鼻腔鼻窦恶性肿瘤的分子机制及眼眶显微解剖学研究
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摘要
研究鼻眼相关部位解剖和鼻腔鼻窦肿瘤对鼻眼相关外科学具有十分重要的临床价值。目前,这一领域在其相关应用基础学方面鲜见报告。本文就鼻眼显微解剖学、鼻腔鼻窦恶性肿瘤中多基因水平分析等几个部分,从肿瘤的病因、病理和浸润转移等方面进行分子机制研究,通过统计学分析得出一组对临床有指导意义的参数。
     第一部分:鼻眼相关显微解剖结构研究
     目的:研究鼻眼相关部位显微解剖结构,探讨其微血管和微淋巴管的分布,为鼻眼相关外科学的基础研究和相关疾病的临床诊断、指导治疗和评估预后提供重要的解剖学依据。
     方法:取兔的鼻眼相关部位组织经固定、脱钙、脱水、浸腊、包埋、切片后分别行HE染色和免疫组织化学染色;人的标本收集病理科保存石蜡标本。
     结果:1.13%EDTA中性溶液加微波脱钙所需时间最短,HE染色效果好,组织清晰,免疫组织化学染色效果好;
     2.兔的眶壁可分成眶上壁、眶前壁、眶下壁和眶后壁,兔最大的鼻窦为上颌窦,兔的鼻眼相关部位于眼眶的前内侧,即眶自前壁;
     3.在兔及人的鼻眼相关部位标本中CD34、D2-40均可见阳性表达,并且CD34阳性表达明显高于D2-40,说明眼眶与鼻窦交界部位有较多微细血管和少量淋巴管存在。
     结论:1.13%EDTA中性溶液加微波脱钙法可以作为目前脱钙方法的首选;
     2.兔有完整的眼眶,可作为眼眶疾病和鼻眼相关疾病研究的动物模型;
     3.鼻眼相关部位有丰富的血管和少量淋巴管分布,可能在鼻眼相关疾病中发挥的作用。
     第二部分鼻腔鼻窦恶性肿瘤临床研究
     目的:研究鼻腔鼻窦恶性肿瘤的流行病学特点和发病规律,为临床的诊断、治疗和评估预后提供依据。
     方法:回顾性分析137例鼻腔鼻窦恶性肿瘤患者的临床资料和病理资料,将收集的病例用spss统计软件进行统计性描述。
     结果和结论:
     (1)病例的发病年龄主要集中在40~76岁年龄段(构成比,105/137);
     (2)鼻腔鼻窦恶性肿瘤的组织病理学类型非常复杂,上皮源性肿瘤多于软组织肿瘤,鳞癌最常见;
     (3)鼻腔鼻窦恶性肿瘤患者侵犯部位多样、临床症状复杂。鼻腔恶性肿瘤以鼻塞、涕血为主要临床症状,上颌窦恶性肿瘤以颌面部疼痛、麻木、肿胀和涕血为主,筛窦肿瘤常出现涕血、头痛、眼球突出和视力下降等;
     (4)内翻性乳头状瘤、横纹肌肉瘤均发生周围组织浸润和侵犯,恶性黑色素瘤和恶性淋巴瘤少见周围组织浸润和侵犯。
     第三部分p53、p63、p73和nm23-H1与鼻腔鼻窦恶性肿瘤
     目的:研究抑癌基因p53、p63、p73和nm23-H1与鼻腔鼻窦恶性肿瘤的相关性,探讨其发病的分子学机制,为鼻腔鼻窦恶性肿瘤的病因学提供重要依据。
     方法:用免疫组化法检测鼻腔鼻窦恶性肿瘤组织、癌旁组织、鼻息肉、内翻性乳头状瘤等组织中p53家族成员p53、p63、p73及nm23-H1等抑癌基因的表达,探讨其与鼻腔鼻窦恶性肿瘤的发生、发展和组织学类型的相关性。
     结果:1.p53和nm23-H1蛋白在鼻腔鼻窦恶性肿瘤、癌旁和对照组中的表达存在统汁学差异(P<0.01);
     2.p53、p63蛋白在鼻腔鼻窦恶性上皮肿瘤和恶性软组织肿瘤中的表达存在统计学差异(P<0.01);
     3.p63、p73蛋白在鼻腔鼻窦恶性肿瘤、癌旁和对照组中的表达无统计学差异(P>0.05);
     4.p73、nm23-H1蛋白在鼻腔鼻窦恶性上皮肿瘤和软组织肿瘤中的表达无统计学差异,p73蛋白在嗅神经母细胞瘤和恶性黑色素瘤中的表达与对照组的表达均无统计学差异(P>0.05);
     5.p53、p63、p73、nm23-H1在有鼻腔鼻窦以外组织侵犯和局限于鼻腔鼻窦的恶性肿瘤中的表达均无统计学差异(P>0.05)。
     结论:1.p53和nm23-H1基因在鼻腔鼻窦恶性肿瘤发生中发挥一定作用,p63和p73与鼻腔鼻窦恶性肿瘤的发生无相关性;
     2.p53和p63基因在不同病理类型的鼻腔鼻窦恶性肿瘤中发挥不同的作用,具有组织特异性,在研究中应根据不同病理类型分类讨论;
     3.p53、p63、p73和nm23-H1基因在鼻腔鼻窦恶性肿瘤的发展中不发挥作用。
     第四部分E-cad、LN、LN-R和ColⅣ与鼻腔鼻窦恶性肿瘤
     目的:研究鼻腔鼻窦恶性肿瘤的浸润性及转移性,为鼻腔鼻窦恶性肿瘤的病因学、诊断学、治疗及评估预后提供重要理论依据。
     方法:用免疫组化方法检测异腔鼻窦恶性肿瘤组织、癌旁组织、鼻息肉、内翻性乳头状瘤等组织中E-Cad、LN、ColⅣ和LN-R的表达,探讨其与不同组织类型、临床分期的鼻腔鼻窦恶性肿瘤的相关性。
     结果:1.E-cad、LN、LN-R和ColⅣ蛋白在鼻腔鼻窦恶性肿瘤、癌旁和对照组中的表达存在统计学差异(P<0.01),LN-R在对照组中鼻息肉或囊肿和内翻性乳头状瘤中的表达也存在统计学差异(P<0.01);
     2.E-cad和LN-R蛋白在鼻腔鼻窦恶性上皮肿瘤和恶性软组织肿瘤中的表达存在统计学差异(P<0.01),LN、ColⅣ在鼻腔鼻窦恶性上皮肿瘤和恶性软组织肿瘤中的表达均无统计学差异(P>0.05);
     3.LN-R、LN在不同侵犯范围的鼻腔鼻窦恶性肿瘤中的表达存在统计学差异(P<0.05),E-cad、ColⅣ在不同侵犯范围的鼻腔鼻窦恶性肿瘤中的表达均无统计学差异(P>0.05)。
     结论:1.E-cad、LN、LN-R和ColⅣ在鼻腔鼻窦恶性肿瘤的发生中发挥作用,并且LN-R在鼻内翻性乳头状瘤的发生过程中发挥一定作用;
     2.E-cad和LN-R在不同病理类型的鼻腔鼻窦恶性肿瘤中发挥不同的作用,具有组织特异性,在研究中应根据不同病理类型分类讨论。而LN和ColⅣ在不同病理类型的鼻腔鼻窦恶性肿瘤中发挥相似的作用;
     3.LN-R和LN在鼻腔鼻窦恶性肿瘤的发展中发挥一定的作用,与鼻腔鼻窦恶性肿瘤的浸润和侵袭有相关性;而E-cad和ColⅣ在鼻腔鼻窦恶性肿瘤的发展中不发挥重要作用。
     第五部分CD34和D2-40与鼻腔鼻窦恶性肿瘤
     目的:研究微血管和微淋巴管在鼻腔鼻窦恶性肿瘤中的作用,为鼻腔鼻窦恶性肿瘤的病因、判断侵袭与转移以及评估预后提供理论依据。
     方法:用免疫组织化学法检测鼻腔鼻窦恶性肿瘤组织、癌旁组织、鼻息肉和内翻性乳头状瘤中CD34和D2-40的表达,并探讨其与不同组织学类型和不同侵犯程度的鼻腔鼻窦恶性肿瘤的相关性。
     结果:1.CD34在鼻腔鼻窦恶性肿瘤、癌旁和对照组中的表达存在统计学差异(P<0.01);
     2.D2-40在鼻腔鼻窦恶性肿瘤、癌旁和对照组中的表达无统计学差异(P>0.05),CD34和D2-40在鼻腔鼻窦恶性上皮肿瘤和软组织肿瘤中的表达均无统计学差异(P>0.05);
     3.CD34和D2-40在不同侵犯范围的鼻腔鼻窦恶性肿瘤中的表达无统计学差异(P>0.05);
     4.用聚类分析法可将MVD计数聚为2类,分别为大于或等于24和小于24两类,经检验得出CD34在鼻腔鼻窦恶性肿瘤、癌旁和对照组中的表达存在统计学差异(P<0.01),这与MVD计数方差分析结果一致。
     结论:1.微血管在鼻腔鼻窦恶性肿瘤的发生中发挥重要作用;微淋巴管在鼻腔鼻窦恶性肿瘤的发生中不发挥作用;
     2.微血管和微淋巴管在不同病理类型的鼻腔鼻窦恶性肿瘤中发挥相似的作用;
     3.微血管和微淋巴管在鼻腔鼻窦恶性肿瘤的发展中不一定发挥作用,与鼻腔鼻窦恶性肿瘤的浸润和侵袭无相关性;
     4.认为聚类分析可以用于MVD计数结果聚类,将聚类结果用于鼻腔鼻腔鼻窦肿瘤与CD34的研究,简化了MVD计数步骤,减少了因标本和医生技术差异等因素而导致的误差。在鼻腔鼻窦肿瘤的研究中,MVD计数时可以将24作为等级分界点。
It's very important to research the anatomy of nasocular correlation and malignant tumor in nose.There is no large amount of report for this aspect.There are a large amount of clinical cases in the study on the level of molecules for multiple genes,etiology,prognosis,and outcome in nasal tumors.There are 5 parts in study. There are important parameters in clinical significance by results from statistical analysis.
     Part 1
     Objective:
     (1) To study the micro anatomic structure of the nasocular correlation;
     (2) To discuss the distribution of the micrangium and micro lymph vessel;
     (3) To provid important anatomic parameter for the clinical diagnosis,treatment and prognosis of surgery about the nasocular correlation.
     Methods:
     The HE and the immunohistchemical technique ware used to detected the fossa orbitalis paries of the rabbit and human.
     Results:
     (1) The 13%ethylene diamine tetracetic acid and microwave(EDTA-MW) is the rapiddest decalcification technique and the best staining of the HE and immunohistochemistry;
     (2) There are four orbital walls on rabbit orbit:paries superior orbitae,paries anterior orbitae,paries inferior orbitae,paries posterior orbitae.The maxillary sinus is the well developed sinus in the rabbit.The paries anterior orbitae is the location of the nasocular correlation;
     (3) The CD34 and D2-40 protein was expressed in structure of the nasocular correlation in the rabbit,and the positive rate of the CD34 is highter than the D2-40.
     Conclusion:
     (1) The 13%EDTA-MW is the first selection of the decalcification techniques;
     (2) There is a complete fossa orbitalis in rabbit head.The rabbit can be an animal model on studying the disease between the fossa orbitalis and the nasocular correlation;
     (3) There are redundant blood vessel and small amounts lymph vessel in the correlated structure of nose and eye.
     Part 2
     Objective:
     (1) To study the epidemiological feature and pathogenetic regularity of the nasal and paranasal sinus malignant tumor(NPMT);
     (2) To provid the important parameter for the clinical diagnosis,treatment and prognosis of the NPMT.
     Methods:
     137 patients with NPMT were reviewed retrospectively.
     Results and Conclusion:
     (1) Age of onset of the NPMT is constrated between 40 and 76 years;
     (2) There are many pathological types in MPMT,the disease incidence of the epithelial tissue tumor is higher than the soft connective tissue tumor,the disease incidence of squamous carcinoma is the highest in NPMT;
     (3) The MPMT encroach many location easily,such as other paranasal sinus,fossa orbitalis,and intracalvarium.The MPMT has complicated clinical symptom;
     (4) The inverted papillorna and rhabdomyosarcoma of the nasal cavity and paranasal sinus can encroach the circum-structure easily,but the malignant melanoma and malignant lymphoma is contradictory.
     Part 3
     Objective:
     (1) To study the clinical significance of the p53,p63,p73 and nm23H1 genes in NPMT,and discuss the molecular mechanism of the genesis and development in the NPMT;
     (2) To provid the important parameter for the etiological factor,diagnosis, treatment and prognosis in the NPMT.
     Methods:
     The immunohistchemical technique was used to detected the expression of p53、p63、p73 and nm23H1 inNPMT.
     Results:
     (1) The positive rate of the p53 and nm23-H1 in NPMT was significantly higher than para-cancer tissues and non-cancer tissues(P<0.01);
     (2) There was a significance on the expression of the p53 and p63 in endepidermis and in soft connective tissue of the NPMT(P<0.01);
     (3) The expression of p63 and p73 was no significance among the NPMT, para-cancer tissues and non-cancer tissues(P>0.05);
     (4) There wasn't statistical significance on the expression of the p73 and nm23H1 both of endepidermis and in soft connective tissue in the NPMT(P>0.05).The expression of p73 was not relative to the nasal and paranasal malignant melanoma nor esthesioneuroblastoma(P>0.05).
     (5) There was not significance on the expression of the p53,p63,p73 and nm23-H1 in different encroachment degree of the NPMT(P>0.05)
     Conclusion:
     (1) The p53 and nm23-H1 perhaps participate in regulation of occurrenc in NPMT;
     (2) The p53 and p63 maybe play different role in different pathotype of the NPMT;
     (3) The expression of p73 may not be associated with tumorgenesis of NPMT.The p53,p63,p73 and nm23-H1 may not be associated with tumorgenesis of NPMT.
     Part 4
     Objective:
     (1) To study the invasion and metastatisis of the NPMT;
     (2) To provid the important parameter for the etiological factor,diagnosis, treatment and prognosis of the NPMT.
     Methods:
     The immunohistchemical technique was used to detected the expression of E-Cad、LN、ColⅣand LN-R in NPMT.
     Results:
     (1) There was a significance on the expression of the E-cad、LN、LN-R and ColⅣin NPMT,para-cancer tissues and non-cancer tissues(P<0.01);and the positive rate of the LN-R in nasal inverting papilloma is significantly higher than that of nasal polyp and cystis(P<0.01);
     (2) There was a significance on the expression of the E-cad and LN-R in endepidermis and soft connective tissue of the NPMT(P<0.01);the expression between LN and ColⅣwas no significance(P>0.05);
     (3) There was a significance on the expression of the LN-R and LN in different encroachment degree of the NPMT(P<0.05);the expression of the E-cad and ColⅣwas not significant(P>0.05).
     Conclusion:
     (1) The E-cad、LN、LN-R and ColⅣperhaps participate in regulation of occurrenc in NPMT,and LN-R perhaps participate in regulation of occurrenc in nasal inverting papilloma;
     (2) The E-cad and LN-R maybe play different role in different pathotype of the NPMT,but the LN and ColⅣmay be play the homoioplastic role:
     (3) The expression of LN-R and LN was associated with invasion and metastatisis, and can evaluate the prognoses of the NPSC.
     Part 5
     Objective:
     (1) To study the role of the micrangium and micro lymphangion in NPMT;
     (2) To provid the important parameter for the etiological factor,diagnosis, treatment and prognosis of the NPMT.
     Methods:
     The immunohistchemical technique was used to detected the expression of CD34 and D2-40 in cases of NPSC.
     Results:
     (1) The positive rate of the CD34 in NPMT was significantly higher than in para-cancer tissues and non-cancer tissues(P<0.01),and the expression of D2-40 was no significance(P>0.05);
     (2) There wasn't a significance on the expression of the CD34 and D2-40 in endepidermis and soft connective tissue of the NPMT(P>0.05),and in different encroachment degree of the NPMT(P>0.05)
     (3) The cluster analysis can be used in MVD counted number in NPMT.According to cluster analysis,the MVD counted number can be clustering two group:≥24 and<24.The analytic result of the cluster is the consonance with MVD counted number.
     Conclusion:
     (1) The micrangium perhaps participate in regulation of occurrenc in NPMT,and the micro lymphangion may not be associated with tumorgenesis of NPMT;
     (2) The micrangium and micro lymphangion maybe play homoioplastic role in different pathotype of the NPMT;
     (3) The micrangium and micro lymphangion may not be associated with development of NPMT;
     (4) The cluster analysis can be used in exploratory study about the MVD counted number in NPMT.It can simplify MVD counted number and reduce relative accuracy.
引文
[1]卜国铉,鼻科学,上海科学技术出版社[J],2000年,第2版.
    [2]黄选兆,汪吉宝.实用耳鼻咽喉科学[J],人民卫生出版社,2001年,第1版.
    [3]王海林,眼科解剖学图谱[J],辽宁科学技术出版社,2002年,第1版.
    [4]卜国铉,鼻眼相关外科学[J],人民卫生出版社,1995年,第1版.
    [5]南开大学实验动物解剖学编写组,实验动物解剖学[J],北京人民教育出版社,1979年,第1版:41-43.
    [6]杨安锋,兔的解剖[J],北京科学出版社,1979年,第1版:134-137.
    [7]朱豫,宋国祥.兔眼眶结构解剖研究[J].眼科研究,1998,16(2):124-125.
    [8]Yamamoto-Fukud T,Shibata Y,Hishikawa Y,Shin M,Yamaguchi A,Kobayashi T,Koji T.Effects of various decalcification protocols on detection of DNA strand breaks by terminal dUTP nick end labeling[J].Histochem J,2000,32(11):697-702.
    [9]席越,王戈平,黄啸原.骨组织病理解剖学技术[J].人民卫生出版社,1997:126-143.
    [10]Cunningham CD 3rd,Schulte BA,Bianchi LM,Weber PC,Schmiedt BN.Microwave decalcification of human temporal bones[J[.Laryngoscope,2001,111(2):278-282.
    [11]Yoon YJ,Anniko M.Distribution of alpha-ANP in the cochlea and the vestibular organs[J].ORL J Otorhinolaryngol Relat Spec,1994,56(2):73-77.
    [12]熊正文,朱光君,李春光,彭东长,黄勇.提高骨组织免疫组织化学方法质量的若干问题探讨[J].中国组织化学与细胞化学杂志,2002,11(1):106-108.
    [13]Shi SR,Cote C,Kalra KL,Taylor CR,Tandon AK.A technique for retrieving antigens in formalin-fixed,routinely acid-decalcified,celloidin-embedded human temporal bone sections for immunohistochemistry[J].J Histochem Cytochem,1992,40(6):787-792.
    [14]Kaneko M,Tomita T,Nakase T,Takeuchi E,Iwasaki M,Sugamoto K,Yonenobu K,Ochi T.Rapid decalcification using microwaves for in situ hybridization in skeletal tissues[J].Biotech Histochem,1999,74(1):49-54.
    [15]曹长安,朱新生.EDTA微波快速脱钙法[J].第一军医大学学报,1997;17(2): 105.
    [16]刘大维,初同伟,张良,邱俊.EDTA微波脱钙骨的免疫组化染色[J].第三军医大学学报,2003;25(1):77-78.
    [17]Arai E,Kuramochi A,Tsuchida T,Tsuneyoshi M,Kage M,Fukunaga M,Ito T,Tada T,Izumi M,Shimizu K,Hirose T,Shimizu M.Usefulness of D2-40 immunohistochemistry for differentiation between kaposiform hemangioendothelioma and tufted angioma[J].J Cutan Pathol,2006,33(7):492-497.
    [18]尹凤兰,庞康,罗红岩.鼻腔鼻窦恶性肿瘤临床治疗分析[J].耳鼻咽喉-头颈外科,1999;6(2):36-39.
    [19]朱又华,李奇志,任庆荣.上颌窦癌的治疗—254例临床分析[J].耳鼻咽喉-头颈外科,1997,4(5):26-30.
    [20]Goldenberg D,Golz A,Fradis M,Martu D,Netzer A,Joachims HZ.Malignant tumors of the nose and paranasal sinuses:a retrospective review of 291 cases[J].Ear Nose Throat J,2001,80(4):272-277.
    [21]Dulguerov P,Jacobsen MS,Allal AS,Lehmann W,Calcaterra T.Nasal and paranasal sinus carcinoma:are we making progress? A series of 220 patients and a systematic review[J].Cancer,2001,92(12):3012-3029.
    [22]Roux FX,Brasnu D,Devaux B,Chabardes E,Schwaab G,Laccourreye O,Menard M,Janot F,Nguyen S.Bertrand J.Ethmoid sinus carcinomas:results and prognosis after neoadjuvant chemotherapy and combined surgery—a10-year experience[J].Surg Neurol,1994,42(2):98-104.
    [23]Christopher D.M.Fletcher[A].周庚寅,刘洪琪,张庆慧主译;廖松林主审.Diagnostic Histopathology of Tumors肿瘤组织病理诊断[J].山东科学技术出版社,2001年.第1版.
    [24]Steven TW,Anna Pou,Francis BQ,Matthew WR.Neoplasms of the Nose and Paranasal Sinuses[J].Grand Rounds Presentation,UTMB,Dept.of Otolaryngology,May19,2004
    [25]Newman AN,Colman M.Jayich SA.Verrucous carcinoma of the frontal sinus:a case report and review of the literature[J].J Surg Oncol,1983;24(4):298-303.
    [26]Piscioli F,Aldovini D,Bondi A.Squamous cell carcinoma with sarcoma-like stroma of the nose and paranasal sinuses: report of two cases[J]. Histopathology, 1984; 8(4):633-639
    
    [27] 宋国祥,吴中耀.眼眶病学[J],人民卫生出版社,1999;第1版.
    
    [28] Frierson HF Jr, Mills SE. Fechner RE, Taxy JB, Levine PA. Sinonasal Undifferentiated carcinoma. An aggressive neoplasm derived from Schneiderian epithelium and distinct from olfactory neuroblastoma[J]. Am J Surg Pathol, 1986; 10(11 ):771-779.
    
    [29] Triche TJ. Diagnosis of small round cell tumors of childhood[J]. Bull Cancer, 1988; 75(3):297-310.
    
    [30] Myers LL, Nussenbaum B, Bradford CR, Teknos TN, Esclamado RM, Wolf GT. Paranasal sinus malignancies: an 18-year single institution experience[J]. Laryngoscope. 2002; 112(11): 1964-1969.
    
    [31] Ozsaran Z, Yalman D, Baltalarli B, Anacak Y, Esassolak M, Haydaroglu A. Radiotherapy in maxillary sinus carcinomas: evaluation of 79 cases[J]. Rhinology. 2003; 41(1):44-48.
    
    [32] Bhattacharyya N. Survival and staging characteristics for non-squamous cell malignancies of the maxillary sinus. Arch Otolaryngol Head Neck Surg. 2003; 129(3):334-337.
    
    [33] Cantu G, Bimbi G, Fabiani F, Guzzo M, Mattavelli F, Pizzi N, Riccio S, Squadrelli M. Lymph node metastases in paranasal sinus carcinoma: prognostic value and treatment. Acta Otorhinolaryngol Ital.2002 ; 22(5):273-279.
    
    [34] Bhattacharyya N. Factors predicting survival for cancer of the ethmoid sinus. Am J Rhinol. 2002; 16(5):281-286.
    
    [35] Yamashita T, Fujii M, Ishiguro R, Tashiro M, Ohno Y, Tokumaru Y, Ranke M, Imanishi Y, Tomita T, Kanzaki J, Inuyama Y. Statistical analysis of maxillary sinus squamous cell carcinoma[J]. Nippon Jibiinkoka Gakkai Kaiho. 2002; 105(6):732-40.
    
    [36]Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumon X, Ferrara P, Mckeon F, Caput D. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancer [J]. Cell, 1997, 90(4)809-819.
    
    [37] Derry WB, Putzke AP, Rothman JH. Caenorhabditis elegans p53: role in apoptosis, meiosis, and stress resistance[J]. Science, 2001, 294(5542): 591-595.
    
    [38] Woo RA. Mclure KG. Lees-miller SP. Rancourt DE, Lee PW. DNA-dependent protein kinase acts upstream of p53 in response to DNA damage [JJ. Nature, 1998. 394(6694):700-704.
    
    [39] Ford JM, Hanawalt PC. Role of DNA excision repair gene defects in the etiology of cancer [J]. Current Topics Microbiology and Immunology. 1997, 221: 47-70.
    
    [40] Hermeking H. Lengauer C. Polyak K. He TC. Zhang L. Thiagalingam S. Kinzler KW, Vogelestein B. 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression [J]. Mol Cell.1997. 1(1):3-11.
    
    [41] Peng CY, Graves PR, Thomas RS, Wu Z, Shaw AS, Piwnica-Worms H. Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25c on serine-216[J].Science, 1997,277(5331): 1501-1505.
    
    [42] Levine A. p53, the cellular gatekeeper for growth and division[J]. Cell, 1997, 88:323-331.
    
    [43] Pfeifer GP, Denissenko MF. Formation and repair of DNA lesions in the p53 gene: relation to cancer mutations?[J]. Environ Mol Mutagen, 1998, 31(3): 197-205.
    
    [44] Lomax ME, Barnes DM, Gilchrist R, Picksley SM, Varley JM, Camplejohn RS. Two functional assays employed to detect an unusual mutation in the oligomerisation domain of p53 in a LI-Fraumeni like family[J]. Oncogene, 1997, 14(15): 1869-1874.
    
    [45] Digiammarino EL, Lee AS, CAdwell C, Zhang W, Bothner B, Ribeiro RC. Zambetti G, Kriwacki RW. A novel mechanism of tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer[J|. Nat Struct Biol. 2002. 9(1):12-16.
    
    [46] De Vries A, Flores ER, Miranda B, Hsieh HM, Van Oostrom CT, Sage J, Jacks T. Targeted point mutations of p53 lead to dominant-negative inhibition of wild-type p53 function[J]. Proc Natl Acad Sci USA. 2002, 99(5): 2948-2953.
    
    [47] Schmale H, Bamberger C. A novel protein with strong homology to the tumor suppressor p53[J]. Oncogene. 1997; 15(11): 1363-1367.
    
    [48] Yang A. Kaghad M. Wang Y, Gillett E. Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death inducing, and dominant-negative activeites [J]. Mol cell. 1998; 2(3):305-316.
    
    [49] Levrero M, De Laurenzi V, Costanzo A, Gong J, Melino G, Wang JY. Structure, function and regulation of p63 and p73[J]. Cell Death Differ. 1999; 6(12): 1146-1153.
    
    [50] Ikawa S, Nakagawara A, Ikawa Y. p53 family genes: structural comparison, expression and mutation. Cell Death Differ[J].1999; 6(12): 1154-1161.
    
    [51] Di Como CJ, Gaiddon C. Prives C. p73 function is inhibited by tumor-derived p53 mutants in mammalian cells[J].Mol Cell Biol. 1999; 19(2): 1438-1449.
    
    [52] Kojima T, Ikawa Y, Katoh I. Analysis of molecular interactions of the p53-family p51(p63) gene products in a yeast two-hybrid system: homotypic and heterotypic interactions and association with p53-regulatory factors[J]. Biochem Biophys Res Commun. 2001; 281(5): 1170-1175.
    
    [53] Tan M, Bian J, Guan K, Sun Y. p53CP is p51/p63, the third member of the p53 gene family: partial purification and characterization[J]. Carcinogenesis.2001; 22(2): 295-300.
    
    [54] Zeng X, Zhu Y, Lu H. NBP is the p53 homolog p63 [J]. Carcinogenesis. 2001; 22(2): 215-219.
    
    [55] Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C, McKeon F. p63 is essential for regenerative proliferation in limb, caraniofacial and epithelial development[J]. Nature. 1999; 398(6729): 714-718.
    
    [56] Celli J. Duijf P, Hamel BC, Bamshad M, Kramer B, Smits AP, Newbury-Ecob R, Hennekam RC, Van Buggenbout G, Van Haeringen A, Woods CG, van Essen AJ, De Waal R, Vriend G, Haber DA. Yang A, Mckeon F, Brunner HG. Van Bokhoven H. Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome[J].Cell.1999; 99(2): 143-153.
    
    [57] Berdon-Zapata V, Granillo-Alvarez M, Valdes-Flores M, Garcia-Ortiz JE, Kofman-Alfaro S, Zenteno JC. p63 gene analysis in Mexican patients with syndromic and non-syndromic ectrodactyly[J]. J Orthop Res. 2004; 22(1): 1-5.
    
    [58] Kaghad M. Bonnet H, Yang A. Creancier L. Biscan JC, Valent A. Minty A, Chalon P. Lelias JM, Dumont X, Ferrara P, McKeon F. Caput D. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers[J]. Cell. 1997, 90(4):809-819.
    
    [59] Pozniak CD, Radinovic S, Yang A, McKeon F. Kaplan DR, Miller FD. An anti-apoptotic role for the p53 family member. p73, during developmental neuron death[J]. Science. 2000; 289(5477): 304-306.
    
    [60] Ishimoto O. Kawahara C. Enjo K. Obinata M, Nukiwa T, Ikawa S. Possible oncogenic potential of DeltaNp73: a newly identified isoform of human p73[J]. Cancer Res. 2002; 62(3):636-641.
    
    [61] Grob TJ, Novak U, Maisse C, Barcaroli D, Luthi AU, Pirnia F, Hugli B, Graber HU, De Laurenzi V, Fey MF, Melino G, Tobler A. Human delta Np73 regulates a dominant negative feedback loop for TAp73 and p53[J]. Cell Death Differ. 2001; 8(12):1213-1223.
    
    [62] Falck J. Mailand N. Syljuasen RG. Bartek J. Lukas J. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis[J]. Nature. 2001; 410(6830):842-847.
    
    [63] Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA. Sobel ME. Evidence for a novel gene associated with low tumor metastatic protential [J]. J Natl Cancer Inst. 1988; 80(3): 200-204 .
    
    [64] Ni X, Gu S, Dai J, Cheng H, Guo L, Li L, Ji C, Xie Y, Ying K, Mao Y. Isolation and characterization of a novel human nm23-H1B gene, a different transcript of nm23-H1[J]. J Hum Genet, 2003; 48(2):96-100.
    
    [65] Leone A, Flatow U, King CR, Sandeen MA, Margulies IM, Liotta LA, Steeg PS. Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23- tranasfected melanoma cells[J]. Cell. 1991, 65(1): 25-35.
    
    [66] Hartsough MT, Steeg PS. Nm23/Nucleoside diphosphate kinase in human cancers[J]. J Bioenerg Biomembr. 2000, 32(3): 301-308.
    
    [67] Sadek CM, Jimenez A. Damdimopoulos AE, Kieselbach T, Nord M, Gustafsson JA. Spyrou G. Davis EC. Oko R. van der Hoorn FA. Miranda-Vizuete A. Characterization of human thioredoxin-like 2. A novel microtuhule-binding thiore- doxin expressed predominantly in the cilia of lung airway epithelium and spermatid mandchette and axoneme[J].Biol Chem,2003,278(15):13133-13142.
    [68]Leticia Quintanilla-Martinez,Marcus Kremer,Gisela Keller,Michaela Nathrath.Armando Gamboa-Dominguez,Abelardo Meneses,Lourdes Luna-Contreras,Antonello Cabras,Heinz Hoefler,Alejandro Mohar,Falko Fend.p53 Mutations in Nasal Natural Killer/T-Cell Lymphoma from Mexico[J].American Journal of Pathology,2001,159(6):2095-2105.
    [69]杨卫平,郭维,姜泗长,杨伟炎.鼻腔鼻窦恶性肿瘤p53基因突变的检测及临床意义[J].临床耳鼻咽喉科杂志,1997;11(5):203-205.
    [70]马世融,何健,何传峰,陈彤,卫旭东,谢宇平.鼻腔及鼻窦恶性肿瘤中p53基因突变的检测[J].中国耳鼻咽喉颅底外科杂志,2002;8(2):135-137.
    [71]包永新,马秀岚.HPV16和p53蛋白在鼻腔鼻窦肿瘤组织中的作用[J].中国医师杂志,2005;7(1):77-78.
    [72]Caruana SM,Zwiebel N,Cocker R,McCormick SA,Eberle RC,Lazarus P.p53alteration and human papilloma virus infection in paranasal sinus cancer[J].Cancer,1997,79(7):1320-1328.
    [73]Fang SY,Yan JJ,Ohyama M.Assessment of p53 protein expression in normal mucosa and benign and malignant lesions of the nasal cavity[J].Oncology,1998,55(2):168-173.
    [74]杨景,柳凤轩,阎晓初,贺光友,王宗前,刘丽梅.鼻及副鼻窦内翻性乳头状瘤的组织学发生及p53、PCNA表达与预后的关系[J].肿瘤防治研究,2000;27(5):332-335.
    [75]贾海英,王继群,山艳春,侯景辉.喉鳞状细胞癌组织中p63表达的临床意义[J].临床耳鼻咽喉科杂志,2006,20(3):119-121.
    [76]Yu YW,Garber ME,Schluns K,Pacyna-Gengelbach M,Petersen I.Evaluation of p63 expression in lung cancer by use of complementary DNA and tissne microarray[J].Zhonghua Bing Li Xue Za Zhi,2004,33(4):324-327.
    [77]Massion PP,Taflan PM,Jamshedur Rahman SM,Yildiz P,Shyr Y,Edgerton ME,Westfall MD,Roberts JR,Pietenpol JA,Carbone DP,Gonzalez AL.Significance of p63 amplification and overexpression in lung cancer development and prognosis[J]. Cancer Res, 2003, 63(21): 7113-7121.
    
    [78] Tannapiel A, Wasner M, Krause K, Geissler F, Katalinic A. Hauss J, Mossner J. Engeland K, Wittekind C. Expression of p73 and its relation to histopathology and prognosis in hepatocellular carcinoma[J]. J Natl Cancer Inst, 1999, 91(13): 1154-1158.
    
    [79] Matos P. Isidro G, Vieira E, Lacerda AF, Martins AG, Boavida MG. p73 expression in neuroblastoma: a role in the biology of advanced tumors?[J]. Pediatr Hematol Oncol, 2001, 18(1):37-46.
    
    [80] Cai YC, Yang GY, Nie Y, Wang LD, Zhao X, Song YL, Seril DN, Liao J, Xing EP, Yang CS. Molecular alterations of p73 in human esophageal squamous cell carcinomas: loss of heterozygosity occurs frequently; loss of imprinting and elevation of p73 expression may be related to defective p53[J]. Carcinogenesis. 2000; 21(4):683-689.
    
    [81] Su ZH, Li JC. Genetic instability of gene nm23H1 in colon cancer of Chinese patient[J]. Shi Yan Sheng Wu Xue Bao, 2003; 36(5): 325-329.
    
    [82] Chen XF, Zhang HT, Qi QY. Sun MM, Tao LY. Expression of E-cadherin and nm23 is associated with the clinicopathological factors of human non-small cell lung cancer in China. Lung Cancer, 2005, 48(1): 69-76.
    
    [83] Erent M, Gonin P, Cherfils J, Tissier P, Raschella G, Giartosio A, Agou F, Sarger C, Lacombe ML, Konrad M, Lascu I. Structural and catalytic properties and homology modelling of the human nucleoside diphosphate kinase C. product of the DRnm23 gene[J]. Eur J Biochem, 2001; 268(7): 1972-1981.
    
    [84] Otsuki Y, Tanaka M, Yoshii S, Kawazoe N, Nakaya K, Sugimura H. Tumor metastasis suppressor nm23Hl regulates Rac1 GTP ase by interaction with Tiaml[.I]. Proc Natl Acad Sci USA. 2001; 98(8): 4385-4390.
    
    [85] Liotta LA, Steeg PS. Clues to the function of nm23 and Awd proteins in development, signal transduction and tumor metaitasis provided by studies of Dictyostelium discoideum [J]. J Natl Cancer Inst, 1990; 82(14): 1170-1172.
    
    [86] Vincent T. De Vita, Jr. Samuel Hellman. Steven A. Rosenberg 徐从高,张茂宏。 杨兴季,邹雄.Cancer Principles&Practice of Oncology(5th Edition)癌-肿瘤学原理和实践(第五版),山东科学技术出版社,2001年:第1版.
    [87] Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator [J]. Science, 1991; 251(5000): 1451-1455.
    
    [88] Geiger B, Ayalon O. Cadherins [J]. Annu Rev Cell Biol, 1992; 8:307-332.
    [89] Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion [J]. Trends Genet, 1993; 9(9):317-321.
    [90] Harrington KJ, Syrigos KN. The role of E-cadherin-catenin complex: more than an intercellular glue?[J]. Ann Surg Oncol, 2000; 7(10):783-788.
    [91] Pelosi G, Scarpa A, Puppa G, Veronesi G, Spaggiari L, Pasini F, Maisonneuve P, Iannucci A, Arrigoni G, Viale G. Alteration of the E-cadherin/β-catenin cell adhesion system is common in pulmonary neuroendocrine tumors and is an independent predictor of lymph node metastasis in atypical carcinoids. Cancer, 2005; 103(6): 1154-1164.
    
    [92] Birchmeier W, Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and prevention of invasiveness [J]. Biochem Biophys Acta, 1994, 1198(1):11-26.
    
    [93] McNeill H, Ozawa M, Kemler R, Nelson WJ. Novel function of the cell adhesion molecule uvomorulin as an inducer of cell surface polarity [J]. Cell, 1990, 62(2): 309-316.
    
    [94] Umbas R, Schalken JA, Aalders TW, Carter BS, Karthaus HF, Schaafsma HE, Debruyne FM, Isaacs WB. Expression of the cellular adhesion molecule E-Cadherin is reduced or absent in high-grade prostate cancer [J]. Cancer Res, 1992; 52(18): 5104-5109
    
    [95] Schipper JH, Unger A, Jahnke K. E-Cadherin as a functional marker of the differentiation and invasiveness of squamous cell carcinoma of the head and neck[J]. Clin Otolaryngol Allied Sci, 1994; 19(5):381-384.
    
    [96] Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW, Birchmeier W, Funke I. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration[J]. Cancer Res. 1993; 53(7): 1690-1695.
    
    [97] Oka H, Shiozaki H, Kobayashi K, Inoue M, Tahara H, Kobayashi T. Takatsuka Y. Matsuyoshi N, Hirano S. Takeichi M. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis [J]. Cancer Res, 1993; 53(7): 1696-701.
    
    [98] Kadowaki T, Shiozaki H. Inoue M. Tamura S, Oka H, Doki Y, Iihara K, Matsui S. Iwazawa T, Nagafuchi A, Tsukita S, Mori T. E-cadherin and alpha-catenin expression in human esophageal cancer[J]. Cancer Res, 1994; 54(1):291-296.
    
    [99] Schipper JH. Frixen UH, Behrens J, Unger A, Jahnke K. Birchmeier W. E-cadherin expression in squamous carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis[J]. Cancer Research, 1991; 51(231):6328-6337.
    
    [100] Sorokin AV, Mikhailov AM, Kachko AV, Protopopova EV, Konovalova SN. Andrianova ME, Netesov SV, Kornev AN, Loktev VB. Human recombinant laminin- binding protein: isolation, purification, and crystallization[J]. Biochemistry (Mosc), 2000;65(5):546-553.
    
    [101] Burgeson RE, Chiquet M, Deutzmann R, Ekblom P, Engel J. Kleinman H. Martin GR, Meneguzzi G, Paulsson M, Sanes J. A new nomenclature for the laminins [J]. Matrix Biol, 1994; 14(3):209-211.
    
    [102] Kibbey MC, Grant DS, Kleinman HK. Role of the SIKVAV site of laminin in promotion of angiogenesis and tumor growth: an in vivo Matrigel modcl[J]. J Natl Caneer Inst, 1992, 84(21): 1633-1638.
    
    [103] Nelson J, Scott WN, Allen WE, Wilson DJ, Harriott P. McFerran NV. Walker B. Murine epidermal growth faetor peptide(33-42) binds to a YIGSR-specific laminin receptor on both tumor and endothelial cells[J]. J Biol Chem. 1996; 271(42): 26179-26186
    
    [104] Colognato H, Yurchenco PD. Form and function: the laminin family of heterotrimers[J].Dev Dyn,2000;218(2):213-234.
    [105]Fodil-Bourahla I,Drubaix I,Robert L.Effect of in vitro aging on the biosynthesis of glycosaminoglycans by human skin fibroblasts.Modulation by the elastin-laminin receptor[J].Mech Ageing Dev,1999;106(3):241-260.
    [106]Hipfel R,Schittek B,Bodingbauer Y,Garbe C.Specifically regulated genes in malignant melanoma tissues identified by subtractive hybridization[J].Br J Cancer,2000;82(6):1149-1157.
    [107]Appierto V,Cavadini E,Pergolizzi R,Cleris L,Lotan R,Canevari S,Formelli F.Decrease in drug accumulation and in tumor aggressiveness marker expression in a fenretinide-induced resistant ovarian tumor cell line[J].Br J Cancer,2001;84(11):1528-1534.
    [108]Martignone S,Menard S,Bufalino R,Cascinelli N,Pellegrini R,Tagliabue E,Andreola S,Rilke F,Colnaghi MI.Prognostic significance of the 67-kilodalton laminin receptor expression in human breast carcinomas[J].J Natl Cancer Inst,1993;85(5):398-402.
    [109]Basolo F,Pollina L,Pacini F,Fontanini G,Menard S,Castronovo V,Bevilacqua G.Expression of the Mr67000 laminin receptor is an adverse prognostic indicator in human thyroid cancer:an immunohistochemical study[J].Clin Cancer Res,1996;2(10):1777-1780.
    [110]Menard S,Tagliabue E,Colnaghi MI.The 67kDa laminin receptor as a prognostic factor in human cancer[J].Breast Cancer Res Treat,1998;52(1-3):137-145.
    [111]Liotta LA,Rao CN,Barsky SH.Tumor invasion and extracellular matrix[J].Lab Invest,1983;49(6):636-649.
    [112]彭庆廉.胶原蛋白及胶原蛋白分子病[J].国外医学分子生物学分册,1980;4(2):155-158.
    [113]李丽平,葛松华,贾朝京.肝病患者血清Ⅳ型胶原蛋白测定及临床意义[J].胃肠病学和肝病学杂志,1998;7(2):186.
    [114]Liu JM,Haroun-Bouhedja F,Boisson-Vidal C.Analysis of the in vitro inhibition of mammary adenocarcinoma cell adhesion by sulphated polysaccharides[J]. Anticancer Res,2000;20(5A):3265-3271.
    [115]Takasaki T,Akiba S,Sagara Y,Yoshida H.Histological and biological characteristics of microinvasion in mammary carcinomas<or 2 cm in diameter[J].Pathol Int,1998;48(10):800-805.
    [116]Knupfer MM,Poppenborg H,Hotfilder M,Kuhnel K,Wolff JE,Domula M.CD44 expression and hyaluronic acid binding of malignant glioma cells[Jl.Clin Exp Metastasis.1999:17(1):71-76
    [117]Knupfer MM,Poppenborg H,Hotfilder M,Domula M,Wolff JE.Hyaluronic acid binding capacity of malignant glioma cells[J].Anticancer Res,1998;18(1A):353-356
    [118]曹锐,李天星,杨玲.肿癌患者血清VEGF、CoⅣ、LN检测及其临床意义[J].第三军医大学学报,2002;24(2):212-213.
    [119]Kusunoki T,Nishida S,Kimoto-Kinoshita S,Murata K,Satou T,Tomura T.Type Ⅳ collagenase and immunostaining of type Ⅳ collagen in human thyroid tumors[J].Auris Nasus Larynx,2000;27(2):161-165.
    [120]Kusunoki T,Nishida S,Kimoto-Kinoshita S,Murata K,Satou T,Tomura T.Type Ⅳ collagen,type Ⅳ collagenase activity and ability of cell proliferation in human thyroid tumours[J].Asian J Surg,2002;25(4):304-308.
    [121]Castera L,Hartmann D J,Chapel F,Guettier C,Mall F,Lons T,Richardet JP,Grimbert S,Morassi O,Beaugrand M,Trinchet JC.Serum laminin and type Ⅳcollagen are accurate markers of histologically severe alcoholic hepatitis in patients with cirrhosis[J].J Hepatol,2000;32(3):412-418.
    [122]张健康,李晓丽,李亮成,徐大毅等.Ⅳ型胶原、层粘连蛋白、纤维粘连蛋白在胃癌中表达及意义[J].山西医科大学学报,2000,31(2):103-104.
    [123]滕晓东,高翠玉.Cath-D、PCNA及p16蛋白在食管癌组织中的表达[J].临床与实验病理学杂志.2002;18(6):669-670.
    [124]Tsuhako K,Nakazato I,Hirayasu T,Sunakawa H,Iwamasa T.Human papillomavirus DNA in adenosquamous carcinoma of the lung[J].J Clin Pathol,1998:51(10):741-759.
    [125] Rodrigo JR, Dominguez F, Suarez V, Canel M, Secades P, Chiara MD. Focal Adhesion Kinase and E-cadherin as markers for nodal metastasis in laryngeal cancer[J]. Arch Otolaryngol Head Neck Surg. 2007; 133(2): 145-150
    [126] Ardini E, Sporchia B, Pollegioni L, Modugno M, Ghirelli C, Castiglioni F, Tagliabue E, Menard S. Identification of a novel function for 67-kDa laminin receptor: increase in laminin degradation rate and release of motility fragInents [J].Cancer Res, 2002; 62(5): 1321-1325.
    
    [127] Givant-Horwitz V, Davidson B, Reich R. Laminin-induced signaling in tumor cells[J].Cancer Lett, 2005; 223(1):1-10.
    
    [128] Lu S, Huang M, Kobayashi Y, Komiyama A, Li X, Katoh R, Kawaoi A. Alterations of basement membrane in di-isopropanolnitrosamine-induced carcinogenesis of the rat thyroid gland: an immunohistochemical study[J]. Virchows Arch, 2000; 436(6): 595-601.
    
    [129] Santos-Garc(?)a A, Abad-Hernandez MM, Fonseca-Sanchez E, Julian-Gonzalez R, Galindo-Villardon P, Cruz-Hernandez JJ, Bullon-Sopelana A. E-cadherin, laminin and collagen IV expression in the evolution from dysplasia to oral squamous cell carcinoma[J]. Med Oral Pathol Oral Cir Bucal, 2006, 11 (2): 100-105.
    [130] Pellegrini R, Martignone S, Tagliabue E, Belotti D, Bufalino R, Cascinelli N, Menard S, Colnaghi MI. Prognostic significance of laminin production in relation with its receptor expression in human breast carcinomas[J]. Breast Caneer Res Treat, 1995; 35(2):195-199.
    
    [131] Folkman J. Tumor angiogenesis: therapeutic implications[J]. N Engl J Med, 1971; 285(21):1182-1186.
    
    1132] Folkman J. What is the evidence that tumors are angiogenesis dependent? [J] J Natl Cancer Inst, 1990; 82(1): 4-6.
    
    [133] Folkman J. Antiangiogenesis in cancer therapy-endostatin and its mechanisms of action[J]. Exp Cell Res, 2006; 312(5):594-607.
    
    [134] Herbst RS, Onn A, Sandier A. Angiogenesis and lung cancer: prognostic and therapeutic implications[J]. J Clin Oncol, 2005; 23(14): 3243-3256.
    [135]熊正文,李春光,丁华野,史景泉.肿瘤组织血管生成及微循环形态学研究技术[J].中国组织化学与细胞化学杂志,1998,7(3):499-500.
    [136]Augustin HG.Antiangiogenic tumour therapy:will it work?[J]Trends Pharmacol Sci,1998;19(2):216-222.
    [137]Woodhouse EC,Chuaqui RF,Liotta LA.General mechanisms of metastasis[J].Cancer,1997;80(8 Suppl):1529-1537.
    [138]Kong HL,Crystal RG.Gene therapy strategies for tumor antiangiogenesis[J].J Natl Cancer Inst,1998;90(4):273-286.
    [139]Schlingemann RO,Rietveld FJ,Kwaspen F,van de Kerkhof PC,de Waal RM,Ruiter DJ.Differential expression of markers for endothelial cells,pericytes,and basal lamina in the microvasculature of tumors and granulation tissue[J].Am J Pathol.1991;138(6):1335-1347.
    [140]Takahashi Y,Bucana CD,Cleary KR,Ellis LM.p53,vessel count,and vascular endothelial growth factor expression in human colon cancer[J].Int J Cancer,1998;79(1):34-38.
    [141]Scoazec JY.Tumor angiogenesis:histologic features[J].Bull Acad Natl Med,2000;184(3):547-554.
    [142]Weidner N.Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors[J].Breast Cancer Res Treat,1995;36(2):169-180.
    [143]Liotta L,SaidelG,Kleierman J,et al The significance of hematogenous tumor cell clumps in the metastatic process[J].Cancer Res,1976;36(3) 889-894
    [144]Stavropoulos NE,Bouropoulos C,Ioachim IE,Michael M,Hastazeris K,Tsimaris I,Kalogeras D,Liamis Z,Stefanaki S,Agnantis NI.Prognostic significance of angiogenesis in superficial bladder cancer[J].Int Urol Nephrol.2004;36(2):163-167.
    [145]熊正文,李永深,李德炳,苏红,黄勇,胡海霞,李宏伟.CD34在78例非小细胞肺癌中的表达及意义[J].实用医学杂志,2005;21(7):685-687.
    [146]Markovic O,Marisavljevic D,Cemerikic V,Vidovic A,Perunicic M,Todorovic M,Elezovic 1,Colovic M.Expression of VEGF and microvessel density in patients with multiple myeloma: clinical and prognostic significance[J]. Med Oncol, 2008; Epub ahead of print.
    
    [147] Cao Y, Veitonmaki N, Keough K, Cheng H, Lee LS. Zurakowski D. Elevated levels of urine angiostatin and plasminogen/plasmin in cancer patients[J]. Int J Mol Med, 2000, 5(5):547-551.
    
    [148] Fujieda S, Sunaga H, Tsuzuki H, Tanaka N, Saito H. Expression of platelet-derived endothelial cell growth factor in oral and oropharyngeal carcinoma[J]. Clin Cancer Res, 1998, 4(7): 1583-1590.
    
    [149] Igarashi M, Dhar DK, Kubota H, Yamamoto A, El-Assal O, Nagasue N. The prognostic significance of microvessel density and thymidine phosphorylase expression in squamous cell carcinoma of the esophagus[J]. Cancer. 1998, 82(7): 1225-1232.
    
    [150] He Y. Rajantie I, Ilmonen M, Makinen T, Karkkainen MJ, Haiko P, Salven P, Alitalo K. Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis[J]. Cancer Res, 2004, 64(11):3737-3740.
    
    [151] Choi WW, Lewis MM, Lawson D, Yin-Goen Q. Birdsong GG, Cotsonis GA, Cohen C, Young AN. Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression[J]. Mod Pathol, 2005; 18(1): 143-152.
    
    [152] Pusztaszeri MP, Seelentag W, Bosman FT. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand Factor, and Fli-1 in normal human tissues|J]. J Histochem Cytochem. 2006; 54(4):385-395.
    
    [153] Kaiserling E. Immunohistochemical identification of lymph vessels with D2-40 in diagnostic pathology[J]. Pathologe, 2004; 25(5):362-374.
    
    [154] Niakosari F. Kahn HJ, Marks A. From L. Detection of lymphatic invasion in primary melanoma with monoclonal antibody D2-40: a new selective immunohistochemical marker of lymphatic endothelium[J]. Arch Dermatol, 2005; 141(4):440-444.
    
    [155] Arigami T, Natsugoe S, Uenosono Y, Arima H, Mataki Y, Ehi K, Yanagida S, Ishigami S,Hokita S,Aikou T.Lymphatic invasion using D2-40 monoclonal antibody and its relationship to lymph node micrometastasis in pN0 gastric cancer[J].Br J Cancer,2005;93(6):688-693.
    [156]Matsuyama K,Chiba Y,Sasaki M,Tanaka H,Muraoka R,Tanigawa N.Tumor angiogenesis as a prognostic marker in operable non-small cell lung cancer[J].Ann Thorac Surg,1998;65(5):1405-1409.
    [157]何青波,苏炳华,钱亢.医学统计学及其软件包[J].上海科学技术文献出版社,2002,第1版.
    [158]张吉凯,胡毅玲,胡巢凤,罗耀星,林伟生,吴赤蓬.聚类在流行病学分层分析中的应用[J].中华流行病学杂志,2003;24(7):615-617.
    [159]Weidner N,Folkman J,Pozza F,Bevilacqua P,Allred EN,Moore DH,Meli S,Gasparini G.Tumor angiogenesis:a new significant and independent prognostic indicator in early-stage breast carcinoma[J].J Natl Cancer Inst,1992;84(24):1875-1887.
    [160]Choi WW,Lewis MM,Lawson D,Yin-Goen Q,Birdsong GG,Cotsonis GA,Cohen C,Young AN.Angiogenic and lymphangiogenic microvessel density in breast carcinoma:correlation with clinicopathologic parameters and VEGF-family gene expression[J].Mod Pathol,2005;18(1):143-152.

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