]. Cancer Res,1998,58:2594.

© 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