Dsg3与肺癌预后相关性的研究
摘要
目的
1.探讨dsg3在非小细胞肺癌(NSCLC)和类癌中的表达情况以及其与患者年龄、性别、肿瘤大小、临床病理分期和肿瘤分化程度的关系;2.探讨dsg3的表达与NSCLC及类癌预后之间的关系。
方法
1.对天津市胸科医院胸外科2002年1月-2004年8月期间手术治疗的肺癌患者进行电话回访,取得详细随访结果的为58例NSCLC和12例类癌患者,利用K-M法计算其3年、5年生存率,并对其临床和病理资料进行分析。2.应用免疫组化法检测58例NSCLC和12例类癌组织中Dsg3的表达水平和分部情况。3.分析Dsg3在肺癌各组织类型间表达的差异及其与患者性别、年龄、肿瘤大小、临床病理分期和肿瘤分化程度之间的关系。4.分析鳞癌、腺癌和类癌患者的术后生存时间与Dsg3表达的关系。
结果
1.本组患者的平均术后生存时间为37.24±18.46月。利用Kaplan-Meier法计算得3年、5年生存率分别为60.34%、43.75%。2.Dsg3表达阳性组3年、5年生存率高于表达阴性组患者(P＜0.01)。对58例NSCLC患者按dsg3的阴/阳性表达绘制了生存曲线,并通过Log-rang检验比较其结果有统计学意义(P＜0.01)。由于类癌组例数较少,未作生存率的检验,但通过t检验对其生存时间进行分析发现表达阴/阳性者生存时间在统计学有显著差异。3.Dsg3的表达与性别、年龄、肿瘤临床病理分期等特征没有相关性(P＞0.05)。4.Dsg3的表达与肿瘤的病理类型、分化程度有相关性(P＜0.05),分化程度高组阳性表达高于分化程度低组。
结论
1.Dsg3在肺癌组织中的表达与否可以作为肺癌预后的一个指标,阳性表达提示预后较好。2.Dsg3的表达与肿瘤组织的病理类型和癌细胞分化程度的高低有相关性。
Objective
1.To investigate the expression of dsg3 in non-small cell lung cancer and carcinoid,and to discuss the reference of dsg3 with the size,staging,differentiation of the tumor tissue and gender,age of the patient. 2.To investigate the relationship of dsg3 and the 3-year, 5-year survival rate of lung cancer, the survival time after surgery of SCC,AD carcinoid and the expression of dsg3.
Methods
1. To follow up the surgery patients of tianjin chest hospital between Jan,2002 and Aug,2004 by telephone.58 non-small cell lung cancer patients and 12 caricinoid patients were obtained as an outcome,and 3-year survival, 5-year survival was also obtained according Keplan-Meier. The cilinical and pathological datas were also given. 2. The expression condition of dsg3 was detected in the 58 NSCLC tissues and 12 carcinoid tissues by immunohistochemical method. 3. Analyze the expression difference of dsg3 in each kind of NSCLC,discussion the relationship of the cilinical characteristic (gender,age) of the patients and size, staging,differentiation of the tumors. 4.Analyze the reference of dsg3 and 3-year survival, 5-year survival of the patients .Analyze the survival time after surgery of SCC,AD carcinoid and the expression of dsg3.
Results
1.The average St was obtained as 37.24±18.46 months,and the 3-year survival ,5-year survival was 60.34% and 43.75% by Kaplan-Meier. 2. The negative or masculine of dsg3 is closely associated with the survival of the patients ,the negative ones have a short survival (P<0.01) .We drawed survival curve of the 58 NSCLC patients,and the survival refered much with the expression of dsg3 .The St of the carcinoid, SCC, AD,patients is considered to be difference by t test (P<0.01) . 3. The expression of dsg3 is not associated with the cilinical factorssuch as age,gender. 4. The experession of dsg3 has a close relationship with the differentiation of the tumors. The low degreedifferentiation ones are negative compared to the high degree ones.
Conclusions:
1. The negative or masculine expression of dsg3 is asociated with the prognosis of lung cancer, and negative expression mostly cue a poor pronosis. 2.The expression of dsg3 is refered to the differentiation of the tumors,this study disclose that the high degree differentiation ones have a better masculine expression.
1.探讨dsg3在非小细胞肺癌(NSCLC)和类癌中的表达情况以及其与患者年龄、性别、肿瘤大小、临床病理分期和肿瘤分化程度的关系;2.探讨dsg3的表达与NSCLC及类癌预后之间的关系。
方法
1.对天津市胸科医院胸外科2002年1月-2004年8月期间手术治疗的肺癌患者进行电话回访,取得详细随访结果的为58例NSCLC和12例类癌患者,利用K-M法计算其3年、5年生存率,并对其临床和病理资料进行分析。2.应用免疫组化法检测58例NSCLC和12例类癌组织中Dsg3的表达水平和分部情况。3.分析Dsg3在肺癌各组织类型间表达的差异及其与患者性别、年龄、肿瘤大小、临床病理分期和肿瘤分化程度之间的关系。4.分析鳞癌、腺癌和类癌患者的术后生存时间与Dsg3表达的关系。
结果
1.本组患者的平均术后生存时间为37.24±18.46月。利用Kaplan-Meier法计算得3年、5年生存率分别为60.34%、43.75%。2.Dsg3表达阳性组3年、5年生存率高于表达阴性组患者(P＜0.01)。对58例NSCLC患者按dsg3的阴/阳性表达绘制了生存曲线,并通过Log-rang检验比较其结果有统计学意义(P＜0.01)。由于类癌组例数较少,未作生存率的检验,但通过t检验对其生存时间进行分析发现表达阴/阳性者生存时间在统计学有显著差异。3.Dsg3的表达与性别、年龄、肿瘤临床病理分期等特征没有相关性(P＞0.05)。4.Dsg3的表达与肿瘤的病理类型、分化程度有相关性(P＜0.05),分化程度高组阳性表达高于分化程度低组。
结论
1.Dsg3在肺癌组织中的表达与否可以作为肺癌预后的一个指标,阳性表达提示预后较好。2.Dsg3的表达与肿瘤组织的病理类型和癌细胞分化程度的高低有相关性。
Objective
1.To investigate the expression of dsg3 in non-small cell lung cancer and carcinoid,and to discuss the reference of dsg3 with the size,staging,differentiation of the tumor tissue and gender,age of the patient. 2.To investigate the relationship of dsg3 and the 3-year, 5-year survival rate of lung cancer, the survival time after surgery of SCC,AD carcinoid and the expression of dsg3.
Methods
1. To follow up the surgery patients of tianjin chest hospital between Jan,2002 and Aug,2004 by telephone.58 non-small cell lung cancer patients and 12 caricinoid patients were obtained as an outcome,and 3-year survival, 5-year survival was also obtained according Keplan-Meier. The cilinical and pathological datas were also given. 2. The expression condition of dsg3 was detected in the 58 NSCLC tissues and 12 carcinoid tissues by immunohistochemical method. 3. Analyze the expression difference of dsg3 in each kind of NSCLC,discussion the relationship of the cilinical characteristic (gender,age) of the patients and size, staging,differentiation of the tumors. 4.Analyze the reference of dsg3 and 3-year survival, 5-year survival of the patients .Analyze the survival time after surgery of SCC,AD carcinoid and the expression of dsg3.
Results
1.The average St was obtained as 37.24±18.46 months,and the 3-year survival ,5-year survival was 60.34% and 43.75% by Kaplan-Meier. 2. The negative or masculine of dsg3 is closely associated with the survival of the patients ,the negative ones have a short survival (P<0.01) .We drawed survival curve of the 58 NSCLC patients,and the survival refered much with the expression of dsg3 .The St of the carcinoid, SCC, AD,patients is considered to be difference by t test (P<0.01) . 3. The expression of dsg3 is not associated with the cilinical factorssuch as age,gender. 4. The experession of dsg3 has a close relationship with the differentiation of the tumors. The low degreedifferentiation ones are negative compared to the high degree ones.
Conclusions:
1. The negative or masculine expression of dsg3 is asociated with the prognosis of lung cancer, and negative expression mostly cue a poor pronosis. 2.The expression of dsg3 is refered to the differentiation of the tumors,this study disclose that the high degree differentiation ones have a better masculine expression.
引文
1.French National Federation of Cancer Centers(FNCLCC).Standards,Options and Recommendations(SOR)for the perioperative treatment of patients with resectable non-small cell lung cancer.Rev Mal Respir.2007 Oct;24(8):1049-64.
2.罗扬,冯奉仪,要洁,等.231例非小细胞肺癌术后生存和预后分析[J].中国肿瘤临床,2005,32(2):92-94.
3.Rea F,MarulliG,CallegaroD,el al.Prognostic sign ificanceof main bronchial lymph nodes involvement in non-small cell lung carcinoma:N_1 or N_2[J].Lung Cancer,2004,45(2):215-220.
4.廖美琳,周允中,丁嘉安,等.围手术期化疗在非小细胞肺癌中的应用探讨[J].中华医学杂志,2003,83(11):962-966
5.Alain D,Bernard M,Denis MS,et al.Preoperative Chemotherapy Followed by Surgery Compared With Primary Surgery in Resectble Stage Ⅰ(Except T_1N_0),Ⅱ,and Ⅲ a Non-Small-Cell Lung Cancer[J].Journal of Clinical Ontology,2002,20(1):247-253.
6.Okada M,Nishio W,Sakamoto T,et al.Effect of tumor size on prognosis in patients with non-small cell lung can cer:the role of segmentectomy as a type of lesser resection.Thorac Cardiovasc Surg,2005,129(1):87-93.
7.Batevik R,Grong K,Segadal L,et al.The female gender has a positive effect on survival independent of background life expectancy following su cal resection of primary non-small cell lung cancer:a study of absolute an d relative survival over 15years.Lung Cancer,2005,47(2):173-181
8.Naruke T,Suemasuk,Ishikawa S.Surgical treatment for lung cancer with metastasis to mediastinal lymph nodes.Thorac Cardiovasc Surg,1976;72:2
9.Mountain CF,Dresler CM.Regional lymphy node classification for lung cancer staging.Chest,1997;111(6):1718
10.廖美琳.肺癌的以手术为主的多学科治疗。中华医学杂志,2003,83,(3):181-182.
11.Riquet M,Hidden G,Debesse B.Direct lymphatic drainage of lung segments to the mediastinal nodes.An anatomic study on 260 adults.Thorac Cardiovasc Surg,1989,97(4):623-32.
12.Ayabe H,Tsuji H,Nakamura A,et al.Evaluation of hilar and mediastinal lymph node metastases in resected cases of bronchogenic carcinoma.Kyobu Geka,1994,47(1):28-32.
13.Watanabe Y,Hayashi Y,Takabatake I,et al.Clinical significance of extended mediastinal lymph node dissection on the basis of clinicopathological analysis of nodal involvement in bronchogenic carcinoma.Kyobu Geka,1994,47(1):4-9.
14.王洲,刘相燕,刘凡英,等.肺癌淋巴结隐匿性微转移的基因诊断及其对预后的意义.癌症,2003,22(11):1204-1208.
15.Keller S M,Adak S,Wagner H,et al.Mediastinal lymph node dissection improves survival in patients with stages Ⅱ and Ⅲ a non-small cell lung cancer.Eastern Cooperative Oncology Group[J].Ann Thorac Surg,2000,70(2):358-366.
16.Non-small Cell Lung Cancer Collaborative Group.Chemotherapy in non-small cell lung cancer:a meta-analysis using updated data on individual patients from 52randomised clinical trails.BMJ,1995,311(7010):899-909.
17.Arriagada R,Bergman B,Dunant A,et al.International Adjuvant Lung Cancer Trial Collaborative Group.Cisplatin-based adjuvant chemotherapy In patients with completely resected non-small cell lung cancer.N Engl Med,2004,350(4):351-360.
18.Matusan K,Dordevic G,Mozetic V,et al.Expression of osteopontin and CD44molecule in papillary renal cell tumors.Pathol Oncol Res,2005,11(2):108-113.
19.Joo M, Lee HK,Kang YK.Expression of E-cadherin,beta-catenin,CD44s and CD44v6 in gastric adenocarcinoma:Relationship with lymph node metastasis. Anticancer Res,2003,23(2B): 1581 -1588.
20.Pinto CA,Carvalho PE,Antonangelo L,et al.Morphometric evaluation of tumor matrix metalloproteinase 9 predicts survival after surgical resection of adenocarcinoma of the lung.Clin Cancer Res,2003,9(8):3098-3104.
21.Fortunato SJ,Menon R. Screening of novel matrix metalloproteinases (MMPs)in human fetal membraces .Assist Repord Genet,2002,19(10):483-486.
22.Stamenkovic I.Extracellular matrix remodeling:the role of matrix Metalloproteinases. Pathol,2003,200(4):448-464.
23.Hojilla CV,Mohammed FF,Khokha R.Matrix metalloproteinases and their Tissue inhibitors direct cell fate during cancer development.Cancer,2003,89(10):1817-1821.
24.Ondo K,Sugio K,Yamazaki K.et al.The significance of serum active matrix metalloproteinase-9 in patients with non-small cell lung cancer. Lung cancer,2004,46(2):205-213.
25.Ylisirnio S,Hoyhtya M,Turpeenniemi-Hujanen T.Serum matrix metalloproteinase-2,-9 and tissue inhibitors of metalloproteinase-1,-2 in lung cancer-TIMP-1 as a prognostic marker.Anticancer Res,2000,20(2B):1311-1316.
26. Bourdon. p53 Family isoforms. Curr Pharm Biotechnol. 2007 Dec;8(6):332-6.
27. Dey A, Verma CS, Lane DP. Updates on p53: modulation of p53 degradation as a therapeutic approach.Br J Cancer. 2008 Jan 15;98(1):4-8. Epub 2008 Jan 8.
28. Wang W, El-Deiry WS. Restoration of p53 to limit tumor growth.Curr Opin Oncol. 2008 Jan;20(1):90-6.
29. Poon GM. Enhancement of oligomeric stability by covalent linkage and its application to the human p53tet domain: thermodynamics and biological implications.Biochem Soc Trans.2007 Dec;35(Pt 6):1574-8.
30.Ohnishi T.The role of the p53 molecule in cancer therapies with radiation and/or hyperthermia.J Cancer Res Ther.2005 Jul-Sep;1(3):147-50.
31.Camins A,Verdaguer E,Folch J.Inhibition of ataxia telangiectasia-p53-E2F-1pathway in neurons as a target for the prevention of neuronal apoptosis.Curr Drug Metab.2007 Oct;8(7):709-15.
32.Ferrara N,Henzel WJ.Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells.Bioehem Biophys Res Cornmun,1989,161(2):851
33.Takahashi A,Sasaki H,Kim SJ,et al.Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis.Cancer Res,1994,54:4233-4237
34.Freeman MR,Sehneek FX,Gagnon ML.et al.Peripheral blood T lymphocytes an d lymphoeytes infiltrating human cancer express vascular endothelial growth factor a potential role for T cells in angiogenesis.Cancer Res,1995,55:4140-4145
35.Plate HK,Breier G,Weieh HA.et al.Vascular endothelial growth factor is a potential tumor an giogenesis factor in human glioma in vivo.Nature,1992,359:845-848
36.李宏江,敬静,汪静.乳腺肿瘤中VEGF的表达和MVD分布.四川大学学报,2005,36(2):288-289
37.曾健,陆云飞,林进令.血管内皮生长因子与乳腺癌淋巴结转移及预后的关系.广西医科大学学报,2001;18(5):607-609
38.Steven M,Albelda.Role of integrins and other cell adhesion molecules in tumor progression and metastasis.Lab Invest.1993,68(1):14-17.
39.Slagle BL,Zhou YZ,Birchmeier W.et al.Deletion of the E-cadherin gene in hepatitis B virus-positive Chinese hepatocellular carcinomas.Hepatology,1993, 18(4): 757-762.
40.Asano K, Duntsch CD, Zhou Q, et al. Correlation of N-cadherin expression in high grade gliomas with tissue invasion.Neurooneol, 2004, 70(1): 13-15.
41.Nakajima S , Doi R , Toyoda E , et al . N-cadherin expression and epithelial-mesenchymal transition in pan creatic carcinoma. Clin Cancer Res, 2004,10(12 Pt 1): 4125-4133.
42.Takamura M, Iehida T, Matsuda Y, et al. Reduced expression of liver-intestine cadherin is associated with progression and lymph node metastasis of human colorectal carcinoma. Cancer Lett, 2004, 212(2): 253-259.
43.Ko S, Chu KM, Luk JM, et al. Overexpression of LI-cadherin in gastric CSflcer is associated with lymph node metastasis. Biochem Biophys Res Commun, 2004 ,319(2): 562-568.
44.Tarone.G, Hirsch E, Brancaecio M, et al. Integrin function and regulation in development. Int J Dev Biol, 2000, 44(6): 725-731.
45.Andrews EJ, Wang JH, Winter DC, et al. Tumor cell adhesion to endothelial cells is increased by endotoxln via an upregulationof beta-1 integrin expression. Surg Res, 2001, 97(1): 14-19.
46.Felding-Habermann B, Fransvea E, Oq'ole TE, et al. Involvement of tumor cell integrin alpha V beta 3 in hematogenous metastasis of human melanoma cells. Clin Exp Metastasis, 2002, 19(5): 427-436.
47.Kroan ME, Koclwijk P, vail der Vecht B, et al. Urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia: implications for capillary-like tube formation in a fibrin matrix. Blood, 2000, 96(8): 2775-2783.
48.Hood JD, Frausto R, Kiosaes WB, et al. Diferential alphav integrin mediated Ras-ERK signaling during two pathways of angiogenesis.Cell Biol, 2003, 162(5): 933-943.
49.Penta K, Vamer JA, Liae L, et al. Dell induces integrin signaling and angiogenesis by ligation of αvβ3.Biol Chem, 1999, 274(16): 11101-11109.
50. Aoka Y,Johnson F, Schatzman R, et al. The embryonic alIgiogenic factor Dell accelerates tumor growth by enhmeing vascular formation. Microvas Res, 2002,64(1): 148-161.
51 .Koren R, Dekel Y,Sherman E.et al. The expression of DCC protein in female breast cancer. Breast Cancer Res Treat. 2003. 80(2): 215-220.
52.Evelyn B,Voura, Ravi A, et al. Involvement of intesrin alpha(v)beta (3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells. Mol Bid Cell, 2ool , 12(9): 2699-2710.
53.Vestweber D, Blanks JE, . Mechanisms that regulate the function of the selectins and their ligands. Physio Rev, 1999, 79(1): 181-213.
54.Flugy A M,D'Amato M , Russo D, et al. E-selectin madulates the malignant properties of T84 colon carcinoma cells. Biochem Biophys Res Comluun,2002. 293(3): 1099-1106.
55.Mccary OJ, Mouse SA, Bray PF, et al. Immobilized platelets support human colon carcinoma cell tethering, rolling and firm adhesion under dyrnamic flow conditions. Blood, 2000, 96(5): 1789-1797.
56.Qian F, Hanahan D, Weissman I. LI-selectin call facilitate metastasis to lymph nodes in a transgenic mouse model of carcinogenesis. Proc Natl Acad Sci USA,2001, 98(7): 3976-3981.
57.Bomig L, Wong R, Hynes R O, et al. Synergistic efects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancersof metastasis. Proc Natl Acad Sci USA. 2002, 99(4): 2193-2198.
58.Shiratori H, Koshino T, Uesugi M , etal. Acceleration of lung metastasis by up-regulation of CD44 expression in osteosarcoma derivod cell transplanted mice.Cancer Lett.2001,170(2):177-182.
59.Weber GF,Bronson RT,ILagan J.et al.Absence of the CD44 gene prevents arcomametastasis.Cancer Res.2002,62(8):2281-2286.
60.Fukuoka J,Dracheva T,Shih JH.et al.Dsg3 as a prognostic factor in lung cancer.Hum Pathol.2007 Feb;38(2):276-83.Epub 2006 Nov 3.
61.刘仲奇,田勇泉,马芙蓉等.桥粒芯糖蛋白3基因在鼻咽癌中表达的初步研究.中华医学杂志,2007.87(36)2541-2543.
62.Wang L,Liu T,Wang Y,et al.Altered expression of desmocollin 3,dsg3,and beta-catenin in oral squamous cell carcinoma:correlation with lymph node metastasis and cell proliferation.Virchows Arch.2007 Nov;451(5):959-66.Epub 2007 Sep 11.
63.Chen YJ,Chang JT,Lee L,et al.DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis.Oncogene.2007 Jan 18;26(3):467-76.Epub 2006 Jul 31.
1. Femiano F . Pemphigus vulgaris: recent advances in our understanding of its pathogenesis.Minerva Stomatol. 2007 Apr;56(4):215-23. Review. English, Italian.
2. Holthofer B,Windoffer R ,Troyanovsky S.et al .Structure and function of desmosomes.Int Rev Cytol. 2007;264:65-163.
3. Stokes DL .Desmosomes from a structural perspective.Curr Opin Cell Biol. 2007 Oct;19(5):565-71. Epub 2007 Oct 22.
4. Dusek RL,Godsel LM, Green KJ.Discriminating roles of desmosomal cadherins:beyond desmosomal adhesion.J Dermatol Sci. 2007 Jan;45(1):7-21. Epub 2006 Dec 1.
5. Cheng X, Den Z, Koch PJ. Desmosomal cell adhesion in mammalian development.Eur J Cell Biol. 2005 Mar;84(2-3):215-23.
6. Muller R,Svoboda V, Wenzel E. et al .IgG against extracellular subdomains of dsg3 relates to clinical phenotype of pemphigus vulgaris.Exp Dermatol. 2008 Jan;17(1):35-43.
7. Garrod DR, Merritt AJ, Nie Z. Desmosomal adhesion: structural basis, molecular mechanism and regulation .Mol Membr Biol. 2002 Apr-Jun;19(2):81-94.
8.Kowalczyk AP,Borgwardt JE,Green KJ. Analysis of desmosomal cadherin-adhesive function and stoichiometry of desmosomal cadherin-plakoglobin complexes.Invest Dermatol. 1996 Sep;107(3):293-300.
9.Yamamoto Y,Aoyama Y,Shu E,et al. Anti-dsg3 (Dsg3) monoclonal antibodies deplete desmosomes of Dsg3 and differ in their Dsg3-depleting activities related to pathogenicity.Biol Chem. 2007 Jun 15;282(24):17866-76. Epub 2007 Apr 11.
l0.Kottke MD,Delva E,Kowalcyk AP. The desmosome: cell science lessons from human diseases.Cell Sci. 2006 Mar 1;119(Pt 5):797-806.
11.Cheng X,Den Z,Koch PJ. Desmosomal cell adhesion in mammalian development.Eur J Cell Biol.2005 Mar;84(2-3):215-23.
12.Chitave VA et al.Cell Sci,1998;111(Pt 14):1942-1949
13.Huber O.Structure and function of desmosomal proteins and their role in development and disease.Cell Mol Life Sci.2003 Sep;60(9):1872-90.
14.Garrod DR,Merritt AJ,Nie Z.Desmosomal cadherins.Curr Opin Cell Biol.2002Oct;14(5):537-45.
15.Lewis JE et al.Cell Biol,1997;136(4):919-934
16.Garrod DR,Merritt AJ,Nie Z.Desmosomal adhesion:structural basis,molecular mechanism and regulation.Mol Membr Biol.2002 Apr-Jun;19(2):81-94.
17.Hatzfeld M.Plakophilins:Multifunctional proteins or just regulators of desmosomal adhesion.Biochim Biophys Acta.2007 Jan;1773(1):69-77.Epub 2006May 6.
18.Sobolik-Delmaire T,Katafiasz D,Keim SA.et al.Decreased plakophilin-1expression promotes increased motility in head and neck squamous cell carcinoma cells.Cell Commun Adhes.2007 Mar-Jun;14(2-3):99-109.
19.McMillan JR,Shimizu H.Desmosomes:structure and function in normal and diseased epidermis.Dermatol.2001 Jun;28(6):291-8.
20.Daneshpazhooh M,Chams-Davatchi C,Khamesipour A.et al.Desmoglein 1 and 3enzyme-linked immunosorbent assay in Iranian patients with pemphigus vulgaris:correlation with phenotype,severity,and disease activity.Eur Acad Dermatol Venereol.2007 Nov;21(10):1319-24.
21.Junya Fukuoka,Tatiana Dracheva,Joanna H.et al.Dsg3 as a prognostic factor in lung cancer.Human Pathogy 2007(38),276-283.
22.刘仲奇,田勇泉,马芙蓉等.桥粒芯糖蛋白3基因在鼻咽癌中表达的初步研究.中华医学杂志,2007,87(36):2541-2543.
23.Mousa SA.Cell adhesion molecules:potential therapeutic & diagnostic implications.Mol Biotechnol. 2008 Jan;38(1):33-40. Epub 2007 Aug 15.
24.Pokutta S,Weis WI. Structure and mechanism of cadherins and catenins in cell-cell contacts.Annu Rev Cell Dev Biol. 2007;23:237-61.
2.罗扬,冯奉仪,要洁,等.231例非小细胞肺癌术后生存和预后分析[J].中国肿瘤临床,2005,32(2):92-94.
3.Rea F,MarulliG,CallegaroD,el al.Prognostic sign ificanceof main bronchial lymph nodes involvement in non-small cell lung carcinoma:N_1 or N_2[J].Lung Cancer,2004,45(2):215-220.
4.廖美琳,周允中,丁嘉安,等.围手术期化疗在非小细胞肺癌中的应用探讨[J].中华医学杂志,2003,83(11):962-966
5.Alain D,Bernard M,Denis MS,et al.Preoperative Chemotherapy Followed by Surgery Compared With Primary Surgery in Resectble Stage Ⅰ(Except T_1N_0),Ⅱ,and Ⅲ a Non-Small-Cell Lung Cancer[J].Journal of Clinical Ontology,2002,20(1):247-253.
6.Okada M,Nishio W,Sakamoto T,et al.Effect of tumor size on prognosis in patients with non-small cell lung can cer:the role of segmentectomy as a type of lesser resection.Thorac Cardiovasc Surg,2005,129(1):87-93.
7.Batevik R,Grong K,Segadal L,et al.The female gender has a positive effect on survival independent of background life expectancy following su cal resection of primary non-small cell lung cancer:a study of absolute an d relative survival over 15years.Lung Cancer,2005,47(2):173-181
8.Naruke T,Suemasuk,Ishikawa S.Surgical treatment for lung cancer with metastasis to mediastinal lymph nodes.Thorac Cardiovasc Surg,1976;72:2
9.Mountain CF,Dresler CM.Regional lymphy node classification for lung cancer staging.Chest,1997;111(6):1718
10.廖美琳.肺癌的以手术为主的多学科治疗。中华医学杂志,2003,83,(3):181-182.
11.Riquet M,Hidden G,Debesse B.Direct lymphatic drainage of lung segments to the mediastinal nodes.An anatomic study on 260 adults.Thorac Cardiovasc Surg,1989,97(4):623-32.
12.Ayabe H,Tsuji H,Nakamura A,et al.Evaluation of hilar and mediastinal lymph node metastases in resected cases of bronchogenic carcinoma.Kyobu Geka,1994,47(1):28-32.
13.Watanabe Y,Hayashi Y,Takabatake I,et al.Clinical significance of extended mediastinal lymph node dissection on the basis of clinicopathological analysis of nodal involvement in bronchogenic carcinoma.Kyobu Geka,1994,47(1):4-9.
14.王洲,刘相燕,刘凡英,等.肺癌淋巴结隐匿性微转移的基因诊断及其对预后的意义.癌症,2003,22(11):1204-1208.
15.Keller S M,Adak S,Wagner H,et al.Mediastinal lymph node dissection improves survival in patients with stages Ⅱ and Ⅲ a non-small cell lung cancer.Eastern Cooperative Oncology Group[J].Ann Thorac Surg,2000,70(2):358-366.
16.Non-small Cell Lung Cancer Collaborative Group.Chemotherapy in non-small cell lung cancer:a meta-analysis using updated data on individual patients from 52randomised clinical trails.BMJ,1995,311(7010):899-909.
17.Arriagada R,Bergman B,Dunant A,et al.International Adjuvant Lung Cancer Trial Collaborative Group.Cisplatin-based adjuvant chemotherapy In patients with completely resected non-small cell lung cancer.N Engl Med,2004,350(4):351-360.
18.Matusan K,Dordevic G,Mozetic V,et al.Expression of osteopontin and CD44molecule in papillary renal cell tumors.Pathol Oncol Res,2005,11(2):108-113.
19.Joo M, Lee HK,Kang YK.Expression of E-cadherin,beta-catenin,CD44s and CD44v6 in gastric adenocarcinoma:Relationship with lymph node metastasis. Anticancer Res,2003,23(2B): 1581 -1588.
20.Pinto CA,Carvalho PE,Antonangelo L,et al.Morphometric evaluation of tumor matrix metalloproteinase 9 predicts survival after surgical resection of adenocarcinoma of the lung.Clin Cancer Res,2003,9(8):3098-3104.
21.Fortunato SJ,Menon R. Screening of novel matrix metalloproteinases (MMPs)in human fetal membraces .Assist Repord Genet,2002,19(10):483-486.
22.Stamenkovic I.Extracellular matrix remodeling:the role of matrix Metalloproteinases. Pathol,2003,200(4):448-464.
23.Hojilla CV,Mohammed FF,Khokha R.Matrix metalloproteinases and their Tissue inhibitors direct cell fate during cancer development.Cancer,2003,89(10):1817-1821.
24.Ondo K,Sugio K,Yamazaki K.et al.The significance of serum active matrix metalloproteinase-9 in patients with non-small cell lung cancer. Lung cancer,2004,46(2):205-213.
25.Ylisirnio S,Hoyhtya M,Turpeenniemi-Hujanen T.Serum matrix metalloproteinase-2,-9 and tissue inhibitors of metalloproteinase-1,-2 in lung cancer-TIMP-1 as a prognostic marker.Anticancer Res,2000,20(2B):1311-1316.
26. Bourdon. p53 Family isoforms. Curr Pharm Biotechnol. 2007 Dec;8(6):332-6.
27. Dey A, Verma CS, Lane DP. Updates on p53: modulation of p53 degradation as a therapeutic approach.Br J Cancer. 2008 Jan 15;98(1):4-8. Epub 2008 Jan 8.
28. Wang W, El-Deiry WS. Restoration of p53 to limit tumor growth.Curr Opin Oncol. 2008 Jan;20(1):90-6.
29. Poon GM. Enhancement of oligomeric stability by covalent linkage and its application to the human p53tet domain: thermodynamics and biological implications.Biochem Soc Trans.2007 Dec;35(Pt 6):1574-8.
30.Ohnishi T.The role of the p53 molecule in cancer therapies with radiation and/or hyperthermia.J Cancer Res Ther.2005 Jul-Sep;1(3):147-50.
31.Camins A,Verdaguer E,Folch J.Inhibition of ataxia telangiectasia-p53-E2F-1pathway in neurons as a target for the prevention of neuronal apoptosis.Curr Drug Metab.2007 Oct;8(7):709-15.
32.Ferrara N,Henzel WJ.Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells.Bioehem Biophys Res Cornmun,1989,161(2):851
33.Takahashi A,Sasaki H,Kim SJ,et al.Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis.Cancer Res,1994,54:4233-4237
34.Freeman MR,Sehneek FX,Gagnon ML.et al.Peripheral blood T lymphocytes an d lymphoeytes infiltrating human cancer express vascular endothelial growth factor a potential role for T cells in angiogenesis.Cancer Res,1995,55:4140-4145
35.Plate HK,Breier G,Weieh HA.et al.Vascular endothelial growth factor is a potential tumor an giogenesis factor in human glioma in vivo.Nature,1992,359:845-848
36.李宏江,敬静,汪静.乳腺肿瘤中VEGF的表达和MVD分布.四川大学学报,2005,36(2):288-289
37.曾健,陆云飞,林进令.血管内皮生长因子与乳腺癌淋巴结转移及预后的关系.广西医科大学学报,2001;18(5):607-609
38.Steven M,Albelda.Role of integrins and other cell adhesion molecules in tumor progression and metastasis.Lab Invest.1993,68(1):14-17.
39.Slagle BL,Zhou YZ,Birchmeier W.et al.Deletion of the E-cadherin gene in hepatitis B virus-positive Chinese hepatocellular carcinomas.Hepatology,1993, 18(4): 757-762.
40.Asano K, Duntsch CD, Zhou Q, et al. Correlation of N-cadherin expression in high grade gliomas with tissue invasion.Neurooneol, 2004, 70(1): 13-15.
41.Nakajima S , Doi R , Toyoda E , et al . N-cadherin expression and epithelial-mesenchymal transition in pan creatic carcinoma. Clin Cancer Res, 2004,10(12 Pt 1): 4125-4133.
42.Takamura M, Iehida T, Matsuda Y, et al. Reduced expression of liver-intestine cadherin is associated with progression and lymph node metastasis of human colorectal carcinoma. Cancer Lett, 2004, 212(2): 253-259.
43.Ko S, Chu KM, Luk JM, et al. Overexpression of LI-cadherin in gastric CSflcer is associated with lymph node metastasis. Biochem Biophys Res Commun, 2004 ,319(2): 562-568.
44.Tarone.G, Hirsch E, Brancaecio M, et al. Integrin function and regulation in development. Int J Dev Biol, 2000, 44(6): 725-731.
45.Andrews EJ, Wang JH, Winter DC, et al. Tumor cell adhesion to endothelial cells is increased by endotoxln via an upregulationof beta-1 integrin expression. Surg Res, 2001, 97(1): 14-19.
46.Felding-Habermann B, Fransvea E, Oq'ole TE, et al. Involvement of tumor cell integrin alpha V beta 3 in hematogenous metastasis of human melanoma cells. Clin Exp Metastasis, 2002, 19(5): 427-436.
47.Kroan ME, Koclwijk P, vail der Vecht B, et al. Urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia: implications for capillary-like tube formation in a fibrin matrix. Blood, 2000, 96(8): 2775-2783.
48.Hood JD, Frausto R, Kiosaes WB, et al. Diferential alphav integrin mediated Ras-ERK signaling during two pathways of angiogenesis.Cell Biol, 2003, 162(5): 933-943.
49.Penta K, Vamer JA, Liae L, et al. Dell induces integrin signaling and angiogenesis by ligation of αvβ3.Biol Chem, 1999, 274(16): 11101-11109.
50. Aoka Y,Johnson F, Schatzman R, et al. The embryonic alIgiogenic factor Dell accelerates tumor growth by enhmeing vascular formation. Microvas Res, 2002,64(1): 148-161.
51 .Koren R, Dekel Y,Sherman E.et al. The expression of DCC protein in female breast cancer. Breast Cancer Res Treat. 2003. 80(2): 215-220.
52.Evelyn B,Voura, Ravi A, et al. Involvement of intesrin alpha(v)beta (3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells. Mol Bid Cell, 2ool , 12(9): 2699-2710.
53.Vestweber D, Blanks JE, . Mechanisms that regulate the function of the selectins and their ligands. Physio Rev, 1999, 79(1): 181-213.
54.Flugy A M,D'Amato M , Russo D, et al. E-selectin madulates the malignant properties of T84 colon carcinoma cells. Biochem Biophys Res Comluun,2002. 293(3): 1099-1106.
55.Mccary OJ, Mouse SA, Bray PF, et al. Immobilized platelets support human colon carcinoma cell tethering, rolling and firm adhesion under dyrnamic flow conditions. Blood, 2000, 96(5): 1789-1797.
56.Qian F, Hanahan D, Weissman I. LI-selectin call facilitate metastasis to lymph nodes in a transgenic mouse model of carcinogenesis. Proc Natl Acad Sci USA,2001, 98(7): 3976-3981.
57.Bomig L, Wong R, Hynes R O, et al. Synergistic efects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancersof metastasis. Proc Natl Acad Sci USA. 2002, 99(4): 2193-2198.
58.Shiratori H, Koshino T, Uesugi M , etal. Acceleration of lung metastasis by up-regulation of CD44 expression in osteosarcoma derivod cell transplanted mice.Cancer Lett.2001,170(2):177-182.
59.Weber GF,Bronson RT,ILagan J.et al.Absence of the CD44 gene prevents arcomametastasis.Cancer Res.2002,62(8):2281-2286.
60.Fukuoka J,Dracheva T,Shih JH.et al.Dsg3 as a prognostic factor in lung cancer.Hum Pathol.2007 Feb;38(2):276-83.Epub 2006 Nov 3.
61.刘仲奇,田勇泉,马芙蓉等.桥粒芯糖蛋白3基因在鼻咽癌中表达的初步研究.中华医学杂志,2007.87(36)2541-2543.
62.Wang L,Liu T,Wang Y,et al.Altered expression of desmocollin 3,dsg3,and beta-catenin in oral squamous cell carcinoma:correlation with lymph node metastasis and cell proliferation.Virchows Arch.2007 Nov;451(5):959-66.Epub 2007 Sep 11.
63.Chen YJ,Chang JT,Lee L,et al.DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis.Oncogene.2007 Jan 18;26(3):467-76.Epub 2006 Jul 31.
1. Femiano F . Pemphigus vulgaris: recent advances in our understanding of its pathogenesis.Minerva Stomatol. 2007 Apr;56(4):215-23. Review. English, Italian.
2. Holthofer B,Windoffer R ,Troyanovsky S.et al .Structure and function of desmosomes.Int Rev Cytol. 2007;264:65-163.
3. Stokes DL .Desmosomes from a structural perspective.Curr Opin Cell Biol. 2007 Oct;19(5):565-71. Epub 2007 Oct 22.
4. Dusek RL,Godsel LM, Green KJ.Discriminating roles of desmosomal cadherins:beyond desmosomal adhesion.J Dermatol Sci. 2007 Jan;45(1):7-21. Epub 2006 Dec 1.
5. Cheng X, Den Z, Koch PJ. Desmosomal cell adhesion in mammalian development.Eur J Cell Biol. 2005 Mar;84(2-3):215-23.
6. Muller R,Svoboda V, Wenzel E. et al .IgG against extracellular subdomains of dsg3 relates to clinical phenotype of pemphigus vulgaris.Exp Dermatol. 2008 Jan;17(1):35-43.
7. Garrod DR, Merritt AJ, Nie Z. Desmosomal adhesion: structural basis, molecular mechanism and regulation .Mol Membr Biol. 2002 Apr-Jun;19(2):81-94.
8.Kowalczyk AP,Borgwardt JE,Green KJ. Analysis of desmosomal cadherin-adhesive function and stoichiometry of desmosomal cadherin-plakoglobin complexes.Invest Dermatol. 1996 Sep;107(3):293-300.
9.Yamamoto Y,Aoyama Y,Shu E,et al. Anti-dsg3 (Dsg3) monoclonal antibodies deplete desmosomes of Dsg3 and differ in their Dsg3-depleting activities related to pathogenicity.Biol Chem. 2007 Jun 15;282(24):17866-76. Epub 2007 Apr 11.
l0.Kottke MD,Delva E,Kowalcyk AP. The desmosome: cell science lessons from human diseases.Cell Sci. 2006 Mar 1;119(Pt 5):797-806.
11.Cheng X,Den Z,Koch PJ. Desmosomal cell adhesion in mammalian development.Eur J Cell Biol.2005 Mar;84(2-3):215-23.
12.Chitave VA et al.Cell Sci,1998;111(Pt 14):1942-1949
13.Huber O.Structure and function of desmosomal proteins and their role in development and disease.Cell Mol Life Sci.2003 Sep;60(9):1872-90.
14.Garrod DR,Merritt AJ,Nie Z.Desmosomal cadherins.Curr Opin Cell Biol.2002Oct;14(5):537-45.
15.Lewis JE et al.Cell Biol,1997;136(4):919-934
16.Garrod DR,Merritt AJ,Nie Z.Desmosomal adhesion:structural basis,molecular mechanism and regulation.Mol Membr Biol.2002 Apr-Jun;19(2):81-94.
17.Hatzfeld M.Plakophilins:Multifunctional proteins or just regulators of desmosomal adhesion.Biochim Biophys Acta.2007 Jan;1773(1):69-77.Epub 2006May 6.
18.Sobolik-Delmaire T,Katafiasz D,Keim SA.et al.Decreased plakophilin-1expression promotes increased motility in head and neck squamous cell carcinoma cells.Cell Commun Adhes.2007 Mar-Jun;14(2-3):99-109.
19.McMillan JR,Shimizu H.Desmosomes:structure and function in normal and diseased epidermis.Dermatol.2001 Jun;28(6):291-8.
20.Daneshpazhooh M,Chams-Davatchi C,Khamesipour A.et al.Desmoglein 1 and 3enzyme-linked immunosorbent assay in Iranian patients with pemphigus vulgaris:correlation with phenotype,severity,and disease activity.Eur Acad Dermatol Venereol.2007 Nov;21(10):1319-24.
21.Junya Fukuoka,Tatiana Dracheva,Joanna H.et al.Dsg3 as a prognostic factor in lung cancer.Human Pathogy 2007(38),276-283.
22.刘仲奇,田勇泉,马芙蓉等.桥粒芯糖蛋白3基因在鼻咽癌中表达的初步研究.中华医学杂志,2007,87(36):2541-2543.
23.Mousa SA.Cell adhesion molecules:potential therapeutic & diagnostic implications.Mol Biotechnol. 2008 Jan;38(1):33-40. Epub 2007 Aug 15.
24.Pokutta S,Weis WI. Structure and mechanism of cadherins and catenins in cell-cell contacts.Annu Rev Cell Dev Biol. 2007;23:237-61.